Integrated Chinese-western therapy versus western therapy alone on survival rate in patients with non-small-cell lung cancer at middle-late stage.
J Tradit Chin Med. 2013 Aug ;33(4):433-8. PMID: 24187861
Guoqiang Lin, Yingqiu Li, Shengxi Chen, Haihe Jiang
OBJECTIVE: To compare the effects of integrated Chinese-Western therapy versus Western therapy alone on the survival rate of patients with non-small-cell lung cancer (NSCLC) at middle-late stage and to evaluate prognostic factors.
METHODS: We selected 98 inpatients with middle-late stage NSCLC diagnosed from March 2009 to March 2011 and randomly divided them into two groups, with 49 cases in each group, and the clinical data were analyzed retrospectively. The control group was treated by the combined methods of Western Medicine, including chemotherapy, supportive treatment and symptomatic treatment. The observation group was treated by injection and prescriptions of Chinese medicine based on Traditional Chinese Medicine syndrome differentiation and by the same combined methods of western treatment used in the control group. After treatment, the survival rates of the patients were compared by the stage of cancer and evaluation of 24 prognostic factors analyzed by a Cox regression model, and the clinical data were statistically analyzed.
RESULTS: The survival rates of all patients were over 90.0% at 1 and 3 months after treatment with no significant differences between the two groups (P>0.05); In the observation group the survival rates at 6 months and 1 year were 93.4% and 42.8%, respectively, being superior to 85.6% and 18.3% in the control group (P<0.05). The median survival time in the observation group was superior to the control group (P<0.05); The effects of 24 prognostic factors were significantly better in the observation group than in the control group (P<0.05).
CONCLUSION: Integrated Chinese-western therapy can significantly improve the survival rate in patients with middle-late stage NSCLC and improve prognostic factors compared with western therapy alone.
Article Published Date : Jul 31, 2013
Traditional chinese medicine in cancer care: a review of controlled clinical studies published in chinese.
PLoS One. 2013 ;8(4):e60338. Epub 2013 Apr 3. PMID: 23560092
Xun Li, Guoyan Yang, Xinxue Li, Yan Zhang, Jingli Yang, Jiu Chang, Xiaoxuan Sun, Xiaoyun Zhou, Yu Guo, Yue Xu, Jianping Liu, Alan Bensoussan
Centre for Evidence-based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China ; Centre for Complementary Medicine Research (CompleMED), University of Western Sydney, Sydney, New South Wales, Australia.
BACKGROUND: Traditional Chinese medicine (TCM) has been widely applied for cancer care in China. There have been a large number of controlled clinical studies published in Chinese literature, yet no systematic searching and analysis has been done. This study summarizes the current evidence of controlled clinical studies of TCM for cancer.
METHODS: We searched all the controlled clinical studies of TCM therapies for all kinds of cancers published in Chinese in four main Chinese electronic databases from their inception to November 2011. We bibliometrically analyzed the included studies and assessed the reporting quality.
RESULTS: A total of 2964 reports (involving 253,434 cancer patients) including 2385 randomized controlled trials and 579 non-randomized controlled studies were included. The top seven cancer types treated were lung cancer, liver cancer, stomach cancer, breast cancer, esophagus cancer, colorectal cancer and nasopharyngeal cancer by both study numbers and case numbers. The majority of studies (72%) applied TCM therapy combined with conventional treatment, whilst fewer (28%) applied only TCM therapy in the experimental groups. Herbal medicine was the most frequently applied TCM therapy (2677 studies, 90.32%). The most frequently reported outcome was clinical symptom improvement (1667 studies, 56.24%) followed by biomarker indices (1270 studies, 42.85%), quality of life (1129 studies, 38.09%), chemo/radiotherapy induced side effects (1094 studies, 36.91%), tumor size (869 studies, 29.32%) and safety (547 studies, 18.45%). Completeness and adequacy of reporting appeared to improve with time.
CONCLUSIONS: Data from controlled clinical studies of TCM therapies in cancer treatment is substantial, and different therapies are applied either as monotherapy or in combination with conventional medicine. Reporting of controlled clinical studies should be improved based on the CONSORT and TREND Statements in future. Further studies should address the most frequently used TCM therapy for common cancers and outcome measures should address survival, relapse/metastasis and quality of life.
Article Published Date : Dec 31, 2012
[Observation of clinical curative effect of "oblique-pulling" maneuver in the treatment of lumbar intervertebral disc herniation].
Zhongguo Gu Shang. 2010 Feb;23(2):84-6. PMID: 20345024
Jun Zhang, Lei Han, Peng Wang, Dong Yu, Min Lu, Ding-kun Lin, Tie-bing Song, Jiang-hao Lin, Shu-chun Sun
Wangjing Hospital of China Academy of Chinese Medicine Sciences, Beijing 100102, China.
OBJECTIVE: To evaluate the clinical curative effect of "oblique-pulling" maneuver in patients with lumbar intervertebral disc herniation (LIDH). METHODS: Sixty-five LIDH cases were randomly divided into experimental group and control group. In the experimental group 32 patients were treated by "oblique-pulling" maneuver, and 32 patients in the control group were treated by lumbar traction therapy. One case were excluded from the study and another one case were dropped from the study. After one course of treatment, the therapeutic effects of the two groups were compared quantitatively by using the JOA and VAS scores, including the improvement of signs, symptoms, living ability, and low back and leg pain. RESULTS: After one course of treatment, in the experimental group, 7 cases were controlled well, 16 cases were marked effect, 8 cases were effect, 1 case was no effect. In the control group, 4 cases were controlled well, 10 cases were marked effect, 13 cases were effect, 4 cases was no effect in control group. The clinical effective rate of the experimental group was 96.86%, which was higher than 87.10% of the control group (P<0.05). In the experimental group the scores of JOA and VAS were obviously improved after treatment (P<0.001) and the improvement was better than that of control group (P<0.01). CONCLUSION: The "oblique-pulling" maneuver has the characteristics of simple operation, repeatability, good efficiency, high safety.
Article Published Date : Feb 01, 2010
Traditional Chinese Medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis.
J Exp Clin Cancer Res. 2009 ;28:112. Epub 2009 Aug 12. PMID: 19674474
Ping Wu, Jean Jacques Dugoua, Oghenowede Eyawo, Edward J Mills
BACKGROUND: Liver cancer is a common malignancy with a high mortality rate. Given the poor prognosis associated with this cancer, many patients seek additional therapies that may improve quality of life or survival. Several Traditional Chinese Medicines (TCM) have been evaluated in clinical trials, but little is known about them outside of China.
METHODS: We searched independently and in duplicate 8 electronic databases, including 2 Chinese language databases, until February 2009. We included any randomized clinical trials (RCT) evaluating a TCM oral preparation for the treatment of hepatocellular cancers. We abstracted data on survival, tumor response, and performance scores. We conducted a random-effects meta-analysis and applied a meta-regression analysis.
RESULTS: We included 45 RCTs (n = 3,236). All studies employed an active control group. In general, the reporting of methodological issues was poor. We analyzed data from 37 trials reporting on complete response effects score (Relative Risk [RR] of 1.26 (95 CI, 1.04-1.52, P = 0.01, I2 = 0%, P = 0.99). Products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34, 95% CI, 1.04-1.71, P = 0.01) than the pooled broad estimate, also the case for astragalus-based treatments (OR 1.35, 95% CI, 1.001-1.80. P = 0.048). We examined survival rates and pooled 15 studies reporting on 6 month outcomes (RR 1.10, 95% CI, 1.04-1.15, P =<0.0001, I2 = 0%, P = 0.60). This effect was consistent at other prospective dates, including 12 months (22 trials, RR 1.26, 95% CI, 1.17-1.36, P =<0.0001, I2 = 7%, P = 0.36), 24 months (15 trials, 1.72, 95% CI, 1.40-2.03, P =<0.0001, I2 = 0%, P = 0.75); and, at 36 months (8 trials, RR 2.40, 95% CI, 1.65-3.49, P =<0.0001, I2 = 0%, P = 0.62).
LIMITATIONS: All included trials were conducted in China where emerging evidence suggests many RCTs are not, in fact, randomized. Publication bias may exist, favouring positive reports.
CONCLUSION: Our meta-analysis displays compelling evidence of effectiveness for hepatocellular cancers that should be evaluated in high-quality and transparent clinical trials.
Article Published Date : Jan 01, 2009
[Manipulative reduction for lumbar intervertebral disc herniation: a controlled clinical trial].
Zhongguo Gu Shang. 2008 Apr;21(4):273-5. PMID: 19102187
Wei-bin Zhang, Yu Cao, Yong-an Sun, Chun-sheng Wang, Ying Wang, Shi-long Dong, Guo-zhong Ren, Ying-xin Yang, Jing-zhong Zhang
The Beifang Hospital of General Hospital of Shenyang Military Command, Shenyang 110032, Liaoning, China.
OBJECTIVE: To investigate the effects of manipulative reduction on pain and clinical curative effect in patients with lumbar intervertebral disc herniation. METHODS: Eleven thousands one hundred and twenty-eight patients with lumbar intervertebral disc herniation from our hospital were enrolled from November 1986 to June 2007. They were randomly divided into control group and treatment group. Patients of the control group received lumbar traction and various physiotherapies. Patients of the treatment group received manipulative reduction, besides the treatment in the control group. The treatment was performed once a day,ten times as a course. Curative effects were assessed three courses later. Pain was evaluated by visual analogue scale before and after the treatment. RESULTS: No significant difference in the score of visual analogue scale was found before the treatment in the two groups (P>0.05). As compared with the score before treatment,it was decreased by 4.73 points after treatment in the control group, and decreased by 6.37 points in the treatment group. The decrease was more significant in the treatment group than the control group (P<0.01). The healing rate was 47.28% and total effective rate was 96.37% in the control group; The healing rate was 73.44% and total effective rate was 98.61% in the treatment group (P<0.01). CONCLUSION: Manipulative reduction for lumbar intervertebral disc herniation can remarkably relieve lumbar pain and improve clinical curative effect.
Article Published Date : Apr 01, 2008
[Clinical and experimental study on retardation of immunosenescence by kidney tonifying principle].
J Med Food. 2007 Dec;10(4):689-93. PMID: 12585100
Zi-yin Shen, Zhen Zheng, Wei-min Guo
Institute of Integrated Traditional Chinese and Western Medicine, Medical Center of Fudan University, Shanghai 200040.
OBJECTIVE: To observe the clinical curative effect of Kidney tonifying method on retardation of immunosenescence and corresponding experimental study.
METHODS: A randomized double blind placebo-controlled trial was used (RCT) on 22 pairs of aged subjects to elucidate the effect of Kidney tonifying recipe on the peripheral T-lymphocyte apoptosis and the Fas/FasL gene expression in them. In rats experimental study, the effects of two kinds of Chinese recipes (Kidney tonifying recipe and blood circulation promoting recipe) on the same parameters as in clinical study as well as on cell apoptosis and gene expression regulation in old rats were also observed.
RESULTS: Clinical study showed that after treatment, the percentage of T-lymphocyte apoptosis and the FasL gene expression in the Kidney tonifying group of aged subjects were lower than those in the placebo group (P<0.01). Animal experiment showed the same result as shown in clinical study in Kidney tonifying recipe treated rats, but not shown in those treated with blood circulation promoting recipe statistically.
CONCLUSION: Kidney tonifying principle has down-regulating effect on the transcription of apoptotic gene in both aged persons and old rats, this is one of the molecular mechanisms of Kidney tonifying method in decreasing over-apoptosis in aged subjects and old rats.
Article Published Date : Dec 01, 2007
Effect of traditional chinese medicine on survival and quality of life in patients with esophageal carcinoma after esophagectomy.
Chin J Integr Med. 2006 Sep;12(3):175-9. PMID: 17005076
Ping Lu, Qiu-dong Liang, Rong Li, Hong-rui Niu, Xiao-ge Kou, Hong-jun Xi
OBJECTIVE: To explore the effect and possible mechanism of traditional Chinese medicine (TCM) on survival and quality of life (QOL) in patients with esophageal carcinoma after esophagectomy. METHODS: Adopting prospective controlled method of study, the authors had 128 post-esophagectomy patients, hospitalized from February 2001 to February 2002, randomly divided into 3 groups: the TCM group, treated with TCM drugs alone; the chemotherapy group, with chemotherapy alone applied; and the synthetic group, treated with chemotherapy combined with Chinese medicine. Their survival rate and QOL were compared. RESULTS: In the TCM group, the chemotherapy group and the synthetic group, the respective 3-year relapse and remote metastasis rate were 71.4%, 76.7%, 53.4%, respectively (chi(2) = 6.53, P<0.05); the 1-year survival rate 42.9%, 46.5%, 72.1%; 2-year survival rate 28.6%, 27.9%, 55.8%, and 3-year survival rate 26.2%, 23.1%, 37.2%, respectively. And the QOL improving rate was 69.0%, 37.2%, 58.1%, respectively, all showing significant difference among them (chi(2) = 6.10, all P<0.05). Moreover, immune function was increased in the TCM and the synthetic groups. CONCLUSION: Integrative Chinese and Western medicinal treatment was the beneficial choice for post-operational patients with esophageal carcinoma. However, long time use of simple Chinese medicine was also advisable, especially for those in poverty.
Article Published Date : Sep 01, 2006
Evaluation of the clinical efficacy of Qingqiao capsule in treating patients with secretory otitis media.
Chin J Integr Med. 2005 Dec;11(4):243-8. PMID: 16417772
Yong-dong Sun, Long-hui Chen, Wen-jian Hu, Yu-liang Jiang, Xiao-lin Chen, Shi-bo Zhang
OBJECTIVE: To observe the clinical efficacy of Qingqiao Capsule (QQC) in treating patients with secretory otitis media (SOM).
METHODS: A total of 90 patients were randomly assigned into the treated group (n = 45) and the control group (n = 45). Patients in the treated group were administrated with QQC, 5 capsules each time, 3 times a day for totally 10-14 days, and those in the control group were given per os cefaclor capsules 0.5 g each time for adult, 3 times a day, or 20 mg/(kg.d) for children, for 10-14 days. The therapeutic efficacy of treatment on the patients was observed and compared after treatment and followed up for 3-6 months.
RESULTS: (1) The clinical efficacy in the treated group was superior to that in the control group with significant statistical difference (P<0.01); (2) Comparison of the efficacies in patients of three different TCM syndrome types (the external pathogenic wind invasion caused auditory orifice stuffiness type, the Gan-Dan damp-heat steaming up auditory orifice type and the Pi-deficiency dysfunction induced dirty dampness blocking ear type) showed no statistically significant difference (P>0.05); (3) The vanishing rate and time needed of the main symptoms and signs in the treated group were superior to those in the control group on ear muffle, tinnitus, hearing impairment, hydrotypanum, pure tone threshold and abnormal tongue figure, and the difference was statistically significant (P<0.05 or P<0.01), only those of earache, otopiesis and abnormal pulse figure were insignificantly different between the two groups (P>0.05).
CONCLUSION: QQC is an effective Chinese composite medicine on patients with SOM, and shows no obvious adverse reaction.
Article Published Date : Dec 01, 2005
Changes in CD23 expression of blood and skin in atopic eczema after Chinese herbal therapy.
Clin Exp Allergy. 1998 Mar;28(3):306-14. PMID: 9543080
P Banerjee, X J Xu, L W Poulter, M H Rustin
Department of Dermatology, Royal Free Hospital School of Medicine, London, UK.
BACKGROUND: Aberrant expression of CD23 (low affinity IgE receptor) on cells of the monocyte/macrophage series in peripheral blood and lesional skin of patients with atopic eczema has been demonstrated. It is not known whether this abnormality results from a fundamental systemic problem of the monocytes of these patients or reflects local changes to cell populations within the skin tissues.
OBJECTIVES: This study was designed to determine whether this aberrant expression was caused by local cutaneous influences on mature cells or fundamental changes in monocyte differentiation. The possible relationship between these aberrations and clinical severity was also investigated by repeating these immunopathological studies after a course of efficacious treatment with Chinese herbal therapy (CHT).
METHODS: Peripheral blood mononuclear cells were obtained from patients with atopic eczema before, and after 8 weeks of treatment. Efficacy of CHT was quantified on clinical grounds. Monocytes were isolated by adherence to plastic and cultured for up to 7 days. Samples were harvested at 2, 5 and 7 days of culture and cytospins prepared. Immunocytochemical staining to identify phenotypic subsets was performed on the monocytes at time 0 and on maturing cells from culture. This immunocytology was quantified using computerized image analysis equipment to determine the emergence of macrophage subsets and their level of CD23 expression. Biopsies were taken from lesional skin before and after treatment and immunohistology was performed on cryostat sections to determine the number of antigen presenting cells expressing CD23 as well as the level of expression of these molecules.
RESULTS: The results showed that increased numbers of monocytes from patients with atopic eczema express CD23 at day 0 and that cultured monocytes from these patients differentiate faster during the 7 day culture period as compared to normal controls. Efficacious treatment did not affect the number of peripheral blood monocytes expressing CD23. However, treatment did lead to a significant decrease in the number of CD23+ mature macrophages in the skin as well as a reduction in the level of expression of this moiety. These results demonstrate that changes in clinical severity are more closely related to the expression of CD23 on mature antigen presenting cells in lesional skin rather than to differentiating peripheral blood monocyte CD23 expression.
CONCLUSIONS: These results suggests that local factors within lesional skin govern the accumulation and the expression of CD23 on mature macrophages and that these factors may be more relevant to the pathogenesis of the disease than aberrations in CD23 expression that may occur systemically.
Article Published Date : Mar 01, 1998
[Mechanism of shen qian gujing granule in the treatment of menorrhagia].
Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992 Dec ;12(12):730-3, 709. PMID: 1304842
H Q Xia, C J Li, J Yu
Obstetrics and Gynecology Hospital, Shanghai Medical University.
Shen Qian Gujing Granule, a Chinese herbal preparation has shown its efficacy of 87.7% in treating menorrhagia. PGE2, PGE2 alpha, TXB2 and 6-Keto-PGF1 alpha levels were measured in the endometrium and menstrual blood of both normal menstrual women and patient with menorrhagia before and after the treatment. Local TXB2 values of endometrial and menstrual blood were significantly higher in menorrhagia patients than that in normal subjects (P<0.05). And the local PGE2 values were higher in patients accompanied with Qi Deficiency (P<0.05) and lower in patients without Qi Deficiency (P<0.05). After the treatment, the local TXB2, PGE2 levels normalized. It suggests that Shen Qian Gujing Granule had a biphasic regulation on local PG values which yields good results for menorrhagia. Some mechanism were discussed.
Article Published Date : Nov 30, 1992
ALK phosphorylates SMAD4 on tyrosine to disable TGF-β tumour suppressor functions.
Nat Cell Biol. 2019 Jan 21;:
Authors: Zhang Q, Xiao M, Gu S, Xu Y, Liu T, Li H, Yu Y, Qin L, Zhu Y, Chen F, Wang Y, Ding C, Wu H, Ji H, Chen Z, Zu Y, Malkoski S, Li Y, Liang T, Ji J, Qin J, Xu P, Zhao B, Shen L, Lin X, Feng XH
Loss of TGF-β tumour suppressive response is a hallmark of human cancers. As a central player in TGF-β signal transduction, SMAD4 (also known as DPC4) is frequently mutated or deleted in gastrointestinal and pancreatic cancer. However, such genetic alterations are rare in most cancer types and the underlying mechanism for TGF-β resistance is not understood. Here we describe a mechanism of TGF-β resistance in ALK-positive tumours, including lymphoma, lung cancer and neuroblastoma. We demonstrate that, in ALK-positive tumours, ALK directly phosphorylates SMAD4 at Tyr 95. Phosphorylated SMAD4 is unable to bind to DNA and fails to elicit TGF-β gene responses and tumour suppressing responses. Chemical or genetic interference of the oncogenic ALK restores TGF-β responses in ALK-positive tumour cells. These findings reveal that SMAD4 is tyrosine-phosphorylated by an oncogenic tyrosine kinase during tumorigenesis. This suggests a mechanism by which SMAD4 is inactivated in cancers and provides guidance for targeted therapies in ALK-positive cancers.
PMID: 30664791 [PubMed - as supplied by publisher]
Expression and effects of leukemia inhibitory factor on nucleus pulposus degeneration.
Mol Med Rep. 2019 Jan 17;:
Authors: Xiao Q, Zeng JH, Zhou H, Qiu QH, Ke B, Deng L, Hu ZM, Roh J, Dai M
Leukemia inhibitory factor (LIF) is a multifunctional cytokine. The present study aimed to determine the expression and effects of LIF on nucleus pulposus generation. Degenerated nucleus pulposus samples were obtained from animal models and patients with lumbar intervertebral disc herniation. Degradation scores of intervertebral discs were evaluated via magnetic resonance imaging (MRI) and histology, and the protein expression levels of LIF were detected. Furthermore, cultured primary human degenerated nucleus pulposus cells (DNPCs) were stimulated with various concentrations of recombinant human LIF protein (rhLIF), and aggrecan and collagen type II α1 (COL2α1) protein expression levels were detected by western blotting. In addition, aggrecan expression was determined by toluidine blue staining. The effects of rhLIF on proliferation and apoptosis of DNPCs were evaluated by Cell Counting Kit‑8 and flow cytometry, respectively. The results revealed that the degradation scores of intervertebral discs were significantly associated with modeling time, as determined by MRI and histology. In addition, the protein expression levels of LIF were initially increased in patients with lumbar disc herniation and in rabbit models, particularly in the 2‑week modeling group; however, its expression decreased with the progression of disc degeneration. Notably, LIF expression in each modeling group was higher than that in the control and 0 week modeling group. The in vitro study revealed that the protein expression levels of aggrecan and COL2α1 were significantly increased in response to rhLIF, in a dose‑dependent manner, and statistical differences were identified between the treatment groups and control group. The results of toluidine blue staining were consistent with this finding. Although rhLIF had no effect on proliferation, it inhibited apoptosis of DNPCs in a concentration‑dependent manner. In conclusion, LIF was upregulated during the process of intervertebral disc degeneration, and may promote the expression of extracellular matrix components. It may also be hypothesized that LIF acts as a potential protective factor by inhibiting apoptosis of DNPCs without affecting cell proliferation.
PMID: 30664218 [PubMed - as supplied by publisher]
ZEB1 promotes tumorigenesis and metastasis in hepatocellular carcinoma by regulating the expression of vimentin.
Mol Med Rep. 2019 Jan 15;:
Authors: Qin Y, Yu J, Zhang M, Qin F, Lan X
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains poor. Epithelial‑to‑mesenchymal transition (EMT)‑induced markers have emerged as key regulators of tumor development and progression in HCC. The aim of the present study was to investigate the role of zinc finger E‑box‑binding homeobox 1 (ZEB1) in the tumorigenesis of HCC and to elucidate the mechanism underlying the correlation between ZEB1 and vimentin (VIM). The expression levels of ZEB1 and VIM were assessed by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction analysis in HCC tissues and cell lines. The biological significance of ZEB1 was examined by downregulating the expression of ZEB1 in Huh‑7 cells. A luciferase reporter assay was used to investigate the association between ZEB1 and VIM. The expression levels of ZEB1 and VIM were higher in tumor tissues compared with those in adjacent normal tissues, and they were significantly associated with a poor prognosis in patients with HCC, whereas ZEB1 silencing led to the attenuation of HCC cell proliferation, invasion and migration. Furthermore, it was observed that ZEB1 was able to bind to a certain site in the VIM promoter and regulate the transcriptional activity of VIM. Therefore, the present study demonstrated that ZEB1 is a potential biomarker of the tumorigenesis and progression of HCC, and it may regulate transcription of the VIM gene.
PMID: 30664206 [PubMed - as supplied by publisher]
β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration.
Mol Med Rep. 2019 Jan 15;:
Authors: Wen F, Yu J, He CJ, Zhang ZW, Yang AF
Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). β-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that β‑ecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that β‑ecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of β‑ecdysterone on IDD was explored by in vitro experiments. The results demonstrated that β‑ecdysterone attenuated the apoptosis induced by tert‑butyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin‑1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by β‑ecdysterone in a dose‑ and time‑dependent manner in nucleus pulposus cells. Inhibition of autophagy with 3‑methyladenine partially abrogated the protective function of β‑ecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of β‑ecdysterone on IDD. Additionally, β‑ecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that β‑ecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that β‑ecdysterone may be a potential therapeutic agent for IDD.
PMID: 30664184 [PubMed - as supplied by publisher]
Weighted gene co‑expression network analysis for identifying hub genes in association with prognosis in Wilms tumor.
Mol Med Rep. 2019 Jan 21;:
Authors: Wang X, Song P, Huang C, Yuan N, Zhao X, Xu C
Wilms tumor (WT) is the most common type of renal malignancy in children. Survival rates are low and high‑risk WT generally still carries a poor prognosis. To better elucidate the pathogenesis and tumorigenic pathways of high‑risk WT, the present study presents an integrated analysis of RNA expression profiles of high‑risk WT to identify predictive molecular biomarkers, for the improvement of therapeutic decision‑making. mRNA sequence data from high‑risk WT and adjacent normal samples were downloaded from The Cancer Genome Atlas to screen for differentially expressed genes (DEGs) using R software. From 132 Wilms tumor samples and six normal samples, 2,089 downregulated and 941 upregulated DEGs were identified. In order to identify hub DEGs that regulate target genes, weighted gene co‑expression network analysis (WGCNA) was used to identify 11 free‑scale gene co‑expressed clusters. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were annotated using KEGG Orthology Based Annotation System annotation of different module genes. The Search Tool for the Retrieval of Interacting Genes was used to construct a protein‑protein interaction network for the identified DEGs, and the hub genes of WGCNA modules were identified using the Cytohubb plugin with Cytoscape software. Survival analysis was subsequently performed to highlight hub genes with a clinical signature. The present results suggest that epidermal growth factor, cyclin dependent kinase 1, endothelin receptor type A, nerve growth factor receptor, opa‑interacting protein 5, NDC80 kinetochore complex component and cell division cycle associated 8 are essential to high‑risk WT pathogenesis, and they are closely associated with clinical prognosis.
PMID: 30664180 [PubMed - as supplied by publisher]
MicroRNA‑601 serves as a potential tumor suppressor in hepatocellular carcinoma by directly targeting PIK3R3.
Mol Med Rep. 2019 Jan 15;:
Authors: Song Y, He S, Zhuang J, Wang G, Ni J, Zhang S, Ye Y, Xia W
Recently, microRNAs (miRNAs) have been acknowledged as important regulators of hepatocarcinogenesis and tumor progression. Therefore, identifying the underlying molecular mechanisms of miRNAs in the occurrence and development of hepatocellular carcinoma (HCC) may be important for understanding the pathogenesis of HCC and aid the identification of potential therapeutic strategies. In the present study, miRNA (miR)‑601 was significantly downregulated in HCC tissues and cell lines; low miR‑601 expression was strongly associated with tumor, node and metastasis staging and lymph node metastasis of patients with HCC. In addition, the overexpression of miR‑601 expression significantly inhibited the proliferation and invasion of HCC cells. Regarding the underlying mechanism, phosphoinositide‑3‑kinase regulatory subunit 3 (PIK3R3) was predicted to be a direct target of miR‑601 in HCC cells. Furthermore, restoration of PIK3R3 expression in these cells counteracted the inhibitory effects of miR‑601 on cell proliferation and invasion in HCC. Notably, miR‑601 overexpression inhibited the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in HCC via the regulation of PIK3R3. Collectively, these results demonstrated that miR‑601 may inhibit the progression of HCC by directly targeting PIK3R3 and regulating the AKT/mTOR signaling pathway. Therefore, miR‑601 may be an effective therapeutic target for the treatment of patients with HCC.
PMID: 30664174 [PubMed - as supplied by publisher]
The estrogen‑like protective effect of Lycium barbarum polysaccharides in reducing oxidative stress on myocardial cells from ovariectomized rats.
Mol Med Rep. 2019 Jan 18;:
Authors: Yu N, Song N, Liu CY, Yang GL
Previous studies have demonstrated that ovariectomy may lead to a reduction in antioxidative biomarkers in the myocardium, thus suggesting that estrogens may serve a protective role in the suppression of oxidative stress. Lycium barbarum polysaccharides (LBP) are a well‑known antioxidant Chinese traditional medicine, which appear to have a similar function to estrogens with regards to the regulation of cardiac function. In the present study, 30 Sprague‑Dawley rats were randomly divided into the following groups: Sham operation group, ovariectomized (OVX) group, estradiol valerate group, high‑dose LBP (LBP‑H) group and low‑dose LBP (LBP‑L) group. All of the rats were provided tap water, estradiol valerate or LBP for 12 weeks. In addition, all rats were ovariectomized, with the exception of rats in the sham operation group, which underwent fat removal only. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH‑px), catalase (CAT) and superoxide dismutase activities were subsequently examined. The protein expression levels of cleaved caspase‑9, cleaved caspase‑3 and phosphorylated‑protein kinase B (p‑Akt) were also assessed. The results demonstrated that high‑dose LBP decreased the enhanced levels of ROS and MDA in OVX rats, whereas GSH‑px and CAT activities were increased in the LBP‑H group compared with in OVX rats. Furthermore, the expression levels of cleaved caspase‑9 and cleaved caspase‑3 were significantly upregulated in the OVX group, whereas high‑dose LBP exerted protective effects on OVX rats by decreasing the expression of apoptotic proteins. Conversely, p‑Akt expression was decreased in the OVX group and was increased in the LBP‑H group. These results indicated that LBP is essentially involved in cardiac protection by inhibiting apoptosis in response to oxidative stress. In addition, improvement of antioxidant status by LBP is associated with the Akt signaling pathway in the myocardium of OVX rats.
PMID: 30664163 [PubMed - as supplied by publisher]
MicroRNA‑31 promotes chondrocyte proliferation by targeting C‑X‑C motif chemokine ligand 12.
Mol Med Rep. 2019 Jan 15;:
Authors: Dai Y, Liu S, Xie X, Ding M, Zhou Q, Zhou X
The present study aimed to investigate the biological function and underlying molecular mechanisms of miR-31 in osteoarthritis (OA). Reverse transcription‑quantitative polymerase chain reaction was used to detect miR‑31 expression, and it was found that miR‑31 was downregulated in the cartilage tissues of OA patients. microRNA.org was used to predict the gene targets of miR‑31, and dual luciferase reporter assays were used to verify that C‑X‑C motif chemokine ligand 12 (CXCL12) was a direct target of miR‑31. The human chondrocyte cell line CHON‑001 was used to perform MTT and cell migration assays. Western blotting was used to measure the protein expression of CXCL12, type I collagen and aggrecan. The results suggested that CXCL12 was a target of miR‑31, and the expression of CXCL12 was negatively regulated by miR‑31 in CHON‑001 cells. miR‑31 increased CHON‑001 cell viability and migration, as well as the expression of type I collagen and aggrecan. Furthermore, the overexpression of CXCL12 eliminated the effects of miR‑31 mimics on CHON‑001 cells. In conclusion, the data indicated that miR‑31 promoted chondrocyte viability and migration by directly targeting CXCL12, which provided evidence for CXCL12 as a potential target in OA therapy.
PMID: 30664157 [PubMed - as supplied by publisher]
Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4 /MyD88/NF-κB signal pathway.
Drug Dev Res. 2019 Jan 21;:
Authors: Zhang Y, Zeng Y
Preclinical Research & Development Curcumin has been shown to possess a series of beneficial effects, such as antiinflammatory, antioxidant, analgesic, and promoting healing. However, the effect and relative mechanism of curcumin on knee osteoarthritis (OA) have not been elucidated. The aim of this study is to explore the protective effect of curcumin on monosodium iodoacetate (MIA)-induced OA. Forty-eight rats were randomized into four experimental groups: control group, OA group, OA + PBS group, and OA + curcumin group, respectively. A single intraarticular injection of MIA was applied to establish the rat model of knee OA. Hematoxylin-eosin staining was used to evaluate histological changes of knee joint. The paw withdrawal threshold was collected and the expression of synovial fluid cytokine levels was measured by ELISA. The protein expression of TRL-4, MyD88, p-IκBα, NF-κB, TNF-α, IL-1β, and IL6 was measured by western blot. Treating with curcumin can significantly reduce joint diameter and Mankin's score, and increase the paw withdrawal threshold. The expression of synovial fluid inflammatory biomarkers, IL-6, IL-1β, and TNF-α in the OA + curcumin group were lower than that in OA and OA + PBS group. The protein expression of the TLR4 receptor was increased in the OA, OA + PBS, and OA + curcumin group compared to the control group. However, curcumin treatment can significantly decrease the expression of MyD88, p-IκBα, NF-κB, TNF-α, IL-1β, and IL6 in OA + curcumin group. These findings may indicate that curcumin could block TLR4/NF-κB signal pathway, and reduce inflammation level to prevent knee wound in OA rats. Curcumin may be a feasible kind of medicament in the treatment of knee OA.
PMID: 30663793 [PubMed - as supplied by publisher]
Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice.
J Vis Exp. 2019 Jan 07;(143):
Authors: Yan ZY, Li XJ, Ding XF, Liu YY, Chen JX
In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall improvement of patients with major depressive disorder (MDD). Therefore, the purpose of this study was to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and then evaluate the anti-depression effect of Xiaoyaosan. Mice were randomly divided into four groups: a control group, a model group, a treatment group with Xiaoyaosan, and a treatment group with fluoxetine. All mice were individually kept in cages, and depression was induced in the mice by exposing them to several designed manipulations of CUMS for 21 days, as described in the protocol. Mice in the control group and model group received 0.5 mL of distilled water, while mice in the treatment groups received either Xiaoyaosan (0.25 g/kg/day) or fluoxetine (2.6 mg/kg/day). The drugs used in the study were given intragastrically daily during the entire three weeks. To estimate the depressive-like behaviors, a series of parameters including the coat state, body weight, open field test score, and sucrose preference test score were recorded. Data analysis showed that behaviors of model mice were significantly changed compared to behaviors of mice in the control group, which were improved by the treatment of Xiaoyaosan and fluoxetine. The current findings demonstrated the anti-depression effects of Xiaoyaosan on the behaviors of CUMS-induced mice and revealed that compounds from the Xiaoyaosan prescription may be worthwhile for treating depression, considering their beneficial effects on depressive-like behaviors.
PMID: 30663637 [PubMed - in process]
Bone morphogenetic protein (BMP) 7 expression is regulated by the E3 ligase UBE4A in diabetic nephropathy.
Arch Physiol Biochem. 2019 Jan 19;:1-4
Authors: Feng Y, Jin MY, Liu DW, Wei L
Mesangial cells played a central role in the pathophysiology of diabetic nephropathy (DN). Our goal was to evaluate the molecular mechanism that regulates loss of BMP7 protein expression in DN. The mRNA and protein levels of BMP7 or UBE4A were detected using qRT-PCR and Western blot respectively. Mass spectrometry and co-immunoprecipitation were used to explore the E3 ligase which regulated BMP7 post-translationally. We initially confirmed that BMP7 protein, but not mRNA, is downregulated when cultured under high glucose mimicking DN conditions, which was rescued by MG-132 treatment. Proteomic analysis of NRK-52E cells ± MG-132 revealed a list of ubiquitin ligases associated with BMP7. Knockdown of the ubiquitin ligase UBE4A stabilized BMP7 expression in NRK-52E cells grown under high glucose conditions. Concurrent overexpression experiments confirmed that UBE4A is the ubiquitin ligase that degrades BMP7. Co-immunoprecipitation analysis confirmed that BMP7 and UBE4A interact. BMP7 expression in DN is regulated by post-translational mechanism.
PMID: 30663414 [PubMed - as supplied by publisher]
Rapid identification of cervus antlers by species-specific PCR assay.
Nat Prod Res. 2019 Jan 19;:1-5
Authors: Yang Y, Zheng Y, Lu B, Jiao Z, Chen L, Gblinwon RT, Jia X, Shen Y, Yang H
A rapid PCR technology was developed to differentiate Cervus antlers species and adulteration based on the difference in mitochondrial genome. Three specifically designed primer sets were confirmed to have high inter-species specificity and good intra-species stability. Limits of detection were estimated to be 1 ng of genomes for reindeer and 10 ng for the other species. Especially, when the mixture of Cervus antlers and reindeer or sambar was assayed, these primer sets still exhibited strong capability of differentiation but not the conventional COI barcoding. By using the newly developed approach, five batches out of fourteen commercial Cervus antler products were identified to be fake products made from reindeer antlers. It has shown its good potential to be extensively applied in the identification of counterfeits or adulterates of Cornu Chinese medicines for their pulverized and processed form, and even the traditional Chinese patent medicines composed of these species.
PMID: 30663383 [PubMed - as supplied by publisher]
Determination and comparison of alkaloids and triterpenes among tissues after oral administration of crude and processed Phellodendri Chinensis Cortex by UPLC-QqQ-MS.
Nat Prod Res. 2019 Jan 19;:1-4
Authors: Lei X, Shan G, Zhang F, Liu P, Meng L, Jia T
Phellodendri Chinensis Cortex is widely used in the clinic of traditional Chinese medicine. In order to enlarge the range of application, it is necessary to processed with honey, salt-water, and rice-wine, respectively. We hope to elucidate the connotation of processing, an UPLC-QqQ-MS method was used for determination and comparison the tissue distribution of alkaloids and triterpenes after oral administration water-extracts of crude and processed products. The results showed that the berberine, phellodendrine, magnoflorine, limonin, and obacunone in crude and processed products were distributed in all tissues, especially in the small intestine and stomach. In this study, we can provide a scientific basis for explaining the processing connotation of Phellodendri Chinensis Cortex processed with salt-water and rice-wine, respectively.
PMID: 30663377 [PubMed - as supplied by publisher]
A new diterpenoid alkaloid from Aconitum hemsleyanum.
Nat Prod Res. 2019 Jan 19;:1-6
Authors: Luo ZH, Chen Y, Sun XY, Fan H, Li W, Deng L, Yin TP
A new C19-diterpenoid alkaloid named hemsleyaline (1), along with fourteen known alkaloids (2-15), were isolated from the roots of Aconitum hemsleyanum Pritz. (Ranunculaceae), a herbal medicine in southwest China. Their structures were established on the basis of extensive spectroscopic analyses. Compound 1 showed mild cholinesterase inhibitory effect with IC50 value of 471 ± 9 μM.
PMID: 30663368 [PubMed - as supplied by publisher]
Aspergillolide, a new 12-membered macrolide from sea cucumber-derived fungus Aspergillus sp. S-3-75.
Nat Prod Res. 2019 Jan 19;:1-7
Authors: Tan JJ, Liu XY, Yang Y, Li FH, Tan CH, Li YM
A new 12-membered macrolide, aspergillolide (1), along with nine known compounds (2-10), were isolated from the fungus Aspergillus sp. S-3-75 associated with the sea cucumber Holothuria nobilis Selenka. The structure and absolute stereochemistry of 1 were elucidated on the basis of extensive spectroscopic methods and single crystal X-ray diffraction analysis.
PMID: 30663348 [PubMed - as supplied by publisher]
The Ibr-7 derivative of Ibrutinib exhibits enhanced cytotoxicity against non-small cell lung cancer (NSCLC) cells via targeting of mTORC1/S6 signaling.
Mol Oncol. 2019 Jan 20;:
Authors: Zhang B, Wang L, Zhang Q, Yan Y, Jiang H, Hu R, Zhou X, Liu X, Feng J, Lin N
Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B-cell malignancies, and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti-cancer activity of Ibrutinib against solid tumors, such as non-small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of Ibrutinib towards lung cancer, we synthesized a series of Ibrutinib derivatives, of which Ibr-7 exhibited superior anti-cancer activity to Ibrutinib, especially against epithelial growth factor receptor (EGFR) wild-type NSCLC cell lines. Ibr-7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by Ibrutinib, thus accounting for the superior anti-cancer activity of Ibr-7 towards NSCLC. Ibr-7 was shown to overcome the elevation of Mcl-1 caused by ABT-199 mono-treatment, and thus exhibited a significant synergistic effect when combined with ABT-199. In conclusion, we used a molecular substitution method to generate a novel Ibrutinib derivative, termed Ibr-7, which exhibits enhanced anti-cancer activity against NSCLC cells as compared to the parental compound.
PMID: 30663221 [PubMed - as supplied by publisher]
The Role of Tauroursodeoxycholic Acid on Dedifferentiation of Vascular Smooth Muscle Cells by Modulation of Endoplasmic Reticulum Stress and as an Oral Drug Inhibiting In-Stent Restenosis.
Cardiovasc Drugs Ther. 2019 Jan 21;:
Authors: Luo H, Zhou C, Chi J, Pan S, Lin H, Gao F, Ni T, Meng L, Zhang J, Jiang C, Ji Z, Lv H, Guo H
PURPOSE: The role of endoplasmic reticulum (ER) stress in cardiovascular disease is now recognized. Tauroursodeoxycholic acid (TUDCA) is known to have cardiovascular protective effects by decreasing ER stress. This study aimed to assess the ability of TUDCA to decrease ER stress, inhibit dedifferentiation of vascular smooth muscle cells (VSMCs), and reduce in-stent restenosis.
METHODS: The effect of TUDCA on dedifferentiation of VSMCs and ER stress was investigated in vitro using wound-healing assays, MTT assays, and western blotting. For in vivo studies, 18 rabbits were fed an atherogenic diet to induce atheroma formation. Bare metal stents (BMS), BMS+TUDCA or Firebird stents were implanted in the left common carotid artery. Rabbits were euthanized after 28 days and processed for scanning electron microscope (SEM), histological examination (HE), and immunohistochemistry.
RESULTS: In vitro TUDCA (10-1000 μmol/L) treatment significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration in VSMCs in a concentration-dependent manner and decreased ER stress markers (IRE1, XBP1, KLF4, and GRP78). In vivo, we confirmed no significant difference in neointimal coverage on three stents surfaces; neointimal was significantly lower with BMS+TUDCA (1.6 ± 0.2 mm2) compared with Firebird (1.90 ± 0.1 mm2) and BMS (2.3 ± 0.1 mm2). Percent stenosis was lowest for BMS+TUDCA, then Firebird, and was significantly higher with BMS (28 ± 4%, 35 ± 7%, 40 ± 1%; respectively; P < 0.001). TUDCA treatment decreased ER stress in the BMS+TUDCA group compared with BMS.
CONCLUSIONS: TUDCA inhibited dedifferentiation of VSMCs by decreasing ER stress and reduced in-stent restenosis, possibly through downregulation of the IRE1/XBP1 signaling pathway.
PMID: 30663009 [PubMed - as supplied by publisher]
Foraminoplasty at the Tip or Base of the Superior Articular Process for Lateral Recess Stenosis in Percutaneous Endoscopic Lumbar Discectomy: A Multicenter, Retrospective, Controlled Study with 2-Year Follow-Up.
Biomed Res Int. 2018;2018:7692794
Authors: Yang JS, Chu L, Chen CM, Wang XF, Xie PG, Deng R, Yu KX, Shi L, Zhang ZX, Rong LM, Hao DJ, Deng ZL
Objective: To compare the clinical efficacy and complications which obtained foraminoplasty at the tip or base of the superior articular process (SAP) for the patients with lateral recess stenosis treated by percutaneous endoscopic lumbar discectomy (PELD).
Methods: Between January 2015 and January 2016, 156 patients of lumbar disc herniation accompanying with lateral recess stenosis were treated with PELD in five tertiary hospitals and fulfilled the 2-year follow-up. Among them, 78 patients obtained a foraminoplasty at the tip of SAP (group A), and foraminoplasty at the base of SAP was performed in the other 78 cases (group B). Clinical efficacy was evaluated using the visual analog scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), and 36-item Short-Form Health Survey (SF-36) score. The intervals of follow-up were scheduled at 1 month, 3 months, 6 months, 1 year, and 2 years after surgery.
Results: Mean operative duration is shorter in group B (55 versus 61 min, P = 0.047). Only one case belonged to group A could not tolerate the neural irritation and required conversion to an open procedure. During the surgery, no dura tears, cauda equina syndrome, or infections were observed. 5 patients experienced transient dysesthesia located at the exiting nerve in group A, while no cases complained dysesthesia in group B. 2 cases who suffered temporary motor weakness all belonged to group A. A total of 5 cases obtained a revision surgery after recurrence in the follow-up, in which 3 patients belonged to group A. Compared to the preoperative data, significant improvements in VAS scores of low back pain and sciatica, ODI, and SF-36 PCS and MC were observed in the follow-up, respectively (P < 0.05, respectively). However, no statistical difference was observed at all time-points after surgery between these two groups (P > 0.05, respectively).
Conclusions: For the patients of LDH accompanying with lateral recess stenosis, compared with the routine foraminoplasty at the tip of SAP, our modified foraminoplastic technique does not only change place of foraminoplasty to the base of SAP but also simplified puncture process in transforaminal PELD. Although there was no significant difference in symptom relief, the modified foraminoplasty showed the advantages in decreasing the incidence of postoperative neural dysfunction and reducing operation time.
PMID: 30662915 [PubMed - in process]
c-Jun N-terminal kinase 3 deficiency protects axotomized retinal ganglion cells via affecting mitochondria involved apoptosis pathway.
Int J Ophthalmol. 2019;12(1):30-37
Authors: Wang RR, Li CF, Wang DZ, Zhang CW, Liu GX
AIM: To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases (JNKs) in mouse optic nerve axotomy induced neurotrauma.
METHODS: We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells (RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction (PCR) and Western blotting assay.
RESULTS: We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomy induced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1 (TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression.
CONCLUSION: It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.
PMID: 30662837 [PubMed]
Metabolic profile analysis of free amino acids in experimental autoimmune uveoretinitis rat plasma.
Int J Ophthalmol. 2019;12(1):16-24
Authors: Guo JG, Guo XM, Wang XR, Tian JZ, Bi HS
AIM: To determine the differences of amino acid (AA) levels in experimental autoimmune uveoretinitis (EAU).
METHODS: AA analysis of the plasma samples in EAU rats induced by interphotoreceptor retinoid-binding protein emulsion were performed with high performance liquid chromatography (HPLC) and phenylisothiocyanate (PITC) pre-column derivation methods were performed. Using partial least squares discriminant analysis (PLS-DA), the potential biomarkers were identified in EAU rat plasma, and the metabolic pathways related to EAU were further analyzed.
RESULTS: The method results showed that linear (r≥0.9957), intra-day reproducible [relative standard deviation (RSD)=0.04%-1.33%], inter-day reproducible (RSD=0.06%-2.07%), repeatability (RSD=0.03%-0.89%), stability (RSD=0.05%-2.48%) and recovery (RSD=1.98%-4.39%), with detection limits of 0.853-11.4 ng/mL. The metabolic profile in EAU rats was different from that in the control groups five AAs concentrations were increased and nine AAs were reduced. Moreover, five metabolic pathways were related to the development of EAU.
CONCLUSION: The developed method is a simple, rapid and convenient for determination of AAs in EAU rat plasma, and these findings will provide a comprehensive insight on the metabolic profiling of the pathological changes in EAU.
PMID: 30662835 [PubMed]
Pharmacokinetics of Eight Flavonoids in Rats Assayed by UPLC-MS/MS after Oral Administration of Drynariae rhizoma Extract.
J Anal Methods Chem. 2018;2018:4789196
Authors: Xu ZL, Xu MY, Wang HT, Xu QX, Liu MY, Jia CP, Geng F, Zhang N
As a traditional Chinese medicine, Drynariae rhizoma (Kunze ex Mett.) J. Sm. has been used to treat osteoporosis and bone resorption for 2500 years. Based on the previous study and literature references, flavonoids were proved to be the most abundant and main active compounds of Drynariae rhizoma for osteoporosis treatment. In order to make good and rational use of Drynariae rhizoma in future, a rapid, sensitive, and selective ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics of eight main flavonoids in rat plasma after oral administration of the Drynariae rhizoma extract, including neoeriocitrin, luteolin-7-O-β-D-glucoside, astragalin, naringin, eriodictyol, luteolin, naringenin, and kaempferol. Plasma samples' pretreatment involved a solid-phase extraction column. The separation was performed on an ACQUITY UPLCTM BEH C18 column with a gradient mobile-phase system of acetonitrile and 1% acetic acid in water. The detection was performed using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface (ESI) by multiple reaction monitoring (MRM) in the positive ion mode. All calibration curves exhibited good linearity (r 2 > 0.9990) over the measured ranges. The intraday and interday precisions (RSD) were within 13.87%, and the accuracy (RE) ranged from -14.57% to -0.25% at three quality control levels. Extraction recovery, matrix effect, and stability were satisfactory. The pharmacokinetic characteristics of the eight flavonoids of interest were clearly elucidated.
PMID: 30662789 [PubMed]
Interaction between BMSCs and EPCs promotes IUA angiogenesis via modulating PI3K/Akt/Cox2 axis.
Am J Transl Res. 2018;10(12):4280-4289
Authors: Yu J, Jiang L, Gao Y, Sun Q, Liu B, Hu Y, Han X
Intrauterine adhesion (IUA) is a common disease among women after uterus operation. BMSCs are commonly used as a therapeutic agent for IUA treatment, but the underlying mechanism is not fully delineated. Here we showed that BMSCs co-cultured with EPCs promotes proliferative ability and decreases apoptosis ratio of BMSCs and EPCs. In addition, BMSCs promote the differentiation of EPCs into vascular endothelial cells, and BMSCs derived epithelial cells are also induced by EPCs. We also found that the levels of Collagen Type I, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony stimulating factor (GM-CSF) and bone morphogenetic protein (BMP-2) are significantly increased in the co-culturing system comparing to those of the BMSCs or EPCs alone group. Of note, PI3K/Akt/Cox2 axis is activated in the co-culturing system and LY294002 abrogates the co-culturing system's effects on cell proliferation, apoptosis and cytokines secretion, which are reversed by synergistically overexpressing Cox2. In conclusion, our in vitro experiments proved that the interaction of BMSCs and EPCs might promote angiogenesis and alleviate IUA pathogenesis by regulating PI3K/Akt/Cox2 axis mediated modulation of cell apoptosis, proliferation, differentiation and angiogenesis-associated cytokines secretion.
PMID: 30662670 [PubMed]
eIF5A2 regulates the resistance of gastric cancer cells to cisplatin via induction of EMT.
Am J Transl Res. 2018;10(12):4269-4279
Authors: Sun J, Xu Z, Lv H, Wang Y, Wang L, Ni Y, Wang X, Hu C, Chen S, Teng F, Chen W, Cheng X
Cisplatin is the first-line chemotherapy drug for gastric cancer (GC), but treatment failure often occurs due to development of resistance. The mechanism of cisplatin resistance remains a mystery. Eukaryotic translation initiation factor 5A2 (eIF5A2) is an important tumor-promoting factor and has been rarely studied in GC. This study aimed to investigate the role of eIF5A2 in cisplatin resistance of GC cells and its relationship with epithelial-mesenchymal transition (EMT). We found that it is negative correlation between cisplatin resistance and eIF5A2's expression in GC cells. Silencing of eIF5A2 enhanced the sensitivity of GC cells to cisplatin, while overexpression of eIF5A2 decreased sensitivity. Cisplatin treatment induced gene expression changes consistent with EMT. EMT was blocked and the sensitivity of GC cells to cisplatin was increased by inhibiting the expression of Twist, indicating that EMT regulates the sensitivity of GC cells to cisplatin. Knockdown of eIF5A2 was associated with upregulation of the epithelial markers E-cadherin and β-catenin, while the expression of mesenchymal markers vimentin and N-cadherin decreased, indicating that eIF5A2 can reverse the EMT process and block the effect of cisplatin on EMT-related markers. Knockdown or overexpression of eIF5A2 did not affect the sensitivity of gastric cancer cells to cisplatin by Twist siRNA. Altogether, these data suggest that eIF5A2 regulates the resistance of gastric cancer cells to cisplatin by mediating EMT, and support the conclusion that eIF5A2 may be a molecular target for anti-tumor therapy.
PMID: 30662669 [PubMed]
Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-κB and NLRP3 inflammasome.
Am J Transl Res. 2018;10(12):4235-4246
Authors: Du Y, Gu X, Meng H, Aa N, Liu S, Peng C, Ge Y, Yang Z
Muscone is the main active monomer of traditional Chinese medicine musk. Previous studies have reported a variety of beneficial effects of muscone. However, the effects of muscone on chronic inflammation after myocardial infarction (MI) are rarely reported. This study evaluated the anti-inflammatory effects of muscone on myocardial infarction by establishing a MI model in mice. We found that muscone remarkably decreased the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), and ultimately improved cardiac function and survival rate. Furthermore, the main anti-inflammatory effect of muscone was alleviating cardiac macrophage-mediated inflammatory response in heart tissues after MI. Bone marrow-derived macrophages (BMDMs) induced with lipopolysaccharide (LPS) were used as an in vitro inflammation model to further clarify anti-inflammatory mechanisms of muscone. Muscone significantly downregulated the levels of LPS-induced inflammatory cytokines and inhibited NF-κB and NLRP3 inflammasome activation in BMDMs. Moreover, ROS and antioxidant indices in LPS-induced BMDMs were also ameliorated after muscone treatment. To sum up, our study found that muscone alleviated cardiac macrophage-mediated chronic inflammation by inhibiting NF-κB and NLRP3 inflammasome activation, thereby improving cardiac function in MI mice. Besides, the inhibitory effect of muscone on inflammation may be related to the scavenging of ROS. It is suggested that muscone may serve as a promising and effective drug for post-MI treatment.
PMID: 30662666 [PubMed]
AMPK-related kinase 5 (ARK5) enhances gemcitabine resistance in pancreatic carcinoma by inducing epithelial-mesenchymal transition.
Am J Transl Res. 2018;10(12):4095-4106
Authors: Wang X, Song Z, Chen F, Yang X, Wu B, Xie S, Zheng X, Cai Y, Chen W, Zhong Z
AMPK-related kinase 5 (ARK5) is a member of the human AMP-activated protein kinase (AMPK) family, which is associated with increased tumor survival and drug resistance in many cancers. However, the function of ARK5 in pancreatic carcinoma (PC) is unclear. Our study investigated the role of ARK5 in the chemo-resistance of PC and its underlying mechanism. PC cell lines that displayed high expression levels of ARK5 had low sensitivity to gemcitabine (GEM). Suppression of ARK5 increased sensitivity to GEM in PC cell lines. Western blotting and immunofluorescence showed that suppression of ARK5 upregulated expression of E-cadherin and downregulated vimentin expression. Suppression of ARK5 also inhibited the epithelial-mesenchymal transition (EMT) efficiency associated with GEM in PC cell lines and upregulation of ARK5 expression enhanced GEM resistance in PC cell lines by inducing Twist-mediated EMT. In addition, we found that suppression of ARK5 increased GEM sensitivity in PC cell lines under hypoxic conditions. ARK5 increases GEM resistance in PC cell lines via EMT, and suppression of ARK5 increases sensitivity to GEM under both normoxic and hypoxic conditions.
PMID: 30662653 [PubMed]
2-Methoxyestradiol improves the apoptosis level in keloid fibroblasts through caspase-dependent mechanisms in vitro.
Am J Transl Res. 2018;10(12):4017-4029
Authors: Zhang MZ, Liu YF, Ding N, Zhao PX, Zhang X, Liu MY, Adzavon YM, Huang JN, Long X, Wang XJ, Wang YB, Qi Z
Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Fibroblasts are the main cellular ingredients in keloid tissue, which has a relatively low apoptosis level. A natural metabolite of estradiol, 2-Methoxyestradiol (2ME2) exerts a pro-apoptotic effect on tumor cells. In this study, the expression levels of key factors in the apoptosis pathway and the expression level of the proliferating cell nuclear antigen (PCNA) were measured to assess the levels of apoptosis and proliferation in both normal skin fibroblasts and keloid fibroblasts. Twelve samples were obtained from 12 patients: 6 keloid patients and 6 non-keloid patients. All 12 of the patients were randomly selected from the Department of Plastic Surgery at Peking Union Medical College Hospital from June 2016 to December 2016. After cell culture, fibroblasts were divided into the following 6 groups: normal skin fibroblasts (S); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (2ME2); keloid fibroblasts treated with DMSO (DMSO); keloid fibroblasts treated with the caspase inhibitor Ac-DEVD-CHO (IN); and keloid fibroblasts treated with both Ac-DEVD-CHO and 2ME2 (IN+2ME2). Fibroblasts at up to passage 3 were used for analysis. Cell activity was measured by the cell counting kit-8. TUNEL staining was used to observe the cell apoptotic morphology. The key apoptosis factors (caspase-3, caspase-8, caspase-9, Bcl-2, Bax, and cytochrome-c) and PCNA expression levels were detected by immunofluorescence analysis and Western blotting. A certain concentration of 2ME2 was also used in group S to evaluate the toxicity. Compared with that in the other groups, 2ME2 significantly inhibited cell activity and led to apoptotic appearance of fibroblasts. In protein analysis, 2ME2 remarkably increased the expression of apoptosis factors and decreased the PCNA expression. Apoptosis levels were reduced by both the caspase inhibitor and 2ME2; thus indicating that the pro-apoptosis effect of 2ME2 was achieved through a caspase-dependent mechanism in keloid fibroblasts. Toxicity assessment showed that 2ME2 had a very low influence on normal skin fibroblasts. 2ME2, considered to be a new promising type of chemotherapy drug, exerts a pro-apoptosis effect by regulating the caspase family and an anti-proliferation effect towards keloid fibroblasts, and it presents low toxicity towards normal fibroblasts in vitro.
PMID: 30662647 [PubMed]
SQYZ granules, a traditional Chinese herbal, attenuate cognitive deficits in AD transgenic mice by modulating on multiple pathogenesis processes.
Am J Transl Res. 2018;10(11):3857-3875
Authors: An H, Wei D, Qian Y, Li N, Wang X
The pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide aggregation, inflammation, oxidative stress, and others. Effective therapeutic drugs for treating AD are urgently needed. SQYZ granules (SQYZ), a Chinese herbal preparation, are mainly composed of the ginsenoside Rg1, astragaloside A and baicalin, and have been widely used to treat dementias for decades in China. In this study, we found the therapeutic effects of SQYZ on the cognitive impairments in an AD mouse model, the β-amyloid precursor protein (APP) and presenilin-1 (PS1) double-transgenic mouse, which co-expresses five familial AD mutations (5XFAD); next, we further explored the underlying mechanism and observed that after SQYZ treatment, the Aβ burden and inflammatory reactions in the brain were significantly attenuated. Through a proteomic approach, we found that SQYZ regulated the expression of 27 proteins, mainly those related to neuroinflammation, stress responses and energy metabolism. These results suggested that SQYZ has the ability to improve the cognitive impairment and ameliorate the neural pathological changes in AD, and the therapeutic mechanism may be related to the modulation of multiple processes related to AD pathogenesis, especially anti-neuroinflammation, promotion of stress recovery and improvement of energy metabolism.
PMID: 30662636 [PubMed]
Diwu Yanggan capsule inhibits the occurrence and development of liver cancer in the Solt-Farber rat model by regulating the Ras/Raf/Mek/Erk signaling pathway.
Am J Transl Res. 2018;10(11):3797-3805
Authors: Ye Z, Gao X, Zhao B, Li H, Wan M, Wu N, Chang M, Cheng S
This study sought to determine the effect and explore the mechanism of the Chinese medicinal compound preparation Diwu Yanggan (DWYG) capsule on the occurrence and development of liver cancer using the Solt-Farber rat model. Sprague-Dawley rats were randomly distributed into a normal group, sham group, DWYG group, sorafenib group, and model group. The DWYG group and sorafenib group were given DWYG capsule and sorafenib tablet, respectively, with induction of the model. Hematoxylin-eosin (HE) staining was used to detect liver pathological changes. The content of nuclear DNA in the liver was detected by Feulgen staining, and the expression of PCNA was detected by immunohistochemical staining. Molecular biology methods were used to detect the expression of liver regeneration-related factors and Ras/Raf/Mek/Erk signaling pathway-related proteins and mRNAs. HE staining showed that compared with those in the model group, the liver pathological changes in the DWYG group were significantly reduced (P < 0.05). The nuclear DNA content in the liver based on Feulgen staining and the expression of PCNA in the DWYG group was lower than that in the model group (P < 0.05). The expression of regeneration-related factors and Ras/Raf/Mek/Erk signaling pathway-related proteins and mRNAs was significantly lower in the DWYG group than in the model group (P < 0.05). In conclusion, DWYG capsules to some degree inhibit the occurrence and development of liver cancer in the Solt-Farber rat model, and the effect is not inferior to that of sorafenib. DWYG capsules likely delay the occurrence and development of liver cancer and improve the liver regeneration microenvironment by regulating the Ras/Raf/Mek/Erk signaling pathway and regeneration-related factors.
PMID: 30662630 [PubMed]
Rosiglitazone affects lumen formation in MDCKII cell through regulating apico-basal polarity.
Am J Transl Res. 2018;10(11):3579-3589
Authors: Cheng Y, Ye CY, Mao ZG, Wang Y, Chen ZJ, Cong WL
This study aimed to investigate the potential mechanisms underlying the effects of Rosiglitazone on the apico-basal polarity in renal epithelial cells. 3D-MDCK model was used to study the lumen formation and localization of polarity proteins at the early stage of the establishment of the apico-basal polarity. The calcium switch model, immunofluorescence staining and measurement of transmembrane electrical impedance are employed to investigate the epithelial apico-basal polarity including the development and maintenance of apical domains and the formation of tight junction. MDCKII cells were cultured with 20 uM rosiglitazone or DMSO. Results showed Rosiglitazone reduced the percentage of single central lumen cysts, but the percentage of multiple lumen cysts increased. At the early stage of MDCKII cysts (2-5 cells), Rosiglitazone induced mislocalization of apical and basolateral membrane proteins. In the repolarization process of MDCKII cell induced by a calcium switch (CS), Rosiglitazone delayed the apical membrane domain development in the early phase of cell polarization; while during the maintenance phase of cell polarity, the apical domain retention was significantly affected by Rosiglitazone. Rosiglitazone significantly delayed the formation of tight junctions (TJs); 24 h after CS, however, there were no apparent differences between control group and Rosiglitazone group; the development of transepithelial electrical resistance (TER) was significantly disturbed in Rosiglitazone group. This study shows Rosiglitazone may affect the development and maintenance of apical domains and the formation of TJs disturbs apical protein delivery to the plasma membrane, eventually leading to the abnormal apico-basal polarity, which affects lumen formation in MDCKII cells.
PMID: 30662609 [PubMed]
CD44 Assists the Topical Anti-Psoriatic Efficacy of Curcumin-Loaded Hyaluronan-Modified Ethosomes: A New Strategy for Clustering Drug in Inflammatory Skin.
Authors: Zhang Y, Xia Q, Li Y, He Z, Li Z, Guo T, Wu Z, Feng N
Background: Psoriasis is a common chronic inflammatory skin disease. Its treatment is challenged by the limited amount of drug reaching the inflamed skin. The overexpressed CD44 protein in inflamed psoriatic skin can serve as a potential target of novel active-targeting nanocarriers to increase drug accumulation in the skin. Methods: Hyaluronic acid (HA) was linked to propylene glycol-based ethosomes by covalent binding to develop a novel topical drug delivery carrier (HA-ES) for curcumin. An imiquimod-induced psoriasis mouse model was established, and curcumin delivery and anti-psoriatic efficacy using HA-ES were compared with those using plain ethosomes (ES). Results: The HA gel network formed on the surface of HA-ES reduced the leakage and release of poorly water-soluble curcumin. Compared with ES, transdermal curcumin delivery was significantly enhanced by using HA-ES as vehicles; the cumulative transdermal amount and the amount retained in the skin in vitro after 8 h were, respectively, 1.6 and 1.4 times those observed with ES, as well as 3.1 and 3.3 times those observed with a curcumin propylene glycol solution (PGS), respectively. The in vivo psoriatic skin retention of curcumin with HA-ES was 2.3 and 4.0 times that of ES and PGS, respectively. CD44 expression in imiquimod-induced psoriasis-like inflamed skin was 2.7 times that in normal skin. Immunostaining revealed similar results, suggesting that the specific adhesion of HA-ES to CD44 increased drug accumulation in the skin. After topical administration to mice, the HA-ES group showed an alleviation of inflammation symptoms; lower TNF-α, IL-17A, IL-17F, IL-22, and IL-1β mRNA levels; and lower CCR6 protein expression compared to the ES and PGS groups. Conclusion: We demonstrated increased topical drug delivery of curcumin to inflamed tissues using HA-ES targeting the highly expressed CD44 protein. This innovative strategy could be applied for the development of topical drug delivery systems targeting inflamed skin.
PMID: 30662553 [PubMed - in process]
The Prophylactic and Therapeutic Effects of Fermented Cordyceps sinensis Powder, Cs-C-Q80, on Subcortical Ischemic Vascular Dementia in Mice.
Evid Based Complement Alternat Med. 2018;2018:4362715
Authors: Chen Y, Fu L, Han M, Jin M, Wu J, Tan L, Chen Z, Zhang X
Corbrin Capsule, a preparation of Cordyceps sinensis analogue, is a pleiotropic traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The neuroprotective effects of Cs-C-Q80, as a substitution of Cordyceps sinensis, have not been fully identified. The objectives of this study were to explore the prophylactic and therapeutic effects of Cs-C-Q80 in vascular dementia mice model. The efficacy of Cs-C-Q80 was investigated in a molecular level as well. The subcortical ischemic vascular dementia was modelled by permanent right unilateral common carotid arteries occlusion (rUCCAO) in adult male mice. The animals were randomly divided and treated by gavage with vehicle (1% CMC-Na solution) (rUCCAO model) or Cs-C-Q80 powder at 0.2 g/kg or 1.0 g/kg, respectively. Preventive treatment was administrated by gavage daily for 7 days before rUCCAO, while therapeutic treatment was administrated continuously from 28 days after rUCCAO. Object recognition test and Morris water maze test were performed to evaluate the learning and working memory. The luxol fast blue stain (Kluver-Barrera method) and immunohistochemistry for myelin basic protein (MBP) were employed to determine the severity of white matter damage. Both preventive and therapeutic treatment with Cs-C-Q80 protected against the rUCCAO-induced memory impair in mice as determined by object recognition and Morris water maze tests. The histopathological analyses revealed significant white matter rarefaction and reduction of MBP expression in corpus callosum after rUCCAO, which could be counteracted by either preventive or therapeutic treatment with Cs-C-Q80. Moreover, the Cs-C-Q80 treatments inhibited rUCCAO-induced astrocytes activation and the tumor necrosis factor α (TNF-α) and interleukin-1β expression, indicating the anti-inflammatory roles of Cs-C-Q80 against subcortical ischemia. Cs-C-Q80 is a potential preparation for the prophylaxis and treatment of subcortical ischemic vascular dementia. The underlying pharmacological efficacy might be associated with suppression of myelin degeneration, glia activation, and inflammatory cytokines release.
PMID: 30662512 [PubMed]
Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type ginsenosides through Escherichia coli engineered with uridine diphosphate glycosyltransferase genes.
J Ginseng Res. 2019 Jan;43(1):116-124
Authors: Yu L, Chen Y, Shi J, Wang R, Yang Y, Yang L, Zhao S, Wang Z
Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes.
Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes.
Results: E. coli engineered with GT95 syn selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3-OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing p2GT95synK1, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20-OH and C3-OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth.
Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.
PMID: 30662300 [PubMed]
Ginsenoside compound K protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury via inhibition of nuclear factor-κB, p38, and JNK MAPK pathways.
J Ginseng Res. 2019 Jan;43(1):95-104
Authors: Lu S, Luo Y, Zhou P, Yang K, Sun G, Sun X
Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated.
Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (ΔΨm) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting.
Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, NF-κB nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK.
Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the NF-κB, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.
PMID: 30662298 [PubMed]
The effect of Glomus intraradices on the physiological properties of Panax ginseng and on rhizospheric microbial diversity.
J Ginseng Res. 2019 Jan;43(1):77-85
Authors: Tian L, Shi S, Ma L, Zhou X, Luo S, Zhang J, Lu B, Tian C
Background: Glomus intraradices is a species of arbuscular mycorrhizal fungi that, as an obligate endomycorrhiza, can form mutually beneficial associations with plants. Panax ginseng is a popular traditional Chinese medicine; however, problems associated with ginseng planting, such as pesticide residues, reduce the ginseng quality.
Methods: In this experiment, we studied the effect of inoculating G. intraradices on several physiological properties and microbial communities of ginseng. UV-Visible Spectrum method was used to detect physical properties. Denaturing gradient gel electrophoresis method was used to analyze microbial communities.
Results: The results indicated that inoculation with G. intraradices can improve the colonization rate of lateral ginseng roots, increase the levels of monomeric and total ginsenosides, and improve root activity as well as polyphenol oxidase and catalase activities. We also studied the bacterial and fungal communities in ginseng rhizospheric soil. In our study, G. intraradices inoculation improved the abundance and Shannon diversity of bacteria, whereas fungi showed a reciprocal effect. Furthermore, we found that G. intraradices inoculation might increase some beneficial bacterial species and decreased pathogenic fungi in rhizospheric soil of ginseng.
Conclusion: Our results showed that G. intraradices can benefit ginseng planting which may have some instructive and practical significance for planting ginseng in farmland.
PMID: 30662296 [PubMed]
Molecular structure regulation and enzyme cascade signal amplification strategy for upconversion ratiometric luminescent and colorimetric alkaline phosphatase detection.
Anal Chim Acta. 2019 Mar 21;1051:160-168
Authors: Chen H, Zhou Z, Lu Q, Wu C, Liu M, Zhang Y, Yao S
Herein, molecular structure regulation and enzyme cascade signals amplification (MRECAmp) strategy was proposed to construct a novel upconversion ratiometric fluorescence and colorimetric dual-readout assay platform for highly sensitive and selective detection of alkaline phosphatase (ALP) activity. The detection strategy is divided into three aspects. Firstly, Ag+ oxidates o-phenylenediamine (OPD) to 2,3-diaminophennazine (OPDox), which can significantly quench upconversion fluorescence at 487 nm based on inner filter effects (IFE) while the upconversion emission at 668 nm was essentially unchanged for Zn2+-doped NaYF4:Yb3+,Er3+,Tm3+ upconversion nanoparticles (UCNPs) probes under the near-infrared (NIR) irradiation. Secondly, ALP catalyzes the hydrolysis of the substrate l-ascorbic acid 2-phosphate (AAP) to ascorbic acid (AA) which can consume part of Ag+ to inhibit the generation of OPDox and the AA was oxidized to dehydroascorbic acid (DHAA). The specific performance of DHAA molecular structure regulation, due to the condensation reaction between dicarbonyl group of DHAA and diamine group of OPD, that is confirmed by ESI-MS and 1H NMR spectra analysis, can remarkably enhance the selectivity of ALP detection, which is conceptually different from the previously reported ALP fluorescent assays. Thirdly, the generated DHAA reacts with OPD to form 3-(dihydroxyethyl)furo [3,4-b]quinoxaline-1-one (DFQ) that further inhibits the generation of OPDox, which makes the enzyme-controlled cascade signal amplification (ECAmp) can be realized with a great fluorescence recovery (60.04%) at 487 nm. Therefore, the fluorescence response signal ((I487/I668)0/(I487/I668)) is amplified by ECAmp strategy, allowing the quantitative analysis of ALP with a detection limit of 0.03 mU/mL. The detection of ALP activity in human serum samples over the conventional methods demonstrates that the MRECAmp method provides a sensing platform for probing ALP activity and shows promising outlook in biomedical studies.
PMID: 30661613 [PubMed - in process]
Analysis and recognition of characteristics of digitized tongue pictures and tongue coating texture based on fractal theory in traditional Chinese medicine.
Comput Assist Surg (Abingdon). 2019 Jan 21;:1-10
Authors: Zhang J, Qian J, Yang T, Dong HY, Wang RJ
Simple fractal dimensions have been proposed for use in the analysis of the characteristics of digitized tongue pictures and tongue coating texture, which could further the establishment of objectified classification criteria under the conditions of expanding sample size. However, detailed descriptions on simple fractal dimensions have been limited. Therefore, BP (back propagation) neural network model classifiers could be designed by further calculation of the multiple fractal spectrum characteristics of digitized tongue pictures in order to classify and recognize the thin/thick or greasy characteristics of tongue coating. The fractal dimensions of sample data of 587 digitized tongue pictures were collected in a standard environment. A statistical analysis was conducted on the calculation results of the sample data, and the sensitivity of the fractal dimensions to the thin/thick and greasy characteristics of digitized tongue pictures was observed. As the overlap region resulted from a range of values of a single parameter, another 8 characteristic parameters of the multiple fractal spectra of the digitized tongue pictures were further proposed as the elements in the input layer of the three-layers BP neural network. Automatic recognition classifiers were designed and trained for the characteristics of digitized tongue pictures and tongue coating textures. The simple fractal dimension was sensitive to the thin/thick and greasy characteristics of digitized tongue pictures and could better judge the characteristics of the thickness of the tongue coating. A classifier with characteristic parameters of multiple fractal spectra as the input vectors identified by the BP neural network models could effectively increase the accuracy rate judged by the characteristics of the tongue coating texture.
PMID: 30661421 [PubMed - as supplied by publisher]
Chemical composition of Erycibe schmidtii and antiproliferative activity of scopoletin on immature dendritic cells.
Nat Prod Res. 2019 Jan 19;:1-8
Authors: Ren W, Wang Y, He Q, Zhou Y, Li C, Wang W, Leng X, Zeng T, Zou Q, Li L
Immature dendritic cells (iDCs) play very important roles in the pathological process of rheumatoid arthritis (RA). Therefore, it is urgent to search for natural products with antiproliferative activity on iDCs for anti-RA drug discovery. Erycibe schmidtii, a traditional Chinese medicine, has been used to treat RA in China. Its bioactive ingredients on RA are still unclear. In this study, twenty compounds including a new caffeoylquinic acid derivative, 3-O-caffeoyl-4-O-syringoylquinic acid methyl ester (16), were isolated from E. schmidtii. Their structures were elucidated by NMR and mass spectroscopic analysis, and comparison with literature data. Seventeen compounds were obtained from this plant for the first time, and ten were first found from the genus Erycibe. Scopoletin (1, 5.0 μM) functionally reduced proliferation level of bone marrow immature dendritic cells (BM-iDCs) more than 50%, relative to vehicle. However, scopoletin (1) exhibited no effect on the phagocytosis or survival of BM-iDCs in vitro.
PMID: 30661400 [PubMed - as supplied by publisher]
Patient perspectives on adapting meaning-centered psychotherapy in advanced cancer for the Chinese immigrant population.
Support Care Cancer. 2019 Jan 19;:
Authors: Leng J, Lui F, Huang X, Breitbart W, Gany F
The Chinese immigrant community faces multiple obstacles to effective cancer support and psychosocial care post diagnosis. Meaning-centered psychotherapy (MCP) is an empirically based treatment (EBT) that has been found to significantly reduce psychological distress while increasing spiritual well-being and a sense of meaning and purpose in life in patients with advanced cancer. However, it has not yet been adapted for Chinese immigrants who have unique linguistic and cultural needs. This study presents a community needs assessment to inform the cultural adaptation of MCP for Chinese patients with advanced cancer using Bernal et al.'s ecological validity model and the cultural adaptation process model of Domenech-Rodriquez and Weiling. Interviews were conducted until saturation with 12 Chinese immigrants with advanced cancer to determine the community's needs and preferences regarding the MCP intervention. Transcripts were translated and analyzed using Atlas.ti and six frequently occurring themes were identified: Coping; End of Life; Family; Culture, Religion, and Language; Immigration; and Specific Adaptations to MCP. Sociocultural values, beliefs, and practices such as filial piety and the use of Traditional Chinese Medicine (TCM) should be considered when adapting EBTs for Chinese immigrant cancer patients.
PMID: 30661201 [PubMed - as supplied by publisher]
Review: the Roles and Mechanisms of Glycoprotein 130 Cytokines in the Regulation of Adipocyte Biological Function.
Inflammation. 2019 Jan 19;:
Authors: Ma D, Wang Y, Zhou G, Wang Y, Li X
Chronic low-grade inflammation is now widely accepted as one of the most important contributors to metabolic disorders. Glycoprotein 130 (gp130) cytokines are involved in the regulation of metabolic activity. Studies have shown that several gp130 cytokines, such as interleukin-6 (IL-6), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1), have divergent effects on adipogenesis, lipolysis, and insulin sensitivity as well as food intake. In this review, we will summarize the present knowledge about gp130 cytokines, including IL-6, LIF, CNTF, CT-1, and OSM, in adipocyte biology and metabolic activities in conditions such as obesity, cachexia, and type 2 diabetes. It is valuable to explore the diverse actions of these gp130 cytokines on the regulation of the biological functions of adipocytes, which will provide potential therapeutic targets for the treatment of obesity and cachexia.
PMID: 30661143 [PubMed - as supplied by publisher]
Biosynthesis of gold nanoparticles using Caffeoylxanthiazonoside, chemical isolated from Xanthium strumarium L. fruit and their Anti-allergic rhinitis effect- a traditional Chinese medicine.
J Photochem Photobiol B. 2019 Jan 04;192:13-18
Authors: Peng Q, Chen R
This study significantly aims to analyze the effect of CFX coated gold nanoparticles on the allergic rhinitis in mouse model. Female BALB/C mice were intraperitoneally injected with ovalbumin and aluminum hydroxide in order to sensitize on 0th, 7th, 14th, and 21st day. Nano‑gold was also nasally inoculated earlier to the intranasal administration of OVA. The acuteness of allergic rhinitis was evaluated based on the nasal indications, interleukin IL-4, and interferon (INF)-γ levels present in the NLF of mice. Also, Hematoxylin-eosin as well as Schiff-periodic acid stain assays were carried out to briefly investigate the histological modifications in the sensitized mice. Nano‑gold reduced the incidence of nasal symptoms as well as minimized the IL-4 production, no impact was showed over the levels of INF-γ. Further, the extent of inflammatory cell intrusion was also influenced by the CFX/AuNPs. These experimental findings manifested that AuNPs may considerably inhibit the allergic inflammation in mice models and may be expected to serve as anti-allergic rhinitis agents.
PMID: 30660926 [PubMed - as supplied by publisher]
The cardioprotective properties and the involved mechanisms of NaoXinTong Capsule.
Pharmacol Res. 2019 Jan 17;:
Authors: Han J, Tan H, Duan Y, Chen Y, Zhu Y, Zahao B, Wang Y, Yang X
NaoXinTong Capsule (NXT), a prescribed traditional Chinese medicine, is made up of 16 natural herbal materials with more than 200 identified bioactive compounds. Multiple protective effects of NXT on cardiovascular diseases including atherosclerosis, coronary artery disease, acute coronary syndrome, coronary microembolization, myocardial infarction, ischemic stroke and ischemia-reperfusion injury, have been reported by both clinical and basic studies. Biologically, these cardioprotective effects can be correlated to the actions of NXT on inflammation, apoptosis, oxidative stress, neovascularization, insulin sensitivity and lipid/glucose metabolism. NXT alone or in combination with the conventional interventions has been demonstrated potent therapeutic effects on cardiovascular diseases without causing significant adverse events, like the major bleeding. Compared with the conventional drugs, patients have a good tolerance and little resistance to NXT treatment. With the data and evidence reported from lab benches to clinical beds, we will update the cardioprotective properties of NXT and the involved mechanisms in this review. We hope the information provided in this review can help readers to better understand the insights for the long practice of this traditional Chinese medicine, and offer fresh perspectives.
PMID: 30660824 [PubMed - as supplied by publisher]
Traditional Chinese medicine Ze-Qi-Tang formula inhibit growth of non-small-cell lung cancer cells through the p53 pathway.
J Ethnopharmacol. 2019 Jan 17;:
Authors: Xu Z, Zhang F, Zhu Y, Liu F, Chen X, Wei L, Zhang N, Zhou Q, Zhong H, Yao C, Zhu X, Gong C, Zhu S, Zou C
ETHNOPHARMACOLOGICAL RELEVANCE: Ze-Qi-Tang (ZQT), a classic Chinese herbal formula, has been for over thousand years used for the treatment of several respiratory ailments like cough, asthma, hydrothorax and lung cancer.
AIM OF STUDY: Cumulative literature on ZQT herbal formula reveals that its several constituent components are potent inducer of apoptosis in different cancer cells. However, the activity of ZQT against non-small-cell-lung cancer (NSCLC) has not been previously examined.The aim of the study is to investigate the molecular mechanism of ZQT on NSCLC cells.
MATERIALS AND METHODS: Cell growth were determined by CCK-8 and colony formation assay. Induction of cellular apoptosis or arrest of cell cycle were determined by flow cytometric analysis using annexin V/ propidium iodide, Hoechst 33342 or TUNEL staining method. In some assay p53 activity of NSCLC ( A549 and H460) cells were blocked with pifithrin-a, prior to treatment with ZQT. The level of expression of cell cycle and apoptosis related marker proteins were estimated by western blot. The anticancer activity of ZQT in vivo were monitored in nude mice that were induced with tumor by subcutaneous inoculation of A549 cells and then treated by ZQT(100mg/kg,200mg/kg,400mg/kg) gavaging for 30 days. Mice' body weight and tumor volume were measured weekly. The survival carve was recorded. Apoptosis from mice' tissue was observed by TUNEL assay. Pathological histology of liver, kidney and heart were detected by H&E staining, and its functions were tested by ELISA.
RESULTS: Dose- and time-dependent inhibition of proliferation of NSCLC ( A549 and H460) cells by ZQT therapy along with induction of cell cycle arrest at G0⁄G1 phase were observed. The arrest of cell cycle arrest and inhibition of cellular proliferation were associated with up regulation of p53 along with down regulation of Cyclin B1 and Cdk2 indicating a mitochondrial related induction of apoptosis with ZQT. A reversal of ZQT-induced apoptosis and G0⁄G1 arrest was observed with pifithrin-a pretreatment. ZQT was also found to suppress the progression of tumor growth in mouse xenograft models and prolong survival. In addition, no hepato- or nephro- or cardio-toxicity with ZQT treatment were detected in mice.
CONCLUSION: These findings suggest that the ZQT formula inhibits the growth of NSCLC cells and is a potential agent of complementary and alternative treatment for lung cancer.
PMID: 30660711 [PubMed - as supplied by publisher]
Melosuavine I, an apoptosis-inducing bisindole alkaloid from Melodinus suaveolens.
Fitoterapia. 2019 Jan 17;:
Authors: Fang ZY, Ren YD, Du SY, Zhang M, Wang YS, Fang L, Zhang H
A new bisindole alkaloid, melosuavine I (1) possessing an aspidosperma- aspidosperma dimeric skeleton, was isolated from the leaves of Melodinus suaveolens. The structure with absolute configuration of 1 was elucidated by a combination of MS, NMR and computational methods. MTT assays indicated that 1 exhibited significant cytotoxicity on human breast cancer BT549 cells with an IC50 value of 0.89 μM. Further study showed that 1 inhibited BT549 cell proliferation by inducing apoptosis through activation of caspase 3 and p53, and down-regulation of Bcl-2.
PMID: 30660654 [PubMed - as supplied by publisher]
Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model.
Clin Immunol. 2019 Jan 17;:
Authors: Wang J, Sui RX, Miao Q, Wang Q, Song LJ, Yu JZ, Li YH, Xiao BG, Ma CG
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system characterized by oligodendrocyte loss and progressive neurodegeneration. The cuprizone (CPZ)-induced demyelination is widely used to investigate the demyelination/remyelination. Here, we explored the therapeutic effects of Hydroxyfasudil (HF), an active metabolite of Fasudil, in CPZ model. HF improved behavioral abnormality and reduced myelin damage in the corpus callosum. Splenic atrophy and myelin oligodendrocyte glycoprotein (MOG) antibody were observed in CPZ model, which were partially restored and obviously inhibited by HF, therefore reducing pathogenic binding of MOG antibody to oligodendrocytes. HF inhibited the percentages of CD4+IL-17+ T cells from splenocytes and infiltration of CD4+ T cells and CD68+ macrophages in the brain. HF also declined microglia-mediated neuroinflammation, and promoted the production of astrocyte-derived brain derived neurotrophic factor (BDNF) and regeneration of NG2+ oligodendrocyte precursor cells. These results provide potent evidence for the therapeutic effects of HF in CPZ-induced demyelination.
PMID: 30660624 [PubMed - as supplied by publisher]
SIRT6 protects retinal ganglion cells against hydrogen peroxide-induced apoptosis and oxidative stress by promoting Nrf2/ARE signaling via inhibition of Bach1.
Chem Biol Interact. 2019 Jan 17;:
Authors: Yu J, Sun W, Song Y, Liu J, Xue F, Gong K, Yang X, Kang Q
Oxidative stress-induced damage of retinal ganglion cells (RGCs) is a major contributor to retinal degenerative diseases, such as glaucoma. Sirtuin 6 (SIRT6) has emerged as a cytoprotective protein against various insults. However, whether SIRT6 exerts a protective effect against oxidative stress-damaged RGCs remains unknown. In this study, we aimed to investigate the potential role and regulatory mechanism of SIRT6 in hydrogen peroxide (H2O2)-induced oxidative damage of RGCs in vitro. We found that SIRT6 expression was significantly downregulated in RGCs with H2O2 treatment. Functional experiments showed that overexpression of SIRT6 improved survival and reduced apoptosis and the production of reactive oxygen species (ROS) in H2O2-treated RGCs. In contrast, SIRT6 knockdown had the opposite effect. Moreover, we found that SIRT6 overexpression promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the activity of antioxidant response element (ARE). In addition, we found that the promotional effect of SIRT6 on Nrf2/ARE signaling was associated with inhibition of BTB and CNC homology 1 (Bach1), an inhibitor of Nrf2. However, overexpression of Bach1 or inhibition of Nrf2/ARE signaling partially reversed the SIRT6-mediated protective effect. Taken together, these results demonstrate that SIRT6 protects RGCs from oxidative stress-induced damage by promoting the activation of Nrf2/ARE signaling via inhibition of Bach1, suggesting a potential role of SIRT6 in retinal degenerative diseases.
PMID: 30660577 [PubMed - as supplied by publisher]
Preparation of titanium ion functionalized polydopamine coated ferroferric oxide core-shell magnetic particles for selective extraction of nucleotides from Cordyceps and Lentinus edodes.
J Chromatogr A. 2019 Jan 11;:
Authors: Zhou DD, Zhang H, Zhang Q, Qian ZM, Li WJ, Li CH, Yang FQ, Chen H
In this study, a titanium ion (Ti4+) functionalized polydopamine coated ferroferric oxide ([email protected]@Ti4+) core-shell magnetic particle was prepared for the selective extraction of nucleotides. Firstly, different metal ions including Ti4+, Zr4+, Fe3+, Al3+, Cu2+, Zn2+, Ni2+ and Mg2+ were respectively immobilized onto [email protected] particles and their extraction efficiency for five nucleotides [cytidine-5'-monophosphate (CMP), uridine-5'-monophosphate (UMP), guanosine-5'-monophosphate (GMP), thymidine-5'-monophosphate (TMP) and adenosine-5'-monophosphate (AMP)] were compared. Among these prepared materials, [email protected]@Ti4+, which exhibited the highest extraction efficiency for nucleotides, was further characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy. After being optimized of the extraction parameters including adsorbent amounts, extraction time, extraction temperature, type and concentration of the eluent, the prepared [email protected]@Ti4+ magnetic particles were successfully applied for the selective extraction and determination of CMP, UMP, GMP, TMP and AMP in Cordyceps and Lentinus edodes. Good linearity (varying from 0.063 to 19.000 μg/mL, R2 > 0.999) and low limit of detection (LODs) (ranging between 0.0047 and 0.0141 μg/mL) for target analytes were achieved. These results demonstrated that the synthesized material in this study had potential for selective extraction of phosphorylated small molecular compounds in complicated matrix.
PMID: 30660442 [PubMed - as supplied by publisher]
Isolation of blue-green eggshell pigmentation-related genes from Putian duck through RNA-seq.
BMC Genomics. 2019 Jan 19;20(1):66
Authors: Bai DP, Lin XY, Wu Y, Zhou SY, Huang ZB, Huang YF, Li A, Huang XH
BACKGROUND: The diversity of avian eggshell colour plays important biological roles in ensuring successful reproduction. Eggshell colour is also an important trait in poultry, but the mechanisms underlying it are poorly understood in ducks. This study aimed to provide insights into the mechanism of blue-green eggshell colour generation.
RESULTS: Here, white-shelled ducks (HBR) and blue-green-shelled ducks (HQR) were selected from Putian black ducks, and white-shelled ducks (BBR) were selected from Putian white ducks. Transcriptional changes in the shell gland were analysed using RNA-sequencing on the Illumina HiSeq 2500. Twenty-seven individual cDNA libraries were sequenced and generated an average of 7.35 million reads per library; 70.6% were mapped to the duck reference genome, yielding an average of 13,794 genes detected, which accounted for approximately 86.39% of all 15,967 annotated duck genes. A total of 899 differentially expressed genes (DEGs) were detected between the HQR and BBR groups, and 373 DEGs were detected between the HQR and HBR groups. We analysed the DEGs in the HQR-vs-BBR and HQR-vs-HBR comparisons. None of these DEGs were directly involved in the eggshell pigmentation process in HQR-vs-HBR, while UDP-glucuronosyltransferase 2A2 (UGT2A2) and UDP-glucuronosyltransferase 1-1-like (UGT1-1-like), which participate in biliverdin breakdown, were two of the DEGs in HQR-vs-BBR. In the RT-qPCR results, delta-aminolevulinic acid synthase 1 (ALAS1) and EPRS glutamyl-prolyl-tRNA synthetase were significantly upregulated in the HBR group compared with the HQR and BBR groups (P < 0.05). Haem oxygenase (HMOX1) was significantly downregulated in BBR compared with HQR and HBR (P < 0.05). Biliverdin reductase A (BLVRA), GUSB glucuronidase beta, cytochrome c-type haem lyase, protohaem IX farnesyltransferase and UGT2A2 were significantly upregulated in HBR and BBR compared with HQR (P < 0.05).
CONCLUSIONS: We conducted a comparative transcriptome analysis of the shell glands of Putian white ducks and Putian black ducks. None of the differentially regulated pathways were directly involved in the eggshell pigmentation process in the HQR-vs-HBR comparison, while 2 DEGs related to biliverdin breakdown were found in HQR-vs-BBR. Based on the RT-qPCR results, we can speculate that both HQR and HBR can produce biliverdin, but HBR cannot accumulate it. Compared with HQR, BBR produced less biliverdin and did not accumulate it.
PMID: 30660177 [PubMed - in process]
The safety and efficacy of acupuncture for erectile dysfunction: A network meta-analysis.
Medicine (Baltimore). 2019 Jan;98(2):e14089
Authors: Wang J, Zhou Y, Dai H, Bao B, Dang J, Li X, Wang B, Li H
BACKGROUND: Erectile dysfunction is a common male disease, the constant pace of life, increasing pressure on life, and changes in diet, living environment, lifestyle, etc., lead to an increase in the number of patients with erectile dysfunction (ED). Acupuncture has been widely used in clinical trials of ED in recent years. There are many clinical trials that confirm that acupuncture can improve male erectile function. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on ED.
METHODS: We will search for PubMed, Cochrane Library, AMED, EMBASE, WorldSciNet; Nature, Science online and China Journal Full-text Database (China National Knowledge Infrastructure), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform an NMA to synthesize direct and indirect evidence.
PMID: 30633219 [PubMed - indexed for MEDLINE]
Acupuncture for perimenopausal depression: A protocol for a systematic review and meta-analysis.
Medicine (Baltimore). 2019 Jan;98(2):e14073
Authors: Xiao X, Zhang J, Jin Y, Wang Y, Zhang Q
BACKGROUND: Depression is one of common disease in the female perimenopausal period. It deprives women of their right to work and live normally, and even destroys the happiness of their families. Acupuncture is a promising treatment for perimenopausal depression.
METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Internet (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and on-line trial registries such as ClinicalTrials.gov (ClinicalTrials.gov/), European Medicines Agency (EMA)(www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp) will be searched from establishment of the database until Oct. 2018. There are no restrictions on the language of publication. The randomized controlled trials of acupuncture (electroacupuncture and manual acupuncture) for perimenopausal depression will be included, and all articles will be screened and collected by 2 reviewers independently. Revman 5.3.5 software will be used for meta-analysis. The specific process will refer to the Cochrane Handbook for Systematic Review.
RESULTS: The efficacy and safety of acupuncture for perimenopausal depression will be comprehensively assessed from the outcomes, including the effective rate, HAMD score, estrogen level and incidence of adverse events.
CONCLUSION: This systematic review will provide evidence for whether acupuncture can improve perimenopausal depression.
ETHICS AND DISSEMINATION: There is no requirement of ethical approval, and the review will be reported in a peer-reviewed journal.
PMID: 30633212 [PubMed - indexed for MEDLINE]
Coreopsis tinctoria Nutt ameliorates high glucose-induced renal fibrosis and inflammation via the TGF-β1/SMADS/AMPK/NF-κB pathways.
BMC Complement Altern Med. 2019 Jan 10;19(1):14
Authors: Yao L, Li J, Li L, Li X, Zhang R, Zhang Y, Mao X
BACKGROUND: Coreopsis tinctoria Nutt is an ethnomedicine widely used in Xinjiang, China. It is consumed as a herbal tea by local Uyghur people to treat high blood pressure and diarrhea. Our previous study confirmed that the ethyl acetate extract of Coreopsis tinctoria (AC) had a protective effect on diabetic nephropathy (DN) in an in vivo experiment. Here we aim to elucidate the protective mechanism of AC and marein, the main ingredient in Coreopsis tinctoria on renal fibrosis and inflammation in vitro under high glucose (HG) conditions.
METHODS: A HG-induced barrier dysfunction model in rat mesangial cells (HBZY-1) was established. The cells were exposed to AC and marein and/or HG for 24 h. Then, the renal protective effects of AC and marein via transforming growth factor-β1 (TGF-β1)/Smads, AMP-activated kinase protein (AMPK), and nuclear factor kappa beta (NF-κB) signaling were assessed.
RESULTS: Both AC and marein suppressed rat mesangial cell hyperplasia and significantly attenuated the expression of HG-disrupted fibrotic and inflammatory proteins in HBZY-1 cells. It was also confirmed that AC and marein remarkably attenuated HG-induced renal inflammation and fibrosis by regulating the AMPK, TGF-β1/Smads, and NF-κB signaling pathways.
CONCLUSION: These results indicated that AC and marein may delay the progression of DN, at least in part, by suppressing HG-induced renal inflammation and fibrosis. Marein may be one of the bioactive compounds in AC.
PMID: 30630477 [PubMed - indexed for MEDLINE]
K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation.
Cell Physiol Biochem. 2018;51(4):1908-1920
Authors: Liu H, Zhang Z, Xu M, Xu R, Wang Z, Di G
BACKGROUND/AIMS: New strategies are required to combat neuronal ischemia-reperfusion injuries. K6PC-5 is a novel sphingosine kinase 1 (SphK1) activator whose potential activity in neuronal cells has not yet been tested.
METHODS: Cell survival and necrosis were assessed with a Cell Counting Kit-8 assay and lactate dehydrogenase release assay, respectively. Mitochondrial depolarization was tested by a JC-1 dye assay. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling components were examined by quantitative real-timePCR and western blotting.
RESULTS: K6PC-5 protected SH-SY5Y neuronal cells and primary murine hippocampal neurons from oxygen glucose deprivation/re-oxygenation (OGDR). K6PC-5 activated SphK1, and SphK1 knockdown by targeted short hairpin RNA (shRNA) almost completely abolished K6PC-5-induced neuronal cell protection. Further work showed that K6PC-5 inhibited OGDR-induced programmed necrosis in neuronal cells. Importantly, K6PC-5 activated Nrf2 signaling, which is downstream of SphK1. Silencing of Nrf2 by targeted shRNA almost completely nullified K6PC-5-mediated neuronal cell protection against OGDR.
CONCLUSION: K6PC-5 activates SphK1-Nrf2 signaling to protect neuronal cells from OGDR. K6PC-5 might be a promising neuroprotective strategy for ischemia-reperfusion injuries.
PMID: 30504702 [PubMed - indexed for MEDLINE]
miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer.
Cell Physiol Biochem. 2018;51(4):1969-1981
Authors: Zhu X, Ma SP, Yang D, Liu Y, Wang YP, Lin T, Li YX, Yang SH, Zhang WC, Wang XL
BACKGROUND/AIMS: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples.
METHODS: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice.
RESULTS: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively.
CONCLUSION: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.
PMID: 30513513 [PubMed - indexed for MEDLINE]
Retaining mTeSR1 Medium during Hepatic Differentiation Facilitates Hepatocyte-Like Cell Survival by Decreasing Apoptosis.
Cell Physiol Biochem. 2018;51(4):1533-1543
Authors: Hou J, Long Y, Hu B, Huang S, Xu G, Gao T, Wu F, Li Y, Wu ZK
BACKGROUND/AIMS: Hepatocyte-like cells derived from human pluripotent stem cells could be an important cell source for hepatocyte transplantation. The present study investigated the effect of retaining mTeSR1 medium during hepatic differentiation on hepatocyte-like cells in vitro.
METHODS: Human embryonic stem cell line H1 were treated with activin A and bone morphogenetic protein 4 (BMP4) for definitive endoderm (DE) cell induction and subsequently treated with BMP2 and fibroblast growth factor 4 (FGF4) for early hepatic cell induction. Hepatocyte growth factor (HGF) and fibroblast growth factor (KGF) were added for early hepatic cell expansion and then mixed with oncostatin-M for maturation. During DE induction, 0%, 25%, 50% and 75% concentrations of mTeSR1 medium were separately added for early hepatic induction and expansion. For optimization, the expression levels of SRY-related HMG-box 17 (SOX17) and forkhead box A2 (FOXA2) at day 4, alpha fetoprotein (AFP) and hepatocyte nuclear factor 4α (HNF4α) at day 15, and albumin (ALB) at day 25 were quantified in differentiated cells by qRT-PCR. The ALB-positive cell proportion was measured by flow cytometry. Functional tests including ALB secretion and indocyanine green (ICG) angiography uptake and release by ELISA, urea production by urea assay kit, and glycogen storage ability by periodic acid Schif reaction (PAS) staining were performed in the differentiated cells. The induced pluripotent stem (iPS) cells were used to examine whether the optimized method was suitable for differentiating iPS cells. DE and hepatic markers were detected by immunostaining, and functional testing was performed as described above. Flow cytometry with an Annexin V-FITC apoptosis detection kit and fluorescence microscopy with Hoechst 33258 were used to analyze apoptosis in differentiated cells derived from H1 cells.
RESULTS: All differentiated cells with retention of 0%, 25%, 50% and 75% mTeSR1 expressed SOX17, FOXA2, AFP, HNF4α, and ALB, while higher expression levels were observed in differentiated cells in the 0% and 25% groups. The flow cytometry results showed that the proportion of ALB-positive differentiated cells derived from H1 cells was higher in the 25% mTeSR1 group than in other groups. However, no significant difference in ALB secretion, urea production, ICG uptake and release and glycogen storage ability was detected between the 25% and 0% groups. The iPS cells could differentiate into hepatocyte-like cells with 25% mTeSR1 retention. The apoptosis ratio of differentiated cells was lower in the 25% mTeSR1 group than in the 0% mTeSR1 group.
CONCLUSION: Retaining 25% mTeSR1 medium during hepatic differentiation has been proposed to increase the percentage of ALB-positive cells and cell survival by decreasing cell apoptosis.
PMID: 30497075 [PubMed - indexed for MEDLINE]
Preventive Effects of Epinephrine for Critically Ill Patients? More Questions Waiting to Be Answered.
Dig Dis Sci. 2019 01;64(1):283-284
Authors: Shi S, Lin Y, Ding R, Chen Y, Wu F, He Z, Wu Z, Liang C
PMID: 30478766 [PubMed - indexed for MEDLINE]
Structure characterization and anti-leukemia activity of a novel polysaccharide from Angelica sinensis (Oliv.) Diels.
Int J Biol Macromol. 2019 Jan;121:161-172
Authors: Liu W, Li W, Sui Y, Li XQ, Liu C, Jing H, Zhang H, Cao W
A new water-soluble polysaccharide, APS-1II, with a molecular weight of 42.1 kDa was isolated from the roots of Angelica sinensis (Oliv.) Diels. APS-1II consists of arabinose (Ara), glucose (Glc) and fucose (Fuc) with a molar ratio of 2.48:1.05:1.00. The backbone of APS-1II is composed of 1,3-α-l-Araf and 1,6-α-d-Glcp with the branches containing 1,5-α-l-Araf, 1,4-β-d-Glcp, T-β-d-Glcp, 1,3-α-l-Fucp and T-α-l-Fucp. APS-1II inhibited the proliferation of human leukemia K562 and mouse L1210 cells in vitro and markedly prolonged the life span of L1210-bearing mice in vivo. APS-1II also increased the numbers of leukocytes and lymphocytes in peripheral blood, and significantly decreased plasma tumor necrosis factor, interleukin-2 and interferon-γ levels in L1210-bearing mice. Moreover, APS-1II administration concentration-dependently promoted the proliferation of the splenocytes, enhanced phagocytic activity of peritoneal macrophages and cytotoxicity of natural killer cells. These results suggest that APS-1II could effectively inhibit leukemia and induce a protective immune response, and it may be used as a suitable candidate reagent for leukemia therapy.
PMID: 30290264 [PubMed - indexed for MEDLINE]
Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7.
EBioMedicine. 2018 Oct;36:29-38
Authors: Lu R, Yuan T, Wang Y, Zhang T, Yuan Y, Wu D, Zhou M, He Z, Lu Y, Chen Y, Fan J, Liang J, Cheng Y
Rabbits (Oryctolagus cuniculus) have been the very frequently used as animal models in the study of human lipid metabolism and atherosclerosis, because they have similar lipoprotein metabolism to humans. Most of hyperlipidemia and atherosclerosis rabbit models are produced by feeding rabbits a high-cholesterol diet. Gene editing or knockout (KO) offered another means of producing rabbit models for study of the metabolism of lipids and lipoproteins. Even so, apolipoprotein (Apo)E KO rabbits must be fed a high-cholesterol diet to induce hyperlipidemia. In this study, we used the CRISPR/Cas9 system anchored exon 7 of low-density lipoprotein receptor (LDLR) in an attempt to generate KO rabbits. We designed two sgRNA sequences located in E7:g.7055-7074 and E7:g.7102-7124 of rabbit LDLR gene, respectively. Seven LDLR-KO founder rabbits were generated, and all of them contained biallelic modifications. Various mutational LDLR amino acid sequences of the 7 founder rabbits were subjected to tertiary structure modeling with SWISS-MODEL, and results showed that the structure of EGF-A domain of each protein differs from the wild-type. All the founder rabbits spontaneously developed hypercholesterolemia and atherosclerosis on a normal chow (NC) diet. Analysis of their plasma lipids and lipoproteins at the age of 12 weeks revealed that all these KO rabbits exhibited markedly increased levels of plasma TC (the highest of which was 1013.15 mg/dl, 20-fold higher than wild-type rabbits), LDL-C (the highest of which was 730.00 mg/dl, 35-fold higher than wild-type rabbits) and TG accompanied by reduced HDL-C levels. Pathological examinations of a founder rabbit showed prominent aortic atherosclerosis lesions and coronary artery atherosclerosis.In conclusion, we have reported the generation LDLR-KO rabbit model for the study of spontaneous hypercholesterolemia and atherosclerosis on a NC diet. The LDLR-KO rabbits should be a useful rabbit model of human familial hypercholesterolemia (FH) for the simulations of human primary hypercholesterolemia and such models would allow more exact research into cardio-cerebrovascular disease.
PMID: 30243490 [PubMed - indexed for MEDLINE]
Cardioprotective effects and underlying mechanism of Radix Salvia miltiorrhiza and Lignum Dalbergia odorifera in a pig chronic myocardial ischemia model.
Int J Mol Med. 2018 Nov;42(5):2628-2640
Authors: Lin R, Duan J, Mu F, Bian H, Zhao M, Zhou M, Li Y, Wen A, Yang Y, Xi M
Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat myocardial ischemia and other cardiovascular diseases. The volatile oil of DO (DOO) is one of the main components of DO. The aim of the present study was to assess the cardioprotective effects and possible underlying mechanisms of SM‑DOO in pigs with ameroid constriction‑induced chronic myocardial ischemia. An ameroid constrictor was placed around the left anterior descending coronary artery of pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial injury markers and blood gas levels were detected. At week 8, coronary angiography, echocardiography and hemodynamics analysis were performed to evaluate myocardial function. Following sacrifice, myocardial tissue was collected and subjected to morphological, histopathological and apoptosis assays. Western blotting was used to detect the protein expression of Bcl‑2 associated X (Bax), Bcl‑2, Akt, phosphorylated (p)‑Akt, glycogen synthase kinase (GSK)‑3β and p‑GSK‑3β. It was revealed that SM‑DOO treatment following chronic myocardial ischemia significantly downregulated the expression of myocardial injury markers, ameliorated myocardial oxygen consumption, increased collateralization, reduced regional cardiac dysfunction and limited the extent of myocardial damage. Furthermore, the results of an apoptosis assay revealed that the apoptosis rate was decreased, the expression of Bax decreased and Bcl‑2 increased, and the ratio of Bcl‑2/Bax was increased. Further experiments indicated that treatment with SM‑DOO increased the phosphorylation of Akt and GSK‑3β. These findings suggest that SM‑DOO treatment ameliorates myocardial injury in a chronic myocardial ischemia model, and that the underlying mechanisms responsible may be associated with the activation of the Akt/GSK‑3β signal pathway. Thus, experimental evidence that SM‑DOO may be an effective drug for the prevention and treatment of chronic myocardial ischemia in clinical applications has been provided.
PMID: 30226574 [PubMed - indexed for MEDLINE]
Potential anti-vitiligo properties of cynarine extracted from Vernonia anthelmintica (L.) Willd.
Int J Mol Med. 2018 Nov;42(5):2665-2675
Authors: Mamat N, Lu XY, Kabas M, Aisa HA
Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the destruction of melanocytes or obstruction of the melanin synthesis pathway. Melanin is a type of skin pigment that determines skin color. The seeds of Vernonia anthelmintica (L.) Willd (Kaliziri) are used for treating skin diseases including vitiligo in traditional Uyghur medicine. 1,5‑Dicaffeoylquinic acid (1,5‑diCQA) is a natural polyphenolic compound widely distributed in plants and extracted from Kaliziri seeds. Therefore, in the present study, the effect of 1,5‑diCQA on melanin synthesis in B16 cell was evaluated, and its molecular mechanism was explored. The results indicated that 1,5‑diCQA treatment of B16 cells stimulated an increase of intracellular melanin level and tyrosinase (TYR) activity without cytotoxicity. Reverse transcription quantitative polymerase chain reaction results also indicated that 1,5‑diCQA may markedly improve the protein expression and RNA transcription of microphthalmia‑associated transcription factor (MITF), melanogenic enzyme Tyr, tyrosinase‑related protein 1 (TRP 1) and tyrosinase‑related protein 2 (TRP 2). Additional results identified that 1,5‑diCQA may promote the phosphorylation of p38 mitogen‑activated protein kinase (p38 MAPK) and extracellular signal‑regulated kinase (ERK) MAPK. Notably, the increased levels of intracellular melanin synthesis and tyrosinase expression induced by 1,5‑diCQA treatment were significantly attenuated by the protein kinase A (PKA) inhibitor H‑89. Intracellular cyclic adenosine monophosphate (cAMP) concentration and phosphorylation of cAMP‑response element binding protein was increased following 1,5‑diCQA treatment. These results indicated that 1,5‑diCQA stimulated melanogenesis via the MAPK and cAMP/PKA signaling pathways in B16 cells, which has potential therapeutic implications for vitiligo.
PMID: 30226537 [PubMed - indexed for MEDLINE]
Neurodevelopmental changes in the relationship between stress perception and prefrontal-amygdala functional circuitry.
Neuroimage Clin. 2018;20:267-274
Authors: Wu J, Geng X, Shao R, Wong NML, Tao J, Chen L, Chan CCH, Lee TMC
Our brain during distinct developmental phases may show differential responses to perceived psychological stress, yet existing research specifically examining neurodevelopmental changes in stress processing is scarce. To fill in this research gap, this functional magnetic resonance imaging (fMRI) study examined the relationship between perceived stress and resting-state neural connectivity patterns among 67 healthy volunteers belonging to three age groups (adolescents, young adults and adults), who were supposed to be at separate neurodevelopmental phases and exhibit different affect regulatory processes in the brain. While the groups showed no significant difference in self-reported general perceived stress levels, the functional connectivity between amygdala and ventromedial prefrontal cortex (vmPFC) was positively and negatively correlated with perceived stress in adolescents and young adults respectively, while no significant correlations were observed in adults. Furthermore, among adolescents, the causal functional interaction between amygdala and vmPFC exhibited bottom-up connectivity, and that between amygdala and subgenual anterior cingulate cortex exhibited top-down connectivity, both of which changed to bilateral directions, i.e. both bottom-up and top-down connections, in both young adults and adults, supporting the notion that the amygdala and prefrontal cortical circuitries undergo functional reorganizations during brain development. These novel findings have important clinical implications in treating stress-related affective disorders in young individuals.
PMID: 30101058 [PubMed - indexed for MEDLINE]
Fibronectin Enhances Cartilage Repair by Activating Progenitor Cells Through Integrin α5β1 Receptor.
Tissue Eng Part A. 2018 07;24(13-14):1112-1124
Authors: Tao T, Li Y, Gui C, Ma Y, Ge Y, Dai H, Zhang K, Du J, Guo Y, Jiang Y, Gui J
This study aimed to determine the effect of fibronectin (FN) on cartilage regeneration through the activation of chondrogenic progenitor cells (CPCs). Cells were isolated from the knee cartilage of mice and cultured in the presence of various concentrations of FN. Proliferation, migration, and chondrogenic differentiation assays were performed in vitro. In some experiments, CPCs were preincubated with anti-integrin α5β1 antibody for 60 min before FN treatment to block the integrin α5β1 receptor. Soluble FN was mixed with Pluronic F-127 and injected into the joint cavity in an early-stage osteoarthritis model. Cartilage repair was evaluated histologically, biochemically, and biomechanically. In vitro, we observed that the isolated CPCs, which exhibited stem cell-relevant markers, proliferated most at a concentration of 20 μg/mL FN (p < 0.05). In addition, FN enhanced the proliferation, migration, and chondrogenic differentiation capacity of CPCs, and the enhancement was significantly decreased by blockade of the integrin α5β1 receptor (p < 0.05). In vivo, FN also significantly promoted cartilage repair along with increased CPC activation and integrin α5β1 expression (p < 0.05). These findings suggest that FN enhances CPC proliferation, migration, and chondrogenic differentiation through the integrin α5β1-dependent signaling pathway. Based on these results, a novel and promising therapy focused on targeted activation of CPCs by FN could be developed for the treatment of cartilage injuries in a clinical setting.
PMID: 29343182 [PubMed - indexed for MEDLINE]
Accuracy and reliability of brain natriuretic peptide (BNP) in predicting the prognosis of non-cardiac patients with sepsis.
J Crit Care. 2018 04;44:475-476
Authors: Zhou X, Wu S, Ye Y
PMID: 29277290 [PubMed - indexed for MEDLINE]