Lipid-Modifying Effects of Chitosan Supplementation in Humans: A Pooled Analysis with Trial Sequential Analysis.
Mol Nutr Food Res. 2018 Feb 16;:
Authors: Huang H, Zou Y, Chi H, Liao D
SCOPE: We performed a pooled analysis with trial sequential analysis (TSA) to evaluate the efficacy and safety of chitosan supplementation on serum lipids in humans.
METHODS AND RESULTS: Medline, EMBASE and CENTRAL databases were queried. Impact was expressed as a weighted mean difference (WMD) and 95% confidence interval (CI). Sensitivity analysis was conducted using the leave-one-out method. Statistical heterogeneity, publication bias, TSA and subgroup analyses were also assessed. Fourteen trials (21 treatment arms) encompassing 1,108 participants were suitable for statistical pooling. Chitosan supplementation significantly improved the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in all patients. The WMDs were -0.20 mmol/L (95% CI, -0.35 to -0.05; P = 0.009) for TC, and -0.20 mol/L (95% CI, -0.26 to -0.15; P = 0.0001) for LDL-C, respectively. TSA demonstrated that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit providing conclusive evidence for the benefit of chitosan. However, no significant changes were seen with high-density lipoprotein cholesterol and triglycerides. Our findings were robust after sensitivity analyses, and no serious adverse events were reported with chitosan intake.
CONCLUSION: Supplementation with chitosan effectively reduces plasma concentrations of TC and LDL-C. Current evidence indicates daily chitosan supplementation as a candidate for therapeutic lipid management strategies. This article is protected by copyright. All rights reserved.
PMID: 29451712 [PubMed - as supplied by publisher]
4-dehydroxyepisarcovagine A, a new steroidal alkaloid from Sarcococca pruniformis Lindl.
Nat Prod Res. 2018 Feb 16;:1-5
Authors: Wu JC, Huo SJ, Du J
A new steroidal alkaloid, 4-dehydroxyepisarcovagine A (1), along with seven known alkaloids, sarcovagine D (2), sarcovagenine C (3), epoxysarcovagenine D (4), Pachysamine L (5), Pachysamine E (6), sarcovagine A (7) and sarcovagine B (8), was isolated from the roots and stems of Sarcococca pruniformis Lindl. The structure of compound 1 was elucidated by means of spectroscopic analysis.
PMID: 29451012 [PubMed - as supplied by publisher]
Application of off-line two-dimensional high-performance countercurrent chromatography on the chloroform-soluble extract of Cuscuta auralis seeds.
J Sep Sci. 2018 Feb 16;:
Authors: Rho T, Yoon KD
In this study, the chloroform-soluble extract of C. auralis was separated successfully using off-line two-dimensional high-performance countercurrent chromatography, yielding a γ-pyrone, two alkaloids, a flavonoid and four lignans. The first-dimensional countercurrent separation using a methylene chloride/methanol/water (11:6:5, v/v/v) system yielded three sub-fractions (fractions I-III). The second-dimensional countercurrent separations, conducted on fractions I-III using n-hexane/ethyl and acetate/methanol/acetic acid (5:5:5:5:0, 3:7:3:7:0 and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol (1), (-)-(13S)-cuscutamine (2), (+)-(13R)-cuscutamine (3), (+)-pinoresinol (4), (+)-epipinoresinol (5), kaempferol (6), piperitol (7) and (9R)-hydroxy-d-sesamin (8). To the best of our knowledge, maltol was identified for the first time in Cuscuta species. Furthermore, this report details the first full assignment of spectroscopic data of two cuscutamine epimers, (-)-(13S)-cuscutamine and (+)-(13R)-cuscutamine. This article is protected by copyright. All rights reserved.
PMID: 29450982 [PubMed - as supplied by publisher]
Automated Pathogenesis-Based Diagnosis of Lumbar Neural Foraminal Stenosis via Deep Multiscale Multitask Learning.
Neuroinformatics. 2018 Feb 15;:
Authors: Han Z, Wei B, Leung S, Nachum IB, Laidley D, Li S
Pathogenesis-based diagnosis is a key step to prevent and control lumbar neural foraminal stenosis (LNFS). It conducts both early diagnosis and comprehensive assessment by drawing crucial pathological links between pathogenic factors and LNFS. Automated pathogenesis-based diagnosis would simultaneously localize and grade multiple spinal organs (neural foramina, vertebrae, intervertebral discs) to diagnose LNFS and discover pathogenic factors. The automated way facilitates planning optimal therapeutic schedules and relieving clinicians from laborious workloads. However, no successful work has been achieved yet due to its extreme challenges since 1) multiple targets: each lumbar spine has at least 17 target organs, 2) multiple scales: each type of target organ has structural complexity and various scales across subjects, and 3) multiple tasks, i.e., simultaneous localization and diagnosis of all lumbar organs, are extremely difficult than individual tasks. To address these huge challenges, we propose a deep multiscale multitask learning network (DMML-Net) integrating a multiscale multi-output learning and a multitask regression learning into a fully convolutional network. 1) DMML-Net merges semantic representations to reinforce the salience of numerous target organs. 2) DMML-Net extends multiscale convolutional layers as multiple output layers to boost the scale-invariance for various organs. 3) DMML-Net joins a multitask regression module and a multitask loss module to prompt the mutual benefit between tasks. Extensive experimental results demonstrate that DMML-Net achieves high performance (0.845 mean average precision) on T1/T2-weighted MRI scans from 200 subjects. This endows our method an efficient tool for clinical LNFS diagnosis.
PMID: 29450848 [PubMed - as supplied by publisher]
Complete chloroplast genome of the medicinal plant Amomum compactum: gene organization, comparative analysis, and phylogenetic relationships within Zingiberales.
Chin Med. 2018;13:10
Authors: Wu ML, Li Q, Xu J, Li XW
Background: Amomum compactum is one of the basic species of the traditional herbal medicine amomi fructus rotundus, with great pharmacology effect. The system position of A. compactum is not clear yet, and the introduction of this plant has been hindered by many plant diseases. However, the correlational molecular studies are relatively scarce.
Methods: The total chloroplast (cp) DNA was extracted according to previous studies, and then sequenced by 454 GS FLX Titanium platform. Sequence assembly was complished by Newbler. Genome annotation was preformed by CPGAVAS and tRNA-SCAN. Then, general characteristics of the A. compactum cp genome and genome comparsion with three Zingiberaceae species was analyzed by corresponding softwares. Additionally, phylogenetical trees were reconstructed, based on the shared protein-coding gene sequences among 15 plant taxa by maximum parsimony (MP) and maximum likelihood (ML) methods.
Results: The A. compactum cp genome with a classic quadripartite structure, consisting of a pair of reverse complement repeat regions (IRa/IRb) of 29,824 bp, a large single copy (LSC, 88,535 bp) region as well as a small single copy (SSC, 15,370 bp) region, is 163,553 bp in total size. The total GC content of this cp genome is 36.0%. The A. compactum cp genome owns 135 functional genes, that 113 genes are unique, containing eighty protein-coding genes, twenty-nine tRNA (transfer RNA) genes and four rRNA (ribosomal RNA) genes. Codon usage of the A. compactum cp genome is biased toward codons ending with A/T. Total 58 SSR loci and 24 large repeats are detected in the A. compactum cp genome. Relative to three other Zingiberaceae cp genomes, the A. compactum cp genome exhibits an obvious expansion in the IR regions. In A. compactum cp genome, the ycf1 pseudogene is 2969 bp away from the IRa/SSC border, whereas in other Zingiberaceae species, it is only 4-5 bp away from the IRa/SSC border. Comparative cp genome sequences analysis of A. compactum with other Zingiberaceae reveals that the gene order and gene content differ slightly among Zingiberaceae species. The phylogenetic analysis based on 67 protein-coding gene sequences supports the phylogenetic position of A. compactum.
Conclusions: The study has identified unique features of the A. compactum cp genome which would be helpful for us to understand the cp genome evolution and offer useful information for phylogenetics and further studies of this traditional medicinal plant.
PMID: 29449878 [PubMed]
Internationalization of traditional Chinese medicine: current international market, internationalization challenges and prospective suggestions.
Chin Med. 2018;13:9
Authors: Lin AX, Chan G, Hu Y, Ouyang D, Ung COL, Shi L, Hu H
Through reviewing the current international market for traditional Chinese medicine (TCM), this paper identified the internationalization challenges for TCM, including unclear therapeutic material basis and mechanism, difficulty of quality control, low preparation level, registration/policy barriers, and shortage of intellectual property. To deal with these challenges, suggestions were given including: (1) product innovation of TCM (study the TCM by using the methods and means of western medicine; innovate the basic theory of TCM; develop TCM health product); (2) standard innovation of TCM; (3) building big data platform of Chinese medicine (big data platform of TCM preparation; big data platform on the quality of TCM).
PMID: 29449877 [PubMed]
Authenticity analyses of Rhizoma Paridis using barcoding coupled with high resolution melting (Bar-HRM) analysis to control its quality for medicinal plant product.
Chin Med. 2018;13:8
Authors: Duan BZ, Wang YP, Fang HL, Xiong C, Li XW, Wang P, Chen SL
Background: Rhizoma Paridis (Chonglou) is a commonly used and precious traditional Chinese medicine. Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz. and Paris polyphylla Smith var. chinensis (Franch.) Hara are the two main sources of Chonglou under the monograph of Rhizoma Paridis in Chinese Pharmacopoeia. In the local marketplace, however, this medicine is prone to be accidentally contaminated, deliberately substituted or admixed with other species that are similar to Rhizoma Paridis in shape and color. Consequently, these adulterations might compromise quality control and result in considerable health concerns for consumers. This study aims to develop a rapid and sensitive method for accurate identification of Rhizoma Paridis and its common adulterants.
Methods: DNA barcoding coupled with high resolution melting analysis was applied in this research to distinguish Rhizoma Paridis from its adulteration. The internal transcribed spacer 2 (ITS2) barcode was selected for HRM analysis to produce standard melting profile of the selected species. DNA of the tested herbal medicines was isolated and their melting profiles were generated and compared with the standard melting profile of P. polyphylla var. chinensis.
Results: The results indicate that the ITS2 molecular regions coupled with HRM analysis can effectively differentiate nine herbal species, including two authentic origins of Chonglou and their seven common adulterants. Ten herbal medicines labeled "Chonglou" obtained from a local market were collected and identified with our methods, and their sequence information was analyzed to validate the accuracy of HRM analysis.
Conclusions: DNA barcoding coupled with HRM analysis is a accurate, reliable, rapid, cost-effective and robust tool, which could contribute to the quality control of Rhizoma Paridis in the supply chain of the natural health product industry (NHP).
PMID: 29449876 [PubMed]
Structural elucidation of a polysaccharide from Flammulina velutipes and its immunomodulation activities on mouse B lymphocytes.
Sci Rep. 2018 Feb 15;8(1):3120
Authors: Wang WH, Zhang JS, Feng T, Deng J, Lin CC, Fan H, Yu WJ, Bao HY, Jia W
A novel polysaccharide FVPB2 was purified from fruiting bodies of Flammulina velutipes. Its structure was elucidated by monosaccharide composition and methylation analyses, UV-Visible and FTIR spectroscopy as well as NMR. FVPB2 was a homogeneous heteropolysaccharide (molecular weight ~ 1.50 × 104 Da) containing D-galactose, D-mannose, L-fucose, and D-glucose at molar ratio of 1.9:1.2:1:2.5. In vitro immunomodulatory studies showed FVPB2 induced proliferation of mouse spleen lymphocytes in a dose-dependent manner. The levels of IgM and IgG, secreted by B cells, increased after FVPB2 treatment. So FVPB2 has potential to be a new important immunomodulatory nutraceutical.
PMID: 29449636 [PubMed - in process]
The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's Disease.
Sci Rep. 2018 Feb 15;8(1):3104
Authors: Cai H, Luo Y, Yan X, Ding P, Huang Y, Fang S, Zhang R, Chen Y, Guo Z, Fang J, Wang Q, Xu J
Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins. In addition, we elucidated the mechanisms of BSYZ action on AD through multiple network analysis, including compound-target network analysis and target-function network analysis. Furthermore, several modules regulated by BSYZ were incorporated into AD-related pathways to uncover the therapeutic mechanisms of this prescription in AD treatment. Finally, further verification experiments also demonstrated the therapeutic effects of BSYZ on cognitive dysfunction in APP/PS1 mice, which was possibly via regulating amyloid-β metabolism and suppressing neuronal apoptosis. In conclusion, we provide an integrative systems pharmacology approach to illustrate the underlying therapeutic mechanisms of BSYZ formula action on AD.
PMID: 29449587 [PubMed - in process]
Binge Alcohol Exposure Causes Neurobehavioral Deficits and GSK3β Activation in the Hippocampus of Adolescent Rats.
Sci Rep. 2018 Feb 15;8(1):3088
Authors: Ji Z, Yuan L, Lu X, Ding H, Luo J, Ke ZJ
Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris water maze. However, alcohol did not alter the spontaneous locomotor activity which was determined by the open field test. GSK3β is a multi-function serine/threonine protein kinase regulating both neuronal survival and neurogenesis and plays an important role in various neurodegenerative disorders. We have previously shown that GSK3β is a key mediator of alcohol-induced neuron apoptosis in the developing brain. We showed here binge alcohol exposure caused GSK3β activation by inducing dephosphorylation at Ser9 without affecting the phosphorylation of Tyr216 in the hippocampus. Thus, GSK3β may be involved in binge alcohol exposure-induced neuronal damage to the adolescent hippocampus.
PMID: 29449568 [PubMed - in process]
Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth.
Cell Death Dis. 2018 Feb 15;9(3):262
Authors: Xu L, Meng X, Xu N, Fu W, Tan H, Zhang L, Zhou Q, Qian J, Tu S, Li X, Lao Y, Xu H
Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition. In this study, we investigated the mechanism of action of GNA in erlotinib-resistant NSCLC and patient-derived cells. The inhibition of GNA on FGFR signaling pathway was examined using biochemical kinase assays. NSCLC cell lines (HCC827, HCC827-Erlotinib-resistant, and H1650) and primary cells from patients with NSCLC with clinical resistance to erlotinib were treated with GNA, erlotinib, or their combination. Both kinase assays and cell- based assays showed that GNA inhibits the phosphorylation of multiple kinases in FGFR signaling pathway in NSCLC. The combination of GNA and erlotinib significantly attenuates the tumor growth of HCC827 and erlotinib-resistant HCC827 xenografts with low toxicity. Importantly, GNA significantly suppresses tumor growth in a lung patient-derived xenograft (PDX) model with FGFR fusion and low EGFR expression. Our findings provide preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy when used as a combined administration.
PMID: 29449529 [PubMed - in process]
The Crescentic Implication of Renal Outcomes in Proliferative Lupus Nephritis.
J Rheumatol. 2018 Feb 15;:
Authors: Cai F, Han F, Wang H, Han H, Le J, Lan L, Xu Y, Chen J
OBJECTIVE: To determine the association between crescents and renal outcomes, and the implications on therapeutic choices.
METHODS: There were 231 patients with biopsy-proven proliferative lupus nephritis (PLN) who were divided into 4 groups: 59 patients were in the noncrescent group (NC); 59 patients exclusively with segmental crescents were in the segmental crescent group (SC); patients with circumferential crescents were categorized into 2 groups according to the crescentic ratio (C1 had 64 patients with ≤ 25%, and C2 had 49 patients with > 25%). Their baseline laboratory tests, histopathological manifestations, and outcomes were compared.
RESULTS: Remission rates in NC, SC, C1, and C2 groups were 92.1%, 85.4%, 95.0%, and 76.1%, respectively. Fewer patients in the C2 group achieved complete remission than the other 3 groups. For longterm outcomes evaluated by serum creatinine (SCr) doubling or endstage renal disease (ESRD), the renal survival rate was lowest in the C2 group (p = 0.003). Including clinical and pathological variables in the Cox proportional hazard regression model separately, the multivariate analysis revealed that these were independent risk factors for SCr doubling or ESRD: baseline SCr (with every 1 mg/dl increase: HR = 1.834, 95% CI 1.465-2.296; p < 0.001), hemoglobin (with every 1 g/l increase: HR = 0.970, 95% CI 0.947-0.992; p = 0.009), the proportions of cellular crescents (with every 1% increase: HR = 1.040, 95% CI 1.015-1.066; p = 0.002) and fibrocellular crescents (with every 1% increase: HR = 1.085, 95% CI 1.013-1.163; p = 0.020), and severe renal tubular atrophy (HR = 5.348, 95% CI 1.278-22.373; p = 0.022).
CONCLUSION: PLN with crescents > 25% had worse renal outcomes both in short and long terms. Proportions of cellular and fibrocellular crescents were independent risk factors for poor renal survival.
PMID: 29449502 [PubMed - as supplied by publisher]
Shikonin suppresses proliferation and induces apoptosis in endometrioid endometrial cancer cells via modulating miR-106b/PTEN/AKT/mTOR signaling pathway.
Biosci Rep. 2018 Feb 15;:
Authors: Huang C, Hu G
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, which exerts anti-cancer effects in various cancers. However, the molecular mechanisms underlying the therapeutic effects of shikonin against endometrioid endometrial cancer (EEC) have not yet been fully elucidated. Herein, we investigated anti-cancer effects of shikonin on EEC cells and explored the underlying molecular mechanism. We observed that shikonin inhibits proliferation in human EEC cell lines with in a dose-dependent manner. Moreover, shikonin-induced apoptosis was characterized by the upregulation of the pro-apoptotic proteins cleaved-Caspase-3 and Bax, and the downregulation of the anti-apoptotic protein Bcl-2. Microarray analyses demonstrated that shikonin induces many miRNAs dysregulation, and the miR-106b was one of the miRNAs being most significantly downregulated. miR-106b was identified to exert pro-cancer effect in various cancers, but in EEC remains unclear. We firstly confirmed that miR-106b is upregulated in EEC tissues and cells, and knockdown of miR-106b suppresses proliferation and promotes apoptosis. Meanwhile, our results validated that the restored expression of miR-106b abrogates the anti-proliferative and pro-apoptotic effects of shikonin. We also identified that miR-106b targets PTEN, a tumor suppressor gene, which in turn modulates AKT/mTOR signaling pathway. Our findings indicated that shikonin inhibits proliferation and promotes apoptosis in human EEC cells by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway, suggesting shikonin could act a potential therapeutic agent in the EEC treatment.
PMID: 29449346 [PubMed - as supplied by publisher]
Salvage tigecycline in high risk febrile neutropenic patients with hematological malignancies: a prospective multicenter study.
Leuk Lymphoma. 2018 Feb 16;:1-7
Authors: Zhou XP, Ye XJ, Shen JP, Lan JP, Jiang HF, Zhang J, Zhang XJ, Li L, Qian SX, Tong HY
The purpose of this prospective, multi-center study was to examine the efficacy and safety of tigecycline as empirical treatment in neutropenic patients with hematological malignancies who failed to respond to first-line antibiotics. A total of 125 patients with persistent fever (>72 h) despite first-line antibiotics received empirical treatment with tigecycline (loading dose of 100 mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not restricted. Treatment success rate was 68.0%. Subgroup analysis revealed a success rate of 73.1% in patients with pneumonia and 35.3% in patients with bacteremia. Toxicities were moderate with gastrointestinal symptoms being the main side effects. In conclusion, tigecycline-based antibacterial regimen was a justifiable empirical treatment in febrile neutropenic patients who failed to respond to first-line antibiotics except those with bacteremia. For patients with bacteremia, trials on higher-dose of tigecycline are needed.
PMID: 29448851 [PubMed - as supplied by publisher]
Effect of Zhizhu Kuanzhong capsule on functional dyspepsia: Protocol for a systematic review and meta-analysis of randomized controlled trials.
Medicine (Baltimore). 2018 Feb;97(6):e9731
Authors: Lin H, Wang X, Du X, Wang J, Li Y, Zhang R
BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder affecting people in the globe. Spleen-deficiency syndrome is one of its basic syndromes. Zhizhu Kuanzhong capsule was the most frequent Chinese herbal formula used in the spleen-deficiency researches. We aim to assess the effectiveness and safety of Zhizhu Kuanzhong capsule on FD.
METHODS: A systematic literature search for randomized controlled trials (RCTs) from their inception until December 31, 2017 will be conducted using 7 databases: PubMed, Cochrane Library, Embase, VIP Database, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese BioMedical Database. Inclusion the trials of Zhizhu Kuanzhong capsule which evaluate motilin level, clinical syndrome, and side effect in people with FD. The primary outcome measures will be motilin level, clinical syndrome integral, and clinical total effective rate. Data extraction and risk of bias assessments will be performed by 2 reviewers independently. Methodological and reporting quality of included studies will be assessed by the consolidated standards of reporting trials for Chinese herbal medicine formulas. All statistical analyses will be conducted using RevMan V.5.3 software. Funnel plots, Begg's test, and Egger's test will be developed to evaluate reporting bias.
RESULTS: This review will assess the effect of Zhizhu Kuanzhong capsule on clinical total effective rate, symptom remission rate, plasma motilin level, and safety of FD in patients.
CONCLUSION: The conclusion of our study will provide updated evidence to judge whether Zhizhu Kuanzhong capsule is an effective intervention for patients with FD.
PMID: 29419664 [PubMed - indexed for MEDLINE]
Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis in hepatocellular carcinoma Bel-7402 cells.
BMC Complement Altern Med. 2018 Jan 16;18(1):17
Authors: Hu B, Zhang T, An HM, Zheng JL, Yan X, Huang XW
BACKGROUND: Based on clinical medications and related studies, we established a Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment. In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension-grown human hepatocellular carcinoma Bel-7402 cells.
METHODS: Bel-7402 cells were cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and treated with YGJDSJ. Anchorage-independent cell growth was detected by cell Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis. Caspases activities were detected by the cleavage of chromogenic substrate. Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. Protein expression was knocked-down by siRNA.
RESULTS: YGJDSJ inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402 cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8 and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated YGJDSJ induced anoikis.
CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS generation and PTK2 downregulation.
PMID: 29338725 [PubMed - indexed for MEDLINE]
Enzymatic characterization of two epsilon-class glutathione S-transferases of Spodoptera litura.
Arch Insect Biochem Physiol. 2018 Mar;97(3):
Authors: Hirowatari A, Chen Z, Mita K, Yamamoto K
Two cDNAs encoding glutathione S-transferase (GST) of the tobacco cutworm, Spodoptera litura, were cloned by reverse transcriptase-polymerase chain reaction. The deduced amino acid sequences of the resulting clones revealed 32-51% identities to the epsilon-class GSTs from other organisms. The recombinant proteins were functionally overexpressed in Escherichia coli cells in soluble form and were purified to homogeneity. The enzymes were capable of catalyzing the bioconjugation of glutathione with 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-3-(4-nitrophenoxy)-propane, and ethacrynic acid. A competition assay revealed that the GST activity was inhibited by insecticides, suggesting that it could be conducive to insecticide tolerance in the tobacco cutworm.
PMID: 29235695 [PubMed - indexed for MEDLINE]
Core-shell structured polypyrrole/mesoporous SiO2 nanocomposite capped with graphene quantum dots as gatekeeper for irradiation-controlled release of methotrexate.
Mater Sci Eng C Mater Biol Appl. 2017 Dec 01;81:206-212
Authors: Liu X, Shou D, Chen C, Mao H, Kong Y, Tao Y
A core-shell structured nanocomposite of polypyrrole/mesoporous SiO2 (PPy/mSiO2) is rationally designed as the nanocarrier for methotrexate (MTX), a chemotherapeutic drug for cancer treatment. Graphene quantum dots (GQDs) are introduced to the outer surface of PPy/mSiO2, and it functions as a gatekeeper for the loaded MTX through the formation of H-bonds with the functionalized mSiO2. In the proposed nanocarrier for MTX, the mesopores in mSiO2 are beneficial for the accommodation of MTX, resulting in enhanced encapsulation capacity of the nanocarrier; on the other hand, PPy can effectively convert the near-infrared (NIR) light to heat. Under the irradiation of NIR light, the H-bonds between GQDs and mSiO2 are broken due to the gradually increased temperature, and therefore the GQDs cap is removed and consequently the encapsulated MTX is released from the nanocarrier. In this study, NIR irradiation-controlled drug delivery is achieved successfully owing to the synergistic effects of PPy, mSiO2 and GQDs, which opens a new window for the construction of smart drug delivery systems.
PMID: 28887966 [PubMed - indexed for MEDLINE]
Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials.
Biomed Res Int. 2017;2017:6274854
Authors: Song X, Qu H, Yang Z, Rong J, Cai W, Zhou H
Background. Whether additional benefit can be achieved with the use of L-carnitine (L-C) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. Methods. Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical (CBM) database, and Chinese Science and Technology Periodicals database (VIP) until September 30, 2016, were identified. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently. Results. 17 RCTs with 1625 CHF patients were included in this analysis. L-C treatment in CHF was associated with considerable improvement in overall efficacy (OR = 3.47, P < 0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, P = 0.01), strike volume (SV) (WMD: 8.21 ml, P = 0.01), cardiac output (CO) (WMD: 0.88 L/min, P < 0.01), and E/A (WMD: 0.23, P < 0.01). Moreover, treatment with L-C also resulted in significant decrease in serum levels of BNP (WMD: -124.60 pg/ml, P = 0.01), serum levels of NT-proBNP (WMD: -510.36 pg/ml, P < 0.01), LVESD (WMD: -4.06 mm, P < 0.01), LVEDD (WMD: -4.79 mm, P < 0.01), and LVESV (WMD: -20.16 ml, 95% CI: -35.65 to -4.67, P < 0.01). However, there were no significant differences in all-cause mortality, 6-minute walk, and adverse events between L-C and control groups. Conclusions. L-C treatment is effective for CHF patients in improving clinical symptoms and cardiac functions, decreasing serum levels of BNP and NT-proBNP. And it has a good tolerance.
PMID: 28497060 [PubMed - indexed for MEDLINE]
Construction of N-halamine labeled silica/zinc oxide hybrid nanoparticles for enhancing antibacterial ability of Ti implants.
Mater Sci Eng C Mater Biol Appl. 2017 Jul 01;76:50-58
Authors: Li Y, Liu X, Tan L, Cui Z, Yang X, Yeung KWK, Pan H, Wu S
The traditional antibiotic treatment for bacterial infections often induces antibiotic resistance in bacteria. In this work, we developed hybrid nanoparticles (NPs) with a self-antibacterial ability on Ti implants using monodispersed polystyrene-acrylic acid (PSA) nanoparticles as colloidal templates followed by the electrostatic adsorption of zinc oxide (ZnO) and the subsequent deposition of silica (SiO2) membrane on the outside. These synthesized PSA-ZnO-SiO2 NPs were pretreated by 5,5-dimethylhydantoin (DMH) before chlorination in a diluted NaClO solution. These nanoparticles (PSA-ZnO-SiO2-DMH) were subsequently labeled by N-halamines and then immobilized on the surface of titanium plates through hydrogen bonding. Field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the modified surface. Antibacterial tests disclosed that the PSA-ZnO-SiO2-DMH-Cl NPs modified surface exhibited excellent antibacterial activity against both Pseudomonas aeruginosa (P.au), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro cell culture results revealed that PSA-ZnO-SiO2-DMH-Cl had no obvious cytotoxicity for an MC3T3-E1 preosteoblast. This novel surface system provides a promising self-antibacterial bioplatform for metallic implants without using antibiotics.
PMID: 28482556 [PubMed - indexed for MEDLINE]
BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.
Aging (Albany NY). 2017 Apr;9(4):1326-1340
Authors: Wang MH, Zhou XM, Zhang MY, Shi L, Xiao RW, Zeng LS, Yang XZ, Zheng XFS, Wang HY, Mai SJ
Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.
PMID: 28455969 [PubMed - indexed for MEDLINE]
Pioglitazone ameliorates Aβ42 deposition in rats with diet-induced insulin resistance associated with AKT/GSK3β activation.
Mol Med Rep. 2017 May;15(5):2588-2594
Authors: Yang S, Chen Z, Cao M, Li R, Wang Z, Zhang M
Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal ﬂuid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression. The levels of insulin‑degrading enzyme (IDE) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, the activation of glycogen synthase kinase 3β (GSK3β) induced by phosphatidylinositol 3‑kinase (PI3K) /protein kinase B (AKT) signaling was detected by western blotting. Results from the present study demonstrated that pioglitazone may enhance peripheral and brain insulin sensitivity in diet‑induced IR model rats. Treatment with pioglitazone ameliorated Aβ42 deposition in the hippocampus by increasing IDE and PPARγ expression. Notably, activation of the PI3K/AKT/GSK3β pathway was also demonstrated to serve a role in pioglitazone‑induced Aβ42 degradation, which was abrogated by the PPARγ antagonist GW9662. Results from the present study indicated that pioglitazone may improve insulin sensitivity and ameliorate Aβ42 accumulation in rats with diet‑induced IR by regulating AKT/GSK3β activation, suggesting that pioglitazone may be a promising drug for AD treatment.
PMID: 28447730 [PubMed - indexed for MEDLINE]
Wiryeongtang regulates hypertonicity-induced expression of aquaporin-2 water channels in mIMCD-3 cells.
Mol Med Rep. 2017 May;15(5):2665-2672
Authors: Kim MG, Lee YJ, Choi ES, Yoon JJ, Han BH, Kang DG, Lee HS
The kidneys have a key role in the homeostasis of water excretion and reabsorption. Water channels, particularly aquaporin-2 (AQP2), are important proteins in water homeostasis in the body through the short‑term and long-term regulation of water permeability. Wiryeongtang (WRT) is a well-known traditional oriental medicine, which is used for the treatment of chronic edema and dysuresia. The aim of the present study was to evaluate the inhibitory effect of WRT on the hypertonicity-induced expression of AQP2 in the inner medullary collecting duct cell line (IMCD‑3). Western blotting, reverse transcription‑polymerase chain reaction and immunofluorescence analysis were performed to determine the effect of WRT under hypertonic stress. WRT attenuated the 175 mM NaCl hypertonic stress‑induced increases in protein and mRNA levels of AQP2 and apical membrane insertion in a concentration‑dependent manner. However, no differences were observed in the levels of AQP1, AQP3 or AQP4 between the hypertonic stress and WRT groups. WRT attenuated the hypertonicity-induced phosphorylation of glucocorticoid-inducible protein kinase 1. In addition, the mRNA expression of tonicity‑responsive enhancer binding protein was attenuated by WRT under hypertonic stress. Pretreatment with WRT also decreased the hypertonic stress‑induced expression of AQP2, as with KT5720, a protein kinase A inhibitor. These results provided evidence of the beneficial effect of the traditional formula WRT in regulating water balance in hypertonic stress of the renal collecting ducts.
PMID: 28447712 [PubMed - indexed for MEDLINE]
Preparation and biocompatibility of demineralized bone matrix/sodium alginate putty.
Cell Tissue Bank. 2017 Jun;18(2):205-216
Authors: Zhang Y, Wang J, Ma Y, Niu X, Liu J, Gao L, Zhai X, Chu K, Han B, Yang L, Wang J
Demineralized bone matrix (DBM) powder is widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, difficulties with handling, tendency to migrate from graft sites and lack of stability after surgery sometimes limit the clinical utility of this material. In this work, the possibility of using sodium alginate (ALG) carrier to deliver DBM powder was assessed. DBM-ALG putty with the DBM:ALG weight ratio of 5:5, 6:4, 7:3, 8:2 were prepared, respectively. The properties of the formed composite, including discrete degree, washout property, pH, equilibrium swelling as well as cytotoxicity in vivo, were adopted to ascertain the optimal ratio of DBM and ALG. The discrete diameter increased from 1.25 cm (5:5) to 2.08 cm (8:2) with the increase of DBM content. There was significant difference between the 8:2 group and the other groups in discrete diameter. The ratio of DBM had a significant effect on the swelling value. The pH of composites showed an increase trend with the DBM ratio's increase, when the ratio reached 7:3, the pH (7.22) was approximately equal to the body fluid. The proliferation of MC3T3-E1 cells was inhibited in the 5:5, 6:4 and 7:3 groups, while a slightly increased in the 8:2 group. The DBM-ALG with the optimal ratio of 7:3 was confirmed based on the results of the above mentioned. The histocompatibility of DBM-ALG (7:3) was examined using a rat model in which the materials were implanted subcutaneously, compared with the polyethylene, ALG and DBM. The study in vivo showed DBM-ALG (7:3) had a lower inflammatory response than DBM, a higher vascularization than ALG. The osteoinduction of DBM-ALG (7:3) was evaluated by co-culturing with MC3T3-E1 in vitro, compared with the DMEM, ALG and DBM. The results indicated calcification area in the DBM-ALG group was similar to that in the DBM group, larger than ALG group and DMEM group. The DBM-ALG (7:3) putty is promising as a directly injectable graft for repair of bone defect.
PMID: 28421389 [PubMed - indexed for MEDLINE]
New Cytotoxic Secondary Metabolites from Marine Bryozoan Cryptosula pallasiana.
Mar Drugs. 2017 Apr 13;15(4):
Authors: Tian XR, Gao YQ, Tian XL, Li J, Tang HF, Li YS, Lin HW, Ma ZQ
A new sterol, (23R)-methoxycholest-5,24-dien-3β-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2'R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2'-triol (7), together with three known sterols (2-4), a lactone (5) and two ceramides (8,9), were isolated from the marine bryozoan Cryptosula pallasiana, collected at Huang Island of China. The structures of the new compounds were elucidated by extensive spectroscopic analyses, chemical methods and quantum electronic circular dichroism (ECD) calculations. Among the isolated compounds, sterol 1 possessed a rare side chain with a methoxy group at C-23, and a double bond between C-24 and C-25. Ceramides 6 and 7 possessed 14 carbons in their long-chain fatty acid base (FAB), which were different from the normal ceramides with 16 carbons in the FAB. Moreover, compounds 5 and 8 were isolated for the first time from marine bryozoans. Compounds 1-9 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901. The results showed that lactone 5 appears to have strong cytotoxicity against the test tumor cell lines, with IC50 values from 4.12 μM to 7.32 μM, and sterol 1 displayed moderate cytotoxicity with IC50 values between 12.34 μM and 18.37 μM, while ceramides 6-9 showed weak cytotoxicity with IC50 ranging from 21.13 μM to 58.15 μM.
PMID: 28406457 [PubMed - indexed for MEDLINE]
Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells.
Oncotarget. 2017 Jan 17;8(3):4051-4061
Authors: Tsai SF, Tao M, Ho LI, Chiou TW, Lin SZ, Su HL, Harn HJ
The endoplasmic reticulum (ER) is a major site of cellular homeostasis regulation. Under the ER stress condition, Glioblastoma multiform (GBM) cells activate the unfolded protein response. In this study, we discovered isochaihulactone, a natural compound extracted from the Chinese traditional herb Nan-Chai-Hu, which can disrupt ER homeostasis in GBM cell lines. It can induce DNA damage inducible transcript 3 (DDIT3) expression which is independent of 78 kDa glucose-regulated protein (GRP78) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression. Flow cytometry results revealed that isochaihulactone trigger the cell cycle arrest at G2/M phase and apoptosis in GBM cells. Isochaihulactone induced DDIT3 led to the expression of NAG-1. The in vivo study showed that isochaihulactone suppressed tumor growth, and DDIT3 and Caspase3 overexpressed in the xenograft model, which is consistent with the in vitro study. Overall, the data revealed that isochaihulactone disrupted ER homeostasis in cancer cells by increasing DDIT3 and NAG-1 expression. Our finding also provides a therapeutic strategy by using isochaihulactone for GBM treatment.
PMID: 27852055 [PubMed - indexed for MEDLINE]
Effect of Gua sha therapy on perimenopausal syndrome: a randomized controlled trial.
Menopause. 2017 Mar;24(3):299-307
Authors: Meng F, Duan PB, Zhu J, Lou QQ, Fang ZH, An HL, Liu LY, Hu Y, Hu Q
OBJECTIVE: This study aims to evaluate the effectiveness and safety of Gua sha therapy on perimenopausal symptoms, quality of life, and serum female hormones in participants with perimenopausal syndrome.
METHODS: A prospective, randomized, controlled clinical trial was conducted at the First Affiliated Hospital of Nanjing University of Chinese Medicine in China. Eighty women with perimenopausal syndrome were recruited and randomized into an intervention group or a control group. Participants in the intervention group received 15-minute Gua sha treatment sessions once a week plus conventional treatment for 8 weeks, whereas participants in the control group received conventional treatment alone. The primary outcome was the change in perimenopausal symptoms and quality of life as obtained through the modified Kupperman Index (KI) and the Menopause-Specific Quality of Life. The secondary outcome was the change of serum female hormones including estrogen, follicle-stimulating hormone, and luteinizing hormone.
RESULTS: Seventy-five out of 80 participants (93.8%) completed the study-38 in the intervention group and 37 in the control group. The baseline levels of demographic and outcome measurements were comparable between the two groups. After eight sessions of intervention, the reduction in the total modified KI score was, however, 16.32 ± 4.38 in the intervention group and 11.46 ± 5.96 in the control group, with a difference of 4.86 ± 6.15 (P < 0.01) between the two groups. Also the reductions of hot flash/sweating, paresthesia, insomnia, nervousness, melancholia, fatigue, and headache were greater in the intervention group than in the control group (P < 0.05). The reduction in the total Menopause-Specific Quality of Life score was 17.87 ± 3.84 in the intervention group and 13.62 ± 7.40 in the control group, with a difference of 4.46 ± 7.52 (P < 0.01) between the two groups. And the scores for vasomotor, psychosocial, and physical domains in the intervention group were significantly lower than those in the control group (P < 0.05). There were no significant differences in serum estrogen, follicle-stimulating hormone, and luteinizing hormone between the two groups.
CONCLUSIONS: The results of this study suggest that Gua sha therapy was effective and safe in relieving perimenopausal symptoms and improving the quality of life in participants with perimenopausal syndrome. The therapy may serve as a promising, effective, nondrug treatment for perimenopausal syndrome in clinical work. Additional research is needed to better understand its effectiveness and examine its mechanism for treating perimenopausal syndrome.
PMID: 27760084 [PubMed - indexed for MEDLINE]