CYBERMED LIFE - ORGANIC  & NATURAL LIVING

Cybermedlife - Therapeutic Actions Fasting-Caloric Restriction

Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells.

Abstract Title: Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells. Abstract Source: J Cell Physiol. 2018 Feb ;233(2):1202-1212. Epub 2017 Jul 11. PMID: 28471474 Abstract Author(s): Oriana Lo Re, Concetta Panebianco, Stefania Porto, Carlo Cervi, Francesca Rappa, Stefano Di Biase, Michele Caraglia, Valerio Pazienza, Manlio Vinciguerra Article Affiliation: Oriana Lo Re Abstract: Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. Article Published Date : Jan 31, 2018

Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis.

Abstract Title: Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. Abstract Source: JBI Database System Rev Implement Rep. 2018 Feb ;16(2):507-547. PMID: 29419624 Abstract Author(s): Leanne Harris, Sharon Hamilton, Liane B Azevedo, Joan Olajide, Caroline De Brún, Gillian Waller, Vicki Whittaker, Tracey Sharp, Mike Lean, Catherine Hankey, Louisa Ells Article Affiliation: Leanne Harris Abstract: OBJECTIVE: To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment. INTRODUCTION: Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited. INCLUSION CRITERIA: This review included overweight or obese (BMI≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events. METHODS: A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses. RESULTS: Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156). CONCLUSIONS: Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review. Article Published Date : Jan 31, 2018

Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats. 📎

Abstract Title: Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats. Abstract Source: Exp Biol Med (Maywood). 2018 Feb ;243(4):334-343. Epub 2018 Jan 7. PMID: 29307281 Abstract Author(s): Bae Kun Shin, Suna Kang, Da Sol Kim, Sunmin Park Article Affiliation: Bae Kun Shin Abstract: Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused withβ-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared tothe Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats. Impact statement Intermittent fasting was evaluated for its effects on cognitivefunction and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. Therefore, intermittent fasting may prevent some of the metabolic pathologies associated with menopause and protect against age-related memory decline. Article Published Date : Jan 31, 2018

Intermittent Fasting Alleviates the Increase of Lipoprotein Lipase Expression in Brain of a Mouse Model of Alzheimer's Disease: Possibly Mediated byβ-hydroxybutyrate. 📎

Abstract Title: Intermittent Fasting Alleviates the Increase of Lipoprotein Lipase Expression in Brain of a Mouse Model of Alzheimer's Disease: Possibly Mediated byβ-hydroxybutyrate. Abstract Source: Front Cell Neurosci. 2018 ;12:1. Epub 2018 Jan 17. PMID: 29386999 Abstract Author(s): Jingzhu Zhang, Xinhui Li, Yahao Ren, Yue Zhao, Aiping Xing, Congmin Jiang, Yanqiu Chen, Li An Article Affiliation: Jingzhu Zhang Abstract: Intermittent fasting has been demonstrated to protect against Alzheimer's disease (AD), however, the mechanism is unclear. Histone acetylation and lipoprotein lipase (LPL) are involved in AD progression. Importantly, LPL has been documented to be regulated by histone deacetylases (HDACs) inhibitors (increase histone acetylation level) in adipocyte and mesenchymal stem cells, or by fasting in adipose and muscle tissues. In brain, however, whether histone acetylation or fasting regulates LPL expression is unknown. This study was designed to demonstrate intermittent fasting may protect against AD through increasingβ-hydroxybutyrate, a HDACs inhibitor, to regulate LPL. We also investigated microRNA-29a expression associating with regulation of LPL and histone acetylation. The results showed LPL mRNA expression was increased and microRNA-29a expression was decreased in the cerebral cortex of AD model mice (APP/PS1), which were alleviated by intermittent fasting. No significant differences were found in the total expression of LPL protein (brain-derived and located in capillary endothelial cells from peripheral tissues) in the cerebral cortex of APP/PS1 mice. Further study indicated that LPL located in capillary endothelial cells was decreased in the cerebral cortex of APP/PS1 mice, which was alleviated by intermittent fasting. LPL and microRNA-29a expression were separately increased and down-regulated in 2 μM Aβ-exposed SH-SY5Y cells, but respectively decreased and up-regulated in 10μM Aβ-exposed cells, which were all reversed byβ-hydroxybutyrate. The increase of HDAC2/3 expression and the decrease of acetylated H3K9 and H4K12 levels were alleviated in APP/PS1 mice by intermittent fasting treatment, as well in 2 or 10 μM Aβ-exposed cells byβ-hydroxybutyrate treatment. These findings above suggested the results from APP/PS1 mice were consistent with those from cells treated with 2 μM Aβ. Interestingly, LPL expression was reduced (0.2-folds) and microRNA-29a expression was up-regulated (1.7-folds) in HDAC2-silenced cells, but respectively increased (1.3-folds) and down-regulated (0.8-folds) in HDAC3-silenced cells. Furthermore, LPL expression was decreased in cells treated with microRNA-29a mimic and increased with inhibitor treatment. In conclusion, intermittent fasting inhibits the increase of brain-derived LPL expression in APP/PS1 mice partly throughβ-hydroxybutyrate-mediated down-regulation of microRNA-29a expression. HDAC2/3 may be implicated in the effect of β-hydroxybutyrate on microRNA-29a expression. Article Published Date : Dec 31, 2017

Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota.

Abstract Title: Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Abstract Source: Cell Metab. 2017 Oct 3 ;26(4):672-685.e4. Epub 2017 Sep 14. PMID: 28918936 Abstract Author(s): Guolin Li, Cen Xie, Siyu Lu, Robert G Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N Brocker, Tingting Yan, Kristopher W Krausz, Rong Xiang, Oksana Gavrilova, Andrew D Patterson, Frank J Gonzalez Article Affiliation: Guolin Li Abstract: While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. Article Published Date : Oct 02, 2017

Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. 📎

Abstract Title: Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. Abstract Source: Oncotarget. 2017 Sep 26 ;8(43):74649-74660. Epub 2017 Aug 16. PMID: 29088814 Abstract Author(s): Pengfei Sun, Huihui Wang, Zhiyong He, Xiangyuan Chen, Qichao Wu, Wankun Chen, Zhirong Sun, Meilin Weng, Minmin Zhu, Duan Ma, Changhong Miao Article Affiliation: Pengfei Sun Abstract: Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells. Article Published Date : Sep 25, 2017

Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice. 📎

Abstract Title: Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice. Abstract Source: J Clin Biochem Nutr. 2017 Sep ;61(2):100-107. Epub 2017 Jul 28. PMID: 28955126 Abstract Author(s): Toshihiko Okada, Takeshi Otsubo, Teruki Hagiwara, Fumika Inazuka, Eiko Kobayashi, Shinji Fukuda, Takuya Inoue, Kazuhide Higuchi, Yuki I Kawamura, Taeko Dohi Article Affiliation: Toshihiko Okada Abstract: Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation. Article Published Date : Aug 31, 2017

Intermittent Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy-Lysosome Pathway.

Abstract Title: Intermittent Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy-Lysosome Pathway. Abstract Source: Autophagy. 2017 Aug 30:0. Epub 2017 Aug 30. PMID: 28853981 Abstract Author(s): Haiyan Liu, Ali Javaheri, Rebecca J Godar, John Murphy, Xiucui Ma, Nidhi Rohatgi, Jana Mahadevan, Krzysztof Hyrc, Paul Saftig, Connie Marshall, Michael L McDaniel, Maria S Remedi, Babak Razani, Fumihiko Urano, Abhinav Diwan Article Affiliation: Haiyan Liu Abstract: Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin-1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in non-obese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes. Article Published Date : Aug 29, 2017

Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype?

Abstract Title: Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype? Abstract Source: Med Hypotheses. 2017 Aug ;105:1-3. Epub 2017 Jun 23. PMID: 28735644 Abstract Author(s): Benito Chiofalo, Antonio Simone Laganà, Vittorio Palmara, Roberta Granese, Giacomo Corrado, Emanuela Mancini, Salvatore Giovanni Vitale, Helena Ban Frangež, Eda Vrtačnik-Bokal, Onofrio Triolo Article Affiliation: Benito Chiofalo Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women. Article Published Date : Jul 31, 2017

Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

Abstract Title: Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition. Abstract Source: Metabolism. 2017 Jun ;71:70-82. Epub 2017 Mar 9. PMID: 28521881 Abstract Author(s): Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund Article Affiliation: Albert E Towers Abstract: BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. RESULTS: A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. CONCLUSIONS: Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Article Published Date : May 31, 2017

Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion.

Abstract Title: Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion. Abstract Source: J Nutr. 2017 May 17. Epub 2017 May 17. PMID: 28515159 Abstract Author(s): Yuan Hu, Ying Yang, Miao Zhang, Min Deng, Jun-Jian Zhang Article Affiliation: Yuan Hu Abstract: Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge.Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively (P<0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively (P<0.05). This suggests that IF has antioxidative and anti-inflammatory effects.Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation. Article Published Date : May 16, 2017

Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

Abstract Title: Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways. Abstract Source: Biogerontology. 2017 May 6. Epub 2017 May 6. PMID: 28478492 Abstract Author(s): Harpal Singh, Taranjeet Kaur, Shaffi Manchanda, Gurcharan Kaur Article Affiliation: Harpal Singh Abstract: Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen. Article Published Date : May 05, 2017

Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. 📎

Abstract Title: Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. Abstract Source: World J Diabetes. 2017 Apr 15 ;8(4):154-164. PMID: 28465792 Abstract Author(s): Terra G Arnason, Matthew W Bowen, Kerry D Mansell Article Affiliation: Terra G Arnason Abstract: AIM: To determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM). METHODS: We describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase. RESULTS: At baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m(2)]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P<0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82± 1.18). The increased fasting duration improved at-goal (<7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ(2) likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P>0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours). CONCLUSION: The results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings. Article Published Date : Apr 14, 2017

Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome - A Randomized Controlled Explorative Study.

Abstract Title: Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome - A Randomized Controlled Explorative Study. Abstract Source: Exp Clin Endocrinol Diabetes. 2017 Apr 13. Epub 2017 Apr 13. PMID: 28407662 Abstract Author(s): Chenying Li, Badri Sadraie, Nico Steckhan, Christian Kessler, Rainer Stange, Michael Jeitler, Andreas Michalsen Article Affiliation: Chenying Li Abstract: There is increasing experimental evidence for beneficial effects of calorie restriction and intermittent fasting in type 2 diabetes mellitus (T2DM). In humans, prolonged fasting is established as a health-promoting complementary treatment in Europe and claimed to improve metabolism by a complex hormetic response. We aimed to investigate effects of a one-week fasting period compared to usual care in T2DM by means of a pilot trial. Patients with manifest T2DM medically treated with oral hypoglycemic agents and/or insulin were randomly assigned to a 7-day fasting program followed by dietary advice or to usual care and dietary advice only. Fasting was performed according to the method of Buchinger with a nutritional energy intake of 300kcal/day by liquids only and stepwise re-introduction of solid food thereafter. Outcomes were assessed baseline and after 4 months. Of 46 enrolled participants, 32 (n=16 each group) completed the trial and were included for final analyses. Fasting was well accepted, there were no serious adverse events. After 4 months mean weight decreased by 3.5 kg and 2.0 kg in the fasting vs. control group (p=0.03) paralleled by greater reduction of abdominal circumference (p=0.001). Fasting led to a significant decrease of systolic/diastolic blood pressure (p=0.01; p=0.003) and increased quality-of-life (p=0.04), while for HbA1c, insulin and HOMA-index only non-significant improvements were observed. Results of this study suggest that prolonged fasting is feasible and might have beneficial clinical effects. The effectiveness of fasting should be proved in larger confirmatory trials that include intermittent fasting in follow-ups to enable morepronounced and long-term effects. Article Published Date : Apr 12, 2017

Positive effects of intermittent fasting in ischemic stroke.

Abstract Title: Positive effects of intermittent fasting in ischemic stroke. Abstract Source: Exp Gerontol. 2017 Mar ;89:93-102. Epub 2017 Jan 20. PMID: 28115234 Abstract Author(s): David Yang-Wei Fann, Gavin Yong Quan Ng, Luting Poh, Thiruma V Arumugam Article Affiliation: David Yang-Wei Fann Abstract: Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory. Article Published Date : Feb 28, 2017
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Therapeutic Actions Fasting/Caloric Restriction

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Differential diagnosis and molecular characterization of Theileria spp. in sika deer (Cervus nippon) in Hokkaido, Japan.

Related Articles Differential diagnosis and molecular characterization of Theileria spp. in sika deer (Cervus nippon) in Hokkaido, Japan. Parasitol Int. 2019 Jan 18;: Authors: Lee SH, Moumouni PFA, Galon EM, Vudriko P, Liu M, Benedicto B, Tumwebaze MA, Boldbaatar D, Umemiya-Shirafuji R, Fukumoto S, Xuan X Abstract Sika deer (Cervus nippon) is widely distributed in Asian countries and is one of the most common wildlife animals in Hokkaido, Japan. Previous studies identified Theileria spp. in sika deer in Japan including Theileria sp. Thrivae belonging to T. cervi group and Theileria sp. sola belonging to T. capreoli group. However, the studies failed to differentiate these two species without sequencing. Therefore, epidemiological information on cervine theileriosis in Hokkaido, Japan is limited. This study differentiated the two Theileria spp. using restriction fragments length polymorphism (RFLP). Based on the PCR-RFLP, Theileria spp. were identified in 103 (88.0%) of 117 samples, and the prevalence of each parasites were 86.3% (n = 101) and 57.3% (n = 67) for Theileria sp. Thrivae and T. capreoli-like, respectively. Phylogenetic analysis based on the 18S rRNA showed a close relationship between Theileria sp. Thrivae and T. cervi in China. In addition, phylogenetic analysis of internal transcribed spacer regions also showed a close relationship between Theileria sp. Thrivae and T. cervi. PMID: 30664981 [PubMed - as supplied by publisher]

Association of physical activity and cardio-respiratory function or BMI and body composition in preterm born individuals: a systematic review.

Related Articles Association of physical activity and cardio-respiratory function or BMI and body composition in preterm born individuals: a systematic review. Acta Paediatr. 2019 Jan 21;: Authors: Spiegler J, Eves R, Mendonça M, Wolke D Abstract AIM: To evaluate the association of physical activity (PA) and forced expiratory volume in 1 second (FEV1), peak oxygen consumption (pVO2), body mass index (BMI) and body composition in preterm born individuals. METHODS: Cochrane Library, EMBASE, MEDLINE, AMED, ERIC, Web of Science and PsycInfo were searched with no restriction on language and date of publication from inception to January 2018. Data were extracted comparing preterm born individuals with different frequencies of PA and the outcome of interest. RESULTS: One randomized controlled, two longitudinal and thirteen cross sectional studies comprising 1922 preterm born individuals aged 5-25 were included. Assessment varied from a PA program to accelerometer data, interviews and self-report questionnaires. In preterm born children, more PA was associated with better cardio-respiratory function in those groups with impaired lung function or with lower BMI in those groups with increased risk factors, but no association was found in unimpaired children. In preterm born adults, more PA was associated with higher pVO2 and lower BMI. CONCLUSION: Only tentative conclusions can be drawn, especially regarding differences of the association of PA between preterm and term born populations. Further studies are needed to analyse the association of PA in preterm born individuals with reduced cardio-respiratory function. This article is protected by copyright. All rights reserved. PMID: 30664798 [PubMed - as supplied by publisher]

Differential response of T cells to an immunogen, a mitogen and a chemical carcinogen in a mouse model system.

Related Articles Differential response of T cells to an immunogen, a mitogen and a chemical carcinogen in a mouse model system. J Biochem Mol Toxicol. 2019 Jan 21;:e22290 Authors: Kaur AP, Saxena N, Chandra NC Abstract In this study, we examined the relative immune response of T-lymphocytes and its intracellular cholesterol homeostasis, in a mouse model system, after treatment with immunogen, mitogen, and carcinogen. We studied the T-lymphocyte percentage, their LDL-receptor expression, along with the levels of serum interleukins (IL-2, IFNγ, IL-4, and IL-10) and intracellular cholesterol concentration (cytoplasmic and nuclear). The mitogen was found to be a better stimulator of T-cell marker expressions than the immunogen; though the immunogen was more effective on immunogenic response as was marked from interleukin levels. The chemical carcinogen benzo-α-pyrene at low concentration acted potentially like a mitogen but a reduced immune response was apparent at a carcinogenic dose. The findings in our study focus on the effect of carcinogenic dose of benzo-α-pyrene (BaP) on T-cell immunity. Benzo-α-pyrene causes immunosuppression through restriction of the T-cell population by targeting intracellular cholesterol. PMID: 30664314 [PubMed - as supplied by publisher]

Anagen hair follicle repair: timely regenerative attempts from plastic extra-bulge epithelial cells.

Related Articles Anagen hair follicle repair: timely regenerative attempts from plastic extra-bulge epithelial cells. Exp Dermatol. 2019 Jan 21;: Authors: Huang WY, Lin ET, Hsu YC, Lin SJ Abstract Anagen hair follicle repair is the regenerative scheme activated to restore the structure and hair growth following injuries to anagen hair follicles. Compared with telogen-to-anagen regeneration and hair follicle neogenesis, anagen hair follicle repair is a clinically important, yet relatively unexplored regenerative feature of hair follicles. Due to their highly proliferative character, germinative cells and matrix cells within hair bulbs are highly susceptible to injuries, such as chemotherapy and radiotherapy. Clinical and experimental observations suggest that damaged anagen hair follicles are able to repair themselves to resume anagen growth, bypassing premature catagen/telogen entry. Mechanistically, extra-bulge epithelial cells in the outer root sheath and the lower proximal cup are quickly mobilized for regeneration. These cells acquire stem cell-like properties, exhibiting high plasticity by breaking lineage restriction to regenerate all cell types in the lower segment of anagen hair follicles. Facilitating extra-bulge epithelial cells' mobilization ameliorates hair loss from chemo- and radio-therapy. On the other hand, quiescent bulge stem cells can also be activated, but only after more severe injuries and with slower activation dynamics. They show limited plasticity and regenerate part of the outer root sheath only. The dysrhythmic activation might render bulge stem cells susceptible to concomitant injuries due to their exit from quiescence. This article is protected by copyright. All rights reserved. PMID: 30664259 [PubMed - as supplied by publisher]

Teratogenicity of antiepileptic drugs.

Related Articles Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019 Jan 16;: Authors: Tomson T, Battino D, Perucca E Abstract PURPOSE OF REVIEW: We review data on the comparative teratogenicity of antiepileptic drugs (AEDs), focusing on major congenital malformations (MCMs), intrauterine growth restriction, impaired cognitive development, and behavioral adverse effects following prenatal exposure. RECENT FINDINGS: Prospective registries and meta-analyses have better defined the risk of MCMs in offspring exposed to individual AEDs at different dose levels. Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent. Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits. In a population-based study, the risk of AED-induced autistic traits was attenuated by periconceptional folate supplementation. SUMMARY: The risk of adverse fetal effects differs in relation to the type of AED and for some AEDs also the daily dose. Although for MCMs the risk is primarily associated with the first trimester of gestation, influences on cognitive and behavioral development could extend throughout pregnancy. Available information now permits a more rational AED selection in women of childbearing potential, and evidence-based counseling on optimization of AED treatment before conception. PMID: 30664067 [PubMed - as supplied by publisher]

Genetic Polymorphisms in LTF/EcoRI and TLR4/AluI loci as candidates for milk and reproductive performance assessment in Holstein cattle.

Related Articles Genetic Polymorphisms in LTF/EcoRI and TLR4/AluI loci as candidates for milk and reproductive performance assessment in Holstein cattle. Reprod Domest Anim. 2019 Jan 21;: Authors: El-Domany WB, Radwan HA, Ateya AI, Ramadan HH, Marghani BH, Nasr SM Abstract The aim of this study was to explore the genetic Polymorphisms in LTF/EcoRI and TLR4/AluI loci and their association with milk and reproductive performance in Holstein cattle. A randomly selected 800 Holstein dairy cows from two dairy farms (400 animals each) in Egypt were used. Based on the two farm records, association between LTF/EcoRI genotypes and milk performance traits (order of lactation, daily milk yield, days in milk, corrected milk at 305 day and dry period) was carried out. Meanwhile, exploring of TLR4/AluI genotypes effect was done on data for reproductive performance (age at first freshening, calving interval, number of services per conception, ovarian rebound and days open). DNA was extracted from blood samples collected from Holstein dairy cows of the both farms and restriction analysis of 301-bp PCR products of LTF gene revealed two genotypes; AA genotype (301-bp) and AB genotype (301, 201 and 100-bp). Meanwhile, restriction analysis of 382-bp PCR products of TLR4 gene digested with AluI yielded two alleles (A and B) and three genotypes (AA, AB and BB). The A allele was indicated by two bands at 300-bp and 82-bp and the B allele resulted in three fragments of 160, 140 and 82-bp. There was a significant association (P ≤ 0.05) between LTF genotypes and milk performance traits except for days in milk. The TLR4 genotypes had significant effects (P ≤ 0.05) on age at first freshening, calving interval, number of services per conception, ovarian rebound and days open. Ordinal logistic regression statistical model also revealed that it is possible to calculate high reproductive performance traits and to predict favorable dairy cows based on LTF and TLR4 genotypes. This research reveals the effectiveness of LTF/EcoRI and TLR4/AluI loci as candidates for reproductive performance assessment in Holstein cattle. This article is protected by copyright. All rights reserved. PMID: 30663809 [PubMed - as supplied by publisher]

Identification of a novel biomarker for pyridoxine-dependent epilepsy: Implications for newborn screening.

Related Articles Identification of a novel biomarker for pyridoxine-dependent epilepsy: Implications for newborn screening. J Inherit Metab Dis. 2019 Jan 21;: Authors: Wempe MF, Kumar A, Kumar V, Choi YJ, Swanson MA, Friederich MW, Hyland K, Yue WW, Van Hove JLK, Coughlin CR Abstract Pyridoxine-dependent epilepsy (PDE) is often characterized as an early onset epileptic encephalopathy with dramatic clinical improvement following pyridoxine supplementation. Unfortunately, not all patients present with classic neonatal seizures or respond to an initial pyridoxine trial, which can result in the under diagnosis of this treatable disorder. Restriction of lysine intake and transport is associated with improved neurologic outcomes, although treatment should be started in the first year of life to be effective. Because of the documented diagnostic delay and benefit of early treatment, we aimed to develop a newborn screening method for PDE. Previous studies have demonstrated the accumulation of Δ1 -piperideine-6-carboxylate and α-aminoadipic semialdehyde in individuals with PDE, although these metabolites are unstable at room temperature limiting their utility for newborn screening. As a result, we sought to identify a biomarker that could be applied to current newborn screening paradigms. We identified a novel metabolite, 6-oxo-pipecolate, which accumulates in substantial amounts in blood, plasma, urine and cerebral spinal fluid of individuals with PDE. Using a stable isotope labeled internal standard, we developed a non-derivatized liquid chromatography tandem mass spectrometry-based method to quantify 6-oxo-pipecolate. This method replicates the analytical techniques used in many laboratories and could be used with few modifications in newborn screening programs. Furthermore, 6-oxo-pipecolate was measurable in urine for four months even when stored at room temperature. Herein, we report a novel biomarker for PDE that is stable at room temperature and can be quantified using current newborn screening techniques. This article is protected by copyright. All rights reserved. PMID: 30663059 [PubMed - as supplied by publisher]

Causes of stillbirths in diabetic and gestational diabetes pregnancies at a NSW tertiary referral hospital.

Related Articles Causes of stillbirths in diabetic and gestational diabetes pregnancies at a NSW tertiary referral hospital. Aust N Z J Obstet Gynaecol. 2019 Jan 20;: Authors: Wang M, Athayde N, Padmanabhan S, Cheung NW Abstract BACKGROUND: Diabetes in pregnancy may result in stillbirth or neonatal death. AIM: This audit examined stillbirths of mothers with pre-existing diabetes in pregnancy (DIP) and gestational diabetes (GDM) to determine maternal and diabetic characteristics implicated in these deaths. MATERIALS AND METHODS: A retrospective cohort study was conducted to identify stillbirths occurring in diabetic pregnancies at Westmead Hospital during 2006-2017. Medical records were reviewed to obtain data relating to maternal factors, diabetes history, glycaemic control and cause of death. RESULTS: There were 37 women (seven with type 1 diabetes [T1DM], 11 with type 2 diabetes [T2DM] and 19 with GDM) who had 38 stillbirths. The leading cause of stillbirth was lethal congenital malformations in nine cases, followed by placental and umbilical abnormalities in six, intra-uterine growth restriction (IUGR) in six, and obstetric factors in four cases. Malformations were predominantly cardiovascular (n = 7), musculoskeletal (n = 5) and gastrointestinal (n = 4). There was no difference in the proportion of stillbirths related to malformations between the DIP and GDM groups (P = 0.22). In the pre-conception period or first trimester, all T1DM subjects and all but two T2DM subjects had HbA1c >7% or there was no measurement. HbA1c was >7% in 6/7 T1DM subjects and 7/11 T2DM subjects at some stage during the pregnancy. CONCLUSION: Stillbirth remains a problem in diabetic pregnancy in the 21st century. Lethal malformations, placental abnormalities and IUGR were the leading causes of stillbirth related to diabetes. Pre-conception counselling and planning to achieve better glycaemic control in pregnancy needs to be improved. PMID: 30663043 [PubMed - as supplied by publisher]

Metabolomics of Pregnancy Complications: Emerging Application of Maternal Hair.

Related Articles Metabolomics of Pregnancy Complications: Emerging Application of Maternal Hair. Biomed Res Int. 2018;2018:2815439 Authors: Delplancke TDJ, Wu Y, Han TL, Joncer LR, Qi H, Tong C, Baker PN Abstract In recent years, the study of metabolomics has begun to receive increasing international attention, especially as it pertains to medical research. This is due in part to the potential for discovery of new biomarkers in the metabolome and to a new understanding of the "exposome", which refers to the endogenous and exogenous compounds that reflect external exposures. Consequently, metabolomics research into pregnancy-related issues has increased. Biomarkers discovered through metabolomics may shed some light on the etiology of certain pregnancy-related complications and their adverse effects on future maternal health and infant development and improve current clinical management. The discoveries and methods used in these studies will be compiled and summarized within the following paper. A further focus of this paper is the use of hair as a biological sample, which is gaining increasing attention across diverse fields due to its noninvasive sampling method and the metabolome stability. Its significance in exposome studies will be considered in this review, as well as the potential to associate exposures with adverse pregnancy outcomes. Currently, hair has been used in only two metabolomics studies relating to fetal growth restriction (FGR) and gestational diabetes mellitus (GDM). PMID: 30662903 [PubMed - in process]

TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population.

Related Articles TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population. Int J Ophthalmol. 2019;12(1):25-29 Authors: Chernykh V, Shevchenko A, Konenkov V, Prokofiev V, Eremina A, Trunov A Abstract AIM: To study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis. PMID: 30662836 [PubMed]

Antiviral Protection by IFITM3 In Vivo.

Related Articles Antiviral Protection by IFITM3 In Vivo. Curr Clin Microbiol Rep. 2018 Dec;5(4):229-237 Authors: Zani A, Yount JS Abstract Purpose of Review: Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human IFITM3 gene and severe virus infections. Recent Findings: Recent publications show that IFITM3 knockout mice experience more severe pathologies than wild-type mice in diverse virus infections, including infections with influenza A virus, West Nile virus, Chikungunya virus, Venezuelan equine encephalitis virus, respiratory syncytial virus, and cytomegalovirus. Likewise, numerous studies of humans of Chinese ancestry have associated the IFITM3 SNP rs12252-C with severe influenza virus infections, though examinations of other populations, such as Europeans, in which this SNP is rare, have largely failed to identify an association with severe infections. A second SNP, rs34481144-A, found in the human IFITM3 promoter has also recently been reported to be a risk allele for severe influenza virus infections. Summary: There is significant evidence for a protective role of IFITM3 against virus infections in both mice and humans, though additional work is required to identify the range of pathogens restricted by IFITM3 and the mechanisms by which human SNPs affect IFITM3 levels or functionality. PMID: 30662816 [PubMed]

Color Doppler sonography of the aortic isthmus in intrauterine growth-restricted fetuses and normal fetuses.

Related Articles Color Doppler sonography of the aortic isthmus in intrauterine growth-restricted fetuses and normal fetuses. Eur J Transl Myol. 2018 Nov 02;28(4):7773 Authors: Younesi L, Ghadamzadeh M, Amjad G, Lima ZS Abstract Intrauterine growth restriction is associated with a significant increase in morbidity and perinatal mortality, and increases the likelihood of fetal death, asphyxia, meconium aspiration, hypoglycemia, and neonatal hypothermia. The aim of this study was to determine aortic isthmus flow difference by using color doppler sonography in Intrauterine growth restriction and normal fetuses. The data presented were obtained from 30 mothers, who referred to the radiology department of Akbarabadi Hospital of Tehran with a diagnosis of intrauterine growth restriction. An ultrasound was performed to determine the status of placenta, fetus, and amniotic fluid. The umbilical arterial doppler assessment was used to confirm diagnosis of intrauterine growth restriction. Thirteen (43.3%) were nulliparous mothers and 17 (56.7%) were multiparous mothers. 30 pregnant women with healthy fetuses were enrolled as control group. According to the ultrasound findings, Dactus Venus wave type was recorded in intrauterine growth restriction fetuses, which was reported as normal (26 subjects; 86.7%) and abnormal (4 subjects; 13.3%). All together, this study provides appropriate guidance to use doppler for delivery timing and to control risk factors. PMID: 30662698 [PubMed]

The Human IL-23 Decoy Receptor Inhibits T-Cells Producing IL-17 by Genetically Engineered Mesenchymal Stem Cells.

Related Articles The Human IL-23 Decoy Receptor Inhibits T-Cells Producing IL-17 by Genetically Engineered Mesenchymal Stem Cells. Int J Cell Biol. 2018;2018:8213912 Authors: Rostami M, Haidari K, Shahbazi M Abstract The immunomodulatory and self-renewable features of human adipose mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin 23 (IL- 23) as a proinflammatory cytokine suppresses T regulatory cells (Treg) and promotes the response of T helper 17 (Th17) and T helper 1 (Th1) cells. This pathway starts inflammation and immunosuppression in several autoimmune diseases. The current study for producing recombinant IL- 23 decoy receptor (RIL- 23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes reducing inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL- 23R was designed and cloned into a pCDH-813A- 1 lentiviral vector. The transduction of hAD-MSCs was performed at MOI (multiplicity of infection) = 50 with pCDH- EFI α- RIL- 23R- PGK copGFP. Expressions of RIL- 23R and octamer-binding transcription factor 4 (OCT- 4) were determined by real-time polymerase chain reaction (real time-PCR). Self-renewing properties were assayed with OCT- 4. Bioactivity of the designed RIL- 23R was evaluated by IL- 17 and IL- 10 expression of mouse splenocytes. Cell differentiation confirmed the true isolation of hAD-MSCs from lipoaspirate. Restriction of the enzyme digestion and sequencing verified the successful cloning of RIL- 23R in the CD813A-1 lentiviral vector. The green fluorescent protein (GFP) positive transduction rate was up to 90%, and real-time PCR showed the expression level of RIL-23R. Oct-4 had a similar expression pattern with nontransduced hAD-MSCs and transduced hAD-MSCs/ RIL-23R indicating that lentiviral vector did not affect hAD-MSCs characteristics. Downregulation of IL-17 and upregulation of IL-10 showed the correct activity of the engineered hAD-MSCs. The results showed that the transduced hAD-MSCs/ RIL- 23R, expressing IL-23 decoy receptor, can give a useful approach for a basic research on cell-based gene therapy for autoimmune disorders. PMID: 30662466 [PubMed]

Post-operative rehabilitation of a distal biceps brachii tendon reattachment in a weightlifter: a case report.

Related Articles Post-operative rehabilitation of a distal biceps brachii tendon reattachment in a weightlifter: a case report. J Can Chiropr Assoc. 2018 Dec;62(3):193-201 Authors: Wentzell M Abstract Objective: To describe the successful rehabilitation of a distal biceps brachii tendon reattachment following an acute traumatic tendon rupture. Clinical Features: A 30-year-old weightlifter presented five days post-op after a left distal biceps tendon repair. A three month one pound weight-restriction was recommended by the attending surgeon. Active and passive elbow and wrist range of motion were markedly reduced with profuse post-operative swelling and bruising noted upon initial inspection. Intervention and Outcome: An accelerated treatment program was prescribed that included soft tissue therapy, scar mobilization, laser therapy, kinesiology tape and rehabilitative exercise. A novel training method known as blood flow restriction (BFR) training was utilized throughout the rehabilitative process to maximize recovery and retain muscle mass and strength. The weightlifter returned to near pre-injury activity level after 3.5 months. Treatment, exercise and BFR protocols are provided. PMID: 30662074 [PubMed]
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