AMP-activated protein kinase is a key regulator of obesity-associated factors.

An imbalance between caloric intake and energy expenditure leads to obesity. Obesity is an important risk factor for the development of several metabolic diseases including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. So, controlling obesity could be effective in the improvement of obesity-related diseases. Various factors are involved in obesity, such as AMP-activated protein kinases (AMPK), silent information regulators, inflammatory mediators, oxidative stress parameters, gastrointestinal hormones, adipokines, angiopoietin-like proteins, and microRNAs. These factors play an important role in obesity by controlling fat metabolism, energy homeostasis, food intake, and insulin sensitivity. AMPK is a heterotrimeric serine/threonine protein kinase known as a fuel-sensing enzyme. The central role of AMPK in obesity makes it an attractive molecule to target obesity and related metabolic diseases. In this review, the critical role of AMPK in obesity and the interplay between AMPK and obesity-associated factors were elaborated.

COVID-19 re-infection in Shahroud, Iran: a follow-up study.

Although many people became infected and recovered during the COVID-19 epidemic, the immunity duration and re-infection in recovered patients have recently attracted many researchers. The aim of this study was to evaluate the recurrence of the infection in recovered individuals over a 9-month period after the onset of the COVID-19 epidemic. In this study, data related to COVID-19 patients in Shahroud city were collected using the electronic system for registering suspicious patients and also by checking patients' hospital records. In this study, from 20 March 2020 to 20 November 2020 (9 months), a total of 8734 suspected patients with respiratory symptoms were observed and followed up. RT-PCR was positive for 4039 patients. During this period, out of the total number of positive cases of COVID-19, 10 cases became re-infected after complete recovery. The risk of re-infection was 2.5 per thousand (0.95 CI 1.2-4.5). The mean time interval between the first infection and re-infection was 134.4 ± 64.5 days (range 41-234 days). The risk of re-infection between male and females was not statistically different (1.98 per 1000 women and 2.96 per 1000 men). Exposure to COVID-19 may not establish long-term protective immunity to all patients and may predispose them to re-infection. This fact can be reminded that the use of masks, social distancing and other preventive measures are very important in recovered patients and should be emphasised especially in health care personnel who are more exposed to the virus.

Inhibiting miR-27a and miR-142-5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway.

The gene Nrf2 (nuclear factor-erythroid 2-related factor 2) is the most important regulator of the cellular antioxidant system and its dysregulation has a role in the etiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association between Nrf2 targeted miRNAs (miR-27a, miR-142-5p, miR-153, and miR-128) with lipid accumulation in vitro and in vivo models of NAFLD. We used two in vivo and in vitro models of NAFLD. The expression of the genes and miRNAs was assessed by real-time PCR and the protein level was evaluated using western blot. To investigate the potential role of miRNAs in NAFLD, the inhibitors or mimics of the miR-27a and miR-142-5p were transfected into HepG2 cells. The mRNA and protein levels of Nrf2 were significantly decreased in the liver of high fat diet-fed mice as well as in HepG2 cells treated with high glucose (HG). Reduced expression of Nrf2 was associated with increased expression levels of miR-27a and miR-142-5p in both models of NAFLD. HG-induced triglyceride accumulation was attenuated by inhibition of miR-27a or miR-142-5p in HepG2 cells. Overexpression of miR-27a or miR-142-5p suppressed the expression of Nrf2 and its downstream antioxidant genes and increased production of reactive oxygen species, whereas inhibition of miR-27a or miR-142-5p reversed these effects. In conclusion, the data of this study may suggest that miR-27a and miR-142-5p are increased in NAFLD, where they suppress Nrf2 expression and contribute to the accumulation of lipids in the hepatocytes.

Effects of DHA-enriched fish oil on gene expression levels of p53 and NF-κB and PPAR-γ activity in PBMCs of patients with T2DM: A randomized, double-blind, clinical trial.

BACKGROUND AND AIMS: Omega-3 polyunsaturated fatty acids (PUFAs) are natural peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands. Activated PPAR-γ protects the cardiovascular system against atherosclerotic lesion formation and exerts its anti-inflammatory role by suppressing cytokines induced by nuclear factor kappa-B (NF-κB) in endothelial cells (ECs), and it is hypothesized that apoptosis and cell cycle arrest induced by PPAR-γ ligands may be mediated by the p53-dependent pathway. The aim of our study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on PPAR-γ activity and mRNA expression levels of p53 and NF-κB. METHODS AND RESULTS: Fifty patients with type 2 diabetes mellitus (T2DM) aged 30-70 years were randomly assigned to receive either 2400 mg/d DHA-rich fish oil or placebo for 8 weeks. Metabolic parameters were assessed at baseline and at the end of the intervention. PPAR-γ activity in the peripheral blood mononuclear cells (PBMCs) was measured using ELISA-based PPAR-γ Transcription Factor Assay Kit, and the gene expression levels of p53 and NF-κB were assessed using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). On the basis of our finding, 8 weeks of treatment with DHA-rich fish oil increased PPAR-γ activity in PBMCs of subjects with T2DM (p < 0.01) compared to that in placebo (p = 0.4). Between-group comparisons of mean PPAR-γ activity changes showed significant differences (p = 0.03), whereas mRNA expression levels of the p53 and NF-κB genes did not show significant differences between studied groups (p = 0.2 and p = 0.5, respectively). CONCLUSION: Our findings indicated that short-term DHA-rich fish oil supplementation may modulate PPAR-γ activity in PBMCs.

Evaluation of lipid ratios and triglyceride-glucose index as risk markers of insulin resistance in Iranian polycystic ovary syndrome women.

BACKGROUND: Insulin resistance has a vital role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have shown that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. The present study was conducted to evaluate the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C), as well as fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR)) among the Iranian women diagnosed with PCOS. METHODS: In the current study, a total of 305 women with PCOS were evaluated. TG/HDL-C, TC/HDL-C, and TyG indices were calculated. Fasting insulin level was measured using ELISA technique. IR was defined as a HOMA-IR value of ≥2.63, FG-IR value of < 8.25, and QUICKI value of < 0.33. RESULTS: The insulin-resistant (IR) and insulin-sensitive (IS) groups, established by the HOMA-IR, FG-IR, and QUICKI values were different in terms of TG/HDL-C, TC/HDL-C, and TyG indices. These indices were associated with IR even after adjusting for age and BMI. ROC curve analyses showed that TyG, TG/HDL-C, and TC/HDL-C strongly predicted HOMA-IR with area under the curve (AUC) of 0.639, 0.619, and 0.623, respectively (P < 0.05). Further, TC/HDL-C was a good predictor of FG-IR with AUC of 0.614 (P = 0.04). CONCLUSION: TyG, TG/HDL-C, and TC/HDL-C indices might be good indicators of IR among Iranian women diagnosed with PCOS.

Does myoinositol supplement improve sperm parameters and DNA integrity in patients with oligoasthenoteratozoospermia after the freezing-thawing process?

Sperm cryopreservation is a routine method in andrology and IVF laboratory. However, the sperm quality and its fertilizing capacity have been decreased during this process. The purpose of this experiment was to determine the role of myoinositol as a supplement in amelioration of total and progressive sperm motility, DNA fragmentation, total antioxidant capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation after the freezing-thawing process on patients with oligoasthenoteratozoospermia (OAT) syndrome. Semen samples obtained from 40 patients were divided into two aliquots and freezed with simple and 2 mg/mL myoinositol (MYO) supplemented freezing media. All samples were thawed and assessed after one month. Semen parameters were analyzed in terms of the motility by CASA, the level of total ROS by fluorimetry, TAC and MDA by colorimetric assay and finally DNA fragmentation by TUNEL assay. Our results clearly showed that MYO could improve total (37.46 vs. 12.91, p < 0.001) and progressive motility (21.92 vs. 6.49, p < 0.001) in experimental group compared to control group. A higher TAC level was observed in the MYO treated group in comparison to control group (1.11 vs. 0.91, p = 0.05). While MYO supplementation could not be effective on ROS level, it reduced DNA fragmentation of sperm after freeze-thaw process (p = 0.01). Therefore, MYO could be a good supplement for sperm freezing to reduce the detrimental effects of freezing process especially on DNA integrity, which is an important factor in the success of ART, in OAT suffered patients.

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

BACKGROUND: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients. METHODS: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). NPC1 gene expression analysis was performed by quantitative real-time PCR, and correlation between the two parameters was assessed. RESULTS: Mean IL-10 serum concentration and peripheral blood mononuclear cells' (PBMCs) gene expression of NPC1, adjusted for drug consumption, age, and BMI, was not significantly different between the patient and control groups (p = 0.6 and 0.67 respectively). However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29). We also observed lower serum concentration of IL-10 in the subjects with lower 25-hydroxyvitamin D serum concentration (p = 0.034). CONCLUSIONS: Our findings supported the previous observations showing the contribution of lysosomal lipid homeostasis of PBMCs to inflammation and pathogenesis of atherosclerosis.

Circulating Levels of IL-35 and Gene Expression of FoxP3 in Coronary Artery Disease: Is There Any Interplay Between Them and 25-Hydroxyvitamin D3?

BACKGROUND: We aimed to evaluate interleukin-35 (IL-35) serum levels and the forkhead box P3 (FoxP3) expression in peripheral blood mononuclear cells (PBMCs) of coronary artery disease (CAD) patients compared with the non-CAD group. Also, we examined the possible relationship between gene expression of FoxP3 and serum levels of IL-35 with several CAD-related clinical parameters. METHODS: This study was conducted on 40 men with CAD and 40 men with a normal coronary artery. The gene expression of FoxP3 was measured by real-time polymerase chain reaction (real-time PCR). The serum concentrations of IL-35 and 25-hydroxyvitamin D3 (25(OH)D3) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FoxP3 gene expression was significantly decreased in patients compared to controls (p = 0.01). Serum concentrations of IL-35 and 25(OH)D3 were significantly reduced in patients in comparison with the control group (both, p < 0.001), and reduction of IL-35 showed an independent association with CAD. IL-35 levels had a significant positive correlation with serum 25(OH)D3 (r = 0.266, p = 0.044) in the whole population. Moreover, there was an inverse correlation between the FoxP3 expression and CAD severity in CAD patients (r = -0.372, p = 0.01). CONCLUSIONS: It appears that reduced mRNA expression of FoxP3 and circulating level of IL-35 are of significance in the context of CAD pathogenesis. However, more studies are required to elucidate underlying mechanisms.

Polysilsesquioxane decorated ZIF-8 as a potential pH-responsive vehicle for topical delivery and release of acyclovir and tetracycline: Investigation of blood compatibility, cytotoxicity and antibacterial properties.

In this research, poly-chloropropylmethyl-silsesquioxanen was prepared and decorated with ZIF-8 in order to investigate its loading capacity for acyclovir and tetracycline. Before and after drug loadings, the composites were characterized by FT-IR, SEM-EDS, XRD, and XPS analyses. Then, the in-vitro release of these drugs was investigated by UV-Vis spectroscopy in different buffers (pH = 5, 7.4, and 9.1). The results showed that the release of ACV reached a maximum amount of 41.3 mg at pH = 7.4 during 12 h. In comparison, the release of TC reached a maximum amount of 22.5 mg at pH = 5 during 6 h. The blood compatibility, in-vitro cytotoxicity on the L929 fibroblast cells line, and antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa were also investigated for this composite as a drug carrier.

In vitro and Molecular Docking Analysis of Quercetin as an Anti-inflammatory and Antioxidant.

INTRODUCTION: Quercetin (3,3',4',5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties. AIMS: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS). METHODS: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes. RESULTS: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD. CONCLUSION: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs.

Crosstalk between autophagy and insulin resistance: evidence from different tissues.

Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.

Are lipid ratios and triglyceride-glucose index associated with critical care outcomes in COVID-19 patients?

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10-1.82, OR = 1.06 CI: 1.02-1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06-1.18, OR = 1.24 CI:1.05-1.48, OR = 1.47 CI:1.19-1.80, OR = 1.52 CI:1.01-2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis.

Anti-inflammatory effects of resveratrol in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic inflammation is one of the most important factors involved in the development and progression of cardiovascular disease (CVDs). Accumulating evidence has described the effect of resveratrol, a natural polyphenolic compound, on biomarkers of inflammation among patients with CVDs; however, findings are controversial. Here we performed a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of resveratrol supplements on TNF-α, IL-6, and CRP levels in CVDs patients. METHODS: Online research was conducted in the following database: MEDLINE, EMBASE, Cochrane Library, Web of Science databases, and Scopus. This systematic review and meta-analysis were conducted to investigate the effects of resveratrol supplements on inflammatory biomarkers among patients with CVDs. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. RESULTS: Six RCTs met the inclusion criteria and were selected for the current meta-analysis. Our results demonstrated that resveratrol significantly decreases serum levels of CRP (MD = -0.63, 95 % CI: -0.1.13, -0.12; p = 0.01), and TNF-α (MD = -0.55, 95 % CI: -1.04, -0.06; p = 0.02), however, resveratrol had not significant effect on serum concentration of IL-6 (MD = -0.12, 95 % CI: -0.52, 0.27; p = 0.53), in patients with CVDs. CONCLUSION: Our results suggest that resveratrol can be used as a potential treatment in patients with CVD by reducing inflammatory conditions.

The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications.

Insulin resistance, the most important characteristic of the type 2 diabetes mellitus (T2DM), is mostly caused by impairment in the insulin receptor (IR) signal transduction pathway. Protein tyrosine phosphatase 1B (PTP1B), one of the main negative regulators of the IR signaling pathway, is broadly expressed in various cells and tissues. PTP1B decreases the phosphorylation of the IR resulting in insulin resistance in various tissues. The evidence for the physiological role of PTP1B in regulation of metabolic pathways came from whole-body PTP1B-knockout mice. Whole-body and tissue-specific PTP1B-knockout mice showed improvement in adiposity, insulin resistance, and glucose tolerance. In addition, the key role of PTP1B in the pathogenesis of T2DM and its complications was further investigated in mice models of PTP1B deficient/overexpression. In recent years, targeting PTP1B using PTP1B inhibitors is being considered an attractive target to treat T2DM. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. We herein summarized the biological functions of PTP1B in different tissues in vivo and in vitro. We also describe the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat T2DM.

The Synergistic Anticancer Traits of Graphene Oxide Plus Doxorubicin Against BT474 and MCF7 Breast Cancer Stem Cells In Vitro.

Breast cancer is among the leading causes of death due to cancers around the globe. Current therapeutic approaches towards healing of breast cancer have been associated with poor outcomes. Graphene and its derivatives have a two-dimensional flat structure, which is characterized by the ability to carry drugs and modify the surface, low cytotoxicity, and high biocompatibility. This study was performed on MCF7 and BT474 human breast cancer cells. Different concentrations of doxorubicin (DOX), graphene oxide (GO), and graphene oxide plus doxorubicin (GO-DOX) were subjected to both cell lines at specified intervals. At the end of the treatments, MTT test was applied to determine the viability of cells, and then flow cytometry, colony formation, and spheroid tests were implemented in both cell lines treated with DOX, GO, and GO-DOX components. We used DLS and TEM to confirm the GO properties. According to the MTT test results, 1 µL of DOX at 10 mg/ml (equivalent to 0.1 mg/ml) caused 50% survival of MCF7 cells at 24 h. In both cell lines, an increase in apoptosis occurred after incubation with GO and DOX. Although a rate of mortality of MCF-7 cells was due to necrosis, the BT474 cell death was merely through the apoptosis. Furthermore, the results of the colony formation test outlined an enhancing inhibitory effect in the presence of GO-DOX as a comparison to the control. Additionally, spheroids formed following treatment with GO-DOX exhibited a significant decrease compared to their control group, with an increase in the number of spheroids in BT474 cells compared to those in the MCF-7. The decreasing effect of compounds against the migration and cell invasion potential was also observed, being higher in MCF7 than BT474 cells. The effects of cytotoxic GO were observed at higher concentrations.

Resveratrol Reduces Lipid Accumulation through Upregulating the Expression of MicroRNAs Regulating Fatty Acid Bet Oxidation in Liver Cells: Evidence from In-vivo and In-vitro Studies.

MicroRNAs have been shown to regulate lipogenesis in liver. The aim of the present study was to investigate whether the effects of resveratrol (RSV) on lipogenesis are associated with the changes in the expression of two miRNAs (miR-107 and miR-10b) that regulate lipogenic pathways. 30 wild type C57BL/6j male mice were randomly fed three diets: a standard chow diet (ND), a high fat diet (HFD, 60% fat) and the high fat diet supplemented with 0.4% RSV (HFD-RSV) for 16 weeks. HepG2 cells were treated with high glucose (33 mM) and RSV (20 µM) for 24 h. The expression of the genes and miRNAs were measured by real-time PCR. Triglyceride level was increased in the liver of mice and HepG2 cells. In both animal and In-vitro experiments, triglyceride level was significantly decreased in groups treated with RSV. The expression of the miR-107 and miR-10b was significantly upregulated in the liver of HFD mice, whereas HFD-RSV group demonstrated a significant lower expression of both miRNAs compared to HFD group. In addition, RSV treatment significantly upregulated the expression of CPT-1a and PPARα genes in the liver of HFD mice. Moreover, treatment with RSV could reduce the expression of miR-107 and miR-10b and increase the expression of CPT-1a and PPARα in HG-treated HepG2 cells. These evidence, as a whole, suggest that RSV could exert its anti-lipogenic effect partially through alterations in the expression of miR-107 and miR-10b in liver cells.

Resveratrol alleviates obesity-induced skeletal muscle inflammation via decreasing M1 macrophage polarization and increasing the regulatory T cell population.

Resveratrol was reported to inhibit inflammatory responses; however, the role of this polyphenol in obesity-induced skeletal muscle inflammation remains unknown. Mice fed a high fat diet (HFD) were treated with resveratrol for 16 weeks. Resveratrol treatment decreased macrophage infiltration into skeletal muscle of HFD-fed mice. Resveratrol also led to the polarization of macrophages to the M2 direction, as well as decreasing the expression of a number of M1 pro-inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 1 ß (IL-1ß) and interleukin 6 (IL-6)]. In addition, increased infiltration of regulatory T cells (Treg cells) was found following resveratrol treatment in skeletal muscle of mice. Decreased intramyocellular lipid deposition was associated with reduced expression levels of toll-like receptors 2 (TLR2) and TLR4 in resveratrol treated mice. We also found that diminished inflammation in skeletal muscle following resveratrol treatment was accompanied by increasing phosphorylation of 5'-adenosine monophosphate-activated protein kinase (AMPK) and decreasing phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Taken together, these findings suggest that resveratrol ameliorates inflammation in skeletal muscle of HFD-induced model of obesity. Therefore, resveratrol might represent a potential treatment for attenuation of inflammation in skeletal muscle tissue.

The effect of resveratrol supplementation on C-reactive protein (CRP) in type 2 diabetic patients: Results from a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: C-reactive protein (CRP) is considered to be an inflammatory marker in type 2 diabetes (T2D) and it is produced by liver cells. The evidence has suggested that resveratrol has anti-inflammatory effect. This study aimed to evaluate the effect of resveratrol supplementation on CRP level in patients with T2D using a systematic review and meta-analysis of randomized controlled trials. METHODS: Electronic databases were completely searched using Medline, ISI Web of Science, EMBASE and Cochrane Library and Scopus until October 2019. Meta-analysis was performed using random-effects model and inverse variance method. Heterogeneity and publication bias were evaluated in selected studies. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Meta-regression was performed to assess the effect of potential confounders on the estimated effect sizes. RESULTS: Six trials comprising a total of 491 subjects were included in this meta-analysis. The results showed significant reduction in the level of CRP [SMD (-0.34 mg/l) (95 % CI, -0.52, to -0.16) p < 0.05] in participants with T2D following supplementation with resveratrol. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects of resveratrol supplementation on CRP level in T2D patients were affected by resveratrol dose and duration of resveratrol. Random-effects meta-regression did not indicate any significant association of CRP level with potential confounders including resveratrol dose, duration of treatment, age and gender of type 2 diabetic patients. CONCLUSION: We found a significant reduction in CRP level in patients with type 2 diabetes, who received resveratrol supplementation.

Chemical Composition and Antimicrobial and Cytotoxic Activities of Foeniculum vulgare Mill Essential Oils.

BACKGROUND AND AIM: Foeniculum vulgare (F. vulgare) Mill, commonly known as fennel, belongs to the Umbelliferae (Apiaceae) family, biennial or perennial herbs disseminated in Mediterranean region and central Europe. This herbal medicine (HM) is considered as a traditional HM, and its parts have been studied. METHODS: In this survey, essential oils from seeds collected from three various regions (Kerman, Golestan, and East Azerbaijan Provinces) of Iran were prepared with hydro-distillation and their components were analyzed with gas chromatography (GC) and chromatography time-of-flight mass spectrometry (GC/MS). Antimicrobial and cytotoxic activities of the essential oils were examined with disk-diffusion method on Muller-Hinton agar and Subaru-dextrose Agar, respectively. Additionally, the MTT assay was assessed on breast cancer cell line (MCF-7). The expression of apoptosis-related genes, Bax and Bcl2, was determined using quantitative real-time PCR (RT-qPCR). RESULTS: The major fractions of essential oils identified by GC and GC/MS included trans-anethole (78.47%, 49.64%, 78.68%), fenchone (10.5%, 8.4%, and 10.2%), and limonene (5.9%, 6.70%, and 5.6%), respectively. Fennel oil collected from three various places exerted inhibitory effects on the bacterial growth and higher cytotoxic effects on MCF-7 cancer cell line. In addition, the essential oil increased the expression of Bax, but decreased Bcl2 gene expression significantly (P < 0.001). CONCLUSION: According to our findings, F. vulgare essential oil can be considered as a promising agent opening venues for novel antimicrobial and anticancer therapies. Owing to side effects and expensiveness of chemotherapy approaches, HM is a new remarkable insight for future therapies.

Resveratrol alleviates non-alcoholic fatty liver disease through epigenetic modification of the Nrf2 signaling pathway.

Recent findings have demonstrated the aberrant DNA methylation of the Nrf2-Keap1 genes in human cancers; however, the epigenetic control of this pathway in non-alcoholic fatty liver disease (NAFLD) is unknown. Resveratrol can modify epigenetic mechanisms. Our objectives in this study were to explore the correlation between promoter methylation of the Nrf2-Keap1 genes and NAFLD, and that investigate the effect of resveratrol on the epigenetic regulation Nrf2-Keap1 in vitro and in vivo models of NAFLD. Resveratrol attenuated high fat-diet (HFD)-induced methylation of the Nrf2 promoter in the liver of mice, and this effect was correlated with reduction in triglyceride level and decrease in the expression of lipogenesis-related genes such as FAS and SREBP-1c. In addition, treatment of HepG2 cells with high glucose (HG) enhanced methylation level of the Nrf2 promoter, whereas resveratrol reversed this effect. Treatment of the cells with resveratrol or 5-aza, a demethylating agent, could prevent HG-induced reactive oxygen species production and expression of Nrf2-controlled antioxidant genes. Moreover, resveratrol or 5-aza could significantly attenuate HG-induced triglyceride accumulation in HepG2 cells. These findings indicate that resveratrol attenuates NAFLD through the epigenetic modification the Nrf2 signaling.