The critical role and functional mechanism of microRNA-146a in doxorubicin-induced apoptosis in breast cancer cells.

BACKGROUND: Breast cancer among women is the most frequently diagnosed cancer and the leading cause of death worldwide. There many advances in diagnosing and treating this disease, early diagnosis and treatment are still a significant challenge in the early stages. In recent years, microRNAs have attracted much attention in cancer diagnosis and treatment. However, the role of miR-146a in breast cancer is still controversial. We aimed to investigate the roles of miR-146a in apoptosis in breast cancer cells. METHODS: A microarray dataset from the GEO database was selected, and using the GEO2R tool, the gene expression profile of this dataset was extracted. Then, the target scan database was used to explore the miR-146a target genes. The link between the signaling pathways was collected. We used miR-146a mimic, which was transfected to the MCF-7 cells to investigate the miR-146a roles in the apoptosis. The expression levels of miR-146a and BAX, BCL-2, and p-21(most essential genes in the apoptosis) were quantified by qPCR and western blot analysis. RESULTS: Our findings indicated that doxorubicin induces miR-146a expression. In addition, overexpression of miR-146a affected MCF-7 cell viability, induced apoptosis, and led to reduced expression levels of BCL-2 and P-21, as well as increased BAX expression levels. CONCLUSION: Considering the role of doxorubicin in inducing apoptosis and increasing the expression of miR-146a, it can be suggested that this miR is involved in inducing apoptosis in BC cells. In addition, miR-146a can be considered a therapeutic candidate.

Investigating the association between the tissue expression of miRNA-101, JAK2/STAT3 with TNF-α, IL-6, IL-1ß, and IL-10 cytokines in the ulcerative colitis patients.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by numerous factors, such as immune system dysfunction and genetic factors. MicroRNAs (miRNAs) play a crucial role in UC pathogenesis, particularly via the JAK-STAT pathway. Our aim was to investigate the association between miRNA-101 and JAK2-STAT3 signaling pathway with inflammatory cytokines in UC patients. METHODS: We enrolled 35 UC patients and 35 healthy individuals as the control group, referred to Shariati Hospital, Tehran, Iran. Patients were diagnosed based on clinical, laboratory, histological, and colonoscopy criteria. RNA and protein extracted from tissue samples. Real-time PCR was used to assess the expression levels of miRNA-101, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-10 genes, while western blot was employed to measure levels of P-STAT3, total STAT3, and JAK2 proteins. RESULTS: Expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 significantly increased, while the expression of IL-10 significantly decreased in the case group versus controls. Additionally, miRNA-101 expression was significantly higher in UC patients. A significant correlation between miRNA-101 and IL-6 expression was observed, indicating their relationship and possible impact on cell signaling pathways, JAK2-STAT3. No significant changes were observed in phosphorylated and total STAT3 and JAK2 protein expression. CONCLUSION: This study provides evidence of increased miRNA-101 expression in UC tissue, suggesting a potential correlation between miRNA-101 and IL-6 expression and their involvement in the JAK2-STAT3 pathway. The study confirms alterations in UC patients' pro-inflammatory cytokines and anti-inflammatory IL-10. However, further investigations are needed to understand the exact role of miRNA-101 in UC pathogenesis fully.

The association between anti-diabetic agents and osteoporosis, sarcopenia, and osteosarcopenia among Iranian older adults; Bushehr Elderly Health (BEH) program.

PURPOSE: Various risk factors are mentioned for osteoporosis, sarcopenia, and osteosarcopenia. Our aim is to assess the impacts of anti-diabetic drugs on these disorders. METHODS: To perform this study, the participants' data was extracted from the Bushehr Elderly Health (BEH) program in Iran. Afterward, the data were categorized into three subgroups: osteoporosis, sarcopenia, and osteosarcopenia, based on WHO and European Working Group on Sarcopenia in Older People (EWGSOP-2) working group definitions. Demographic characteristics, anthropometric measures, past medical history, and current medications were recorded. Pearson chi-squared and simple/multiple logistic regression using Python (3.11.4) and R (4.3.1) programming software assessed the association between anti-diabetic agents and these bone disorders. RESULTS: Out of 1995 participants, 820, 848, and 404 had osteoporosis, sarcopenia, or osteosarcopenia, respectively. Among all types of anti-diabetic drugs, a significant protective association between osteoporosis and consumption of second-generation sulfonylureas was found; Adjusted Odd Ratio (AOR) = 0.65 ([95% CI: 0.45-0.94], p-value = 0.023). No associations were found between sarcopenia and consumption of anti-diabetic agents. A significant association was observed between using Meglitinides and the risk of osteosarcopenia; AOR = 4.98 ([95% CI: 1.5-16.55], p-value = 0.009). CONCLUSION: In conclusion, a protective association between consumption of second-generation sulfonylureas and osteoporosis was found. Moreover, a positive association was found between the consumption of meglitinides and osteosarcopenia. However, to support these findings, further studies are recommended.

Crosstalk between Alzheimer's disease and diabetes: a focus on anti-diabetic drugs.

Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) are two of the most common age-related diseases. There is accumulating evidence of an overlap in the pathophysiological mechanisms of these two diseases. Studies have demonstrated insulin pathway alternation may interact with amyloid-ß protein deposition and tau protein phosphorylation, two essential factors in AD. So attention to the use of anti-diabetic drugs in AD treatment has increased in recent years. In vitro, in vivo, and clinical studies have evaluated possible neuroprotective effects of anti-diabetic different medicines in AD, with some promising results. Here we review the evidence on the therapeutic potential of insulin, metformin, Glucagon-like peptide-1 receptor agonist (GLP1R), thiazolidinediones (TZDs), Dipeptidyl Peptidase IV (DPP IV) Inhibitors, Sulfonylureas, Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors, Alpha-glucosidase inhibitors, and Amylin analog against AD. Given that many questions remain unanswered, further studies are required to confirm the positive effects of anti-diabetic drugs in AD treatment. So to date, no particular anti-diabetic drugs can be recommended to treat AD.

Salivary and serum periostin in kidney transplant recipients.

INTRODUCTION: End-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN. METHODS: In this study, serum and saliva samples were taken from 23 transplant patients with normal function (NF) and 29 transplant patients with graft failure (GF). At least one year had passed since the transplant. Before sampling, a complete oral examination was performed. Salivary and serum POSTN was examined by ELISA. The results were analyzed by SPSS software. RESULTS: The POSTN level in the serum of the NF group (191.00 ± 33.42) was higher than GF patients (178.71 ± 25.68), but the difference was not significant (P = 0.30). Salivary POSTN in NF patients (2.76 ± 0.35) was significantly higher than GF patients (2.44 ± 0.60) (P = 0.01). CONCLUSIONS: The superiority of saliva as a diagnostic fluid includes ease of collection and storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum.

Combination therapy of metformin and p-coumaric acid mitigates metabolic dysfunction associated with obesity and nonalcoholic fatty liver disease in high-fat diet obese C57BL/6 mice.

Metformin (MET) has been demonstrated to have favorable impact on nonalcoholic fatty liver disease (NAFLD); however, the combined effect of this drug with p-coumaric acid (PCA) on liver steatosis is unclear. The aim of the current study was to evaluate the combined effects of MET and PCA on NAFLD in a high-fat diet (HFD)-induced NAFLD mouse model. The obese mice received MET (230 mg/kg), PCA (200 mg/kg) monotherapies, and MET combination with PCA in the diet for 10 weeks. Our results showed that the combination of MET and PCA markedly ameliorated weight gain and fat deposition in HFD fed mice. Furthermore, the combination of MET and PCA lowered liver triglyceride (TG) content which was accompanied by decreased expression of lipogenic and increased expression of ß-oxidation related genes and proteins. In addition, combination therapy of MET and PCA mitigated liver inflammation through inhibiting hepatic macrophage infiltration (F4/80), switching macrophage from M1 into M2 phenotype, and ameliorating nuclear factor-κB (NF-κB) activity in comparison with the monotherapy of MET or PCA. Furthermore, we found that MET and PCA combination therapy upregulated thermogenesis-related genes in BAT and sWAT. Combination therapy results in stimulating brown-like adipocyte (beige) formation in the sWAT of HFD mice. Taken together, these findings indicate that MET combined with PCA can improve NAFLD through decreasing lipid accumulation, inhibiting inflammation and inducing thermogenesis, and adipose tissue browning.

The combination of metformin with morin alleviates hepatic steatosis via modulating hepatic lipid metabolism, hepatic inflammation, brown adipose tissue thermogenesis, and white adipose tissue browning in high-fat diet-fed mice.

AIM: The valuable effects of metformin (MET) and morin (MOR) in the improvement of NAFLD have been proposed, nevertheless, their combination impacts were not investigated so far. We determined the therapeutic effects of combined MET and MOR treatment in high-fat diet (HFD)-induced Non-alcoholic fatty liver disease (NAFLD) mice. METHODS: C57BL/6 mice were fed on an HFD for 15 weeks. Animals were allotted into various groups and supplemented with MET (230 mg/kg), MOR (100 mg/kg), and MET + MOR (230 mg/kg + 100 mg/kg). KEY FINDINGS: MET in combination with MOR reduced body and liver weight in HFD-fed mice. A significant decrease in fasting blood glucose and improvement in glucose tolerance was observed in HFD mice treated with MET + MOR. Supplementation with MET + MOR led to a decline in hepatic triglyceride levels and this impact was associated with diminished expression of fatty-acid synthase (FAS) and elevated expression of carnitine palmitoyl transferase 1 (CPT1) and phospho-Acetyl-CoA Carboxylase (p-ACC). Moreover, MET combined with MOR alleviates hepatic inflammation through the polarization of macrophages to the M2 phenotype, decreasing the infiltration of macrophages and lowering the protein level of NF-kB. MET and MOR in combination reduce the size and weight of epididymal white adipose tissue (eWAT), and subcutaneous WAT (sWAT), whereas improves cold tolerance, BAT activity, and mitochondrial biogenesis. Combination therapy results in stimulating brown-like adipocyte (beige) formation in the sWAT of HFD mice. SIGNIFICANCE: These results suggest that the combination of MET and MOR has a protective effect on hepatic steatosis, which may use as a candidate therapeutic for the improvement of NAFLD.

Metformin-chlorogenic acid combination reduces skeletal muscle inflammation in c57BL/6 mice on high-fat diets.

BACKGROUND: Inflammation at the low-grade level has been found to contribute to obesity-induced insulin resistance in the skeletal muscle (SM). This study investigated the anti-inflammatory potential of metformin (MET) combined with chlorogenic acid (CGA) in SM of mice fed a high-fat diet (HFD). MATERIALS AND METHODS: The C57BL/6 mice were divided into five groups of ten each, normal diet, HFD, HFD + MET, HFD + CGA and HFD + MET + CGA. RESULTS: The results revealed that MET and CGA, alone or in combination, have a reducing effect on weight gain, plasma triglyceride, glucose and insulin levels. MET in combination with CGA led to attenuation of SM inflammation, an effect that was associated with decreasing macrophages infiltration rate. Combined treatment of MET and CGA also resulted in switching macrophages from M1 to M2 phenotype, presented by the higher expression levels of arginase and CD206 (M2 markers) and lower expression levels of iNOS and cd11c markers (M1). In addition, combination treatment was more effective in increasing the anti-inflammatory cytokines expression (IL-10) and decreasing the expression of pro-inflammatory mediators (TNF-α, IL-1ß, MCP-1 and IL-6). CONCLUSION: These findings suggest that the combination treatment of MET and CGA is likely to be a promising approach to control SM inflammation in the HFD-fed model.

A systematic review and meta-analysis of randomized controlled trials investigating the effect of the curcumin and piperine combination on lipid profile in patients with metabolic syndrome and related disorders.

Metabolic syndrome is characterized by multiple metabolic disorders. Several studies indicated that curcumin plus piperine could affect lipids profiles in various diseases. The present meta-analysis aims to assess the effect of curcumin plus piperine on lipid profiles in patients with MetS and associated disorders using a systematic review and meta-analysis of randomized controlled trials. Trials were searched by several electronic databases up to May 2022. The Comprehensive Meta-Analysis (CMA) version3 software carried out this systematic review and meta-analysis. Random-effects model and the inverse variance method were used to conduct the meta-analysis. We evaluated the publication bias and heterogeneity of all eligible studies. In addition, subgroup analyses and sensitivity assessments were performed to assess potential sources of heterogeneity. The combined results by the random-effects model demonstrated that curcumin plus piperine significantly decreased total cholesterol and LDL-C in patients suffering from metabolic syndrome. In comparison, the results of the overall effect size did not show any significant change in triglyceride concentrations. Our results were robust in sensitivity analysis and were not dependent on the dose of curcumin, the dose of piperine, and the duration of treatment. Our results showed that co-administration of piperine and curcumin supplementation improves the lipid profile in metabolic syndrome. However, further long-term RCTs are required to ascertain their clinical benefit.

Multiple novel functions of circular RNAs in diabetes mellitus.

Circular RNAs (circRNAs), as an emerging group of non-coding RNAs (ncRNAs), have received the attention given evidence indicating that these novel ncRNAs are implicated in various biological processes. Due to the absence of 5' and 3' ends in circ-RNAs, their two ends are covalently bonded together, and they are synthesised from pre-mRNAs in a process called back-splicing, which makes them more stable than linear RNAs. There is accumulating evidence showing that circRNAs play a critical role in the pathogenesis of diabetes mellitus (DM). Moreover, it has been indicated that dysregulation of circRNAs has made them promising diagnostic biomarkers for the detection of DM. Recently, increasing attention has been paid to investigate the mechanisms underlying the DM process. It has been demonstrated that there is a strong correlation between the expression of circRNAs and DM. Hence, our aim is to discuss the crosstalk between circRNAs and DM and its complications.

D-allose: Molecular Pathways and Therapeutic Capacity in Cancer.

BACKGROUND: Despite the implementation of various cancer therapies, adequate therapeutic efficacy has not been achieved. A growing number of studies have been dedicated to the discovery of new molecules to combat refractory cancer cells efficiently. Recently, the use of a rare type of sugar, D-allose, has attracted the attention of research communities. In combination with the first-line treatment of cancers, including different types of radiotherapies and chemotherapies, D-allose has been detected with favorable complementary effects. Understanding the mechanism of therapeutic target molecules will enable us to develop new strategies for cancer patients that do not currently respond to the present therapies. OBJECTIVE: We aimed to provide a review of the effects of D-allose in cancer treatment, its mechanisms of action, and gaps in this field that require more investigations. DISCUSSION: With rare exceptions, in many cancer types, including head and neck, lung, liver, bladder, blood, and breast, D-allose consistently has exhibited anticancer activity in vitro and/or in vivo. Most of the D-allose functions are mediated through thioredoxin-interacting protein molecules. D-allose exerts its effects via reactive oxygen species regulation, cell cycle arrest, metabolic reprogramming, autophagy, apoptosis induction, and sensitizing tumors to radiotherapy and chemotherapy. CONCLUSION: D-allose has shown great promise for combating tumor cells with no side effects, especially in combination with first-line drugs; however, its potential for cancer therapy has not been comprehensively investigated in vitro or in vivo.

Chlorogenic acid improves anti-lipogenic activity of metformin by positive regulating of AMPK signaling in HepG2 cells.

Metformin improves lipid profile, however, combination therapy is developing to increase its effectiveness and reduce the deleterious effects of metformin. Chlorogenic acid (CGA) has exhibited lipid-lowering effects. This study aimed to investigate the combined effect of metformin and CGA on lipid accumulation, as well as to elucidate the engaged mechanism in HepG2 cells. To find the non-lethal doses of metformin and CGA, MTT assay was performed. High Glucose (HG) at 33 mM was used to induce lipogenesis in HepG2 cells. Following treatment with different concentrations of metformin and CGA, total lipid content (Oil Red O-staining), triglyceride level, the genes expression of SREBP-1c and FAS, and phosphorylation of AMPK and ACC were measured. Both Metformin and CGA decreased HG-induced lipid accumulation individually, by decreasing total lipid content and triglyceride level. The lowest effective doses of metformin and CGA were 0.25 mM and 5 µM, respectively, which significantly reduced SREBP-1c and FAS genes expression. The combination of these concentrations reinforced these effects. The phosphorylation of AMPK and ACC were more increased by metformin in combination with CGA than both individually. Our findings suggest that CGA synergistically enhances metformin lipid reducing action via the regulating of involved factors in fatty acid synthesis. Therefore, co-administration of metformin with CGA may have further medical value in treating lipid metabolism disorders.

Association between the Expression Levels of MicroRNA-101, -103, and -29a with Autotaxin and Lysophosphatidic Acid Receptor 2 Expression in Gastric Cancer Patients.

Background: Gastric cancer (GC) is regarded as the most prevalent malignancy with the high mortality rate, worldwide. However, gastroscopy, a biopsy of suspected sample, and detecting CEA, CA19-9, and CA72-4 are presently used, but these diagnostic approaches have several limitations. Recently, microRNAs as the most important member of noncoding RNAs (ncRNAs) have received attention; recent evidence demonstrates that they can be used as the promising candidate biomarkers for GC diagnosis. We aimed to investigate the association between the microRNA-29a, -101, and -103 expression and autotaxin (ATX) and lysophosphatidic acid receptor 2 (LPA2) expression in GC patients. Material and Methods. The present study was conducted on 40 paired samples of primary GC tissue and adjacent noncancerous tissue. The gene expression levels of miR-101, -103, -29, ATX, and LPA2 were analyzed by quantitative reverse-transcription PCR (qRT-PCR). Besides, the protein levels of ATX and LPA2 were evaluated using western blot. Results: The expression levels of miR-29 and miR-101 were significantly lower (p value < 0.0001), but the miR-103 and LPA2 were significantly higher in gastric tumor samples compared to the corresponding nontumor tissues (p value < 0.0001). Moreover, the diagnostic accuracy of miRs to discrimine the GC patients from noncancerous controls was reliable (miR-101, sensitivity: 82.5% and specificity: 85%; miR-103, sensitivity: 72.5% and specificity: 90%; miR-29, sensitivity: 77.5% and specificity: 70%). Conclusion: It seems that determining the expression level of miR-101, -103, and -29, as the novel diagnostic biomarkers, has diagnostic value to distinguish GC patients from healthy individuals.

Association of rs2954029 and rs6982502 Variants with Coronary Artery Disease by HRM Technique: A GWAS Replication Study in an Iranian Population.

Background: Genome-wide association studies (GWAS) have been the primary tool for an unbiased study of the genetic background of coronary artery disease (CAD). They have identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). In this study, we aimed to replicate the association of rs2954029 and rs6982502, a GWAS identified SNP, to CAD in an Iranian population. Methods: A sample of 285 subjects undergoing coronary angiography, including 134 CAD patients and 151 healthy. The genotype determination of rs2954029 and rs6982502 SNPs performed using the high-resolution melting analysis (HRM) technique. Results: Our results revealed that the TT genotype of rs2954029 (p= 0.009) and rs6982502 (p< 0.001) were significantly higher in CAD patients compared with controls. Binary logistic regression showed that rs6982502 and rs2954029 increase the risk of CAD incidence (2.470 times, p= 0.011, 95% CI= [1.219-4.751], and 2.174 times, p= 0.033, 95% CI= [1.066-4.433] respectively). After adjusting for confounders, we found that rs6982502 and rs2954029 are significantly associated with CAD risk. Conclusion: These data showed that the TT genotype of rs2954029 and rs6982502 is associated with the risk of CAD in a hospital-based sample of the Iranian population, which has replicated the result of recent GWAS studies.

Molecular study of the proliferation process of beta cells derived from pluripotent stem cells.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder, increasing in the number of patients and poses a severe threat to human health. Significant advances have been made in DM treatment; the most important of which is differentiation and proliferation of beta cells from IPSCs. METHODS: Data were collected from PUBMED at various time points up to the academic year of 2020. The related keywords are listed as follows: "Induced pluripotent stem cell", "Proliferation", "Growth factor", "Small molecule", "cardiotoxicity" and "Scaffold." RESULT: The use of growth factors along with small molecules can be a good strategy for beta-cell proliferation. Also, proliferation of beta cells on nanofibers scaffolds can create a similar in vivo environment, that leads to increased function of beta-cell. Some transcription factors that cause beta cells proliferation play an important role in inflammation; so, it is essential to monitor them to prevent inflammation. CONCLUSION: Finally, the simultaneous use of growth factors, micronutrients and scaffolds can be an excellent strategy to increase the proliferation and function of beta cells derived from IPSCs.

Higher serum level of CTRP15 in patients with coronary artery disease is associated with disease severity, body mass index and insulin resistance.

BACKGROUND: CTRP15 is a prologue of adiponectin which has shown to have favourable effects on glucose and lipid metabolism. Studies have reported lower levels of CTRP15 in T2DM and metabolic syndrome; however, its circulating levels have not been evaluated in CAD patients. METHODS: This case-control study was conducted on 190 angiographically confirmed coronary artery disease (CAD) patients and 70 controls. Serum levels of CTRP15, adiponectin, TNF-α, and IL-6 were measured using the ELISA technique. RESULTS: CTRP15 was shown to occur in higher levels in CAD patients compared with controls. In CAD patients, CTRP15 showed a positive correlation with BMI, FBS, insulin, HOMA-IR, IL-6, and TNF-α and a negative correlation with HDL-C and adiponectin. CONCLUSION: Elevated levels of CTRP15 in CAD patients and the relation of CTRP15 with pathogenic conditions such as insulin resistance, inflammation, and decreased adiponectin and HDL-C suggest a possible compensatory response to these conditions in CAD patients.

Metformin reduces lipid accumulation in HepG2 cells via downregulation of miR-33b.

INTRODUCTION: Here, we aimed to investigate whether the beneficial effects of metformin on lipid accumulation is mediated through regulation of miR-33b. METHODS: The expression of the genes and miRNAs and protein levels were evaluated using real-time PCR and western blot, respectively. To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells. RESULTS: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT. Overexpression of miR-33b significantly prevented the decreasing effect of metformin on lipid content and intra and extra triglyceride levels. Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT. CONCLUSION: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.

Aberrant methylation of miR-124 upregulates DNMT3B in colorectal cancer to accelerate invasion and migration.

The dysregulation of microRNA expression is significantly associated with the initiation and development of CRC. miR-124 is markedly downregulated in colorectal cancer. In the present study, the effects of methylation, over expression and downregulation of miR-124 and its target gene DNMT3B on the proliferation, migration and invasion of colorectal cell line were investigated. The promoter methylation status of miR-124 in the CRC was investigated by methylation specific PCR (MSP). The potential role of miR-124 expression in CRC cells was investigated using the demethylation reagent 5-Aza-CdR and transfection of miR-124 mimic/antimir. MSP revealed that miR-124 promoter region was hypermethylated, result in its significant downregulation in tumour tissues. We showed miR-124 expression was upregulated following 5-AZA-CdR treatment. Transfected Hct-116 cell line with miR-124 leads to decreased DNMT3B expression, cell proliferation, migration and invasion of HCT-116. In conclusion, our data indicate that miR-124 suppress colorectal cancer proliferation, migration and invasion through downregulating DNMT3B level.

Nutritional approach for increasing public health during pandemic of COVID-19: A comprehensive review of antiviral nutrients and nutraceuticals.

Background: The novel coronavirus (COVID-19) is considered as the most life-threatening pandemic disease during the last decade. The individual nutritional status, though usually ignored in the management of COVID-19, plays a critical role in the immune function and pathogenesis of infection. Accordingly, the present review article aimed to report the effects of nutrients and nutraceuticals on respiratory viral infections including COVID-19, with a focus on their mechanisms of action. Methods: Studies were identified via systematic searches of the databases including PubMed/ MEDLINE, ScienceDirect, Scopus, and Google Scholar from 2000 until April 2020, using keywords. All relevant clinical and experimental studies published in English were included. Results: Protein-energy malnutrition (PEM) is common in severe respiratory infections and should be considered in the management of COVID-19 patients. On the other hand, obesity can be accompanied by decreasing the host immunity. Therefore, increasing physical activity at home and a slight caloric restriction with adequate intake of micronutrients and nutraceuticals are simple aids to boost host immunity and decrease the clinical manifestations of COVID-19. Conclusion: The most important nutrients which can be considered for COVID-19 management are vitamin D, vitamin C, vitamin A, folate, zinc, and probiotics. Their adequacy should be provided through dietary intake or appropriate supplementation. Moreover, adequate intake of some other dietary agents including vitamin E, magnesium, selenium, alpha linolenic acid and phytochemicals are required to maintain the host immunity.

Metformin in combination with genistein ameliorates skeletal muscle inflammation in high-fat diet fed c57BL/6 mice.

Although the beneficial effects of metformin (MET) and genistein in ameliorating inflammation have been elucidated, their combined impacts on skeletal muscle inflammation have not been clearly understood. This study aimed to examine the possible preventive effect of MET in combination with genistein on skeletal muscle inflammation in high-fat diet (HFD) fed C57BL/6 mice. Fifty C57BL/6 male mice were fed on an HFD for 10 weeks. The mice were categorized into five groups, control, HFD, HFD + MET (0.23%), HFD + genistein (0.2%), and HFD + MET + genistein for 12 weeks. The results showed that treatment with MET and genistein, either alone or in combination, led to reduced weight gain, fasting blood glucose, plasma insulin, HOMA-IR levels, and Area Under the Curves (AUCs) in ipGTT. MET in combination with genistein demonstrated a decreasing effect on macrophages infiltration rate compared to genistein and MET groups alone. The expression of iNOS was reduced, whereas the expression of M2 macrophage markers was increased in combined treatment of MET and genistein. Furthermore, MET in combination with genistein reduced the expression of TNF-α, IL-1ß, MCP-1, and IL-6 and increased the expression of IL-10 in comparison with genistein and MET groups alone. Plasma and skeletal muscle triglycerides and intra-myocellular lipid deposition were reversed by treatment with MET and genistein, alone or in combination. These results imply that the combination therapy of MET and genistein may have therapeutic potential for decreasing obesity-induced skeletal muscle inflammation in the HFD-fed model.