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Introduction: Sirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro. Methods: HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns. Results: The semi-quantitative results of Oil red (p <.03) and TG level (p <.009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p <.05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar. Conclusion: Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection is strongly related to peptic ulcer disease, chronic gastritis, and gastric malignancies. Therefore, H. pylori eradication is necessary in these cases. This study was aimed to compare the efficacy of 14-day reverse hybrid therapy with standard 14-day concomitant regimen for H. pylori eradication in Iran. Methods: Of the 317 patients with dyspepsia and H. pylori infection enrolled in the study, 153 and 164 patients were randomly assigned to reverse hybrid and concomitant groups, respectively. The reverse hybrid regimen containing pantoprazole, amoxicillin, clarithromycin, and metronidazole was taken every 12 hours in the first 7 days, however, Clarithromycin and Metronidazole were discontinued within the next 7 days. Patients in the concomitant group also received the same drugs for 14-day. Eradication confirmation tests were used 8 weeks after the end of treatments. Results: A crowd of 281 patients continued the trial until the end. H. pylori eradication rates based on intention to treat analysis were 71.2% (109/153) and 83.5% (137/164) in reverse hybrid and concomitant groups, respectively (P = 0.007). By the per-protocol analysis, rates of eradication were 85.8% (109/127) and 89% (137/154), respectively (P = 0.428). Severe side effects were few in both groups. More side effects were observed in concomitant group (p < 0.001), however, the severity of side effects was not statistically different between the two regimens (P = 0.314). Reverse hybrid regimen was better tolerated (98% vs. 91.5%, P = 0.009). Conclusion: Both 14-day reverse hybrid and concomitant regimens have a fair response rate in Iran. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We compared the efficacy of two different regimens for H. pylori eradication in areas with high antibiotic resistance. Background: Helicobacter pylori (H. pylori) is a gram-negative bacillus that has a strong association with chronic gastritis and peptic ulcer disease. Different regimens with varying degrees of effectiveness have been used for H. pylori eradication. Methods: The current randomized controlled trial (RCT) randomly assigned 217 patients who had indications for H. pylori eradication therapy to two groups. One group were administered concomitant quadruple therapy (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) for 14 days, and the second group received 14 days of high-dose dual therapy, consisting of esomeprazole 40 mg BID and amoxicillin 1g TDS. H. pylori eradication was assessed eight weeks after the end of treatment. Results H. pylori eradication rates by PP analysis for 14 days concomitant quadruple therapy and high-dose dual therapy were 88.6% (95% CI, 80.3-92.8) and 82.2% (95% CI, 74.8-89.5), respectively (p = 0.19). According to intention-to-treat (ITT) analysis, the eradication rates were 81.6% (95% CI, 74.5-88.6) and 80.6% (95% CI, 73-88.1), respectively (p = 0.58). Overall drug side effects were 20.8% in high-dose dual therapy and 49.6% in concomitant quadruple therapy (p < 0.001). Conclusion: Fourteen days concomitant quadruple therapy can be considered as a relatively acceptable regimen for H. pylori eradication in areas with high clarithromycin and metronidazole resistance. It seems that high-dose dual therapy could be a promising alternative regimen in these areas. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori ( H. pylori ) infection is strongly related to peptic ulcer disease, chronic gastritis, and gastric malignancies. Therefore, H. pylori eradication is necessary in these cases. This study was aimed to compare the efficacy of 14-day reverse hybrid therapy with standard 14-day concomitant regimen for H. pylori eradication in Iran., Methods: Of the 317 patients with dyspepsia and H. pylori infection enrolled in the study, 153 and 164 patients were randomly assigned to reverse hybrid and concomitant groups, respectively. The reverse hybrid regimen containing pantoprazole, amoxicillin, clarithromycin, and metronidazole was taken every 12 hours in the first 7 days, however, Clarithromycin and Metronidazole were discontinued within the next 7 days. Patients in the concomitant group also received the same drugs for 14-day. Eradication confirmation tests were used 8 weeks after the end of treatments., Results: A crowd of 281 patients continued the trial until the end. H. pylori eradication rates based on intention to treat analysis were 71.2% (109/153) and 83.5% (137/164) in reverse hybrid and concomitant groups, respectively ( P = 0.007). By the per-protocol analysis, rates of eradication were 85.8% (109/127) and 89% (137/154), respectively ( P = 0.428). Severe side effects were few in both groups. More side effects were observed in concomitant group ( p < 0.001), however, the severity of side effects was not statistically different between the two regimens ( P = 0.314). Reverse hybrid regimen was better tolerated (98% vs. 91.5%, P = 0.009)., Conclusion: Both 14-day reverse hybrid and concomitant regimens have a fair response rate in Iran., Competing Interests: The authors declare that they have nothing to disclose.

Pulmonary fibrosis (PF) is a lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. Paraquat is commonly used in agricultural settings to control weed growth and is one of the important risk factors for PF. Additionally, emerging evidence has demonstrated Capparis spinosa ( C. spinose ) fruit extract has anti-fibrotic, anti-inflammatory, and antioxidant properties. We aimed to evaluate whether C. spinose fruit hydroalcoholic extract has a positive effect against Paraquat-induced PF in rats. 30 male Wistar rats were randomly divided into 5 groups, which included: a control group, a Paraquat control group, a C. spinose group with a dose of 20 mg/kg, a C. spinose group with a dose of 30 mg/kg, a C. spinose group with a dose of 50 mg/kg. After 21 days of the treatment, levels of hydroxyproline and malondialdehyde (MDA) in lung tissue were assessed and lung indices and semi-quantitative histopathological changes were determined. The results showed that treatment with C. spinose , led to increased weight gain, whereas reduced lung weight.  C. spinose demonstrated a decreasing effect on levels of MDA, and hydroxyproline in lung tissue. Moreover, histopathological data and the number of lung indices indicated the preventive role of C. spinose Paraquat-induced PF in rats., (© The Author(s).)

Aim: The current study aimed to report a pooled analysis of the association of the circulating levels of liver enzymes and total bilirubin with severe and non-severe COVID-19., Background: The ongoing coronavirus outbreak is an important threat to health worldwide. Epidemiological data representing greater risk of liver failure in patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)., Methods: Electronic databases were comprehensively searched using Medline, ISI Web of Science, EMBASE, and the Cochrane Library up to July 2020. Outcomes from each relevant study were pooled using a random-effects model. Heterogeneity was analyzed by Q test and I 2 statistics. Sensitivity analysis was also evaluated., Results: A total of 24 studies were included (4,246 patients) in this study. We found a significant association of COVID-19 severity with increased levels of ALT [SMD: 1.40 U/L; 95% CI (0.93, 1.88); P < 0.05, I 2 = 96.5%, P Heterogenity = 0.000 ], AST [SMD: 2.11 U/L; 95% CI (1.40, 2.83); P < 0.05, I 2 = 97.9%, P Heterogenity = 0.000], LDH [SMD: 3.88 U/L; 95% CI (2.70, 5); P < 0.05, I 2 = 98.7%, P Heterogenity = 0.000] and TBil [SMD: 1.08 mol/L; 95% CI (0.44, 1.72); P = 0.001, I 2 = 97.7, P Heterogenity = 0.000], whereas, ALP values [SMD: 0.31; 95% CI (-1.57, 2.20); P = 0.74] was not significant between severe and non-severe COVID-19 patients. Moreover, elevated liver enzymes were found more in males [OR: 1.52, (95% CI 1.26, 1.83), P < 0.05] with severe COVID-19 infection than in females., Conclusion: The alterations of liver function indexes caused by SARS-CoV-2 infection suggested a potential prognosis biomarker for screening of severe patients at early stages of the disease.

Obesity is associated with higher postmenopausal breast cancer incidence. Visfatin level alteration is one of the mechanisms by which obesity promotes cancer. Ligand-independent activation of estrogen receptor alpha (ERα) is also associated with carcinogenesis. The activity of ERα is modulated through phosphorylation on multiple sites by a number of protein kinases. Here we investigated the effect of visfatin as a novel adipocytokine on the phosphorylation and activity of ERα in MCF-7 breast cancer cells. We showed that exogenous administration of visfatin significantly increased the phosphorylation of ERα at serine 118 (Ser118) and 167 (Ser167) residues. Visfatin-induced Ser118 phosphorylation was diminished after treatment of cells with U0126 (MEK1/2 inhibitor). Furthermore, our results showed that visfatin-induced Ser167 phosphorylation is mediated through both MAPK and PI3K/Akt signaling pathways. Inhibition of the enzymatic activity of visfatin by FK866 had no effect on phosphorylation of ERα. We also showed that visfatin enhanced the estrogen response element (ERE)-dependent activity of ER in the presence of 17-β estradiol (E2). Additional study on T47D cells showed that visfatin also increased Ser118 and Ser167 phosphorylation of ERα and enhanced ERE-dependent activity in the presence of E2 in these cells.