The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19. PATIENTS AND METHODS: In this prospective cohort study, 60 hospitalized T2DM patients with COVID-19 on metformin plus standard anti-COVID-19 treatments compared to 40 hospitalized T2DM patients with COVID-19 on other diabetic pharmacotherapy like insulin and sulfonylurea, were recruited. Inflammatory and oxidative stress biomarkers and radiological and clinical outcomes were assessed at admission time and at the time of discharge. RESULTS: The results of this study illustrated that metformin treatment in T2DM patients with COVID-19 was more effective in reducing inflammatory and oxidative stress biomarkers with significant amelioration of radiological scores and clinical outcomes compared to T2DM patients with COVID-19 on another diabetic pharmacotherapy. CONCLUSIONS: Our findings highlighted that metformin efficiently managed T2DM patients with COVID-19 by reducing inflammatory and oxidative stress with mitigating effects on the radiological scores and clinical outcomes.

Chlorogenic acid derived from Moringa oleifera leaf as a potential antiinflammatory agent against cryptosporidiosis in mice.

Cryptosporidiosis is a serious illness in immunodeficient patients, and there is still no drug that can completely remove the parasite from the host. The present study represents the first report investigating the impact of the active molecule chlorogenic acid (CGA), naturally isolated from Moringa oleifera leaf extract (EMOLE), on immunosuppressed, Cryptosporidium parvum-infected BALB/c mice. Mice were divided into five groups: normal mice, infected immunosuppressed mice, and infected immunosuppressed mice treated with EMOLE, CGA, and nitazoxanide (NTZ) drugs. Parasitological, immunological, and histopathological investigations were recorded besides differences in the mice' body weight. Infected control mice showed elevated levels of oocyst shedding throughout the study. The EMOLE- and CGA-treated groups showed 84.2% and 91.0% reductions in oocyst shedding, respectively, with no significant difference compared to the drug control. The inflammatory markers IFN-γ, IL-6, IL-1ß, and TNF-α were significantly higher in the infected control group. Treatment with 300 mg/kg/day of EMOLE or 30 mg/kg/day of CGA significantly downregulated pro-inflammatory cytokine levels compared to the infected group, although they did not change significantly compared to the NTZ-treated group. Histopathology of intestinal sections showed inflammatory and pathological changes in the infected control group. Low-grade tissue changes and an obvious improvement in villi structure were seen in mice treated with CGA. This study highlighted the role of CGA, isolated and purified from EMOLE, as an effective anti-inflammatory agent in eradicating C. parvum infection.

Chlorogenic acid derived from Moringa oleifera leaf as a potential antiinflammatory agent against cryptosporidiosis in mice

@#Cryptosporidiosis is a serious illness in immunodeficient patients, and there is still no drug that can completely remove the parasite from the host. The present study represents the first report investigating the impact of the active molecule chlorogenic acid (CGA), naturally isolated from Moringa oleifera leaf extract (EMOLE), on immunosuppressed, Cryptosporidium parvum-infected BALB/c mice. Mice were divided into five groups: normal mice, infected immunosuppressed mice, and infected immunosuppressed mice treated with EMOLE, CGA, and nitazoxanide (NTZ) drugs. Parasitological, immunological, and histopathological investigations were recorded besides differences in the mice’ body weight. Infected control mice showed elevated levels of oocyst shedding throughout the study. The EMOLE- and CGA-treated groups showed 84.2% and 91.0% reductions in oocyst shedding, respectively, with no significant difference compared to the drug control. The inflammatory markers IFN-γ, IL-6, IL-1β, and TNF-α were significantly higher in the infected control group. Treatment with 300 mg/kg/day of EMOLE or 30 mg/kg/day of CGA significantly downregulated pro-inflammatory cytokine levels compared to the infected group, although they did not change significantly compared to the NTZ-treated group. Histopathology of intestinal sections showed inflammatory and pathological changes in the infected control group. Low-grade tissue changes and an obvious improvement in villi structure were seen in mice treated with CGA. This study highlighted the role of CGA, isolated and purified from EMOLE, as an effective anti-inflammatory agent in eradicating C. parvum infection.

Interplay between TGF-b1 and miRNA-122 biomarkers in hepatocellular carcinoma progression in patients with chronic hepatitis C.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy and clinically validated medications have not yet been developed since there are no reliable diagnostic and prognostic biomarkers. Based on bioinformatics tools, TGF-b1 gene was the first target gene of miRNA-122, therefore this study was intended to assess the potential interconnection between TGF-b1 and miRNA-122 as a diagnostic and prognostic biomarker in the progression of HCC in patients with chronic hepatitis C (CHC) genotype (4). In this study, 100 people were included and split into two groups; group I: CHC patients without HCC that were classified into patients CHC without cirrhosis and CHC cirrhotic patients, group II: CHC patients with HCC, and healthy volunteers as control. The expression of miRNA-122 and TGF-b1 genes were analyzed using Real-Time PCR. An upregulation of miRNA-122 gene in cirrhotic and HCC patients compared to both chronic HCV non-cirrhotic, and cirrhotic patients, while, a decrease in expression of TGF-b1 was found in cirrhotic patients compared to HCV non-cirrhotic patients. Although significantly downregulated in HCC patients. Regression analysis indicated that the expression levels of miRNA-122 and TGF-b1 could be regarded as important indicators of the alterations in cirrhotic and HCC patients versus HCV non-cirrhotic patients, also with the chances of HCC versus cirrhosis patients. Our data indicated an interaction between miRNA-122 and TGF-b1, regulated gene expression and recommended the use of these parameters as noninvasive predictive biomarkers and therapeutic targets for HCV induced liver cirrhosis and HCC.

Interplay between TGF-b1 and miRNA-122 biomarkers in hepatocellular carcinoma progression in patients with chronic hepatitis C

@#Hepatocellular carcinoma (HCC) is a highly lethal malignancy and clinically validated medications have not yet been developed since there are no reliable diagnostic and prognostic biomarkers. Based on bioinformatics tools, TGF-b1 gene was the first target gene of miRNA-122, therefore this study was intended to assess the potential interconnection between TGF-b1 and miRNA-122 as a diagnostic and prognostic biomarker in the progression of HCC in patients with chronic hepatitis C (CHC) genotype (4). In this study, 100 people were included and split into two groups; group I: CHC patients without HCC that were classified into patients CHC without cirrhosis and CHC cirrhotic patients, group II: CHC patients with HCC, and healthy volunteers as control. The expression of miRNA-122 and TGF-b1 genes were analyzed using Real-Time PCR. An upregulation of miRNA-122 gene in cirrhotic and HCC patients compared to both chronic HCV non-cirrhotic, and cirrhotic patients, while, a decrease in expression of TGF-b1 was found in cirrhotic patients compared to HCV non-cirrhotic patients. Although significantly downregulated in HCC patients. Regression analysis indicated that the expression levels of miRNA-122 and TGF-b1 could be regarded as important indicators of the alterations in cirrhotic and HCC patients versus HCV non-cirrhotic patients, also with the chances of HCC versus cirrhosis patients. Our data indicated an interaction between miRNA-122 and TGF-b1, regulated gene expression and recommended the use of these parameters as noninvasive predictive biomarkers and therapeutic targets for HCV induced liver cirrhosis and HCC.

Impact of Allium sativum ethanol extract on immuno-regulatory T cells and anti-inflammatory cytokine profile in murine schistosomiasis.

Parasite immune response against schistosomal antigens involves both the innate and adaptive immune response. Tregs have a suppressive effect and play a role on the parasite's immune evasion. This study aimed to evaluate active compounds of Allium sativum (AS) ethanol extract and the impact of AS extract alone or in combination with praziquantel on Tregs and anti-inflammatory cytokines TGF- ß and IL-10 in mice infected with S. mansoni . Phytochemical screening of AS bulbs for various active constituents and qualitative and quantitative analysis of the flavonoids and phenolic acids were done using HPLC. Measurement of splenocytes Treg cell phenotypes and anti-inflammatory cytokines TGF- ß and IL-10 was done by flow cytometric analysis. The data are expressed as mean ± SD. Statistical significance was determined by one-way ANOVA utilizing the statistical package (SPSS version 17.0). HPLC of AS ethanol extract revealed presence of 22 and 18 compounds of flavonoids and phenolic acids, respectively. S. mansoni infection upregulated the Treg cells subsets (CD4, CD25, Foxp3) frequencies and the levels of TGF- ß and IL-10 anti-inflammatory cytokines when compared to healthy control. AS ethanol extract alone or combined with PZQ decreases the production of Treg cells from spleen in addition to the reduction in anti- inflammatory cytokines IL-10 and TGF- ß. This study recommends that the combination of AS ethanol extract and PZQ may play a role in maintaining the homeostasis of the immune system during schistosomiasis by decreasing Tr eg cells and anti-inflammatory cytokines IL- 10 and TGF- ß production.

Impact of Allium sativum ethanol extract on immuno-regulatory T cells and anti-inflammatory cytokine profile in murine schistosomiasis

@#Parasite immune response against schistosomal antigens involves both the innate and adaptive immune response. Tregs have a suppressive effect and play a role on the parasite’s immune evasion. This study aimed to evaluate active compounds of Allium sativum (AS) ethanol extract and the impact of AS extract alone or in combination with praziquantel on Tregs and anti-inflammatory cytokines TGF-β and IL-10 in mice infected with S. mansoni. Phytochemical screening of AS bulbs for various active constituents and qualitative and quantitative analysis of the flavonoids and phenolic acids were done using HPLC. Measurement of splenocytes Treg cell phenotypes and anti-inflammatory cytokines TGF-β and IL-10 was done by flow cytometric analysis. The data are expressed as mean ± SD. Statistical significance was determined by one-way ANOVA utilizing the statistical package (SPSS version 17.0). HPLC of AS ethanol extract revealed presence of 22 and 18 compounds of flavonoids and phenolic acids, respectively. S. mansoni infection upregulated the Treg cells subsets (CD4, CD25, Foxp3) frequencies and the levels of TGF-β and IL-10 anti-inflammatory cytokines when compared to healthy control. AS ethanol extract alone or combined with PZQ decreases the production of Treg cells from spleen in addition to the reduction in antiinflammatory cytokines IL-10 and TGF-β. This study recommends that the combination of AS ethanol extract and PZQ may play a role in maintaining the homeostasis of the immune system during schistosomiasis by decreasing Treg cells and anti-inflammatory cytokines IL10 and TGF-β production.

[Choice of optimal surgical reconstruction at patients with critical limb ischemia due to infrainguinal atherosclerotic arterial occlusive disease].

One hundred and four patients with atherosclerotic lesion of femoro-popliteal segment and III-IV stage of ischemia underwent vascular surgical procedures. Results of these operations were analyzed depending on state of distal arterial bed. Autovenous femoro-popliteal bypass (FPB) with reversed autovein was performed at 49 (47.1%) patients, femoro-tibial bypass (FTB) with autovein in situ - at 55 (52.9%). Clinical and angiographic variants of favorable and unfavorable prognosis of FBP and FTB are described. It is demonstrated that severe lesion of outflow distal arteries is the main cause of bypasses thrombosis. Protective arteriovenous fistula in the region of FTB distal anastomosis improves significantly short-term results of operation.