Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases.
There is a limited understanding of molecular and cellular events that derive disease progression in patients with COVID-19. Receptor for Advanced Glycation End Products (RAGE) is hyperactive in development and complications of several diseases by mediating oxidative stress and in ammation in the body. The present study aims to explore activation of RAGE signaling in patients infected with SARS-CoV-2 with preexisting comorbidities. Enhanced levels of ligands of RAGE including AGEs, S100, and HMGB-1 were observed in Covid 19 patients with severe diseases, however, their level was signi cantly higher in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. The Expression of RAGE in parallel to ligands accumulation, was signi cantly increased in patients with severe disease and comorbidities as compared to COVID-19 patients with sever disease without comorbidities. The expression of downstream effectors of RAGE including STAT-3 and NF-kB were also enahnced and their activity was increaed in COVID-19 patients with comorbisdities. Levels of in ammatory and oxidative stress biomarkers were markeldy in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. We conclude that upregulated RAGE axis is favorable to worsen the severity of the SARS-CoV-2 infection in patients with preexisting comorbidities and partly explain in ammatory and oxidative stress strom in severe COVID-19 patietnts.
There is a limited understanding of molecular and cellular events that derive disease progression in patients with COVID-19. Receptor for Advanced Glycation End Products (RAGE) is hyperactive in development and complications of several diseases by mediating oxidative stress and inflammation in the body. The present study aims to explore activation of RAGE signaling in patients infected with SARS-CoV-2 with preexisting comorbidities. Enhanced levels of ligands of RAGE including AGEs, S100, and HMGB-1 were observed in Covid 19 patients with severe diseases, however, their level was significantly higher in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. The Expression of RAGE in parallel to ligands accumulation, was significantly increased in patients with severe disease and comorbidities as compared to COVID-19 patients with sever disease without comorbidities. The expression of downstream effectors of RAGE including STAT-3 and NF-kB were also enahnced and their activity was increaed in COVID-19 patients with comorbisdities. Levels of inflammatory and oxidative stress biomarkers were markeldy in COVID-19 patients with comorbidties as compared to COVID-19 patients without comorbidties. We conclude that upregulated RAGE axis is favorable to worsen the severity of the SARS-CoV-2 infection in patients with preexisting comorbidities and partly explain inflammatory and oxidative stress strom in severe COVID-19 patietnts.
This study aimed to explore the present status of utilization of the available educational opportunities designed and available for the girls and their counterparts. First of all, to gather the information from the various secondary level sources, a table was designed. Therefore, the authority and the websites of the Census, CBSE, Delhi, ICSE, Delhi, and Allahabad Board, UP was contacted. After seeking their permission, the data was collected and compiled in the designed tables, so that it could fulfill the objectives of the undertaken research. Similarly, focused group discussions were also held with the parents and community members to identify the factors responsible for the girl’s education. The findings of the study reveal that girls have been able to raise their academic status within the available educational opportunities.
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