Ameliorating Effect Of Quercetin On Ethanol-Induced Liver Injury Via Targeting RISC Machinery

Background: Over the past few decades, increased alcohol consumption has had deleterious effects on human health. Alcoholic fatty liver disease (AFLD) is becoming a major global challenge, as the currently approved drugs for AFLDs are subject to several side effects. This has broadened the scope of the use of natural compounds as therapeutics. Recent advances in nutraceuticals as therapeutics have shed light on flavonoids such as Quercetin. It is a natural antioxidant of multiple dietary origins and has been extensively studied for its beneficial role as an anti-inflammatory and anti-cancer agent. Objective: Based on this framework, in the proposed study, we investigated the therapeutic role of Quercetin in Ethanol-induced liver damage using the Swiss Albino mice model and the hepatic cell line HepG2. Methodology: WST-1 assay was performed to access the effect of Quercetin on cell proliferation. The impact of Ethanol on the body and liver weights of mice was measured, and liver injury was determined by H&E staining and TMS. The mRNA expression levels of inflammatory genes (TNF-α, IL-6, and IL-1β) and SND1, a significant unit of the RNA-induced silencing complex (RISC), were analyzed. The liver enzyme levels were also measured. Results: Our experimental results showed that HepG2 cells treated with ethanol had a lower proliferation rate, which was later mitigated by treatment with quercetin. In the mice model, a considerable reduction in body weight was detected after ethanol treatment. Conversely, there was a significant elevation in liver weight and enzyme activity. All of these effects were ameliorated by Quercetin treatment. Immunohistochemistry data revealed an improvement in the inflammation and fibrosis characteristics in liver tissues of the Quercetin-treated group. Decreased expression of inflammatory markers and SND1 levels were also observed in the Quercetin-treated group. Conclusion: Based on our results it may be concluded that Quercetin demonstrated hepatoprotective activity in both ethanol-treated HepG2 cell line and ethanol-induced liver injury in mice model. Here, we elucidated a novel and possible therapeutic role of Quercetin in Alcohol-Related Liver Disease (ARLD) by targeting the RISC machinery

Eventration of Diaphragm: A Rare Cadaveric Case Report

The respiratory diaphragm is a barrier between the thoracic and abdominal cavities. It is a chief skeletal muscle of respiration that plays a critical role in the process of inspiration. The defective diaphragm may be clinically present with or without obvious symptoms. Depending on the severity of its defects, it can lead to mild to severe fatal consequences. Protrusion of abdominal contents into the thoracic cavity through the weakened or defective part of the diaphragm is known as a diaphragmatic hernia. Such herniations will exist either in the form of congenital birth defects or acquired defects in the diaphragm. An acquired hernia may be due to spontaneous or iatrogenic causative factors. Congenital Diaphragmatic Hernia (CDH) can occur due to the disruption of various cellular mechanisms involved in organogenesis during the gestation period. Such herniations may exist with or without content protrusions into the cavity of the thorax, later referred to as Eventration of the Diaphragm (ED). In the Department of Anatomy at JSS Medical College, Mysuru, Karnataka, India, a rare case of diaphragmatic eventration was noticed in a male cadaver aged about 70 years, during the routine dissection class of preclinical medical students. In this rare case report, diaphragmatic eventration along with various factors involved in its presentation would be considered holistically

Elevated serum Homocysteine levels a possible non-invasive diagnostic biomarker in patients with Non-alcoholic fatty liver disease

Lack of independent biomarkers is very much evident in NAFLD. Early detection of NAFLD is difficult due to the absence of specific diagnostic and prognostic markers and clinical symptoms. We retrospectively collected the information of patients hospitalised with NAFLD diagnosis and metabolic syndrome during 2019-2020 using the tertiary care hospital inpatient sample database and evaluated the changes in their serum homocysteine levels. We found that 59.063% of NAFLD in the male population and 41.667% of NAFLD in the female population had increased serum homocysteine. This shows that elevated serum homocysteine can act as a potential biomarker for NAFLD

Multifunction Protein Staphylococcal Nuclease Domain Containing 1 (SND1) Promotes Tumor Angiogenesis in Human Hepatocellular Carcinoma through Novel Pathway That Involves Nuclear Factor κB and miR-221

Staphylococcal nuclease domain-containing 1 (SND1) is a multifunctional protein that is overexpressed in multiple cancers, including hepatocellular carcinoma (HCC). Stable overexpression of SND1 in Hep3B cells expressing a low level of SND1 augments, whereas stable knockdown of SND1 in QGY-7703 cells expressing a high level of SND1 inhibits establishment of xenografts in nude mice, indicating that SND1 promotes an aggressive tumorigenic phenotype. In this study we analyzed the role of SND1 in regulating tumor angiogenesis, a hallmark of cancer. Conditioned medium from Hep3B-SND1 cells stably overexpressing SND1 augmented, whereas that from QGY-SND1si cells stably overexpressing SND1 siRNA significantly inhibited angiogenesis, as analyzed by a chicken chorioallantoic membrane assay and a human umbilical vein endothelial cell differentiation assay. We unraveled a linear pathway in which SND1-induced activation of NF-κB resulted in induction of miR-221 and subsequent induction of angiogenic factors Angiogenin and CXCL16. Inhibition of either of these components resulted in significant inhibition of SND1-induced angiogenesis, thus highlighting the importance of this molecular cascade in regulating SND1 function. Because SND1 regulates NF-κB and miR-221, two important determinants of HCC controlling the aggressive phenotype, SND1 inhibition might be an effective strategy to counteract this fatal malady

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR

Anti-snake venom potential of Clerodendrum serratum extracts on Bungarus caeruleus and Daboia russelii venom

Anti-snake venom therapy is the only treatment for snake bite but leads to acute and chronic conditions which may be severe. The medicinal plants have gained importance over years to find an effective alternative to anti-snake venom. The present study focused on evaluating the potential of Clerodendrum serratum for the anti-snake venom activity. Phytochemicals were extracted from the C. serratum with different solvents. The ethyl acetate and methanolic extracts were found to neutralize the major enzyme toxins (phospholipase A2, protease and hyaluronidase) of Bungarus caeruleus and Daboia russelii venom at a concentration of 100 µg/mL. The fibrinogenolytic activity of both the venoms were neutralized. The study proves that the plant C. serratum possesses certain compounds which inhibit the toxins present in the venom of B. caeruleus and D. russelii. Video Clip of Methodology: Hyaluronidase assay:   3 min  30 sec   Full Screen    Alternat

Gestational diabetes mellitus – The modern Indian perspective

Gestational diabetes mellitus (GDM) is a serious and most frequent health complication during pregnancy which is associated with a significant increase in the risk of maternal and neonatal outcomes. GDM is usually the result of β-cell dysfunction along with chronic insulin resistance during pregnancy. Seshiah et al. pioneer work led to the adoption of Diabetes in Pregnancy Study Group in India criteria as the norm to diagnose GDM, especially in the community setting. In 2014, the Maternal Health Division of the Ministry of Health and Family Welfare, Government of India, updated guidelines and stressed upon the proper use of guidelines such as using a glucometer for self-monitoring and the use of oral hypoglycaemic agents. The 2018 Government of India guidelines stress the importance of counselling about lifestyle modifications, weight control, exercise, and family planning