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

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

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

Staphylococcal nuclease domain containing-1 (SND1) promotes migration and invasion via angiotensin II type 1 receptor (AT1R) and TGFβ signaling

Staphylococcal nuclease domain containing-1 (SND1) is overexpressed in human hepatocellular carcinoma (HCC) patients and promotes tumorigenesis by human HCC cells. We now document that SND1 increases angiotensin II type 1 receptor (AT1R) levels by increasing AT1R mRNA stability. This results in activation of ERK, Smad2 and subsequently the TGFβ signaling pathway, promoting epithelial–mesenchymal transition (EMT) and migration and invasion by human HCC cells. A positive correlation was observed between SND1 and AT1R expression levels in human HCC patients. Small molecule inhibitors of SND1, alone or in combination with AT1R blockers, might be an effective therapeutic strategy for late-stage aggressive HCC

Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer.

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. At molecular level, TQ and TAM synergistically lowers XIAP expression resulting in binding and activation of caspase-9 in apoptotic cascade, and interfere with cell survival through PI3-K/Akt pathway by inhibiting Akt phosphorylation. Cleaved caspase-9 further processes other intracellular death substrates such as PARP thereby shifting the balance from survival to apoptosis, indicated by rise in the sub-G1 cell population. This combination also downregulates the expression of Akt-regulated downstream effectors such as Bcl-xL, Bcl-2 and induce expression of Bax, AIF, cytochrome C and p-27. Consistent with these results, overexpression studies further confirmed the involvement of XIAP and its regulatory action on Akt phosphorylation along with procaspase-9 and PARP cleavage in TQ-TAM coadministrated induced apoptosis. The ability of TQ and TAM in inhibiting XIAP was confirmed through siRNA-XIAP cotransfection studies. This novel modality may be a promising tool in breast cancer treatment