Earticle

Bipolar disorder is a mental illness characterized by extreme mood and behavioral swings, such as highs of euphoria and lows of depression. It is a socially significant disorder in which people with the disorder experience intense mood swings and, for those with severe bipolar disorder, it is even difficult leading a normal life. High stress levels in people with mental illness can lead to neuroendocrine disruption, and it is strongly linked to aging. When the neuroendocrine system becomes vulnerable to these mental illnesses and stress, it is likely to accelerate aging. And it's the epigenetic clock that can measure the extent of this accelerated aging. The Epi clock, a pan tissue clock, measures aging through DNA methylation, and the degree of methylation is modified and changed by environmental conditions in the body. Therefore we wanted to check the changes in the epigenetic age of the patients with bipolar disorder. While we found no significant differences in epigenetic age, we did confirm the possibility that people with bipolar disorder have different methylation than normal people. We also found that the EPIC array data fit better on the Epi clock than on the Horvath clock with age-accelerated data from normal people.

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual – Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. A role in the regulation of cell proliferation and/or differentiation is suggested by the differentiation status-specific expression of gasdermin proteins in epithelial tissues. One of the GSDM protein is Gasdermin A (GSDMA), which decreased in stomach and esophageal cancers, suggesting a tumor suppressor role. GSDMA receptor antagonists have been researched as potential treatments for inflammatory diseases and baldness. GSDMA's significance in a wide range of disorders makes it an important therapeutic target. As a result, homology modelling of the GSDMA receptor was undertaken in the current study using the crystal structures of Mus musculus (GSDMA3), Human gasdermin D (GSDMD), and Murine gasdermin D (murine GSDMD). The best model was chosen based on the validation results after 20 models were developed utilising single template-based approaches. The generated structures can be used for further binding site and docking studies in the future.