H3K9 methyltransferase (G9a) and its relevant molecule GLP are the SET domain proteins that specifically add mono, di and trimethyl groups on to the histone H3K9, which lead to the transcriptional inactivation of chromatin and reduce the expression of cancer suppressor genes, which trigger growth and progress of several cancer types. Various studies have demonstrated that overexpression of H3K9 methyltransferase G9a and GLP in different kinds of tumors, like lung, breast, bladder, colon, cervical, gastric, skin cancers, hepatocellular carcinoma and hematological malignancies. Several G9a and GLP inhibitors such as BIX‐01294, UNC0642, A‐366 and DCG066 were developed to combat various cancers; however, there is a need for more effective and less toxic compounds. The current molecular docking study suggested that the selected new compounds such as ninhydrin, naphthoquinone, cysteamine and disulfide cysteamine could be suitable molecules as a G9a and GLP inhibitors. Furthermore, detailed cell based and preclinical animal studies are required to confirm their properties. In the current review, we discussed the role of G9a and GLP mediated epigenetic regulation in the cancers. A thorough literature review was done related to G9a and GLP. The databases used extensively for retrieval of information were PubMed, Medline, Scopus and Science‐direct. Further, molecular docking was performed using Maestro Schrodinger version 9.2 software to investigate the binding profile of compounds with Human G9a HMT (PDB ID: 3FPD, 3RJW) and Human GLP MT (PDB ID: 6MBO, 6MBP).

Background Psoriasis is a chronic autoimmune skin disease characterized by hyperproliferation of keratinocytes. Wide treatment options used to treat psoriasis is associated with various adverse effects. To overcome this nanoformulation is prepared. Selenium is an essential trace element and plays major role in oxidation reduction system. Toxicity and stability limits the applications of selenium. Toxicity can be reduced and stabilized upon preparation into nanoparticles. Results Selenium nanoparticles (SeNPs) exhibit potent apoptosis through the generation of reactive oxygen species (ROS) with cell cycle arrest. SeNPs topical gel application produced significant attenuation of psoriatic severity with the abrogation of acanthosis and splenomegaly. SeNPs reduced the phosphorylation and expressions of MAPKs, STAT3, GSK-3β, Akt along with PCNA, Ki67, and cyclin-D1. Conclusion SeNPs inhibit various inflammation and proliferation mediated pathways and could be an ideal candidate for psoriasis therapy. Materials and methods SeNPs were characterized and various techniques were used to determine apoptosis and other molecular mechanisms. In vivo studies were performed by inducing psoriasis with imiquimod (IMQ). SeNPs were administered via topical route. Graphic Abstract

No abstract

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory disease associated with pulmonary edema, alveolar dysfunction, hypoxia, and inflammatory cell accumulation. The most contagious form of COVID-19 associated with ARDS caused by SARS-CoV-2. SARS-CoV-2 majorly produces the cytokine storm and severe lung inflammation and ultimately leads to respiratory failure. ARDS is a complex disease and there is no proper therapeutics for effective therapy. Still, there is a huge scope to identify novel targets to combat respiratory illness. In the current study, we have identified the epigenetic regulating protein BRD4 and developed siRNA based nanomedicine to treat the ARDS. The liposomes were prepared by thin-film hydration method, where BRD4 siRNA complexed with cationic lipid and exhibited 96.24 ± 18.01 nm size and stable even in the presence of RNase. BRD4 siRNA lipoplexes (BRD4-siRNA-LP) inhibited inflammatory cells in lungs and suppressed the lipopolysaccharide (LPS) induced the neutrophil infiltration and mast cell accumulation. Also, BRD4 siRNA based nanomedicine significantly reduced the LPS induced cytokine storm followed by inflammatory signaling pathways. Interestingly, BRD4-siRNA-LP suppressed the LPS-induced p65 and STAT3 nuclear translocation and ameliorated the lung inflammation. Thus, BRD4-siRNA-LP could be a plausible therapeutic option for treating ARDS and might be useful for combating the COVID-19 associated respiratory illness.

No abstract