Haseeb Ahsan

COVID-19 is a global pandemic caused by severe acute respiratory syndrome (SARS) coronavirus- 2 (SARS-CoV-2). The three main receptors used by SARS-CoV-2 to bind and gain entry into human cells are ACE, TMPRSS2, and CD147. These molecular factors have crucial roles in human metabolism and homeostasis, but the upregulation of these factors causes severe diseases such as myocarditis, prostate cancer, and other endocrine-related cancers. Studies have found that once humans come into contact with SARS-CoV-2, the chances of being affected by such disorders increase; indeed, infection with the virus is associated with increased morbidity and mortality from heart attacks and pulmonary inflammation. Notably, exposure to some pesticides, such as chlorpyrifos, cypermethrin, and imidacloprid, which are identified as potential endocrine disruptors, causes such disorders by interfering with hormonal signaling pathways, such as the insulinglucagon pathway and the thyroid pathway. This review focuses on the potential role of pesticides in exacerbating the comorbidities linked with SARS-CoV-2 and their effect on the molecular factors associated with SARS-CoV-2. Understanding the potential therapeutic implications of this link between SARS-CoV-2 severity and pesticides requires further clinical trials and investigations.

In the present study, we investigated the interaction of alpha-2-macroglobulin (& alpha;2M) with naringenin using multi-spectroscopic, molecular docking, and molecular simulation approaches to identify the functional changes and structural variations in the & alpha;2M structure. Our study suggests that naringenin compromised & alpha;2M anti-proteinase activity. The results of absorption spectroscopy and fluorescence measurement showed that naringenin-& alpha;2M formed a complex with a binding constant of (k(b))& SIM;10(4), indicative of moderate binding. The value of & UDelta;G & DEG; in the binding indicates the process to be spontaneous and the major force responsible to be hydrophobic interaction. The findings of FRET reveal the binding distance between naringenin and the amino acids of & alpha;2M was 2.82 nm. The secondary structural analysis of & alpha;2M with naringenin using multi-spectroscopic methods like synchronous fluorescence, red-edge excitation shift (REES), FTIR, and CD spectra further confirmed the significant conformational alterations in the protein. Molecular docking approach reveals the interactions between naringenin and & alpha;2M to be hydrogen bonds, van der Waals forces, and pi interactions, which considerably favour and stabilise the binding. Molecular dynamics modelling simulations also supported the steady binding with the least RMSD deviations. Our study suggests that naringenin interacts with & alpha;2M to alter its confirmation and compromise its activity.Communicated by Ramaswamy H. Sarma

Background: Coronavirus disease 2019 (Covid-19) is a novel disease caused by coronavirus-2 that causes severe acute respiratory syndrome (SARS-CoV-2). Although it primarily affects the respiratory system, the virus may also target the pancreas. It was suggested that upregulation of angiotensin-converting enzyme II (ACE-II) cell receptors or inflammatory cytokines play a major role in predisposing pancreatic injury in SARS-CoV-2 patients. Our aim was to conduct a critical evaluation of in order to provide an insight into the possibility of pancreatic injury. Methods: A case control study was conducted in the Department of Biochemistry IIMS&R, Integral University, Lucknow. Two groups of subjects (70 adults consisting of 35 Covid-19 survivors and 35 controls) aged between 35 to 70 years were selected for the study with mild to moderate Covid-19 diagnosed using RT-PCR/rapid antigen test and a control group of healthy individuals without history of Covid-19. The serum amylase was determined by the direct substrate method and serum lipase by the turbidimetric UV method using a semi-autoanalyzer. Results: The study showed that the serum amylase (p=0.023) and lipase (p=0.002) levels were significantly elevated in Covid-19 patients compared to the control subjects. The findings indicated that Covid-19 patients had a substantially higher mean serum amylase and lipase levels than the control subjects. Conclusions: The Covid-19 patients are prone to pancreatic injury.

A biomarker is any measurable biological moiety that can be assessed and measured as a potential index of either normal or abnormal pathophysiology or pharmacological responses to some treatment regimen. Every tissue in the body has a distinct biomolecular make-up, which is known as its biomarkers, which possess particular features, viz., the levels or activities (the ability of a gene or protein to carry out a particular body function) of a gene, protein, or other biomolecules. A biomarker refers to some feature that can be objectively quantified by various biochemical samples and evaluates the exposure of an organism to normal or pathological procedures or their response to some drug interventions. An in-depth and comprehensive realization of the significance of these biomarkers becomes quite important for the efficient diagnosis of diseases and for providing the appropriate directions in case of multiple drug choices being presently available, which can benefit any patient. Presently, advancements in omics technologies have opened up new possibilities to obtain novel biomarkers of different types, employing genomic strategies, epigenetics, metabolomics, transcriptomics, lipid-based analysis, protein studies, etc. Particular biomarkers for specific diseases, their prognostic capabilities, and responses to therapeutic paradigms have been applied for screening of various normal healthy, as well as diseased, tissue or serum samples, and act as appreciable tools in pharmacology and therapeutics, etc. In this review, we have summarized various biomarker types, their classification, and monitoring and detection methods and strategies. Various analytical techniques and approaches of biomarkers have also been described along with various clinically applicable biomarker sensing techniques which have been developed in the recent past. A section has also been dedicated to the latest trends in the formulation and designing of nanotechnology-based biomarker sensing and detection developments in this field.

The cell cycle has the capacity to safeguard the cell’s DNA from damage. Thus, cell cycle arrest can allow tumor cells to investigate their own DNA repair processes. Cancer cells become extremely reliant on G1-phase cyclin-dependent kinases due to mutated oncogenes and deactivated tumor suppressors, producing replication stress and DNA damage during the S phase and destroying checkpoints that facilitate progression through the S/G2/M phase. DNA damage checkpoints activate DNA repair pathways to prevent cell proliferation, which occurs when the genome is damaged. However, research on how cells recommence division after a DNA lesion-induced arrest is insufficient which is merely the result of cancer cells’ susceptibility to cell cycle arrest. For example, defects in the G1 arrest checkpoint may cause a cancer cell to proliferate more aggressively, and attempts to fix these complications may cause the cell to grow more slowly and eventually die. Defects in the G2-M arrest checkpoint may enable a damaged cell to enter mitosis and suffer apoptosis, and attempts to boost the effectiveness of chemotherapy may increase its cytotoxicity. Alternatively, attempts to promote G2-M arrest have also been linked to increased apoptosis in the laboratory. Furthermore, variables, such as hyperthermia, contact inhibition, nucleotide shortage, mitotic spindle damage, and resting phase effects, and DNA replication inhibitors add together to halt the cell cycle. In this review, we look at how nucleotide excision repair, MMR, and other variables, such as DNA replication inhibitors, hyperthermia, and contact inhibition, contribute to the outlined processes and functional capacities that cause cell cycle arrest.

Introduction: Many clinical studies have demonstrated that continuous exposure to pesticides, especially organophosphates and pyrethroids, causes toxicities such as carcinogenicity and neurotoxicity that lead to disorders such as diabetes, lung cancer, and neurodegenerative diseases. The mechanism underlying pesticide-induced neurotoxicity involves the production of ROS, which causes neuronal injury through oxidative stress. Methods: In the present study, the neuronal SHSY5Y cell line was used to investigate the effect of the pesticides chlorpyrifos (organophosphate), aldicarb (carbamate), and deltamethrin (pyrethroid) on ROS-mediated toxicity and the protective effect of alpha-2-macroglobulin (a2M), a protease inhibitor and beta-amyloid plaque scavenger in the human brain. For cell viability and cytotoxicity, the MTT assay was performed. To monitor ROS production, assays such as DCFHDA, H2O2, and MDA were performed, along with assays of the activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Results: The experimental findings suggest a cytoprotective role for a2M in ROS-mediated toxicity that causes neuronal injury in humans. Conclusion: Hence, a2M could be possibly used as a protective agent against oxidative neurotoxicity caused by pesticides.