Vol 31, No 41 (2024)

Background:Parasitic diseases are a public health problem despite the existence of drugs for their treatment. These treatments have variable efficacy and, in some cases, serious adverse effects. There has been interest in the enzyme carbonic anhydrase (CA) in the last two decades since it is essential in the life cycle of various parasites due to its important participation in processes such as pyrimidine synthesis, HCO3 - transport across cell membranes, and the maintenance of intracellular pH and ion transport (Na+, K+, and H+), among others.

Objective:In this review, CA was analyzed as a pharmacological target in etiological agents of malaria, American trypanosomiasis, leishmaniasis, amoebiasis, and trichomoniasis. The CA inhibitors´ design, binding mode, and structure-activity relationship are also discussed.

Conclusion:According to this review, advances in discovering compounds with potent inhibitory activity suggest that CA is a candidate for developing new antiprotozoal agents.

:Periodontitis (PD) is a chronic inflammatory disease of the periodontium characterized by the formation of gingival pockets and gingival recession. The local inflammatory environment can lead to the destruction of the extracellular matrix and subsequent bone loss. The pathophysiology of PD involves interactions between genetic predisposition, lifestyle, environmental factors, the oral microbiota condition, systemic health disorders, innate and adaptive immune responses, and various host defenses. The review highlighted the importance of the oral cavity condition in systemic health. Thus, a correlation between harmful oral microbiota and cardiovascular disease (CVD)/diabetes/ arthritis, etc, progressions through inflammation and bacterial translocation was highlighted. Antecedents increase an individual's risk of developing PD, trigger initiate microbe-host immunologic responses, and mediators sustain inflammatory interactions. Generally, this review explores the antecedents, triggers, and mediators along the pathophysiological continuum of PD. An analysis of modern approaches to treating periodontitis, including antibiotics for systemic and local use, was carried out. The potential role of natural ingredients such as herbal extracts, phytoconstituents, propolis, and probiotics in preventing and treating PD was highlighted.

:Stress is a critical factor in the etiology of inflammation and neurodegeneration. The risk factor for the majority of psychiatric disorders is oxidative stress-induced depression. Mitochondrial damage and oxidative stress are associated with the development of neurodegenerative disorders. During aging, the brain and associated regions become more susceptible due to oxidative stress. The leading cause of oxidative stress is the continuous generation of ROS (reactive oxygen species) and RNS (Reactive nitrogen species) endogenously or exogenously. In this review, discussion on a potent antioxidant natural constituent "curcumin" has been made to alleviate many pathological and neurological disorders. A focused compilation of vast and informative research on the potential of curcumin as a magical moiety used therapeutically has been done in search of its role in controlling the neurological and similar disorders induced by oxidative stress.

:Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented.

Background:Systemic multi-organ dysfunction resulting from dysregulated immune responses in the host triggered by microbial infection or other factors is a major cause of death in sepsis, and secretory pathways play an important role in it.

Methods:GSE57065, GSE65682, GSE145227, and GSE54514 from Gene Expression Omnibus (GEO) were derived for this study. Secretory pathways single sample gene set enrichment analysis (ssGSEA) scores in sepsis and normal samples were exposed. Gene modules associated with secretory pathways were selected by weighted gene coexpression network analysis (WGCNA) for Protein-Protein Interaction Networks (PPI) assessment, and crossover genes in both were evaluated by eXtreme Gradient Boosting (XGBoost) model in feature selection to identify hub genes in sepsis. In addition, we explored the immune cells and signaling pathways regulated by hub genes.

Results:Remarkable dysregulation of secretory pathways was demonstrated in sepsis. The secretory pathways-associated gene modules were intimately involved in cytokine and immune responses in infection. Four crossover genes (CD163, FCER1G, C3AR1, ARG1) were present in WGCNA and PPI, and training in the XGBoost model revealed the best diagnostic performance of these 4 genes, meaning that these genes were the hub genes for sepsis. The 4-hub genes showed a significant negative correlation with T cell activity and a significant positive correlation with inflammatory immune cells. In addition, we found that the 4-hub genes markedly positively regulated INFLAMMATORY RESPONSE, IL6 JAK STAT3 SIGNALING.

Conclusion:Based on WGCNA, PPI, and XGBoost models, we identified hub genes that play an important regulatory role in sepsis. We also developed novel molecular models for the diagnosis of sepsis.