A bioinformatics approach to elucidate conserved genes and pathways in C. elegans as an animal model for cardiovascular research.

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in CVD research. Caenorhabditis elegans, a nematode species, has emerged as a prominent experimental organism widely utilized in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilization for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, and aha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signaling pathway, the FoxO signaling pathway, the MAPK signaling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.

Identification of potential regulatory mechanisms and therapeutic targets for lung cancer.

Lung cancer poses a significant health threat globally, especially in regions like India, with 5-year survival rates remain alarmingly low. Our study aimed to uncover key markers for effective treatment and early detection. We identified specific genes related to lung cancer using the BioXpress database and delved into their roles through DAVID enrichment analysis. By employing network theory, we explored the intricate interactions within lung cancer networks, identifying ASPM and MKI67 as crucial regulator genes. Predictions of microRNA and transcription factor interactions provided additional insights. Examining gene expression patterns using GEPIA and KM Plotter revealed the clinical relevance of these key genes. In our pursuit of targeted therapies, Drug Bank pointed to methotrexate as a potential drug for the identified key regulator genes. Confirming this, molecular docking studies through Swiss Dock showed promising binding interactions. To ensure stability, we conducted molecular dynamics simulations using the AMBER 16 suite. In summary, our study pinpoints ASPM and MKI67 as vital regulators in lung cancer networks. The identification of hub genes and functional pathways enhances our understanding of molecular processes, offering potential therapeutic targets. Importantly, methotrexate emerged as a promising drug candidate, supported by robust docking and simulation studies. These findings lay a solid foundation for further experimental validations and hold promise for advancing personalized therapeutic strategies in lung cancer.Communicated by Ramaswamy H. Sarma.

"Unravelling the impacts of climatic heat events on cardiovascular health in animal models".

Climate change has led to an increase in high ambient temperatures, causing extreme heat events worldwide. According to the World Meteorological Organization (WMO), July 2023 marked a historic milestone as the Earth reached its hottest recorded temperature, precisely hitting the critical threshold of 1.5 °C set by the Paris Agreement. This distressing development led to a stark warning from the United Nations, signaling the dawn of what they call "an era of global boiling". The increasing global temperatures can result in high heat stress which leads to various physiological and biochemical alterations in the human body. Given that cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally, heat events exacerbate this public health issue. While clinical and in-vitro studies have suggested a range of pathophysiological and biochemical mechanisms underlying the body's response to heat stress, the complex nature of organ-system level interactions makes precise investigation challenging. To address this knowledge gap effectively, the use of animal models exposed to acute or chronic heat stress can be invaluable. These models can closely replicate the multifaceted effects observed in humans during heat stress conditions. Despite extensive independent reviews, limited focus has been shed on the high heat-induced cardiovascular complications and their mechanisms, particularly utilizing animal models. Therefore, in this comprehensive review, we highlight the crucial biomarkers altered during heat stress, contributing significantly to various CVDs. We explore potential mechanisms underlying heat-induced cardiovascular dysfunction and damage, delving into various animal models. While traditional rodent models are commonly employed, we also examine less conventional models, including ruminants, broilers, canines, and primates. Furthermore, we delve into various potential therapeutic approaches and preventive measures. These insights hold significant promise for the development of more effective clinical interventions against the effects of heat stress on the human cardiovascular system.

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for Establishing Caenorhabditis elegans as an Animal Model for Cardiovascular Diseases.

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research. Caenorhabditis elegans , a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, and aha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.

Tachyplesin and CyLoP-1 as efficient anti-mycobacterial peptides: A novel finding.

Mycobacterium tuberculosis is an etiological agent of tuberculosis (TB) known to be a highly contagious disease and is the major cause of mortality from a single infectious agent worldwide. Emergence of multi-drug resistant and extremely drug resistant strains of M. tuberculosis has made TB management extremely challenging eliciting the urgent need for alternative therapeutics. Peptide based therapeutic strategies are an emerging area that can be employed as a prospective alternative to the currently existing therapeutic regime for TB treatment. Here, we are reporting the anti-mycobacterial activity of two peptides, Tachyplesin and CyLoP-1, derived from marine horseshoe crab and snake toxin respectively, with potent anti-mycobacterial activity against various mycobacterium species. Both the peptides exhibit appreciable antimicrobial and anti-biofilm activities against mycobacterium species with minimum cytotoxicity towards macrophage cells. They are also effective in eliminating mycobacterium cells from infected macrophage cells. Tachyplesin acts on mycobacterium cells in a lytic manner with outer membrane disruption confirmed by propidium iodide uptake with slight membrane depolarization and reactive oxygen species (ROS) production. CyLoP-1, on the other hand, does not rupture the mycobacterium cells even at high concentrations. It seems to follow intracellular pathway of killing mycobacterium cells by production of more ROS and membrane depolarization. Both the peptides do not lead to apoptotic way of mycobacterium cell death. These results suggest an effective peptide-based antimicrobial strategy for development of future anti-TB therapeutics.