Charan Psvv

Over the last three decades, we have witnessed three major outbreaks—SARS, MERS, and COVID-19—resulting in approximately 35 million infections worldwide. SARS-CoV-2, in particular, has developed sophisticated methods to hijack host mechanisms, often involving differentially expressed genes and long non-coding RNAs (lncRNAs), which our lab has studied extensively over the past five years. This study investigates whether the SARS-CoV-2 genome mimics elements of the host genome to facilitate replication, evade the immune system, and hijack host machinery. We achieved this by analyzing sequence similarities between the viral genome and the human genome, including the mitochondrial genome. Our work presents the mechanisms associated with SARS-CoV-2 transgression and explores the plausible implications of lateral gene transfer.

Cancer stem cells (CSCs) are a self-renewing population often linked to tumor initiation, metastasis, relapse, and resistance to therapy. While bulk tumor cells are often dependent on glycolysis, CSCs demonstrate metabolic plasticity can switch between glycolysis and OXPHOS (oxidative phosphorylation) depending on context. Mitochondria buffer against stress and allow for a metabolic reprogramming towards apoptosis evasiveness, making mitochondrial function crucial to CSC survival. The acquisition of stem-like traits coincides with the rewiring of mitochondrial metabolism, as newly emerging CSCs intermittently upregulate respiration, ROS detoxification, and metabolic plasticity to satisfy cellular demands. Several regulators converge on this mitochondrial metabolism axis. For instance, the co-activator peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and partner estrogen-related receptor α (ERRα) promote mitochondria biogenesis and OXPHOS while promoting tumor sphere formation and expression of stemness genes. Conversely, knockdown of PGC-1α reduces sphere formation and stemness. Similarly, a crucial process - mitophagy via AMP-activated protein kinase (AMPK) and related kinases regulate organelle turnover and quality control to promote CSC viability against stress. Mitochondrial dynamics (fission/fusion) also decides the fate of CSCs. The CSC metabolism is further influenced by the tumor microenvironment (TME). Hypoxia-inducible transcription factors, along with tumor stromal signals such as CAF-derived metabolites induce metabolic rewiring and strengthen antioxidant defenses in CSCs, thereby making it easier for CSCs to survive in unfavourable niches. The abundance of mitochondrial DNA and basal respiratory activity has been linked to CSC features such as increased ATP, stem cell markers and chemoresistance. Over the past few years, significant progress has been made in targeting mitochondrial metabolism of CSCs, yet is still a developing area with tremendous therapeutic scope. More research is required to identify mitochondrial vulnerabilities that are specific to therapy and then translate those findings into effective, precision-based cancer treatments. In this review, we try to provide a comprehensive overview of mitochondrial metabolism in regulating behaviour of CSCs, origin and characteristics of CSCs, the metabolic reprogramming for OXPHOS and glycolytic flexibility, molecular regulators of mitochondrial function, mitochondrial dynamics in stemness pathways and how the TME regulates these processes. We also review novel diagnostic techniques and therapies that target mitochondrial vulnerabilities to eliminate CSCs and provide better clinical outcomes.

Cancer Stem Cells (CSCs) represent a heterogeneous group of tumor cells that possess the innate ability to self-renew and differentiate, which also contributes to their resistance to first-line therapies. What sets CSCs apart from others is their crucial role in the recurrence of cancer, metastasis, and varied clinical responses against anti-cancer drugs, which makes them challenging to target. In recent years, there has been growing evidence that therapies capable of eliminating CSC niches or specifically targeting their core survival mechanisms are a potential means of providing a sustainable, long-term response to therapy and increasing disease-free survival rates. Bioactive compounds from natural sources have gained immense interest for their bio-efficacy, low toxicity profiles, and wide therapeutic index (TI), especially with their broad-spectrum ability of targeting multiple pathways while having little or no systemic side effects. Bioactive compounds can target major signaling pathways (Wnt/β-catenin, Notch, Hippo-YAP/TAZ, Hedgehog, PI3K/Akt/mTOR, NF-κB) to induce apoptosis, inhibit epithelial-mesenchymal transition (EMT), disrupt cancer stem cell niches, and other effects that suggest they resensitize to chemotherapeutic agents. Plant-derived biologics may be used as unique strategies targeting CSCs or as adjuncts reconstituted with custom conventional treatment plans, to mitigate drug resistance with mechanisms that involve targeting CSC metabolism, blocking protective autophagy, and the epigenetic landscape. The use of nanotechnology for targeted delivery of bioactive compounds is anticipated to provide better stability, bioavailability, and tumor accumulation. In this review, we outline a range of approaches using bioactive compounds for the eradication of CSCs, focusing on the mechanisms by which they work, the preclinical and clinical evidence supporting them, and their role in combination therapy approaches. This review also gives a comprehensive understanding of various other strategies and latest advancements that do not directly target the CSCs, including differentiation therapy, metabolic targeting, and immunomodulation, which, when used in conjunction with bioactive compounds, may resensitize the drug-resistant CSC population. We also discuss the therapeutic and translational potential of bioactive compounds and the future possibilities of combination, multi-targeted, CSC-based treatment strategies to eliminate tumor recurrences and improve cancer outcomes for patients. Graphical Abstract

Community awareness and rural development play a crucial role in achieving the Sustainable Development Goals (SDGs). To effectively address the global challenges outlined by the SDGs, gathering relevant data and insights at the grassroots is essential. Addressing global problems requires implementing localised solutions tailored to the specific needs of each community, recognizing that these needs vary across different communities. The potential of a flexible real-time geospatial survey platform that helps in finding such solutions is explored here. The geo-tagged empirical data gathered through the platform encompasses infrastructure, socioeconomic, natural resource, and environmental data. Prioritising informed consent and privacy protection, participants are made aware of the purpose of data collection and its use. The example of the N agarcoil Water Survey highlights the collection of data related to water availability, quality, and usage patterns, enabling valuable insights for water resource management. Future improvements may involve incorporating advanced data collection methods, integrating with existing datasets, ensuring data integrity by removal of duplicate and outdated data, and integrating with government portals like Open Government Data and GatiShakti.