Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.

Plants are an essential component of our daily diet, and their nutritional value has been thoroughly studied for many years. The ability of plants to adapt to changing environmental conditions through signaling systems is an essential component of their survival. Plants undergo an array of physiological alterations to respond to stress from biotic sources. Secondary compounds frequently accumulate in crops that are sensitive to stress, particularly those with several eliciting agents or signaling molecules. Plants contain various types of bioactive compounds, including phytosterols, alkaloids, glycosides, and polyphenols, which make them valuable for the food and pharmaceutical industries. The increased production of secondary metabolites via elicitation has opened up a new field of study with the potential to provide substantial financial gains for the pharmaceutical and nutraceutical industries. These elicitors are pharmacological compounds that activate specific transcription factors and up-regulate genes to activate metabolic pathways. Thus, the current review discusses the mechanism of biotic elicitation and various elicitation techniques using biotic (proteins, carbohydrates, rhizobacteria, fungi, and hormones) elicitors that may increase the yield of secondary metabolites, particularly in medicinal plants, which is advantageous to the agrochemical and therapeutic industries.

Cyclotriazadisulfonamide (CADA) is a macrocyclic compound known for its unique mechanism in inhibiting HIV infection by downregulating the CD4 T-cell receptor, a crucial entry point for the virus. Unlike other antiretrovirals, CADA exhibits activity against a wide range of HIV strains, as all HIV variants require CD4 binding for infection. Furthermore, CADA has shown a synergistic effect with clinically approved anti-HIV drugs, offering potential for enhanced therapeutic strategies (Vermeire & Schols, [65]). One proposed mechanism for CADA’s inhibition of the CD4 receptor involves blocking the gates of the Sec61 channel, thereby preventing its translocation. However, CADA suffers from poor solubility and bioavailability. To address this, the study aimed to design CADA analogs with improved binding to the Sec61 channel, enhanced bioavailability, and reduced toxicity. The analogs were designed using SeeSAR, with Avogadro and Meeko used for 3D configuration and pseudoatom placement, respectively. AutoDock Vina version 1.2.4 was employed to predict the binding energies of these analogs. Of the 113 analogs designed, 93 demonstrated a more negative binding energy to the Sec61 channel compared to CADA. Structure-binding energy analyses were done to the top-binding analogs to show favorable structural modifications. Enzyme-ligand interactions were analyzed to elucidate the forces contributing to these binding energies. Additionally, 33 of the 113 analogs were deemed bioavailable using a bioavailability criteria specific for macrocycles. Toxicity predictions using PASS Online and StopTox identified analogs JGL023, JGL024, JGL032, and JGL047 as potential drug candidates. Molecular dynamics simulations using Gromacs-2020.4 revealed that JGL023 and JGL032 exhibited the most favorable binding to the Sec61 channel, as determined by evaluating ligand and residue flexibility, compactness, contact frequency, motion pathways, free energy, and other relevant parameters. Synthetic routes for these four analogs were proposed for future studies. The results of this study offer a new perspective on developing drugs to inhibit HIV entry.

Zamzam water (ZW), a naturally occurring alkaline mineral water with a distinctive ionic and trace-element composition, has attracted growing scientific interest due to its reported pharmacological properties and emerging biological effects relevant to cancer research. This review provides a comprehensive mechanistic synthesis that links the physicochemical characteristics of ZW to molecular and cellular processes implicated in cancer biology. Integrating evidence from cancer biology, redox pharmacology, mitochondrial physiology, and cellular signaling, this review examines how the unique mineral composition and mildly alkaline pH of ZW may collectively influence pathways associated with the hallmarks of cancer. Preclinical studies demonstrate context-dependent modulation of cell proliferation, apoptosis, oxidative stress, mitochondrial function, cell-cycle progression, and signaling pathways, including mitogen-activated protein kinase (MAPK) and cyclic AMP (cAMP) networks, across multiple cancer models. Beyond its reported antiproliferative activity, ZW also exhibits antioxidant, anti-inflammatory, and organ-protective effects in non-malignant systems. Importantly, this review proposes a conceptual framework for investigating the relative contributions of mineral ions, ionic homeostasis, redox regulation, and physicochemical properties to the biological effects of ZW, and identifies key mechanistic and methodological gaps. ZW has exhibited cancer-associated biological effects in experimental animals; however, its therapeutic effectiveness has yet to be validated. Future studies integrating standardized physicochemical characterization, molecular validation, multi-omics approaches, and clinical investigations are required to establish its translational relevance in complementary oncology.

Background: Rehabilitation is a core component of universal health coverage, yet it remains inadequately integrated into primary healthcare systems in many low- and middle-income countries, limiting early intervention, functional recovery, and long-term quality of life. This study aims to explore global models and innovative strategies for strengthening the integration of rehabilitation into primary healthcare in Bangladesh to inform context-appropriate policy and service reforms. Methods: A narrative review was conducted using a structured literature search of major bibliographic databases (Sciverse Scopus, PubMed, Embase, Web of Science, and Cochrane Library) and World Health Organization institutional repositories for literature published between 2014 and 2025. The search terms covered rehabilitation integration, primary healthcare, health system strengthening, and technological innovations. Studies from global and low- and middle-income countries were prioritised. Study selection and screening followed a structured selection process, and the included studies were thematically synthesized to develop a context-specific framework for Bangladesh. Results: Physical disabilities represent a significant share of rehabilitation needs; however, access to and the quality of available rehabilitation services remain limited. In Bangladesh, service provision is primarily influenced by three factors: inadequate physical infrastructure, shortages of trained personnel, and insufficient financing, which contribute to the concentration of services in urban areas. Although community-based rehabilitation initiatives have demonstrated improved service reach and acceptability, the integration of physical and mental health rehabilitation within primary healthcare remains limited. International experiences, including Chile’s comprehensive rehabilitation system and selected models from the Brazil, Russia, India, China, South Africa countries, highlight effective approaches to integrating rehabilitation into primary healthcare. Technological applications, particularly telerehabilitation and other low-cost digital platforms, have the potential to expand access to services. Conclusion: Strengthening rehabilitation in Bangladesh’s primary health care requires integrating basic services, training health workers, and establishing referral pathways, alongside expanding low-cost digital and community-based care to improve access in underserved areas.