Biopress Journal of Advanced Pharmacology (BJAP)
Biopress Journal of Advanced Pharmacology (BJAP) is a leading peer-reviewed, open-access journal published under the prestigious Biopress Journals series, dedicated to advancing cutting-edge research across all domains of pharmacological sciences. As an international platform, we bring together researchers, clinical pharmacologists, pharmaceutical scientists, and healthcare professionals to share transformative discoveries that bridge fundamental research with therapeutic applications.
Hibiscus Sabdariffa L. As A Medicinal Plant for Management of Hypertension
A significant cause of morbidity and mortality worldwide, hypertension is a chronic cardiovascular disease marked by consistently high arterial blood pressure. Long-term blood pressure control is still subpar despite the availability of numerous effective antihypertensive medications because of side effects, expense, and low patient adherence. The investigation of medicinal plants as supplemental or alternative therapeutic options has been prompted by these constraints. In traditional medical systems, Hibiscus sabdariffa L., or roselle, is frequently used to treat cardiovascular conditions, especially hypertension. Anthocyanins, flavonoids, and phenolic acids, which have antioxidant, vasorelaxant, and angiotensin-converting enzyme inhibitory properties, are abundant in the plant's calyces. With a focus on its traditional use, phytochemical composition, mechanisms of action, preclinical and clinical evidence, and safety profile, this review critically assesses Hibiscus sabdariffa L.'s function in managing hypertension. The significance of Hibiscus sabdariffa as a natural, affordable, and easily accessible medicinal agent is emphasized in this review. However, to confirm its effectiveness and guarantee its incorporation into contemporary pharmacotherapy for hypertension, more extensive clinical trials and formulation standardization are required.
Complications Associated With Hypertension
Pathophysiology and Allopathic Management Of Hypertension
Traditional Use Of Hibiscus Sabdariffa L., Pharmacological Activities
Hospital Microbial Contamination, Aseptic Technique Compliance, and Microbial Spread among Healthcare Workers: A Narrative Review
Healthcare associated infections (HAIs) represent one of the primary challenges to healthcare systems worldwide and are associated with a high incidence of mortality, morbidity, long hospital stays and elevated healthcare costs. Hospital environments are potent sources of pathogenic microorganisms which spread through contaminated environmental surfaces, devices, airborne vectors and direct contact with health care professionals. Aseptic techniques including hand hygiene, sterilization, and the correct use of personal protective equipment are not implemented sufficiently by healthcare workers. Health care professionals themselves are central to the transmission of the microorganisms which may even lead to increased cases of infections from multidrug-resistant organisms such as MRSA and resistant Gram- negative bacteria. This narrative review will cover the principal microbial reservoirs of contamination found in hospitals, the extent to which healthcare professionals comply with aseptic techniques and spread of microbes within a hospital setting as well as the ever-increasing threat of antibiotic resistance. Effective infection prevention and control measures such as the disinfection of hospitals, encouraging hand hygiene, antimicrobic control and continuous worker education will be highlighted as strategies which may reduce the rate of healthcare associated infections.
Green Pharmacy Approaches to Reduce Carbon Footprint in Healthcare: Sustainable Strategies for Pharmaceutical Manufacturing
Climate change and environmental contamination are growing worldwide issues, and the healthcare and pharmaceutical industries play a substantial role through their carbon emissions, waste production, and intensive use of resources. Drug manufacturing involves high energy consumption, solvent-based chemical synthesis, significant packaging waste, and multifaceted distribution systems, all of which heighten the environmental impact of healthcare delivery. As a result, green pharmacy has gained attention as a sustainable concept designed to reduce ecological damage while maintaining therapeutic performance. The review focuses on how green chemistry, eco-friendly drug development, and sustainable production technologies can help reduce the pharmaceutical sector’s carbon emissions. Approaches including additive manufacturing, microfluidics, mechanochemistry, spray congealing, and continuous processing help reduce solvent consumption, energy demand, and waste generation. Circular pharmaceutical economy practices, such as recycling programs, medication take-back initiatives, and eco-friendly packaging, further enhance environmental responsibility. Support from regulatory policies and international sustainability frameworks promotes wider implementation of green practices in healthcare. Case studies, including sustainable ibuprofen synthesis and enzyme-based drug production, highlight real-world applications. Collectively, embedding green pharmacy approaches within drug development, manufacturing processes, and healthcare delivery is key to lowering environmental burden and advancing sustainable healthcare. Ongoing advancements in green technologies, regulatory support, and multidisciplinary collaboration are expected to further enhance environmentally conscious pharmaceutical innovation.
Efficacy of GLP-1 Receptor Agonists (E.G., Semaglutide) In Non- Diabetic Obesity Management
The problem of obesity has now been recognized as one of the most important problems in the world. There has been an alarming rise in the incidence of obesity, which has also caused morbidity and mortality. Various health hazards of obesity include cardiovascular disease, metabolic disease, and cancer. It is accepted that lifestyle modification is an important factor in the management of obesity. However, it is difficult to achieve long-term management of obesity. This has necessitated the pharmacological management of obesity. Currently, there are a number of persons who understand that there is a potential for a new way of treating obesity by utilizing glucagon-like peptide-1 receptor agonists. Although most of these medications were developed for the purpose of treating type 2 diabetes, they have also shown that they can be used for the purpose of treating obesity. It is believed that semaglutide is the most potent of all the GLP-1 modulators, as it not only slows down the rate of gastric emptying but also suppresses appetite and induces society Substantial weight loss in body weight, body mass index, and waist circumference has also been reported in nondiabetic patients in recent clinical trials of semaglutide treatment versus placebo.Aside from weight loss, there are reports that improvements in other aspects of cardiometabolic risk factors are also seen. The safety profile of the drug is also acceptable. The most common adverse effects experienced by the patient are gastrointestinal upsets such as nausea and vomiting.
Exploring Ethnobotanical Approaches for Herbal Drug Discovery and Pharmacological Potential of Medicinal Plants
Ethnobotany is essential in connecting traditional knowledge with current pharmaceutical innovation, particularly in the discovery and development of herbal therapies. The current study focuses on a wide range of medicinal plants, including Phyllanthus amarus, Oroxylum indicum, Tinospora sinensis, Picrorhiza kurroa, Curcuma longa, Withania somnifera, and Azadirachta indica, among others, that have been widely used in traditional medical systems such as Ayurveda. These plants contain a high concentration of bioactive phytoconstituents such as alkaloids, flavonoids, glycosides, terpenoids, and phenolic compounds, which contribute to their important pharmacological properties. Recent scientific studies have demonstrated their therapeutic promise in the treatment of a variety of ailments, including liver problems, cancer, inflammation, microbial infections, metabolic disorders, and neurological conditions. For example, Phyllanthus amarus has potent hepatoprotective and antiviral effects, but Oroxylum indicum is anticancer and antioxidant. Similarly, Tinospora sinensis and Tinospora cordifolia are known for their immunomodulatory properties, whilst Picrorhiza kurroa has showed promise in liver protection and immunological modulation, with prospective use in viral infections. The combination of ethnobotanical knowledge with improved pharmacological screening, molecular docking, and nanotechnology-based drug delivery methods has increased the medicinal potential of these natural resources. This study emphasizes the significance of preserving traditional knowledge while encouraging scientific validation in order to assist the creation of safe, effective, and sustainable herbal medications. The findings highlight the importance of ongoing research to fully realize the therapeutic potential of these medicinal plants and convert them into clinically effective formulations.
Cervical cancer is a significant health concern for women worldwide. More than 600,000 women are diagnosed annually with cervical cancer, and approximately 340,000 of those women die from it each year. The leading cause of cervical cancer is called HPV, particularly high-risk HPV strains (e.g. HPV 16 and 18). The virus can enter your body and slowly alter your normal cells into cancer cells by producing the harmful proteins E6 and E7. Although vaccinations (i.e. Gardasil) are effective in protecting young girls from developing cervical cancer, adult women must continue to get regular screening for cervical cancer. The older methods used for screening women for cervical cancer (i.e. Pap smear) are only able to detect between 50% to 70% of all cervical abnormalities, and they rely upon laboratory technicians who have the expertise to read the sample. PCR tests can accurately identify approximately 95% of cervical cancer cases; however, these tests take 1 to 3 days to process, cost $40 per test, must be performed in a specialized laboratory, and require cold storage (i.e. refrigeration) until they are used – making them unsuitable for many villages and small health care clinics.Biosensors are the promise for the future of cervical cancer detection. Biosensors are small, easy to use test devices similar to blood sugar testing strips. They consist of a “catcher,” like an antibody or DNA fragment, which is used to capture the presence of HPV from a single swab taken from a woman’s neck. The results of the test are then visualized using either a light signal, color change or weight change – within 10 minutes, for $5. Electrically-activated biosensors are the least expensive and easiest to manufacture using printed testing strips with ultra-sensitive gold nanoparticles combined with either electrical or optical detection; therefore biosensors will produce an accuracy rate matching that of PCR tests but can be performed in any location, resulting in a 40% reduction in cervical cancer mortality rates in impoverished regions such as Pune. Here we will discuss biosensor construction and their advantages.(2)(11)(13)
Homoeopathic Bowel Nosodes and Gut Microbiome: A New Perspective in Gastrointestinal Health
The human gut microbiome has emerged as a critical determinant of health and disease, influencing metabolic, immune, neurological, and gastrointestinal functions. Homoeopathy has long recognized the significance of intestinal microbial balance through the concept of bowel nosodes. Introduced in the early twentieth century through the work of John Paterson, bowel nosodes were developed from intestinal bacterial cultures and used in homoeopathic therapeutics to address chronic diseases associated with intestinal dysbiosis. Recent scientific advances in microbiome research have renewed interest in these remedies, suggesting potential links between gut microbial imbalance and conditions such as colorectal cancer, autoimmune diseases, metabolic disorders, and neuropsychiatric illnesses. This review article explores the history, development, and therapeutic applications of bowel nosodes, their role in gut microbiome modulation, and emerging evidence supporting their use in various clinical conditions. Additionally, the article highlights contemporary approaches integrating dietary interventions such as microbiota-accessible carbohydrates with homoeopathic bowel nosodes for comprehensive gut health management.
Multidimensional Analysis of Self-medication among Undergraduate Students Focusing on Determinants and Health Outcomes
Background and Objective: Self-medication is a significant public health concern, particularly among university students in health-science disciplines who frequently bypass professional medical consultations. This study aims to analyze the behavioral determinants influencing self-medication practices and evaluate the associated health outcomes among undergraduate pharmacy students. Methods: A cross-sectional, questionnaire-based observational study was conducted over three months among undergraduate students aged 18–25 years at Srinivas College of Pharmacy, Mangalore. Students were stratified based on academic year, and proportional random sampling was applied. A total of 50 participants were included as part of a pilot exploratory study. Data were collected using a structured, pre-validated questionnaire (Cronbach’s alpha = 0.78) reviewed by subject experts. Data were analyzed using IBM SPSS Statistics 30. Descriptive statistics and chisquare test were applied, with p < 0.05 considered statistically significant. Results: The prevalence of self-medication was 72%. Major determinants included perceived mildness of illness (75%), easy drug availability (72%), and prior experience (69%). Commonly used drugs were analgesics (78%) and antipyretics (64%), with 36% reporting antibiotic use without prescription. While 80% reported symptom relief, 20% experienced adverse drug reactions (ADRs), and 22% reported delayed diagnosis. A significant association was observed between frequent self-medication and adverse outcomes (χ² = 6.80, p = 0.009). Conclusion: Self-medication is highly prevalent among pharmacy students. Despite pharmacological knowledge, inappropriate practices such as antibiotic misuse pose potential clinical risks. Targeted pharmacovigilance education and stricter regulatory enforcement are recommended.
DNA Damage Response in Cancer: Molecular Mechanisms and Therapeutic Exploitation
The DNA damage response (DDR) represents a highly conserved network of signaling pathways and repair mechanisms that are crucial for preserving genomic integrity. Cancer, which is marked by extensive genomic instability, often develops due to inherited or acquired deficiencies within these pathways. Paradoxically, these very defects can make tumor cells susceptible to therapeutic approaches that target the systems they are unable to regulate effectively. This review offers a thorough synthesis of DDR mechanisms, their dysfunction in the context of oncogenesis, and the emerging paradigm of targeting DDR components in cancer treatment. Particular emphasis is placed on the notion of synthetic lethality and its clinical application through poly(ADP-ribose) polymerase (PARP) inhibitors in tumors with BRCA mutations. Additionally, we explore new resistance mechanisms, the influence of the tumor microenvironment, and future prospects for functional biomarkers and personalized therapeutic strategies.
The Ketamine Paradox: Why the Weaker Enantiomer May Prove the Stronger Antidepressant
Ketamine — a dissociative anaesthetic and uncompetitive NMDA receptor antagonist — represents the most significant advance in depression pharmacology in half a century. As a racemic mixture of (S)-ketamine (esketamine) and (R)-ketamine (arketamine), it harbours a central paradox: the enantiomer with weaker NMDA binding appears, in preclinical models, to produce stronger and more durable antidepressant effects with fewer adverse effects. Esketamine has received FDA approval for treatment-resistant depression (TRD) and major depressive disorder with acute suicidal ideation, yet arketamine — despite being pharmacologically inferior on the receptor affinity metric used to justify esketamine — consistently outperforms it in animal models. This review examines the mechanistic, clinical, and critical dimensions of this paradox, arguing that NMDA affinity is an incomplete framework for predicting antidepressant potency and that the field has perhaps been measuring the wrong thing.
Nano-bio Hybrid Systems: a New Frontier in Targeted and Personalized Medicine
The advancement of drug delivery systems has significantly improved therapeutic outcomes; however, conventional approaches continue to face limitations such as poor bioavailability, non-specific targeting, and systemic toxicity. Nanotechnology has emerged as a powerful tool to overcome these challenges by enabling controlled and targeted drug delivery. Among recent innovations, nano-bio hybrid systems have gained considerable attention due to their ability to integrate synthetic nanomaterials with biological components, thereby enhancing therapeutic efficiency and biocompatibility. The objective of this review is to provide a comprehensive overview of nano-bio hybrid systems and their role in targeted and personalized medicine. The article discusses various types of hybrid systems, preparation techniques, characterization methods, and mechanisms of drug delivery. In addition, their applications in cancer therapy, infectious diseases, chronic disorders, and gene therapy are explored. Nano-bio hybrid systems demonstrate improved targeting efficiency, reduced toxicity, and controlled drug release owing to the incorporation of biomolecules such as proteins, lipids, and nucleic acids. Recent advances, including smart nanocarriers, artificial intelligence-assisted design, and theranostic applications, have further expanded their clinical potential. In conclusion, nano-bio hybrid systems represent a promising strategy for personalized medicine by enabling patient-specific therapy with enhanced safety and efficacy. Despite challenges related to scalability and regulatory approval, ongoing research is expected to facilitate their clinical translation in the near future.
Ethnobotanical Gut Healing Therapies of Indian Tribes: Microbiome Modulation and Ayurvedic Perspectives
The human microbiota is crucial for digestion, immunity, metabolism, and wellness. Dysbiosis, an imbalance in gut bacteria, is linked to conditions such as irritable bowel syndrome, inflammatory bowel disease, peptic ulcers, and metabolic disorders. Both conventional and traditional medicines use herbs to treat digestive issues and improve gastrointestinal health. Indian cultures have a rich tradition of using medicinal herbs for gastrointestinal ailments, such as digestive disorders, diarrhea, constipation, gastritis, and indigestion, often prepared as decoctions, powders, fermented mixtures, or kadha. These plants alter the microbiota composition, eliminate harmful strains, and boost short-chain fatty acid levels. Their chemical components, including polyphenols, alkaloids, flavonoids, tannins, and terpenoids, have anti-inflammatory, antimicrobial, and antioxidant properties that protect the gut lining. Ayurvedic remedies align with the vata, pitta, and kapha, maintaining the tri doshas balance. This review highlights the Indian tribal use of herbs for gastrointestinal health and how modern science and Ayurveda can enhance the understanding of their benefits. Ancient wisdom and microbiome research together offer improved, cost-effective, and culturally relevant solutions for gastrointestinal issues.
Successful Management of Dadru Kushtha (Tinea Corporis) with Ethnobotanical and Herbo-Mineral Approach: A Case Study
Background: Dadru Kushtha is classified in Ayurvedic classics as a Kshudra Kushtha with predominant Kapha and Pitta Dosha vitiation, manifesting as Kandu (intense itching), Raga (erythema), and Utsanna Mandala (elevated, ring- shaped lesions), secondary to derangement of Twak, Rakta, Mamsa, and Lasika Dushyas. Its closest modern correlate is tinea corporis (ICD-10: B35.4), a superficial dermatophyte infection commonly caused by Trichophyton rubrum and related species that colonize the keratinized skin layers, forming characteristic annular, scaly plaques. In an era of rising antifungal resistance and frequent recurrence after synthetic treatment, there is a pressing need for holistic, root-cause- directed therapeutic approaches. Case Summary: A 57-year-old male presented to the Outpatient Department (OPD) in February 2026 with a 2-week history of severe itching, irritation, and erythema over both forearms, accompanied by loss of sleep and appetite. He was subsequently admitted as an In-Patient Department (IPD) case at Parul Institute of Ayurved, Parul University, Vadodara, Gujarat. Intervention: Shamana (palliative and corrective) therapy was administered for 15 days, comprising: internal medications — Tab. Eranda Bhrishta Haritaki, Tab. Gandhaka Rasayana, Tab. Panchatiktaghrita Guggulu with Panchatikta Kashaya 15 ml, and Tab. Agni Tundi Vati, along with an external Lepa (medicated paste) of Tankana Bhasma, Gandhaka, Neem, and Haridra kalka in Ghrita Kumari Swarasa, applied twice daily. Outcomes: Marked and progressive relief was documented in itching, irritation, and erythema; lesion spread was significantly reduced; and sleep quality and appetite improved. One post-discharge follow-up confirmed ongoing regression of the condition with no new lesions. Conclusion: This case demonstrates the clinical efficacy of a well-reasoned, multi-target Ayurvedic Shamana protocol in managing Dadru Kushtha, offering a safe, recurrence-preventing alternative to conventional antifungal monotherapy.
Role of Vetiveria Zizanioides Linn. In The Treatment of Hepatotoxicity: A Review
Hepatotoxicity, a prevalent form of liver injury caused by xenobiotics, pharmaceuticals, and environmental pollutants, necessitates effective therapeutic interventions. Vetiveria zizanioides Linn., an aromatic grass widely used in traditional medicine systems like Ayurveda, has garnered attention for its potential hepatoprotective properties. This review consolidates and analyzes scientific evidence from peer-reviewed studies to elucidate the therapeutic role of Vetiveria zizanioides in managing hepatotoxicity. A systematic literature search across databases including PubMed, Scopus, and Web of Science, covering publications from 2000 to 2023, identified in vitro, in vivo, and limited clinical studies. The analysis highlights that bioactive constituents such as vetiverol, khusimol, and essential oils from vetiver roots exert hepatoprotective effects by mitigating oxidative stress, reducing lipid peroxidation, and elevating antioxidant enzyme activities like superoxide dismutase and catalase. Preclinical models exposed to hepatotoxins such as carbon tetrachloride, paracetamol, and heavy metals show significant reductions in elevated liver enzymes (e.g., alanine aminotransferase, aspartate aminotransferase) and improved histopathological profiles. Mechanistic insights point to the modulation of inflammatory pathways, inhibition of cytochrome P450-mediated toxin activation, and enhancement of cellular detoxification processes. Despite these promising outcomes, gaps persist in standardized dosing, long-term safety, and human trials. This review advocates for Vetiveria zizanioides as a viable natural adjunct in hepatotoxicity treatment, emphasizing the need for further clinical validation and phytochemical standardization to harness its full therapeutic potential.
Green Remedies for the Mind: Translation Potential of Medicinal Plants in Future Mental Healthcare
Stress and anxiety are becoming more common mental health issues in modern culture, owing primarily to lifestyle changes, work pressure, and social barriers. Conventional pharmaceutical therapies are effective, but they are frequently linked with side effects, dependence, and expensive costs. In this context, medicinal plants present a potential, safer, and more cost-effective option for stress and anxiety relief. Various ancient medical systems, such as Ayurveda, Unani, and ancient Chinese Medicine, have long used plant-based therapies to promote mental health. Several medicinal plants, including Withania somnifera (Ashwagandha), Bacopa monnieri (Brahmi), Ocimum sanctum (Tulsi), Valeriana officinalis, and Passiflora incarnata, have been shown to have anxiolytic and stress-relieving properties through mechanisms involving neurotransmitter modulation, antioxidant activity, and hypothalamic-pituitary-adrenal (HPA) axis regulation. This article presents an overview of medicinal plants used to treat stress and anxiety, including their active elements, pharmacological activities, and scientific data supporting their efficacy. The increased interest in green therapies demonstrates their potential to improve mental health with few side effects.
AI-Driven Reverse Pharmacology & Accelerated Drug Repurposing Using Ancient Indian Manuscripts – A Comprehensive Review
This paper presents a comprehensive literature review on AI-driven drug repurposing, contrasting traditional pharmacological methods with advanced AI-based approaches to elucidate their respective strengths and limitations. It systematically explores key computational techniques—such as network pharmacology, molecular docking, and deep learning—and their role in identifying drug-target interactions and predicting novel therapeutic indications. Special emphasis is placed on the digitalization and AI validation of traditional medical knowledge, particularly reverse pharmacology’s “bedside-to-bench” paradigm, which transforms historical clinical narratives into testable hypotheses. Through analysis of prominent case studies, the paper highlights both the transformative potential of AI integration in accelerating drug repurposing and the persistent challenges related to data heterogeneity and regulatory complexities. The vision of this review is to establish a holistic framework that synergizes computational innovations with ancestral wisdom, positioning AI-driven reverse pharmacology as a paradigm shift with the capacity to revolutionize drug discovery and therapeutic innovation. The mission is to provide critical insights and guide future research toward overcoming existing barriers, thereby enhancing the effectiveness and scope of medication repurposing strategies.
Evaluating the Impact of AI on Drug Discovery and Clinical Transition
Artificial intelligence (AI) is reshaping the medicament production by transfigure drug realization, optimizing evolution pipelines, and amplify clinical transitions. Traditional drug discovery is hindered by lofty attrition rates, long schedule, and escalating costs, and ameliorate clinical success rates, whereas AI-driven approaches leverage machine learning, deep neural matrix, and generative models to analyse vast abstracts, envision atomic properties, and design novel admixtures with unprecedented efficiency. These capabilities compress discovery cycles from years to months and intensify patient stratification and reconciling trial designs, contributing to up to 85% advancement rates in Phase I–III trials. AI’s integration into translational medicine bridges the gap between laboratory fact-finding and clinical application, facilitating biomarker discovery and personalized treatment strategies. Despite its life-changing potential, provocation remain in data quality, model interpretability, and regulatory validation, necessitating hybrid human-AI approaches. Breakthroughs such as AlphaFold’s protein structure prediction and generative adversarial webbing for de novo drug design have demonstrated corporeal acceleration, reducing discovery cycles from years to months. AI further strengthens translational panacea by integrating real-world evidence, biomarker discovery, and patient stratification, thereby improving clinical trial triumph rates and advancing individualize therapeutics. Applications span target identification, virtual screening, ADMET prediction, drug repurposing, and trial optimization, with ventures like Insilico Medicine, Benevolent AI, and Exscientia successfully advancing AI-designed molecules into clinical juncture. Despite these advances, challenges remain in data quality, model interpretability, and regulatory substantiate, underscoring the need for hybrid human-AI approaches. This review explores AI’s multifaceted role across drug discovery, repurposing, optimization, and clinical trials, highlighting actuality applications and future directions in simply drug innovation. Overall, AI represents a transformative force in pharmaceuticals, bridging the gap between laboratory research and clinical practice, while promising faster, safer, and more cost-effective therapeutic innovations.
ER-Mitochondria Crosstalk in Mitophagy Failure: Implication for Neurodegenerative Disorders
The critical association between mitochondria-associated membranes (MAMs), which are endoplasmic reticulum (ER)-mitochondria contact sites, and mitophagy failure in neurodegenerative diseases is the subject of this review. Because of the high energy demands and restricted regeneration of neurons, they rely on specific mechanisms of mitochondrial quality control (MQC) including biogenesis, dynamics, and mitophagy to counteract ROS damage, bioenergetic deficits or collapse of proteostasis. By activating PINK1-Parkin-dependent ubiquitination of outer mitochondrial membrane proteins or receptor-mediated pathways, mitochondria degrades dysfunctional mitochondria through mitophagy, while its impairment damages toxic organelles, exacerbating diseases like PD, AD and amyotrophic lateral sclerosis (ALS). Additionally, MAMs function as active centers for Ca2+ mechanistic interactions. How does this explain the development of Parkinson's disease? Despite the maintenance of optimal 10-65 nm spacing by tethering proteins like MFN2, VAPB-PTPIP51, and PDZD8, disruptions such as MNF2 mutations in Charcot-MarieTooth disease or TDP-43 aggregates on ALS cause wide gaps, blunt signaling, (via PINK1/Parkin recruitment) or stall binding to LC3 adaptors. In this state, disease-specific insults converge as: - synuclein overloads MAM in PD, A/tau disrupts Ca2+ flux in AD, mutant SOD1/VAPB impairs contacts in the ALS, and mHTT blocks HD mitophagy blockade, ROS surges, inflammation (NLRP3 at MAFs), and neuronal death. By discussing mitophagy pathways, MAM architecture and crosstalk functions as well as failure mechanisms and disorder links, this synthesis concludes: "MAM stabilizers (e.g, the anti-tumor P-like pridopidine), with or without food coke, inducer[M] and ER stress modulators (4-PBA] are therapeutically effective in returning homeostasis to normal cells.". In the future, super-resolution imaging, CRISPR screens and biomarkers will be used for precision interventions balancing clearance with biogenesis.
Fisetin as a Neuroprotective Flavonoid in Alzheimer's Disease; Targeting Bdnf and TAU Pathways
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes cognitive decline, synaptic dysfunction, neuronal loss, and characteristic pathologies such as Tau hyperphosphorylation and neurofibrillary tangle formation. In addition to amyloid and Tau pathology, impaired brain-derived neurotrophic factor (BDNF) signaling, oxidative stress, and chronic neuroinflammation all play important roles in disease development. Current therapeutic approaches only provide symptomatic alleviation, emphasizing the critical need for diseasemodifying medicines capable of addressing numerous pathogenic pathways. Fisetin, a naturally occurring dietary flavonoid, has received increased interest due to its extensive neuroprotective potential in AD. Preclinical investigations show that fisetin has antioxidant and anti-inflammatory properties while also improving neuronal survival and synaptic plasticity. Fisetin regulates BDNF signaling by increasing BDNF expression and activating downstream pathways such as Trk-B, CREB, PI3K/Akt, and MAPK, so promoting learning and memory processes. Fisetin reduces Tau pathology by suppressing hyperphosphorylation and aggregation. It does this by regulating important kinases such glycogen synthase kinase-3β (GSK-3β), which helps stabilize microtubules and maintain neuronal integrity. Despite convincing preclinical evidence, the clinical translation of fisetin is hampered by issues such as inadequate bioavailability, insufficient human research, and a lack of knowledge of its pharmacokinetics. Future research should focus on enhancing fisetin delivery using innovative formulations, verifying its efficacy in clinical trials, and investigating synergistic effects with existing AD medications. Fisetin stands out as a promising multitarget option for Alzheimer's disease prevention and treatment since it targets both BDNF-mediated neurotrophic support and Tau-associated neurodegenerative pathways.
Predictive Modeling Analysis to Predict Complications after Laparotomy: A PRISMA-Based Systematic Review
Background Postoperative complications following laparotomy remain a major contributor to surgical morbidity, mortality, prolonged hospitalization, and increased healthcare burden. Traditional perioperative risk assessment tools demonstrate limited predictive accuracy at the individual patient level, prompting increasing interest in predictive modeling approaches, including machine learning–based techniques, to enhance risk stratification and clinical decision-making. Objective To systematically evaluate predictive modeling approaches used to forecast postoperative complications after laparotomy and to analyze their methodological characteristics, predictive performance, and clinical applicability. Methods A PRISMA-based systematic review was conducted to identify studies evaluating predictive models developed to estimate postoperative complications following laparotomy or major abdominal surgery. Electronic databases were systematically searched for relevant studies published within the defined time frame. Eligible studies included those employing traditional statistical models or machine learning–based algorithms for postoperative risk prediction. Data extraction focused on study design, patient population, predictors used, modeling techniques, performance metrics, validation methods, and reported clinical outcomes. Risk of bias and methodological quality were evaluated in accordance with established systematic review and prediction modeling reporting standards. Results The included studies demonstrated increasing utilization of machine learning–based approaches alongside traditional regression models for predicting postoperative complications. Predictive performance across studies showed moderate to good discrimination, commonly reported using AUROC values ranging from approximately 0.70 to 0.85. Models incorporating dynamic perioperative variables including intraoperative parameters and early postoperative physiological data demonstrated improved predictive performance compared with models relying solely on static preoperative predictors. However, external validation remained limited, and calibration reporting was inconsistent. Conclusions Predictive modeling represents a promising strategy for improving early identification of high-risk patients undergoing laparotomy. Machine learning approaches offer potential advantages in handling complex perioperative data; however, their superiority over traditional statistical models appears context-dependent. Greater emphasis on external validation, methodological transparency, and integration into clinical decision-support systems is essential for translating predictive models into routine surgical practice.
Artificial Intelligence–Driven Molecular Docking for Selection of Antibacterial Agents in Periodontitis Therapy: From Pathophysiology to Target Validation
Periodontitis is a chronic inflammatory disease that leads to destruction of the supporting structures of teeth and eventually tooth loss. The disease is initiated by pathogenic bacteria and modified by host immune responses. Although mechanical cleaning remains the foundation of therapy, antibiotics are often required in moderate to severe cases. However, empirical drug selection, increasing resistance, and variable patient response limit treatment success. Artificial intelligence (AI) and molecular docking have recently emerged as powerful tools for improving precision in antimicrobial selection. These technologies allow prediction of drug–target interactions, screening of potential molecules, and optimization of therapy before clinical use. This review discusses the pathophysiology of periodontitis, the role of antibiotics such as minocycline and clindamycin, and the growing importance of AI-assisted molecular docking in periodontal drug discovery and validation.
Green Nanomedicine & Drug Delivery: Emerging Role of Nanoparticles in Targeted Therapy
In contemporary drug delivery methods, green nanomedicine has become a viable and biocompatible strategy. By integrating concepts of green chemistry with nanotechnology, ecofriendly nanoparticles are manufactured using biological sources such as plants, microbes, and biopolymers. These green-synthesized nanoparticles exhibit higher therapeutic efficacy, lower toxicity, and improved targeting ability compared to traditional nanocarriers. This study covers the concept of green nanomedicine, types of nanoparticles employed in drug delivery, their involvement in targeted therapy, analytical characterisation techniques, therapeutic uses, associated obstacles, and future possibilities in clinical translation.
A Comprehensive Review on Berberis Aristata DC: Phytochemistry, Pharmacology, and Therapeutic Potential
Berberis aristata DC, commonly known as Indian barberry or Daruharidra, is a medicinal plant extensively used in traditional systems of medicine such as Ayurveda, Siddha, and Unani. The plant is particularly valued for its rich content of isoquinoline alkaloids, of which berberine is the most prominent and pharmacologically active constituent. In recent years, scientific research has increasingly focused on berberine and Berberis aristata due to their wide spectrum of pharmacological activities, including antidiabetic, hypolipidemic, antimicrobial, antiinflammatory, hepatoprotective, neuroprotective, and anticancer effects. This literature review aims to provide a comprehensive and systematic evaluation of the botanical characteristics, phytochemical composition, pharmacological properties, mechanisms of action, clinical evidence, safety profile, and future prospects of Berberis aristata, with particular emphasis on berberine. Although berberine demonstrates significant therapeutic potential across multiple disease conditions, its clinical application is limited by poor oral bioavailability and pharmacokinetic challenges. Recent advancements in formulation strategies and drug delivery systems aimed at enhancing berberine absorption are also discussed. Overall, Berberis aristata represents a promising medicinal plant with potential applications in modern pharmacotherapy; however, further well-designed clinical studies and standardization efforts are required to establish its efficacy and safety conclusively.
Ginkgo Biloba’s Neuroprotective Potential in Alzheimer’sDementia
Alzheimer's disease (AD), which is characterized by increasing cognitive impairment and neuroinflammation, is a growing global health concern. Ginkgo biloba extract (standardized as EGb 761) has attracted a lot of interest among botanical therapies because to its many neuroprotective qualities. The main reason for its effectiveness is the combination of terpene lactones and flavonoid glycosides, which work in concert to tackle the underlying pathophysiology of dementia via multiple different pathways. Ginkgo biloba's strong antioxidant capability is the primary basis of its neuroprotective potential. The extract reduces the oxidative stress that usually precedes neuronal death in AD patients by scavenging reactive oxygen species (ROS) and increasing the activity of superoxide dismutase. Additionally, Ginkgo biloba exhibits a special capacity to maintain mitochondrial integrity, which stabilizes cellular energy production and prevents pro-apoptotic signals from being activated. In addition to protecting cells, the extract modifies the amyloid cascade by preventing peptides from aggregating into harmful oligomers, hence lowering the "plaque load" that interferes with synaptic transmission. According to clinical studies, ginkgo biloba is especially useful for stabilizing or delaying the deterioration of cognitive abilities and enhancing the ability of people with mild-to-moderate dementia to perform activities of daily living (ADL). The clinical data is still a little inconsistent because of variations in extract concentrations and patient demographics, even though it also improves cerebral microcirculation and lowers blood viscosity, offering a secondary vascular advantage. Ginkgo biloba ultimately functions as a clinically useful, well-tolerated adjunct therapy that tackles the complexity of neurodegeneration through a multi-target pharmacological approach, even though it is not a disease-modifying solution.
Neurobehavioral Consequences of Circadian Rhythm Disturbances: Insights into Mood Disorders and Cognitive Decline
Circadian rhythms are endogenous biological oscillations with an approximately 24-hour periodicity that synchronize behavioural and physiological processes with the environmental light–dark cycle. In humans, the circadian timing system regulates sleep-wake behaviour, hormonal secretion, neurotransmission, and higher cognitive functions. This system is hierarchically organised, with the suprachiasmatic nucleus (SCN) acting as the central pacemaker and coordinating peripheral clocks through transcription-translation feedback loops involving core clock genes such as CLOCK, BMAL1, PER, and CRY. Disruption of circadian rhythms, driven by light exposure, shift work, irregular sleep schedules, aging, and chronic stress, has emerged as a major contributor to neurobehavioral dysfunction. Growing evidence links circadian misalignment to mood disorders, including depression, bipolar disorder, and anxiety, as well as to cognitive decline. Mechanistically, circadian disruption impairs sleep-dependent memory consolidation, alters synaptic plasticity, dysregulates neuroendocrine pathways such as the hypothalamic-pituitary–adrenal axis, and disturbs the rhythmic release of neurotransmitters including serotonin, dopamine, glutamate, and GABA. At the molecular level, clock gene dysregulation, neuroinflammation, mitochondrial dysfunction, oxidative stress, and reduced neurogenesis collectively compromise emotional regulation and cognitive resilience. Age-related weakening of circadian rhythmicity further increases vulnerability to mood instability and neurodegenerative processes. This review integrates molecular, neurochemical, behavioural, and clinical evidence linking circadian rhythm disturbances to mood disorders and cognitive decline, and highlights emerging chronotherapeutic, light-based, pharmacological, and lifestyle interventions aimed at restoring circadian alignment and promoting brain health.
Whole-Exome Sequencing in Cancer Chemoprevention: Tracking Mutational Trajectories in High-Risk Populations
Whole-exome sequencing (WES) has revolutionized understanding of cancer chemoprevention by enabling comprehensive characterization of mutational landscapes in high-risk populations and monitoring of clonal evolution during prevention interventions. This review synthesizes current knowledge on WES applications in cancer prevention, emphasizing tracking of mutational trajectories from normal epithelium through dysplasia to invasive carcinoma. We examine discovery of driver mutations and mutational burden as chemoprevention biomarkers, computational approaches for inferring genetic progression (PhylogicNDT), and longitudinal monitoring of clonal evolution using circulating cell-free DNA in prevention trials. Particular emphasis is placed on oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED) as model systems where WES has identified key early driver mutations (TP53, NOTCH1, PIK3CA, CDKN2A) enabling molecular stratification of malignant transformation risk and personalization of prevention strategies. The review discusses universal cancer screening with WES identifying occult cancer predisposition syndromes, prospectively validated genetic progression models (gMART) predicting dysplasia-to-carcinoma risk, and emerging single-cell sequencing approaches revealing subclonal heterogeneity driving prevention failures. Integration of WES with spatial transcriptomics and single-cell RNA-seq provides unprecedented mechanistic insight into how dysplastic lesions acquire transformative mutations, enabling identification of optimal intervention windows during clonal evolution. Clinical applications including window-of-opportunity trials, real-time ctDNA monitoring of chemopreventive efficacy, and evolution-informed adaptive treatment strategies are discussed. We address critical challenges including tumor heterogeneity interpretation, distinguishing driver from passenger mutations in premalignant lesions, clinical translation of discovery findings, and cost-effectiveness of universal WES screening in prevention cohorts.
Clonal Evolution and Genomic Stability as Endpoints of Chemoprevention: Evidence from WES Studies
Cancer chemoprevention has historically relied on clinical endpoints (tumor incidence, survival) as measures of efficacy, requiring decades of follow-up and large patient cohorts. Whole-exome sequencing-enabled molecular monitoring of clonal evolution and genomic stability now offers mechanistic alternatives enabling real-time assessment of whether chemopreventive agents successfully suppress high-risk clones or inadvertently select for resistant populations. This comprehensive review synthesizes evidence that clonal evolution dynamics measured through circulating cell-free DNA (cfDNA) monitoring, subclonal architecture reconstruction, and variant allele frequency changes represent sensitive, biologically-meaningful endpoints of chemoprevention efficacy. We examine how WES reveals whether prevention agents achieve true elimination of transformative clones versus mere delay of inevitable progression, a critical distinction with different clinical implications. Suppression of high-risk clones carrying driver mutations (TP53, NOTCH1, PIK3CA) is discussed alongside mechanisms including genomic instability enhancement, immune checkpoint activation, and senescence induction. Integration of clonal evolution endpoints with genomic stability assessment quantified through measures including mutational burden dynamics, copy number variation stability, and DNA repair gene expression provides comprehensive evaluation of chemoprevention-induced evolutionary constraints. Case studies demonstrate successful clonal suppression in chronic lymphocytic leukemia under targeted therapy, osimertinib-resistant lung cancer clones under combination approaches, and emerging oral dysplasia suppression through immune checkpoint blockade. Critical challenges including distinguishing adaptive clonal responses from true suppression, heterogeneity in clonal fitness landscapes, and translating molecular suppression to clinical benefit are addressed. The review discusses adaptive trial designs leveraging clonal evolution endpoints, mathematical modeling of clonal evolutionary trajectories, and future integration with spatial transcriptomics and single-cell technologies enabling unprecedented resolution of prevention mechanisms.
Mutation Signatures and Genome Protection: Applications of WES in Chemoprevention Trials
Whole-exome sequencing (WES) has emerged as a transformative technology for understanding cancer initiation and progression through the lens of mutational signatures characteristic patterns of somatic mutations imprinted on cancer genomes by underlying mutagenic processes. This review synthesizes current knowledge on the application of WES-derived mutation signatures as biomarkers and endpoints in cancer chemoprevention trials, with emphasis on genomic approaches to preventing malignant transformation. We examine mechanistic underpinnings of major carcinogen-specific signatures (tobacco, ultraviolet, alcohol, aging), discuss technical considerations for implementing WES as a clinical platform, and outline strategies for integrating mutation signature analysis into adaptive trial designs. Particular focus is given to oral squamous cell carcinoma (OSCC) prevention, where loss of heterozygosity (LOH) profiling and emerging somatic mutation burden metrics offer unprecedented opportunities for patient enrichment and molecular monitoring. We review the paradigm shift from histologic endpoints (intraepithelial neoplasia) to genomic endpoints (tumor mutational burden, signature composition, clonal evolution), and discuss how mutation signatures can guide personalized chemoprevention through synthetic lethal approaches targeting DNA damage response deficiencies. The integration of multi-omic biomarkers, liquid biopsy, and adaptive trial designs promises to accelerate the clinical translation of genome protection strategies, ultimately improving cancer prevention outcomes in high-risk populations.
Integrating Whole-Exome Sequencing with Clinical and Histopathological Endpoints in Chemoprevention Studies: A Framework for Mechanistically Informed Prevention Trials
The integration of whole-exome sequencing (WES) with classical clinical and histopathological endpoints represents a paradigm shift in cancer chemoprevention trial design, enabling mechanistically informed patient stratification and molecular monitoring of intervention efficacy. This review examines the state-of-the-art in multi-endpoint chemoprevention studies, with emphasis on (1) correlating somatic mutations detected via WES with histopathological dysplasia grade and regression, (2) designing chemoprevention trials with composite endpoints combining molecular, histological, and clinical measures, and (3) strengthening causal inference regarding biomarker-guided interventions through mediation analysis, reverse validation, and mechanistic studies. We synthesize evidence from landmark studies including the Oral Cancer Prediction Longitudinal Study (LOH validation), Erlotinib Prevention of Oral Cancer (EPOC) trial, Mallery freeze-dried black raspberry trial, and emerging protocols such as the SAVER (Sodium Valproate for Epithelial Dysplasia) trial. Key challenges addressed include the dysplasia paradox (wherein histology is a poor independent predictor of progression), the surrogate endpoint paradox (wherein biomarker improvement does not guarantee clinical benefit), intratumor heterogeneity, field cancerization, and technical standardization of WES for clinical-grade implementation. We provide a practical framework for integrating WES data with endpoints, discuss FDA biomarker qualification pathways, and outline future directions including multi-omic integration, liquid biopsy-based monitoring, and artificial intelligence-driven discovery of progression biomarkers.
Challenges, Ethics, and Cost-Effectiveness of Using Whole Exome Sequencing for Chemoprevention Assessment
Whole-exome sequencing (WES) has emerged as a powerful tool for enhancing cancer chemoprevention by enabling genomic risk stratification, pharmacogenomic tailoring, and mechanistic insight beyond traditional clinical risk models. This comprehensive review evaluates the feasibility, ethical considerations, regulatory landscape, and cost-effectiveness of implementing WES in cancer prevention settings. We synthesize evidence demonstrating that WES can identify high- and moderate-penetrance germline variants, inform polygenic risk assessment, and guide personalized chemoprevention and surveillance strategies, particularly in enriched high-risk populations. However, widespread adoption is constrained by substantial infrastructure requirements, challenges in defining evidence-based surveillance intervals, and unresolved ethical issues surrounding incidental findings, informed consent, genetic discrimination, and equity across diverse ancestries. Regulatory frameworks for WES-guided prevention remain heterogeneous and continue to evolve, while economic evaluations suggest context-dependent cost-effectiveness influenced by population risk, healthcare system structure, and downstream intervention costs. We propose an integrated, equity-centered implementation framework emphasizing standardized risk protocols, genetic counseling integration, transparent consent processes, and prospective evidence generation to responsibly advance WES-guided precision chemoprevention.