Mani Sharma

Background: Huntington’s disease is a slowly progressive autosomal dominant neurodegeneration caused by mutant huntingtin-induced proteomic disturbances such as mitochondrial dysfunction, oxidative stress, protein homeostasis disturbance, synaptic degeneration, and neuroinflammation. Resveratrol, a polyphenol derived from Vitis vinifera, has emerged as a repurposed activator of Sirtuin 1 (SIRT1) with neuroprotective potential in Huntington’s disease. Aim: This manuscript aimed to evaluate the therapeutic potential of resveratrol in Huntington’s disease, with a focus on its SIRT1-mediated effects on proteomic abnormalities and related pathogenic pathways. Methods: This paper presents an analytical discussion and mechanistic analysis based on pre-clinical evidence, proteomics research, network pharmacology, and experimental studies concerning resveratrol, the SIRT1 pathway, and Huntington’s disease model systems. This manuscript combines evidence collected from experiments using iPSC-derived neurons, transgenic mice, and other neurodegeneration experiments to elucidate the molecular rationale for resveratrol repurposing. Results: According to this review, resveratrol can stimulate SIRT1 through allostery to promote mitochondrial biogenesis, antioxidant defence, autophagy, proteostasis, suppression of neuroinflammation, and recovery of synaptic and metabolic protein networks affected by Huntington’s disease. However, it is limited by poor absorption, rapid metabolism, and an inability to cross the blood-brain barrier. Major Findings: Resveratrol from Vitis vinifera appears to be a promising repurposed SIRT1 activator that may alleviate Huntington

This manuscript reviews tailored organocatalysis as a key part of green chemistry. It highlights metal-free, recyclable systems that support sustainable synthesis. Tailored organocatalysts include proline derivatives, thioureas, Cinchona alkaloids, and N-heterocyclic carbenes (NHCs). They achieve high conversion rates of over 95% in aldol additions, Michael additions, and C-C couplings under mild conditions, such as water or deep eutectic solvents (DES). Proline derivatives enable biodegradable aldol reactions with greater than 95% enantiomeric excess (ee). Squaramides allow for high-turnover cascades in DES, which can be recycled without using toxic solvents. Custom catalysts also reach over 95% efficiency in CO2 conversion and biomass upgrades, remaining recyclable for over 10 cycles and outperforming traditional methods with less than 40% atom economy. Atomic economy hits 98% in regioselective Fe/Co/Ni systems and 100% in photocatalytic Cu clusters for C-H activation. This helps minimize byproducts through enamine/iminium and hydrogenbonding activation. Single-atom Pd catalysts ensure a 90% reduction in waste for boration/C-C couplings at room temperature. AuLaMnCuO3 perovskites achieve 95% conversion of ethanol to acetaldehyde at 225°C with stability for 500 hours. Biocatalyst hybrids made from agro-waste reach 99% enantiopurity in water-based esterifications, which supports circular economies. These innovations replace stoichiometric agents, drastically reducing E-factors and enabling scalable pharmaceutical processes that produce over 99% ee products.

Artificial Intelligence (AI) is transforming drug delivery and discovery, promising faster timelines, enhanced efficacy, and personalized treatments. AI has achieved significant advancements in cancer detection, cardiovascular theranostics, and bioinformatics. Machine learning algorithms expedite drug candidate identification by predicting efficacy and safety, streamlining drug development, and enabling precision therapies. AI-driven models also design nanoscale delivery systems for targeted drug release, minimizing side effects and maximizing efficacy. In personalized medicine, AI analyzes genomics, proteomics, and clinical data to identify biomarkers, predict treatment responses, and optimize therapeutic regimens, shifting from one-size-fits-all to tailored interventions based on individual genetic profiles.

Artificial Intelligence (AI) is transforming drug delivery and discovery, promising faster timelines, enhanced efficacy, and personalized treatments. AI has achieved significant advancements in cancer detection, cardiovascular theranostics, and bioinformatics. Machine learning algorithms expedite drug candidate identification by predicting efficacy and safety, streamlining drug development, and enabling precision therapies. AI-driven models also design nanoscale delivery systems for targeted drug release, minimizing side effects and maximizing efficacy. In personalized medicine, AI analyzes genomics, proteomics, and clinical data to identify biomarkers, predict treatment responses, and optimize therapeutic regimens, shifting from one-size-fits-all to tailored interventions based on individual genetic profiles.

Background: Alzheimer’s Disease (AD) involves Amyloid-Beta (Aβ) plaque accumulation, endothelial dysfunction, and cerebral hypoperfusion, with Ginkgo biloba flavonoids (e.g., quercetin, kaempferol glycosides in EGb761) emerging as nutraceuticals that enhance endothelial Nitric Oxide (NO) pathways for vasodilation while inhibiting Aβ fibrillisation. Aim: To review the dual mechanisms of Ginkgo flavonoids in boosting cerebral blood flow via endothelial Nitric Oxide Synthase (eNOS) activation and preventing Aβ aggregation, alongside their nutraceutical applications, preclinical/clinical evidence, and safety profile for AD management. Methods: Comprehensive literature synthesis from in vitro (e.g., DPPH, Thioflavin T (ThT) assays), animal models (e.g., hippocampal perfusion in AD rodents), clinical trials (e.g., EGb761 with donepezil), and network pharmacology analyses, structured around phytochemical profiles, mechanistic pathways, formulations, and future directions. Results: Flavonoids upregulate eNOS via PI3K/Akt (20-50% NO increase, 15-25% flow enhancement), scavenge Reactive Oxygen Species (ROS), inhibit arginase, and promote glymphatic clearance; They bind Aβ1-42 (Kd 1-5 μM), reduce fibril formation (40-82% ThT inhibition), downregulate Beta site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1), and suppress neuroinflammation. Clinical data show cognitive gains (+2.4 Korean Mini-Mental State Examination (K-MMSE) points) and Aβ oligomer reduction in adjunct therapy, with safe dosing (120-240 mg/day EGb761). Major Findings: Ginkgo flavonoids offer multifaceted AD benefits through NO-mediated perfusion and anti-amyloid actions, ideal for functional foods and supplements.

Background: Pyrostegia venusta, an evergreen climber belonging to Bignoniaceae, native to South America, naturalised in tropical parts, including India, has been found to possess good ethnomedicinal properties. Traditionally used in treating respiratory infections, wounds, skin problems, inflammation, and as a tonic, the plant’s above-ground parts, such as flowers, leaves, stems, and roots, are used in infusion or decoction forms. Aim: The present review is an interdisciplinary approach that consolidates evidence from ethnobotanical, phytochemical, and pharmacological standpoints, explaining the anti-inflammatory mechanism, therapeutic potential, and prospects of P. venusta with respect to natural product-based drug development targeting inflammation-related disorders. Methods: A total literature survey integrated traditional uses from ethnopharmacological records with modern studies employing in vivo models (e.g., carrageenan-induced paw oedema, leukocyte migration inhibition), in vitro assays (e.g., DPPH radical scavenging, enzyme inhibition), phytochemical analyses [GC-MS, HPLC for flavonoids/sterols], and histological evaluations for wound healing. Data from Brazilian folk medicine, animal toxicity tests, and molecular pathway analysis, such as COX-2, NOS, and cytokines, were synthesised in the absence of primary experimentation. Results: The hydroethanolic/methanolic extracts were very effective against inflammation through COX-2/NOS inhibition, reduction of TNF-α/IL-6, and antioxidant activity, superior to controls in oedema models. The acceleration of wound healing with enhanced collagen-hydroxyproline content, tensile strength, and modulated cytokines, antinociceptive activity comparable to standards in pain models, along with ancillary antimicrobial action against S. aureus/E. coli, hepatoprotection, immunomodulation, and low acute toxicity-LD50 (>2000 mg/kg)-all support their use. Phytoconstituents such as oleanolic acid and flavonoids correlated well with multi-target modulation of the oxidative/inflammatory cascades. Conclusion: Pyrostegia venusta promises to be one of the most workable phytotherapies for inflammation, lesions, and pain, which the traditional and scientific data support with a very low level of toxicity. Future research should emphasise clinical trials, enhancement of bioavailability, and molecular docking for drug leads, thus advocating for sustainable integration into evidence-based medicine. Major Findings: Pyrostegia venusta extracts demonstrate potent anti-inflammatory effects by inhibiting COX-2, NOS, TNF-α, and IL-6, while reducing oxidative stress via flavonoids like quercetin and oleanolic acid.

Objective: This study aimed to develop and optimize a folic acid conjugated liposomal formulation of docetaxel (FA-Opt-DTXL) for enhanced delivery and cytotoxic efficacy against folate receptor–overexpressing A549 lung adenocarcinoma cells. Methods: A Box–Behnken design (BBD) coupled with response surface methodology was employed to optimize critical formulation parametersoya lecithin quantity, cholesterol content, and sonication timeaffecting liposomal characteristics. The optimized docetaxel-loaded liposomes (Opt-DTXL) were characterized for particle size, entrapment efficiency, and zeta potential. FA–PEG–Cholesterol conjugate was synthesized via NHS-activated ester coupling and incorporated into preformed liposomes using the post-insertion method to yield FA-Opt-DTXL. Morphological analysis was performed using TEM, and cytotoxicity was assessed via IC₅₀ determination and fluorescence-basedapoptosisassays. Results: The optimized Opt-DTXL formulation exhibited a particle size of 239.60 nm, entrapment efficiency of 84.03%, and zeta potential of –22.85 mV, closely matching predicted values. TEM imaging confirmed spherical, well-defined vesicles. Compared to Pure-DXT and Opt-DTXL, FA-Opt-DTXL demonstrated superior cytotoxicity, with an IC₅₀ of 16.67 µg/mL. Apoptotic assays revealed dominant red fluorescence and chromatin fragmentation in FA-Opt-DTXL–treated cells, indicating enhanced receptor-mediated uptake and intracellular drug accumulation.The integration of statistical optimization and Network pharmacology and folate-targeted surface modification yielded a potent nanocarrier system with improved cytotoxicity against A549 lung adenocarcinoma cells. Conclusion: FA-Opt-DTXL represents a promising platform for site-specific docetaxel delivery in folate receptor–positive malignancies, offering translational potential for targeted cancer therapy, also supported by network pharmacology and molecular docking studies.

Cancer presents a formidable challenge in oncology due to its aggressive nature and propensity for metastasis. This chapter delves into advanced drug delivery strategies and theranostic innovations tailored specifically for cancer. Theranostics, integrating diagnostic and therapeutic functionalities, are explored for their potential in personalized cancer treatment modalities as they are crucial for accurate diagnosis, disease staging, and treatment response assessment. Regulatory guidelines and clinical trials governing the development and approval of novel cancer therapeutics are comprehensively enveloped. Also, the chapter forecasts a future where personalized therapies and tailored drug delivery systems. Ultimately, the chapter emphasizes the transformative impact of advanced drug delivery and theranostics in cancer therapy, heralding a future marked by enhanced efficacy, safety, and precision in treatment interventions..