Neem gum, a biocompatible and biodegradable polysaccharide, has broad applications in drug delivery and tissue engineering. Its hydrophilic and bioadhesive properties make it ideal for controlled drug release and scaffold fabrication. This review examines the role of neem and its derivatives in pharmaceutical formulations, wound healing, and regenerative medicine, while addressing stability, scalability, and regulatory considerations. Future directions include the integration of nanotechnology and chemical modifications for enhanced biomedical applications. Neem gum has been developed into various forms, including hydrogels, nanoparticles, films, and coatings, for targeted drug delivery and tissue regeneration. Its antimicrobial, antioxidant, and anti-inflammatory properties enhance wound healing and infection control, but challenges like batch variability and mechanical limitations remain. Neem gum is a promising natural biomaterial for pharmaceutical and biomedical applications. Further research on stability, large-scale processing, and clinical validation is essential for commercialisation and clinical use.

This review discusses recent advances in 4-hydroxycoumarin (4-HC) and its derivatives, emphasising its promise as a versatile pharmacological agent with diverse bioactivities.

Stress granules (SGs) are membraneless cytoplasmic condensates formed through liquidliquid phase separation (LLPS) in response to diverse cellular stressors. These dynamic macromolecular complexes serve as critical signaling hubs that orchestrate adaptive responses by sequestering translationally stalled mRNAs, RNA-binding proteins, and key signaling molecules. Substantial evidence implicates SGs in the pathogenesis of numerous disorders, where they dysregulate essential cellular pathways, including stress-induced cell death cascades. While regulated cell death constitutes a physiological process vital for tissue homeostasis, aberrant or excessive cell death represents a pathogenic driver in neurodegeneration, ischemic injuries, autoimmune disorders, infectious diseases, and oncological pathologies. Consequently, deciphering the molecular governance of cell death holds great potential for developing novel therapeutics. Although proteomic analyses reveal that SGs sequester multiple cell death regulators, the precise mechanisms through which these components modulate death pathways remain incompletely resolved. This review systematically examines the causal relationships between SGs dynamics and major cell death modalities, including apoptosis, necroptosis, pyroptosis, and ferroptosis. By synthesizing recent advances in SG biology and cell death regulation, we elucidate how stress-adapted SG proteomes functionally contribute to death pathway activation or suppression. This mechanistic synthesis not only resolves current controversies regarding SGs' function in different cell death models but also identifies targetable vulnerabilities at the SGs-death pathway interface, offering innovative frameworks for treating SGsassociated pathologies.

Parkinson's Disease (PD) is a neurological disease marked by the buildup of α-synuclein. The main symptom of the disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Gene therapy may be a treatment option for PD and has been used in clinical trials to treat a variety of illnesses in the human brain. Currently, the majority of gene therapy clinical studies are being conducted to treat PD. The primary objective is to enhance medications that address motor issues. Patients with PD have been the subjects of several gene therapy treatment techniques that have been developed and tested. Genes are typically transported to neurons in brain regions relevant to PD, such as the striatum, using viral vectors. It may only be necessary to administer these gene delivery methods once, and they may induce expression to persist for an extended time. Several neurotrophic factors, including neurturin, GDNF, BDNF, CDNF, and VEGF-A, have demonstrated promising outcomes in preclinical models as potential disease-modifying targets that may slow disease development. Currently available treatment regimens for PD mostly comprise the administration of levodopa (L-DOPA), dopamine agonists or MAO-B inhibitors, or surgery in the form of deep brain stimulation or neuroablative surgery, among other options. Many different targeting moieties for PD treatment, as well as current treatment techniques and gene therapy methodologies, are covered in this review article. The research reviewed the relevant literature on the potential role of gene therapy for the treatment of PD. The research articles are obtained through various databases, including ScienceDirect, Scopus, PubMed, and Google Scholar. This review includes various targeting moieties for the treatment of PD, current PD treatment strategies, PD treatment using gene therapy, comparison of risk-benefit ratios of gene therapy vs. DBS/drugs, and gene vector technology in the treatment of PD. This review compiles data on Parkinson's disease, its current treatment strategies, and the potential role of gene therapy in its treatment.

The increasing rise of multidrug-resistant bacteria necessitates an urgent need for the discovery of novel antibacterial agents. Natural products have long been a source for identifying and isolating novel antibacterial agents. Anacardic acids (AAs), a phenolic lipid isolated from solventextracted cashew nutshell liquid (CNSL) of Anacardium occidentale (Family Anacardiaceae), have garnered potential attention for their potent antibacterial properties. Besides Anacardium occidentale, different analogues of AAs have also been isolated from various natural sources. These natural and structurally optimized derivatives exhibited potential antibacterial properties against other bacterial strains. Although AAs are associated with a high level of antimicrobial activity against P. acnes, S. mutans, S. pyogenes, H. pylori, and methicillin-resistant S. aureus, their poor physicochemical properties are a major concern for their clinical translation. Encapsulating AAs in nanoformulations could be beneficial, as it can improve their poor pharmacokinetic properties, prevent enzymatic degradation during transport in the body, and facilitate site-specific release, thereby enhancing their therapeutic potential. Among the different nanocarriers studied, zein nanoparticles loaded with anacardic acid showed strong antibiofilm activity against E. faecalis, S. aureus, and P. aeruginosa. In contrast, the DNase-chitosan-coated solid lipid nanoparticles (Ana-SLNs-CH-DNase) demonstrated superior activity in disrupting mature S. aureus biofilms. Additionally, we have discussed the structure-activity relationship and mechanism of action of AAs, where it was found that AAs disrupt cell membrane functioning, inhibit bacterial respiration, quorum sensing, and cellular respiration, among other effects. These findings suggest that AAs and their analogues exhibit promising antibacterial activity, while nanoformulations offer a promising strategy to optimize their therapeutic potential.

MicroRNAs (miRNAs) are integral to the regulation of gene expression pertinent to cardiovascular health, affecting various biological processes, such as cell adhesion, inflammation, and lipid metabolism. Certain miRNAs (miR-1, miR-133a, miR-133b, miR-208a, etc.) have been associated with a range of cardiovascular disorders, including atherosclerosis, arrhythmias, and myocardial infarction, indicating their potential utility as therapeutic targets and biomarkers. Nevertheless, the therapeutic application of miRNAs is constrained by their inherent instability and suboptimal cellular uptake, which can be attributed to their negative charge and vulnerability to degradation. To mitigate these challenges, a variety of delivery systems have been developed, encompassing both viral vectors (such as adeno-associated viruses, adenoviruses, and lentiviral vectors) and non-viral vectors (including liposomes and polymer nanoparticles). Besides, the integration of nanoparticles, extracellular vesicles, and a hydrogel system can enhance the stability, targeting, and efficiency of miRNA delivery. Furthermore, advanced systems, such as intelligent responsive delivery mechanisms and multifunctional joint delivery systems, are currently under investigation to improve therapeutic outcomes. Notably, studies exploring poly (β-amino esters) as a non-viral gene delivery vector have demonstrated potential in advancing gene therapy for cardiovascular diseases. This article reviews the role of miRNAs in cardiovascular disease pathogenesis and therapy, discusses recent progress in miRNA delivery strategies, and summarizes clinical challenges and highlights the critical need for continuous innovation in delivery systems to enhance treatment efficacy, ensure safety, and facilitate industrial scalability.

Polysaccharide-based iron oxide nanoparticles, particularly PSC-iron oxide nanoparticles, have emerged as promising agents for brain cancer diagnosis and therapy. Originally approved for anemia treatment, PSC-iron oxide nanoparticles leverage extended circulation time, biocompatibility, and MRI contrast capabilities to serve dual diagnostic and therapeutic roles. This review highlights its application in brain tumor management, focusing on enhanced MRI visualization of tumor vascularization and macrophage activity compared to gadolinium-based agents, which improve tumor delineation and treatment monitoring. Additionally, PSC-iron oxide nanoparticles exhibit immune- modulating properties that promote anti-tumor macrophage responses. Preclinical evidence supports the synergistic effects of this approach with existing therapies and its potential in hyperthermia applications. Challenges in clinical translation, including dosage optimization and safety, require further investigation. This review highlights the potential of PSC-iron oxide nanoparticles in current findings to advance precision medicine or nanomedicine approaches for brain tumors.

Assisted reproductive techniques still have limitations regarding embryonic development and the achievement of clinical pregnancy. Animal venoms represent a biological library with the potential to trigger relevant cellular mechanisms. This study aimed to evaluate, through a literature review and computational screening, the activity of natural venoms and their derivatives on germ cells.

Phenothiazine and its N-substituted derivatives are pivotal in heterocyclic chemistry, serving as potential building blocks in chemical and pharmaceutical sciences. Over the past decade, extensive research has focused on the medicinal potentials of these compounds, exploring their anticancer, analgesic, anti-tumor, anti-inflammatory, and antibacterial properties. Due to their distinctive chemical compositions, phenothiazine and its N-substituted derivatives have facilitated the development of novel substitutions that are less hazardous. This paper reviews recent advancements in the synthesis of phenothiazine and its N-substituted derivatives, with an emphasis on their potential biological roles, including combating cancer, viruses, fungi, bacteria, histamine, inflammation, multidrug resistance (MDR), seizures, and free radicals. Numerous investigations have identified various types of phenothiazine and its N-substituted derivatives that exhibit compelling biological characteristics. The review analyses synthetic challenges and advancements in the applications of these derivatives in pharmaceutical and synthetic chemistry reported in recent decades. It discusses the impact of different functional groups on phenothiazine at the N-substitution, specifically Cl, CF₃, OH, N(C₂H₅)₂, and (CH₂)₅CH₃. Furthermore, the relationship between the biological activities and the structural characteristics of the compounds is examined, identifying the chemical groups and structural alterations that enhance bioactivity, reduce toxicity, and improve handling.

Introduction: Isatin (1H-indole-2,3-dione) and indole are versatile scaffolds with diverse pharmacological activities, including antimicrobial, anticancer, antiviral, anticonvulsant, antiinflammatory, and analgesic effects. Isatin-indole hybrids have emerged as multifunctional agents with significant potential in drug discovery.

Methods: A literature survey (2010-2025) across major databases (PubMed, Google Scholar, ACS, etc.) included reports on synthesis, biological evaluation, and structure-activity relationship (SAR) analysis.

Results: Numerous synthetic approaches, including both conventional and green methods, have yielded a diverse range of isatin-indole derivatives. Many exhibited potent antimicrobial, anticancer, antioxidant, and antitubercular activities, with SAR studies highlighting the impact of substitution patterns on activity and selectivity.

Discussion: This review aims to provide a comprehensive overview of hybrid molecules in which the isatin core is covalently linked to an indole scaffold. It focuses on their synthesis, diverse biological activities and structure-activity relationship (SAR) studies from 2001 onwards.

Conclusion: This review provides a concise summary of the latest developments and future outlook for the therapeutic potential of isatin-indole hybrids in the development of potent bioactive drugs.

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As the main fermentation product of Aspergillus fumigatus (A. fumigatus), fumagillin is directly related to the gene of A. fumigatus and exhibits a variety of biological activities. However, its clinical application is limited by low yield and toxicity. It is of great significance to improve the yield and safety of fumagillin using A. fumigatus. Currently, research on fumagillin at home and abroad primarily focuses on a single direction and lacks a systematic review of its biosynthesis, structure-activity relationship, and strain modification technology, as well as a comprehensive theoretical framework. This study systematically reviews the biosynthesis mechanism, activity characteristics, and targeted strain modification technology of fumagillin, providing theoretical support for breakthroughs in production, toxicity regulation, and clinical transformation of fumagillin.

Anthelmintic resistance in livestock is an escalating global concern, as synthetic anthelmintics tend to lose their efficacy within 2-10 years of their routine usage. This rapid development of resistance results in significant economic losses and threatens the sustainability of livestock production systems. Gastrointestinal (GI) parasitism, a primary health challenge in ruminants, significantly impairs productivity, fertility, and overall animal welfare. Environmental factors such as high humidity, temperature fluctuations, and poor management practices further predispose animals to certain parasitic infections. In recent years, the search for alternative solutions has led to a growing interest in plant-derived anthelmintics. These botanical compounds, rich in bioactive phytochemicals, offer a promising and eco-friendly approach to controlling parasites by targeting their metabolism, reproduction, and structural integrity. Unlike synthetic drugs, herbal anthelmintics are often associated with fewer side effects, reduced toxicity, and a lower risk of developing possible resistance. Several medicinal plants, such as Azadirachta indica, Allium sativum, Artemisia absinthium, and Fumaria parviflora, have demonstrated potent anthelmintic properties in both in vitro and in vivo studies. Furthermore, synergistic effects among multiple phytochemicals can enhance efficacy and broaden the spectrum of activity against diverse helminths. This review highlights the efficacy, mechanisms of action, and practical applications of herbal remedies in controlling parasitic infections in ruminants. Emphasizing the integration of natural remedies into sustainable livestock health programs, this approach holds great potential to reduce reliance on synthetic drugs while improving animal health, productivity, and farm profitability.

The primary feature of Parkinson's disease (PD), a progressive neurodegenerative disease that results in both motor and non-motor dysfunctions, is the degeneration of dopaminergic neurons in the substantia nigra. In recent years, indole-based compounds have emerged as promising candidates for developing novel treatments for Parkinson's disease due to their diverse pharmacological properties. Among the significant pathogenic targets against which indole derivatives exhibit potent activity are monoamine oxidase (MAO), NMDA receptors, oxidative stress, and neuroinflammation. This review provides an in-depth analysis of synthetic indole derivatives as potential therapeutic agents for Parkinson's disease. We explore how these compounds may reduce the pathology associated with Parkinson's disease, identify molecular targets, and analyze the relationships between their structure and activity. We also discuss recent advances in computational and medicinal chemistry that aim to enhance indole structures. Potential challenges and upcoming prospects for the therapeutic application of indole-based therapies are also considered in the review. The ultimate objective of this study is to elucidate the potential applications of synthetic indole derivatives in the development of innovative therapies for Parkinson's disease.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally; however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence. Beta-2 adrenergic receptors (β2-ARs) play a significant role in both the aetiology and management of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and potential synergistic effects with other medications. They are well-tolerated and effective in improving the quality of life and reducing exacerbations, making them an essential component of COPD treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD. This article provides an extensive overview of natural β2 agonists. The current study emphasizes the rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4- benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5- (2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular docking studies.This paper also highlights numerous structure-activity relationship investigations and various novel β2 agonists currently in clinical trials and patents. The present review will significantly aid in fostering the research of COPD.

Inflammation is the body's defensive response to injury, infection, or external stimuli. While NSAIDs and corticosteroids are widely used to treat inflammatory diseases, their long-term application often leads to severe side effects, including gastrointestinal damage and cardiovascular toxicity, as well as drug resistance. This underscores the urgent need for developing safer and more effective anti-inflammatory agents. Natural products, particularly terpenoids, as the largest class of bioactive compounds, have garnered significant attention due to their potent anti-inflammatory properties and structural diversity. Through systematic structural modifications, researchers have developed numerous terpenoid derivatives with enhanced anti-inflammatory efficacy, providing valuable insights for drug discovery. This review comprehensively summarizes the antiinflammatory mechanisms and therapeutic potential of terpenoids and their derivatives over the past decade, offering new perspectives for anti-inflammatory drug development and identifying promising candidates for further investigation.

Imidazo[2,1-b][1,3,4]thiadiazoles, a class of fused bicyclic heterocycles, have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly their anticancer properties. Over recent decades, extensive research has been conducted to explore and enhance their therapeutic potential. This comprehensive review spans six decades of research on the imidazo[2,1-b][1,3,4]thiadiazole scaffold, focusing on structural variations at C-2, C-5, and C-6 position on this scaffold and their implications for anticancer activity. Modifications at these positions have been shown to significantly impact the compound's efficacy against various cancer cell lines. Continuous exploration and optimization of these substitutions hold promise for the development of novel anticancer therapeutics.

The extensive array of Natural Products (NPs), ranging from plants to microbes, is wellknown for their varied chemical characteristics and significant biological activity. Historically significant in drug discovery, natural products provide distinctive stereochemistry and complexity generated by diverse biosynthetic pathways. Structural alterations improve effectiveness and diminish adverse effects, driven by advancements in screening, chemistry, and bioinformatics. Natural products have been approved as drug candidates despite the laborious process involved in their isolation and elucidation, demonstrating their relevance. Cinnamaldehyde (CA), derived from Cinnamomum tree bark, exhibits antibacterial, anti-inflammatory, anticancer, antioxidant, neuroprotective, antifungal, and anti-diabetic properties by affecting cellular processes and signaling pathways like PI3K/AKT/mTOR, TGF-β/Smad, NF-κB, TLR4/MyD88/NF-κB, MAPKs, JAK/STAT, and Nrf2/HO-1. Small molecular entities, along with the presence of α,β-unsaturated carbonyl functionality, offer intriguing possibilities within the research framework of synthetic chemistry. Synthetic analogues of CA have been produced; nonetheless, their biological actions remain largely unexamined. The review highlights the pharmacological significance of cinnamoyl functionality, indicating its potential for creating multi-targeted drugs through unexamined structural changes. This review adopts a comprehensive study design, featuring an extensive search of databases like PubMed, Science Direct and Scopus using keywords such as "cinnamoyl compounds," "synthetic derivatives," "therapeutic flexibility," and "pharmacological pathways." Studies were selected based on their relevance to the pharmacological activities of cinnamoyl compounds' synthetic derivatives and their effects on multiple signaling pathways in therapeutic contexts, including experimental data. This article aims to provide theoretical support for the promising development of cinnamoyl compounds as potential candidates for new discoveries and therapeutic advancements.

Despite recent advances in both preclinical and cancer therapies, the growing problem of treatment resistance remains one of the most critical challenges in oncology. To overcome the drawbacks of current oncologic treatments, there is a pressing need for new approaches and potential therapeutic strategies. The interaction between the host microbiome and cancer has recently attracted significant research. Among the various routes of microbiome-cancer interaction, microbiome- derived exosomes also offer an intriguing avenue. Exosomes, which are small extracellular vesicles, originate from several distinct types of cells, including microbiome-associated cells. These vesicles participate in intra- and intercellular communication as well as alteration of the tumour microenvironment. Emphas In light of their possible functions as treatment response modifiers and mediators, this review seeks to explain an intricate link between cancer therapy resistance and exosomes produced from the microbiome. Preclinical studies reveal that microbiome-derived exosomes operate through horizontal transfer of resistance-conferring enzymes and TLR4/MYD88-dependent signalling, demonstrating 2-5 fold upregulation of resistance-associated miRNAs in drug-resistant models. Clinical evidence shows Akkermansia muciniphila improves anti-PD-1 immunotherapy outcomes. Fusobacterium nucleatum- derived vesicles promote oxaliplatin resistance through autophagy activation. We investigate how microbiota-derived exosomes might leverage resistance to conventional cancer treatments and their consequences for these treatments. However, limitations include inter-individual microbiome variability, challenging isolation protocols, and regulatory hurdles under FDA guidelines. We examine the possible applications of microbiome-derived exosomes as therapeutic and diagnostic tools, thereby reflecting the applicability of these findings in clinical practice. This offers an interesting path for new therapeutic approaches meant to solve treatment resistance and raise patient survival.

Psoriasis is a chronic inflammatory skin disorder affecting 2-3% of the global population. It is increasingly recognized for its systemic comorbidities, especially cardiovascular diseases (CVDs). Notably, severe psoriasis independently increases cardiovascular disease (CVD) risk. This elevation occurs beyond conventional risk factors, such as hypertension and diabetes. It suggests that shared inflammatory pathways underlie the association between severe psoriasis and atherosclerotic conditions, like coronary artery disease (CAD). Atherosclerosis, characterized by lipid-laden plaque formation in arterial walls, remains a leading contributor to CVD-related morbidity and mortality. Emerging evidence underscores the interplay of inflammatory cell heterogeneity and immune dysregulation in its pathogenesis, mirroring mechanisms observed in psoriasis. The overlapping systemic inflammation and immune dysfunction in both diseases suggest potential therapeutic synergies. CD4+ regulatory T cells (Tregs), pivotal immunosuppressive modulators, have shown promise in mitigating autoimmune responses, yet their therapeutic exploitation in psoriasis-atherosclerosis comorbidity remains underexplored. This review summarizes current insights into Tregs' roles in psoriasis and atherosclerosis, emphasizing their dual regulatory functions; in psoriasis, Treg dysfunction exacerbates interleukin-17 (IL-17)/23-driven keratinocyte hyperproliferation, while in atherosclerosis, impaired Treg activity permits pro-inflammatory cytokine cascades and foam cell formation. We, herein, highlight emerging approaches to enhance Treg stability and function, such as nanotechnology-based targeting antibodies and traditional Chinese medicine (TCM). By delineating Treg-centric mechanisms across both diseases, this review proposes a paradigm shift toward immunomodulatory therapies addressing psoriasis-atherosclerosis crosstalk, offering novel strategies to alleviate systemic inflammation and cardiovascular burden in psoriatic patients. Further research into Treg heterogeneity and microenvironmental cues may unlock precision therapies for this comorbid axis.

Lung cancer remains a significant contributor to cancer mortality for several reasons. First, lung cancer is a molecularly heterogeneous disease. When combined with the dramatic resistance to treatment mediated by a tumor microenvironment (TME) that is inherently immunosuppressive, this explains the continued high mortality associated with lung cancer. The new era of treating non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as well as achieving long-lasting treatment responses, is driven by immune checkpoint inhibitors (ICIs) targeting PD- 1, PD-L1, and CTLA-4. This treatment revolution may, in the future, be applied to isolated cases of relapse and recurrent disease, resulting in sustained therapeutic responses. In this review, we outline recent advances, including novel agent combinations and combination regimens tested in clinical trials that have become milestones, such as Nivolumab, Pembrolizumab, Durvalumab, and emerging bispecific combinations. Targeted therapeutic delivery is now possible through nanotechnology and biomaterials, such as polymer nanoparticles and smart hydrogels, which allow high local drug concentration at the tumor site while reducing systemic toxicity. Predictive biomarkers, including PD-L1 expression, tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and radiomic features, are increasingly used to select patients and assess treatment responses in real time. Despite these advances, resistance to immunotherapy and immunerelated adverse events (irAEs) remain major challenges, emphasizing the need for ongoing innovation in personalized management, toxicity mitigation, and treatment strategies. Industry leaders are now exploring artificial intelligence to optimize treatment selection and predict adverse events and outcomes early. Ultimately, improved survival rates and enhanced patient experiences may be achieved through the integration of novel biomarkers, precision technologies, and more effective immunotherapies for lung cancer patients. Significant research is still required to overcome resistance mechanisms, optimize combination therapies, and enable individualized care in this rapidly advancing field.