Numerous mysteries of cell and molecular biology have been resolved through extensive research into intracellular processes, which has also resulted in the development of innovative technologies for the treatment of infectious and non-infectious diseases. Some of the deadliest diseases, accounting for a staggering number of deaths, have been caused by viruses. Conventional antiviral therapies have been unable to achieve a feat in combating viral infections. As a result, the healthcare system has come under tremendous pressure globally. Therefore, there is an urgent need to discover and develop newer therapeutic approaches against viruses. One such innovative approach that has recently garnered attention in the research world and can be exploited for developing antiviral therapeutic strategies is the PROteolysis TArgeting Chimeras (PROTAC) technology, in which heterobifunctional compounds are employed for the selective degradation of target proteins by the intracellular protein degradation machinery. This review covers the most recent advancements in PROTAC technology, its diversity and mode of action, and how it can be applied to open up new possibilities for creating cutting-edge antiviral treatments and vaccines.

Neuroprotectin D1 (NPD1) has emerged as an integral lipid mediator with significant implications for maintaining neurological health. Being derived from docosahexaenoic acid (DHA), NPD1 is a specialized pro-resolving lipid mediator (SPM), consisting of a unique structure that attributes potent anti-inflammatory and neuroprotective properties crucial for maintaining nervous system homeostasis. It exerts its actions through diverse mechanisms, including the inhibition of proinflammatory cytokines, modulation of apoptosis, and promotion of cellular survival pathways. The dysregulation or deficiency of NPD1 has been implicated in the onset and progression of several neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and stroke, underscoring its critical role in maintaining neuronal health and disease prevention. Abnormal NPD1 signalling is associated with neuroinflammation, oxidative stress, and neuronal apoptosis, which in turn contribute significantly to the progression of neurological disorders. Understanding these pathways offers insights into potential therapeutic strategies aimed at targeting NPD1 to mitigate neurodegenerative processes and facilitate neural repair. The efforts in developing NPD1 analogs or mimetics are focused on enhancing endogenous NPD1 levels, attenuating neuroinflammation, and preserving neuronal integrity in disease contexts. This review provides a comprehensive exploration of NPD1, encompassing its structural characteristics, biochemical pathways, physiological roles, pathophysiological implications, and potential therapeutic applications in neurological disorders. Further, research into elucidating the precise mechanisms of NPD1 reveals that its clinical efficacy is crucial for harnessing its full potential as a therapeutic tool for neuroprotection and neural repair.

Diabetes mellitus arises from complex interactions between biological susceptibility and diverse environmental influences that extend beyond traditional "genes versus lifestyle" models. The exposome is defined as the aggregate of non-genetic environmental exposures and their biological consequences across the life course. It provides a systems-level framework to evaluate this interaction, spanning chemical, physical, social, and behavioral domains while integrating them with internal molecular responses to decode how environments shape metabolic health. Emerging assessment strategies, including exposome-wide association studies (ExWAS), high-resolution mass spectrometry-based biomonitoring, geospatial and remote-sensing platforms, and wearable exposure sensors, enable characterization of multi-exposure profiles rather than single agents in isolation. Within exposome domains, air pollution, endocrine-disrupting chemicals, food-borne contaminants, exposome characteristics of the built environment, and chronic psychosocial stress have each been shown to contribute to the development and progression of both type 1 and type 2 diabetes. These diverse exposures often share common pathogenic mechanisms of chronic low-grade inflammation, oxidative and nitrosative stress, alterations in the gut microbiome, and epigenetic changes that ultimately lead to glucose dysregulation. Recent progress in metabolomics, lipidomics, and epigenomics is elucidating the "internal exposome," providing molecular fingerprints that encode prior exposure and detect early metabolic disruption. This integrated approach argues for a paradigm adjustment in diabetes prevention from behavior-centered strategies to those that also target upstream environmental determinants. Exposomic information can improve risk prediction, inform precision public health and medical practice, and inform policy regarding air pollution, chemical use, urban planning, and food systems. This review summarizes the current state of knowledge of the exposome in diabetes, describing its conceptual underpinnings, major tools of assessment, major epidemiologic findings, and biological mechanisms, and identifying the key challenges and opportunities for exposomics to inform effective approaches to diabetes prevention and planetary health.

The substantial interest in plant-based drugs or plant-derived phytocompounds drives researchers to conduct comprehensive investigations on their therapeutic properties. Mollugin, one of the major active constituents of Rubia cardifolia, has been well-studied for its pharmacological properties, demonstrating potent anti-inflammatory properties by suppressing the TAK-1-mediated activation of NF-κB/MAPK and enhancing the Nrf2/HO-1-mediated antioxidant response. It exhibits strong anticancer effects through ferroptosis via IGF2BP3/GPX4 pathways, induces mitochondrial apoptosis, and targets NF-κB, ERK, and PI3K/Akt/mTOR to suppress tumor progression. Mollugin also inhibits JAK2/STAT and PARP1 pathways, suppressing IL-1β expression via the modulation of ZFP91. Moreover, it regulates the MAPK/p38 pathway, promotes neuroprotection, and improves cognitive performance through GLP-1 receptor activation. Mollugin promotes osteogenesis by activating the BMP-2/Smad1/5/8 signaling pathway and downregulates MAPK, Akt, and GSK3β expression, leading to the inhibition of osteoclastogenesis. It overcomes multidrug resistance by downregulating MDR1/P-gp, CREB, NF-κB, and COX-2 through AMPK activation. Its antibacterial effect is mediated by strong binding to FUR, UDP, and IpxB proteins in Enterobacter xiangfangensis. Mollugin mitigates Klebsiella pneumoniae infection, suppresses adipogenesis without causing cytotoxicity, and protects endothelial cells via the BDNF/TrkB-Akt signaling pathway. Synthetic derivatives of mollugin, such as oxomollugin and azamollugin, have shown enhanced anticancer and anti-inflammatory effects by regulating EGFR, PKM2, TLR4/MyD88/IRAK/TRAF6, and NF-κB/IRF3 pathways with improved solubility and stability. Collectively, these findings emphasize the broad-spectrum activity of mollugin. This review provides a critical interpretation of the mechanistic pathways regulated by mollugin and its derivatives, emphasizing their pharmacological significance and exploring their potential for future translation as multitarget drug candidates.

Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent for treating various malignancies, autoimmune diseases (AIDs), and inflammatory disorders. Despite its therapeutic efficacy, long term or high‐dose MTX treatment is associated with a significant risk of hepatotoxicity, leading to MTX‐induced liver injury (MTX‐LI). The pathogenesis of MTX‐LI involves multiple mechanisms, including oxidative stress, mitochondrial dysfunction, inflammation, and altered metabolic processes, which collectively contribute to hepatocellular damage and fibrosis. Clinically, MTX‐LI manifests as elevated liver enzymes, hepatic steatosis, and, in severe cases, cirrhosis, posing a challenge to treatment regimens. To mitigate MTX‐LI, a growing body of research has focused on exploring therapeutic and/or preventive potential and pharmacological mechanisms of phytochemicals and pharmaceuticals. Phytochemicals, including flavonoids, terpenoids, alkaloids, and polyphenols, exhibit hepatoprotective effects attributed to their antioxidant, anti‐inflammatory, and antiapoptotic properties that can counteract MTX‐induced hepatic damage. Additionally, various pharmaceutical agents possessing antioxidants and anti‐inflammatory properties and favorably modulate metabolic pathways have shown promise in reducing the severity or progression of of MTX‐LI. The phytochemicals or pharmaceuticals showed beneficial in MTX‐LI primarily act by scavenging reactive oxygen species (ROS), modulating inflammatory pathways, and improving liver regeneration. Integrated together, its apparent that naturally occurring many phytochemicals as well as synthetic agents of pharmaceutical relevance are capable of preventing or alleviating MTX‐LI. However, the optimal strategies for integrating these agents into clinical practice require further investigations to highlight safety and efficacy in humans followed by pharmacological rationale of their possible use in therapeutics. Future directions should focus on elucidating the precise molecular mechanisms, establish safety and efficacy in humans, conducting regulatory toxicology studies and randomized clinical trials, and developing combination therapies for promotion as protective agents or adjuvants to maximize efficacy and minimize adverse effects.

Adelmidrol is a bioactive semi-synthetic compound with significant therapeutic potential, particularly in resolving inflammation since inflammation plays a key role in the pathogenesis of several diseases. The mechanisms of action of adelmidrol are multifaceted, involving interactions with specific receptors like the PPAR-γ and modulation of signaling pathways associated with inflammation. Adelmidrol demonstrates efficacy in conditions such as inflammatory bowel disease, colon inflammation, and urothelial inflammation by regulating the level of pro-inflammatory cytokines. In dermatological conditions like atopic and allergic dermatitis, adelmidrol plays a key role in modulating immune responses and enhancing skin barrier function by reducing inflammation while offering an alternative to conventional therapies. Additionally, adelmidrol plays a critical role in wound healing and diabetic foot ulcers by facilitating cell migration and proliferation, thus accelerating wound closure and reducing infection risk. Adelmidrol has been shown to reduce joint inflammation and improve functionality, making it a candidate for adjunct therapy in musculoskeletal disorders like osteoarthritis. The compound also addresses pulmonary conditions, such as pulmonary fibrosis, by mitigating inflammatory responses and improving respiratory function. Furthermore, applications of adelmidrol in liver diseases, including liver ischemia and non-alcoholic steatohepatitis (NASH), highlight its potential in resolving hepatic inflammation. This review emphasizes the therapeutic promise of adelmidrol across various inflammatory diseases, advocating for further clinical studies to establish its full potential and optimize its clinical use all the while providing an overview of the properties, mechanisms of action, and therapeutic applications of adelmidrol.