Urolithiasis is a common and recurrent urinary tract disorder in which stone size, composition, location, anatomy, and patient factors influence the choice and success of treatment. Although shock wave lithotripsy (SWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) provide effective treatment for many patients, residual fragments, difficult calyceal access, repeated procedures, tissue trauma, and procedure-specific risks remain relevant clinical challenges. These limitations have encouraged investigation of miniature, wirelessly controlled systems that could reach confined regions of the urinary tract and perform localized diagnostic or therapeutic tasks. This review examines magnetically actuated microrobots and related magnetic microdevices for kidney stone navigation, detection, fragmentation, dissolution, and fragment retrieval. Particular attention is given to rotational, oscillatory, and gradient-driven actuation; magnetic materials and biocompatible coatings; integration with ultrasound, magnetic resonance imaging, and other sensing approaches; and hybrid magnetic–acoustic or drug-delivery platforms. Rather than treating all microrobotic studies as equivalent, the review distinguishes direct urolithiasis evidence from evidence transferred from other biomedical applications. The available evidence remains predominantly preclinical. Demonstrations include urinary-tract phantoms, microfluidic models, ex vivo experiments, and selected animal studies, while human clinical trials of magnetically actuated microrobots for kidney stone diagnosis or treatment have not been established in the literature reviewed here. Accordingly, the principal value of these systems at present is technological feasibility rather than demonstrated clinical superiority. Key barriers include real-time localization, magnetic-force attenuation with depth, safe deployment and retrieval, obstruction or urothelial injury, material fate, manufacturing reproducibility, regulatory classification, and cost-effectiveness. Future clinical claims should therefore be considered prospective and conditional on rigorous validation.
Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and polymodal sensor of noxious heat, protons, capsaicin and endogenous lipids. The wide variety of functions of TRPV1 in pain transmission, inflammatory pathways and neurological disorders has triggered efforts to understand the molecular mechanisms underlying these functions, particularly pain and neuroinflammation. The molecular structure and its tetrameric structure, temperature and ligand dependent activation and post-translational modification are discussed. It also covers the Ca2⁺-dependent signalling pathways such as CaMKII/Nrf2, MAPK, NF-κB and PI3K/ERK, and the localization of TRPV1 in sensory neurons, microglia, astrocytes, T lymphocytes and brain tissues. Other notable mentions are the involvement of TRPV1 in acute inflammatory, neuropathic, and visceral pain as well as in neuroinflammatory and neurodegenerative diseases like multiple sclerosis, Alzheimer's disease and Parkinson's disease. Evidence that comes from the various studies suggests that TRPV1 may cause a number of different responses depending on the cell and disease context, whether pro-inflammatory or neuroprotective. Therapeutic strategies directed to TRPV1 such as desensitizing agents, allosteric and state-selective modulators, peptide-based and natural-product based ligands, and gene-directed strategies, are also taken into account. To conclude, the context-dependent activity of TRPV1 signalling holds promise for therapeutic applications, and highlights the importance for context-specific, local and precise targeting of TRPV1 in clinical practice.
Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia worldwide. Although the classical pathological hallmarks of AD include extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, increasing evidence indicates that neuroinflammation plays a central role in disease initiation and progression. Among the key mediators of neuroinflammatory responses, cytokines have emerged as critical regulators of immune communication within the central nervous system. Activated microglia and reactive astrocytes release a wide range of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and interferon-γ, which contribute to synaptic dysfunction, neuronal injury, and amplification of inflammatory signaling pathways. Conversely, anti-inflammatory cytokines such as interleukin-10, interleukin-4, and transforming growth factor-β participate in regulating immune homeostasis and may exert neuroprotective effects by suppressing excessive inflammatory responses. This review provides a comprehensive overview of cytokine-mediated neuroinflammation in Alzheimer's disease, focusing on the cellular sources of cytokine production within the brain, including microglia, astrocytes, neurons, and endothelial cells. Key intracellular signaling pathways involved in cytokine activity, such as nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and mitogen-activated protein kinase (MAPK) pathways, are also discussed in relation to their roles in inflammatory amplification and neurodegeneration. Furthermore, the complex interactions between cytokine signaling, amyloid-β accumulation, and tau pathology are examined to highlight the interconnected mechanisms underlying disease progression. Finally, emerging therapeutic strategies targeting cytokine-driven neuroinflammatory pathways are explored, emphasizing their potential in the development of novel anti-inflammatory and disease-modifying treatments for Alzheimer's disease.
Osteoarthritis is a prevalent and progressive musculoskeletal disorder characterized by a complex interplay of mechanical stress, low-grade inflammation, oxidative stress, extracellular matrix degradation, chondrocyte dysfunction, and subchondral bone remodeling. Current pharmacological and surgical approaches primarily provide symptomatic relief and have limited capacity to modify the underlying structural progression of the disease. Curcumin, a major bioactive polyphenol derived from Curcuma longa, has attracted considerable interest as a potential therapeutic candidate because of its ability to influence multiple interconnected pathways involved in osteoarthritis pathogenesis. Unlike many phytochemicals investigated primarily through single mechanistic targets, curcumin has been extensively studied for its coordinated effects on inflammatory signaling, oxidative stress, apoptosis, extracellular matrix turnover, and cellular homeostasis. This review critically examines the molecular mechanisms, preclinical evidence, clinical findings, pharmacokinetic limitations, and emerging delivery strategies associated with curcumin in osteoarthritis. Particular emphasis is placed on the relationship between curcumin's multitarget pharmacology and its translational limitations, including poor aqueous solubility, low systemic bioavailability, rapid metabolism, variability among formulations, and heterogeneity of clinical studies. Evidence from experimental models supports anti-inflammatory, antioxidant, chondroprotective, and tissue-preserving effects, whereas clinical studies mainly indicate potential benefits for pain and functional outcomes. However, current evidence remains insufficient to establish curcumin as a disease-modifying therapy. Recent advances in nanotechnology, lipid-based systems, targeted delivery, and curcumin analogues may improve exposure and therapeutic efficacy, although their clinical translation remains to be established. Overall, curcumin represents a biologically plausible multitarget candidate for osteoarthritis, but larger, well-designed, standardized clinical trials incorporating structural and molecular endpoints are required to determine its therapeutic and disease-modifying potential.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder driven by the convergence of amyloid-β (Aβ) accumulation, tau hyperphosphorylation, synaptic failure, and chronic neuroinflammation, for which effective disease-modifying therapies remain elusive. Increasing evidence identifies dysregulated retinoid signaling as a critical yet underexplored contributor to AD pathogenesis. Retinoic acid, acting through retinoic acid receptors (RARs) and retinoid X receptors (RXRs), is essential for maintaining neuronal homeostasis, synaptic plasticity, and neuroimmune equilibrium in the adult central nervous system. In AD, impairment of RAR/RXR signaling shifts amyloid precursor protein (APP) processing toward amyloidogenic pathways, sustains NF-κB-driven inflammatory cascades, and promotes microglial dysfunction, thereby accelerating the progression of neurodegenerative processes. This review integrates mechanistic, preclinical, and translational evidence supporting acitretin, a second-generation synthetic retinoid, as a multi-target therapeutic candidate for AD. Acitretin enhances ADAM10-mediated non-amyloidogenic APP cleavage, increases soluble APP-α production, and reduces Aβ generation in transgenic AD models, while concurrently modulating microglial activation to attenuate pro-inflammatory cytokine signaling, including IL-6 and TNF-α, and preserve synaptic integrity. Importantly, biomarker-based clinical studies demonstrate increased cerebrospinal fluid APP-α following acitretin administration, confirming central target engagement in humans. Although definitive clinical efficacy remains to be established, acitretin's pleiotropic mechanism, established pharmacological profile, and biomarker responsiveness position it as a promising repurposed candidate within biomarker-guided and combination-based therapeutic strategies for AD.
Alzheimer’s disease (AD) remains a major therapeutic challenge owing to its complex and multifactorial pathogenesis, as well as the limited clinical efficacy of conventional therapeutics caused by poor pharmacokinetic properties, rapid systemic clearance, and restricted transport across the blood–brain barrier (BBB). Curcumin, a naturally derived polyphenolic compound, has gained considerable attention as a potential therapeutic agent for AD due to its broad neuroprotective and disease-modifying properties. Curcumin has been reported to inhibit amyloid-β (Aβ) aggregation and fibril formation, destabilize preformed amyloid plaques, suppress tau protein aggregation, reduce oxidative stress–induced neuronal damage, preserve mitochondrial integrity, modulate metal ion–induced neurotoxicity, and protect neuronal cells against apoptosis. Despite these promising therapeutic effects, the clinical translation of curcumin remains significantly limited by poor aqueous solubility, low chemical stability, rapid metabolism, limited systemic bioavailability, and insufficient BBB permeability. This review critically summarizes recent advances in curcumin-based nanocarrier systems for brain-targeted delivery in AD, with particular emphasis on pharmaceutical formulation strategies, physicochemical characterization, encapsulation efficiency, controlled drug release, colloidal stability, and preclinical therapeutic performance. Particular attention is given to the ability of curcumin nanoformulations to modulate neuroinflammatory pathways, including microglial activation, pro-inflammatory cytokine production, oxidative stress, and NLRP3 inflammasome signaling, which are central contributors to AD progression. This review focuses on polymeric nanoparticles, liposomes, nanoemulsions, and biomimetic nanoplatforms engineered to enhance BBB transport and improve brain biodistribution. Collectively, nanocarrier-mediated curcumin delivery represents a promising pharmaceutical strategy to improve brain-specific bioavailability and enable effective multitarget therapeutic intervention in AD.
Multiple sclerosis is a neurodegenerative disorder marked by axonal damage and demyelination; however, existing immunomodulatory treatments are ineffective requiring development of new therapeutic approaches. Aegle marmelos, a traditional medicinal plant rich in bioactive phytochemicals. This study examined the neuroprotective effects of Aegle marmelos ethanolic fruit extract (AME) in a cuprizone (CPZ)-induced MS rat model. AME GC–MS analysis and molecular docking analysis were performed. Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2
Inflammation resulting from the unfolded protein response to glycosylation dysfunction may be the key driver in the progression of Alzheimer's disease. Stress increases the risk of Alzheimer's disease, in part, by depleting essential cofactors required by enzymes involved in N-glycosylation (the first and third, second, fourth, and fifth enzymes-essential cofactors required for dolichol diphosphate-sugar conjugate synthesis are, respectively: DHRSX-NAD/NADPH, SRD5A3-NADPH, DOLK-Zn2+, and DPAGT1-Mg2+). Lithium reduces the risk of Alzheimer's disease by: (1) increasing transcription of DPAGT1, the gene for the first committed enzyme of N-glycosylation, stimulating levels of β-catenin through glycogen synthase kinase 3-β (GSK-3β) inhibition; (2) increasing transcription of SRD5A3, DHRSX, and DOLK, the genes for the enzymes of dolichol phosphate synthesis, stimulating levels of transcription factors through GSK-3β inhibition; and (3) inositol monophosphatase (IMPase) inhibition-increased autophagy clearance of amyloid produced by N-glycosylation pathway dysfunction. Together, lithium, magnesium, and zinc constitute a regulatory axis for protein N-glycosylation, in which lithium levels determine the threshold for pathology during magnesium and zinc depletion under stress. Magnesium is also required by the oligosaccharyltransferase complex, which catalyzes the conversion of dolichol-pyrophosphate-GlcNAc2-Mana9-Glc3 and a protein asparaginyl residue to an N-glycosylated protein and dolichol-pyrophosphate. Stress-induced Mg2+ deficiency impairs the oligosaccharyltransferase complex by affecting MAGT1 (magnesium transporter 1) and the STT3A component, resulting in N-glycan defects and hypoglycosylation. Endoplasmic reticulum stress, resulting from the unfolded protein response, stimulates N-glycan branching (bisected N-glycans) and hyperglycosylation due to the effect on TUSC3 (a regulator of Mg2+ influx) and the STT3B component of the oligosaccharyltransferase complex.
Multiple sclerosis is a chronic inflammatory disease characterized by the demyelination of nerve cells. So, it is mandatory to find out such phytochemicals that may prove to be helpful in treating neurodegeneration. Yucca filamentosa possesses anti-inflammatory, antioxidant and healing properties for the damaged neurons. Yucca filamentosa extract (YFE) was prepared and GCMS fingerprinting and molecular docking was performed. Animals divided as Normal, Demyelination disease model, Standard care group, and three treatment groups as YFE 250 mg/kg, 500 mg/kg and 750 mg/kg. Cuprizone 0.2
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition characterized by immunological dysregulation, inflammation, and oxidative stress, affecting multiple organs. The need for safer therapeutic alternatives is highlighted by the substantial side effects and inconsistent effectiveness of current treatments. The current study employed integrated computational and experimental methods to examine the potential effects of β-sitosterol against pristane induced SLE. Network pharmacology, Molecular docking and MD simulations were conducted to discover possible molecular targets of β-sitosterol in SLE. Antioxidant and anti-inflammatory assays were assessed though in vitro experiments. SLE was induced in BALB/c mice by administration of pristane, followed by treatment with β-sitosterol (100, 200, and 400 mg/kg, p.o.) or prednisone (10 mg/kg). Progression of the disease was evaluated through proteinuria, behavioral assessment, paw edema, hematological parameters, cytokine quantification, radiographic and histopathological analysis. 68 common BS-SLE targets were identified by network pharmacology, where TNF-α, PPARG, and MAPK3 emerged as major hub proteins with stable interaction demonstrated by docking and molecular dynamics. β-sitosterol demonstrated considerable antioxidant and anti-inflammatory properties in vitro and showed a favorable acute safety profile at 300 mg/kg, while one mortality was observed at 2000 mg/kg. In in vivo experiments, β-sitosterol substantially diminished proteinuria, serum creatinine, BUN, TNF-α, IL-6, paw oedema, and joint inflammation, while improving anxiety-like behavior, motor coordination, and hematological parameters. Considerable protection against kidney, brain and joint tissue injury was demonstrated by histopathological investigations, especially at 400 mg/kg. These findings suggest that β-sitosterol may mitigate lupus-associated inflammation and multiorgan injury through the modulation of inflammatory and metabolic pathways predicted by network pharmacology. The integrated computational and experimental evidence supports further mechanistic investigation and translational studies rather than establishing β-sitosterol as a definitive therapeutic agent for SLE.
Caspase-1 is a key protease that regulates inflammation by mediating the maturation of pro-inflammatory cytokines IL-1β and IL-18 as well as inducing the pyroptotic cell death. Dysregulation in caspase-1 activity is implicated in various inflammatory, autoimmune and metabolic disorders. This review systematically analyzes natural, synthetic and computationally predicted caspase-1 inhibitors, emphasizing their structural, mechanistic and pharmacological characteristics. We provide data on cellular and enzymatic inhibition, including IC₅₀ values when they are available and list the compounds that have moved on to preclinical or clinical trials. Selective inhibition of caspase-1 remains challenging because the catalytic domain and substrate-binding pocket are highly conserved among caspase family, which makes it challenging to design specific inhibitors. Although, numerous candidates reported exhibit promising caspase-1 inhibitory activities, however, there is still a lack of research regarding caspase–1-specific inhibitors, and further studies are required to investigate novel and effective caspase-1 inhibitors, through in vivo, in vitro, and in silico approaches and their cytotoxicity, bioavailability and solubility.
Aspirin is widely used in obstetric practice, but its effects in pregnancy depend strongly on indication, dose, and timing. Contemporary practice guidelines support low-dose aspirin for selected pregnant women at increased risk of preeclampsia, while historical reports of adverse outcomes often involve higher analgesic doses, prolonged exposure, or older non-selective NSAID-era data. We conducted a narrative review of the literature on aspirin use in pregnancy and organized the evidence by study design and clinical theme, including mechanism of action, indications, efficacy, maternal safety, fetal safety, guideline recommendations, and ongoing research. Evidence from randomized trials, meta-analyses, and guideline statements supports low-dose aspirin for prevention of preeclampsia in appropriately selected high-risk pregnancies. NICE recommends 75–150 mg daily from 12 weeks until birth in women at high risk or with more than one moderate risk factor, while US practice summaries of ACOG guidance describe 81 mg daily beginning after the first trimester for comparable risk groups. In the ASPRE trial, a 150 mg regimen begun between 11 and 14 weeks in screened high-risk women reduced preterm preeclampsia before 37 weeks by 62
Alzheimer’s disease (AD) is a multifactorial and progressive neurodegenerative condition characterized by the interaction of various molecular, cellular and systemic mechanisms that culminate in synaptic dysfunction, neuronal loss and memory decline. Therapeutic success remains limited despite decades of research, and accumulating evidence suggests that an exclusive focus on single-pathology mechanisms may have contributed to the limited efficacy of many therapeutic strategies. The interplay of pathogenic mechanisms seems to contribute to the disorder in a dynamic and continuous manner, much like the growing evidence supporting a network-based model. This review engages with 30 major pathogenic pathways contributing to AD, including amyloid-β and tau pathology, neuroinflammation, oxidative stress and mitochondrial dysfunction, synaptic and neurotransmitter dysfunction, metabolic and vascular dysfunction, calcium signaling, proteostasis ,gut-brain axis and hormone-related pathways. The study also presents emerging mechanisms such as metal ion dishonesties, prion-like propagation and Wnt/β-catenin Signaling. Particular emphasis is placed on neuroinflammatory and immunometabolism pathways, which mediate the clearance of amyloid, propagation of tau, maintenance of synaptic integrity, and regulation of neurovascular function. In addition, the review examines therapeutic strategies targeting these pathways, including monoclonal antibodies, inflammasome inhibitors, metabolic modulators, and emerging gene- and RNA-based therapies. Multi-target and precision medicine approaches represent promising strategies for potential disease modification, although their clinical efficacy remains under investigation.Overall, this review makes a case for integrative, pathway-based therapeutic models, and multiple approaches may facilitate for drug development, biomarker identification and patient management in Alzheimer’s disease.
Alzheimer’s disease (AD), the leading cause of age-related cognitive decline and dementia, represents a growing neurological and socioeconomic burden, while currently approved therapies offer limited symptomatic benefit and minimal disease modification. Bacopa monnieri (L.) Wettst. (BM), a traditional Ayurvedic nootropic herb, has emerged as a promising phytotherapeutic candidate owing to its bioactive bacosides, which target multiple molecular pathways implicated in AD pathogenesis. This review, conducted following PRISMA 2020 principles, critically synthesizes evidence on the therapeutic relevance of BM in AD and cognitive decline. Literature from PubMed, Scopus, Web of Science and Cochrane Library was evaluated to examine phytochemistry, pharmacological mechanisms, preclinical and clinical evidence, cognitive outcomes, pharmacokinetics, safety, formulation strategies, comparative medicinal plant mechanisms and pharmacoeconomic positioning. Mechanistically, bacosides exert neuroprotective effects through cholinergic modulation, attenuation of amyloid-β accumulation, suppression of tau hyperphosphorylation via GSK-3β regulation, enhancement of brain-derived neurotrophic factor (BDNF)-mediated neuroplasticity and mitigation of oxidative stress and neuroinflammation through NF-κB signaling modulation. Preclinical findings consistently demonstrate improvements in cognition, synaptic plasticity and neuronal survival, whereas clinical studies using standardized extracts report favorable effects on memory, attention and processing speed with acceptable tolerability. Comparative analysis positions BM among promising neuroprotective medicinal plants for cognitive enhancement and supports its relevance to SDGs 3, 12 and 15. Nevertheless, variability in extract standardization, limited long-term clinical evidence and absent Alzheimer-specific pharmacoeconomic evaluations warrant biomarker-driven, large-scale randomized trials to clarify its therapeutic utility in AD.
Ulcerative colitis (UC) involves recurrent colonic mucosal inflammation and impaired epithelial repair. Current therapies are limited due to safety concerns. The TXNIP-NLRP3 inflammasome axis serves as a critical link between oxidative stress and inflammation in UC. The present study evaluated the protective role of dimethyl itaconate (DMI), a cell-permeable itaconate derivative, in a chronic dextran sulfate sodium (DSS)-induced ulcerative colitis model with verapamil as a positive control. Chronic colitis was induced in male BALB/c mice with repeated cycles of 3
This study was conducted to investigate the anti-arthritic effect of three different doses of aripiprazole based on its previously reported anti-inflammatory activity. Aripiprazole, an atypical antipsychotic, has been used in the present study in animal models. Histamine model was used to verify the documented property of aripiprazole to treat inflammation. In-silico evaluation included molecular docking that was done by Auto-Dock of Chemical Computing Group. In-vitro studies involved heat evoked BSA protein degradation and egg albumin degradation and maintenance of human RBCs membrane test, whereas in-vivo studies encompassed, formaldehyde evoked arthritis CFA evoked arthritis. Acute histamine model was carried out for four hours. Formaldehyde provoked arthritic disease in Sprague Dawley rats was studied to appraise anti-arthritic action of three respective doses of aripiprazole at 5 mg/kg, 10 mg/kg and 15 mg/kg oral dose for 10 days while the time period for study of same activity was twenty eight days with Complete Freund adjuvant and diameter of rat hind paw, arthritic index, body weight, radiological and histopathological investigation of ankles joints were performed. Variety of inflammation causing bio-markers (interleukin-1β, interleukin-6, nuclear factor-Kβ, tumor necrosis factor-α, Cox-2, interleukin-4, interleukin-10 and PGE2) had been investigated by real time-polymerase chain reaction and ELISA. Aripiprazole significantly suppressed paw edema in acute inflammatory model of histamine at dose of 15 mg/kg of aripiprazole showed significant (p < 0.0001) prevention of paw edema showing percentage inhibition of (56.10
Endometriosis is a chronic inflammatory and estrogen-dependent disease in which pain remains the leading cause of impaired quality of life. Hormonal therapies constitute the cornerstone of medical management and include progestins, combined estrogen–progestin contraceptives, gonadotropin-releasing hormone (GnRH) agonists and antagonists, selective estrogen and progesterone receptor modulators, and aromatase inhibitors. Although these treatments effectively suppress ovarian function and reduce estrogen-dependent lesion activity, their clinical benefits are frequently limited by adverse effects, contraceptive implications, and symptom recurrence after treatment discontinuation. Increasing evidence indicates that the persistence of endometriosis-associated pain cannot be explained solely by hormonal dysregulation. A sustained inflammatory microenvironment, characterized by innate immune cell activation, pro-inflammatory cytokine production, and neuroimmune interactions, contributes to peripheral and central sensitization, thereby limiting the effectiveness of therapies targeting endocrine pathways alone. These disease-driven mechanisms provide a biological explanation for the heterogeneous response to hormonal treatment observed in clinical practice. This review summarizes the mechanisms of action, clinical efficacy, safety profile and limitations of current hormonal therapies for endometriosis-associated pain. In addition, it discusses the inflammatory and neuroimmune mechanisms underlying persistent pain and highlights the rationale for combining endocrine therapies with emerging anti-inflammatory and immunomodulatory strategies. Such integrated approaches may improve long-term pain control, reduce recurrence, and contribute to more personalized management of endometriosis.
Helicobacter pylori is a bacterium that has been identified as a causative agent in the development of chronic gastritis, peptic ulcers, and gastric cancer. Current eradication therapies, based on antibiotic combination, are suffering from lack of patient compliance and primary antibiotic resistance. The traditional use and the scientific literature both report the gastroprotective role of natural extracts containing ellagitannins, suggesting an intriguing hypothesis about the potential impact on H. pylori-related gastritis. Anti-inflammatory and antibacterial effects of Castanea sativa Mill. extract standardized to contain castalagin have been previously demonstrated in human gastric epithelial cells. This experimental work aimed at investigating the role of a food grade chestnut leaf extract in complex models of H. pylori infection. The biological properties of chestnut leaf extract and castalagin have been validated, firstly in a novel murine gastric organoid cell model of H. pylori infection, and, secondly, in an in vivo infection model. Some NF-κB pathway genes, including ligands for CXCR2 and CXCR3 receptors, were found to be suppressed by both the extract and the pure compound. Furthermore, both strongly suppressed H. pylori colonisation and gastric inflammatory mediators in mice. The infiltration of immune cells, mainly neutrophils and monocytes, was also reduced. The results of this work demonstrate the significant potential for the translation of innovative food supplements as co-adjuvants in the prevention and/or treatment of H. pylori-induced gastritis.
Topical and transdermal drug delivery methods provide an enticing option to conventional oral administration of non-steroidal anti-inflammatory medications (NSAIDs) by diminishing gastrointestinal complications and bypassing hepatic first-pass metabolism. However, the therapeutic performance of topical NSAID formulations is commonly restricted by the barrier characteristics of the stratum corneum, causing poor drug diffusion and suboptimal concentrations at the desired region. Transethosomes, a cutting-edge generation of ultra-deformable lipid vesicles formed from phospholipids, ethanol, and edge activators, have shown as viable nanocarriers for mitigating these limits. The improved pliability, compact vesicle size, and remarkable skin-penetration capacity support the effective transfer of encapsulated medicines through the skin, culminating in better bioavailability and therapeutic benefits. This review thoroughly outlines the composition, physicochemical characteristics, mechanisms of skin permeation, methods of preparation, and characterization techniques of transethosomal vesicles. Special attention is directed towards their use in the transdermal delivery of NSAIDs, underscoring results from preclinical studies that reveal improved skin permeation, greater drug retention, prolonged drug release, and enhanced anti-inflammatory effectiveness. Current challenges, such as formulation stability, large-scale manufacturing, and clinical translation, are thoroughly examined. Transethosomal vesicles serve as a versatile and promising platform for improving transdermal delivery of NSAIDs, potentially playing a significant role in the advancement of safer and more effective therapeutic strategies for inflammatory disorders.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia and progressive multi-organ complications driven by oxidative stress, inflammation, and metabolic dysfunction. Accumulating experimental evidence identifies the thioredoxin-interacting protein (TXNIP)–NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome axis as a critical molecular link between hyperglycemia-induced oxidative stress and inflammatory cell death, although its therapeutic modulation in diabetes remains under active investigation. Activation of TXNIP promotes assembly of the NLRP3 inflammasome, leading to caspase-1 activation, maturation of interleukin (IL)-1β and IL-18, and subsequent pyroptosis. This pathway has been increasingly implicated in the pathogenesis of diabetic complications, including nephropathy, retinopathy, neuropathy, cardiomyopathy, and diabetic osteopathy. Therefore, therapeutic strategies targeting upstream regulators of inflammasome activation have gained considerable attention. Allopurinol, a xanthine oxidase (XO) inhibitor traditionally used for the management of gout and hyperuricemia, possesses well-established antioxidant and anti-inflammatory properties that extend beyond urate lowering. By inhibiting XO-mediated reactive oxygen species (ROS) generation, allopurinol attenuates oxidative stress, improves endothelial function, and modulates inflammatory signaling pathways associated with diabetic tissue injury. Emerging experimental evidence suggests that suppression of XO-derived oxidative stress may indirectly influence TXNIP–NLRP3 inflammasome activation and downstream pyroptotic pathways, although whether allopurinol directly modulates this pathway has not yet been conclusively established. This review critically examines the mechanistic relationship between XO-derived oxidative stress, TXNIP–NLRP3 inflammasome signaling, and pyroptosis in diabetes. We distinguish experimentally validated mechanisms from biologically plausible hypotheses and critically evaluate current evidence supporting the potential role of allopurinol as an upstream modulator of inflammasome activation, with particular emphasis on the emerging and underexplored field of diabetic osteopathy.
