One of the major challenges in the treatment of inflammatory bowel disease (IBD) is the development of an oral drug delivery system that can provide extended GI residence time. In this work, a nanoformulation formed by Rebamipide (Re) encapsulated into mucin DEAE-dextran armored nanoparticles (M@D@Re-SCNPs) is introduced, which utilizes the core of caprylic acid (C)/6-O-stearoyl ascorbic acid (S). These M@D@Re-SCNPs were fabricated to provide both gastro-resistant and mucoadhesion properties of the nanoparticles. The M@D@Re-SCNPs showed pH-independent structural integrity in the gastric environment and proved to have a good mucosal binding capacity in the colon for long intestinal retention of up to 48 h. In terms of therapeutic efficacy, post-oral administration of M@D@Re-SCNPs strongly reduce the colon inflammatory status and the expression of inflammatory biomarkers like nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and phosphoinositide 3-kinase (PI3K) when compared with free rebamipide. The trapped rebamipide inhibits the production of pro-inflammatory mediators and promotes the production of mucin 2 (Muc2) protein, which promotes colon mucosal regeneration and goblet cell viability. Based on the necessity of controlling drug release and regulation of drug action for complete IBD treatment, we believe that the M@D@Re-SCNPs are a promising drug delivery system for UC treatment.

Autoimmune diseases (AIDs) affect millions of individuals worldwide, impacting ≈10% of the population, with women being more susceptible to them than men. AIDs include multiple sclerosis (MS), type 1 diabetes (T1D), and rheumatoid arthritis (RA), which arise when the immune system unintentionally targets healthy cells. A complex interaction among immunological, environmental, and genetic factors causes AIDs by impairing the capacity of the immune system to discriminate between self‐ and non‐self‐antigens. This impairment makes the immune system of the body attack its own tissues, causing inflammation and damage. Gut microbiota, also referred to as the “forgotten organ,” is crucial for immune system control, with dysbiosis causing or worsening AIDs. Nanotechnology provides innovative approaches to targeted medicine delivery, reduction of adverse effects, and improved treatment efficacy, providing novel avenues for treating AIDs at nanoscale. Liposomes, hydrogels, and polymeric nanoparticles are used as drug carriers to directly deliver drugs to the impacted tissues. This technology increases treatment precision, while lowering systemic toxicity, guaranteeing localized and regulated drug release—an advantage valuable for long‐term management of AIDs. In this comprehensive review, the pathophysiological connection among AIDs, role of gut microbiota, and combined nanotechnology‐based management of these diseases are addressed.

Ulcerative colitis (UC) is a major subcategory of inflammatory bowel disease, driven by complex mechanisms such as leukocyte infiltration, oxidative stress, and microbial dysbiosis. Oral administration is the most preferred route of drug administration but faces major limitations such as inefficient targeting, instability in the harsh gastric conditions, lack of mucoadhesiveness, and low colon residence time due to frequent diarrhea and rapid peristalsis. NLRP3 inflammasome is critical to the pathogenesis of UC, which augments inflammation by releasing of IL-1 beta and IL-18. Glibenclamide (Glib), a hydrophobic sulfonylurea and BCS class-II drug, is a potent NLRP3 inhibitor with poor solubility and bioavailability, which limit its therapeutic efficacy. Thus, it remains underexplored for the therapeutic alleviation of UC. To address this limitation, we engineered lipid-based gastroresistant zein-eicosapentaenoic acid smart nanocarriers (ZESNs) to develop a gastroresistant esterase-responsive nanocarrier system, with triglycerol monostearate (TGMS, an amphiphilic stabilizer), eicosapentaenoic acid (EPA, an omega-3 fatty acid), and a mucoadhesive coating of zein to bypass the harsh gastrointestinal environment. ZESNs exhibited high encapsulation efficiency and stability along with excellent cytocompatibility and anti-inflammatory potential in RAW 264.7 cells. Oral administration of Glib-loaded ZESNs (G@ZESNs) markedly restored the gut barrier integrity, improved goblet cell expression, and diminished mucosal ulceration in mice with colitis, moreover G@ZESNs also demonstrating colonic residence up to 48 h. In conclusion, the above findings validate G@ZESNs as a promising therapeutic nanoplatform, offering the dual advantage of improved drug solubility and inflammation-responsive immune system modulation. This study underlines the translational capabilities of biomaterial-based smart nanocarrier systems as next-generation therapeutic strategies for UC.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage breakdown, synovial inflammation, and subchondral bone changes. Chondrocyte apoptosis is a key contributor to cartilage degradation in OA. Poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme involved in DNA repair and apoptosis regulation, is associated with various degenerative diseases. However, its role in OA pathogenesis remains unclear. Therefore, we aimed to investigate the role of PARP-1 in OA pathogenesis using PARP-1 knockout (KO) mice and primary chondrocytes. METHODS: OA was induced in wild-type (WT) and PARP-1 KO mice via destabilization of the medial meniscus (DMM). Histological analysis was performed to assess cartilage degeneration, while chondrocyte apoptosis in joint tissues was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In vitro experiments were conducted using primary chondrocytes isolated from WT and PARP-1 KO mice, and PARP-1 activity was pharmacologically inhibited using 3-aminobenzamide (3-AB). Apoptosis was assessed by TUNEL staining and immunoblot analysis of cleaved PARP-1, poly(ADP-ribose), and caspase-3. The expression of anabolic and catabolic markers was also evaluated under inflammatory conditions. RESULTS: PARP-1 KO mice exhibited significantly greater cartilage degeneration and chondrocyte apoptosis than did WT controls following DMM surgery. In vitro, PARP-1 deficiency or pharmacological inhibition significantly increased apoptosis and disrupted the balance between anabolic and catabolic factors under inflammatory conditions, thereby exacerbating cartilage degradation. CONCLUSIONS: This study demonstrates that PARP-1 plays a protective role in preserving cartilage integrity under OA conditions. Its deficiency leads to increased apoptosis and cartilage degeneration both in vivo and in vitro. These findings highlight the regulatory role of PARP-1 in OA pathogenesis and underscore the need for further investigation into its underlying mechanisms.

Plant-based diets have been garnering increasing attention for their ability to reshape gut microbiota, reduce systemic inflammation, and alleviate joint pain in rheumatoid arthritis (RA). However, dietary responses are not uniform, as substantial inter-individual variability arises from genetic polymorphisms, metabolic diversity, and immune heterogeneity. In some patients, specific foods may exacerbate disease activity, emphasizing the need to identify personal dietary triggers and implement individualized nutritional strategies. Nutrigenomics, which integrates nutrition with genetic profiling, provides a valuable framework for understanding the influence of genetic variants on nutrient absorption, metabolism, inflammatory signaling, and immune regulation. Notably, dietary bioactive compounds can also modulate RA pathogenesis through epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA-mediated regulation, thereby altering gene expression programs associated with autoimmunity and chronic inflammation. Diet-derived metabolites and microbial products further interact with host genomic and epigenomic networks, creating a dynamic nutrient–gene–microbiome axis that shapes RA susceptibility, disease severity, and therapeutic responsiveness. Recent advances in multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome profiling, have offered deeper insights into nutrient-driven molecular pathways and immune dysregulation in RA. These findings enable precision dietary interventions enriched with anti-inflammatory nutrients and functional bioactive to improve symptom control and long-term outcomes. Artificial intelligence (AI) offers an emerging strategy by integrating multi-omics, clinical, and dietary data to generate actionable personalized nutrition approaches. This review highlights current evidence on nutrigenomic and epigenetic regulation in RA and discusses AI-driven precision nutrition as a future strategy to enhance disease management and patient wellbeing. Nutrigenomics uses genetic differences to tailor specific dietary interventions for individuals. Plant-based foods lower RA inflammation by boosting antioxidants, improving gut health, and cutting saturated fats. Bioactive compounds in food directly modulate immune responses and inflammatory pathways in RA. Nutrition alters gene expression through epigenetic mechanisms, directly influencing how the disease progresses. Combining multi-omics data with AI enables precise nutrition strategies to improve RA management.

Osteoarthritis (OA) is a common age-associated joint disorder driven not only by mechanical wear but also by progressive intracellular stress, metabolic imbalance, and chronic inflammation that culminate in cartilage degeneration and functional disability. Increasing evidence identifies mitochondrial dysfunction and endoplasmic reticulum stress (ERS) as central pathological hubs regulating chondrocyte survival, extracellular matrix (ECM) integrity, and inflammatory signaling. Mitochondrial impairment promotes excessive reactive oxygen species (ROS) generation, defective ATP production, disturbed mitochondrial dynamics, and inadequate mitophagy, collectively accelerating ECM catabolism and chondrocyte apoptosis. In parallel, ERS activates the unfolded protein response (UPR) to restore proteostasis through the PERK, IRE1α, and ATF6 pathways; however, sustained UPR activation shifts from adaptive signaling to maladaptive outcomes, amplifying inflammation, oxidative injury, and cell death in OA cartilage. Notably, emerging data highlight bidirectional crosstalk between mitochondria and ER, particularly via mitochondria-associated membranes (MAMs), as a key driver of Ca²⁺ dysregulation, inflammasome activation, and degenerative joint remodeling. Therapeutic strategies targeting these stress pathways including mitochondrial antioxidants, NAD⁺-boosting agents, mitophagy modulators, chemical chaperones, and selective UPR regulators have demonstrated potential to attenuate cartilage destruction and restore joint homeostasis. This review synthesizes current mechanistic insights into mitochondrial ERS signaling in OA and critically evaluates evolving disease-modifying interventions aimed at intracellular stress reprogramming. Finally, we discuss translational challenges and future directions for developing precision therapies that exploit organelle stress pathways to improve long-term joint health.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by persistent synovial inflammation, cartilage erosion, and systemic manifestations, including cognitive and neuropsychiatric complications. Increasing evidence highlights the bidirectional interplay of the joint-brain axis between peripheral inflammation and central nervous system dysfunction as a critical contributor to RA pathogenesis. Current frontline treatments, such as methotrexate (M), face challenges, including poor bioavailability, off-target toxicity, and limited efficacy in addressing neuroinflammation. To address these limitations, we developed methotrexate-loaded tryptophan-Poly(lactic-co-glycolic acid)-glutathione nanomicelles (M-WPG NMs), an advanced enzyme- and pH-responsive drug delivery platform designed for targeted release at inflamed joints. In collagen-induced arthritis (CIA) models, M-WPG NMs demonstrated superior therapeutic efficacy by significantly reducing joint inflammation, downregulating pro-inflammatory cytokines, and preserving joint architecture. Additionally, M-WPG NMs attenuated microglial activation and mitigated associated neuroinflammation in chronic RA, offering dual modulation of both peripheral and central inflammatory responses. This multifunctional nanocarrier improves methotrexate delivery, enhances therapeutic outcomes, and addresses the often-overlooked neurological components of RA. Our findings support the application of M-WPG NMs as a next-generation nanomedicine for comprehensive RA management, capable of controlling disease progression while offering protection against RA-induced cognitive dysfunction.

Weaning stress often impairs growth, metabolic function, gut barrier integrity, and microbial balance in piglets, underscoring the need for effective nutritional interventions to enhance post-weaning health. This study evaluated the effects of dietary curcumin-loaded mesoporous silica nanoparticles (SL@Cur) on growth performance, serum biochemical profiles, antioxidant capacity, gut epithelial integrity, gut microbial diversity, and fecal noxious gas emissions in weaned piglets. Thirty-six piglets (Duroc × [Yorkshire × Landrace]; 28 ± 1 days of age; 6-7 kg) were randomly assigned to diets containing 0, 30, or 60 mg/kg SL@Cur for 21 days. Piglets fed 30 or 60 mg/kg SL@Cur exhibited significantly higher final body weight, weight gain and average daily gain compared with control diet (p < 0.05). Myogenic gene expressions such as Pax7, Myf5 and Myf6 were significantly enhanced in piglets fed at 60 mg/kg SL@Cur compared to the control diet (p < 0.05). Serum triglycerides and total cholesterol levels were significantly reduced at 30 mg/kg (p < 0.05). The 30 mg/kg dose of SL@Cur also significantly decreased alanine aminotransferase and increased high-density lipoprotein concentrations than the control diet (p < 0.05). Serum glucose declined dose-dependently, whereas superoxide dismutase and cortisol remained unaffected. Gut barrier integrity was enhanced, as evidenced by significantly increased expression of tight junction proteins, zonula occludens-1 (ZO-1) and claudin-2 concentrations in SL@Cur supplied diets (p < 0.05). Analyzing the piglets' intestinal microbiomes showed that different dietary treatments lead to variations in their bacterial communities. As a result, the lower dose increased the presence of probiotics and lactic acid bacteria, while the higher dose showed more bacterial taxa and a mixed microbial shift. Additionally, SL@Cur markedly reduced fecal NH₃ and H2S gas emissions (p < 0.05). Overall, SL@Cur supplementation enhanced growth performance, improved metabolic and intestinal health parameters, and reduced enteric gas emissions in weaned piglets.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is both a significant risk factor for and a potential consequence of type 2 diabetes mellitus (T2D). The relationship between sarcopenia and T2D is complex and bidirectional, involving interconnected metabolic and molecular mechanisms that impair neuromuscular performance and muscle integrity during aging. The key pathways linking these conditions include insulin resistance, chronic low-grade inflammation, oxidative stress, and accumulation of advanced glycation end products. This review aims to critically examine the interplay between sarcopenia and T2D, with a focus on underlying pathophysiological mechanisms, nutritional determinants, and clinical implications. Dysregulated glucose metabolism, alterations in myostatin signaling, and activation of the ubiquitin-proteasome system are major contributors to muscle atrophy in this context. Furthermore, we highlight the role of targeted interventions, including resistance exercise, nutritional optimization, and emerging pharmacological strategies, in mitigating muscle loss and improving metabolic outcomes. A comprehensive understanding of these interconnected pathways is essential for developing integrated therapeutic approaches to improve the clinical outcomes and quality of life of affected individuals.

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon part of the large intestine.

Introduction Pelvic organ prolapse (POP) is a very common concern for women that can often necessitate surgical intervention, including sacral colpopexy. There are multiple surgical approaches, including vaginal, extraperitoneal, and intraperitoneal. This study aims to identify predictors of the outcomes with the different surgical approaches. Methods This retrospective study utilized data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) gynecologic-specific database for those who underwent sacral colpopexy for POP. The group was subdivided into surgical approaches that included abdominal, vaginal extraperitoneal, and vaginal intraperitoneal. ANOVA analysis was performed between the three groups, and a multivariate logistic regression was performed to determine the 30-day complication rate. Results Among the 1,275 cases analyzed, 326 (25.6%) utilized an abdominal approach, 425 (33.3%) utilized a vaginal approach, and 524 (41.1%) utilized an extraperitoneal approach. The mean age was significantly higher for patients undergoing a vaginal extraperitoneal (64.5 years) compared to abdominal (62.1 years) and vaginal intraperitoneal (61.6 years). There was no difference in the 30-day complication rate between the surgical approaches on adjusted analysis; however, the vaginal extraperitoneal approach had the longest hospital stay, days from operation to discharge, and total operation time. Conclusion A variety of surgical approaches for sacral colpopexy can be employed. In our study, we show that the 30-day complication rate was similar between the three approaches; however, the complications were only significant with the abdominal approach showing an increased occurrence of bleeding transfusions when compared to the extraperitoneal approach.

CRISPR/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing and modulation of gene function with an unparalleled precision and effectiveness. Among the various applications and prospects of this technology, the opportunities it offers in unraveling the molecular underpinnings of a myriad of central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, and developmental abnormalities, are unprecedented. In this review, we highlight the applications of CRISPR/Cas9-based therapeutics as a promising strategy for management of Alzheimer’s disease and transformative impact of this technology on AD research. Further, we emphasize the role of CRISPR/Cas9 in generating accurate AD models for identification of novel therapeutic targets, besides the role of CRISPR-based therapies aimed at correcting AD-associated mutations and modulating the neurodegenerative processes. Furthermore, various delivery systems are reviewed and potential of the non-viral nanotechnology-based carriers for overcoming the critical limitations of effective delivery systems for CRISPR/Cas9 is discussed. Overall, this review highlights the promise and prospects of CRISPR/Cas9 technology for unraveling the intricate molecular processes underlying the development of AD, discusses its limitations, ethical concerns and several challenges including efficient delivery across the BBB, ensuring specificity, avoiding off-target effects. This article can be helpful in better understanding the applications of CRISPR/Cas9 based therapeutic approaches and the way forward utilizing enormous potential of this technology in targeted, gene-specific treatments that could change the trajectory of this debilitating and incurable illness.

Sargassum horneri is an edible brown seaweed used as traditional medicine in various East Asian countries, such as China and Korea. Its therapeutic effects, including antioxidant and anti-inflammatory activities, have been reported in animal models of respiratory diseases and allergic disorders. However, its specific effects on liver health remain ambiguous. Therefore, in this study, we aimed to examine the effects of S. horneri extract (SHE) on acetaminophen (APAP)-induced hepatotoxicity, a common clinical cause of drug-induced liver injury. SHE-pretreated male mice were injected with a high dose of APAP. SHE alleviated APAP-induced liver injury and inhibited lipid peroxidation and glutathione (GSH) depletion. It also enhanced the hepatic total antioxidant capacity in APAP-treated mice, exhibiting direct radical scavenging activity against APAP-induced oxidative stress. Levels of the hepatic antioxidant enzymes, superoxide dismutase-1/2 and GSH peroxidase 1, were unaffected by SHE; however, catalase levels decreased by APAP were restored by the extract. Protein levels of the APAP-metabolizing enzymes, uridine 5'-diphospho-glucuronosyltransferase 1a6, sulfotransferase 1a1, GSH S-transferase a1, cytochrome P450 (Cyp)-1a2, Cyp2e1, and Cyp3a, were unaffected; however, Cyp1a activity was reduced by SHE. Plasma concentrations of APAP-GSH and APAP-cysteine conjugates were reduced by SHE in APAP-treated mice, indicating that SHE alleviates APAP hepatotoxicity by inhibiting Cyp1a-mediated metabolic activation of APAP. In conclusion, our results suggest that the increase in cellular antioxidant capacity and inhibition of APAP bioactivation are possible mechanisms underlying the hepatoprotective effects of SHE against high-dose APAP-induced acute liver injury.