Recent Advances in Inflammation & Allergy Drug Discovery最新文献

{"title":"Synovial Microdialysis for Evaluating Methotrexate Disposition in Male Sprague-dawley Rats: A Translational Approach to Anti-rheumatoid Drug Discovery.","authors":"Saivishal Daripelli, Amol A Raje, Vishwottam Kandikere, Palur Ramakrishnan Anand Vijaya Kumar","doi":"10.2174/0127722708478721260921113250","DOIUrl":"https://doi.org/10.2174/0127722708478721260921113250","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of Rheumatoid Arthritis (RA) treatment depends on adequate drug exposure within the joint; however, intra-articular pharmacokinetics remain poorly understood. Synovial microdialysis enables continuous measurement of unbound drug concentrations in joints. This study aimed to evaluate the applicability of techniques like microdialysis and lavage collection as preclinical tools for measuring unbound intra-articular drug exposure by characterizing methotrexate (MTX) pharmacokinetics in rats.</p><p><strong>Methods: </strong>In this study, male Sprague-Dawley (SD) rats were used for evaluating the kinetics of MTX. A linear probe was implanted in the knee joint of anesthetized rats to perform synovial microdialysis. An intravenous dose of 1 and 3 mg/kg was administered for synovial microdialysis, while lavage was performed in a parallel group at 3 mg/kg for comparison. Plasma protein binding was determined using the equilibrium dialysis method. Pharmacokinetic parameters were derived using non-compartmental analysis, and inter-method agreement was evaluated.</p><p><strong>Results: </strong>MTX showed moderate plasma protein binding (~51% unbound) and dose-proportional systemic exposure at tested doses. Microdialysis data revealed rapid joint penetration (Tmax ≈ 0.25 h) and synovial half-life comparable to unbound plasma kinetics. At 3 mg/kg, microdialysis and lavage demonstrated close agreement (2.9% difference, ~2% CV), with microdialysis yielding slightly higher concentrations, likely due to its ability to measure unbound drug without dilution bias.</p><p><strong>Discussion: </strong>The strong concordance between microdialysis and lavage confirms both methods capture intra-articular MTX exposure. However, microdialysis offers superior physiological relevance by continuously quantifying unbound drug without dilutional artifacts. The alignment of synovial and plasma half-life supports rapid equilibration between systemic and joint compartments, reinforcing its utility for mechanistic and PK-PD studies.</p><p><strong>Conclusion: </strong>Synovial microdialysis provides a robust and physiologically relevant approach for quantifying active drug exposure in the joint and offers clear advantages over synovial lavage for preclinical evaluation of anti-rheumatic therapies.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Inflammatory and Immune-mediated Kidney Disorders (IMKD): From Pathogenesis to Precision Therapy.","authors":"Shashi Ranjan Singh, Arvind Kumar Patel, Dharmendra Kumar, Laliteshwar Pratap Singh, Neha Singh, Shankul Kumar, Pawan Kumar Goswami, Vinod Kumar Singh","doi":"10.2174/0127722708501881260913025236","DOIUrl":"https://doi.org/10.2174/0127722708501881260913025236","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory and immune-mediated kidney disorders (IMKD) comprise a diverse group of renal diseases and are a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Despite advancements in supportive care, longterm renal outcomes remain suboptimal due to disease heterogeneity and limitations of conventional immunosuppressive therapies.</p><p><strong>Methods: </strong>A narrative review of recent literature was conducted, focusing on immunological mechanisms, genetic and epigenetic regulation, biomarker innovations, and advancements in targeted biologic therapies. Particular emphasis was given to translational research integrating multi-omics technologies with clinical applications to enhance disease understanding and management.</p><p><strong>Results: </strong>Advances in immunological research have clarified key pathogenic mechanisms, including autoantibody production, complement system activation, cytokine and chemokine dysregulation, and immune cell imbalance. Emerging biomarkers, such as urinary proteins and exosomal microRNAs, have improved early diagnosis and therapeutic monitoring. Novel therapeutic agents, including B-cell inhibitors, complement inhibitors, and cytokine modulators, demonstrate improved efficacy and safety over traditional treatments. Additionally, molecular profiling and computational tools enable identification of disease endotypes, supporting response- based therapeutic strategies.</p><p><strong>Discussion: </strong>The integration of molecular insights with clinical practice has significantly enhanced the understanding of IMKD pathogenesis and progression. The use of advanced biomarkers and targeted therapies represents a paradigm shift from generalized immunosuppression to mechanism-specific interventions. However, challenges remain in translating these advances into routine clinical practice, including cost, accessibility, and the need for standardized protocols.</p><p><strong>Conclusion: </strong>The management of IMKD is evolving toward precision nephrology, emphasising individualised, mechanism-based therapies, biomarker-guided decision-making, and personalized patient care to improve clinical outcomes.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Synovial Inflammation and Joint Destruction: Therapeutic Potential of Nigella sativa Seeds in Rheumatoid Arthritis.","authors":"Shahbaz Khan, Mohd Rizvan, Himank Varshney, Alka Lohani","doi":"10.2174/0127722708496311260911114837","DOIUrl":"https://doi.org/10.2174/0127722708496311260911114837","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid Arthritis (RA) is a systemic autoimmune disorder characterized by persistent synovial inflammation and progressive joint destruction. Conventional therapies, including NSAIDs, corticosteroids, and DMARDs, may cause adverse effects, highlighting the need for safer, multi-targeted agents. This study evaluated the anti-inflammatory and anti-arthritic effects of Nigella sativa seed extract in carrageenan- and Complete Freund's Adjuvant (CFA)-induced rat models.</p><p><strong>Materials and methods: </strong>Anti-inflammatory activity was assessed using carrageenan-induced paw edema, while anti-arthritic activity was evaluated using CFA-induced arthritis in Wistar rats. Paw volume, body weight, motor coordination, hematological parameters, and joint histopathology were assessed.</p><p><strong>Results: </strong>Acute toxicity studies showed that the extract was safe up to 2000 mg/kg. Nigella sativa produced a significant, dose-dependent reduction in carrageenan-induced paw edema. In CFA-induced arthritis, the extract reduced paw swelling, prevented body-weight loss, improved motor activity, and attenuated alterations in RBC, WBC, Hb, and ESR. Histopathological examination demonstrated reduced inflammatory cell infiltration, improved trabecular thickness, and preservation of bone architecture.</p><p><strong>Discussion: </strong>The observed effects are consistent with the reported anti-inflammatory potential of Nigella sativa, which may involve suppression of inflammatory mediators and pathways. The findings support its multi-targeted activity against inflammation and joint damage.</p><p><strong>Conclusion: </strong>Nigella sativa seed extract demonstrated promising anti-inflammatory and antiarthritic effects, suggesting potential as a therapeutic agent for inflammatory disorders such as RA.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl Jasmonate Attenuates Doxorubicin-induced Myocardial Damage Through Multifaceted Cellular and Molecular Mechanisms: An Integrated In Vitro, In Vivo Approach.","authors":"Ujwal N Katolkar, Sanjay J Surana","doi":"10.2174/0127722708467146260908074948","DOIUrl":"https://doi.org/10.2174/0127722708467146260908074948","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin (Dox) is a widely used antineoplastic drug that often causes cardiomyopathy, leading to congestive heart failure through the production of Reactive Oxygen Species (ROS) within the myocardium. This investigation examines the protective effects of Methyl Jasmonate (MeJA) against Dox-induced cardiotoxicity by modulating cellular signaling pathways through in vitro and in vivo analyses.</p><p><strong>Methods: </strong>Initially, physicochemical properties were evaluated via in silico (ADMET) studies to assess MeJA's pharmacokinetic profile, including Ames toxicity, in comparison with the reference drug amifostine. Additionally, an in vitro cytotoxicity assay was performed on embryonic rat cardiac myoblasts (H9c2 cells) using the MTT method, along with measurements of proapoptotic, oxidative, and pro-inflammatory markers. Furthermore, in vivo studies assessed the impact of MeJA on Dox-induced cardiotoxicity in rats, employing hemodynamic measurements (e.g., ST height, heart rate, SAP, MAP, DAP), biochemical analyses (e.g., cardiac injury, liver enzymes, oxidative and pro-inflammatory markers), and histopathological examinations.</p><p><strong>Results: </strong>In silico ADMET analysis via the BOILED-Egg model indicated that MeJA exhibits excellent Blood-Brain Barrier (BBB) penetration and lacks Ames toxicity. In vitro, MeJA significantly reduced Dox-induced cytotoxicity, oxidative stress, and inflammation in H9c2 cells.</p><p><strong>Discussion: </strong>MeJA protects rat cardiac tissues by enhancing hemodynamic functions, lowering cardiac injury indicators, and averting histological damage, according to in vivo investigations that supported these findings.</p><p><strong>Conclusion: </strong>Together, the findings of this study suggest that MeJA possesses cardioprotective potential against Dox-induced cardiotoxicity. The observed changes in inflammatory and apoptosis- related biomarkers are consistent with a potential protective role of MeJA; however, further molecular, preclinical, and clinical studies are required to confirm its mechanisms and therapeutic applicability.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribotoxic Stress, ZAK Activation and the Orchestration of Inflammatory Signaling Networks in Human Disease.","authors":"Kamlesh Sahu, Trilochan Satapathy","doi":"10.2174/0127722708494997260901111356","DOIUrl":"https://doi.org/10.2174/0127722708494997260901111356","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Ribotoxic stress is an evolutionarily conserved intracellular surveillance mechanism that detects disturbances in translational fidelity and links ribosomal damage to inflammatory and stress-responsive signaling pathways. Diverse pathological stimuli, including microbial toxins, oxidative stress, metabolic dysfunction, and oncogenic translational overload, disrupt ribosome integrity and induce ribosome stalling and collision events. This review aims to summarize current advances in the molecular mechanisms underlying ribotoxic stress sensing, with particular emphasis on the ribosome-associated sterile alpha motif and leucine zipper-containing kinase (ZAK/MAP3K20), downstream Mitogen-Activated Protein Kinase (MAPK) signaling, and the contribution of ribotoxic stress to inflammation and disease pathogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This review was conducted as a critical narrative synthesis of the available literature. Relevant studies were identified through systematic searches of PubMed, Scopus, Web of Science, and Google Scholar databases. Experimental, structural, molecular, and translational studies investigating ribotoxic stress, ribosome collision sensing, ZAK activation, MAPK signaling, and inflammatory responses were critically evaluated using predefined inclusion and exclusion criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Current evidence indicates that ribosome collisions serve as central molecular triggers of ribotoxic stress signaling. Collision-induced activation of ZAK through autophosphorylation initiates p38 and JNK MAPK pathways, converting translational perturbations into coordinated transcriptional responses that regulate inflammation, apoptosis, stress adaptation and tissue remodeling. Accumulating studies demonstrate that persistent or dysregulated ribotoxic stress signaling contributes to the pathogenesis of infectious diseases, autoimmune disorders, metabolic inflammation, neurodegenerative conditions and cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The emerging understanding of ribotoxic stress highlights its role as a fundamental mechanism linking translational surveillance to innate immune and inflammatory responses. Unlike classical pathogen-recognition pathways, ribotoxic signaling detects functional disturbances in the translational machinery itself, providing an additional layer of cellular defense. The growing recognition of ZAK-mediated signaling as a central regulator of inflammatory and stress responses underscores its potential importance in disease progression and therapeutic intervention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Ribotoxic stress represents a critical interface between translational quality control and inflammatory signaling networks. Advances in understanding ribosome collision sensing and ZAK-dependent MAPK activation have revealed important mechanisms underlying cellular adaptation and disease development. Although several mechanistic questions remain unresolved,","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into Ulcerative Colitis and Associated Diarrhea: Exploring the Interplay of Cellular and Molecular Axis with Advancement in Treatments.","authors":"Shagun Pathania, Avijit Mazumder, Saumya Das","doi":"10.2174/0127722708482649260907065539","DOIUrl":"https://doi.org/10.2174/0127722708482649260907065539","url":null,"abstract":"<p><p>Ulcerative Colitis (UC)-associated diarrhea is a debilitating symptom of persistent intestinal inflammation that significantly reduces a patient's quality of life. Epithelial ion transport failure, tight junction remodeling, dysregulated mucus secretion, immunological overactivation, gut microbiota dysbiosis, and mitochondrial oxidative stress all interact intimately to cause its pathogenesis. While cytokine-mediated suppression of ENaC, NHE3 (Na+/H+ exchanger 3), DRA (SLC26A3), and PAT1 (SLC26A6) significantly reduces fluid and electrolyte absorption, chronic inflammation promotes \"claudin switching\" and tight junction breakdown, increasing paracellular permeability. Mucosal barrier failure is sustained and inflammatory cascades are intensified by concurrent deregulation of the NF-κB, JAK/STAT, and PXR signaling pathways. Recent findings highlight the critical role of immune-microbiota crosstalk and reactive oxygen species formed from mitochondria in sustaining this pathogenic cycle. Recent developments in biologics, targeted small molecules, colon-specific hydrogels, and nanomedicine offer potential approaches for site-specific drug delivery, immunologic control, and epithelial barrier restoration, in addition to traditional pharmacotherapies. This review highlights future options for tailored, multi-targeted therapies. It provides a framework for mechanism-guided management of UC-associated diarrhea by synthesizing existing mechanistic insights and translational therapeutic advancements.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Acne Vulgaris: From Pathogenesis to Innovative Drug Delivery.","authors":"Dixit, Anjali Sharma, Vishnu Mittal, Devkant Sharma","doi":"10.2174/0127722708479232260908063710","DOIUrl":"https://doi.org/10.2174/0127722708479232260908063710","url":null,"abstract":"<p><strong>Introduction: </strong>Acne vulgaris (AV) is a common chronic inflammatory disorder of the pilosebaceous unit that affects adolescents and adults globally. Despite the availability of multiple therapeutic approaches, limitations such as poor patient adherence, adverse effects, and antibiotic resistance necessitate improved treatment strategies. This review explores recent advances in acne pathogenesis and innovative drug delivery systems to improve therapeutic outcomes.</p><p><strong>Methods: </strong>This narrative review is based on a comprehensive analysis of published literature. Relevant data were collected from peer-reviewed journals, scientific databases, and recent publications focusing on acne pathophysiology and advanced drug delivery approaches. No ethical approval was required as the study involved a secondary data analysis of published literature.</p><p><strong>Results: </strong>Acne pathogenesis is multifactorial, involving increased sebum production, Cutibacterium acnes proliferation, follicular hyperkeratinization, inflammation, and emerging epigenetic factors, such as DNA methylation. Conventional therapies, including topical retinoids, antimicrobials, systemic antibiotics, and hormonal treatments, remain standard but have limitations. Novel drug delivery systems, such as microsponges, vesicular carriers (liposomes, niosomes, transfersomes, and bilosomes), lipid-based nanocarriers (solid lipid nanoparticles, nanostructured lipid carriers, and nanoemulsions), and polymeric/dendrimeric systems, have demonstrated improved follicular targeting, controlled drug release, enhanced stability, and reduced skin irritation.</p><p><strong>Discussion: </strong>Integrating advanced drug delivery systems addresses key challenges in conventional therapies by improving drug bioavailability, minimising systemic exposure, and enhancing patient compliance. Targeting emerging pathogenic mechanisms, including epigenetic modulation, may further optimise acne management strategies.</p><p><strong>Conclusion: </strong>Acne vulgaris poses a significant clinical and socioeconomic burden. Innovative drug delivery systems offer promising solutions to overcome the limitations of traditional therapies. However, further clinical validation, long-term safety studies, and regulatory alignment are essential for successful translation into routine clinical practice.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sepsis-reloaded: Next Generation Diagnostics, Biomarkers and Treatment Strategies.","authors":"Vidyacharan S, Roopesh R, Balamurugan T, Kousalya S","doi":"10.2174/0127722708440655260829134856","DOIUrl":"https://doi.org/10.2174/0127722708440655260829134856","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome driven by a dysregulated host response to infection, resulting in high global morbidity, mortality, and economic burden. Despite advances in critical care, sepsis remains a major challenge, especially in low-and-middle-income countries where the incidence and mortality are highest. The condition arises from diverse infections, and it is characterized by rapid disease progression, variable clinical presentations, and emerging antimicrobial resistance. Prompt diagnosis is crucial; however, conventional tools such as clinical criteria and standard biomarkers often lack adequate sensitivity and specificity. Sepsis is very dangerous, so clinicians must diagnose it early. Traditional methods may often give false results; therefore, newer biomarkers have been explored. Procalcitonin can detect sepsis in about 75-80% of true cases, with a similar rate of correctly ruling out non-sepsis, achieving an AUC of around 0.78 (95% CI 0.74-0.82). Presepsin shows an AUC of 0.89-0.95 and performs even better, accurately identifying sepsis with a sensitivity of about 85-90% in medium-to-large clinical studies. Interleukin-6 is a key pro-inflammatory cytokine that rises rapidly within 1-2 hours during sepsis, driving cytokine storms and predicting severity and mortality, with strong diagnostic performance (sensitivity around 80-85%, AUC 0.86-0.94). However, due to its elevation in non-infectious inflammatory conditions, it is most effective when used in combination with other markers, such as procalcitonin or clinical scoring systems (e.g., QSOFA), to achieve diagnostic accuracy above 90%. MicroRNAs are small non-coding RNAs that are dysregulated in sepsis; they enable early diagnosis and prognosis via blood or plasma detection and can predict organ failure and mortality, but still require robust clinical validation. These biomarkers collectively offer improved diagnostic accuracy and risk stratification. Contemporary management emphasizes early recognition, rapid administration of intravenous antibiotics and fluids, and individualized targeted, supportive therapies (e.g., immunomodulators, monoclonal antibodies), pathogen- associated molecule removal, and novel drug delivery systems (e.g., nanoparticles), which aim to enhance precision and minimize toxicity. Imaging and microbiological investigations remain essential for identifying infection sources and guiding therapy. Key challenges include diagnostic delays, altered pharmacokinetics due to organ dysfunction, inadequate drug targeting, and limited resources in vulnerable populations. Future directions involve integrating multi-omics diagnostics, personalized therapeutics, and equitable resource allocation to reduce the overall global impact of sepsis. Continued research and international collaboration are vital for advancing diagnosis, innovative treatments, and comprehensive prevention strategies.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin's Role in Modulating the Tumor Microenvironment and Immune Response in Cancer Therapy.","authors":"Shivangi Pandey, Ranjeet Kumar, Dharmendra Kumar","doi":"10.2174/0127722708478606260824115447","DOIUrl":"https://doi.org/10.2174/0127722708478606260824115447","url":null,"abstract":"<p><p>Metformin, a primary treatment for T2DM, is increasingly recognized for its anticancer properties, particularly its ability to modulate the TME and enhance antitumor immunity. By activating AMPK, metformin disrupts cancer metabolism, inhibits the PI3K/Akt/mTOR pathway, and reduces mitochondrial oxygen consumption, thereby alleviating tumor hypoxia. These metabolic shifts promote the infiltration of CD8+ and NK cells while reducing immunosuppressive populations such as Tregs and MDSCs. Furthermore, metformin facilitates the repolarization of TAMs from a pro-tumor M2 to an anti-tumor M1 phenotype. Clinical evidence suggests that metformin synergizes with chemotherapy, radiotherapy, and ICIs, offering a promising adjuvant strategy to overcome therapy resistance and improve patient outcomes. This review summarizes the molecular mechanisms and clinical potential of metformin in immunometabolic cancer therapy.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarrier-enabled Gene and Nucleic Acid Therapeutics for Rheumatoid Arthritis: Advances, Translational Evidence, and Regulatory Challenges.","authors":"Sai Geetha Meka, Sarfaroz Shaik A, Vandana Dasari, Omer Abdlgader Ibrahim Ali, Yamini Yeddhu, Nimitha Kuragala, Venu Gudisinti, Bhargav E","doi":"10.2174/0127722708482830260826121447","DOIUrl":"https://doi.org/10.2174/0127722708482830260826121447","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, cartilage degradation, and bone erosion. Conventional diseasemodifying antirheumatic drugs and biologics, although effective in many patients, are limited by systemic toxicity, variable responsiveness, and loss of efficacy over time. Recent advances in nanomedicine have enabled the development of non-viral and viral gene delivery platforms designed to modulate pathogenic pathways at the molecular level. Non-viral nanocarriers, including liposomes, polymeric nanoparticles, lipid nanoparticles, and hybrid systems, have demonstrated efficient delivery of siRNA, antisense oligonucleotides, and mRNA targeting key inflammatory mediators such as TNF-α and NF-κB, resulting in significant disease attenuation in preclinical RA models. Viral vectors, particularly adeno-associated viruses and lentiviruses, provide sustained intra-articular gene expression but raise concerns related to immunogenicity and long-term safety. Emerging gene-editing strategies, notably CRISPR/Cas-based approaches, offer the potential to precisely and durably modulate disease-driving genes. But clinical translation is restricted by off-target effects, ethical considerations, and regulatory barriers. Collectively, the available evidence underscores both the therapeutic potential and inherent complexity of nanocarrier-mediated gene and nucleic acid therapies for RA, emphasizing the necessity for optimized delivery strategies, rigorous safety assessments, and biomarker-guided patient stratification to achieve successful clinical translation. This review comprehensively covered various gene delivery modalities, including non-viral and viral vectors, and gene editing (CRISPR/Cas) approaches. At the end, preclinical and clinical evidence, along with extensive case studies, for RA treatment were also highlighted. This review also outlined challenges and future directions in the management of arthritis.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}