Current Reviews in Clinical and Experimental Pharmacology最新文献

{"title":"Role of Lysosomal Genes for Parkinson's Pathogenesis: Insights from Molecular Mechanism to Therapeutic Strategies.","authors":"Vidhan Chand Bala, Asheesh Kumar Gupta, Amit Kumar, Mukesh Kumar Singh, Arvind Kumar Patel, Sunil Kumar Tiwari, Sushil Kumar","doi":"10.2174/0127724328441801260406095625","DOIUrl":"https://doi.org/10.2174/0127724328441801260406095625","url":null,"abstract":"<p><p>Current review aims to clarify the role of lysosomal genes in the pathogenesis of Parkinson's Disease (PD), directing on the molecular mechanisms underlying lysosomal dysfunction and its involvement to α-synuclein accumulation. To deliberates PD-related genes including GBA1, LRRK2, VPS35, PRKN, PINK1, TMEM175, ATP13A2, ATP10B, and DJ1, highlighting their contribution in lysosomal damage. It investigates the disorder of lysosomal enzymes such as cathepsins, glucocerebrosidase, galactocerebrosidase, and acid sphingomyelinase, and the consequent impairment of the autophagic-lysosomal pathway, which helps pathological α-synuclein accumulation. Therapeutic approaches targeting lysosomal dysfunction and α-synuclein pathology are reviewed, including pharmacological chaperones, immunization strategies, enzyme replacement therapies, and small-molecule oligomer modulators. While recent clinical trials expose certain limitations, combinatorial treatment strategies show potential to improve therapeutic efficacy. Lysosomal pathways are critical contributors to PD pathogenesis and denote promising targets for intervention. Integrating mechanistic understandings with developing therapies underlines the importance of targeting lysosomal dysfunction to mitigate α-synuclein aggregation and advance PD treatment.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975974","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":"Cannabidiol-Loaded Smart Hydrogels for Advanced Wound Healing: Drug Delivery Innovations and Therapeutic Perspectives.","authors":"Ayushi Bhandari, Shikha Baghel Chauhan, Indu Singh, Chirag Jain","doi":"10.2174/0127724328453813260323115317","DOIUrl":"https://doi.org/10.2174/0127724328453813260323115317","url":null,"abstract":"<p><p>Chronic wounds are a leading healthcare burden worldwide, fueled by intricate pathophysiology and the inadequacy of standard therapies. The present review critically discusses the novel paradigm of incorporating cannabidiol (CBD), a phytocannabinoid with significant anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative capacities, into advanced smart hydrogel platforms for better wound healing and tissue regeneration. We summarize the strong rationale for CBD, focusing on its multimodal pharmacological effects on central pathways (e.g., proinflammatory cytokines, oxidative stress, fibroblast activity, angiogenesis, endocannabinoid system) and reconciling its inherent delivery issues (poor solubility, instability, pharmacokinetics). The review comprehensively addresses the engineering of stimulus-responsive hydrogels (pH-, temperature-, enzyme-, redox-sensitive) to surmount these challenges. Material properties of key interest-biocompatibility, biodegradation tuneability, mechanical cues emulating ECM, and microenvironment control-are addressed together with innovative crosslinking mechanisms (dynamic covalent bonds, supramolecular interactions) as well as state-of-the-art fabrication techniques (3D/4D bioprinting, electrospinning, microfluidics). We have outlined the mechanisms of controlled release of CBD by wound-specific cues and investigated the synergistic interaction between CBD delivery dynamics and hydrogel characteristics in regulating key cellular events (macrophage polarization, re-epithelialization, ECM remodeling). Preclinical proof of principle for CBD-hydrogel therapeutic utility in various wound models (diabetic, infected, burn) is assessed, with discussion of the landscape of clinical translation, regulatory avenues, and ongoing challenges (scalability, standardization, long-term safety). Lastly, the review points to future frontiers such as closed-loop \"sense-and-respond\" systems, AI-assisted design, personalized point-of-- care manufacturing, and combinatorial strategies. We conclude that smart CBD-loaded hydrogels hold a promising approach to meeting unmet needs in treating chronic wounds by delivering localized, sustained, and physiologically responsive release to realize CBD's full therapeutic potential for regenerative medicine.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723919","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":"Cardioprotective Effect of Apelin and Apela: The Receptor and Signaling Mechanism.","authors":"Leonid N Maslov, Sergey V Popov, Alexandr V, Alisa S Slidnevskaya, Natalia V Naryzhnaya, Alexander S Gorbunov, Mikhail Kilin, Viacheslav N Azev, Feng Fu, Philipp A Ilinykh, Huijie Ma","doi":"10.2174/0127724328447640260323172816","DOIUrl":"https://doi.org/10.2174/0127724328447640260323172816","url":null,"abstract":"<p><p>The development of new approaches for the treatment of acute myocardial infarction (AMI) remains a major goal of modern medicine. The objective of the review is an analysis of data on the signaling mechanism of apelin-induced cardiac tolerance to ischemia/reperfusion (I/R). There is evidence that apelin and apela act as autocrine and paracrine factors rather than circulating hormones with a short in vivo half-life. Apelin and apela increase cardiac tolerance to I/R. These peptides decrease infarct size and improve recovery of ventricular function in reperfusion. Apelin activates three signaling pathways: Gi/o protein dependent, Gq/11 protein dependent, and β-arrestin mediated. All three pathways could be involved in the cardioprotective effect of apelin. The following enzymes mediate apelin-induced cardioprotection: NO-synthase (NOS), epidermal growth receptor kinase, phospholipase C (PLC), protein kinase C (PKC), phosphoinositide 3-kinases (PI3K), Src kinase, Akt kinase (Akt), AMP-activated protein kinase (AMPK), guanylyl cyclase (GC), and extracellular signal-regulated kinase (ERK). ATP-sensitive K+ channel (KATP channel) opening and mitochondrial permeability transition (MPT) pore closure may also be involved in apelin-induced cardiac tolerance to I/R. Apelin and apela molecules may form the basis for the creation of new drugs for the treatment of AMI.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723863","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":"Cannabidiol as a Modulator of the Gut-Liver Axis: Clinical and Pharmacological Insights into Hepatic and Metabolic Disorder Therapies.","authors":"Shikha Baghel Chauhan, Indu Singh, Khushi Dahiya, Chirag Jain","doi":"10.2174/0127724328431124260314092422","DOIUrl":"https://doi.org/10.2174/0127724328431124260314092422","url":null,"abstract":"<p><p>A non-intoxicating substance produced from Cannabis sativa, cannabidiol (CBD) has shown promise as a treatment for metabolic and hepatic diseases, primarily due to its capacity to alter the gut-liver axis. A vital bidirectional communication pathway, the gut-liver axis is where substances produced from the liver affect gut homeostasis and gut-derived microbial products and metabolites influence liver health. Conditions including alcoholic liver disease (ALD), metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) are mostly caused by dysregulation of this axis. According to preclinical research, CBD has hepatopro-tective benefits via improving the integrity of the gut barrier, decreasing intestinal permea-bility, altering the gut microbiota, and suppressing inflammatory signaling pathways such NF-κB and NLRP3 inflammasome activation. Furthermore, CBD improves insulin sensitivi-ty and lowers hepatic steatosis via modifying lipid and glucose metabolism via the PPARγ and CB1/CB2 receptor pathways. Its antioxidant qualities also help to lessen cellular dam-age and oxidative stress in hepatic tissues. Despite these encouraging results, there is still inconsistency in the clinical data because of variations in dosage, formulation, administra-tion method, and patient-specific variables including liver function and microbiota makeup. Furthermore, broad therapeutic usage is restricted by issues with hepatic metabolism, pos-sible drug-drug interactions, and regulatory obstacles. This review highlights information gaps, critically assesses the available preclinical and clinical evidence, and investigates the mechanisms underlying CBD's impact on the gut-liver axis. Additionally, it identifies po-tential avenues for future optimization of CBD-based therapies targeting liver and metabol-ic illnesses through personalized medicine, sophisticated delivery methods, and standard-ized clinical trial procedures.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618860","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":"Exploring TRPM7 Channel-Kinase for Disease Modulation: A Translational Approach.","authors":"Ishita Mitra, Priyanka Chakraborty, Sailee Chowdhury, Koyel Kar","doi":"10.2174/0127724328432668260302192316","DOIUrl":"https://doi.org/10.2174/0127724328432668260302192316","url":null,"abstract":"<p><strong>Introduction: </strong>This review examines the multifaceted involvement of the transient receptor potential melastatin-7 (TRPM7) channel-kinase in human disease and evaluates its suitability as a selective therapeutic target. Particular emphasis is placed on the integrated ion channel and serine/threonine kinase functions of TRPM7 and their contribution to pathogenic mechanisms across oncological, neurological, cardiovascular, and immunological disorders.</p><p><strong>Methods: </strong>A structured survey of the literature published between 2010 and 2025 was undertaken using major biomedical databases. Evidence from molecular, cellular, experimental, and clinical investigations was synthesized, with specific attention to TRPM7-dependent regulation of cell proliferation, migration, apoptosis, and immune signaling.</p><p><strong>Results: </strong>Collective findings identify TRPM7 as a key regulator of intracellular Mg2+ and Ca2+ homeostasis, thereby influencing multiple signaling pathways. Aberrant TRPM7 expression or activity is consistently associated with the onset and progression of diverse pathological conditions, including malignancy, neurodegeneration, cardiovascular dysfunction, and autoimmune disease. Pharmacological modulation of TRPM7 has demonstrated beneficial effects in preclinical models, supporting its therapeutic relevance.</p><p><strong>Discussion: </strong>The distinctive channel-kinase architecture of TRPM7 enables coordinated control of ionic flux and phosphorylation-dependent signaling, positioning it at central nodes of inflammation, oxidative stress, and pathological cellular remodeling. Its context-dependent roles across tissues highlight opportunities for selective intervention.</p><p><strong>Conclusion: </strong>TRPM7 emerges as a pivotal mediator of disease-related signaling and a promising molecular target. Continued development of selective TRPM7 modulators may facilitate translation of mechanistic insights into clinically effective therapies.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259858","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":"Daprodustat vs Recombinant Human Erythropoietin for Anemia and Cardiovascular Safety in Dialysis-Dependent and Non-Dialysis-Dependent CKD Patients - A Systematic Review and Meta-analysis.","authors":"Hara Prasad Mishra, Rachna Gupta, Shubhima Grover, Lalit K Gupta","doi":"10.2174/0127724328377421251117050736","DOIUrl":"https://doi.org/10.2174/0127724328377421251117050736","url":null,"abstract":"<p><strong>Background: </strong>Anemia is a prevalent complication in chronic kidney disease (CKD) that remains challenging to manage effectively. Daprodustat was recently approved for anemia in CKD. This meta-analysis aims to provide evidence-based insights for the clinical use of daprodustat in CKD-related anemia.</p><p><strong>Method: </strong>A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines, with searches conducted in databases such as PubMed and ClinicalTrials.gov, encompassing studies published up to August 30, 2024. Data from 12 randomized controlled trials involving 9,278 CKD patients (both dialysis-dependent (DD) and non-dialysis-dependent (NDD)) were analyzed.</p><p><strong>Results: </strong>Daprodustat significantly increased hemoglobin (Hb) levels compared to placebo in both NDD (MD = 1.92, 95% CI [0.67, 3.02], p = 0.001) and DD (MD = 1.72, 95% CI [0.34, 3.65], p = 0.01) patients. However, no significant difference in Hb levels was observed between daprodustat and recombinant human erythropoietin (rhEPO) (MD = 0.05, 95% CI [-0.10, 0.21], p = 0.50). Daprodustat improved iron metabolism by significantly lowering hepcidin and increasing total ironbinding capacity (TIBC) compared to rhEPO. Cardiovascular safety analysis showed no significant difference in major adverse cardiovascular events (MACE) between daprodustat and rhEPO (RR = 1.02, 95% CI [0.92, 1.14], p = 0.83), though a significant reduction in MACE incidence was observed in DD patients (RR = 0.98, 95% CI [0.87, 1.15], p = 0.02). Serious adverse events were significantly lower with daprodustat compared to rhEPO (RR = 0.82, 95% CI [0.66, 0.84], p = 0.02 in DD; RR = 0.61, 95% CI [0.48, 0.78], p = 0.008 in NDD patients).</p><p><strong>Conclusion: </strong>Daprodustat offers a promising alternative to traditional anemia treatments in CKD, with efficacy comparable to rhEPO and a favorable cardiovascular safety profile, which marks its potential as a valuable therapeutic option.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935459","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":"Genetic Determinants of Statin-induced Myopathy: A Network Meta-analysis of Observational Studies.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.2174/0127724328356429250315163111","DOIUrl":"10.2174/0127724328356429250315163111","url":null,"abstract":"<p><strong>Introduction: </strong>Statin-induced myopathy (SIM) is a prevalent adverse event impacting treatment adherence. Despite extensive exploration of single nucleotide polymorphisms (SNPs), conflicting evidence obscures their role in SIM incidence, prompting this network meta-analysis.</p><p><strong>Methods: </strong>Observational studies meeting eligibility criteria (patients on any statin with reported SNPs and SIM details) were systematically reviewed. Severe SIM was defined as creatine kinase elevations exceeding 10 times the upper limit of normal. Mixed treatment comparison pooled estimates were generated from direct and indirect pooled estimates, represented by odds ratios (OR) with 95% confidence intervals (CI), and validated via bootstrap analysis.</p><p><strong>Results: </strong>Thirty-four studies (26,152 participants) examining genotypes spanning drug transporters, metabolizing enzymes, reactive oxygen species production, and myopathy-related genes were analyzed. Significant associations were observed with drug transporters (OR: 1.4; 95% CI: 1.04, 1.5). Notably, solute carrier organic anion transporter 1B1 (SLCO1B1) (rs4149056) exhibited a moderate association with SIM (OR: 2.1; 95% CI: 1.7, 2.6), validated by bootstrap analysis (OR: 2.1; 95% CI: 1.7, 2.8). Similar associations were found for severe SIM with SLCO1B1 (rs4149056) (OR: 3.8; 95% CI: 1.4, 10.4) and ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs2373588) (OR: 2.8; 95% CI: 1.4, 5.4). Intraclass differences in genetic predictor risks were noted among statins.</p><p><strong>Conclusion: </strong>Our meta-analysis underscores the significant association of SLCO1B1 with SIM, supporting its clinical utility. Further research is warranted to clarify additional genetic predictors. These findings endorse current guidelines advocating for SLCO1B1 genotyping in statin therapy decisions.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"75-91"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774439","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":"Efficacy and Safety of Ezetimibe for Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.","authors":"Amir Reza Boskabadi, Sajad Khodabandelu, Yasaman Rahimi, Alireza Motamedi, Pooria Asili, Azadeh Ghasempour, Ali Keshavarzian, Shokoofeh Noori, Mohammad Rahmanian","doi":"10.2174/0127724328371387250606060831","DOIUrl":"10.2174/0127724328371387250606060831","url":null,"abstract":"<p><strong>Background and aim: </strong>Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. It is associated with life-threatening conditions such as cardiovascular disease and hepatocellular carcinoma. This systematic review and meta-analysis aimed to evaluate ezetimibe in patients with NAFLD.</p><p><strong>Methods: </strong>A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to August 8th, 2024, to identify relevant articles. The most used keywords for searching are \"Ezetimibe\" and \"Nonalcoholic Fatty Liver Disease.\" A random-effects model evaluated the standardized mean difference (SMD) and its 95% confidence interval (CI). All analyses were performed using the \"meta\" package in the R programming language version 4.3.1.</p><p><strong>Results: </strong>Ten studies included in our study (five non-controlled and six controlled trials, with a total of 516 participants) investigated the effect of ezetimibe on different parameters. Ezetimibe significantly improves AST (SMD: -0.63, 95% CI: (-1.12, -0.14)), ALT (SMD: -0.50, 95% CI: (-0.91, - 0.10)), GGT (SMD: -0.30, 95% CI: (-0.49, -0.10)), and LDL (SMD: -0.85, 95% CI: (-1.16, -0.54)), but was unable to improve HDL, TG, and BMI. Ezetimibe was also able to improve steatosis (SMD: -0.30, 95% CI: (-0.49, -0.10)), but inflammation (SMD: 0.06, 95% CI: (-0.57, 0.69)), ballooning (SMD: -0.62, 95% CI: (-1.55, 0.31)), and fibrosis (SMD: 0.03, 95% CI: (-0.25, 0.31)) were not improved.</p><p><strong>Conclusion: </strong>Based on the findings, the administration of ezetimibe can reduce liver enzymes as well as the hepatic steatosis, but its effects on liver inflammation and fibrosis remain controversial. Further research is required to study its effects in combination with other treatments.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"147-159"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327032","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":"Dipeptidyl Peptidase-4 Inhibitors and Risk of Fractures in Type 2 Diabetes Mellitus Patients: A Bayesian Network Meta-Analysis.","authors":"Tufail Ahmad, Mohammad Adil, Mohammad Azharuddin, Shamsuzzaman Ansari, Divya Vohora, Manju Sharma","doi":"10.2174/0127724328373328250624065307","DOIUrl":"10.2174/0127724328373328250624065307","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) contributes to an increased fracture risk and impaired bone health. The impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on bone fracture risk is unclear. We performed a network meta-analysis (NMA) to assess the impact of DPP-4i on fracture risk in patients with T2DM.</p><p><strong>Methods: </strong>A comprehensive systematic literature search was conducted on PubMed/Medline, Cochrane Library, and ClinicalTrials.gov until June 2024 to identify RCTs reporting fracture events with DPP-4i among T2DM patients. A Bayesian NMA has been performed to calculate the odds ratio (OR) and 95% credible intervals (CrI). Surface under the cumulative ranking analysis (SUCRA) was utilized to assess the rank probability of DPP-4i.</p><p><strong>Results and discussion: </strong>A total of 85 RCTs were identified, including 89,965 T2DM patients with 1,083 fracture events. In the direct meta-analysis, DPP-4i did not elevate fracture risk compared to placebo or other oral anti-diabetics (OADs) (OR (95%CI): 1.04 (0.91-1.18); p = 0.57 and 1.18 (0.79-1.74); p = 0.96, respectively). Alogliptin and sitagliptin indicated a non-significant trend towards reducing fracture risk compared to placebo (OR (95%CI): 0.59 (0.31-1.15); p = 0.12) and OADs (OR (95%CI): 0.73 (0.41-1.30); p = 0.28), respectively. In the NMA, alogliptin significantly reduced fracture risk compared to linagliptin and SGLT2i (OR (95%CrI): 0.41 (0.16-0.93) and 0.16 (0.017-0.83), respectively). Conversely, linagliptin increased fracture risk compared to sulfonylurea (OR (95%CrI): 2.3 (1.1-5.2). According to SUCRA, alogliptin (84%) ranked as the preferred treatment for reducing fracture risk in T2DM patients.</p><p><strong>Conclusion: </strong>Overall, DPP-4i was not associated with an increased risk of fractures in patients with T2DM. However, alogliptin demonstrated a reduced risk of fractures when compared to both linagliptin and SGLT2i. Further long-term clinical studies are needed to confirm the present findings.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"259-268"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609688","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":"Resolving Pain: Preclinical Insights into the Analgesic Mechanisms of RvD1.","authors":"Geovana Martelossi-Cebinelli, Tiago H Zaninelli, Rubia Casagrande, Sergio M Borghi, Waldiceu A Verri","doi":"10.2174/0127724328436999251223054038","DOIUrl":"10.2174/0127724328436999251223054038","url":null,"abstract":"<p><p>Pain is a protective mechanism of the body that is intensified during inflammatory processes through the sensitization of nociceptive neurons. Although current drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and opioids, are effective, their side effects reinforce the search for safer alternatives. In this context, studies investigating the analgesic effects of specialized pro-resolving mediators (SPMs), derived from polyunsaturated fatty acids, stand out. Resolvin D1 (RvD1), derived from the omega-3 fatty acid docosahexaenoic acid, acts in a multimodal manner to modulate pain and inflammation by regulating immunological, neuronal, and glial responses. Thus, RvD1 is a promising molecule for resolving inflammatory and painful processes. Herein, we address the main analgesic mechanisms of RvD1 in different preclinical models.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"269-280"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147460426","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}