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Nox4 inhibition with GKT137831 protects against diabetic cardiomyopathy: Insights from functional and transcriptomic analysis GKT137831抑制Nox4可预防糖尿病性心肌病:来自功能和转录组学分析的见解
Pharmacological Research - Reports Pub Date : 2025-12-01 Epub Date: 2025-07-17 DOI: 10.1016/j.prerep.2025.100053
Sivarupa Raji , Rohini Dhat , Sandhya L. Sitasawad
{"title":"Nox4 inhibition with GKT137831 protects against diabetic cardiomyopathy: Insights from functional and transcriptomic analysis","authors":"Sivarupa Raji ,&nbsp;Rohini Dhat ,&nbsp;Sandhya L. Sitasawad","doi":"10.1016/j.prerep.2025.100053","DOIUrl":"10.1016/j.prerep.2025.100053","url":null,"abstract":"<div><h3>Objective</h3><div>NADPH oxidase 4 (Nox4) is abundantly expressed in the heart and is the primary source of reactive oxygen species (ROS) in the cardiac tissue associated with cardiovascular diseases. We sought to determine whether Nox4 plays a major role in modulating diabetic cardiomyopathy (DCM) and the mechanisms involved.</div></div><div><h3>Research design and methods</h3><div>Diabetes was induced in male Wistar rats with a single dose of streptozotocin, followed by a daily dose of GKT137831 for 3 months. The characteristics of DCM were evaluated by electrocardiography (ECG) and hemodynamic measurements. Western blot analysis, histopathological evaluation, and immunohistochemical staining were performed to assess ROS, fibrosis, and apoptosis. Additionally, transcriptome analysis via RNA sequencing was conducted to investigate the role of Nox4 in cardiac dysfunction in diabetic rats.</div></div><div><h3>Results</h3><div>Rats with DCM presented significant left ventricular dysfunction with elevated levels of cardiac damage markers, Nox4 expression, ROS, cardiac fibrosis markers, and apoptotic proteins. We found that treatment with the Nox4 specific inhibitor GKT137831 ameliorated effects in DCM. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, RNA sequencing revealed that GKT137831 treatment prevented the upregulation of genes associated with contractility abnormalities, such as <em>Myl4, Cacna2d2, Cacnb3, Atp2a1, Cox6b2, Cacnb1, and Cacna2d3</em> in the diabetic cardiac tissue.</div></div><div><h3>Conclusion</h3><div>Nox4 inhibition with GKT137831 may exert a protective effect on DCM by improving cardiac dysfunction, indicating its translational value in clinical settings.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703947","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}
引用次数: 0
Mapping research trends and hotspots of artificial intelligence, and machine learning in medicine and health within the Eastern Mediterranean region‎: A comprehensive bibliometric analysis 绘制研究趋势和热点的人工智能和机器学习在医学和卫生东地中海地区:一个全面的文献计量分析
Pharmacological Research - Reports Pub Date : 2025-12-01 Epub Date: 2025-06-17 DOI: 10.1016/j.prerep.2025.100048
Arwa M. Al-Dekah
{"title":"Mapping research trends and hotspots of artificial intelligence, and machine learning in medicine and health within the Eastern Mediterranean region‎: A comprehensive bibliometric analysis","authors":"Arwa M. Al-Dekah","doi":"10.1016/j.prerep.2025.100048","DOIUrl":"10.1016/j.prerep.2025.100048","url":null,"abstract":"<div><h3>Background</h3><div>Artificial Intelligence (AI) and Machine Learning (ML) literature on medicine and healthcare within the Eastern Mediterranean Region (EMR) is proliferating, and the volumes of scientific data are getting increasingly complex to analyze. It is essential to comprehensively analyze the current state of research in this area. This study performs comprehensive bibliometric analysis to evaluate the productivity and impact of publications on AI and ML in medicine and health within the EMR and to anticipate future research directions in the field.</div></div><div><h3>Methods</h3><div>The literature between 1996 and 2024 was retrieved from Scopus and Web of Science (WoS) databases. Microsoft Excel, the R package \"bibliometrix\" and VOSviewer were employed to perform bibliometric analysis and to map the landscape research, identify key themes, and explore trends.</div></div><div><h3>Results</h3><div>A total of 2365 eligible publications were identified, showing an average annual growth rate of 22.92 % over the past two decades. Iran (37.1 %), Saudi Arabia (25.1 %) were the most productive countries in this field. The author with the most publications was Leili Tapak. The journal with the most publications was Scientific Reports, and the most active affiliation was Tehran University of Medical Sciences. The most frequent keywords were \"<em>machine learning</em>\", \"<em>COVID-19</em>\", and \"<em>artificial intelligence</em>\".</div></div><div><h3>Conclusion</h3><div>AI/ML research in the EMR is expanding rapidly, driven by a few high-output countries and concentrated around clinical and diagnostic themes. The findings underscore the need for enhanced intra-regional collaboration, strategic investment in AI infrastructure, and the inclusion of underrepresented countries to ensure equitable AI development across the region.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313967","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}
引用次数: 0
Alpha-lipoic acid alleviates testicular dysfunction induced by olanzapine in male rats, involvement of adiposity, oxidative stress, inflammation, and male hormonal factors α -硫辛酸可减轻奥氮平引起的雄性大鼠睾丸功能障碍、肥胖、氧化应激、炎症和雄性激素因素的参与
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-05-20 DOI: 10.1016/j.prerep.2025.100043
Samir AE Bashandy , Fatma A. Morsy , Yousef S. Bashandy , Marawan A. Elbaset , Bassim M.S.A. Mohamed
{"title":"Alpha-lipoic acid alleviates testicular dysfunction induced by olanzapine in male rats, involvement of adiposity, oxidative stress, inflammation, and male hormonal factors","authors":"Samir AE Bashandy ,&nbsp;Fatma A. Morsy ,&nbsp;Yousef S. Bashandy ,&nbsp;Marawan A. Elbaset ,&nbsp;Bassim M.S.A. Mohamed","doi":"10.1016/j.prerep.2025.100043","DOIUrl":"10.1016/j.prerep.2025.100043","url":null,"abstract":"<div><div>Olanzapine, classified as an atypical antipsychotic pharmacological agent, has been linked with the onset of metabolic syndrome and reproductive dysfunction. The objective of this investigation was to examine the protective properties of alpha-lipoic acid (ALA) in counteracting the metabolic and reproductive disturbances induced by olanzapine in a rat model. Adult Wistar rats were allocated into four distinct groups: a control group, an olanzapine-treated group (10 mg/kg), and two groups receiving olanzapine in conjunction with alpha-lipoic acid (50 or 100 mg/kg). The treatment regimen was administered over a duration of 8 weeks. The group exposed to olanzapine exhibited statistically significant reductions in luteinizing hormone, testosterone levels, sperm motility, sperm count, and relative weights of reproductive organs, alongside an elevation in inflammatory markers (TNF-α and IL-6), oxidative stress (MDA, SOD and GSH), sperm abnormalities, body weight gain, and fat deposition when contrasted with control subjects. Notably, the concomitant administration of alpha-lipoic acid (at doses of 50 or 100 mg/kg) resulted in a partial, dose-dependent amelioration of the adverse effects induced by olanzapine. Specifically, alpha-lipoic acid (100 mg/kg) alleviated the harmful consequences of olanzapine on reproductive hormones, sperm quality metrics, organ weights, oxidative stress levels, and inflammatory markers. Furthermore, alpha-lipoic acid exhibited advantageous effects on body weight and fat accumulation. These observations indicate that alpha-lipoic acid may serve as a viable adjunctive therapeutic strategy to mitigate the metabolic and reproductive side effects associated with olanzapine administration. Additional investigations are necessary to clarify the underlying mechanisms of these protective effects and their potential clinical ramifications.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107930","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}
引用次数: 0
Pretreatment with acetylsalicylic acid alleviates UVB irradiation-induced skin pathology in hairless mice and BOC-2 (an ALX/FPR2 receptor antagonist) reduces its activity 乙酰水杨酸预处理可减轻UVB照射引起的无毛小鼠皮肤病理,而bac -2(一种ALX/FPR2受体拮抗剂)可降低其活性
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2024-12-16 DOI: 10.1016/j.prerep.2024.100024
Renata M. Martinez , Priscila Saito , Ingrid C. Pinto , Camilla C.A. Rodrigues , Victor Fattori , Cristina P.B. Melo , Allan J.C. Bussmann , Larissa Staurengo-Ferrari , Tiago H. Zaninelli , Telma Saraiva-Santos , Michel F. Otuki , Daniela A. Cabrini , Marcela M. Baracat , Sandra R. Georgetti , Waldiceu A. Verri Jr. , Rubia Casagrande
{"title":"Pretreatment with acetylsalicylic acid alleviates UVB irradiation-induced skin pathology in hairless mice and BOC-2 (an ALX/FPR2 receptor antagonist) reduces its activity","authors":"Renata M. Martinez ,&nbsp;Priscila Saito ,&nbsp;Ingrid C. Pinto ,&nbsp;Camilla C.A. Rodrigues ,&nbsp;Victor Fattori ,&nbsp;Cristina P.B. Melo ,&nbsp;Allan J.C. Bussmann ,&nbsp;Larissa Staurengo-Ferrari ,&nbsp;Tiago H. Zaninelli ,&nbsp;Telma Saraiva-Santos ,&nbsp;Michel F. Otuki ,&nbsp;Daniela A. Cabrini ,&nbsp;Marcela M. Baracat ,&nbsp;Sandra R. Georgetti ,&nbsp;Waldiceu A. Verri Jr. ,&nbsp;Rubia Casagrande","doi":"10.1016/j.prerep.2024.100024","DOIUrl":"10.1016/j.prerep.2024.100024","url":null,"abstract":"<div><div>This work aims to investigate if the biological activity of acetylsalicylic acid (ASA) against UVB irradiation-induced skin inflammatory and oxidative injury in hairless mice would be amenable by treatment with BOC-2, an antagonist of the formyl peptide receptor 2 receptor (ALX/FPR2). Mice were treated with BOC-2 and after 30 minutes, they received ASA or Aspirin-Triggered 15-epi-lipoxin A<sub>4</sub> (AT-LXA<sub>4,</sub> an agonist of ALX/FPR2), and after 1 hour, they were exposed to UVB irradiation (dose of 4.14 J/cm<sup>2</sup>). UVB stimulation induced neutrophil and mast cell recruitment, edema, matrix metalloproteinase-9 (MMP-9) activity, collagen degradation, sunburn cell formation, and cytokine production (TNF-α, IL-1β and IL-6). All these parameters were inhibited by ASA or AT-LXA<sub>4</sub>. In addition, ASA and AT-LXA<sub>4</sub> enhanced anti-inflammatory cytokines (IL-10 and TGF-β), and attenuated UVB-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, free radical scavenging, reduced glutathione levels, catalase activity, superoxide anion production, Nrf2, Nqo1, and gp91<sup>phox</sup> mRNA expression. These therapeutic effects of ASA and AT-LXA<sub>4</sub> were reversed by BOC-2. Our results demonstrate that ALX/FPR2 receptor plays an important role in ASA activity against UVB-induced skin pathologies.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152928","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}
引用次数: 0
Potentiation of endocannabinoid signaling alleviates depressive-like behavior in diabetic mice 内源性大麻素信号增强可减轻糖尿病小鼠的抑郁样行为
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-04-10 DOI: 10.1016/j.prerep.2025.100037
Anuradha Kesharwani , Devidas Lahamge , Shubhankar Kumar Singh , Velayutham Ravichandiran , Vipan Kumar Parihar
{"title":"Potentiation of endocannabinoid signaling alleviates depressive-like behavior in diabetic mice","authors":"Anuradha Kesharwani ,&nbsp;Devidas Lahamge ,&nbsp;Shubhankar Kumar Singh ,&nbsp;Velayutham Ravichandiran ,&nbsp;Vipan Kumar Parihar","doi":"10.1016/j.prerep.2025.100037","DOIUrl":"10.1016/j.prerep.2025.100037","url":null,"abstract":"<div><div>People with poorly managed diabetes frequently feel repressed pleasure and are more prone to developing anxiety and depression. The molecular reasons causing the increased incidence of mood and cognitive impairments after hyperglycemia remain unknown. However, current research suggests that disturbances in the endocannabinoid (eCB) system play a critical role in the initiation and progression of diabetes-related mood and cognitive deficits. Our findings reveal that lower levels of two critical eCB, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in the medial prefrontal cortex (mPFC) are related to increased anxiety-like and depressive-like behavior in diabetic mice. Additionally, the brains of diabetic mice exhibit elevated levels of Fatty Acid Amide Hydrolase (FAAH), an important enzyme involved in the metabolism of AEA and 2AG, which contributes to the polarization of microglia and the promotion of chronic neuroinflammation. Furthermore, cannabidiol (CBD), a non-psychoactive component of cannabis, administered intraperitoneally for two weeks, improves mood and memory in diabetic mice via transforming the eCB system, as evidenced by higher levels of AEA and 2-AG. The cellular changes induced by CBD treatment in the mPFC included notable modulation of microglia towards a beneficial anti-inflammatory M2 phenotype and a reduction in microglial hypertrophy. CBD therapy resulted in several beneficial molecular alterations in the mPFC, such as a reduction in proinflammatory cytokine levels, an elevation in 2AG and AEA, and a suppression of HMGB1-TLR4 pathway activation. The administration of CBD did not influence the activity of the NAPE-PLD and DAGL-α enzymes, responsible for the synthesis of 2AG and AEA. This indicates that the therapeutic benefits of CBD are not dependent on the enhanced synthesis of AEA and 2AG. Additionally, the administration of CBD significantly reduces fasting blood glucose levels in diabetic mice, indicating that the positive effects of CBD on the brain function of diabetic mice are likely facilitated by enhanced glucose metabolism.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833816","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}
引用次数: 0
Alzheimer's disease – An overview of nano herbal formulations 阿尔茨海默病-纳米草药配方概述
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-05-19 DOI: 10.1016/j.prerep.2025.100042
Vishal Shivaji Patil , Swapnali Sachin Patil , Snehal Rajendra Patil , Akanksha Shahaji Pawar , Amol Somnath Shete
{"title":"Alzheimer's disease – An overview of nano herbal formulations","authors":"Vishal Shivaji Patil ,&nbsp;Swapnali Sachin Patil ,&nbsp;Snehal Rajendra Patil ,&nbsp;Akanksha Shahaji Pawar ,&nbsp;Amol Somnath Shete","doi":"10.1016/j.prerep.2025.100042","DOIUrl":"10.1016/j.prerep.2025.100042","url":null,"abstract":"<div><h3>Background</h3><div>The progressive neurological condition known as Alzheimer’s disease (AD) mainly affects elderly persons. Memory loss, cognitive decline, and the build-up of beta-amyloid (Aβ) plaques and neurofibrillary tangles in the brain are some of its distinguishing characteristics. The benefits of current treatment choices are limited, generally fail to effectively stop progression of the disease, and are typically linked to adverse effects that lower quality of life.</div></div><div><h3>Main body</h3><div>Herbal medicines are viable solutions for treating AD, according to recent research, especially when paired with nanotechnology. These formulations seek to overcome important issues with traditional treatments, such as poor permeability and low solubility across the blood-brain barrier (BBB). When used with herbal medicine, nanotechnology provides creative answers to these problems that may improve therapeutic delivery and efficacy. With an emphasis on their use in treatment of AD, this paper examines the relationship between herbal medicine and nanotechnology. It looks at the legal environment and intellectual property rights surrounding herbal nanoformulations, emphasizing need for more thorough research to fully comprehend their modes of action and prospective applications. Additionally, it compiles information on patents and ongoing studies, offering a summary of developments in area.</div></div><div><h3>Conclusion</h3><div>The therapy of Alzheimer's disease can be revolutionized by incorporating herbal treatments into nanostructured compositions. Such advances have the potential to transform treatment approaches by boosting therapeutic results and delivery systems. This review highlights the significance of ongoing research and development in this area, providing promise for improved outcomes and more efficient management of Alzheimer's disease patients.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123233","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}
引用次数: 0
Chemical structures, extraction methods and health benefits of okra-derived polysaccharides (ODPs): emphasis on their antioxidant, antihyperlipidemic and antidiabetic actions 秋葵多糖的化学结构、提取方法及保健作用:重点介绍其抗氧化、抗高脂血症和抗糖尿病作用
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-04-26 DOI: 10.1016/j.prerep.2025.100038
Ahmed Olatunde , Abdulazeez Ridwanullah Eyitayo , Abdulrashid Mohammed , Suleiman Yusuf Alhaji , Abubakar Ibrahim Bawa
{"title":"Chemical structures, extraction methods and health benefits of okra-derived polysaccharides (ODPs): emphasis on their antioxidant, antihyperlipidemic and antidiabetic actions","authors":"Ahmed Olatunde ,&nbsp;Abdulazeez Ridwanullah Eyitayo ,&nbsp;Abdulrashid Mohammed ,&nbsp;Suleiman Yusuf Alhaji ,&nbsp;Abubakar Ibrahim Bawa","doi":"10.1016/j.prerep.2025.100038","DOIUrl":"10.1016/j.prerep.2025.100038","url":null,"abstract":"<div><div>Okra-derived polysaccharides (ODPs) are among the most predominant and prominent complex compounds in okra (<em>Abelmoschus esculentus</em> L. Moench) and have caused increasing interest in the area of functional foods due to their wide applications. Although the literature on their pharmacological properties is still scanty, ODPs show structural diversity and related therapeutic actions, including alleviation of diabetes and related disorders including impaired lipid accumulation and cellular oxidation. In support of their therapeutic potential, these complex compounds confer low toxicity and relatively good bioavailability profiles. The extraction methods for these complex carbohydrates have a significant influence on their extraction yields, monosaccharide compositions, structural characteristics and pharmacological properties. In line with this, rhamnogalacturonan I, II and homogalacturonan were reported to be the most common types. The monomers constituting these complex polysaccharides from okra, including arabinose; galactose; galacturonic acid; glucose; glucuronic acid; mannose and rhamnose, were extracted by different techniques such as ultrasound-assisted, microwave-assisted, pressurized water and hot-water extractions. The present review comprehensively highlights the documented preclinical (<em>in vitro</em> and <em>in vivo</em>) studies on the ameliorative roles of ODPs against diabetes, oxidative stress and hyperlipidemia. However, clinical trials of ODPs against several disorders, including diabetes are yet to be documented. Therefore, these compounds are recommended for clinical investigations and more preclinical studies to further unveil their effectiveness and health-promoting functions against diabetes and related impairments such as cellular oxidation and defective lipid accumulations. Also, this will further establish these complex polysaccharides from okra as functional function agents with therapeutic properties.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888127","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}
引用次数: 0
Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects 脊髓性肌萎缩症(SMA):治疗策略、挑战和未来前景
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-01-20 DOI: 10.1016/j.prerep.2025.100031
Nikunja Kishor Mishra, Amiyakanta Mishra
{"title":"Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects","authors":"Nikunja Kishor Mishra,&nbsp;Amiyakanta Mishra","doi":"10.1016/j.prerep.2025.100031","DOIUrl":"10.1016/j.prerep.2025.100031","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal muscular atrophy (SMA) is a pediatric neuromuscular disorder that is distinguished by a defect or mutation in the survival motor neuron1 (SMN1) gene. It is a profoundly impactful childhood motor neuron disorder. In its most severe instances and in the absence of treatment, it tragically results in death within the initial two years of life. The disease is identified by muscle weakness and atrophy, predominating in proximal limb muscles. The most common mutation causing SMA is a homozygous deletion of exon 7 of SMN1. Recent therapeutic breakthroughs provide hope to families and patients by tackling the deficiency in SMN protein using gene therapy or alternative genetic manipulation techniques. It is becoming increasingly clear that none of these therapies alone will provide a cure for SMA. Therefore, the objective of the study is to review the correlation between SMN protein levels in tissues and the pathology of SMA. It also aims to provide a comprehensive review of the three currently licensed therapies for SMA, offering a brief overview of their preclinical and clinical studies that led to marketing authorization, coupled with real-world data analysis. Additionally, the study delves into discussions surrounding combined therapy, supplementary therapeutic approaches, challenges in clinical care, and future prospects for the treatment of SMA.</div></div><div><h3>Materials and methods</h3><div>The data for this study were gathered from a range of scholarly sources, including PubMed, Scopus, Springer and other relevant search engines. These sources were selected to ensure access to the latest and most comprehensive literature on SMA management, reflecting current treatment paradigms and advancements in the field.</div></div><div><h3>Results</h3><div>Both preclinical and clinical investigations of risdiplam, onasemnogene abeparvovec, and nusinersen have elucidated the restoration of functional SMN protein and its distribution in both peripheral tissues and central nervous system (CNS) motor neurons, representing a promising therapeutic benefit for the treatment of SMA.</div></div><div><h3>Discussion</h3><div>Clinical trials and real-world data provide robust support for the efficacy and safety profiles of the available drugs. Three therapies, nusinersen, onasemnogene abeparvovec, and risdiplam, aim to increase SMN levels in patients with SMA. Currently, an improvements in safety, efficacy, and motor function have been observed in combination therapies, such as the TOPAZ study (Nusinersen with Aptiegromab), the RESPOND study (Nusinersen with Onasemnogene abeparvovec) and the SAPPHIRE study (Aptiegromab alongside nusinersen or risdiplam).</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Maresin 2 reduces nociceptive and anxious-like behaviors inhibiting IL-1β in spinal and prefrontal cortex of type 1-diabetic rats 马瑞辛2减少1型糖尿病大鼠脊髓和前额叶皮层的伤害性和焦虑样行为,抑制IL-1β
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-06-04 DOI: 10.1016/j.prerep.2025.100045
Gabrielle Oliveira Guilherme , Matheus Vinicius Ferreira , Jaderson Pedro Bonfim da Costa , Bruno Liebl , Waldiceu Aparecido Verri , Janaína Menezes Zanoveli , Joice Maria da Cunha
{"title":"Maresin 2 reduces nociceptive and anxious-like behaviors inhibiting IL-1β in spinal and prefrontal cortex of type 1-diabetic rats","authors":"Gabrielle Oliveira Guilherme ,&nbsp;Matheus Vinicius Ferreira ,&nbsp;Jaderson Pedro Bonfim da Costa ,&nbsp;Bruno Liebl ,&nbsp;Waldiceu Aparecido Verri ,&nbsp;Janaína Menezes Zanoveli ,&nbsp;Joice Maria da Cunha","doi":"10.1016/j.prerep.2025.100045","DOIUrl":"10.1016/j.prerep.2025.100045","url":null,"abstract":"<div><div>Neuropathic pain and anxiety, or depression are common and debilitating complications of diabetes mellitus (DM), with few effective therapeutic options available. Given the significant role of neuroinflammation in the development and persistence of these complications, in addition to the known antinociceptive effects in inflammatory pain models induced by Maresin 2 (MaR2), a specialized pro-resolving mediator, we aimed to explore its therapeutic potential in mitigating mechanical hypersensitivity and anxiety/depressive-like behaviors in chemically induced DM male <em>Wistar</em> rats. Following the induction of experimental type-1 diabetes <em>mellitus</em> (T1DM) using streptozotocin (60 mg/kg, i.p.), rats were treated with MaR2 (1, 3, or 10 ng/rat, i.p.) or vehicle (VEH), starting 14 days after T1DM induction and continuing until the fourth week. Mechanical allodynia was assessed using the electronic Von Frey test (VFT) one day before STZ administration (baseline) and at multiple time points during MaR2 treatment. In the fourth week after STZ induction, behavioral assessments were performed using the open-field test (OFT), elevated plus-maze (EPM), and modified forced swimming test (MFST). Furthermore, samples from the spinal cord (L4-L6), hippocampus, and prefrontal cortex (pFC) were analyzed to measure levels of the pro-inflammatory cytokine IL-1β. MaR2 treatment significantly reduced mechanical allodynia (at all tested doses) and anxiety-like behavior (only at a dose of 3 ng) in diabetic rats, normalizing IL-1β expression in the pFC and spinal cord. However, it did not reverse depressive-like behavior. These results highlight MaR2's potential as a therapeutic agent for pain and anxiety in experimental diabetes, likely via its anti-inflammatory effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241028","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}
引用次数: 0
Exosomes and their roles in major depressive disorder: An overview of the research progress and perspectives 外泌体及其在重度抑郁症中的作用:研究进展与展望
Pharmacological Research - Reports Pub Date : 2025-03-01 Epub Date: 2025-03-29 DOI: 10.1016/j.prerep.2025.100035
Mei Tian , Shuo Yi , Zhao Li , Linzhi Li , Liwen Fang , Qin Ru
{"title":"Exosomes and their roles in major depressive disorder: An overview of the research progress and perspectives","authors":"Mei Tian ,&nbsp;Shuo Yi ,&nbsp;Zhao Li ,&nbsp;Linzhi Li ,&nbsp;Liwen Fang ,&nbsp;Qin Ru","doi":"10.1016/j.prerep.2025.100035","DOIUrl":"10.1016/j.prerep.2025.100035","url":null,"abstract":"<div><div>Major depressive disorder, a debilitating neurological disorder, remains enigmatic in its etiology, and current treatments are still inadequate. Therefore, unraveling its pathogenesis and discovering novel therapeutics is imperative. Exosomes are small extracellular nanoscale vesicles containing biomolecules, such as lipids, proteins, and nucleic acids, and have the ability to facilitate intercellular communication. Their potential as diagnostic indicators and therapeutic agents in conditions like autoimmune diseases, cardiovascular diseases, and cancer has been increasingly recognized. This review briefly introduces the relationship between exosomes and major depressive disorder, providing a systematic overview of how exosomal constituents contribute to the pathogenesis and progression. Furthermore, it underscores the significance of exosome research for advancing diagnostic and therapeutic approaches in major depressive disorder, offering a promising avenue for developing more effective clinical strategies.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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