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Mitochondrial dysfunction and mitophagy in ADHD: Cellular and molecular mechanisms ADHD的线粒体功能障碍和线粒体自噬:细胞和分子机制
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102212
Mohammed M. Almutairi , Abdulrahman Althekair , Fahad Almutairi , Mohammed Alatabani , Abdulaziz Alsaikhan
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent, age-inappropriate levels of inattention and/or hyperactive-impulsive behaviors. Previous investigations reveal that disrupted mitochondrial physiological homeostasis may contribute to ADHD. Several factors, including environmental factors, metabolic dysregulation, oxidative stress, neuroinflammation, and genetic abnormalities, can lead to mitochondrial dysfunction and impaired mitophagic pathways. Several investigations have been established a connection between mitochondrial dysfunction in ADHD and variations in monoaminergic genes, including dopamine receptors, dopamine transporters, norepinephrine transporters, serotonin transporters, and synaptic genes. The interplay between mitochondrial homeostasis and mitophagy in ADHD provides a promising research area and understating this interaction may help in the investigation of pathophysiological mechanisms and the innovation of novel therapeutic approaches to ADHD. Accordingly, this review explores previous studies that have investigated the mitochondrial abnormalities and dysfunctions in mitophagy at the cellular and molecular level in the development of ADHD.
注意缺陷多动障碍(ADHD)是一种神经发育障碍,其特征是持续的、与年龄不相称的注意力不集中和/或多动冲动行为。先前的研究表明,线粒体生理稳态的破坏可能导致ADHD。多种因素,包括环境因素、代谢失调、氧化应激、神经炎症和遗传异常,可导致线粒体功能障碍和线粒体自噬途径受损。一些研究已经建立了多动症线粒体功能障碍与单胺能基因变异之间的联系,包括多巴胺受体、多巴胺转运体、去甲肾上腺素转运体、血清素转运体和突触基因。注意缺陷多动障碍(ADHD)中线粒体稳态和线粒体自噬之间的相互作用提供了一个有前景的研究领域,了解这种相互作用可能有助于研究ADHD的病理生理机制和创新新的治疗方法。因此,本文回顾了以往在细胞和分子水平上研究ADHD发展过程中线粒体异常和线粒体自噬功能障碍的研究。
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引用次数: 0
Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market 沙特市场双氯芬酸分散片的药品质量
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102206
Samiah Alhabardi, Gamal Mahrous, Asma Alshahrani, Ehab Taha
The fundamental objective in developing any drug delivery approach is to achieve effective and safe therapy. Medications classified as generics are those that contain the same active ingredients and have the same quality as the reference medications. Several generic drugs are available on the market, all at a reasonable cost. In this study, the quality of Three generic brands of diclofenac dispersible tablets available in the Saudi market was assessed, namely: G1 and G2, and G3.
Except for the borderline performance of one generic formulation (G3), all formulations passed in vitro quality tests according to the United States Pharmacopoeia. According to the US Pharmacopoeia, every generic formulation passed in vitro quality tests, except for one generic formulation (G3) that performed inconclusively. All brands showed low weight variation, minimum weight loss in the friability test, and a rapid dispersion time of around 5 s. The chemical potency results demonstrated that all three brands complied with United States Pharmacopeia (USP) specifications, typically falling between 90% and 110% of the labeled amount. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with additional samples. G1 and G2 tablets passed the USP Acceptance criteria in stage one, and G3 tablets met the requirements in stage two. G1 showed the highest DE (%78.83), followed by G2 (%72.23), and G3 (%67.50). The G1 dissolution data, which showed the highest dissolution efficiency, were used as the reference product to calculate the similarity factor (f2 (ratio. G1 (Reference) and G2 with an f2 of (58.3) have similar dissolution profiles, however, the dissolution profiles for the two products may be considered similar without f2 calculation since more than 85% of the drug was dissolved within 15 min (SFDA Guidelines for Bioequivalence, Similarity while G3, with an f2 of (47.5) suggest a lack of similarity between the two dissolution profiles. This study highlights the importance of post-marketing evaluations of generic drug performance.
开发任何给药方法的基本目标都是实现有效和安全的治疗。被归类为仿制药的药物是指那些含有与参考药物相同的有效成分并具有相同质量的药物。市场上有几种仿制药,价格都很合理。本研究对沙特市场上销售的三种双氯芬酸分散片的质量进行了评价,分别是:G1、G2和G3。除了一个仿制制剂(G3)的临界性能外,所有制剂都通过了根据美国药典进行的体外质量测试。根据美国药典,每个仿制制剂都通过了体外质量测试,除了一个仿制制剂(G3)表现不确定。所有品牌均表现出较低的重量变化,易碎性试验中重量损失最小,分散时间在5 s左右。化学效力结果表明,所有三个品牌都符合美国药典(USP)规范,通常在标签量的90%至110%之间。G1和G2第一次尝试通过了内容均匀性测试。G3最初的含量均匀性测试不合格,但在补充样品后重新测试合格。G1、G2片通过第一阶段USP验收标准,G3片符合第二阶段要求。G1组DE最高(%78.83),其次为G2 (%72.23), G3(%67.50)。以溶出效率最高的G1溶出度数据作为参比,计算相似因子(f2)比。G1(参考文献)和G2 (f2为(58.3))具有相似的溶出度特征,然而,由于超过85%的药物在15分钟内溶解(SFDA生物等效性指南,相似性),因此在不计算f2的情况下,两种产品的溶出度特征可以被认为相似(SFDA生物等效性指南,相似性),而G3 (f2为(47.5))表明两种产品的溶出度特征缺乏相似性。本研究强调了仿制药上市后性能评价的重要性。
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引用次数: 0
Phyto-pharmacological wonders of genus Ficus: Ethnopharmacological insights and phytochemical treasures from natural products 榕树属植物药理学的奇迹:民族药理学的见解和天然产物的植物化学宝藏
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102211
Hasin Hasnat , Safaet Alam , Suriya Akter Shompa , Tanoy Saha , Fahmida Tasnim Richi , Md. Hemayet Hossain , Anika Zaman , Chunlai Zeng , Chuxiao Shao , Shuanghu Wang , Peiwu Geng , Abdullah Al Mamun
Natural products have perennially served as a cornerstone for the genesis of novel medicinal compounds. Most clinical therapeutics originate from ancestral herbal remedies and their formulations. Scholars and practitioners have always aimed to extract better remedies to treat various ailments. Genus Ficus, consisting of over 800 varieties, is a substantial tree native to tropical regions, characterized by its deciduous or evergreen nature. Various parts of this plant, including its bark, roots, leaves, fruit, and latex, find extensive use in treating a multitude of ailments. This review aims to update the ethnopharmacology, chemistry, and potential clinical applications of extracts and active ingredients from the ten most prevalent Ficus species. Major databases like Chemical Abstracts, ScienceDirect, SciFinder, PubMed, Scopus, etc. have all been used to generate references for this review. According to a thorough review of the literature, the many species of Ficus have a wide range of biological properties, including antioxidant, cytotoxic, antibacterial, antiviral, antifungal, anti-inflammatory, antiallergenic, antiasthmatic, larvicidal, antiplasmodial, antidiabetic, hepatoprotective and cardioprotective activity. A bunch of different secondary metabolites, such as flavonoids, saponins, alkaloids, tannins, phenolic acids, phytosterols, etc., were also reported, which can be responsible for exerted medicinal actions as well as play a crucial role in the field of new drug discovery and development. However, most species are missing well-controlled and double-blind clinical investigations. Thus, we still recommend further extensive exploration of this miraculous genus.
天然产物长期以来一直是新药物化合物产生的基石。大多数临床疗法起源于古老的草药疗法及其配方。学者和从业者一直致力于提取更好的药物来治疗各种疾病。榕树属,由800多个品种组成,是一种原产于热带地区的重要树木,其特点是落叶或常绿。这种植物的不同部分,包括它的树皮、根、叶、果实和乳胶,被广泛用于治疗多种疾病。本文综述了10种常见榕属植物的民族药理学、化学和活性成分的最新研究进展。主要的数据库如Chemical Abstracts, ScienceDirect, SciFinder, PubMed, Scopus等都被用来为本综述生成参考文献。根据文献综述,许多种类的榕树具有广泛的生物学特性,包括抗氧化、细胞毒、抗菌、抗病毒、抗真菌、抗炎、抗过敏、平喘、杀幼虫、抗疟原虫、抗糖尿病、保护肝脏和心脏的活性。黄酮类化合物、皂苷类化合物、生物碱类化合物、单宁类化合物、酚酸类化合物、植物甾醇类化合物等次生代谢物也被报道出来,它们具有重要的药理作用,在新药的发现和开发中发挥着重要作用。然而,大多数物种缺乏良好的对照和双盲临床研究。因此,我们仍然建议进一步广泛探索这个神奇的属。
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引用次数: 0
Identification and validation of lung adenocarcinoma (LUAD)-associated targets for monascin from the extracts of Monascus purpureus-fermented rice: Compound preparation, high-throughput genome sequencing and bioinformatics analysis 紫红曲霉发酵大米提取物中红曲霉素肺腺癌相关靶点的鉴定与验证:化合物制备、高通量基因组测序和生物信息学分析
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102215
Xilinqiqige Bao , Hanqing Li , Jiayin Xu , Xiaoqing Liu , Runa A , Jianming Chen , Fengzheng Chen , Nan Ya , Rigula Sa
Despite the remarkable bioactivities exhibited by monascin against several tumors, its therapeutic targets remain unexplored. In this study, our objective is to identify therapeutic targets based on the antitumor activity of monascin against lung adenocarcinoma (LUAD) A549 cells. The compound monascin was derived from extracts of Monascus purpureus-fermented rice. Its chemical structure was determined using spectroscopic methods, while the physicochemical properties of monascin were investigated through thermal behavior analysis. Herein, antitumor studies indicated that monascin significantly inhibited the viability of A549 cells, with an IC50 value of 2.05 μM; RNA-sequencing revealed 12 up-regulated and 29 down-regulated genes as differentially expressed genes (DEGs) for A549 cells in response to monascin; RT-qPCR validation supported the plausibility of the RNA-sequencing results. Moreover, utilizing data from the Cancer Genome Atlas (TCGA) database, univariate and multivariate Cox regression analyses provided evidence supporting GPR37 and FAM83A as potential candidate genes for predicting disease progression in LUAD patients. Additionally, the LASSO Cox regression and nomogram analyses confirmed that FAM83A and GPR37 genes had the potential to predict overall survival for LUAD patients. Finally, molecular docking studies suggested that monascin could interact with both GPR37 and FAM83A proteins through the hydrogen bonding and hydrophobic interactions; Western blotting assays indicated that monascin inhibited the expression levels of both GPR37 and FAM83A proteins. Overall, the clinical prognosis of GPR37 and FAM83A highlights the rationale for targeting these specific genes with monascin. Additionally, there findings provide compelling evidence for the polypharmacological properties of monascin against LUAD.
尽管红曲霉素对几种肿瘤具有显著的生物活性,但其治疗靶点仍未被探索。在这项研究中,我们的目的是基于monascin对肺腺癌(LUAD) A549细胞的抗肿瘤活性来确定治疗靶点。化合物红曲霉素是从红曲发酵大米中提取的。利用光谱学方法确定了其化学结构,通过热行为分析研究了monascin的理化性质。其中,抗肿瘤研究表明,monascin显著抑制A549细胞的活力,IC50值为2.05 μM;rna测序结果显示,A549细胞在monascin作用下有12个上调基因和29个下调基因作为差异表达基因(DEGs);RT-qPCR验证支持rna测序结果的合理性。此外,利用癌症基因组图谱(TCGA)数据库的数据,单因素和多因素Cox回归分析提供了支持GPR37和FAM83A作为预测LUAD患者疾病进展的潜在候选基因的证据。此外,LASSO Cox回归和nomogram分析证实FAM83A和GPR37基因具有预测LUAD患者总生存的潜力。最后,分子对接研究表明,monascin可以通过氢键和疏水相互作用与GPR37和FAM83A蛋白相互作用;Western blotting检测显示,monascin抑制GPR37和FAM83A蛋白的表达水平。总之,GPR37和FAM83A的临床预后突出了monascin靶向这些特异性基因的合理性。此外,这些发现为monascin抗LUAD的多药理学特性提供了令人信服的证据。
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引用次数: 0
Analyzing trends and factors influencing price changes in public pooled drugs procurement system in Malaysia: Exploring market competition 马来西亚公共集中药品采购制度价格变化趋势及影响因素分析:市场竞争探讨
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102214
Farahwahida Mohd Kasim , Ernieda Hatah , Lokhman Hakim Osman , Adliah Mhd Ali , Zaheer-Ud-Din Babar

Background

Pooled procurement is key to managing drug spending amid rising healthcare costs, but conclusive evidence on its sustained impact is lacking, driven by market competition.

Objective

This study aims to evaluate the trends and factors influencing the price changes of drugs awarded for pooled procurement systems utilizing a drug price index analysis.

Methods

This retrospective study involved a review of secondary data on public pooled procurement of drugs in Malaysia. Drugs were selected through purposive sampling and focused on eight therapeutic subgroups that showed significant patterns of expenditure and consumption. The observed data are retrieved from centralized contracts that were managed through a tendering process spanning from 2010 to 2021. A price index was computed to assess fluctuations in pharmaceutical pricing and market competition. To assess the influence of potential variables on market competition, quantified through the drug price index, a multiple linear regression analysis was utilized. The variables studied include product age, quantity index, bidding periods, therapeutic subgroups, and market competition elements such as types and number of competing products, dosage form, and types of procurements. The significance level was set at p < 0.05.

Results

The median price index, derived from the analysis of 88 drugs involved in 335 tenders over 10 years was 89.28 (range between 1.91 and 123.81). The observed trends indicated a consistent decline in the median drug price index throughout the bidding periods. The regression model, encompassing 19 selected variables, demonstrated the ability to predict the drug price index shown by the F-statistic (F (19, 315) = 68.022, p < 0.0005) with adj. R2 = 0.79. The coexistence of innovative or reference products and their generic or biosimilar equivalents in a market may promote competition. Five to eight competing products resulted in remarkably low drug prices.

Conclusion

Pooled procurement is one of the approaches to cost containment that is potentially subject to the dynamics of market competition. Time can be a limiting factor that hinders the realization of greater savings. Therefore, it is important to strike a delicate balance when considering regulatory measures, such as patents and barriers to market entry, in order to maintain a fair and competitive landscape within the industry.
在医疗成本不断上升的背景下,集中采购是管理药品支出的关键,但在市场竞争的推动下,缺乏关于其持续影响的确凿证据。目的利用药品价格指数分析方法,探讨集中采购制度下授予药品的价格变化趋势及影响因素。方法:本回顾性研究回顾了马来西亚公共集中采购药品的二手数据。通过有目的的抽样选择药物,并将重点放在8个治疗亚组上,这些亚组显示出显著的支出和消费模式。观察到的数据是从2010年至2021年通过招标过程管理的集中合同中检索的。计算价格指数以评估药品价格波动和市场竞争。为了评估潜在变量对市场竞争的影响,通过药品价格指数进行量化,采用多元线性回归分析。研究的变量包括产品年龄、数量指数、投标期、治疗亚组和市场竞争因素,如竞争产品的类型和数量、剂型和采购类型。显著性水平设为p <;0.05.结果10年335份招标中88种药品的价格指数中位数为89.28(1.91 ~ 123.81)。观察到的趋势表明,在整个招标期间,药品价格指数中位数持续下降。该回归模型包含19个选定变量,F统计量(F (19,315) = 68.022, p <;0.0005), R2 = 0.79。创新产品或参考产品及其仿制药或生物类似药在市场上共存可能会促进竞争。5到8种竞争产品导致药品价格非常低。结论集中采购是控制成本的一种方式,但可能受到市场竞争动态的影响。时间可能是阻碍实现更大节省的限制因素。因此,在考虑监管措施(如专利和市场进入壁垒)时,为了保持行业内公平和竞争的格局,重要的是要取得微妙的平衡。
{"title":"Analyzing trends and factors influencing price changes in public pooled drugs procurement system in Malaysia: Exploring market competition","authors":"Farahwahida Mohd Kasim ,&nbsp;Ernieda Hatah ,&nbsp;Lokhman Hakim Osman ,&nbsp;Adliah Mhd Ali ,&nbsp;Zaheer-Ud-Din Babar","doi":"10.1016/j.jsps.2024.102214","DOIUrl":"10.1016/j.jsps.2024.102214","url":null,"abstract":"<div><h3>Background</h3><div>Pooled procurement is key to managing drug spending amid rising healthcare costs, but conclusive evidence on its sustained impact is lacking, driven by market competition.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the trends and factors influencing the price changes of drugs awarded for pooled procurement systems utilizing a drug price index analysis.</div></div><div><h3>Methods</h3><div>This retrospective study involved a review of secondary data on public pooled procurement of drugs in Malaysia. Drugs were selected through purposive sampling and focused on eight therapeutic subgroups that showed significant patterns of expenditure and consumption.<!--> <!-->The observed data are retrieved from centralized contracts that were managed through a tendering process spanning from 2010 to 2021. A price index was computed to assess fluctuations in pharmaceutical pricing and market competition. To assess the influence of potential variables on market competition, quantified through the drug price index, a multiple linear regression analysis was utilized. The variables studied include product age, quantity index, bidding periods, therapeutic subgroups, and market competition elements such as types and number of competing products, dosage form, and types of procurements. The significance level was set at p &lt; 0.05.</div></div><div><h3>Results</h3><div>The median price index, derived from the analysis of 88 drugs involved in 335 tenders over 10 years was 89.28 (range between 1.91 and 123.81). The observed trends indicated a consistent decline in the median drug price index throughout the bidding periods. The regression model, encompassing 19 selected variables, demonstrated the ability to predict the drug price index shown by the F-statistic (F (19, 315) = 68.022, p &lt; 0.0005) with adj. R<sup>2</sup> = 0.79. The coexistence of innovative or reference products and their generic or biosimilar equivalents in a market may promote competition. Five to eight competing products resulted in remarkably low drug prices.</div></div><div><h3>Conclusion</h3><div>Pooled procurement is one of the approaches to cost containment that is potentially subject to the dynamics of market competition. Time can be a limiting factor that hinders the realization of greater savings. Therefore, it is important to strike a delicate balance when considering regulatory measures, such as patents and barriers to market entry, in order to maintain a fair and competitive landscape within the industry.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102214"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolomics advances in chronic atrophic gastritis diagnosis and the integration of traditional Chinese medicine 代谢组学在慢性萎缩性胃炎诊断及中西医结合中的研究进展
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102213
Yanqun Luo , Haiping Xue , Hongyu Chen , Ying Gao , Guang Ji , Tao Wu
Chronic atrophic gastritis (CAG) is a prevalent digestive system disorder characterized by the recurrent damage to the gastric mucosal epithelium, with the potential to progress to gastric cancer. Traditional Chinese medicine (TCM), with its holistic perspective and treatment modalities grounded in syndrome differentiation, provides a distinctive approach to both the prevention and treatment of CAG. This review aims to encapsulate the recent advancements in the application of metabolomics to the diagnosis, pathogenesis, and the TCM-based prevention and treatment of CAG, offering novel insights into the therapeutic and preventive strategies for the disease. A systematic analysis was performed on the literature from 2013 to 2024, focusing on studies that utilized metabolomics to investigate the effects of TCM on CAG. The data was sourced from reputable electronic databases including PubMed and Web of Science. The review emphasizes the utility of metabolomics in identifying biomarkers and metabolic pathways associated with CAG and illustrates the capacity of TCM to influence and ameliorate CAG conditions through various mechanisms, including the regulation of gut microbiota and modulation of specific metabolic pathways. This review presents that metabolomics can offer new perspectives for the application of TCM in CAG management, demonstrating significant potential in elucidating the pathogenesis of CAG and in identifying potential therapeutic targets. The convergence of TCM with metabolomics heralds a promising avenue for the personalized treatment of CAG.
慢性萎缩性胃炎(CAG)是一种常见的消化系统疾病,其特征是胃粘膜上皮的反复损伤,有发展为胃癌的潜力。中医以其整体视角和基于辨证论治的治疗方式,为CAG的预防和治疗提供了独特的方法。本文综述了近年来代谢组学在CAG诊断、发病机制和中医防治中的应用进展,为CAG的治疗和预防策略提供新的见解。对2013 - 2024年的文献进行系统分析,重点关注利用代谢组学研究中药对CAG影响的研究。数据来源于著名的电子数据库,包括PubMed和Web of Science。这篇综述强调了代谢组学在识别与CAG相关的生物标志物和代谢途径方面的应用,并说明了中医药通过各种机制影响和改善CAG状况的能力,包括调节肠道微生物群和调节特定的代谢途径。本文综述了代谢组学可以为中医在CAG治疗中的应用提供新的视角,在阐明CAG的发病机制和确定潜在的治疗靶点方面具有重要的潜力。中医与代谢组学的融合预示着CAG个性化治疗的前景广阔。
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引用次数: 0
Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies 老年性骨病的药物输送:从治疗目标到常见和新兴治疗策略
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-24 DOI: 10.1016/j.jsps.2024.102209
Jiaming Bi , Jiawei Zeng , Xiaohao Liu , Chuzi Mo , Mingyan Yao , Jing Zhang , Peiyan Yuan , Bo Jia , Shuaimei Xu
With the accumulation of knowledge on aging, people have gradually realized that among the many factors that cause individual aging, the accumulation of aging cells is an essential cause of organ degeneration and, ultimately, age-related diseases. Most cells present in the bone microenvironment gradually age over time, leading to an imbalance of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis. This imbalance contributes to age-related bone loss and the development of age-related bone diseases, such as osteoporosis. Bone aging can prolong the lifespan and delay the development of age-related diseases. Nanoparticles have controllable and stable physical and chemical properties and can precisely target different tissues and organs. By preparing multiple easily modified and biocompatible nanoparticles as different drug delivery carriers, specifically targeting various diseased tissues for controlled-release and sustained-release administration, the delivery efficiency of drugs can be significantly improved, and the toxicity and side effects of drugs can be substantially reduced, thereby improving the therapeutic effect of age-related bone diseases. In addition, other novel anti-aging strategies (such as stem cell exosomes) also have significant scientific and practical significance in anti-aging research on age-related bone diseases. This article reviews the research progress of various nano-drug-loaded particles and emerging anti-aging methods for treating age-related bone diseases, offering new insights and directions for precise targeted clinical therapies.
随着衰老知识的不断积累,人们逐渐认识到,在导致个体衰老的诸多因素中,衰老细胞的积累是器官退化并最终导致老年相关疾病的重要原因。存在于骨骼微环境中的大多数细胞会随着时间的推移逐渐衰老,从而导致骨生成、破骨细胞生成、脂肪生成和软骨生成的失衡。这种失衡会导致与年龄相关的骨质流失,并引发与年龄相关的骨病,如骨质疏松症。骨骼老化可以延长寿命,延缓老年性疾病的发生。纳米粒子具有可控、稳定的物理和化学特性,可精确靶向不同的组织和器官。通过制备多种易修饰、生物相容性好的纳米颗粒作为不同的给药载体,特异性地靶向各种病变组织进行控释和缓释给药,可显著提高药物的给药效率,大幅降低药物的毒性和副作用,从而提高老年性骨病的治疗效果。此外,其他新型抗衰老策略(如干细胞外泌体)在老年相关骨病的抗衰老研究中也具有重要的科学和现实意义。本文综述了各种纳米载药颗粒和新兴抗衰老方法治疗老年性骨病的研究进展,为临床精准靶向治疗提供了新的见解和方向。
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引用次数: 0
Impacts of Anabolic-androgenic steroid supplementation on female health and offspring: Mechanisms, side effects, and medical perspectives 合成代谢雄性类固醇补充剂对女性健康和后代的影响:机制、副作用和医学视角
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-22 DOI: 10.1016/j.jsps.2024.102205
Beatriz Menegate Santos , Jessica Peres Alves de Souza , Luísa Rodrigues de Paula Goulart , Jéssica Castro Pereira Petrine , Fernando Henrique Ferrari Alves , Bruno Del Bianco-Borges
The increasing prevalence of Anabolic–androgenic steroids (AAS) among women, driven by the pursuit of improved body aesthetics, characterized by higher lean mass and reduced adipose tissue, raises significant health concerns, particularly due to the limited knowledge regarding their effects on the female organism. Prolonged use and/or high doses of AAS are linked to various harmful side effects, including mood changes, psychiatric disorders, voice deepening, clitoromegaly, menstrual irregularities, and cardiovascular complications, prompting medical societies to discourage their widespread use due to insufficient evidence supporting their safety and efficacy. Studies in female rodents have shown that AAS can lead to increased aggression, inflammation, reduced neuronal density, and negative impacts on the myocardium and blood vessels. Additionally, maternal administration of androgens during pregnancy can adversely affect offspring’s reproductive, neuronal, and metabolic health, resulting in long-term impairments. The complexity of the mechanisms underlying AAS effects, and their potential genotoxicity remains poorly understood. This review aims to elucidate the various ways in which AAS can impact female physiology and that of their offspring, highlight commonly used anabolic substances, and discuss the positions of medical societies regarding AAS use.
女性越来越普遍地使用合成代谢雄性类固醇(AAS),这是由于她们追求以增加瘦体重和减少脂肪组织为特征的身体美感,这引起了人们对健康的极大关注,特别是由于人们对其对女性机体的影响了解有限。长期使用和(或)高剂量的 AAS 与各种有害的副作用有关,包括情绪变化、精神失常、声音加深、阴蒂肥大、月经不调和心血管并发症,由于没有足够的证据支持其安全性和有效性,医学协会不鼓励广泛使用。对雌性啮齿动物的研究表明,AAS 可导致攻击性增强、炎症、神经元密度降低以及对心肌和血管的负面影响。此外,母体在怀孕期间服用雄激素会对后代的生殖、神经元和新陈代谢健康产生不利影响,导致长期损害。人们对 AAS 作用机制的复杂性及其潜在的基因毒性仍然知之甚少。本综述旨在阐明 AAS 影响女性及其后代生理机能的各种方式,重点介绍常用的同化物质,并讨论医学会对使用 AAS 的立场。
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引用次数: 0
Bioadhesive hybrid system of niosomes and pH sensitive in situ gel for itraconazole ocular delivery: Dual approach for efficient treatment of fungal infections 用于伊曲康唑眼部给药的niosomes和pH敏感原位凝胶生物黏附混合系统:高效治疗真菌感染的双重方法
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-22 DOI: 10.1016/j.jsps.2024.102208
Mohamed M. Badran , Areej Alsubaie , Mounir M. Salem Bekhit , Abdullah H. Alomrani , Aliyah Almomen , Mohamed Abbas Ibrahim , Doaa Hasan Alshora
Itraconazole (ITZ) is a highly effective antifungal agent. However, its oral application is associated with systemic toxicity and poor topical use. The present study aims to improve the antifungal activity of ITZ by loading it into bioadhesive niosomes. This approach is considered to enhance the ocular permeation of ITZ, thereby boosting its efficacy against fungal infections. Therefore, it was encapsulated into niosomes (F1) and subsequently coated with hyaluronic acid (HA; F2), chitosan (CS; F3), or a bilayer of CS/HA (F4). In addition, they were further incorporated into pH-sensitive in situ gels. This dual approach is expected to increase the amount of corneal-permeated ITZ, facilitating more effective management of ocular fungal infection.
Firstly, the niosomes were prepared by hydrating proniosomes using span 60, cholesterol, and phospholipid. ITZ-niosomes showed an increase in vesicle size from 165.5 ± 3.4 (F1) to 378.2 ± 7.2 nm (F3). The zeta potential varied within −20.9 ± 2.1 (F1), −29.5 ± 3.1 (F2), 32.3 ± 1.9 (F3), and 22.6 ± 1.3 mV (F4). The high EE% values ranged from 78.1 ± 2.2 % to 86.6 ± 2.9 %. Regarding ITZ release, F1 demonstrated a high release profile, whereas bioadhesive niosomes showed sustained release patterns. Furthermore, in situ gels containing niosomes displayed excellent gelling capacity and viscosity. Remarkably, F3 laden-in situ gels (F3-ISG) demonstrated the highest ex vivo corneal permeability of ITZ and antifungal activity with a safety effect. These results indicate that F3-ISG presents a promising strategy for boosting the ocular delivery of ITZ, that could help in treating ocular fungal infections.
伊曲康唑(ITZ)是一种高效的抗真菌剂。然而,其口服应用具有全身毒性,局部使用效果不佳。本研究旨在通过将伊曲康唑装入生物粘附性iosomes 来提高其抗真菌活性。这种方法被认为能增强 ITZ 的眼部渗透,从而提高其对真菌感染的疗效。因此,先将 ITZ 包封在 niosomes(F1)中,然后用透明质酸(HA;F2)、壳聚糖(CS;F3)或 CS/HA 双层(F4)包覆。此外,它们还被进一步加入对 pH 值敏感的原位凝胶中。这种双重方法有望增加角膜渗透 ITZ 的数量,从而更有效地治疗眼部真菌感染。首先,使用 span 60、胆固醇和磷脂水合原代物,制备出了新生物体。ITZ-niosomes的囊泡尺寸从165.5 ± 3.4(F1)增至378.2 ± 7.2 nm(F3)。zeta 电位在 -20.9 ± 2.1 (F1)、-29.5 ± 3.1 (F2)、32.3 ± 1.9 (F3) 和 22.6 ± 1.3 mV (F4) 范围内变化。高 EE% 值从 78.1 ± 2.2 % 到 86.6 ± 2.9 % 不等。在 ITZ 释放方面,F1 显示出较高的释放曲线,而生物黏附性iosomes 则显示出持续释放模式。此外,含有niosomes的原位凝胶显示出优异的胶凝能力和粘度。值得注意的是,含有 F3 的原位凝胶(F3-ISG)显示出最高的 ITZ 体内外角膜渗透性和抗真菌活性,并具有安全效应。这些结果表明,F3-ISG 是促进 ITZ 眼部给药的一种有前途的策略,有助于治疗眼部真菌感染。
{"title":"Bioadhesive hybrid system of niosomes and pH sensitive in situ gel for itraconazole ocular delivery: Dual approach for efficient treatment of fungal infections","authors":"Mohamed M. Badran ,&nbsp;Areej Alsubaie ,&nbsp;Mounir M. Salem Bekhit ,&nbsp;Abdullah H. Alomrani ,&nbsp;Aliyah Almomen ,&nbsp;Mohamed Abbas Ibrahim ,&nbsp;Doaa Hasan Alshora","doi":"10.1016/j.jsps.2024.102208","DOIUrl":"10.1016/j.jsps.2024.102208","url":null,"abstract":"<div><div>Itraconazole (ITZ) is a highly effective antifungal agent. However, its oral application is associated with systemic toxicity and poor topical use. The present study aims to improve the antifungal activity of ITZ by loading it into bioadhesive niosomes. This approach is considered to enhance the ocular permeation of ITZ, thereby boosting its efficacy against fungal infections. Therefore, it was encapsulated into niosomes (F1) and subsequently coated with hyaluronic acid (HA; F2), chitosan (CS; F3), or a bilayer of CS/HA (F4). In addition, they were further incorporated into pH-sensitive <em>in situ</em> gels. This dual approach is expected to increase the amount of corneal-permeated ITZ, facilitating more effective management of ocular fungal infection.</div><div>Firstly, the niosomes were prepared by hydrating proniosomes using span 60, cholesterol, and phospholipid. ITZ-niosomes showed an increase in vesicle size from 165.5 ± 3.4 (F1) to 378.2 ± 7.2 nm (F3). The zeta potential varied within −20.9 ± 2.1 (F1), −29.5 ± 3.1 (F2), 32.3 ± 1.9 (F3), and 22.6 ± 1.3 mV (F4). The high EE% values ranged from 78.1 ± 2.2 % to 86.6 ± 2.9 %. Regarding ITZ release, F1 demonstrated a high release profile, whereas bioadhesive niosomes showed sustained release patterns. Furthermore, <em>in situ</em> gels containing niosomes displayed excellent gelling capacity and viscosity. Remarkably, F3 laden-<em>in situ</em> gels (F3-ISG) demonstrated the highest <em>ex vivo</em> corneal permeability of ITZ and antifungal activity with a safety effect. These results indicate that F3-ISG presents a promising strategy for boosting the ocular delivery of ITZ, that could help in treating ocular fungal infections.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102208"},"PeriodicalIF":3.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Model-informed drug discovery and development approaches to inform clinical trial design and regulatory decisions: A primer for the MENA region 以模型为依据的药物发现和开发方法,为临床试验设计和监管决策提供信息:中东和北非地区入门指南
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-21 DOI: 10.1016/j.jsps.2024.102207
Mohammed S. Alasmari , Salwa Albusaysi , Marwa Elhefnawy , Ali M. Ali , Khalid Altigani , Mohammed Almoslem , Mohammed Alharbi , Jahad Alghamdi , Abdullah Alsultan
Model-Informed Drug Discovery and Development (MID3) represents a transformative approach in pharmaceutical research, integrating quantitative models to inform and optimize decision-making throughout the drug development process. This review explores the current applications, challenges, and future prospects of MID3 within the Middle East and North Africa (MENA) region. By leveraging local data and advanced computational techniques, MID3 has the potential to significantly enhance the efficiency and success rates of drug development tailored to regional health priorities. We discussed successful case studies of applying MID3 at different phases of drug development and clinical trials. Furthermore, we emphasized the critical need for MENA countries to embrace MID3 by investing in workforce training, aligning regulatory frameworks, and fostering collaborative research initiatives. This call to action underscores the importance of a robust MID3 ecosystem, urging policymakers, academic institutions, and industry stakeholders to prioritize and support its integration into the MENA region’s healthcare.
模型信息药物发现与开发 (MID3) 是制药研究领域的一种变革性方法,它整合了定量模型,为整个药物开发过程提供信息并优化决策。本综述探讨了 MID3 在中东和北非地区的当前应用、挑战和未来前景。通过利用本地数据和先进的计算技术,MID3 有可能显著提高针对地区健康优先事项的药物开发效率和成功率。我们讨论了在药物开发和临床试验的不同阶段应用 MID3 的成功案例研究。此外,我们还强调中东和北非国家亟需通过投资劳动力培训、调整监管框架和促进合作研究计划来接受 MID3。这一行动呼吁强调了建立一个强大的 MID3 生态系统的重要性,敦促政策制定者、学术机构和行业利益相关者优先考虑并支持将 MID3 纳入中东和北非地区的医疗保健领域。
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引用次数: 0
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Saudi Pharmaceutical Journal
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