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Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats 苯乙酰甘氨酸通过β2AR对大鼠脑缺血再灌注损伤的神经保护作用
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-01 DOI: 10.1016/j.jsps.2024.102210
Wenjie Hu , Xueyan Kuang , Yao Zhang , Yimin Luo , Litao Zhang
Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (P = 0.0024) and improved the neurobehavioral outcomes (P = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (P = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (P = 0.0018), IL-1β (P = 0.0310), and IL-6 (P = 0.0017), thereby reducing neuronal apoptosis (P = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (P = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation via β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings.
苯乙酰甘氨酸(Phenylacetylglycine, PAGly)是一种由苯丙氨酸在肠道中通过甘氨酸降解和偶联而产生的小分子。它与动脉粥样硬化的进展和对心肌的保护作用有关。本研究探讨了PAGly在大鼠脑缺血再灌注(I/R)损伤模型中的作用及其机制。结果显示,PAGly可明显减轻I/R损伤后脑梗死面积(P = 0.0024),改善I/R损伤后神经行为结局(P = 0.0149)。PAGly在结构上与儿茶酚胺相似,与小胶质细胞上的β2-肾上腺素能受体(β2AR)结合,但不改变这些受体的表达(P = 0.9137),而是抑制它们的活性。当β2AR参与小胶质细胞时,PAGly抑制TNF-α (P = 0.0018)、IL-1β (P = 0.0310)和IL-6 (P = 0.0017)的释放,从而减少神经元凋亡(P = 0.000003)。此外,在给予β 2ar特异性激动剂非诺特罗后,PAGly的保护作用减弱(P = 0.0055)。这些数据表明,PAGly通过β2AR抑制小胶质细胞炎症来减轻脑I/R损伤,突出了其作为治疗剂的潜力。这些发现使PAGly成为脑血管损伤治疗干预的有希望的候选药物,值得在临床环境中进一步探索。
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引用次数: 0
Mitochondrial dysfunction and mitophagy in ADHD: Cellular and molecular mechanisms
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.
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引用次数: 0
Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market
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.
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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
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.
{"title":"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","authors":"Xilinqiqige Bao ,&nbsp;Hanqing Li ,&nbsp;Jiayin Xu ,&nbsp;Xiaoqing Liu ,&nbsp;Runa A ,&nbsp;Jianming Chen ,&nbsp;Fengzheng Chen ,&nbsp;Nan Ya ,&nbsp;Rigula Sa","doi":"10.1016/j.jsps.2024.102215","DOIUrl":"10.1016/j.jsps.2024.102215","url":null,"abstract":"<div><div>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 <em>Monascus purpureus</em>-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 IC<sub>50</sub> 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.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102215"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164408","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
Analyzing trends and factors influencing price changes in public pooled drugs procurement system in Malaysia: Exploring market competition
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.
{"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
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.
{"title":"Metabolomics advances in chronic atrophic gastritis diagnosis and the integration of traditional Chinese medicine","authors":"Yanqun Luo ,&nbsp;Haiping Xue ,&nbsp;Hongyu Chen ,&nbsp;Ying Gao ,&nbsp;Guang Ji ,&nbsp;Tao Wu","doi":"10.1016/j.jsps.2024.102213","DOIUrl":"10.1016/j.jsps.2024.102213","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102213"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164410","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
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。
{"title":"Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies","authors":"Jiaming Bi ,&nbsp;Jiawei Zeng ,&nbsp;Xiaohao Liu ,&nbsp;Chuzi Mo ,&nbsp;Mingyan Yao ,&nbsp;Jing Zhang ,&nbsp;Peiyan Yuan ,&nbsp;Bo Jia ,&nbsp;Shuaimei Xu","doi":"10.1016/j.jsps.2024.102209","DOIUrl":"10.1016/j.jsps.2024.102209","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102209"},"PeriodicalIF":3.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720560","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
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。
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引用次数: 0
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Saudi Pharmaceutical Journal
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