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Navigating Scientific Peer Review with ChatGPT: Ally or Adversary? 使用 ChatGPT 浏览科学同行评审:盟友还是对手?
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-29 DOI: 10.34172/apb.2024.053
ArunSundar MohanaSundaram
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引用次数: 0
Harnessing the Therapeutic Potential of Mesenchymal Stem Cells in Cancer Treatment. 利用间充质干细胞在癌症治疗中的治疗潜力。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.052
Parisa Kangari, Reza Salahlou, Somayeh Vandghanooni

Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton's jelly (WJ), adipose tissue and dental pulp (DP). These cells are capable of differentiating into the osteoblasts, chondrocytes, and adipocytes. Due to the unique characteristics of MSCs such as paracrine effects, immunomodulation, tumor-tropism, and migration, they are considered promising candidates for cancer therapeutics. Currently, MSCs are an excellent living carrier for delivery of therapeutic genes and chemical agents to target tumor sites. Also, exosomes, the most important extracellular vesicle released from MSCs, act as a strong cell-free tool for cancer therapeutics. MSCs can prevent cancer progression by inhibiting several signaling pathways, such as wnt/β-catenin and PI3K/AKT/mTOR. However, there are several challenges associated with the use of MSCs and their exosomes in the field of therapy that need to be considered. This review explores the significance of MSCs in cell-based therapy, focusing on their homing properties and immunomodulatory characteristics. It also examines the potential of using MSCs as carriers for delivery of anticancer agents and their role in modulating the signal transduction pathways of cancer cells.

癌症是一种复杂的疾病,被认为是导致全球死亡的主要原因之一。虽然已经制定了各种癌症治疗策略,但一些问题限制了治疗效果。近几十年来,为了找到有效的治疗方案,研究人员广泛关注干细胞在抑制癌症方面的能力。间充质干细胞(MSCs)是一种多能基质细胞,可从骨髓(BM)、胎盘、脐带(UC)、月经血、沃顿果冻(WJ)、脂肪组织和牙髓(DP)等各种来源中广泛提取。这些细胞能够分化成成骨细胞、软骨细胞和脂肪细胞。由于间充质干细胞具有旁分泌效应、免疫调节、肿瘤向性和迁移等独特特性,因此被认为是癌症治疗的理想候选细胞。目前,间充质干细胞是将治疗基因和化学制剂输送到肿瘤靶点的绝佳活载体。此外,间充质干细胞释放的最重要的细胞外囊泡--外泌体也是一种强大的无细胞癌症治疗工具。间充质干细胞可通过抑制多种信号通路(如 wnt/β-catenin 和 PI3K/AKT/mTOR)来防止癌症进展。然而,在治疗领域使用间叶干细胞及其外泌体还面临着一些挑战,需要加以考虑。这篇综述探讨了间充质干细胞在细胞疗法中的意义,重点关注其归宿特性和免疫调节特性。它还探讨了将间充质干细胞用作输送抗癌药物载体的潜力,以及间充质干细胞在调节癌细胞信号转导途径中的作用。
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引用次数: 0
Sex Differences on the Pharmacokinetics of Drugs for Children with Chronic Kidney Disease: A Narrative Review. 慢性肾病儿童药物药代动力学的性别差异:叙述性综述。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-30 DOI: 10.34172/apb.2024.056
Toktam Faghihi, Farahnak Assadi

Effective optimal pharmacotherapy requires a comprehensive understanding of the drug's pharmacokinetic properties. Chronic kidney disease (CKD) influences medication pharmacokinetics. However, whether sex differences exist in the pharmacokinetics of drugs for children with CKD is unknown. The primary aim of this article was to evaluate the effect of sex on pharmacokinetics of drugs commonly used for CKD treatment in children. Secondary outcome was to address the impact of sex in CKD disease progression. Electronic databases, PubMed, EMBASE, Google Scholar, and Web of Science were searched from inception, using Mesh terms in English for sex differences in the pharmacokinetics of drugs in children with CKD. No studies have documented sex-related differences in the pharmacokinetics of drugs for the treatment of CKD in children. As a consequence, it is difficult to predict the effect of sex on pharmacokinetics by extrapolating data from adult studies to children. Evidence to date suggests that girls generally have a higher prevalence and disease progression of CKD when compared to boys regardless of age. Understanding the pharmacokinetics and pharmacodynamics of drugs provides practical consideration for dosing optimal medication regimens. Future kinetic studies are needed evaluating the effect of sex on the pharmacokinetics and pharmacodynamics of drugs in children with CKD.

有效优化药物治疗需要全面了解药物的药代动力学特性。慢性肾脏病(CKD)会影响药物的药代动力学。然而,CKD 患儿的药代动力学是否存在性别差异尚不清楚。本文的主要目的是评估性别对儿童 CKD 治疗常用药物药代动力学的影响。次要结果是探讨性别对 CKD 疾病进展的影响。从一开始,我们就使用 Mesh 英文术语在 PubMed、EMBASE、Google Scholar 和 Web of Science 等电子数据库中搜索了 CKD 儿童药物代谢动力学中的性别差异。没有任何研究记录了治疗儿童慢性肾脏病药物的药代动力学中与性别相关的差异。因此,很难通过将成人研究数据外推至儿童来预测性别对药物代谢动力学的影响。迄今为止的证据表明,与男孩相比,无论年龄大小,女孩的 CKD 患病率和疾病进展率普遍较高。了解药物的药代动力学和药效学可为最佳用药方案的剂量提供切实可行的考虑。未来需要开展动力学研究,评估性别对 CKD 儿童药物的药代动力学和药效学的影响。
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引用次数: 0
The Effect of Statin Therapy on Bone Metabolism Markers and Mineral Density: Aa GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. 他汀类药物治疗对骨质代谢标志物和矿物质密度的影响:经 GRADE 评估的系统综述和随机对照试验的剂量反应元分析》。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.051
Seyyed Mostafa Arabi, Mahla Chambari, Leila Sadat Bahrami, Ali Jafari, Hossein Bahari, Željko Reiner, Amirhossein Sahebkar

Purpose: Statin therapy is widely used for the management of dyslipidemia and the prevention of cardiovascular diseases (CVDs). However, there is a growing concern about its potential effects on bone metabolism markers and mineral density. The aim of this systematic review and meta-analysis was to investigate the effect of statin therapy on these parameters.

Methods: PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords.

Results: After screening 2450 articles, 16 studies that met the inclusion criteria were included, of which 12 randomized controlled trials (RCTs) were used for meta-analysis. The findings showed that statin therapy significantly reduced bone-specific alkaline phosphatase (B-ALP) levels (WMD=-1.1 U/L; 95% CI -2.2 to -0.07; P=0.03; I2=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm2; 95% CI -0.08 to -0.04; P<0.001; I2=97.7%, P<0.001). However, this treatment did not have a significant effect on osteocalcin, serum C-terminal peptide of type I collagen (S-CTx), serum N-telopeptides of type I collagen (NTx) concentration, or overall fracture risk.

Conclusion: This systematic review and meta-analysis provide evidence that statin therapy is associated with a significant reduction in B-ALP levels and BMD at different sites of the skeleton. Further studies are needed to investigate the long-term effects of statin therapy on bone health and to identify the potential underlying mechanisms.

目的:他汀类药物疗法被广泛用于治疗血脂异常和预防心血管疾病(CVDs)。然而,人们越来越关注他汀类药物对骨代谢指标和矿物质密度的潜在影响。本系统综述和荟萃分析旨在研究他汀类药物治疗对这些参数的影响:方法:使用 MESH 术语和关键词检索了 PubMed/MEDLINE、Scopus 和 Clarivate Analytics Web of Science 数据库,检索期从开始到 2023 年 8 月:结果:在筛选了2450篇文章后,纳入了16项符合纳入标准的研究,其中12项随机对照试验(RCT)被用于荟萃分析。研究结果表明,他汀类药物治疗可显著降低骨特异性碱性磷酸酶(B-ALP)水平(WMD=-1.1 U/L;95% CI -2.2 to -0.07;P=0.03;I2=0%)和不同部位的骨矿物质密度(BMD)(WMD=-0.06 g/cm2;95% CI -0.08 to -0.04;P2=97.7%;PC):本系统综述和荟萃分析提供的证据表明,他汀类药物治疗与 B-ALP 水平和骨骼不同部位 BMD 的显著降低有关。需要进一步研究他汀类药物治疗对骨骼健康的长期影响,并找出潜在的内在机制。
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引用次数: 0
Cytobiological Alterations Induced by Celecoxib as an Anticancer Agent for Breast and Metastatic Breast Cancer. 作为乳腺癌和转移性乳腺癌抗癌剂的塞来昔布诱导的细胞生物学变化
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-29 DOI: 10.34172/apb.2024.055
Maher Monir Akl, Amr Ahmed

Breast cancer remains a formidable public health challenge worldwide, characterized by its initiation within the breast's diverse tissues, particularly the ducts and lobules. This malignancy is predominantly categorized into three subtypes based on receptor status and genetic markers: hormone receptor-positive, HER2-positive, and triple-negative. Each subtype exhibits distinct biological behaviors and responses to treatment, which significantly influence the prognosis and management strategies. The development and metastatic spread of breast cancer are complex processes mediated by interactions between tumor cells and the host microenvironment, involving various cellular and molecular mechanisms. This review highlights the potential therapeutic role of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addressing the multifaceted aspects of breast cancer progression. Specifically, celecoxib modulates angiogenesis by reducing the levels of vascular endothelial growth factor (VEGF) through decreased PGE2 production, enhances the immune response by alleviating PGE2-mediated immunosuppression, and inhibits metastasis by limiting the activity of matrix metalloproteinases (MMPs). These mechanisms collectively hinder tumor growth, immune evasion, and metastatic spread. By synthesizing recent findings and analyzing the impact of celecoxib on these pathways, this paper seeks to delineate the integrated approaches necessary for managing metastatic breast cancer effectively.

乳腺癌仍然是全球公共卫生面临的一项严峻挑战,其特点是起病于乳房的不同组织,尤其是乳腺导管和乳腺小叶。这种恶性肿瘤主要根据受体状态和遗传标记分为三种亚型:激素受体阳性、HER2 阳性和三阴性。每种亚型都表现出不同的生物学行为和对治疗的反应,这对预后和治疗策略有重大影响。乳腺癌的发展和转移扩散是肿瘤细胞与宿主微环境相互作用的复杂过程,涉及各种细胞和分子机制。本综述强调了塞来昔布(一种选择性环氧化酶-2(COX-2)抑制剂)在解决乳腺癌进展的多方面问题中的潜在治疗作用。具体来说,塞来昔布通过减少 PGE2 的产生,降低血管内皮生长因子(VEGF)的水平,从而调节血管生成;通过减轻 PGE2 介导的免疫抑制,增强免疫反应;通过限制基质金属蛋白酶(MMPs)的活性,抑制转移。这些机制共同阻碍了肿瘤的生长、免疫逃避和转移扩散。通过综合最新研究结果并分析塞来昔布对这些途径的影响,本文试图阐明有效治疗转移性乳腺癌所需的综合方法。
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引用次数: 0
PGV-1 Causes Disarrangement of Spindle Microtubule Organization Resulting in Aberrant Mitosis in HLF and HuH6 Cells Associated with Altered MYCN Status. PGV-1 导致纺锤体微管组织混乱,导致 HLF 和 HuH6 细胞有丝分裂异常,并与 MYCN 状态改变有关。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.34172/apb.2024.058
Nadzifa Nugraheni, Ummi Maryam Zulfin, Beni Lestari, Novia Permata Hapsari, Muthi Ikawati, Rohmad Yudi Utomo, Yusuke Suenaga, Yoshitaka Hippo, Edy Meiyanto

Purpose: The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib.

Methods: We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay.

Results: PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA.

Conclusion: PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.

目的:HLF和HuH-6细胞系代表肝细胞癌(HCC),其染色体含量的不同可能导致不同的药物反应。在此,PGV-1 试图挑战其对 HLF 和 HuH-6 的生长抑制作用,并追踪其与索拉非尼相比的分子靶点作用机制:方法:采用MTT细胞毒性试验、集落形成试验、流式细胞术分析、免疫荧光试验和Western blot试验:结果:PGV-1 对 HLF 和 HuH-6 具有细胞毒性作用,IC-50 值分别为 1 µM 和 2 µM,而索拉非尼的细胞毒性较弱,IC-50 值分别为 5 µM 和 8 µM。PGV-1 能永久抑制细胞生长,而索拉非尼则不能。索拉非尼没有改变两种细胞的细胞周期图谱,但 PGV-1 使细胞停滞在 G2/M,具有衰老细胞和有丝分裂紊乱的特征。PGV-1 和索拉非尼在下调 p-EGFR 方面表现出相同的效果,这表明这两种化合物在表皮生长因子受体活化或作为酪氨酸激酶抑制剂方面具有相同的靶点。PGV-1抑制了HuH-6和HLF细胞中MYCN的表达,但稳定了cMYC-T58,这表明即使MYCN被下调,细胞仍保持着cMYC的活性形式。在这方面,PGV-1 还能稳定 PLK-1 和 AurA 的表达:结论:与索拉非尼相比,PGV-1具有更强的细胞毒性。结论:与索拉非尼相比,PGV-1具有更强的细胞毒性,MYCN表达越低,PGV-1的细胞毒性作用越强。通过抑制表皮生长因子受体,PGV-1可抑制两种细胞在有丝分裂期的细胞周期进展,并稳定PLK-1和AurA,这与抑制MYCN表达有关。
{"title":"PGV-1 Causes Disarrangement of Spindle Microtubule Organization Resulting in Aberrant Mitosis in HLF and HuH6 Cells Associated with Altered MYCN Status.","authors":"Nadzifa Nugraheni, Ummi Maryam Zulfin, Beni Lestari, Novia Permata Hapsari, Muthi Ikawati, Rohmad Yudi Utomo, Yusuke Suenaga, Yoshitaka Hippo, Edy Meiyanto","doi":"10.34172/apb.2024.058","DOIUrl":"10.34172/apb.2024.058","url":null,"abstract":"<p><strong>Purpose: </strong>The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib.</p><p><strong>Methods: </strong>We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay.</p><p><strong>Results: </strong>PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA.</p><p><strong>Conclusion: </strong>PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566534","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
Novel Advances in Cell-Free Therapy for Premature Ovarian Failure (POF): A Comprehensive Review. 无细胞疗法治疗卵巢早衰(POF)的新进展:全面回顾。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.34172/apb.2024.059
Yahya Yahyavi, Niloufar Kheradi, Abbas Karimi, Abbas Ebrahimi-Kalan, Fatemeh Ramezani, Soudabe Yousefi, Shirin Teymouri Nobari, Hourieh Sadrekarimi, Mohammad Nouri, Mahdi Edalati

Premature ovarian failure (POF), is a condition characterized by the early decline of ovulation function. POF is a complex disorder that can be caused by various factors, and the idiopathic form represents a significant proportion of POF patients. Hormone replacement therapy (HRT) is currently considered the first-line treatment for POF. This review aims to provide a comprehensive overview of recent advancements in platelet-rich plasma (PRP), in vitro activation (IVA), stem cell therapy, exosome therapy, microRNAs, and mitochondrial targeting therapies as a promising cell-free therapeutic approach in reproductive medicine. PLT-Exos, a new generation of cells, has been used to treat POF for more than a decade and has been shown to attenuate oocyte morphology and promote the differentiation of theca cells through the upregulation of PI3K/Akt and Bcl2, as well as the downregulation of the Smad and Bax signaling pathways. This review summarizes the current state of the art in the field of PLT-Exos and discusses the advantages and limitations of their potential clinical applications.

卵巢早衰(POF)是一种以排卵功能提前衰退为特征的疾病。POF是一种复杂的疾病,可由多种因素引起,特发性POF患者占相当大的比例。激素替代疗法(HRT)目前被认为是治疗 POF 的一线疗法。本综述旨在全面综述富血小板血浆(PRP)、体外激活(IVA)、干细胞疗法、外泌体疗法、微RNA和线粒体靶向疗法作为生殖医学领域一种前景广阔的无细胞疗法的最新进展。PLT-Exos是新一代细胞,用于治疗POF已有十多年的历史,研究表明它能通过上调PI3K/Akt和Bcl2以及下调Smad和Bax信号通路,减弱卵母细胞形态并促进theca细胞分化。本综述总结了PLT-Exos领域的技术现状,并讨论了其潜在临床应用的优势和局限性。
{"title":"Novel Advances in Cell-Free Therapy for Premature Ovarian Failure (POF): A Comprehensive Review.","authors":"Yahya Yahyavi, Niloufar Kheradi, Abbas Karimi, Abbas Ebrahimi-Kalan, Fatemeh Ramezani, Soudabe Yousefi, Shirin Teymouri Nobari, Hourieh Sadrekarimi, Mohammad Nouri, Mahdi Edalati","doi":"10.34172/apb.2024.059","DOIUrl":"10.34172/apb.2024.059","url":null,"abstract":"<p><p>Premature ovarian failure (POF), is a condition characterized by the early decline of ovulation function. POF is a complex disorder that can be caused by various factors, and the idiopathic form represents a significant proportion of POF patients. Hormone replacement therapy (HRT) is currently considered the first-line treatment for POF. This review aims to provide a comprehensive overview of recent advancements in platelet-rich plasma (PRP), in vitro activation (IVA), stem cell therapy, exosome therapy, microRNAs, and mitochondrial targeting therapies as a promising cell-free therapeutic approach in reproductive medicine. PLT-Exos, a new generation of cells, has been used to treat POF for more than a decade and has been shown to attenuate oocyte morphology and promote the differentiation of theca cells through the upregulation of PI3K/Akt and Bcl2, as well as the downregulation of the Smad and Bax signaling pathways. This review summarizes the current state of the art in the field of PLT-Exos and discusses the advantages and limitations of their potential clinical applications.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566615","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
Development of Gentamicin Bilosomes Laden In Situ Gel for Topical Ocular Delivery: Optimization, In Vitro Characterization, Toxicity, and Anti-microbial Evaluation. 用于局部眼部给药的庆大霉素双体载体原位凝胶的开发:优化、体外表征、毒性和抗微生物评估。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.34172/apb.2024.057
Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid

Purpose: The eye drops are the prominent preparation used to treat surface eye disease (bacterial conjunctivitis). However, they have some limitations i.e., short corneal residence, resulting in low ocular bioavailability and necessitating frequent dose administration. The present study developed gentamicin (GE) bilosomes (BM)- laden in situ gel to improve therapeutic activity. The in situ gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.

Methods: The GE-BM was developed using the thin film hydration technique and optimized by D-optimal design. GE-BM was characterized for vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform electron microscope (FTIR). The optimized GE-BM (GE-BMopt) was incorporated into an in situ gel and assessed for physicochemical characteristics. GE-BMopt in situ gel was evaluated for in vitro release, ex vivo permeation, toxicity, and antimicrobial study.

Results: GE-BMopt has a vesicle size of 185.1±4.8nm, PDI of 0.254, zeta potential of 27.6 mV, entrapment efficiency of 81.86±1.29 %, and spherical morphology. The FTIR study presented no chemical interactions between GE and excipients. GE-BMopt in situ gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and ex-vivo bio-adhesion. GE-BMopt-IG4 showed significant high and sustained release of GE (78.08±4.73% in 12h). GE-BMopt-IG4 displayed 3.27-fold higher ex-vivo goat corneal permeation than a pure GE solution. GE-BMopt-IG4 showed good corneal tolerance without any damage or irritation. GE-BMopt-IG4 showed significantly (P<0.05) higher anti-bacterial activity (ZOI) against Staphylococcus aureus and Escherichia coli than pure GE solution.

Conclusion: The study determined that the BM in situ gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.

目的:滴眼液是治疗表面眼病(细菌性结膜炎)的主要制剂。然而,眼药水也有一些局限性,如在角膜停留时间短,导致眼部生物利用度低,需要频繁给药。本研究开发了含有庆大霉素(GE)双载体(BM)的原位凝胶,以提高治疗活性。该原位凝胶系统在给药前最初为溶胶状,在眼部生理条件下转化为凝胶状:方法:利用薄膜水合技术开发了 GE-BM,并通过 D-优化设计进行了优化。对 GE-BM 的囊泡大小、包埋效率、zeta 电位、形态和傅立叶变换电子显微镜(FTIR)进行了表征。将优化后的 GE-BM (GE-BMopt)加入原位凝胶中,并对其理化特性进行评估。对 GE-BMopt 原位凝胶进行了体外释放、体内渗透、毒性和抗菌研究评估:结果:GE-BMopt 的囊泡大小为 185.1±4.8nm,PDI 为 0.254,zeta 电位为 27.6 mV,夹带效率为 81.86±1.29%,形态为球形。傅立叶变换红外光谱研究表明,GE 与辅料之间没有化学作用。GE-BMopt原位凝胶(GE-BMoptIG4)显示出优异的粘度、胶凝强度和体内外生物粘附性。GE-BMopt-IG4 显示出显著的高持续释放性(12 小时内释放 78.08±4.73%)。与纯 GE 溶液相比,GE-BMopt-IG4 的体外山羊角膜渗透率高出 3.27 倍。GE-BMopt-IG4 显示出良好的角膜耐受性,没有任何损伤或刺激。与纯 GE 溶液相比,GE-BMopt-IG4 的金黄色葡萄球菌和大肠杆菌数量明显减少:该研究确定了 BM 原位凝胶系统可作为 GE 的替代载体,以提高其治疗效果,但还需要进一步的临床前研究。
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引用次数: 0
NLC Delivery of EGFP Plasmid to TM4 Cell Nuclei for Targeted Gene Therapy. NLC 将 EGFP 质粒输送到 TM4 细胞核,实现靶向基因治疗。
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.050
Nurul Jummah, Satrialdi Satrialdi, Aluicia Anita Artarini, Anindyajati Anindyajati, Diky Mudhakir

Purpose: This study evaluated whether a nanostructured lipid carrier (NLC) delivery system could safely and accurately deliver nucleic acids to the cell nucleus using the enhanced green fluorescent protein (EGFP)-C1 plasmid model.

Methods: The NLC was formulated using the emulsification method and equipped for cationic lipid-mediated transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which interacts electrostatically with nucleic acid. The NLC attributes, including size, polydispersity index, and zeta potential, were assessed by dynamic light scattering (DLS). The morphological structure was analyzed using transmission electron microscopy. Entrapment efficiency was evaluated by a direct method. Cellular uptake mechanisms of pEGFP-C1-NLC and the ability of pEGFP-C1 to penetrate the nucleus of TM4 cells to express EGFP were observed using confocal microscopy.

Results: pEGFP-C1-NLC exhibited particle sizes in the range 56-88 nm with a particle charge range of -6.0 to+1.3 mV. The polydispersity index<0.5 showed good size uniformity, and entrapment efficiency of pEGFP-C1in the NLC was 92.06±2.295%. The NLC formulation was internalized predominantly via caveolae-mediated endocytosis, as indicated by EGFP expression following successful delivery of pEGFP by the NLC into the cells.

Conclusion: NLC formulation could deliver genetic material to the nucleus and could be considered a gene therapy candidate for spermatogenesis.

目的:本研究以增强型绿色荧光蛋白(EGFP)-C1质粒为模型,评估了纳米结构脂质载体(NLC)递送系统能否安全、准确地将核酸递送至细胞核:方法:采用乳化法配制了NLC,并在阳离子脂质介导的转染中加入了1,2-二油酰-3-三甲基铵丙烷(DOTAP),DOTAP能与核酸发生静电相互作用。通过动态光散射(DLS)评估了 NLC 的属性,包括尺寸、多分散指数和 zeta 电位。透射电子显微镜分析了其形态结构。采用直接法评估了包埋效率。使用共聚焦显微镜观察了 pEGFP-C1-NLC 的细胞摄取机制以及 pEGFP-C1 穿透 TM4 细胞核表达 EGFP 的能力。结论:NLC 配方可将遗传物质输送到细胞内:NLC制剂能将遗传物质输送到细胞核,可作为精子发生基因治疗的候选药物。
{"title":"NLC Delivery of EGFP Plasmid to TM4 Cell Nuclei for Targeted Gene Therapy.","authors":"Nurul Jummah, Satrialdi Satrialdi, Aluicia Anita Artarini, Anindyajati Anindyajati, Diky Mudhakir","doi":"10.34172/apb.2024.050","DOIUrl":"10.34172/apb.2024.050","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated whether a nanostructured lipid carrier (NLC) delivery system could safely and accurately deliver nucleic acids to the cell nucleus using the enhanced green fluorescent protein (EGFP)-C1 plasmid model.</p><p><strong>Methods: </strong>The NLC was formulated using the emulsification method and equipped for cationic lipid-mediated transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which interacts electrostatically with nucleic acid. The NLC attributes, including size, polydispersity index, and zeta potential, were assessed by dynamic light scattering (DLS). The morphological structure was analyzed using transmission electron microscopy. Entrapment efficiency was evaluated by a direct method. Cellular uptake mechanisms of pEGFP-C1-NLC and the ability of pEGFP-C1 to penetrate the nucleus of TM4 cells to express EGFP were observed using confocal microscopy.</p><p><strong>Results: </strong>pEGFP-C1-NLC exhibited particle sizes in the range 56-88 nm with a particle charge range of -6.0 to+1.3 mV. The polydispersity index<0.5 showed good size uniformity, and entrapment efficiency of pEGFP-C1in the NLC was 92.06±2.295%. The NLC formulation was internalized predominantly via caveolae-mediated endocytosis, as indicated by EGFP expression following successful delivery of pEGFP by the NLC into the cells.</p><p><strong>Conclusion: </strong>NLC formulation could deliver genetic material to the nucleus and could be considered a gene therapy candidate for spermatogenesis.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566609","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
Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology. 探索癌症发展过程中沃伯格效应与糖脂毒性之间的相互作用:癌症病因学的新视角
IF 3.1 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI: 10.34172/apb.2024.049
Maher Monir Akl, Amr Ahmed

The Warburg effect, first observed by Otto Warburg in the 1920s, delineates a metabolic phenomenon in which cancer cells exhibit heightened glucose uptake and lactate production, even under normoxic conditions. This metabolic shift towards glycolysis, despite the presence of oxygen, fuels the energy demands of rapidly proliferating cancer cells. Dysregulated glucose metabolism, characterized by the overexpression of glucose transporters and the redirection of metabolic pathways towards glycolysis, lies at the crux of this metabolic reprogramming. Consequently, the accumulation of lactate as a byproduct contributes to the creation of an acidic tumor microenvironment, fostering tumor progression and metastasis. However, recent research, notably proposed by Maher Akl, introduces a novel perspective regarding the role of glycolipids in cancer metabolism. Akl's glucolipotoxicity hypothesis posits that aberrant glycolipid metabolism, specifically the intracellular buildup of glycolipids, significantly influences tumor initiation and progression. This hypothesis underscores the disruptive impact of accumulated glycolipids on cellular homeostasis, thereby activating oncogenic pathways and promoting carcinogenesis. This perspective aims to synthesize the intricate mechanisms underlying both the Warburg effect and glucolipotoxicity, elucidating their collective contributions to tumor growth and malignancy. By comprehensively understanding these metabolic aberrations, novel avenues for therapeutic intervention targeting the fundamental drivers of cancer initiation and progression emerge, holding promise for more efficacious treatment strategies in the future.

沃伯格效应是奥托-沃伯格在 20 世纪 20 年代首次观察到的,它描述了一种新陈代谢现象,即即使在常氧条件下,癌细胞也会表现出更高的葡萄糖摄取量和乳酸生成量。尽管存在氧气,这种向糖酵解的代谢转变仍能满足快速增殖的癌细胞的能量需求。以葡萄糖转运体过度表达和代谢途径转向糖酵解为特征的葡萄糖代谢失调是这种代谢重编程的关键所在。因此,作为副产品的乳酸盐的积累有助于形成酸性的肿瘤微环境,促进肿瘤的进展和转移。不过,最近的研究,特别是马希尔-阿克勒(Maher Akl)提出的研究,为糖脂在癌症代谢中的作用引入了一个新的视角。Akl 的糖脂毒性假说认为,糖脂代谢异常,特别是糖脂在细胞内的堆积,对肿瘤的发生和发展有重大影响。这一假说强调了积累的糖脂对细胞稳态的破坏性影响,从而激活致癌途径并促进癌变。这一观点旨在综合沃伯格效应和糖脂毒性的复杂机制,阐明它们对肿瘤生长和恶性肿瘤的共同作用。通过全面了解这些代谢畸变,我们将发现针对癌症发生和发展的基本驱动因素进行治疗干预的新途径,为未来制定更有效的治疗策略带来希望。
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Advanced pharmaceutical bulletin
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