{"title":"Harnessing the Therapeutic Potential of Mesenchymal Stem Cells in Cancer Treatment.","authors":"Parisa Kangari, Reza Salahlou, Somayeh Vandghanooni","doi":"10.34172/apb.2024.052","DOIUrl":"10.34172/apb.2024.052","url":null,"abstract":"<p><p>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.</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/PMC11530882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566315","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}
{"title":"Sex Differences on the Pharmacokinetics of Drugs for Children with Chronic Kidney Disease: A Narrative Review.","authors":"Toktam Faghihi, Farahnak Assadi","doi":"10.34172/apb.2024.056","DOIUrl":"10.34172/apb.2024.056","url":null,"abstract":"<p><p>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.</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/PMC11530871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566725","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}
{"title":"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.","authors":"Seyyed Mostafa Arabi, Mahla Chambari, Leila Sadat Bahrami, Ali Jafari, Hossein Bahari, Željko Reiner, Amirhossein Sahebkar","doi":"10.34172/apb.2024.051","DOIUrl":"10.34172/apb.2024.051","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords.</p><p><strong>Results: </strong>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; <i>P</i>=0.03; I<sup>2</sup>=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm<sup>2</sup>; 95% CI -0.08 to -0.04; <i>P</i><0.001; I<sup>2</sup>=97.7%, <i>P</i><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.</p><p><strong>Conclusion: </strong>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.</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/PMC11530883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566729","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}
{"title":"Cytobiological Alterations Induced by Celecoxib as an Anticancer Agent for Breast and Metastatic Breast Cancer.","authors":"Maher Monir Akl, Amr Ahmed","doi":"10.34172/apb.2024.055","DOIUrl":"10.34172/apb.2024.055","url":null,"abstract":"<p><p>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.</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/PMC11530885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566287","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}
{"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}
Yahya Yahyavi, Niloufar Kheradi, Abbas Karimi, Abbas Ebrahimi-Kalan, Fatemeh Ramezani, Soudabe Yousefi, Shirin Teymouri Nobari, Hourieh Sadrekarimi, Mohammad Nouri, Mahdi Edalati
{"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}
Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid
{"title":"Development of Gentamicin Bilosomes Laden <i>In Situ</i> Gel for Topical Ocular Delivery: Optimization, <i>In Vitro</i> Characterization, Toxicity, and Anti-microbial Evaluation.","authors":"Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid","doi":"10.34172/apb.2024.057","DOIUrl":"10.34172/apb.2024.057","url":null,"abstract":"<p><strong>Purpose: </strong>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 <i>in situ</i> gel to improve therapeutic activity. The <i>in situ</i> gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.</p><p><strong>Methods: </strong>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 <i>in situ</i> gel and assessed for physicochemical characteristics. GE-BMopt <i>in situ</i> gel was evaluated for <i>in vitro</i> release, <i>ex vivo</i> permeation, toxicity, and antimicrobial study.</p><p><strong>Results: </strong>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 <i>in situ</i> gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and <i>ex-vivo</i> 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 <i>ex-vivo</i> 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 (<i>P</i><0.05) higher anti-bacterial activity (ZOI) against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> than pure GE solution.</p><p><strong>Conclusion: </strong>The study determined that the BM <i>in situ</i> gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.</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/PMC11530890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566291","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}
{"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}
{"title":"Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology.","authors":"Maher Monir Akl, Amr Ahmed","doi":"10.34172/apb.2024.049","DOIUrl":"10.34172/apb.2024.049","url":null,"abstract":"<p><p>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.</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/PMC11530886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566280","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}