DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Repurposing metformin as a potential anticancer agent using in silico technique.","authors":"Mona Mahfauz, Ozel Yuruker, Rasime Kalkan","doi":"10.1007/s40199-024-00523-0","DOIUrl":"10.1007/s40199-024-00523-0","url":null,"abstract":"<p><strong>Background: </strong>The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.</p><p><strong>Objective: </strong>This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.</p><p><strong>Methods: </strong>A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.</p><p><strong>Results: </strong>9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.</p><p><strong>Conclusion: </strong>This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"549-555"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity relationship of pharmacophores and toxicophores: the need for clinical strategy.","authors":"Saganuwan Alhaji Saganuwan","doi":"10.1007/s40199-024-00525-y","DOIUrl":"10.1007/s40199-024-00525-y","url":null,"abstract":"<p><strong>Objectives: </strong>Sometimes clinical efficacy and potential risk of therapeutic and toxic agents are difficult to predict over a long period of time. Hence there is need for literature search with a view to assessing cause of toxicity and less efficacy of drugs used in clinical practice.</p><p><strong>Method: </strong>Hence literatures were searched for physicochemical properties, chemical formulas, molecular masses, pH values, ionization, receptor type, agonist and antagonist, therapeutic, toxic and structure-activity relationship of chemical compounds with pharmacophore and toxicophore, with a view to identifying high efficacious and relative low toxic agents. Inclusion criteria were manuscripts published on PubMed, Scopus, Web of Science, PubMed Central, Google Scholar among others, between 1960 and 2023. Keywords such as pharmacophore, toxicophore, structure-activity-relationship and disease where also searched. The exclusion criteria were the chemicals that lack pharmacophore, toxicophore and manuscripts published before 1960.</p><p><strong>Results: </strong>Findings have shown that pharmacophore and toxicophore functional groups determine clinical efficacy and safety of therapeutics, but if they overlap therapeutic and toxicity effects go concurrently. Hence the functional groups, dose, co-administration and concentration of drugs at receptor, drug-receptor binding and duration of receptor binding are the determining factors of pharmacophore and toxicophore activity. Molecular mass, chemical configuration, pH value, receptor affinity and binding capacity, multiple pharmacophores, hydrophilic/lipophilic nature of the chemical contribute greatly to functionality of pharmacophore and toxicophore.</p><p><strong>Conclusion: </strong>Daily single therapy, avoidance of reversible pharmacology, drugs with covalent adduct, maintenance of therapeutic dose, and the use of multiple pharmacophores for terminal diseases will minimize toxicity and improve efficacy.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"781-800"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the effect of sodium alginate and sodium carboxymethylcellulose on pulmonary delivery of levofloxacin spray-dried microparticles.","authors":"Hanieh Alizadeh, Peyman Khoshhal, Maryam Sadat Mirmoeini, Kambiz Gilani","doi":"10.1007/s40199-024-00526-x","DOIUrl":"10.1007/s40199-024-00526-x","url":null,"abstract":"<p><strong>Background: </strong>Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time.</p><p><strong>Objective: </strong>In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF.</p><p><strong>Methods: </strong>The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test.</p><p><strong>Results: </strong>The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 μm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability.</p><p><strong>Conclusion: </strong>The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"557-571"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.","authors":"Anahita Shobeirean, Hossein Attar, Reyhaneh Varshochian, Mohammad Amin Rezvanfar","doi":"10.1007/s40199-024-00532-z","DOIUrl":"10.1007/s40199-024-00532-z","url":null,"abstract":"<p><strong>Background: </strong>Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency.</p><p><strong>Objectives: </strong>In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance.</p><p><strong>Methods: </strong>The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics.</p><p><strong>Results: </strong>The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml^-1h^-1. The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly.</p><p><strong>Conclusion: </strong>It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"649-664"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of different oral iron salts in the management of iron deficiency anemia.","authors":"Manoj A Suva, Pravin R Tirgar","doi":"10.1007/s40199-024-00517-y","DOIUrl":"10.1007/s40199-024-00517-y","url":null,"abstract":"<p><strong>Background: </strong>Anemia affects one-fourth of the world's population and is caused mostly by iron deficiency. Iron supplementation is the most essential strategy for preventing iron deficiency anemia. Conventional oral iron salts have many drawbacks such as poor absorption & bioavailability, and poor tolerability resulting in poor clinical outcomes.</p><p><strong>Objective: </strong>To compare the effectiveness and safety of ferrous ascorbate, ferrous fumarate, ferrous bis-glycinate, and Sucrosomial iron in the management of iron deficiency anemia.</p><p><strong>Method: </strong>The study is a retrospective observational clinical study comprising 260 subjects with hemoglobin between 7-10 g/dl. The patients were divided into four groups I, II, III, and IV, and received ferrous fumarate, ferrous ascorbate, ferrous bis-glycinate, and Sucrosomial iron respectively. Hematological profile and iron store indices were measured at baseline and month 3. One-way ANOVA followed by Tukey multiple comparison test was used to assess statistical significance (P < 0.05) using GraphPad Prism V.9.3.1 software.</p><p><strong>Results: </strong>The observational study showed that hemoglobin levels were significantly increased in the ferrous ascorbate group (11.86 ± 0.09; P < 0.0001), ferrous fumarate group (11.72 ± 0.08; P < 0.0001), ferrous bis-glycinate group (11.69 ± 0.11; P = 0.0003) and Sucrosomial iron group (12.20 ± 0.1; P < 0.0001) compared to the baseline. The Sucrosomial iron-supplemented group showed significantly higher improvement in hemoglobin levels and serum ferritin levels compared to conventional oral iron salts (P < 0.05) with a better safety profile.</p><p><strong>Conclusion: </strong>The Sucrosomial iron showed significantly higher improvement in hemoglobin levels and higher improvement in iron store indices parameters along with a good tolerability profile compared to other conventional oral iron salts.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"485-494"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Royal jelly and its hormonal effects in breast cancer: a literature review.","authors":"Farzaneh Aavani, Roja Rahimi, Pouya Goleij, Hossein Rezaeizadeh, Roodabeh Bahramsoltani","doi":"10.1007/s40199-024-00513-2","DOIUrl":"10.1007/s40199-024-00513-2","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.</p><p><strong>Methods: </strong>Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.</p><p><strong>Results: </strong>According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.</p><p><strong>Conclusion: </strong>Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"745-760"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.","authors":"Gomaa F El Fawal, Marwa M Abu-Serie","doi":"10.1007/s40199-024-00527-w","DOIUrl":"10.1007/s40199-024-00527-w","url":null,"abstract":"<p><strong>Background: </strong>Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).</p><p><strong>Objectives: </strong>This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.</p><p><strong>Methods: </strong>The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.</p><p><strong>Results: </strong>The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.</p><p><strong>Conclusion: </strong>The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"573-583"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.","authors":"Darya Almasi, Sohrab Kazemi, Mohammad Hossien Asghari, Seyed Mohammad Hosseini, Ali Akbar Moghadamnia","doi":"10.1007/s40199-024-00537-8","DOIUrl":"10.1007/s40199-024-00537-8","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"675-687"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting resistant breast cancer stem cells in a three-dimensional culture model with oleuropein encapsulated in methacrylated alginate microparticles.","authors":"Ozlem Altundag-Erdogan, Rumeysa Tutar, Elif Yüce, Betül Çelebi-Saltik","doi":"10.1007/s40199-024-00512-3","DOIUrl":"10.1007/s40199-024-00512-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cancer stem cells (CSCs) are a subpopulation of cancer cells that are believed to be responsible for tumor initiation, progression, metastasis, and resistance to conventional therapies. Oleuropein as a natural compound found in olive leaves and olive oil, has potential therapeutic effects in cancer treatment, particularly in targeting CSCs. It induces apoptosis in CSCs while sparing normal cells, inhibit proliferation, migration, and invasion, and suppress the self-renewal ability of CSCs. Additionally, oleuropein has shown synergistic effects with conventional chemotherapy drugs, enhancing their efficacy against CSCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aims to selectively target therapeutically resistant cancer stem cells (CSCs) within a heterogeneous tumor population by utilizing oleuropein (OLE) encapsulated in methacrylated alginate (OLE-mALG) within an in vivo-like microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to target therapeutically resistant cancer stem cells (CSCs) with oleuropein (OLE) encapsulated in the methacrylated alginate (OLE-mALG) in a heterogeneous tumor population with an in vivo-like microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Co-culture of CSCs with non-tumorogenic MCF-12 A cells was performed, the 3D breast cancer model was supported with methocel/matrigel/collagen-I, and vascularization was ensured with human umbilical vein endothelial cells (HUVEC). Then, OLE-loaded methacrylated alginate microparticles (mALG) were formed by dual crosslinking in the presence of both ionic and visible light obtained with a droplet based microfluidic system. The characterization and effectiveness of the produced OLE-mALG were evaluated by the FTIR, swelling/degradation/release analysis. Before producing OLE loaded mALG microparticles, a preliminary study was carried out to determine the effective dose of OLE for cells and the duration of OLE action on MCF-7, CSCs and MCF-12 A. Subsequently, CSC viability (WST-1), apoptosis (Bcl-2, Bax, caspase-3, caspase-9), stemness (OCT3/4, NANOG, SOX2), EMT profile (E-cadherin, Vimentin, Slug) and proliferation (SURVIVIN, p21, CYCLIN D1) after OLE-mALG treatment were all evaluated in the 3D model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;OLE was encapsulated in mALG with an efficiency of 90.49% and released 73% within 7 h. OLE-mALG induced apoptosis through the decrease in anti-apoptotic Bcl-2 and an increase in pro-apoptotic Bax, caspase-3, and caspase-9 protein levels. While Vimentin and Slug protein levels decreased after 200 µg/mL OLE-mALG treatment to 3D breast cancer culture, E-cadherin levels increased. OLE-mALG treatment to CSC co-culture led to a decrease in proliferation by triggering p21/SURVIVIN expressions, and also resulted in an increase in stemness genes (OCT3/4/NANOG/SOX2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;200 µg/mL OLE-loaded mALG microparticles suppressed epithelial-to-mesenchymal transition by suppressing Vimentin and Slug","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"471-483"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic DPYD allele variant frequencies: A comprehensive analysis across an ancestrally diverse Iranian population.","authors":"Negar Sarhangi, Fatemeh Rouhollah, Negar Niknam, Farshad Sharifi, Shekoufeh Nikfar, Bagher Larijani, George P Patrinos, Mandana Hasanzad","doi":"10.1007/s40199-024-00538-7","DOIUrl":"10.1007/s40199-024-00538-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population.</p><p><strong>Methods: </strong>The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip.</p><p><strong>Results: </strong>The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%.</p><p><strong>Conclusion: </strong>The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"715-727"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}