Advanced pharmaceutical bulletin最新文献

{"title":"Evaluating the Efficacy of a Semi-Solid Formulation with Clove Oil and Curcumin versus Clindamycin in the Treatment of Acne Vulgaris: A Comprehensive Study of Preclinical and Clinical Findings.","authors":"Peymaneh Dastgir, Setareh Tehrani, Setareh Haghighat, Sepideh Arbabi Bidgoli, Solmaz Ghaffari","doi":"10.34172/apb.025.45153","DOIUrl":"10.34172/apb.025.45153","url":null,"abstract":"<p><strong>Purpose: </strong>Acne vulgaris is a chronic inflammatory condition affecting the pilosebaceous units. With the rise of antibiotic resistance and the potential side effects associated with conventional treatments, there is increasing interest in exploring natural alternatives for treating acne. This study aimed to formulate and clinically evaluate a topical gel containing clove oil and curcumin in patients with mild to moderate acne vulgaris, using topical clindamycin as a standard comparator.</p><p><strong>Methods: </strong>The antibacterial activity of clove oil and curcumin against <i>Propionibacterium acnes</i> and <i>Staphylococcus epidermidis</i> was assessed by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Based on these findings, semisolid gel formulations were developed and subjected to in vitro evaluations. Subsequently, a single-blind, randomized, comparative clinical study was conducted in 31 participants diagnosed with mild to moderate acne. Volunteers applied clindamycin gel in the morning and the clove oil-curcumin gel in the evening, or vice versa, over a 4-week period. Clinical outcomes, including acne lesion counts, Acne Severity Index (ASI), and patient satisfaction, were assessed.</p><p><strong>Results: </strong>The clove oil-curcumin gel demonstrated comparable efficacy to clindamycin in reducing acne lesions, papules, and ASI. While no significant differences were observed between the two groups in comedone reduction, patient satisfaction increased in clove oil-curcumin gel group.</p><p><strong>Conclusion: </strong>Topical application of a gel containing clove oil and curcumin demonstrated promising results as an effective and well-tolerated alternative or adjunctive therapy for acne vulgaris. These findings support the potential of plant-based formulations in acne management.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"606-616"},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766730","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":"A Newly Developed TGF-Β-Responsive CAR T Cell for Enhanced Proliferation and Cytokine Secretion.","authors":"Shafieeh Mansoori, Mohammad Ali Shokrgozar, Monireh Gholizadeh, Shahriyar Abdoli, Soheila Ajdary, Zahra Sharifzadeh","doi":"10.34172/apb.025.45483","DOIUrl":"10.34172/apb.025.45483","url":null,"abstract":"<p><strong>Purpose: </strong>Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising cancer treatment. Nevertheless, the tumor microenvironment (TME) of solid tumors provides substantial challenges to CAR T cell efficacy. Tumor growth factor-beta (TGF-β), a potent immunosuppressive cytokine in the TME, impedes T cell activation, proliferation, and cytotoxicity, diminishing the anti-tumor potency of CAR T cells. This study investigates whether TGF-βRII CAR T cells can overcome these barriers and remain functional in TGF-β-rich environments.</p><p><strong>Methods: </strong>We developed a novel TGF-βRII CAR T cell (TGF-βRII-CD28CD3z) and a dominant-negative TGF-β receptor (dnTβRII) T cell utilizing Jurkat cells. Transduction efficiency and surface expression were confirmed using flow cytometry. T cell activation and proliferation were assessed by CD69 and Ki-67 expression, respectively. IL-2 and IFN-γ secretion were quantified using ELISA kits.</p><p><strong>Results: </strong>Flow cytometry confirmed the successful cell surface expression of the designed receptors: 62% and 24% for TGF-βRII CAR and dnTβRII, respectively. TGF-βRII CAR T cells were markedly activated in a dose-dependent manner, with optimal responses at 10 ng/mL TGF-β. The Ki-67 expression of CAR T cells, used as a proliferation marker, increased 1.21-fold (from 79.5% to 96%) upon exposure to 10 ng/mL TGF-β. At 5 ng/mL TGF-β, the cells' proliferation was maintained at a 1.04-fold increase. Cytokine analysis revealed a 1.9-fold increase in IL-2 (130±4 pg/mL) and a 2.7-fold increase in IFN-γ (146±21.9 pg/mL) secretion at 10 ng/mL TGF-β. Additionally, at 5 ng/mL TGF-β, IL-2 secretion increased 1.6-fold (110±10.7 pg/mL), and IFN-γ secretion increased 1.7-fold (94.3±10.2 pg/mL). In contrast, dnTβRII T cells also produced IL-2 (95 pg/mL±22, 2.7-fold increase) but failed to sustain proliferation or IFN-γ production at 10 ng/mL TGF-β.</p><p><strong>Conclusion: </strong>Our findings demonstrate that the TGF-βRII CAR T cells not only resist TGF-β-mediated suppression but also promote activation, proliferation, and cytokine release in the presence of TGF-β. This underscores their therapeutic potential as an innovative approach to overcome TGF-β-driven immunosuppression and improve the CAR T cell therapy efficacy in solid tumors.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"646-656"},"PeriodicalIF":4.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766743","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":"Continuous Uptake of MiR-181a-2 Mimetic Induces Constitutive Overexpression of Cellular MiR-181a-2 in MCF-7 Breast Cancer Cells: Links with Progression of Drug Resistance.","authors":"Olga Evgen'evna Andreeva, Danila Vladimirovich Sorokin, Svetlana Vladimirovna Vinokurova, Pavel Borisovich Kopnin, Nadezhda Viacheslavovna Elkina, Danila Sergeevich Elkin, Maria Dmitrievna Fedorova, Alexander Mikhailovich Scherbakov, Mikhail Aleksandrovich Krasil'nikov","doi":"10.34172/apb.025.43440","DOIUrl":"10.34172/apb.025.43440","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to elucidate the mechanisms underlying the formation and maintenance of drug resistance in cancer cells. Previously, we demonstrated that prolonged treatment of estrogen-dependent MCF-7 breast cancer cells with exosomes derived from estrogen-resistant MCF-7/T cells leads to a partial loss of estrogen sensitivity in MCF-7 cells. Moreover, repeated transfection with one of the exosomal microRNAs-microRNA-181a-2-induced an irreversible decrease in hormonal sensitivity in the recipient cells. In the present work, to further investigate the possible mechanism of miR-181a-2-induced acquired resistance, we analyzed the effect of multiple miR-181a-2 transfections on the expression of cellular miR-181a-2 and related signaling proteins.</p><p><strong>Methods: </strong>miR-181a-2 was ectopically expressed by mimetic transfection or suppressed by antisense oligonucleotides. miR-181a-2 precursor/MIR181A2HG expression (qRT-PCR) and MIR181A2 locus copy number (qPCR) were assessed. wtSnail was expressed via transient transfection. Tamoxifen sensitivity was measured by MTT assay. Protein expression was studied by immunoblotting, estrogen receptor α/Snail transcriptional activity was evaluated by reporter analysis.</p><p><strong>Results: </strong>We found that multiple transfections with miR-181a-2 resulted in a marked increase in cellular miR-181a-2 precursor levels, whereas single transfection had no such effect. Similarly, stable transfection with miR-181a-2 led to increased levels of cellular miR-181a-2 and its host gene, MIR181A2HG, which was associated with partial resistance to tamoxifen. Analysis of the genomic DNA encoding miR-181a-2 revealed no changes in copy number in transfected cells. Furthermore, we identified the transcription factor Snail as a key mediator of miR-181a-2-induced resistance and demonstrated its role in the formation of an autoregulatory loop of miR181a-2 and the maintenance of cell resistance.</p><p><strong>Conclusion: </strong>Overall, these results reveal a novel mechanism of resistance-associated signaling pathway rearrangement based on the formation of a miR-181a-2 autoregulatory loop.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"678-685"},"PeriodicalIF":4.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766569","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":"Preclinical and Limited Clinical Evidence for Spirulina in Ulcerative Colitis: A Systematic Review and Meta-analysis.","authors":"Khadije Gorgi, Zahra Ghanbarzadegan, Amir Darkhosh, Sara Shojaei-Zarghani, Seyed Vahid Hosseini","doi":"10.34172/apb.025.46031","DOIUrl":"10.34172/apb.025.46031","url":null,"abstract":"<p><strong>Purpose: </strong>Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. This study aimed to systematically review available animal and clinical studies on the effects of spirulina (<i>Arthrospira platensis</i>), a natural anti-inflammatory and antioxidant agent, on the condition of UC.</p><p><strong>Methods: </strong>We conducted a systematic search in the PubMed, Scopus, Web of Science, and Embase databases for studies published from 1980 to April 2024. Experimental studies involving animal (mammalian) models or patients with UC were included. Pooled effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 1,321 documents were identified through the systematic search. Following screening, 16 animal studies and 3 randomized controlled trials (RCTs), derived from one trial, were included. The beneficial effects of spirulina on body weight (MD=8.61, 95% CI=2.98 to 14.25, I²: 99.78%), clinical features (SMD=-2.39, 95% CI=-2.95 to -1.83, I²: 5.89%), colon length (MD=1.25, 95% CI=0.59 to 1.91, I²: 95.80%), oxidative stress, inflammatory markers, and gut microbiota in animal models of UC were reported. However, no effect of spirulina on disease activity was reported in the only RCT conducted. Nonetheless, improvements in quality of life, oxidative stress, sleep disturbances, stress scores, and anemia were noted.</p><p><strong>Conclusion: </strong>Available animal studies suggest beneficial effects of spirulina on UC; however, the limited number of RCTs precludes definitive conclusions.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"793-805"},"PeriodicalIF":4.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462584","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 <i>Cuscuta epithymum's</i> Effect on Neuroinflammation, Tyrosine Kinase Activity and Macrophage Counts in Spleen and Liver: Revealing Their Roles in Stress Responses.","authors":"Leila Ghassemifard, Narjes Khavasi, Ehsan Saboory, Fatemeh Madani, Saeed Sardari","doi":"10.34172/apb.025.45554","DOIUrl":"10.34172/apb.025.45554","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic stress usually causes immunosuppression, activates tyrosine kinase (TK), and increases inflammatory responses. Based on Persian medicine, the spleen is crucial for the immune system and stress response. Cuscuta epithymum (CE) contains antioxidant properties and is beneficial to the immune system.</p><p><strong>Methods: </strong>In this experimental study, 28 male and 56 female rats were randomly divided into four groups and exposed to stress from restraint. Simultaneously, Cuscuta's extract was given to the other two groups while normal saline was given to the control and stressed rats. Four different coupling combinations were created by mating control and experimental rats: McFc, MsFs, McFc+EX, and MsFs+EX (M: male, F: female, C: control, S: stress, and EX: extract). The TK level, megakaryocyte, and macrophage cell number in the liver and spleen were then assessed after certain parents and male pups were dissected on postnatal day (PND) 25. Western blot analysis was used to measure the brain's quantitative levels of TNF-α and IL-1β protein expression.</p><p><strong>Results: </strong>Rats under stress had much higher levels of TK and macrophage cells in their liver and spleen tissues than the other rats, while the stress+CE group had significantly lower levels. While megakaryocyte cells increased in CE-treated animals, they dramatically declined in the stress group. The brain homogenate's TNF-α and IL-1β levels were considerably lowered by <i>Cuscuta</i> extract.</p><p><strong>Conclusion: </strong>Our study showed the significant role of the <i>Cuscuta</i> in decreasing the adverse effects of stress on the liver and spleen immune system, as well as a remarkable anti-neuroinflammatory effect.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"657-666"},"PeriodicalIF":4.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766781","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":"Sulfur-Dependent Disulfide Bond Disruption in Insulin Resistance: A Hypothesis.","authors":"Maher Monir Akl, Amr Ahmed","doi":"10.34172/apb.025.46067","DOIUrl":"10.34172/apb.025.46067","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 4","pages":"691-692"},"PeriodicalIF":4.1,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12980271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462377","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":"Pathological and Molecular Significance of HER2/neu Overexpression in Familial Breast Cancer Among Egyptian Women: A Comprehensive Study on Diagnostic and Prognostic Implications.","authors":"Amoura M Abou-El-Naga, Afaf M El Saied, Maher Monir Akl, Sahar A Abd El-Aziz","doi":"10.34172/apb.025.43866","DOIUrl":"10.34172/apb.025.43866","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer remains the most prevalent malignancy among women worldwide, with a strikingly high incidence in Egypt, particularly in familial cases. This study aims to comprehensively elucidate the pathological and molecular significance of ERBB2 (HER2/neu) overexpression in Egyptian familial breast cancer, highlighting its role in tumor aggressiveness, immune evasion, and precision oncology.</p><p><strong>Methods: </strong>We enrolled 44 Egyptian breast cancer patients along with 35 daughters and 24 sisters (2013-2015, Mansoura University Hospital). Comprehensive analyses included serum biochemical assays, histopathological evaluation, immunohistochemical staining for ERBB2, and molecular detection of ERBB2 amplification using first-round and nested PCR. Associations with clinical, hormonal, and metabolic variables were also explored.</p><p><strong>Results: </strong>Serum biochemical profiling revealed significantly elevated ALT (6.6±0.55 U/mL), LDH (16.8±1.4 U/mL), and CA15 3 (160±13.33 U/mL), with reduced AST (2.6±0.22 U/mL) compared to controls (<i>P</i>≤0.05). Histopathology confirmed invasive ductal carcinoma with dense stromal desmoplasia. Immunohistochemistry demonstrated ERBB2 overexpression in>10% of tumor cells. Nested PCR detected ERBB2 amplification in 72% of patients, and in daughters (17%) and sisters (20%). Notably, higher ERBB2 expression was observed in unmarried patients (100%), pre-menopausal women (73-72%), and those with diabetes or hypertension, suggesting hormonal and metabolic modulation via PI3K/AKT/mTOR and MAPK/ERK pathways. ERBB2 mutations were identified in 14% of patients, 2.1% of daughters, and 1.2% of sisters. Furthermore, ERBB2 may upregulate PD-L1, contributing to immune evasion.</p><p><strong>Conclusion: </strong>Our findings highlight ERBB2 as a pivotal diagnostic and prognostic biomarker in Egyptian familial breast cancer and support integrating HER2-targeted therapies with immune checkpoint inhibitors and metabolic interventions. This approach could transform outcomes in high-risk familial cohorts. The study emphasizes the importance of genetic screening and precision medicine strategies that consider molecular, hormonal, and metabolic contexts in breast cancer care.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"637-645"},"PeriodicalIF":4.1,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766796","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":"siRNA and mRNA-Based Preventive and Therapeutic Strategies for HPV-Induced Cervical Cancer.","authors":"Mansi Khari, Neha Jain, Shreya Kaul, Manisha Pandey, Nitin Sharma","doi":"10.34172/apb.025.45456","DOIUrl":"10.34172/apb.025.45456","url":null,"abstract":"<p><p>Human papillomavirus (HPV), specifically types 16 and 18, is the main cause of cervical cancer and a significant cause of death among women. Specifically, HPV E6 and E7 oncogenes hinder the normal cell cycle regulation, resulting in uncontrolled cell growth and cervical cancer. The available therapy options include surgery, radiotherapy, and chemotherapy, which show success but also demonstrate notable complications. SiRNA (small interfering RNA) and mRNA (messenger RNA) therapies have emerged as precise and effective tools to silence the HPV E6 and E7 oncogenes and stimulate the immune system to fight against HPV infection, respectively, presenting a targeted therapy approach and overcoming the available therapy challenges. Nanoparticles and Pegylated liposomes are the delivery systems that increase the efficacy and safety of siRNA and mRNA therapies. This review critically appreciates the effective targeting of siRNA and mRNA-based therapies by highlighting their key advantages and limitations. Despite being a target-specific and effective approach, there are certain challenges like scale-up, cost-effectiveness, and developing stable delivery systems, which are required to be discussed. In addition, other precision medicine approaches, such as CRISPR/CAS-9, antisense oligonucleotides, or immunotherapy, have also been included as compared to siRNA/mRNA therapies. Their preclinical, patent, and clinical translations have also been discussed exhaustively.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"552-573"},"PeriodicalIF":4.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766760","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 Use of Rare Earth Glass Microspheres and Graphene Quantum Dots Glass Microspheres for Biological Applications: Cancer Insight.","authors":"Jéssica Ingrid Faria De Souza, Natália Cristina Gomes-da-Silva, Filipe Ferreira Ascenção, Beatriz Da Silva Batista, Luciana Magalhães Rebelo Alencar, Pierre Basílio Almeida Fechine, Eduardo Ricci-Junior, Ralph Santos-Oliveira","doi":"10.34172/apb.025.45113","DOIUrl":"10.34172/apb.025.45113","url":null,"abstract":"<p><strong>Purpose: </strong>This study explores the use of glass microspheres doped with rare earth elements, specifically samarium (Sm) and neodymium (Nd), and graphene quantum dots (GQDs) in biological applications, particularly cancer therapy.</p><p><strong>Methods: </strong>Glass microspheres were synthesized using an eco-friendly approach with recycled glass and subsequently doped with Sm, Nd, or GQDs. The samples were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). In vitro cytotoxicity was assessed in MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines.</p><p><strong>Results: </strong>In vitro assays demonstrated that these doped microspheres significantly reduced cell viability in breast (MCF-7) and prostate (DU-145) cancer cell lines. The GQD microspheres showed a marked reduction in cell proliferation, attributed to mechanisms involving apoptosis and reactive oxygen species (ROS) production. Sm and Nd microspheres also decreased cell survival, with Nd microspheres showing the highest efficacy.</p><p><strong>Conclusion: </strong>The study highlights the potential of rare earth elements and GQDs in developing advanced nanotherapeutic agents for cancer treatment, emphasizing their role in disrupting cellular functions and promoting cytotoxic effects in tumor cells.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"627-636"},"PeriodicalIF":4.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766765","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":"Serine/Arginine Protein Kinase Inhibitors Potentiate Melanoma Cell Death and Metastatic Inhibition Through Apoptotic Protein Triggering and Vimentin Dysregulation.","authors":"Atit Silsirivanit, Chaturong Inpad, Jesadagorn Siriwath, Sittiruk Roytrakul, Sukanya Horpaopan, Kanyanut Kotanart, Worasak Kaewkong","doi":"10.34172/apb.025.43291","DOIUrl":"10.34172/apb.025.43291","url":null,"abstract":"<p><strong>Purpose: </strong>Melanoma arises from the malignant transformation of melanocytes, a serious health problem in high UV-exposure countries. Ineffective treatments and metastasis have led to poor prognosis and high mortality among melanoma patients. Several underlying mechanisms are suspected. The splicing-error in many genes has been frequently reported in melanoma, therefore, targeting splicing regulator Serine/Arginine protein kinases (SRPKs) is promising.</p><p><strong>Methods: </strong>SRPKs expression in the TCGA dataset was analyzed by GEPIA. A375 and MNT-1 were comparatively treated by SRPK inhibitors, SRPIN340 and SPHINX31. Effects on viability and growth were measured by MTT and hanging drop assay. Apoptotic death was examined by flow cytometry and western blotting. Invasive ability was determined by transwell assay. Invasive-associated genes, proteins, and enzymes were tracked by RT-PCR, western blotting, immunofluorescence, and gelatin zymography.</p><p><strong>Results: </strong>SRPIN340 exhibited higher inhibitory effects on the viability and growth of melanoma cells than SPHINX31. Apoptotic induction was found with downregulated Bcl-2 and upregulated cytochrome c, especially in A375 cells. For metastatic inhibition in A375, lower numbers of invaded cells were counted. Downregulated vimentin mRNA and transcription factors-snail, as well as altered vimentin protein expression and localization were marked. Remarkably, the activities of MMP2 and MMP9 were suppressed.</p><p><strong>Conclusion: </strong>SRPK inhibitors potentially suppressed melanoma cell survivability and metastasis through the triggering of apoptotic proteins and dysregulating vimentin. These collected data serve as a basis for utilizing new alternative therapeutic strategies by targeting splicing regulator SRPK, for melanoma treatment.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"15 3","pages":"617-626"},"PeriodicalIF":4.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766750","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}