Iranian Journal of Pharmaceutical Research最新文献

{"title":"Secondary Autoimmune Dermatological Disorders Induced by Multiple Sclerosis Biological Immunotherapy Agents: A Systematic Review of Case Reports.","authors":"Mohammad Ali Sahraian, Shahboddin Emami, Sara Ataei, Fahime Nasr Esfahani, Nasibeh Ghalandari","doi":"10.5812/ijpr-166426","DOIUrl":"10.5812/ijpr-166426","url":null,"abstract":"<p><strong>Context: </strong>Multiple sclerosis (MS) is a devastating autoimmune neurodegenerative disease, for which disease-modifying drugs (DMDs) have been associated with secondary autoimmune dermatological disorders.</p><p><strong>Objectives: </strong>This systematic review of case reports seeks to examine documented case reports involving biological medications utilized in managing MS attacks and disease progression that correlate with such dermatological complications.</p><p><strong>Evidence acquisition: </strong>A systematic search was conducted in the Google Scholar, Scopus, and PubMed databases for studies published until January 2024. The search strategy employed combinations of keywords such as \"multiple sclerosis\" with specific biological agents (\"Natalizumab\" OR \"Ocrelizumab\" OR \"Rituximab\" OR \"Alemtuzumab\" OR \"Ofatumumab\" OR \"Ublituximab\") and \"case report\", incorporating relevant Medical Subject Headings (MeSH) terms. All articles, if full texts were available, on case reports and case series of autoimmune dermatological complications of biological medication of MS were analyzed. The quality of the case reports was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist.</p><p><strong>Results: </strong>A total of 19 articles fulfilled the inclusion criteria and were included in this review. The highest frequency of secondary autoimmune complications was documented with alemtuzumab administration, whereas rituximab demonstrated the lowest incidence of dermal autoimmune manifestations in MS patients.</p><p><strong>Conclusions: </strong>The employed injectable MS immunotherapies demonstrate various autoimmune adverse reactions that have been documented across numerous case reports. This review examines different categories of secondary autoimmune complications and explores the theoretical mechanisms underlying their development.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e166426"},"PeriodicalIF":1.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878271","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":"Ellagic Acid Ameliorates Diabetic Cardiomyopathy by Inhibiting Ferroptosis Through the Modulation of the SIRT1/p53 Pathway in Streptozotocin-Induced Diabetic Rats.","authors":"Qingmei Wang, Xuanguo Zhang, Li Xi","doi":"10.5812/ijpr-166600","DOIUrl":"10.5812/ijpr-166600","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) involves ferroptosis, an iron-dependent cell death pathway. Ellagic acid (EA), a natural antioxidant flavonoid, may offer therapeutic potential; however, its mechanisms in DCM remain unexplored.</p><p><strong>Objectives: </strong>This study investigated the cardioprotective effects of EA in experimental DCM, focusing on its capacity to mitigate ferroptosis via the sirtuin 1 (SIRT1)/p53 pathway.</p><p><strong>Methods: </strong>The EA (25, 50, or 100 mg/kg/day) was orally administered to streptozotocin (STZ)-induced diabetic rats for 60 days. We assessed cardiac function, histology, metabolic parameters, oxidative stress, inflammation, and key markers of ferroptosis and the SIRT1/p53 axis. Data were analyzed by one-way analysis of variance (ANOVA) with Tukey's post-hoc test.</p><p><strong>Results: </strong>The EA treatment dose-dependently attenuated cardiac hypertrophy, myocardial injury, and metabolic dysregulation, with maximal benefits at 100 mg/kg. It also reduced oxidative stress and inflammation. Crucially, EA inhibited ferroptosis, as evidenced by reduced iron overload and upregulation of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). These benefits were associated with the upregulation of SIRT1 and downregulation of p53 in cardiac tissue.</p><p><strong>Conclusions: </strong>The EA mitigates DCM by suppressing ferroptosis, potentially through modulation of the SIRT1/p53 pathway, thereby improving cardiac function and metabolic homeostasis. However, as this study utilized an STZ-induced model of type 1 diabetes, further research is warranted to confirm its efficacy in type 2 diabetic contexts.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e166600"},"PeriodicalIF":1.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878331","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":"Biosynthesis and Characterization of Selenium Nanoparticles by <i>Kocuria</i> Strain Bm3: Evaluating Their Synergistic Antimicrobial Activity with <i>Chlorella</i> <i>vulgaris</i> Crude Extract Against Multidrug-Resistant Bacteria.","authors":"Hamid Babavalian, Fatemeh Shakeri, Atefeh Safarpour, Iman Hassankhani, Zohre Nasrollahzadeh, Mohammad Ali Amoozegar","doi":"10.5812/ijpr-164350","DOIUrl":"10.5812/ijpr-164350","url":null,"abstract":"<p><strong>Background: </strong>Mangrove ecosystems are rich in halotolerant microorganisms capable of synthesizing antimicrobial nanoparticles. Exploring these microorganisms for the development of novel antimicrobial agents is increasingly important, particularly given the escalating problem of multidrug resistance.</p><p><strong>Objectives: </strong>This study aimed to confirm the biosynthesis of selenium nanoparticles (SeNPs) by the <i>Kocuria</i> strain Bm3, isolated from the Hera mangroves in Iran, and to evaluate the antimicrobial efficacy of SeNPs in combination with <i>Chlorella vulgaris</i> crude extract (<i>C. vulgaris</i> CE) against various bacterial strains.</p><p><strong>Methods: </strong>The synthesized SeNPs were characterized with respect to morphology and size. Antimicrobial activity was assessed by measuring inhibition zones; minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined. Synergistic effects were calculated using the Fractional Inhibitory Concentration Index (ΣFIC). Additionally, cytotoxic effects on MCF-7 cell lines were evaluated.</p><p><strong>Results: </strong>The combination of <i>C. vulgaris</i> CE and SeNPs significantly enhanced antibacterial activity against various strains, most notably a clinical isolate of <i>Escherichia coli</i>, which exhibited marked growth inhibition and reduced MIC values (P < 0.001). While <i>Staphylococcus aureus</i> did not demonstrate significant differences among treatments, <i>Staphylococcus epidermidis</i> and <i>Staphylococcus saprophyticus</i> showed improved sensitivity with the combination treatment, achieving substantial growth inhibition zones (P < 0.001). In contrast, the clinical isolate of <i>Acinetobacter baumannii</i> displayed potential resistance, with no growth inhibition observed when treated alone. The MTT assay revealed that <i>C. vulgaris</i> CE and SeNPs each exhibited low cytotoxicity individually, resulting in MCF-7 cell viability percentages of 49.75 ± 3.75% and 44.46 ± 4.26%, respectively; however, their combination significantly reduced cell viability to 29.36 ± 2.64% (P < 0.001).</p><p><strong>Conclusions: </strong>The SeNPs synthesized by the <i>Kocuria</i> strain Bm3 significantly enhance the antimicrobial properties of <i>C. vulgaris</i> CE, indicating their potential as a therapeutic strategy against multidrug-resistant infections. Further investigation into their cytotoxic effects is warranted to evaluate safety and efficacy for clinical applications.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164350"},"PeriodicalIF":1.8,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677602","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":"Phenolic Compounds and Flavonoids in Various Extracts of <i>Ferula tadshikorum</i> and <i>Ferula sumbul</i> Grown in vitro Conditions.","authors":"Dilafruz Jamalova Ne'matilla Qizi, Gulsauir Kurbaniyazova Tanirbergen Kizi, Imene Caliscan Tatar, Atoeva Rukhsora Odilovna, Nargiza Achilova Tuxtanazarovna, Azima Saitova Kaljanovna, Rabiga Esemuratova Xoshmuratovna, Boon Chin Tan, Azizbek Aliyor Oʻgʻli Togʻayev, Ulugbek Kodirov Hamrokulovich, Ziyoviddin Yusupov Olimjon Ugli","doi":"10.5812/ijpr-163731","DOIUrl":"10.5812/ijpr-163731","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Flavonoids, which are bioactive compounds found in medicinal plant extracts, are recognized for their significant therapeutic properties. To efficiently isolate these compounds from fresh plant materials, it is essential to optimize extraction methods. The most widely used approach involves solvent extraction using solvents such as methanol, ethanol, acetone, and hexane. This study aimed to determine the optimal extraction methods for isolating phenolic compounds and flavonoids from callus and regenerating plants of two medicinal species of the genus &lt;i&gt;Ferula&lt;/i&gt; cultivated in vitro with or without indole-3-butyric acid (IBA) and 6-benzylaminopurine (BAP). This study focuses on &lt;i&gt;Ferula tadshikorum&lt;/i&gt; and &lt;i&gt;Ferula sumbul&lt;/i&gt;, with extracts analyzed quantitatively using high performance liquid chromatography (HPLC). The results revealed the presence of flavonoids such as kaempferol, quercetin, p-coumaric acid, and cinnamic acid at varying concentrations across different solvents. Notably, extracts from &lt;i&gt;F. sumbul&lt;/i&gt; plants grown with Murashige and Skoog (MS) medium containing IBA and BAP exhibited higher levels of p-coumaric acid (9.588 µg/mL) in methanol, and kaempferol (9.595 µg/mL) in hexane. For &lt;i&gt;F. tadshikorum&lt;/i&gt;, ethanol extraction yielded a significant amount of p-coumaric acid (29.9 µg/mL). Quercetin and cinnamic acid were detected in minimal quantities in both extracts, whereas kaempferol was notably higher (2.61 µg/mL) than in the methanol extract (0.617 µg/mL).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The present study represents the first attempt to determine the phenolic compounds in regenerating plants obtained through in vitro methods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In vitro regenerated plants of &lt;i&gt;F. tadshikorum&lt;/i&gt; and &lt;i&gt;F. sumbul&lt;/i&gt;, cultured on MS basal medium supplemented with IBA (0.5 mg/mL) and BAP (0.5 mg/mL), were ground into a fine powder in liquid nitrogen and then dried in a drying oven at 50°C before chemical analyses. The bioactive compounds were extracted by soaking the powders in methanol, ethanol, and hexane overnight. The extracts were filtered and evaporated under a vacuum at 35 - 36°C. The resultant slurry was partitioned with equal volumes of ethyl acetate (EA) and water to remove excess polar compounds. The EA fraction was vacuum-dried, and the mass of the crude extract was recorded. The extract was subsequently dissolved in methanol, ethanol, and hexane to achieve a concentration of 1 mg/mL. Finally, the solution was filtered through a 0.45 µm PTFE filter (German Acrodisc 13 CR) before analysis by HPLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We then analyzed methanol, ethanol, and hexane extracts from in vitro &lt;i&gt;F. tadshikorum&lt;/i&gt; and &lt;i&gt;F. sumbul&lt;/i&gt; plants grown under various combinations of hormones and hormone-free conditions using HPLC. When comparing extracts prepared with 3 solvents from 2 different samples of the &lt;i&gt;F. sumbul&lt;/i&gt;, plants obtained in a combination of IB","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e163731"},"PeriodicalIF":1.8,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878049","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":"In vitro Multi-targeted Anti-cancer Effects of Bavachinin in Papillary Thyroid Carcinoma Cell Line: Dual Pathway Inhibition and Cytokine Downregulation.","authors":"Gang Duan, Zahra Zahid Piracha, Umar Saeed, Yanrong Tian","doi":"10.5812/ijpr-166894","DOIUrl":"10.5812/ijpr-166894","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer is the most common endocrine malignancy, with aggressive subtypes frequently demonstrating resistance to conventional therapies. Bavachinin, a natural flavonoid derived from <i>Psoralea corylifolia</i>, has exhibited anti-cancer activity in various tumor models; however, its effects on thyroid cancer remain largely undefined.</p><p><strong>Objectives: </strong>The aim of this study is to evaluate the anti-cancer activity of bavachinin in the papillary thyroid carcinoma TPC-1 cell line and elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>TPC-1 cells were treated with bavachinin (5 - 20 μM) for 24 - 72 hours. Cell viability was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay); morphological changes were visualized by confocal microscopy. Migration and invasion were analyzed by wound-healing and Transwell assays, respectively. Cytokine secretion was measured using enzyme-linked immunosorbent assay (ELISA). Gene and protein expression levels of protein kinase B (AKT), mechanistic target of rapamycin (mTOR), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Apoptosis was confirmed by assessing the B-cell lymphoma-2-associated X protein (BAX)/B-cell lymphoma-2 (BCL-2) ratio and cleaved caspase-3 activity. All experiments were performed in triplicate, and data are presented as mean ± standard deviation (SD). Statistical significance was determined by one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test (P < 0.05).</p><p><strong>Results: </strong>Bavachinin significantly reduced cell viability, migration, and invasion in a dose-dependent manner (20 μM reduced viability by approximately 50% at 72 hours, P < 0.01). It suppressed the phosphorylation of AKT and ERK1/2, downregulated mTOR expression, and decreased secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Apoptosis was confirmed by an increased BAX/BCL-2 ratio and elevated cleaved caspase-3 levels.</p><p><strong>Conclusions: </strong>Bavachinin exerts multi-targeted anti-cancer effects in thyroid carcinoma cells through dual inhibition of the phosphoinositide-3-kinase (PI3K)/AKT/mTOR and mitogen-activated protein kinase (MAPK)/ERK pathways, along with suppression of pro-inflammatory cytokines, culminating in apoptosis and impaired invasiveness.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e166894"},"PeriodicalIF":1.8,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878463","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":"Oncogenic Function of miR-182-5p Versus Tumor-Suppressive Activities of miR-203, miR-150-5p, and miR-139-5p via Target Gene Regulation in Colon Cancer Metastasis.","authors":"Sheryar Afzal, Ali Attiq","doi":"10.5812/ijpr-164911","DOIUrl":"10.5812/ijpr-164911","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) play key roles in colorectal cancer (CRC) progression and metastasis. miR-182-5p acts as an oncogenic metastamiR, frequently upregulated in cancers and promoting cell migration and invasion. In contrast, miR-203, miR-150-5p, and miR-139-5p function as tumor suppressors and are often downregulated in CRC.</p><p><strong>Methods: </strong>Expression levels of these four miRNAs were quantified in three CRC cell lines using real-time polymerase chain reaction (RT-PCR). Functional assays, including cell viability, migration, and invasion, were conducted after silencing miR-182-5p or overexpressing the tumor-suppressive miRNAs through mimic transfection.</p><p><strong>Results: </strong>The miR-182-5p was significantly overexpressed and positively correlated with metastatic potential, while miR-203, miR-150-5p, and miR-139-5p were downregulated and inversely associated with metastatic traits. Modulation of these miRNAs reduced CRC cell viability, migration, and invasion. Mechanistically, miR-182-5p enhanced metastasis via ANLN and PDE4D regulation, whereas miR-203, miR-150-5p, and miR-139-5p suppressed metastasis through PDE4D, NEGR1, and ATP11A pathways, respectively.</p><p><strong>Conclusions: </strong>These results highlight the opposing roles of miR-182-5p and the tumor-suppressive miRNAs in CRC metastasis and suggest their potential as biomarkers and therapeutic targets.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164911"},"PeriodicalIF":1.8,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877907","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":"Effects of Acacetin on the Pharmacokinetics of Diazepam in vivo and in vitro.","authors":"Ailian Hua, Li Wang, Yao Zhu, Quan Zhou, Abdullah Al Mamun, Shuanghu Wang, Fan Wu, Minzhi Xu","doi":"10.5812/ijpr-164825","DOIUrl":"10.5812/ijpr-164825","url":null,"abstract":"<p><strong>Background: </strong>Herb-drug interactions (HDIs) have garnered significant attention in recent years.</p><p><strong>Objectives: </strong>To investigate the effects of acacetin on the pharmacokinetics of diazepam both in vivo and in vitro.</p><p><strong>Methods: </strong>Rat liver microsomes (RLMs) were incubated with diazepam and acacetin to determine the half-maximal inhibitory concentration (IC₅₀) and inhibition constant (Ki) values of acacetin, as well as to evaluate its inhibitory effect on diazepam metabolism in vitro. For the in vivo experiment, twelve male Sprague-Dawley rats were randomly allocated into two groups (n = 6) and received either 50 mg/kg acacetin or vehicle for two weeks. Subsequently, diazepam (10 mg/kg) was administered to each rat. Blood samples (300 μL) were collected from the tail vein at 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, and 8 hours post-administration. The plasma concentrations of diazepam and its metabolites were quantified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).</p><p><strong>Results: </strong>The IC₅₀ values for temazepam and nordiazepam in RLMs were 2.065 μM and 5.2 μM, respectively. The Ki values for temazepam and nordazepam demonstrated that acacetin inhibits diazepam metabolism in vitro. In vivo, pretreatment with acacetin increased the area under the curve (AUC) and maximum plasma concentration (Cmax) of diazepam, while significantly decreasing its apparent clearance (CLz/F, P < 0.05). The AUC values for temazepam and nordiazepam decreased, whereas their CLz/F values increased significantly (P < 0.05). PyMOL simulations indicated that acacetin and diazepam share the same cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19) binding pocket, suggesting that acacetin inhibits diazepam metabolism via competitive inhibition.</p><p><strong>Conclusions: </strong>Acacetin significantly altered the pharmacokinetics of diazepam both in vivo and in vitro, indicating a potential interaction between acacetin and diazepam. Therefore, the concomitant use of acacetin and diazepam in clinical practice should be approached with caution.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164825"},"PeriodicalIF":1.8,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878372","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":"Quercetin Inhibits Gastric Cancer Progression via Suppression of HOTAIR/mir-217/GPC5 Axis.","authors":"Zhuqing Qiu, Chonglei Qu, Xiaoying Wu","doi":"10.5812/ijpr-165480","DOIUrl":"10.5812/ijpr-165480","url":null,"abstract":"<p><strong>Background: </strong>Long noncoding RNA (lncRNA) hox transcript antisense intergenic RNA (HOTAIR) is implicated in the progression of gastric cancer (GC) by promoting the microRNA-217 (miR-217)-glypican-5 (GPC5) axis. Quercetin (QCT), a well-known flavonoid, has demonstrated anticancer effects against various malignancies, including GC. However, the impact of QCT on HOTAIR expression and its downstream mediators remains unclear.</p><p><strong>Objectives: </strong>This study aimed to elucidate the antitumor mechanisms of QCT and its regulatory effects on the HOTAIR/miR-217/GPC5 axis in AGS and MKN-45 GC cell lines.</p><p><strong>Methods: </strong>Cellular viability, apoptosis, cell cycle progression, invasion, and oxidative stress markers were assessed using the MTT assay, annexin V-FITC/PI staining, real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and spectrophotometry. Expression levels of HOTAIR, miR-217, and GPC5 were quantified.</p><p><strong>Results: </strong>The QCT significantly downregulated HOTAIR and GPC5 while upregulating miR-217 in both cell lines (P < 0.001). The QCT induced dose-dependent apoptosis and cell cycle arrest, and reduced invasion through upregulation of TP53/PTEN (P < 0.05). Oxidative stress modulation displayed lineage-specific differences, with a marked reduction in malondialdehyde (MDA) in MKN-45 cells (P = 0.013). AGS cells exhibited greater sensitivity to QCT than MKN-45 cells.</p><p><strong>Conclusions: </strong>These findings highlight QCT's ability to inhibit GC progression via the HOTAIR/miR-217/GPC5 axis, with molecular heterogeneity influencing therapeutic response. The QCT emerges as a promising candidate for further investigation as a multifaceted agent against GC, though validation in preclinical models is necessary.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e165480"},"PeriodicalIF":1.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12680949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700925","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":"Design, Expression, and Binding Interactions Study of the Recombinant Engineered IL-6R.","authors":"Elham Mehdizadeh Marzenaki, Mojgan Bandehpour, Adel Haghighi, Sepideh Ghani, Maryam Tabarzad, Mahya Nasrollahi, Bahram Kazemi","doi":"10.5812/ijpr-165026","DOIUrl":"10.5812/ijpr-165026","url":null,"abstract":"<p><strong>Background: </strong>The trans-signaling pathway mediated by soluble interleukin-6 receptor (IL-6R) plays a crucial role in the pathogenesis of chronic inflammatory diseases, autoimmune disorders, and various cancers.</p><p><strong>Objectives: </strong>The present study aimed to model amino acid residues 121 to 300 of the IL-6R and to predict the effect of this selected fragment on reducing its interaction with glycoprotein 130 (gp130) using molecular docking.</p><p><strong>Methods: </strong>The engineered selected sequence interleukin-6 receptor (seIL-6R) was designed to diminish interaction with gp130. Physicochemical parameters were evaluated using the ProtParam tool. Structural modeling and prediction were performed using AlphaFold. Molecular docking was conducted using ClusPro. Subsequently, the seIL-6R gene was recombinantly expressed in the Chinese hamster ovary (CHO)-K1 cell line. The expression of recombinant seIL-6R was evaluated by Western blotting, and its secondary structure was examined by Fourier transform infrared (FTIR) spectroscopy.</p><p><strong>Results: </strong>Evaluation of the physicochemical parameters of the recombinant seIL-6R protein demonstrated improved stability and solubility, along with a reduced molecular weight (20.6 kDa). Molecular docking results indicated reduced binding of seIL-6R to gp130. Expression of the recombinant seIL-6R protein was confirmed by Western blotting. Furthermore, FTIR spectroscopy revealed that the secondary structure of seIL-6R was preserved and consistent with predicted structural models.</p><p><strong>Conclusions: </strong>This engineered protein has potential for further investigation as a promising and cost-effective therapeutic agent targeting IL-6-related pathologies.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e165026"},"PeriodicalIF":1.8,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12680950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700999","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":"Traditional Chinese Medicine Approach to Renal Cell Carcinoma: Jing-Si Herbal Tea Triggers Apoptosis and Ferroptosis in HK-2 Cells.","authors":"Yao-Chou Tsai, Chung-Che Tsai, Jin-Yin Chang, Hsu-Hung Chang, Chan-Yen Kuo","doi":"10.5812/ijpr-166286","DOIUrl":"10.5812/ijpr-166286","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney, with clear cell renal cell carcinoma (ccRCC) representing its predominant subtype. Despite significant advances in targeted and immune therapies, treatment resistance and recurrence continue to pose major challenges, underscoring the urgent need for novel therapeutic strategies. Jing-Si Herbal Tea (JSHT), a traditional Chinese medicine (TCM) formulation, has demonstrated anti-tumor, anti-inflammatory, and antioxidant properties; however, its mechanisms of action in kidney disease and cancer remain poorly understood.</p><p><strong>Methods: </strong>Human proximal tubule epithelial (HK-2) cells were treated with various concentrations of JSHT (0%, 4%, and 8%) for 24 and 48 hours. Cell viability was assessed using the WST-1 assay. The expression levels of cleaved-caspase 3, glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were analyzed by western blotting and quantified relative to β-actin.</p><p><strong>Results: </strong>The JSHT significantly reduced HK-2 cell viability in a time- and concentration-dependent manner. Treatment with JSHT resulted in upregulation of cleaved-caspase 3, indicating activation of apoptosis, while concurrently downregulating GPX4 and SLC7A11, which are key regulators of ferroptosis resistance. These findings demonstrate that JSHT induces two forms of regulated cell death - ferroptosis and apoptosis - in renal epithelial cells.</p><p><strong>Conclusions: </strong>The JSHT exhibits antiproliferative effects in HK-2 cells by promoting apoptosis and sensitizing cells to ferroptosis through suppression of GPX4 and SLC7A11. These results provide preliminary mechanistic insights into the effects of JSHT and indicate its potential relevance for future research in RCC. However, validation in RCC-specific models and in vivo systems is necessary. A notable limitation of this study is the use of a non-cancerous renal cell line; thus, the in vitro findings may not fully recapitulate tumor biology. Future studies employing RCC cell lines, patient-derived tumor models, and in vivo validation are warranted to elucidate the therapeutic potential of JSHT as a complementary approach for RCC management.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e166286"},"PeriodicalIF":1.8,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677659","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}