Research in Pharmaceutical Sciences最新文献

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Effects of PPARα, PPARγ, and dual PPARα/γ agonists on liver tissue and biochemical markers in NAFLD-induced Wistar rats. PPARα、PPARγ和双PPARα/γ激动剂对nafld诱导Wistar大鼠肝组织和生化指标的影响。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_182_25
Elham Khoshbakht, Negar Dinarvand, Hamid Yaghooti, Behrouz Taheri, Narges Mohammadtaghvaei
{"title":"Effects of PPARα, PPARγ, and dual PPARα/γ agonists on liver tissue and biochemical markers in NAFLD-induced Wistar rats.","authors":"Elham Khoshbakht, Negar Dinarvand, Hamid Yaghooti, Behrouz Taheri, Narges Mohammadtaghvaei","doi":"10.4103/RPS.RPS_182_25","DOIUrl":"10.4103/RPS.RPS_182_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder worldwide, affecting approximately 25% of the global population. Peroxisome proliferator-activated receptor (PPAR) agonists play an important role in NAFLD management through modulation of lipid metabolism and insulin sensitivity. This study compared the effects of fenofibrate (PPARα agonist), pioglitazone (PPARγ agonist), and saroglitazar (dual PPARα/γ agonist) in a high-fat diet (HFD)-induced NAFLD rat model.</p><p><strong>Experimental approach: </strong>NAFLD was induced in Wistar rats by feeding a high-fat diet. Animals were assigned to control, HFD, and HFD-treated groups receiving saroglitazar (3 mg/kg), pioglitazone (30 mg/kg), or fenofibrate (100 mg/kg) for six weeks. Anthropometric parameters, serum liver enzymes, lipid profile, fasting blood glucose, and HOMA-IR were assessed. Histopathological changes were evaluated using H&E and Masson's trichrome staining. Hepatic expression of FGF21, CPT-1, PPARa, SREBP-1c, and ACC was analyzed by quantitative RT-PCR.</p><p><strong>Findings/results: </strong>All three PPAR agonists significantly improved hepatic steatosis, inflammation, and fibrosis compared with the HFD group, despite variability in biochemical and metabolic parameters. Among the treatments, saroglitazar demonstrated the most pronounced histological improvement, although systemic metabolic improvements were comparable among all three agents.</p><p><strong>Conclusion and implications: </strong>Fenofibrate, pioglitazone, and saroglitazar exert beneficial effects on NAFLD progression through partially distinct mechanisms. Dual PPARα/γ activation appears to preferentially enhance hepatic histological outcomes, supporting the therapeutic relevance of saroglitazar in NAFLD.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"292-304"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of pomegranate seed extract and ellagic acid on miR-16-5p and miR-34a-5p expression, cell cycle, and apoptosis in MCF-7 cells. 石榴籽提取物和鞣花酸对MCF-7细胞中miR-16-5p和miR-34a-5p表达、细胞周期和凋亡的影响。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_247_24
Zahra Sadeghi, Mohammadreza Sharifi, Mehrnoush Malekzadeh, Sho'leh Ghaedamini, Batool Hashemibeni
{"title":"Effects of pomegranate seed extract and ellagic acid on miR-16-5p and miR-34a-5p expression, cell cycle, and apoptosis in MCF-7 cells.","authors":"Zahra Sadeghi, Mohammadreza Sharifi, Mehrnoush Malekzadeh, Sho'leh Ghaedamini, Batool Hashemibeni","doi":"10.4103/RPS.RPS_247_24","DOIUrl":"10.4103/RPS.RPS_247_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>The expression of <i>Homo sapiens (has)-miR-16-5p</i> and <i>hsa-miR-34a-5p</i> with anti-tumor effects is downregulated in cancer cells. To maintain these gene expressions in cancer cells, we evaluated the effects of pomegranate seed extract (PSE) and ellagic acid (EA) on <i>hsa-miR-16-5p</i> and <i>hsa-miR- 34a-5p</i> expression, cell cycle regulation, and apoptotic induction in the MCF-7 cells encapsulated in the alginate hydrogel, a 3D culture system.</p><p><strong>Experimental approach: </strong>MCF-7 cells were encapsulated in 3-D alginate scaffolds and cultured (experimental groups: EA, PSE, EA and PSE, and the control group). Cell viability (using MTT assay), cell apoptosis <i>(via</i> flow cytometry), the level of malondialdehyde (MDA), and the expression levels of <i>hsa-miR-16-5p, hsa-miR- 34a-5p,</i> B-cell lymphoma 2 <i>(BCL-2),</i> cyclin D1 <i>(CCND1),</i> and sirtuin 1 <i>(SIRT1)</i> were measured (via real-time PCR).</p><p><strong>Findings/results: </strong>The combination of PSE and EA exhibited the greatest effects on MCF-7 cells. EA and PSE increased the expression of <i>hsa-miR-16-5p</i> and <i>hsa-miR-34a-5p</i> and decreased the expression of the <i>SIRT1</i> and <i>CCND1</i> genes. In addition, the antiapoptotic <i>BCL-2</i> gene was downregulated in the experimental group. Both antioxidants significantly increased the population of MCF-7 cells in the G1 phase. Additionally, antioxidants reduce the level of MDA in cancer cells.</p><p><strong>Conclusion and implications: </strong>EA and PSE antioxidants increased <i>hsa-miR-16-5p</i> and <i>hsa-miR-34a-5p</i> expression, induced apoptosis, decreased cell proliferation, and stopped cancer cells in the G1 phase. Therefore, they can be considered promising compounds for helping the treatment of breast cancer.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"333-345"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New 5-(pyridin-3-yl)-1,3,4-oxadiazoles derivatives as VEGFR2 inhibitors: in silico study, synthesis, and cytotoxicity evaluation. 新的5-(吡啶-3-基)-1,3,4-恶二唑衍生物作为VEGFR2抑制剂:硅研究,合成和细胞毒性评价。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_222_25
Ahmed Nasser Abdulhussein, Mohammed Abdulameer Oleiwi
{"title":"New 5-(pyridin-3-yl)-1,3,4-oxadiazoles derivatives as VEGFR2 inhibitors: <i>in silico</i> study, synthesis, and cytotoxicity evaluation.","authors":"Ahmed Nasser Abdulhussein, Mohammed Abdulameer Oleiwi","doi":"10.4103/RPS.RPS_222_25","DOIUrl":"10.4103/RPS.RPS_222_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Angiogenesis, regulated by vascular endothelial growth factor receptor 2 (VEGFR-2), has a key role in tumor progression, especially in common cancers, including colorectal and renal cancer. Inhibiting VEGFR-2 is a promising therapeutic approach. This research aimed to design, synthesize, and biologically evaluate new 5-(pyridine-3-yl)-1,3,4-oxadiazole derivatives as potential VEGFR-2 inhibitors.</p><p><strong>Experimental approach: </strong>A new series of derivatives (AM3-AM6) was synthesized through S-alkylation of 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol and hydrazinolysis reactions, followed by condensation with aldehydes. The compounds were analyzed using FT-IR,<sup>1</sup>H-NMR, and <sup>13</sup>C-NMR spectroscopy. Molecular modelling studies, including docking (PDB ID: 4ASD), ADMET prediction, and molecular dynamics (MD) simulations, were performed to evaluate binding affinity, pharmacokinetic properties, and complex stability. Cytotoxicity was assessed <i>via</i> MTT assay against HT-29 (colorectal), ACHN (renal), and L929 (normal) cell lines.</p><p><strong>Findings/results: </strong>Docking results revealed strong binding to VEGFR-2, with compound AM3 showing the best docking score (ΔG = -11.613 kcal/mol). MD simulations confirmed the high stability of the AM3-VEGFR-2 complex with consistent RMSD values and persistent interactions with GLU885 and ASP1046. <i>In vitro,</i> AM4 exhibited a significant cytotoxic effect against HT-29 cells (IC<sub>50</sub> = 38.94 μM), compared to sorafenib (IC<sub>50</sub> = 9.73), while all compounds were non-toxic toward L929 cells.</p><p><strong>Conclusions and implications: </strong><i>In silico</i> and <i>in vitro</i> results demonstrated that the new 5-(pyridine-3-yl)-1,3,4-oxadiazole derivatives possess favorable drug-like properties and selective anti-proliferative activity against colorectal and renal cancer cells. These findings suggest that this scaffold is a valuable starting point for developing novel selective VEGFR-2 inhibitors as anticancer agents.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"278-291"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing soluble expression and purification of a bispecific scFv antibody in Escherichia coli using chaperones. 利用伴侣蛋白增强大肠杆菌双特异性scFv抗体的可溶性表达和纯化。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_10_24
Zahra Alidousti-Shahraki, Afrooz Amini-Dehkordi, Nafiseh Esmaeil, Vajihe Akbari
{"title":"Enhancing soluble expression and purification of a bispecific scFv antibody in <i>Escherichia coli</i> using chaperones.","authors":"Zahra Alidousti-Shahraki, Afrooz Amini-Dehkordi, Nafiseh Esmaeil, Vajihe Akbari","doi":"10.4103/RPS.RPS_10_24","DOIUrl":"10.4103/RPS.RPS_10_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>The use of a bispecific antibody engineered as a tandem single-chain fragment variable antibody (scFv-BsAb) offers several advantages over full-length antibodies, including enhanced tissue penetration and the potential for production in bacterial cells. However, production of them in bacteria usually results in the formation of inclusion bodies. The current work aimed to facilitate proper folding and soluble expression of a recombinant scFv-BsAb targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) by co-expression with molecular chaperones.</p><p><strong>Experimental approach: </strong><i>Escherichia coli</i> BL21(DE3) cells harboring pET28a-scFv-BsAb and pKJE7 plasmids were used as host cells for protein expression. The effect of different temperatures and IPTG concentrations on the expression of soluble protein with or without expression of chaperones was investigated by SDS-PAGE and densitometry analysis. Subsequently, the expressed protein was subjected to native purification using a Ni-NTA affinity column. Then, the binding ability of the scFv-BsAb to the receptors on peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry.</p><p><strong>Findings/results: </strong>Co-expression with chaperones slightly enhanced the expression of soluble scFv-BsAb. The optimal condition for soluble expression of protein is at a temperature of 30 °C and an IPTG concentration of 1 mM when co-expressed with chaperones. The final yield of protein in co-expression with chaperones was 2.9 mg protein per 1 L of culture.</p><p><strong>Conclusion and implications: </strong>Optimization of culture conditions and co-expression with molecular chaperones may be useful for the production of soluble and functionally bioactive scFv antibodies in <i>E. coli.</i></p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"323-332"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aseptic meningitis induced by monoclonal antibodies used in cancer treatment: a systematic review. 单克隆抗体诱导无菌性脑膜炎在癌症治疗中的应用:系统综述。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_236_24
Nasibeh Ghalandari, Sara Ataei, Fahime Nasr Esfahani, Shahaboddin Emami
{"title":"Aseptic meningitis induced by monoclonal antibodies used in cancer treatment: a systematic review.","authors":"Nasibeh Ghalandari, Sara Ataei, Fahime Nasr Esfahani, Shahaboddin Emami","doi":"10.4103/RPS.RPS_236_24","DOIUrl":"10.4103/RPS.RPS_236_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Monoclonal antibodies (MAbs) have revolutionized cancer treatment but are associated with a spectrum of adverse events, including neurological complications. Understanding the mechanism and management of complications is crucial for optimizing patient care. The present systematic review aimed to identify case reports of MAbs used for cancer treatment that resulted in aseptic meningitis (AM).</p><p><strong>Methods: </strong>Databases including Google Scholar, PubMed, and Scopus were searched for studies published until March 2024 (updated in May 2025). The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the quality of case report studies, and the methodological quality of the included studies was considered acceptable.</p><p><strong>Findings/results: </strong>In total, 32 articles were analyzed in the present systematic review. Cetuximab had the highest reported incidence of AM, while rituximab, daratumumab, and apolizumab had the lowest prevalence. The quality of the studies was also acceptable.</p><p><strong>Conclusion and implications: </strong>AM appears to occur more frequently with monoclonal antibodies than with conventional drug structures. Prompt recognition of the underlying mechanisms can help physicians manage these complications more effectively.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"262-277"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Thymoquinone and pentoxifylline modulate 5-fluorouracil-induced senescence and apoptosis in colorectal cancer spheroids. 百里醌和己酮茶碱调节5-氟尿嘧啶诱导的结直肠癌球体的衰老和凋亡。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_175_25
Fatemeh Makalani, Ali Ghanbari, Mohammad Reza Tabandeh, Touraj Zamir Nasta, Alborz Jafaei Souq, Cyrus Jalili
{"title":"Thymoquinone and pentoxifylline modulate 5-fluorouracil-induced senescence and apoptosis in colorectal cancer spheroids.","authors":"Fatemeh Makalani, Ali Ghanbari, Mohammad Reza Tabandeh, Touraj Zamir Nasta, Alborz Jafaei Souq, Cyrus Jalili","doi":"10.4103/RPS.RPS_175_25","DOIUrl":"10.4103/RPS.RPS_175_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Targeting senescent tumor cells with senotherapeutic agents represents a novel therapeutic strategy in overcoming chemotherapy resistance during 5-fluorouracil (5-FU) treatment of colorectal cancer (CRC). This study aimed to evaluate the senotherapeutic potential of thymoquinone (TQ) and pentoxifylline (PTX) in a 3D spheroid model of CRC subjected to 5-FU-induced senescence.</p><p><strong>Experimental approach: </strong>Caco-2 spheroids were generated <i>via</i> the hanging drop method on Poly-HEMA-coated plates with conditioned medium derived from HFF cells. Spheroids were treated for 24 h with 5-FU (60 μΜ; 50% of IC<sub>50</sub>), TQ (30 μΜ; 50% of IC<sub>50</sub>), and PTX (3.5 mM; 50% of IC<sub>50</sub>). Cell viability was measured using the MTT assay. ROS and IL-8 levels were measured. Cell death and apoptosis were evaluated using Calcein-AM and Annexin V/PI assays, and western blotting was used to assess the expression of SASP and apoptosis-associated proteins. β-galactosidase activity was measured as a marker of senescence.</p><p><strong>Findings/results: </strong>5-FU effectively induced senescence and apoptosis in Caco-2 spheroids, as evidenced by an increased expression of p53, p16, p21, and γ-H2AX, as well as an elevated secretion of ROS. Co-treatment with TQ and PTX acted as senotherapeutic agents by enhancing apoptotic cell death through modulation of Bax/Bcl2/cleaved caspase-3 and β-galactosidase activity, and by increasing oxidative stress. Notably, the combination of TQ and PTX was shown to support a greater senotherapeutic effect.</p><p><strong>Conclusion and implications: </strong>Findings indicated that TQ and PTX acted as senotherapeutic agents in 5-FU-induced senescent CRC spheroids and may have potential as adjuvants to enhance CRC therapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"305-322"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular docking, synthesis, and cytotoxic evaluation of novel quinazoline-quinazolinone hybrid compounds. 新型喹唑啉-喹唑啉酮杂化化合物的分子对接、合成及细胞毒性评价。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_150_24
Majid Azarmi, Saman Rahimi, Maryam Hormozi, Rezvan Rezaeinasab
{"title":"Molecular docking, synthesis, and cytotoxic evaluation of novel quinazoline-quinazolinone hybrid compounds.","authors":"Majid Azarmi, Saman Rahimi, Maryam Hormozi, Rezvan Rezaeinasab","doi":"10.4103/RPS.RPS_150_24","DOIUrl":"10.4103/RPS.RPS_150_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cancer represents a significant public health challenge and a leading cause of mortality globally. Quinazolinones represent a class of privileged structures that exhibit a broad spectrum of biological activities such as anticancer, antihypertensive, antifungal, antibacterial, and anti-inflammatory properties. In the present study, the synthesis of quinazoline-quinazolinone hybrids as anticancer agents and their cytotoxic evaluation are reported.</p><p><strong>Experimental approach: </strong>Initial studies were done by molecular docking of five analogs of quinazoline- quinazolinone hybrids, erlotinib, and doxorubicin against the epidermal growth factor receptor. Treatment of 3-amino quinazolinone with 4-chloro-2-phenylquinazoline afforded final compounds by the nucleophilic substitution of the chloride with the amine of 3-amino quinazolinone derivatives. The cytotoxic effects of the final compounds were determined <i>in vitro</i> against the MCF-7 cell line using the MTT assay.</p><p><strong>Findings/results: </strong>Compound <b>5b</b> (7-hydroxy-2-methyl-3-(2-phenylquinazolin-4-ylamino) quinazolin-4(3H)- one) showed the highest docking score of -10.1 kcal/mol. Additionally, compound <b>5d</b> (2-methyl-7-nitro-3-(2- phenylquinazolin-4-ylamino) quinazolin-4(3H)-one) exhibited remarkable <i>in-vitro</i> cytotoxic activity at 100 μM against the MCF-7 cells.</p><p><strong>Conclusion and implications: </strong>In the present study, quinazoline-quinazolinone hybrids were synthesized, and their cytotoxic effects on the MCF-7 cell line were evaluated. Among them, compound <b>5d</b> exhibited the most significant cytotoxic activity. The insertion of a nitro group at the 7 position of quinazolinone enhanced the cytotoxic efficacy against MCF-7 cells, likely attributable to electronic influences. Consequently, this compound could serve as a lead compound in the search for new classes of effective anticancer agents.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"375-385"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cells via NF-κB inflammatory modulation. 重组IGFBP-3和顺铂通过NF-κB炎症调节对hpv18阳性HeLa细胞的协同细胞毒性
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_62_25
Hourolein Arab, Mohammad Shokrzadeh, Tahoora Mousavi, Mohammad Reza Mofid
{"title":"Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cells <i>via</i> NF-κB inflammatory modulation.","authors":"Hourolein Arab, Mohammad Shokrzadeh, Tahoora Mousavi, Mohammad Reza Mofid","doi":"10.4103/RPS.RPS_62_25","DOIUrl":"10.4103/RPS.RPS_62_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>Insulin-like growth factor-binding protein-3 (IGFBP-3), a tumor suppressor and inhibitor of nuclear factor kappa B (NF-kB), has emerged as a promising candidate for therapeutic application across diverse pathological conditions. Given NF-kB's role in cervical cancer development and cisplatin resistance, this study examines the effects of recombinant human IGFBP-3 (rhIGFBP-3), alone and in combination with cisplatin, on NF-kB levels, inflammatory modulation, and apoptotic response in HeLa cells, and investigates whether rhIGFBP-3 can reduce the cisplatin dose.</p><p><strong>Experimental approach: </strong>The impact of rhIGFBP-3, alone and in combination with cisplatin, on HeLa cells' viability was evaluated by assessing cell viability (MTT assay); apoptosis (cell cycle analysis, TUNEL, annexin V/PI staining, Bax/Bcl-2 ratio, caspase activity); and NF-kB p65 levels (western blot). Gene expression of inflammatory cytokines and enzymes (IL-6, IL-8, COX-2, iNOS) was analyzed by RT-PCR.</p><p><strong>Findings/results: </strong>Cisplatin and rhIGFBP-3 inhibited HeLa cell growth in a concentration-dependent manner (IC<sub>50</sub> = 6.06 μg/mL and 1.12 μg/mL, respectively). Their combination exhibited synergistic cytotoxicity (combination index < 1), allowing ~2.1-fold reductions in concentration to 2.53 μg/mL cisplatin and 0.46 μg/mL rhIGFBP-3 for 45% growth inhibition. Compared to monotherapy, the combination significantly enhanced apoptosis and DNA fragmentation, sub-G1 accumulation, caspase-8/9/3/7 activation, and BAX/BCL-2 ratio. It also considerably reduced NF-kB p65 and inflammatory markers in comparison with cisplatin alone.</p><p><strong>Conclusion and implications: </strong>Our study demonstrated that rhIGFBP-3 enhanced cisplatin efficacy by promoting apoptosis and attenuating inflammation, highlighting its potential as both a cisplatin adjuvant and a monotherapy in HeLa cells.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"386-402"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ferula gummosa in colorectal cancer: a bioinformatics and experimental validation study. 结直肠癌中的牙龈阿魏:生物信息学和实验验证研究。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_246_24
Abbas Alibakhshi, Shima Gharibi, Ali Shojaeian, Atefeh Asgari, Razieh Amini, Mehdi Rahimmalek, Shahrzad Ahangarzadeh, Antoni Szumny
{"title":"<i>Ferula gummosa</i> in colorectal cancer: a bioinformatics and experimental validation study.","authors":"Abbas Alibakhshi, Shima Gharibi, Ali Shojaeian, Atefeh Asgari, Razieh Amini, Mehdi Rahimmalek, Shahrzad Ahangarzadeh, Antoni Szumny","doi":"10.4103/RPS.RPS_246_24","DOIUrl":"10.4103/RPS.RPS_246_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Colorectal cancer (CRC) is a significant global health challenge, necessitating a comprehensive molecular understanding for personalized treatments. Molecular profiling has elucidated key biomarkers that are essential for prognosis, treatment responsiveness, and targeted therapeutic interventions.</p><p><strong>Experimental approach: </strong>This study explored the role of indigenous phytochemicals, using bioinformatics and experimental assays to identify potential CRC-specific therapeutic targets.</p><p><strong>Findings/results: </strong>A system biology and drug-target network analysis identified four proteins (ANG, DPP4, INSR, and MAPK14) as potential targets for further investigation. Molecular docking studies showed that the cauferoside from <i>Ferula gummosa</i> has a strong binding affinity for these proteins. Molecular dynamics simulations confirmed the stability of the compound-protein complexes. <i>In vitro</i> assays demonstrated the cytotoxic effects of <i>F. gummosa</i> extracts on CRC cells. The leaf extract significantly downregulated the expression of the <i>ANG</i>, <i>DPP4</i>, <i>INSR</i>, and <i>MAPK14</i> genes, while the root extract exhibited differential effects on gene expression.</p><p><strong>Conclusion and implications: </strong>The findings suggest the potential therapeutic efficacy of <i>F. gummosa</i> against CRC and emphasize the importance of a dual methodology involving bioinformatics and experimental validation in drug discovery. Further in <i>vivo</i> and clinical studies are warranted to validate these findings and facilitate potential therapeutic applications.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"346-363"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caffeic acid phenethyl ester protects mice against nicotine-induced seizures by attenuating oxidative stress and inflammation. 咖啡酸苯乙酯通过减轻氧化应激和炎症来保护小鼠免受尼古丁引起的癫痫发作。
IF 2.3
Research in Pharmaceutical Sciences Pub Date : 2026-05-10 eCollection Date: 2026-06-01 DOI: 10.4103/RPS.RPS_3_25
Mahdieh Sadat Badiee, Ali Vadizadeh, Mehrnoosh Moosavi, Fereshtesadat Fakhredini, Hadi Kalantar, Sirous Rafiei Asl, Mohammad Javad Khodayar
{"title":"Caffeic acid phenethyl ester protects mice against nicotine-induced seizures by attenuating oxidative stress and inflammation.","authors":"Mahdieh Sadat Badiee, Ali Vadizadeh, Mehrnoosh Moosavi, Fereshtesadat Fakhredini, Hadi Kalantar, Sirous Rafiei Asl, Mohammad Javad Khodayar","doi":"10.4103/RPS.RPS_3_25","DOIUrl":"10.4103/RPS.RPS_3_25","url":null,"abstract":"<p><strong>Background and purpose: </strong>A seizure is a neurological disorder in the brain that is caused by changes in the function of brain neurons. Caffeic acid phenetyl ester (CAPE), as a polyphenol, has antioxidant, anti-inflammatory, and anticancer effects. Since the effects of CAPE on the neurotoxins and neurotoxic medicinal agents have not been widely investigated, this study aimed to investigate the effect of CAPE on the nicotine (NIC)-induced seizures in mice.</p><p><strong>Experimental approach: </strong>Thirty-three male mice were divided into five groups of 6-8 as follows: sham group (normal saline), NIC group (5 mg/kg single dose on day 7), treatment groups (CAPE at 4 and 8 mg/kg for 7 days), and diazepam group (1 mg/kg single dose on day 7). At the end, the animals were anesthetized, and mortality, convulsive behavior, total thiol, thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and the expression of nuclear factor kappa B (NF-kB) protein in the brain frontal cortex were measured, and histological studies were performed.</p><p><strong>Findings/results: </strong>Treatment with CAPE decreased the levels of TBARS, TNF-α, and NO and increased the levels of total thiol, CAT, SOD, GPx, and NF-kB protein expression compared to the NIC group. Seizure behavioral tests and histopathological investigations confirmed these results.</p><p><strong>Conclusion and implications: </strong>According to the antioxidant effects of CAPE in various studies, it seems that CAPE can improve seizures by reducing inflammation and inhibiting oxidative stress.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"21 3","pages":"364-374"},"PeriodicalIF":2.3,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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