Amir Safi, Shakila Mohammadi, Mina Emami, Alireza Radaei, Ali Kalantari-Hesari, Ali Nouri, Mohammad Rahimi-Madiseh, Reza Ahmadi
{"title":"Thymoquinone mitigates diclofenac-induced hepatorenal toxicity in male Wistar rats by balancing the redox state and modulating Bax/Bcl-2/caspase-3 apoptotic pathways and NF-κB signaling.","authors":"Amir Safi, Shakila Mohammadi, Mina Emami, Alireza Radaei, Ali Kalantari-Hesari, Ali Nouri, Mohammad Rahimi-Madiseh, Reza Ahmadi","doi":"10.4103/RPS.RPS_141_24","DOIUrl":"10.4103/RPS.RPS_141_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Diclofenac (DF), a widely used non-steroidal anti-inflammatory drug, can induce hepatotoxicity and nephrotoxicity. This study investigated the protective effects of thymoquinone (TQ), a bioactive compound from <i>Nigella sativa</i>, against DF-induced organ damage in rats.</p><p><strong>Experimental approach: </strong>Forty-eight male rats were divided into six groups (8 each) and treated orally for seven days as follows: group 1 (control): normal saline; group 2: DF (50 mg/kg); group 3: DF (50 mg/kg) + silymarin (50 mg/kg); groups 4-6: DF (50 mg/kg) + TQ at 10, 20, or 40 mg/kg, respectively. Serum biochemical parameters, hepatorenal oxidative stress markers, pro-inflammatory cytokines, and apoptosis-related genes were assessed. Histopathological examinations of liver and kidney tissues were also performed.</p><p><strong>Findings/results: </strong>DF administration induced significant liver and kidney damage, evidenced by elevated serum biochemical markers, increased oxidative stress, inflammation, apoptosis-related gene expression, and histopathological alterations. TQ treatment, particularly at the highest dose (40 mg/kg) effectively attenuated these changes. TQ improved liver and kidney function, reduced oxidative stress markers, suppressed inflammation, modulated apoptosis-related gene expression, and ameliorated histopathological damage.</p><p><strong>Conclusion and implication: </strong>TQ exerted significant protective effects against DF-induced hepatorenal toxicity in rats, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These findings suggest that TQ may be a promising therapeutic agent for mitigating DF-induced organ damage. However, further research, including clinical trials, is needed to confirm its efficacy and safety in humans.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"95-108"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796163","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}
Sepideh Hassani, Hassan Malekinejad, Mohammad Hassan Khadem-Ansari, Ata Abbasi, Fatemeh Kheradmand
{"title":"Dietary silymarin supplementation enhances chemotherapy efficacy of capecitabine and irinotecan and mitigates hepatotoxicity in a mouse model of colon cancer.","authors":"Sepideh Hassani, Hassan Malekinejad, Mohammad Hassan Khadem-Ansari, Ata Abbasi, Fatemeh Kheradmand","doi":"10.4103/RPS.RPS_204_24","DOIUrl":"10.4103/RPS.RPS_204_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>The flavonoid silymarin (SMN) has shown promise due to its antioxidant, anti-inflammatory, and anticancer properties. SMN has been widely used in preclinical and clinical studies to treat various types of cancer, alone and with chemotherapy agents. Recent research suggests that SMN may increase conventional chemotherapy efficacy and reduce adverse effects. Herein, we investigated the therapeutic efficacy of SMN and its combination with capecitabine (CAP) and irinotecan (IRI) in a mouse model of colon cancer.</p><p><strong>Experimental approach: </strong>Following 1,2 dimethylhydrazine-induced colon cancer, a modified diet supplemented with SMN (2500 ppm) and mono- and combined therapy of CAP and IRI was used. Serum samples were analyzed for lipid profile, liver function, and inflammatory cytokines. Oxidative stress and inflammation markers, including malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in colonic, hepatic, and circulatory samples. Colonic BAX and Bcl-2 levels were examined <i>via</i> western blotting and histopathological analysis of colon sections was conducted.</p><p><strong>Findings/results: </strong>SMN alone and combined with chemotherapeutic agents significantly mitigated the elevated inflammatory cytokines liver function enzyme levels, and hyperlipidemia. Furthermore, SMN supplementation with chemotherapy agents enhanced antioxidant activity and reduced lipid peroxidation and inflammatory markers. Significant upregulation of BAX and downregulation of Bcl-2 were observed. In addition, treatment regimens ameliorated carcinogen-induced polyp multiplicity, adenoma formation, dysplastic changes, and lymphocytic aggregation.</p><p><strong>Conclusion and implications: </strong>Our results demonstrated that the potential anticancer properties of SMN could enhance chemotherapy efficacy and reduce carcinogen- and chemotherapy-induced hepatotoxicity.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"77-94"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796079","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":"Prognostic markers and molecular pathways in primary colorectal cancer with a high potential of liver metastases: a systems biology approach.","authors":"Fatemeh Bahramibanan, Amir Taherkhani, Rezvan Najafi, Neda Alizadeh, Hamidreza Ghadimipour, Nastaran Barati, Katayoun Derakhshandeh, Meysam Soleimani","doi":"10.4103/RPS.RPS_128_23","DOIUrl":"10.4103/RPS.RPS_128_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Colorectal cancer (CRC) holds the position of being the third most prevalent cancer and the second primary cause of cancer-related fatalities on a global scale. Approximately 65% of CRC patients survive for 5 years following diagnosis. Metastasis and recurrence frequently occur in half of CRC patients diagnosed at the late stage. This study used bioinformatics analysis to identify key signaling pathways, hub genes, transcription factors, and protein kinases involved in transforming primary CRC with liver metastasis potential. Prognostic markers in CRC were also identified.</p><p><strong>Experimental approach: </strong>The GSE81582 dataset was re-analyzed to identify differentially expressed genes (DEGs) in early CRC compared to non-tumoral tissues. A protein interaction network (PIN) was constructed, revealing significant modules and hub genes. Prognostic markers, transcription factors, and protein kinases were determined. Boxplot and gene set enrichment analyses were performed.</p><p><strong>Findings/results: </strong>This study identified 1113 DEGs in primary CRC compared to healthy controls. PIN analysis revealed 75 hub genes and 8 significant clusters associated with early CRC. The down-regulation of SUCLG2 and KPNA2 correlated with poor prognosis. SIN3A and CDK6 played crucial roles in early CRC transformation, affecting rRNA processing pathways.</p><p><strong>Conclusion and implications: </strong>This study demonstrated several pathways, biological processes, and genes mediating the malignant transformation of healthy colorectal tissues to primary CRC and may help the prognosis and treatment of patients with early CRC.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"121-141"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796082","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}
Leila Safaeian, Zahra Haghighatian, Mohammadreza Zamani
{"title":"Cardioprotective potential of protocatechuic acid against doxorubicin-induced cardiotoxicity in rats.","authors":"Leila Safaeian, Zahra Haghighatian, Mohammadreza Zamani","doi":"10.4103/RPS.RPS_220_23","DOIUrl":"10.4103/RPS.RPS_220_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Chemotherapy with doxorubicin (DOX) is associated with toxicity in many organs including cardiac tissue. A large body of evidence has suggested that phenolic acids, such as protocatechuic acid (PCA), have beneficial effects on cardiovascular problems. This investigation was conducted to evaluate the ameliorative properties of PCA against DOX-induced cardiotoxicity in Wistar rats.</p><p><strong>Experimental approach: </strong>Animals were treated with PCA (50, 100, and 200 mg/kg, orally) for 10 days. On the 7<sup>th</sup> day, a single injection of DOX (20 mg/kg/day, i.p.) was administered to induce cardiotoxicity. Electrocardiography, biochemical analysis of cardiac markers, and histological inspections were performed.</p><p><strong>Findings/results: </strong>Pretreatment with PCA, especially at the doses of 100 and 200 mg/kg for 7 days before the administration of DOX, significantly improved cardiac rhythm and pathological changes, reduced serum levels of creatine phosphokinase-MB, lactate dehydrogenase, aspartate aminotransferase, lipid peroxides and also prevented heart weight rise.</p><p><strong>Conclusions and implications: </strong>The <i>in-vivo</i> findings of the current study revealed that PCA exhibits protective effects against DOX-induced cardiotoxicity. These results suggest that PCA, a natural phenolic acid, may serve as a promising candidate for cardioprotective interventions in clinical trials involving chemotherapy with DOX.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"55-64"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796093","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":"Development and evaluation of Sahasthara Thai medicine remedy in a film-forming spray for topical anti-inflammatory therapy.","authors":"Ninnart Intharit, Arunporn Itharat, Chadchom Choockong, Weerachai Pipatrattanaseree, Wichan Ketjinda, Neal M Davies, Raimar Löbenberg","doi":"10.4103/RPS.RPS_22_24","DOIUrl":"10.4103/RPS.RPS_22_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>The study aimed to develop a localized topical anti-inflammatory treatment using a Thai medicinal herbal remedy called \"Sahasthara,\" known for its anti-inflammatory properties, to create a film-forming spray (FFS).</p><p><strong>Experimental approach: </strong>This research evaluated and developed an FFS formulated with Sahasthara ethanolic extract (SHTe). Subsequently, the optimized formulation was investigated for <i>in vitro</i> anti-inflammatory activity, cell culture toxicity assessment, pharmacological effects, and stability studies.</p><p><strong>Findings/results: </strong>An optimized formulation (F12) was identified, consisting of 1% w/w SHTe and PVP K90, glycerol, PEG 400, sesame oil, a eutectic blend, and ethanol. This clear, smooth surface, yellowish film releases 42.37%, 38.67%, and 68.93% at 8 h, corresponding to a flux of 20.94, 1.92, and 26.32 µg/cm2/h of piperine, plumbagin, and β-asarone, respectively. F12 was determined to have a viscosity, drying time, and spray angle of 20 cps, 4.57 min, and 66.0 degrees. <i>In-vitro</i> anti-inflammatory activity demonstrated nitric oxide (NO) inhibition with an IC50 of 9.18 µg/mL. No apparent toxicity was observed in a skin cell line. This formulation was developed to be physically stable after undergoing freeze-thaw cycles. Although thermodynamic stability studies under accelerated conditions revealed a minor decrease in piperine and β-asarone within the film, the results indicate no statistically significant changes in its anti-inflammatory activity.</p><p><strong>Conclusion and implications: </strong>SHTe FFS offers optimal spray ability, a high <i>in-vitro</i> drug release profile, potent inhibition of anti-inflammatory markers, and stability under accelerated conditions. These findings suggest that SHTe FFS can serve as an innovative topical anti-inflammatory treatment.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"25-40"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796061","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":"Synthesis and <i>in vitro</i> evaluation of self-assembling biocompatible heparin-based targeting polymeric micelles for delivery of doxorubicin to leukemic cells.","authors":"Jaber Emami, Moloud Kazemi, Mina Mirian","doi":"10.4103/RPS.RPS_197_24","DOIUrl":"10.4103/RPS.RPS_197_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Biodegradable polymeric micelles have emerged as one of the most promising platforms for targeted drug delivery. In the present study, a polymeric micelle composed of folic acid (FA), heparin (HEP), dexamethasone (DEX), and (FA-PEG-HEP-CA-TOC) was developed for the delivery of doxorubicin (DOX) to leukemic cells.</p><p><strong>Experimental approach: </strong>FA-HEP-DEX was synthesized and characterized by 1H-NMR. DOX-loaded micelles were prepared using a dialysis method. The impact of various processing variables, including polymer-to-drug ratio, dialysis temperature, and solvent type, on the physicochemical properties of the micelles were evaluated. In vitro, cellular uptake and cytotoxicity of the micelles in folate receptor-positive (K562) and negative (HepG2) cells were evaluated.</p><p><strong>Findings/results: </strong>The 1H-NMR results confirmed the successful synthesis of FA-HEP-DEX. DOX-loaded micelles exhibited an average particle size of 117 to 181 nm with a high drug entrapment efficiency (36% to 71%). DOX-loaded micelles also showed sustained drug-release behavior. DOX-loaded FA-HEP-DEX micelles exhibited higher cellular uptake and <i>in vitro</i> cytotoxicity than free DOX and DOX-loaded HEP-DEX micelles in K562 cells.</p><p><strong>Conclusions and implications: </strong>DOX was well incorporated into the micelles with high entrapment efficiency due to high solubility of DOX in DEX as the hydrophobic component of the micelle structure. The higher cellular uptake and cell toxicity of targeted micelles correspond to the presence of FA on the micelle surface, which promotes cell internalization of the micelles <i>via</i>specific receptor-mediated endocytosis. Our results indicated the potential of DOX-loaded heparin-based micelles with desirable antitumor activity as a targeted drug delivery system in cancer therapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"142-164"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796085","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}
Hadi Bakhtiari, Hamed Naghoosi, Sina Sattari, Mahmoud Vahidi, Mehdi Shakouri Khomartash, Ali Faridfar, Mohsen Rajaeinejad, Mohsen Nikandish
{"title":"A novel hybrid approach to overcome defects of CE-SELEX and cell-SELEX in developing aptamers against aspartate β-hydroxylase.","authors":"Hadi Bakhtiari, Hamed Naghoosi, Sina Sattari, Mahmoud Vahidi, Mehdi Shakouri Khomartash, Ali Faridfar, Mohsen Rajaeinejad, Mohsen Nikandish","doi":"10.4103/RPS.RPS_134_23","DOIUrl":"10.4103/RPS.RPS_134_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Aptamers, a new category of molecular probes, are overthrowing antibodies in molecular diagnostics. However, there are serious problems with using aptamers for this application including poor or non-specific binding <i>in vivo</i> conditions. Systematic evolution of aptamers is achieved through various approaches including CE-SELEX and Cell-SELEX, each suffering its inevitable weaknesses. The shortcomings of negative selection and the lengthy procedure are Cell-SELEX's main problems, while CE-SELEX is deprived of native targets. Here, we introduced a kind of hybrid CE-Cell-SELEX, named CEC hybrid-SELEX, for addressing these limitations in creating aptamer probes detecting human aspartate β-hydroxylase (ASPH), which is a well-established tumor biomarker, in cancer diagnostic investigations.</p><p><strong>Experimental approach: </strong>In our approach, the selected oligomer pool from the last cycle of CE-SELEX was sequenced and then subjected to 3 additional rounds of Cell-SELEX which provides native ASPH (CEC hybrid-SELEX). High-throughput sequencing was applied to achieve a comprehensive sight of the enriched pools. Further confirmatory investigations on oligomers with higher copy numbers were performed using flow cytometry.</p><p><strong>Findings/results: </strong>Three selected oligomers, AP-CEC 1, AP-CEC 2, and AP-CEC 3, showing Kd values of 43.09 nM, 34.85 nM, and 35.92 nM, respectively, were achieved based on the affinity assessment of the ASPH-expressing cells.</p><p><strong>Conclusion and implications: </strong>Our research suggested that CEC hybrid-SELEX could help recognize which oligomers from CE-SELEX are more capable of binding native ASPH <i>in vivo</i>.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"65-76"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796076","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}
Satrialdi, Cellina Pratiwi, Ryan Novia Khaeranny, Diky Mudhakir
{"title":"The development of mitochondria-targeted quercetin for rescuing Sertoli cells from oxidative stress.","authors":"Satrialdi, Cellina Pratiwi, Ryan Novia Khaeranny, Diky Mudhakir","doi":"10.4103/RPS.RPS_226_23","DOIUrl":"10.4103/RPS.RPS_226_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>The imbalance between reactive oxygen species (ROS) production and endogenous antioxidant capacity leads to oxidative stress, which may damage several cellular functions, particularly spermatogenesis. This condition is a leading cause of male infertility, so controlling ROS levels is crucial. The ROS level can be controlled by supporting the endogenous antioxidant system through antioxidant therapy. Mitochondria are the prime target for antioxidant therapy due to the majority of endogenous ROS produced in mitochondria and their critical role in providing energy during fertilization. This research aimed to develop mitochondria-targeted hybrid nanoplatforms by combining liposomes with dequalinium's mitochondriotropic agent (DQ) to deliver quercetin for targeted antioxidant therapy to mitochondria.</p><p><strong>Experimental approach: </strong>The quercetin-loaded nanocarrier was constructed using the hydration method. We varied the concentration of DQ to investigate its impact on physical characteristics, encapsulation efficiency, intracellular trafficking, and <i>in vitro</i> antioxidant activity.</p><p><strong>Findings/results: </strong>The impact of different DQ densities on particle size, encapsulation efficiency, and mitochondria targeting was insignificant. However, lowering the DQ density reduced the zeta potential. Minimizing oxidative stress on TM4 cells was only achieved with low-density DQ (Q-LipoDQ LD), while high-density DQ (Q-LipoDQ HD) failed to mitigate the negative impact.</p><p><strong>Conclusion and implications: </strong>According to the findings, LipoDQ LD preserves a promising potential as mitochondria-targeted nanoplatforms and validates the importance of mitochondria as a target for antioxidant therapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"109-120"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796107","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":"Advancing high-throughput anti-HCV drug screening: a novel dual-reporter HCV replicon model with real-time monitoring.","authors":"Kanokwan Chitsombat, Sarin Chimnaronk, Khanit Sa-Ngiamsuntorn, Mullika Traidej Chomnawang, Krit Thirapanmethee","doi":"10.4103/RPS.RPS_249_23","DOIUrl":"10.4103/RPS.RPS_249_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Hepatitis C virus (HCV) infection is a global health concern due to its substantial impact on morbidity and mortality. The burden of diseases related to HCV continues to escalate, particularly as infections progress to late-stage liver conditions, resulting in hepatocellular carcinoma on a global scale. Direct-acting antivirals effectively target HCV replication; however, their unreasonable costs and adverse effects emphasize the need for accessible and efficient therapeutic alternatives with minimal side effects. The primary aim of this study was to devise an HCV replicon system featuring a dual-reporter mechanism to facilitate high-throughput screening of potential novel antiviral agents.</p><p><strong>Experimental approach: </strong>The full-length HCV genome (pJFH1) was used to construct an HCV replicon system. The glycoprotein regions (E1 and E2) were substituted with a red fluorescent reporter, mCherry, enabling visualization of protein synthesis within the replicon. In addition, an adjacent green fluorescent reporter, dBroccoli, was strategically introduced in proximity to the NS5B stop codon to serve as a reliable indicator of HCV replication activity by monitoring the fluorescence signals.</p><p><strong>Findings/results: </strong>The findings of this study unequivocally validated the effectiveness of the novel HCV replicon system for transfecting Huh-7 cells. Furthermore, the replicon system demonstrated a concentration-dependent response to anti-HCV pharmaceutical agents including telaprevir and sofosbuvir.</p><p><strong>Conclusion and implications: </strong>These compelling results underscored the potential utility of the proposed HCV replicon system as an innovative model for the expeditious high-throughput screening of prospective anti-HCV agents within a short timeframe.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"41-54"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796090","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}
Parvin Zarei, Peyman Adibi Sedeh, Ahmad Vaez, Ammar Hassanzadeh Keshteli
{"title":"Using metabolomics to investigate the relationship between the metabolomic profile of the intestinal microbiota derivatives and mental disorders in inflammatory bowel diseases: a narrative review.","authors":"Parvin Zarei, Peyman Adibi Sedeh, Ahmad Vaez, Ammar Hassanzadeh Keshteli","doi":"10.4103/RPS.RPS_273_23","DOIUrl":"10.4103/RPS.RPS_273_23","url":null,"abstract":"<p><p>Individuals with inflammatory bowel disease (IBD) are at a higher risk of developing mental disorders, such as anxiety and depression. The imbalance between the intestinal microbiota and its host, known as dysbiosis, is one of the factors, disrupting the balance of metabolite production and their signaling pathways, leading to disease progression. A metabolomics approach can help identify the role of gut microbiota in mental disorders associated with IBD by evaluating metabolites and their signaling comprehensively. This narrative review focuses on metabolomics studies that have comprehensively elucidated the altered gut microbial metabolites and their signaling pathways underlying mental disorders in IBD patients. The information was compiled by searching PubMed, Web of Science, Scopus, and Google Scholar from 2005 to 2023. The findings indicated that intestinal microbial dysbiosis in IBD patients leads to mental disorders such as anxiety and depression through disturbances in the metabolism of carbohydrates, sphingolipids, bile acids, neurotransmitters, neuroprotective, inflammatory factors, and amino acids. Furthermore, the reduction in the production of neuroprotective factors and the increase in inflammation observed in these patients can also contribute to the worsening of psychological symptoms. Analyzing the metabolite profile of the patients and comparing it with that of healthy individuals using advanced technologies like metabolomics, aids in the early diagnosis and prevention of mental disorders. This approach allows for the more precise identification of the microbes responsible for metabolite production, enabling the development of tailored dietary and pharmaceutical interventions or targeted manipulation of microbiota.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"20 1","pages":"1-24"},"PeriodicalIF":2.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796171","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}