{"title":"Antifungal Potential of Streptomyces-Derived Metabolites Against Fluconazole-Resistant Oral Candida albicans: In vitro Evaluation and Mechanistic Insights.","authors":"Mahtab Karami-Feli, Zahra Jahanshiri, Akram Sadeghi","doi":"10.61186/ibj.4937","DOIUrl":"https://doi.org/10.61186/ibj.4937","url":null,"abstract":"<p><strong>Background: </strong>Oropharyngeal candidiasis, primarily caused by C. albicans, is the most common opportunistic fungal infection in patients with head and neck cancer. The increasing emergence of FLZ resistance has led to higher morbidity and mortality rates. Streptomyces, a genus of Actinomycetes, produces bioactive molecules with antimicrobial effects. This study investigated the antifungal potential of S. monomycini strain 615 against FLZ-resistant C. albicans clinical isolates in vitro.</p><p><strong>Methods: </strong>S. monomycini strain 615 was cultured, and an aqueous crud extract containing its metabolites was prepared. The effects of extract were tested on five FLZ-resistant C. albicans isolates. Key pathogenic factors such as protease activity, biofilm formation, and gene expressions related to virulence (SAP1, SAP2, HWP1, and ERG11) and azole resistance (ERG11) were evaluated. Cytotoxicity of the extract (1.8-0.0008 µg/ml) was assessed on KYSE-30 esophageal epithelial cells using the MTT assay.</p><p><strong>Results: </strong>Strain 615 showed strong antifungal activity with MIC values of 0.0008-0.0035 µg/ml and MFC values of 0.0017-0.0035 µg/ml after 48 hours. The extract significantly reduced ergosterol content by 31.81%, completely inhibited phospholipase and proteinase activities at 0.0035 µg/ml and suppressed biofilm formation at 0.0035-0.0140 µg/ml. Expression of all tested virulence genes decreased except for ERG11, indicating a possible mechanism to overcome azole resistance. The highest extract concentration caused 76.7% cytotoxicity in KYSE-30 cells after 72 hours.</p><p><strong>Conclusion: </strong>S. monomycini strain 615 could serve as an alternative or adjunct therapy for FLZ-resistant OPC in head and neck cancer patients, warranting further research to confirm safety and efficacy.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Novel Approach to Overcome Cisplatin Resistance in Ovarian Cancer: Revealing the Synergistic Potential of Quercetin-Loaded Solid Lipid Nanoparticles","authors":"Masoumeh Shamsi, Hossien Babaahmadi-Rezaei, Azam Khedri, Mahdi Hatami, Mojtaba Rashidi","doi":"10.61186/ibj.4543","DOIUrl":"https://doi.org/10.61186/ibj.4543","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) remains the leading cause of mortality among gynecological cancers, mainly because of resistance to platinum-based chemotherapy, particularly cisplatin. This study investigated the potential of quercetin (QU)-loaded solid lipid nanoparticles (SLNs) to address cisplatin resistance in OC cells.</p><p><strong>Methods: </strong>The efficacy of QU-SLN was assessed in vitro on the cisplatin-resistant SK-OV-3 and cisplatin-sensitive A2780s human OC cell lines. Various assays, including cytotoxicity, cell viability, clonogenicity, flow cytometry, quantitative RT-PCR, and wound healing assays, evaluated the combined effects of QU and QU-SLN with cisplatin on cell viability, apoptosis, gene expression levels related to cisplatin resistance, and cell migration.</p><p><strong>Results: </strong>Combining QU-SLN with cisplatin resulted in significantly reduced cell viability and colony formation, accompanied by increased apoptotic rates compared to each treatment alone. Moreover, there was a notable reduction in the expression level of genes associated with cisplatin resistance, particularly ABCG2, MT-2A, GST-pi, and XIAP, in the combined treatment. Wound healing assays indicated that the QU-SLN and cisplatin combination severely impaired OC cell motility compared to cisplatin monotherapy.</p><p><strong>Conclusion: </strong>QU-SLN and cisplatin combination enhances the therapeutic response in cisplatin-resistant OC cells. By reducing cell proliferation, promoting apoptosis, and downregulating drug resistance genes, QU-SLN might present a promising strategy to improve treatment outcomes for OC patients resistant to cisplatin.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"20-35"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005063","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":"Protective Immunity of a Novel Multi-Epitope Vaccine Encoding OMP31, TF, BLS, SOD, BP26, and L9 Against Brucella spp. Infection","authors":"Sogol Sattari Sarvari, Razieh Rezaei Adriani, Shahram Nazarian, Arghavan Fotouhi, Seyed Latif Mousavi Gargari","doi":"10.61186/ibj.4933","DOIUrl":"https://doi.org/10.61186/ibj.4933","url":null,"abstract":"<p><strong>Background: </strong>Brucella is a type of bacteria that causes a disease known as brucellosis in both humans and animals. Many different vaccine formulations are available for this disease; however, vaccines based on epitopes have shown to be effective, especially in combating this pathogen. In the present study, we designed a multi-epitope vaccine against brucellosis using a chimeric protein that combines segments from various Brucella proteins known to contain both B- and T-cell epitopes.</p><p><strong>Methods: </strong>In this study, a vaccine candidate was developed using multiple epitopes derived from various proteins, including OMP31, TF, BLS, SOD, BP26, and L9. These epitopes were selected based on their high density of both B-cell and T-cell epitopes. The construct of the vaccine candidate was inserted into a pEGFP-N1 vector and introduced into HEK-293T cells. Subsequently, the vaccine was tested on different groups of mice; some received the expressed protein in E. coli, while others received the DNA vaccine candidate. An ELISA assay was employed to evaluate the humoral immune response.</p><p><strong>Results: </strong>Both the MEB protein (Pro/Pro) and pCI-MEB plasmid/MEB protein (DNA/Pro) groups showed a specific humoral response. The anti-DNA vaccine antibody titer did not rise as high as that of the protein groups; however, the observed protection indicated the efficiency of the DNA vaccine in activating the immune system.</p><p><strong>Conclusion: </strong>While the chimeric DNA vaccine candidate induced a weaker humoral response, it remained effective in protecting against virulent strains of B. abortus and B. melitensis in the challenge route.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"36-48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996201","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":"Role of hsa_Circ_0001821 in Colorectal Cancer Pathogenesis and Response to 5-Fluorouracil through miR-203a-3p/FGF-2 Axis","authors":"Pejman Molaei, Ali Mahdavinezhad, Rezvan Najafi, Mehrdad Hashemi, Leili Tapak, Saeid Afshar","doi":"10.61186/ibj.4942","DOIUrl":"https://doi.org/10.61186/ibj.4942","url":null,"abstract":"<p><strong>Background: </strong>Chemoresistance, the primary cause of disease relapse and treatment failure, poses a significant challenge in the treatment of colorectal cancer (CRC). Understanding the molecular mechanisms that underlie the pathogenesis and chemoresistance of colorectal tumor cells, as well as identifying novel therapeutic strategies, would be crucial. This study aimed to evaluate the role of hsa_Circ_0001821 in response to 5-fluorouracil (5-FU) in CRC, a topic that has not been examined to date.</p><p><strong>Methods: </strong>The current study investigated the effect of hsa_Circ_0001821 suppression using interfering RNAs on the response of colorectal tumor cells to 5-FU. The expression levels of hsa_Circ_0001821, hsa-miR-203a-3p, BAX, BCL-2, and FGF-2 were determined via quantitative RT-PCR. Cell survival, migration rate, and apoptosis induction of colorectal tumor cells subjected to 5-FU treatment were assessed using the MTT test, scratch assay, and flow cytometry analysis, respectively.</p><p><strong>Results: </strong>Knockdown of hsa_Circ_0001821 with siRNA increased the expression level of hsa-miR-203a-3p and decreased the expression level of FGF-2. Additionally, the knockdown of hsa_Circ_0001821 enhanced the sensitivity of colorectal tumor cells to 5-FU. This circRNA significantly affected the viability, apoptosis, and migration of tumor cells.</p><p><strong>Conclusion: </strong>Our study reveals the potential role of hsa_Circ_0001821 in controlling the tumor cell viability and response to 5-FU by targeting the hsa-miR-203a-3p/FGF-2 axis. These findings enhance our understanding of the molecular mechanisms that influence chemotherapy response in CRC, paving the way for the identification of more effective treatments for this disease.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"82-89"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990086","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":"Antioxidant Potentials, Protease Inhibitory, and Cytotoxic Activities of Various Isolated Extracts from Salvia aegyptiaca.","authors":"Ali Hosseini, Mahmoodreza Moein, Zahra Sabahi, Soheila Moein, Salar Hafez Ghoran, Moslem Naderian, Zahra Zebarjad","doi":"10.61186/ibj.4567","DOIUrl":"https://doi.org/10.61186/ibj.4567","url":null,"abstract":"<p><strong>Background: </strong>Natural compounds can regulate the growth and progression of cancer cells with low toxicity to normal cell; therefore, these compounds are unique targets for cancer treatment. Recently, extracts from Salvia species have shown promising antiproliferative potential. This study aimed to isolate and characterize bioactive compounds from Salvia aegyptiaca and evaluate their antioxidant, cytotoxic, and protease-inhibitory activities.</p><p><strong>Methods: </strong>In this study, various extracts of S. aegyptiaca were prepared, and several compounds, including ursolic acid, oleanolic acid, luteolin-7-O-glucoside, quercetin-3-O-rutoside, and rosmarinic acid, were isolated and characterized using different spectroscopic methods. Finally, the antioxidant activity, protease inhibitory activity, and cytotoxicity of the crude extract, multiple fractions, and isolated compounds were examined.</p><p><strong>Results: </strong>According to the results obtained, rosmarinic acid demonstrated the highest antioxidant performance, as indicated by the following assays: DPPH (IC50: 28.39 ± 0.75 µg/mL), ABTS (39.52 ± 0.72 µg/mL), FRAP (31.87 ± 0.67 µg/mL), NO scavenging (71.44 ± 1.04 µg/mL), and ORAC values (0.6 TE/mg). Furthermore, both cynaroside and rosmarinic acid exhibited the most potent antiproliferative effects against the Hep G2 cell line, with IC50 value of 34.4 ± 2.34 and 47.84 ± 5.87 µg/mL, respectively. The EtOAc fraction and rosmarinic acid also showed higher protease inhibitory activity, with IC50 of 17.6 ± 0.10 and 17.0 ± 0.30 µg/mL, respectively, as compared to other compounds.</p><p><strong>Conclusion: </strong>Our findings suggest that the identified compounds may be responsible for the antiproliferative effects of S. aegyptiaca. Overall, S. aegyptiaca could serve as a valuable natural antioxidant and anticancer agent in both pharmaceutical and food industries</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"57-67"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001139","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}
Mahdie Jafari, Shahriyar Abdoli, Majid Asgari, Masoud Moghaddam Pour, Mohammad Ali Shokrgozar, Zahra Sharifzadeh
{"title":"Combination Therapy of Oncolytic Newcastle Virus and Lenalidomide Enhanced Cytotoxicity in Prostate Cancer Cells","authors":"Mahdie Jafari, Shahriyar Abdoli, Majid Asgari, Masoud Moghaddam Pour, Mohammad Ali Shokrgozar, Zahra Sharifzadeh","doi":"10.61186/ibj.4367","DOIUrl":"https://doi.org/10.61186/ibj.4367","url":null,"abstract":"<p><strong>Background: </strong>Despite existing treatments, advanced solid tumors, such as prostate cancer (PCa), require the development of novel anticancer therapies. Oncolytic viruses (OVs) present a potential treatment option for solid tumors. Newcastle disease virus (NDV) is one of the most promising OVs that can replicate within and destroys human cancer cells. This study aimed to evaluate the cytotoxic and apoptotic effects of the NDV strain on human PCa cells in vitro. Additionally, We examined a novel treatment for PCa by combining Lenalidomide (Len) with NDV.</p><p><strong>Methods: </strong>NDV strains La Sota, B1, and I2 were tested for cytotoxicity against several cell lines. A safety assessment was conducted in primary cells using peripheral blood mononuclear cells (PBMCs). Also, apoptosis induction was measured using annexin V/7AAD staining. Finally, the cytotoxic effects of NDV alone and in combination with Len, were assessed using MTT.</p><p><strong>Results: </strong>The NDV showed cytotoxic effects on tumor cell lines and induced apoptosis in infected prostate cells compared to control cells. The NDV La Sota strain exhibited significant oncolytic capacity, reducing the viability of LNCaP and DU145 cells to less than 40% at specific concentrations, while showing no cytotoxic effects on primary PBMCs. Also, NDV induced apoptosis in the prostate cell line by 60%. Furthermore, Len enhanced the cytotoxicity of PCa cells when combined with NDV.</p><p><strong>Conclusion: </strong>Our study confirms the efficacy of oncolytic NDV treatment for PCa, particularly utilizing the La Sota strain. When combined with Len, NDV indicates an enhanced effectiveness in destroying tumor cells. These findings suggest a prospective treatment approach that needs more preclinical and clinical studies to improve outcomes in PCa treatment.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"9-19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005037","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":"Expression Pattern Study of miR-200a and XIAP Gene in the Non-small Cell Lung Cancer Patients’ Blood","authors":"Tara Fereydouni, Seyed Jalal Zargar, Sharareh Seifi, Mojgan Sheikhpour","doi":"10.61186/ibj.4354","DOIUrl":"https://doi.org/10.61186/ibj.4354","url":null,"abstract":"<p><strong>Background: </strong>In non-small cell lung cancer (NSCLC), miR-200a plays a significant role in apoptosis. One of the genes involved in this pathway is XIAP, which has been shown anti-apoptotic activity. Research has indicated a significant association between miR-200a and the XIAP gene in this pathway. The present study investigated the expression profiles of miR-200a and the XIAP gene in NSCLC patients compared to normal individuals, as well as cancer cells compared to normal and apoptosis-inducing conditions.</p><p><strong>Methods: </strong>In this study, 40 blood specimens were collected from NSCLC patients and 40 from healthy individuals. After isolating plasma and peripheral blood mononuclear cells from these samples, we analyzed the miR-200a and XIAP gene expression levels using real-time PCR. Subsequently, normal and lung cancer cells were treated with paclitaxel as a model of apoptosis. The antiproliferative effects and induction of apoptosis were then evaluated using the MTT and flow cytometry assays, respectively. Finally, the expression patterns of miR-200a and the XIAP gene were investigated through a real-time PCR method.</p><p><strong>Results: </strong>Results indicated that the miR-200a expression level was lower in NSCLC patients than in healthy ones, while the expression level of XIAP gene increased in the NSCLC Patients’ blood. The MTT and flow cytometry results demonstrated a decreased proliferation and increased apoptosis rates in two lung line cells (A549 and MRC5) treated with paclitaxel. XIAP expression level also decreased in A549 cells treated with paclitaxel compared to untreated A549 cells.</p><p><strong>Conclusion: </strong>MiR-200a may be associated with the XIAP gene expression and the induction of the apoptosis pathway in NSCLC.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"49-56"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001058","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":"Unraveling Leishmania major Metacyclogenesis: A Comprehensive Analysis of Transcriptomic \u0000and Metabolomic Profiles","authors":"Mansour Aminzadeh, Fariborz Bahrami, Zeynab Piryaei, Mahdi Vasighi, Zahra Kalantari, Mohammad Arjmand, Soheila Ajdary","doi":"10.61186/ibj.4899","DOIUrl":"https://doi.org/10.61186/ibj.4899","url":null,"abstract":"<p><strong>Background: </strong>Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and study, we integrated metabolomics and transcriptomics data to gain deeper molecular mechanisms of Leishmania major metacyclogenesis.</p><p><strong>Methods: </strong>The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis conducted to distinguish different metabolites between the two forms. Metabolic pathway analysis was performed using the KEGG database to identify the metabolic pathways that significantly altered and overrepresented in the metabolomic profile. Finally, the differential gene expression and pathway enrichment analyses were conducted on transcriptomic data retrieved from public repositories.</p><p><strong>Result: </strong>Multivariate statistical analysis revealed that 44 metabolites and ten pathways were significantly different between the two forms. Transcriptome genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.</p><p><strong>Conclusion: </strong>Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":"29 1 & 2","pages":"68-81"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12040638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009520","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}