{"title":"Targeting TPX2 to Enhance Metastasis Control and Radiosensitivity in Esophageal Squamous Cell Carcinoma Through PI3K/AKT Pathway Modulation.","authors":"Fang Meng, Jiaru Hu, Shiqiang Zhang, Qifeng Shi, Na Chang, Yaqun Zhu","doi":"10.30498/ijb.2025.549444.4243","DOIUrl":"10.30498/ijb.2025.549444.4243","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) faces challenges of metastasis and variable radiosensitivity. The role of Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) in regulating these ESCC-related traits is unclear, needing investigation.</p><p><strong>Objectives: </strong>This study investigates the functional role of TPX2 in regulating metastasis and radiosensitivity in ESCC.</p><p><strong>Materials and methods: </strong>Differential expression of TPX2 in ESCC versus normal tissues was verified using bioinformatics (The Cancer Genome Atlas Program, Gene Expression Omnibus) and experimental analyses (Immunohistochemistry, Western blot). ESCC cell lines with stable TPX2 overexpression were established to evaluate effects on migration (wound healing assay), invasion (Transwell assay), and radiotherapy response via colony formation and apoptosis assays. <i>In vivo</i>, xenograft and lung homing mouse models (n=5/group) were employed to assess tumor growth, metastatic potential, and radiosensitivity. Additionally, exosome-mediated TPX2 transfer and its impacts on recipient cells were examined.</p><p><strong>Results: </strong>TPX2 was significantly upregulated in ESCC tissues and cell lines. TPX2 overexpression enhanced <i>in vitro</i> cell migration, invasion, and radiosensitivity, while promoting <i>in vivo</i> metastasis and modulating radiation response. Exosome-mediated TPX2 transfer induced comparable aggressive phenotypes in recipient cells. Mechanistically, TPX2 activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway (p-AKT/AKT ratio increased by ~2.5-fold), which directly contributed to enhanced metastatic potential and altered radiosensitivity.</p><p><strong>Conclusion: </strong>TPX2 acts as a key regulator of malignant progression and therapeutic response in ESCC by promoting epithelial-mesenchymal transition and activating the PI3K/AKT pathway.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Dynamic Interplay of Carbon Nanotubes with Apoptosis <i>In-vitro</i> and <i>In-vivo</i>: Insights from Bcl-2 and IAP Families.","authors":"Shirin Lotfipanah, Leila Saremi, Yasaminsadat Rafieitabatabaei, Masoud Asgari, Zahra Hajebrahimi","doi":"10.30498/ijb.2026.535086.4204","DOIUrl":"10.30498/ijb.2026.535086.4204","url":null,"abstract":"<p><strong>Background: </strong>Carbon nanotubes (CNTs) are carbon-based nanomaterials. They have been widely used in environmental technologies and in biomedical fields.</p><p><strong>Objectives: </strong>This study examines the impact of carboxyl-functionalized multi-walled (MWCNTs) and single-walled carbon nanotubes (SWCNTs) on apoptosis in Jurkat cells and Wistar rats.</p><p><strong>Materials and methods: </strong>The methods included functionalizing CNTs, conducting cell culture experiments with Jurkat cells, and performing <i>in-vivo</i> studies on male Wistar rats. Gene expression, particularly the <i>Bcl-2</i> family, was analyzed using real-time PCR, and statistical analyses assessed group differences.</p><p><strong>Results: </strong>Results showed successful CNT functionalization and a slight reduction in cell viability in exposed groups. Gene expression analysis in Jurkat cells treated by MWCNTs and SWCNTs revealed significant upregulation of pro-apoptotic genes (<i>BAD</i>, <i>BAX</i>, <i>BID</i>, <i>BCL2L11</i>) and anti-apoptotic genes (<i>Bcl-2</i>, <i>BCL2L1</i>). Additionally, significant increases in IAP family members, <i>BIRC2</i> and <i>BIRC3</i>, were observed in these cells. In treated animals, a transient increase in <i>Bcl-2</i> and BAD expression was observed after 30 days, with no significant changes after 60 days. Unlike <i>Bcl-2</i> family members, IAP family gene expression (<i>BIRC2</i>, <i>BIRC3</i>) remained unchanged in the treated animal model over the same periods.</p><p><strong>Conclusion: </strong>CNT exposure led to significant modulation of apoptotic pathways in Jurkat cells, including alterations in gene expression of some members of the <i>Bcl-2</i> and <i>IAP</i> family, while the animal models showed transient changes in <i>Bcl-2</i> family gene expression but no alterations in <i>IAP</i> gene expression. These findings highlight the complex interactions between CNTs and biological systems, underscoring the need for further research on the long-term effects and adaptation mechanisms in organisms exposed to CNTs.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Potential of Ginkgolic Acid C17:1 in Modulating PTEN/mtDNA/TLR9 Axis for Alleviating Chronic Pseudomonas Aeruginosa Infection in Bronchiectasis.","authors":"Shuke Rao, Huiyan Jiang, Jieyi Huang, Huafeng Li, Weiliang Yuan, Lichong Chen, Jiamin Xie, Chenli Xie","doi":"10.30498/ijb.2026.567525.4342","DOIUrl":"10.30498/ijb.2026.567525.4342","url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> (PA) colonization drives persistent infection and inflammation in bronchiectasis, a condition lacking targeted biotherapies. Phosphatase and tensin homolog (PTEN) is a key regulator of immune homeostasis, and its plant-derived activator, Ginkgolic acid C17:1 (GAC 17:1), has emerged as a potential biotechnological therapeutic agent due to its anti-inflammatory properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the therapeutic potential of GAC 17:1, a natural compound, in alleviating PA-induced airway injury by targeting the PTEN/mtDNA/TLR9 axis, thereby evaluating its role as a novel biotechnological intervention for immune modulation in bronchiectasis.</p><p><strong>Materials and methods: </strong>A rat model of chronic PA-induced bronchial injury was established and divided into four groups: Control, PA-infected, PA-infected + GAC 17:1 (PTEN activator, 2 mg.kg<sup>-1</sup>), and PA-infected + SF1670 (PTEN inhibitor, 1.5 mg.kg<sup>-1</sup>). Lung pathology, function (FEV<sub>0.3</sub>, FVC, PEF), PTEN/TLR9/NF-κB expression (RT-qPCR, Western blot), mtDNA content, cytokine levels (IL-6, IL-17, TGF-β; ELISA), and Th17/Treg cell proportions (flow cytometry) were assessed.</p><p><strong>Results: </strong>PA infection downregulated PTEN, elevated mtDNA/TLR9/NF-κB, increased IL-6/IL-17 and Th17 cells, reduced TGF-β and Tregs, and impaired lung function. Treatment with GAC 17:1, the plant-derived PTEN activator, effectively restored PTEN expression, suppressed mtDNA release and TLR9/NF-κB signaling, rebalanced Th17/Treg immunity, reduced inflammatory cytokines, and significantly improved pulmonary function. Conversely, PTEN inhibition worsened all parameters.</p><p><strong>Conclusions: </strong>This study demonstrates that GAC 17:1, a natural bioactive compound, exerts potent significant effects in PA-related bronchiectasis by activating PTEN and inhibiting the mtDNA/TLR9/NF-κB pathway. Our findings highlight GAC 17:1 as a promising biotechnological candidate for developing plant-derived immunomodulatory therapies against chronic airway infections.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of Gut Microbiota Metabolites in Chronic Kidney Disease-Associated Pruritus Using Network Pharmacology and Molecular Docking.","authors":"Lingling Sun, Yining He, Min Jiang, Weiming He","doi":"10.30498/ijb.2025.560394.4299","DOIUrl":"10.30498/ijb.2025.560394.4299","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and distressing symptom in patients with renal dysfunction, yet its biological mechanisms are still not well defined. Growing evidence suggests that gut microbiota-derived metabolites may participate in systemic inflammatory regulation, providing a potential entry point for exploring CKD-aP pathogenesis.</p><p><strong>Objectives: </strong>This study aimed to elucidate how gut microbial metabolites interact with host molecular targets involved in CKD-aP, and to identify candidate metabolites with therapeutic relevance through integrative bioinformatics approaches.</p><p><strong>Materials and methods: </strong>Gut metabolite data were retrieved from the gutMGene database, and CKD-aP-related genes were collected from GeneCards, DisGeNET, and OMIM. Intersection targets were processed through STRING-based protein-protein interaction (PPI) analysis, followed by Gene Ontology and KEGG pathway enrichment using the DAVID platform. An integrated microbiota-substrate-metabolite-target (MSMT) network was constructed to visualize microbial-metabolic interactions. Key metabolites were subsequently examined by molecular docking to assess binding affinity with pivotal targets.</p><p><strong>Results: </strong>A total of 44 overlapping genes were identified between microbial metabolites and CKD-aP, among which IL6, AKT1, and PPARG were highlighted as major hub regulators. MSMT network analysis indicated strong associations among Lacticaseibacillus paracasei, tryptophan-related metabolites, and linoleic-acid-derived compounds in modulating CKD-aP. KEGG results emphasized pathways enriched in inflammatory and immune responses, including IL-17, C-type lectin receptor, and Toll-like receptor signaling. Docking simulations supported robust interactions for several metabolites, particularly 10-keto-12Z-octadecenoic acid with PPARG, Genipin with CASP3, and Urolithin A with CYP1A1.</p><p><strong>Conclusion: </strong>Our findings suggest that gut microbial metabolites may alleviate CKD-aP by targeting IL6, AKT1, and PPARG through inflammatory signaling pathways. Notably, 10-keto-12Z-octadecenoic acid from Lacticaseibacillus paracasei demonstrates strong binding affinity with PPARG, highlighting the potential of probiotic-derived metabolites as novel therapeutic strategies for managing pruritus in chronic kidney disease patients.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From Breakthrough to Access: How Biotechnology and Artificial Intelligence are Reshaping the Scalability and Precision of Cancer Immunotherapy.","authors":"Babak Jahangiri, Elahe Asadollahi, Alireza Zomorodipour","doi":"10.30498/ijb.2026.580902.4424","DOIUrl":"10.30498/ijb.2026.580902.4424","url":null,"abstract":"","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Gut Microbiome and Metabolic Pathways on Obesity: A Two-Sample Mendelian Randomization and Case-Control Study.","authors":"Xiaoyu Fu, Yu Xia, Jing Han, Wei Wang, Boning Zhang, Heyuan Liu, Xue Yang, Shengnan Han, Chenggang Zhang","doi":"10.30498/ijb.2025.559624.4295","DOIUrl":"10.30498/ijb.2025.559624.4295","url":null,"abstract":"<p><strong>Objectives: </strong>We employed Mendelian randomization (MR) and case-control studies to identify causal associations and validate biological relevance.</p><p><strong>Materials and methods: </strong>Two-sample MR using genome-wide association studies (GWAS) summary statistics prioritized inverse variance-weighted analysis, supplemented by weighted median and MR-Egger regression. Sensitivity analyses included leave-one-out cross-validation, MR-PRESSO global test, and Cochran's Q test for heterogeneity/pleiotropy. False Discovery Rate (FDR) correction identified robust associations. Clinical validation involved 16S rRNA sequencing and untargeted metabolomics in obese and case-control cohorts.</p><p><strong>Results: </strong>MR identified two microbiota (<i>Streptococcus thermophilus</i>, OR = 0. 98, 95% CI: 0.96-0.99, <i>P</i> < 0.01; <i>Lachnospiraceae bacterium 5_1_63FAA</i>, OR = 0.98, 95% CI: 0.97-0.99, <i>P</i> < 0.001) and two pathways (4-aminobutanoate degradation V, OR = 0.95, 95% CI: 0.92-0.97, <i>P</i> < 0.001; Pyridoxal 5 phosphate biosynthesis I (OR = 0.96, 95% CI: 0.94-0.98, <i>P</i> < 0.001) significantly associated with reduced obesity risk. Sensitivity analyses confirmed no heterogeneity/pleiotropy. Clinical data validated these findings: obese participants exhibited lower abundances of <i>Streptococcus thermophilus</i> and <i>Lachnospiraceae bacterium</i> 5_1_63FAA, reduced serum 4-aminobutanoate and pyridoxal 5-phosphate levels.</p><p><strong>Conclusion: </strong><i>Lachnospiraceae bacterium 5_1_63FAA</i> and <i>Streptococcus thermophilus</i>, alongside 4-aminobutanoate degradation and pyridoxal 5-phosphate biosynthesis, represent protective factors against obesity. Targeted modulation of these targets may exert beneficial effects on the prevention and treatment of obesity.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serum GPX4 and LPO as Biomarkers for Perioperative Oxidative Stress: Impact of Ciprofol Anesthesia in A Randomized Controlled Trial.","authors":"Qiuyuan Ji, Yongheng Hou","doi":"10.30498/ijb.2026.571655.4355","DOIUrl":"10.30498/ijb.2026.571655.4355","url":null,"abstract":"<p><strong>Background: </strong>Perioperative oxidative stress contributes to postoperative organ dysfunction, but sensitive mechanistic biomarkers are limited.</p><p><strong>Objectives: </strong>This study uses serum GPX4 and lipid peroxides to quantify oxidative stress, explore ferroptosis-related pathways, and evaluate the antioxidative effects of ciprofol anesthesia in patients undergoing thoracoscopic lung cancer surgery.</p><p><strong>Materials and methods: </strong>Patients scheduled for video-assisted thoracoscopic surgery (VATS) for lung cancer at the Fourth Affiliated Hospital of Soochow University were enrolled and randomly assigned to one of three groups (n=50 per group): a Ciprofol group, a Propofol group, and a Sevoflurane group. The Ciprofol group received Ciprofol for induction and continuous intravenous maintenance; the Propofol group received Propofol for both induction and maintenance; and the Sevoflurane group received Ciprofol for induction followed by Sevoflurane inhalation for maintenance. Arterial blood samples were collected at four time points: before anesthesia induction (T0), after induction (T1), at the end of surgery (T2), and 24 hours postoperatively (T3). Serum levels of GPX4 and LPO were measured. Hemodynamic changes were compared among the three groups under the different anesthetic regimens. A549 lung adenocarcinoma cells were treated with varying concentrations of Ciprofol (10 µM, 25 µM, 50 µM and 100 µM) for 24 hours. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the EdU assay. After treatment, RNA was extracted from the treated and control groups for qRT-PCR analysis to measure GPX4 expression levels as an indicator of oxidative stress.</p><p><strong>Results: </strong>In the Ciprofol group, serum GPX4 levels significantly increased, while LPO levels markedly decreased at T2 and T3. In the Propofol group, GPX4 levels were significantly higher and LPO levels significantly lower at T2 and T3 compared to the Sevoflurane group (P<0.01). At T1, the heart rate in the Propofol group was significantly higher than in the Ciprofol group. At T2, heart rates in both the Propofol and Sevoflurane groups were higher than in the Ciprofol group (all P<0.01). Ciprofol treatment at 100 µM significantly inhibited tumor cell growth, with the strongest effect observed at this concentration. The subsequent experiments were conducted at 50 µM. After 24 hours, a significant decrease in GPX4 expression was observed in the treated group compared to the control group. Additionally, Ciprofol significantly inhibited tumor cell proliferation, as shown by a marked reduction in EdU-positive cells.</p><p><strong>Conclusion: </strong>Ciprofol elevates postoperative serum GPX4 and reduces LPO, alleviating oxidative stress in thoracoscopic lung cancer surgery with minimal effects on heart rate. Monitoring GPX4 and LPO may assess perioperative oxidative stress. In A549 lung adenocarcinoma cells, Cipr","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In vivo</i> Reverse Transcription of A Heterologous RNA Virus by <i>Cauliflower Mosaic Virus</i> Reverse Transcriptase During Co-Infection.","authors":"Hakimeh Ighani Mayan, Nemat Sokhandan Bashir, Davoud Koolivand","doi":"10.30498/ijb.2025.563738.4317","DOIUrl":"10.30498/ijb.2025.563738.4317","url":null,"abstract":"<p><strong>Background: </strong>Reverse transcriptase (RT) is central to the replication of retroviruses and pararetroviruses. <i>Cauliflower mosaic virus</i> (CaMV), a plant pararetrovirus, replicates via RT using its own viral RNA. Simultaneous infection with two or more viruses in a plant is a common phenomenon that, in addition to affecting the severity of the symptoms, may affect the concentration of infecting viruses. Interactions between viruses in mixed infections can alter disease dynamics.</p><p><strong>Objective: </strong>This study investigated whether CaMV RT can transcribe complementary DNA (cDNA) from the genomic RNA of a co-infecting RNA virus, <i>Cucumber mosaic virus</i> (CMV), <i>in planta</i>, and explored the consequences of this interaction.</p><p><strong>Materials and methods: </strong>Cauliflower plants were singly infected with CaMV or CMV, or co-infected with both. Symptom development was monitored. Total DNA was extracted from co-infected plants and subjected to PCR using CMV-specific primers, without an <i>in vitro</i> reverse transcription step, to probe for CMV-derived cDNA. Control PCRs on DNA from singly CMV-infected plants and on viral RNA were performed. The identity of PCR products was confirmed by sequencing. The impact of CaMV on CMV accumulation was assessed through dsRNA extraction and quantification at 20 and 45 days post-infection (dpi).</p><p><strong>Results: </strong>CMV-specific cDNA was successfully amplified directly from the total DNA of the co-infected plants, indicating <i>in vivo</i> reverse transcription of CMV RNA by CaMV RT. This direst PCR-amplification was not due to plant endogenous RTs or <i>Taq</i> polymerase activity because PCR assays on total DNA and CMV RNA from plants with single CMV-infection gave no amplification. Concurrently, in the co-infections, CMV-associated symptoms (vein clearing and banding) diminished after ~45 dpi, and a quantitative dsRNA analysis showed a ~55% reduction in CMV genome concentration by 45 dpi compared to that in single infections.</p><p><strong>Conclusions: </strong>This study provides the first direct evidence of CaMV RT transcribing a heterologous viral RNA (CMV) into cDNA within plant cells. This interviral activity not only elucidates a mechanism behind the suppression of an RNA virus in a mixed infection but also reveals a novel principle that reflects unexpected genetic interactions of the CaMV RT enzyme substrate due to its flexibility in cDNA synthesis from competitor's RNA, opens new avenues for understanding viral interactions in viral ecology.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Analysis of Hypervirulent <i>Klebsiella pneumoniae</i> ST1-KL122.","authors":"Yu Yang, Zhien He, Yuanyuan Dai, Huaiwei Lu, Yujie Li, Yuchen Zhang, Baolin Sun, Shusheng Zhou","doi":"10.30498/ijb.2025.562396.4312","DOIUrl":"10.30498/ijb.2025.562396.4312","url":null,"abstract":"<p><strong>Background: </strong>Hypervirulent <i>Klebsiella pneumoniae</i> (hvKp) is often characterized by hypervirulence and hypermucoviscosity, traits classically associated with the virulence regulators <i>rmpA</i> and <i>rmpA2</i>. However, some clinically virulent isolates lack these canonical regulators, suggesting the existence of non-canonical pathways driving hypervirulence.</p><p><strong>Objective: </strong>This study aimed to investigate the genetic basis of hypervirulence and hypermucoviscosity in clinical K. pneumoniae isolates that lack the <i>rmpA</i> and <i>rmpA2</i>.</p><p><strong>Materials and methods: </strong>A total of 20 clinical isolates were collected. Virulence was assessed using the <i>Galleria mellonella</i> infection model. The hypermucoviscous phenotype was determined using the string test and mucoviscosity assay. Whole-genome sequencing (WGS) and comparative genomic analysis were performed to identify genetic variations, with a particular focus on an ST1-KL122 isolate (1744) that exhibited hypervirulence and hypermucoviscosity despite the absence of <i>rmpA</i> and <i>rmpA2</i>.</p><p><strong>Results: </strong>All 20 isolates induced at least 25% mortality in <i>G. mellonella</i>. Most isolates displayed a hypermucoviscous phenotype, except for isolates 2355, 2324, and 1951. WGS confirmed the absence of <i>rmpA</i> and <i>rmpA2</i> in isolates 2355, 2324, 1951, and the hypermucoviscous isolate 1744. In the hypervirulent and hypermucoviscous ST1-KL122 isolate 1744, comparative genomic analysis identified two nonsynonymous mutations in the <i>wzc</i> gene, which encodes a tyrosine kinase involved in capsular polysaccharide (CPS) export: c.1397A>C (p.Asn466Thr) and c.1721A>T (p.His574Leu).</p><p><strong>Conclusions: </strong>Our findings provide evidence that mutations in the <i>wzc</i> suggest a potential non-canonical regulatory mechanism that may drive CPS-mediated hypermucoviscosity and hypervirulence in <i>rmpA</i>/<i>rmpA2</i>-negative hvKp. Further verification in more clinical strains is warranted.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiajia Li, Jinxin Cao, Zhipeng Wu, Wenjie Qi, Yingmin Ma
{"title":"Screening of Biomarkers Related to Mitophagy in Severe Pancreatitis Based on Bioinformatics Methods.","authors":"Jiajia Li, Jinxin Cao, Zhipeng Wu, Wenjie Qi, Yingmin Ma","doi":"10.30498/ijb.2026.559698.4296","DOIUrl":"10.30498/ijb.2026.559698.4296","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify mitophagy-related biomarkers in severe acute pancreatitis through integrated bioinformatics and machine-learning approaches, and to elucidate their potential regulatory mechanisms and diagnostic value.</p><p><strong>Materials and methods: </strong>Differentially expressed genes (DEGs) related to SAP were screened based on the GSE194331 dataset (human whole blood samples), and candidate genes were obtained by taking the intersection with the mitophagy gene set. Key genes were screened by combining the least absolute shrinkage and selection operator (LASSO) regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms; the diagnostic efficacy was evaluated using the ROC curve, and a nomogram model was constructed. Furthermore, gene functions and regulatory mechanisms were revealed through Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), immune infiltration analysis, and ceRNA network, and potential targeted drugs were predicted using molecular docking.</p><p><strong>Results: </strong>A total of 16 DEGs related to mitophagy were identified. Functional enrichment analysis showed that they were significantly associated with metabolic and immune regulation pathways. Machine learning and expression level validation jointly screened PGD and LMNB1 genes as two key genes. The key genes showed significant expression differences in the training set and external validation set (upregulated in the SAP group), and had excellent diagnostic efficacy (area under the curve (AUC) > 0.85). Immune infiltration analysis showed that the infiltration of 13 types of immune cells increased in the SAP group, and PGD was highly positively correlated with immune cells such as activated dendritic cells (r = 0.82). Molecular docking indicated that estradiol and progesterone might target and regulate PGD and LMNB1.</p><p><strong>Conclusion: </strong>PGD and LMNB1 are key genes related to mitophagy in SAP and have excellent diagnostic value. This study provides a theoretical basis for the analysis of the molecular mechanism of SAP and the development of precise diagnosis and treatment strategies.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"24 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}