Mengzao He, Yejun Zhao, Jinping Jiang, Weinong Mo, Qiang Yao
{"title":"Efficacy and Safety of High-Dose Erythropoietin Combined with Hypothermia Therapy in Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review and Meta-Analysis.","authors":"Mengzao He, Yejun Zhao, Jinping Jiang, Weinong Mo, Qiang Yao","doi":"10.1007/s12033-025-01419-3","DOIUrl":"https://doi.org/10.1007/s12033-025-01419-3","url":null,"abstract":"<p><p>This study was conducted to systematically evaluate the effectiveness and safety of high-dose erythropoietin (EPO) combined with hypothermia in treating neonatal hypoxic-ischemic encephalopathy (HIE) using meta-analysis (MA) and providing insights for the clinical application of this treatment approach. Clinical randomized controlled trials on EPO combined with hypothermia for neonatal HIE were identified through computer searches of databases, including Chinese National Knowledge Infrastructure (CNKI), Web of Sciences, Embase, and PubMed up to May 20, 2024. Screening, data extraction, and quality assessment were independently performed by two researchers, with MA conducted using RevMan5.3. 12 studies involving 1562 infants were included. MA results indicated greatly lower odds in the EPO group (EG) versus the Control group (CG) for mortality, acute brain injury, intellectual developmental index < 70, and motor developmental index < 70 [odds ratio (OR) = 0.65, 95%CI = 0.47-0.91, p = 0.01; OR = 0.51, 95%CI = 0.25-1.01, p = 0.05; OR = 0.47, 95%CI = 0.22-1.00, p = 0.05; OR = 0.44, 95%CI = 0.20-1.00, p = 0.05]. EG and CG demonstrated neglectable differences in terms of hospital stay duration, renal failure/injury rate, incidence of neurological developmental abnormalities, and antiepileptic drug usage (p > 0.05). High-dose EPO combined with hypothermia in the treatment of neonatal HIE effectively reduced mortality rates and improved intellectual and motor developmental outcomes.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Potential of NF-κB Inhibition in Glioblastoma: Gene Therapy Approach with rAAV-5 Mediated IκBαM Overexpression.","authors":"Ceera Manikandan, Amit Kumar Jaiswal","doi":"10.1007/s12033-025-01418-4","DOIUrl":"https://doi.org/10.1007/s12033-025-01418-4","url":null,"abstract":"<p><p>Current treatment strategies for glioblastoma, including resection followed by concurrent chemotherapy/radiotherapy are not curative. Angiogenesis and hypoxia are two major factors responsible for GBM growth and resistance to existing therapies, leading to poor clinical outcomes. The transcription factor NF-κB induces tumour progression by activating genes associated with cell proliferation and angiogenesis. It is expressed constitutively in gliomas and is known to regulate the expression of HIF-1α and VEGF in GBM. As a result, NF-κB can be a potent target that can inhibit tumour growth/invasiveness by reducing hypoxia and angiogenesis, as well as preventing macrophage and microglia infiltration and generating inflammatory cytokines that cause gliomagenesis. AAV vectors are the typical transducing agents for gene therapy because they can infect a broad range of dividing and non-dividing cell types. AAVs have emerged as one of the most widely used methods for delivering genes into the central nervous system because of their broad range of infectivity, ability to induce long-term transgenic expression, and lack of toxicity. The present study aims to inhibit NF-κB activity by blocking its nuclear translocation via overexpression of IκBα utilising recombinant adeno-associated virus-5 plasmid as a gene therapy vector.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Marine Carotenoids: Unlocking Advanced Antioxidant Mechanisms and Therapeutic Applications for Oxidative Stress.","authors":"Fatima Iftikhar Shah, Hassan Imran, Fatima Akram, Tooba Khalid, Somia Shehzadi","doi":"10.1007/s12033-025-01420-w","DOIUrl":"https://doi.org/10.1007/s12033-025-01420-w","url":null,"abstract":"<p><p>Marine ecosystems are a rich source of bioactive compounds, with carotenoids like astaxanthin, fucoxanthin, and zeaxanthin demonstrating significant antioxidant properties. These carotenoids neutralize reactive oxygen species (ROS), protecting against oxidative damage. This review examines their molecular structures, biosynthesis pathways, and mechanisms of action, including radical scavenging and involvement in key signaling pathways. Antioxidant assays confirm their potent ability to mitigate oxidative stress, with therapeutic implications for chronic diseases such as cancer, cardiovascular disorders, neurodegenerative diseases, and diabetes. Carotenoids also show promise in food, cosmetic, and nutraceutical applications, emphasizing the importance of sustainable sourcing. This review highlights the role of carotenoids in preventive health strategies and their potential to address oxidative stress-related diseases.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofeng Li, Zhihao Chen, Tao Wang, Zhongyuan Wang, Bing Yang
{"title":"Unveiling the Hub Genes Associated with the Enhanced Effects of Selenium on Pancreas Function in Diabetic Mice.","authors":"Xiaofeng Li, Zhihao Chen, Tao Wang, Zhongyuan Wang, Bing Yang","doi":"10.1007/s12033-025-01415-7","DOIUrl":"https://doi.org/10.1007/s12033-025-01415-7","url":null,"abstract":"<p><p>To elucidate the molecular mechanisms underlying the protective effects of selenium on pancreatic function in diabetes mellitus, we performed a comprehensive bioinformatics analysis of the GSE55636 dataset from the Gene Expression Omnibus (GEO). This dataset comprised pancreatic tissue samples from streptozotocin-induced diabetic mice, including three mice administered 0.8 mg/kg body weight sodium selenate (Na<sub>2</sub>SeO<sub>3</sub>, SS) and three matched controls. Our investigation revealed 838 differentially expressed genes (DEGs) in SS-treated pancreatic tissue, with 500 up-regulated and 338 down-regulated genes. Through protein-protein interaction (PPI) network analysis, we identified 20 hub genes (including FOS, PTGS2, CXCL1, IL5, CCL7, IRF1, PTPRC, EGR2, and CD80) exhibiting the highest connectivity scores. Gene Ontology (GO) enrichment analysis demonstrated these hub genes were predominantly associated with critical biological processes: Chromosomal segregation, Mitotic cell cycle regulation, Inflammatory response modulation, Immune system activation. KEGG pathway analysis further revealed their significant enrichment in key signaling pathways: TNF-α, NF-κB, MAPK, IL-17-mediated inflammation, Chemokine-mediated immune regulation. Notably, the identified pathways demonstrated strong associations with pancreatic β-cell survival, insulin secretion regulation, and oxidative stress mitigation. These findings systematically characterize the selenium-responsive molecular network in diabetic pancreatic tissue, providing novel insights into the nutrigenomic mechanisms of selenium's pancreatic protection. The 20 hub genes identified may serve as potential therapeutic targets for diabetes management through selenium supplementation.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Khadija Shams, Ibrar Khan, Sajjad Ahmad, Asad Ullah, Sadiq Azam, Zainab Liaqat, Huma Jalil, Faisal Ahmad, Norah Abdullah Albekairi, Abdulrahman Mohammed Alshammari, Dong-Qing Wei
{"title":"Highly Drug-Resistant Escherichia coli from Hospital Wastewater with Several Evolutionary Mutations: An Integrated Insights from Molecular, Computational, and Biophysics.","authors":"Khadija Shams, Ibrar Khan, Sajjad Ahmad, Asad Ullah, Sadiq Azam, Zainab Liaqat, Huma Jalil, Faisal Ahmad, Norah Abdullah Albekairi, Abdulrahman Mohammed Alshammari, Dong-Qing Wei","doi":"10.1007/s12033-025-01410-y","DOIUrl":"https://doi.org/10.1007/s12033-025-01410-y","url":null,"abstract":"<p><p>Many people around the world are still unable to get access to clean drinking water. Escherichia coli is a common waterborne pathogen that frequently results from insufficient hygiene measures and needs attention to address health problems. The present study aimed to evaluate antibiotic resistance of Escherichia coli isolated from wastewater and drinking water samples of hospital and non-hospital settings at Peshawar. Out of 462 samples collected, 111 tested positive for E. coli. The majority of isolates were resistant to many antibiotics including Ampicillin, Gentamicin, Tobramycin, Imipenem, Meropenem, Tetracycline, Cefepime, Amikacin, Piperacillin, Levofloxacin, Ciprofloxacin, Ceftriaxone, and Cefazolin. However, they showed susceptibility to Chloramphenicol, Fosfomycin 200 mg, Colistin, and Tigecycline. Genetic analysis revealed various antibiotic resistance genes within the isolates, i.e., marA(20%), marB(40%) marR(30%), rob(30%), and soxS(35%). Following PCR, the resulting products underwent next-generation sequencing. marA exhibited T10P and D101H mutations, while MarR showed substitutions at M1G, V142S, L143P, and P144C positions. In Rob, D2I, A4P, L10F, I12N, and L253P mutations were observed. The SoxS displayed alterations at H105P, R106A, and L107V positions. Asinex antibacterial library was used to study molecular docking based on virtual screening. SWISS ADME was used to in silico evaluate the pharmacokinetics of these substances. 100 ns molecular dynamics simulation was conducted to estimate free binding energies, confirmation, and stability of the binding mode of the identified compounds. Screening results revealed that LAS-52505571, LAS52171241, LAS52202332, and LAS22461675 compounds showed high affinity to MarA, MarR, SoxS, and Rob proteins, respectively, with the lowest binding energies across the library. In brief, the current study aimed at establishing potential chemical entities that could facilitate the evolution of silicon drugs against antibiotic-resistant E. coli strains.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adoption of Multi-omics Approaches to Address Drought Stress Tolerance in Rice and Mitigation Strategies for Sustainable Production.","authors":"Nabarun Roy, Prasenjit Debnath, Hari Shankar Gaur","doi":"10.1007/s12033-025-01400-0","DOIUrl":"https://doi.org/10.1007/s12033-025-01400-0","url":null,"abstract":"<p><p>Drought is considered one of the major limiting factors for crop production. Drought-affected areas are consistently expanding. As rice stands as a primary grain widely consumed as a staple food by people across the globe, with a particular prominence in Asian countries. Due to its short root structure, thin cuticular wax layer and quick stomatal closure, rice is considered as drought-sensitive crop. The impact of drought on rice amplifies with plant growth and its adverse effects are more pronounced during the reproductive phase, including stages such as blooming, filling and maturity. Every year rice growers are facing a considerable deterioration of yield due to abiotic stresses specially drought. To address this undesirable consequences, multi-omics approaches are successfully being utilized as a mitigation strategy. A thorough, precise and systematic comprehension of the fundamental biological and cellular mechanisms activated by crop plants during stress is achieved through a range of omics technologies, including genomics, transcriptomics, proteomics and metabolomics. The integration of multi omics approaches offers a holistic understanding of cellular dynamics during drought or other stress conditions. These omics-based tools can identify and manipulate drought-tolerant genes. Utilizing omics approaches to stack these genes in rice contributes to the development of a drought resistant plant architecture. This review article aims to compile the latest published strategies on the application of multi omics approaches to accelerate the development of drought-tolerant rice plants.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K M Veena, V Mohammed Hasil, Prashanth Shenoy, R Abhijna Ballal, Sanath Kumar Shetty
{"title":"Drug-Induced Gingival Enlargement: A Comparative Study on the Effect of Phenytoin, Gabapentin, and Cyclosporin on Gingival Fibroblast Cells.","authors":"K M Veena, V Mohammed Hasil, Prashanth Shenoy, R Abhijna Ballal, Sanath Kumar Shetty","doi":"10.1007/s12033-025-01397-6","DOIUrl":"https://doi.org/10.1007/s12033-025-01397-6","url":null,"abstract":"<p><p>Drug-induced gingival enlargement (DIGE) is an abnormal overgrowth that may occur as a side effect in some patients when calcium channel blockers, immunosuppressants, or anticonvulsants are taken. The prevalence of DIGE was shown to be 70% for phenytoin (30% for other anticonvulsant medicines) and 50-80% for cyclosporine. The usage of these medications is increasing as new indications emerge. These drugs act through a common mechanism of action at the cellular level by inhibiting intracellular calcium influx. DIGE is characterized by the presence of varied quantities of inflammatory infiltrates, primarily plasma cells, and an excessive build-up of extracellular matrix like-collagen. Fibroblasts, the cells responsible for collagen synthesis, may become hyperactive, leading to the excessive production of collagen fibers. This increased collagen content can result in the enlargement of gingival tissues. As collagen deposits increase, it hinders normal oral care routines, masticatory processes, and esthetics. In this study, we compared the cytotoxicity of phenytoin, gabapentin, and cyclosporine on gingival fibroblast cells using the methyl thiazolyl-tetrazolium assay to understand their effect on gingival fibroblast cells. Phenytoin had the greatest half-maximal inhibitory concentration (IC50) with a value of 305.78 µg/ml, followed by gabapentin with a value of 260.44 µg/ml and cyclosporin with a value of 243.79 µg/ml. Understanding the cytotoxic thresholds of these medications is essential for improving patient outcomes and minimizing the incidence of gingival enlargement in those requiring long-term therapy. According to the study, cytotoxicity increases along with medication concentration. These findings will assist medical professionals in selecting the drug that poses the least risk of adverse effects on gingival health, ultimately guiding more informed prescribing practices.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Promoter Methylation of WIF1 is Involved in IL-17-Induced Chondrocyte Inflammatory Injury and Matrix Degradation via Promoting Wnt5a/MAPK-JNK Signaling.","authors":"Xi Chen, Xu Chen, Jing Xie, Donggeng Guo","doi":"10.1007/s12033-025-01378-9","DOIUrl":"https://doi.org/10.1007/s12033-025-01378-9","url":null,"abstract":"<p><p>The activity of Wnt inhibitory factor 1 (WIF1) is reduced upon promoter methylation and is involved in cartilage degradation in osteoarthritis. This study aims to investigate the mechanism by which WIF1 methylation is involved in chondrocyte damage in ankylosing spondylitis (AS). A model of chondrocyte inflammatory injury in AS was constructed by stimulation with interleukin (IL)-17. WIF1 level in injured chondrocytes was detected by western blot and RT-qPCR. ELISA kits were used to assess the levels of inflammatory cytokines. The expressions of MMP9, MMP13, collagen II, and ADAMTS-4 were tested by western blot and RT-qPCR. Wnt5a/mMAPK signaling and associated phosphorylated protein expressions were observed using western blot. After overexpression of Wnt5a, the same assays were used to evaluate the above indexes. The methylation level of the WIF1 promoter was measured by MSP-PCR assay. WIF1 expression declined in IL-17-induced chondrocytes. Overexpression of WIF1 decreased the levels of inflammatory factors TNFα, IL-1β, and IL-6, as well as downregulated the expressions of MMP9, MMP13, collagen II, and ADAMTS-4. Likewise, elevated WIF1 inhibited the Wnt5a/MAPK signaling and phosphorylation of JNK. However, upregulation of Wnt5a in IL-17-treated chondrocytes attenuated these responses. Besides, in damaged chondrocytes, WIF1 expression was reduced due to promoter methylation, while it was upregulated after demethylation. In summary, WIF1 exhibits high methylation levels in AS and is involved in inflammatory injury and matrix degradation in chondrocytes by regulating the Wnt5a/MAPK-JNK pathway.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome Mining for Hub Genes Related to Endoplasmic Reticulum Stress in Pancreatitis: A Perspective from In Silico Characterization.","authors":"Huiwei Ye, Laifa Kong","doi":"10.1007/s12033-025-01388-7","DOIUrl":"https://doi.org/10.1007/s12033-025-01388-7","url":null,"abstract":"<p><p>Pancreatitis, as a common exocrine pancreatic disease, poses a daunting challenge to patients' health and the medical system. Endoplasmic reticulum stress (ERS) plays an essential role in the pathologic process of pancreatitis. However, its mechanism is not fully understood. Therefore, this study was designed to deepen the understanding of the pathogenic mechanism of the disease by screening key ERS-related genes (ERSRGs) associated with pancreatitis. Pancreatitis mRNA data for GSE194331 (Normal: 32, Pancreatitis: 87) and pancreatitis GSE143754 (Normal: 9, Pancreatitis: 6) were downloaded from the GEO database and were used as a training and validation set, respectively. First, the training set GSE194331 was differentially expressed and intersected with the ERSRGs (n = 265) obtained from the MSigDB database to result in 42 differentially expressed ERSRGs (DE-ERSRGs). Subsequently, five candidate genes were further screened by PPI network and MCC and MCODE algorithms. However, according to the ROC curve results, AUC values of CCND1, BCL2, PIK3R1, and BCL2L1 were all greater than 0.6, indicating that they had good diagnostic performance, which was verified by the GSE143754 data set. Based on the GeneMANIA network, it was found that hub genes BCL2 and BCL2L1 may be the key factors in the regulation of mitochondrial metabolism. 24 differentially expressed pancreatitis-related genes (DE-PRGs) were found by difference analysis and Venn analysis. Hub genes BCL2 and PIK3R1 that were significantly correlated with 24 DE-PRGs were determined by Spearman analysis. ssGSEA algorithm was further used to reveal the significant correlation between these hub genes and the immune microenvironment of pancreatitis. The miRNA and lncRNA targeting hub genes were predicted using miRWalk, TargetScan, miRDB, and ENCORI databases, providing research directions for the mechanism of pancreatitis. Finally, the Network Analyst website was used to predict potential compounds associated with the hub gene. In conclusion, this study not only further supports the role of ERS in the development of pancreatitis but also provides a new perspective and direction for the development of biomarkers and mechanism of pancreatitis. At the same time, the results of this study provide a reliable research direction for the targeted treatment of pancreatitis.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}