Biomedicines最新文献

{"title":"Causal Relationships Between Iron Deficiency Anemia, Gut Microbiota, and Metabolites: Insights from Mendelian Randomization and In Vivo Data.","authors":"He Zhou, Zhenzhen Fan, Yu Da, Xiaoning Liu, Chen Wang, Tiantian Zhang, Jiaqi Zhang, Tong Wu, Jie Liang","doi":"10.3390/biomedicines13030677","DOIUrl":"10.3390/biomedicines13030677","url":null,"abstract":"<p><p><b>Background</b>: Iron deficiency anemia (IDA) is a common type of anemia in children and pregnant women. The effects of iron deficiency on gut microbiota and metabolic profiles are not fully understood. <b>Methods:</b> Mendelian randomization (MR) analysis was conducted to explore associations among IDA, gut microbiota, and metabolites. MR analysis was conducted using computational methods, utilizing human genetic data. Data were obtained from genome-wide association studies (GWAS), with inverse-variance-weighted (IVW) as the primary method. Animal models evaluated the effects of IDA on gut microbiota and metabolic profiles. <b>Results:</b> IVW analysis revealed significant associations between gut microbial taxa and IDA. The genus <i>Desulfovibrio</i> was protective (OR = 0.85, 95% CI: 0.77-0.93, <i>p</i> = 0.001), while <i>Actinomyces</i> (OR = 1.12, 95% CI: 1.01-1.23, <i>p</i> = 0.025) and family <i>XIII</i> (OR = 1.16, 95% CI: 1.01-1.32, <i>p</i> = 0.035) increased IDA risk. Glycine was protective (OR = 0.95, 95% CI: 0.91-0.99, <i>p</i> = 0.011), whereas medium low density lipoprotein (LDL) phospholipids increased risk (OR = 1.07, 95% CI: 1.00-1.15, <i>p</i> = 0.040). Animal models confirmed reduced <i>Desulfovibrio</i>, increased <i>Actinomyces</i>, and altered metabolites, including amino acids and phospholipids. <b>Conclusions:</b> IDA significantly impacts gut microbiota and metabolic profiles, offering insights for therapeutic strategies targeting microbiota and metabolism.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photosensitized Methylene Blue Nanoparticles: A Promising Approach for the Control of Oral Infections.","authors":"Magali Parizzi, Aline Rosa Almeida, Gabriel Salvador, Diogo Dominguini, Mylena Fernandes, Daniela Becker, Michael Ramos Nunes, Anelise Viapiana Masiero, Cleonice Gonçalves da Rosa","doi":"10.3390/biomedicines13030673","DOIUrl":"10.3390/biomedicines13030673","url":null,"abstract":"<p><p><b>Introduction:</b> Oral infections pose significant public health challenges, often exacerbating other comorbidities and increasing systemic health risks. Traditional treatments often fail to eliminate persistent micro-organisms and contribute to the rise of antimicrobial resistance. Nanoparticulate systems offer a promising solution by delivering active agents directly to targeted sites, providing more effective and localized treatment options. <b>Objective:</b> This study aimed to synthesize and characterize methylcellulose nanoparticles containing methylene blue at different concentrations using the nanoprecipitation method. We also evaluated their biocompatibility and antimicrobial activity against key micro-organisms commonly found in oral infections. <b>Methods:</b> The study involved physicochemical and morphological characterizations, including encapsulation efficiency, particle size, polydispersity index, zeta potential, and transmission electron microscopy (TEM). Additionally, controlled release profiles, antimicrobial efficacy against major oral pathogens, and biocompatibility in vitro assessments were performed. <b>Results:</b> The results revealed encapsulation efficiency between 99.1 and 98.8%, with particle sizes ranging from 186 to 274 nm and a zeta potential of 1.7 to 2.9 mV achieved at lower concentrations of methylene blue and methylcellulose. The nanoparticles demonstrated sustained drug release of 85% for the smaller particles and 45% for the larger particles for more than 10 h. The nanoparticles exhibited superior antimicrobial activity compared to pure methylene blue. Cell viability studies indicated that the nanoparticles were biocompatible with approximately 40% cell viability at lower concentrations of the nanoparticles. <b>Conclusions:</b> These findings suggest that methylene blue nanoparticles could serve as a promising adjunct in dental treatments. They offer targeted antimicrobial action while potentially reducing the development of antimicrobial resistance.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Biomarkers in Patent Ductus Arteriosus in Preterm Infants: A Narrative Review.","authors":"Manuela Cucerea, Raluca Marian, Marta Simon, Madalina Anciuc-Crauciuc, Andreea Racean, Andrea Toth, Zsuzsánna Simon-Szabó, Mihaela-Georgiana Fadur, Valeriu Moldovan, Elena Moldovan","doi":"10.3390/biomedicines13030670","DOIUrl":"10.3390/biomedicines13030670","url":null,"abstract":"<p><p><b>Background</b>: Patent ductus arteriosus (PDA) in preterm infants presents a significant challenge in neonatal care, marked by ongoing debates about its definition, diagnosis, treatment options, and effects on patient outcomes. Plasma biomarkers assess mediators involved in PDA closure and hemodynamic responses, assisting in identifying newborns at higher risk of developing potentially serious neonatal conditions. The purpose of this review was to investigate the relationship between PDA and various plasma biomarkers used to evaluate and diagnose ductal patency during perinatal life, as outlined in the relevant literature. <b>Methods</b>: We conducted an electronic search of the National Library of Medicine (MEDLINE)/PubMed and Web of Science for relevant studies published up to December 2024, including prospective, retrospective, cohort, and cross-sectional studies, as well as reviews and meta-analyses. The keywords used in the search included \"preterm infant\", \"persistent ductus arteriosus\", \"patent ductus arteriosus\", \"PDA\", \"neonatal biomarkers\", \"cardiac biomarkers\", and \"vasoactive biomarkers\". <b>Results</b>: Out of the 813 identified articles, 85 were included in our review of cardiac biomarkers: Natriuretic peptides (NPs), Cardiac troponin T (cTnT), vasoactive biomarkers (Mid-regional pro-adrenomedullin (MR-proADM), Endothelin-1 (ET-1), Copeptin, and Isoprostanes (IPs)), and inflammatory biomarkers (Interleukin-6 (IL-6), IL-8, IL-10, Growth Differentiation Factor 15 (GDF-15), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), Macrophage Inflammatory Protein-1α (MIP-1α/CCL3)) in relation to PDA. <b>Conclusions</b>: Even if research shows a strong correlation between specific biomarkers and echocardiographic parameters in patients with PDA, clinical judgment must take these evaluations into account, particularly when determining whether to treat a PDA. Future research should focus on investigating new biomarkers associated with the underlying mechanisms of perinatal ductus arteriosus dynamics in preterm infants.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Biological Fighters Against Cancer: Viruses, Bacteria, Archaea, Fungi, Protozoa, and Microalgae.","authors":"Pathea Shawnae Bruno, Peter Biggers, Niyogushima Nuru, Nicholas Versaci, Miruna Ioana Chirila, Costel C Darie, Anca-Narcisa Neagu","doi":"10.3390/biomedicines13030665","DOIUrl":"10.3390/biomedicines13030665","url":null,"abstract":"<p><p>Despite the progress made in oncological theranostics, cancer remains a global health problem and a leading cause of death worldwide. Multidrug and radiation therapy resistance is an important challenge in cancer treatment. To overcome this great concern in clinical practice, conventional therapies are more and more used in combination with modern approaches to improve the quality of patients' lives. In this review, we emphasize how small biological entities, such as viruses, bacteria, archaea, fungi, protozoans, and microalgae, as well as their related structural compounds and toxins/metabolites/bioactive molecules, can prevent and suppress cancer or regulate malignant initiation, progression, metastasis, and responses to different therapies. All these small biological fighters are free-living or parasitic in nature and, furthermore, viruses, bacteria, archaea, fungi, and protozoans are components of human and animal microbiomes. Recently, polymorphic microbiomes have been recognized as a new emerging hallmark of cancer. Fortunately, there is no limit to the development of novel approaches in cancer biomedicine. Thus, viral vector-based cancer therapies based on genetically engineered viruses, bacteriotherapy, mycotherapy based on anti-cancer fungal bioactive compounds, use of protozoan parasite-derived proteins, nanoarchaeosomes, and microalgae-based microrobots have been more and more used in oncology, promoting biomimetic approaches and biology-inspired strategies to maximize cancer diagnostic and therapy efficiency, leading to an improved patients' quality of life.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials.","authors":"Consolato M Sergi, Mervin Burnett, Eugeniu Jantuan, Mariam Hakoum, Shawn T Beug, Roger Leng, Fan Shen","doi":"10.3390/biomedicines13030664","DOIUrl":"10.3390/biomedicines13030664","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor's immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copeptin and Mid-Regional Proadrenomedullin Are Not Useful Biomarkers of Cardiometabolic Disease in Patients with Acromegaly-A Preliminary Study.","authors":"Martyna Strzelec, Eliza Kubicka, Justyna Kuliczkowska-Płaksej, Katarzyna Kolačkov, Łucja Janek, Marek Bolanowski, Aleksandra Jawiarczyk-Przybyłowska","doi":"10.3390/biomedicines13030666","DOIUrl":"10.3390/biomedicines13030666","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cardiovascular complications are a leading cause of premature mortality in patients with acromegaly. Copeptin (CPP) correlates strongly with plasma osmolality and is regulated by non-osmotic stimuli involved in the pathophysiology of cardiovascular disease. Mid-regional proadrenomedullin (MR-proADM), synthesized mainly in the adrenal medulla, vascular endothelial cells, and the heart, has vasodilatory effects. The study aimed to assess two cardiovascular biomarkers (CPP and MR-proADM) in acromegaly patients in relation to disease activity and compare findings with a control group. <b>Methods:</b> The study examined CPP and MR-proADM levels alongside hormonal and biochemical parameters and cardiovascular and metabolic disease prevalence in 53 acromegaly patients and 26 controls. <b>Results:</b> No significant differences in CPP or MR-proADM concentrations were observed between the two groups. However, a positive correlation occurred between growth hormone (GH) and CPP concentrations, and there was a negative correlation between fasting glucose and CPP concentrations in acromegaly patients. The study also found a positive correlation between low-density lipoprotein (LDL) cholesterol and MR-proADM concentrations and between high-density lipoprotein (HDL) cholesterol and MR-proADM levels in the study group. Moreover, atherogenic dyslipidemia was significantly more common in the active form of acromegaly and pituitary macroadenoma patients than in the control group. Acromegaly patients had significantly higher fasting glucose and fasting insulin levels compared to controls, and the homeostasis model assessment of the insulin resistance (HOMA-IR) index was significantly lower in the study group than in the controls. <b>Conclusions:</b> Neither CPP or MR-proADM are significant diagnostic or monitoring indicators of cardiovascular or metabolic complications in acromegaly.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Biomarkers in Laryngeal Squamous Cell Carcinoma and Their Clinical Implications: Preliminary Results.","authors":"Barbara Verro, Carmelo Saraniti, Diana Di Liberto, Giovanni Pratelli, Marianna Lauricella, Daniela Carlisi","doi":"10.3390/biomedicines13030667","DOIUrl":"10.3390/biomedicines13030667","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Laryngeal squamous cell carcinoma represents one of the most common head and neck cancers with a five-year survival rate that, despite diagnostic and therapeutic advances, has not shown any significant improvement in recent decades. Oxidative stress, generated by an imbalance between reactive oxygen species and cellular antioxidant systems, is considered a central mechanism in the carcinogenesis of laryngeal squamous cell carcinoma, causing DNA damage and genomic alterations. <b>Methods</b>: This prospective observational paired case-control study focused on the evaluation of antioxidant proteins, such as superoxide dismutase, catalase, heme-oxygenase 1, vimentin, metallothionein, and nuclear factor erythroid 2-related factor 2, in cancer tissues from fifteen patients with laryngeal squamous cell carcinoma, using adjacent healthy tissues as controls. <b>Results</b>: The results show a statistically significant overexpression of all proteins analyzed in cancer tissues compared to controls, with relevant correlations between specific biomarkers and clinical characteristics, age, sex, smoking habits, and degree of tumor differentiation. <b>Conclusions</b>: These preliminary studies, while limited by sample size and the complexity of molecular regulation, indicate that the overexpression of antioxidant enzymes in laryngeal squamous cell carcinoma tissues, along with their correlations with key clinical parameters, underscores a context-dependent role of oxidative stress in tumor progression. A deeper understanding of oxidative stress mechanisms could contribute to advance personalized management strategies for laryngeal squamous cell carcinoma, potentially improving treatment outcomes and patient prognosis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of LncRNA Biomarkers in Extracellular Vesicle of Amniotic Fluid Associated with Antenatal Hydronephrosis.","authors":"Ying Fu, Qiaoshu Liu, Ruojin Yao, Yimei Fu, Lei Dai, Wenyan Jian, Weishe Zhang, Jingzhi Li","doi":"10.3390/biomedicines13030668","DOIUrl":"10.3390/biomedicines13030668","url":null,"abstract":"<p><p><b>Background</b>: Antenatal hydronephrosis (ANH) is the most common congenital renal and urinary tract anomaly, and parenchymal damage and renal fibrosis due to pathological hydronephrosis are the main causes of end-stage renal disease in children and chronic kidney disease in adults. At present, there is no validated biomarker for ANH, and diagnostic criteria other than prenatal ultrasonography (US) assessment are lacking. Therefore, we assessed to determine if biomarkers extracted from amniotic fluid small extracellular vesicles (sEVs) might be used as ANH diagnosis. <b>Methods</b>: With congenital ureteropelvic junction obstruction (UPJO) as the ultimate diagnosis, 10 pregnant women with Grade III-IV ANH and 10 normal pregnant women were recruited. The sEVs were extracted from amniotic fluid supernatant of all samples. Transcriptomic sequencing of sEVs in the discovery cohort identified the differential expression profiles for ANH. The known differentially expressed lncRNAs (DE-lncRNAs) were assessed by qRT-PCR in the validation cohort. <b>Results</b>: We explored the global RNA expression in sEVs from amniotic fluid. The differential expression profiles of both mRNAs and lncRNAs were related to fetal kidney development. Six known DE-lncRNAs were identified for ANH, and three of those with high expression were verified in more ANH samples. In particular, the upregulated LINC02863 and its target genes were associated with renal development and morphogenesis. The four predicted novel lncRNAs in high expression were also related to mesenchymal morphogenesis and the STAT3 signaling pathway and may play roles in ANH. <b>Conclusions</b>: We identified differentially expressed RNAs of all species in the sEVs from amniotic fluid, and the validated known DE-lncRNAs might serve as promising diagnostic biomarkers for ANH.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Pain and Pruritus in Keloids from the Perspective of Neurological Dysfunction: Where Are We Now?","authors":"En Yang, Ruoqing Xu, Hanrui Zhang, Wenzheng Xia, Xin Huang, Tao Zan","doi":"10.3390/biomedicines13030663","DOIUrl":"10.3390/biomedicines13030663","url":null,"abstract":"<p><p>Keloids are a typical skin fibroproliferative disease that can cause severe aesthetic and functional concerns. Pain and pruritus are the most common clinical symptoms of keloids, but the mechanisms underlying these symptoms remain unclear. The peripheral nervous system plays a pivotal role in the transmission of superficial sensation signals. Mounting evidence has shown potential correlations between disturbance in the peripheral nervous system and pain and pruritus in keloids. Here, we summarize the role of neurological dysfunction in the development of pain and pruritus, with a specific focus on neuroanatomical alterations, the dysfunction of sensory nerves, and neurogenic inflammation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Polymorphisms on TNFA, TNFRSF1A, and TNFRSF1B Genes Predict the Effectiveness of Anti-TNF-α Treatment in Inflammatory Bowel Disease Patients.","authors":"Michelangelo Rottura, Igor Pirrotta, Domenico Antonio Giorgi, Natasha Irrera, Vincenzo Arcoraci, Federica Mannino, Rosario Campisi, Chiara Bivacqua, Laura Patanè, Giuseppe Costantino, Socrate Pallio, Walter Fries, Anna Viola, Giovanni Pallio","doi":"10.3390/biomedicines13030669","DOIUrl":"10.3390/biomedicines13030669","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on <i>TNFA</i>, <i>TNFRSF1A</i>, and <i>TNFRSF1B</i> genes could affect anti-TNF-α treatment effectiveness in IBD patients. <b>Methods:</b> In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and <i>TNF-α</i> (rs1800629, rs361525, rs1799724), <i>TNFRSF1A</i> (rs767455), and <i>TNFRSF1B</i> (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. <b>Results:</b> A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; <i>p</i> = 0.025 and 32.6% vs. 10.3%; <i>p</i> = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03-0.69; <i>p</i> = 0.016 and OR = 0.10; 95% CI = 0.02-0.60; <i>p</i> = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; <i>p</i> = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15-36.38). <b>Conclusions:</b> These results suggest that the evaluation of SNPs in <i>TNF-α</i>, <i>TNFR1A</i>, and <i>TNFR1B</i> genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}