Biomedicines最新文献

{"title":"Heparin Binding Protein in Sepsis-A Comprehensive Overview of Pathophysiology, Clinical Usage and Utility as Biomarker.","authors":"Foteini Tasouli, Eleni Georgopoulou, Christodoulos Chatzigrigoriadis, Dimitrios Velissaris, Christos Michailides","doi":"10.3390/biomedicines13092315","DOIUrl":"10.3390/biomedicines13092315","url":null,"abstract":"<p><p>The heparin-binding protein (HBP) is an enzymatically inactive protein of the serine protease family that plays an important role in host response to stress, especially infection and sepsis. It is produced by activated neutrophils due to a variety of stimuli and is part of the immune response that leads to macrophage, lymphocyte, and neutrophil activation and monocyte adhesion. Its most common repository is the azurophilic granules of the neutrophils. HBP has been studied as a biomarker for several infections, including central nervous system infection, respiratory tract infection, and urinary tract infection, and in several settings, including the Emergency Department and Intensive Care Unit, with promising results. As a biomarker for infection and sepsis, HBP has been compared to other commonly used biomarkers such as Neutrophil to Lymphocyte Ratio, White Blood Count, C-reactive protein, and Procalcitonin, with at least comparable performance. Its sharp increase is promising for the early detection of sepsis. The ability to differentiate inflammatory conditions from infections and bacterial from non-bacterial causes of infection has also been demonstrated. The sepsis-related organ damage, as it is represented by the Sequential Organ Failure Assessment score, can also be reflected by the proportional increase in HBP. Consequently, HBP could be a helpful and promising biomarker for sepsis and infection.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172829","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":"The Diagnostic Role of Novel Echocardiography Indices and Arterial Stiffness in Diabetic Cardiomyopathy.","authors":"Elina Khattab, Stefanos Sokratous, Michaela Kyriakou, Georgios Parpas, Ioannis Korakianitis, Paraskevi Papakyriakopoulou, Nikolaos P E Kadoglou","doi":"10.3390/biomedicines13092317","DOIUrl":"10.3390/biomedicines13092317","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Diabetic cardiomyopathy (DBCM) is characterized by cardiac dysfunction in the absence of ischemic heart disease, hypertension, or valvular disease, often manifesting as heart failure with preserved ejection fraction (HFpEF). Early recognition of DBCM is clinically important, as it enables timely initiation of tailored therapies and may slow down the progression to overt heart failure with reduced ejection fraction (HFrEF). This study aimed to evaluate the diagnostic utility of advanced echocardiographic techniques-myocardial work (MW), diastolic stress echocardiography (DSTE), Cardio-Ankle Vascular Index (CAVI)-and selected serum biomarkers in identifying DBCM. <b>Methods</b>: In this prospective observational study with 12-month follow-up, 125 diabetic patients with preserved ejection fraction and symptoms of HF or recent HF hospitalization were enrolled. Using the Heart Failure Association Pre-test Probability of HFpEF criteria, 37 were classified as DBCM-HFpEF and 88 as diabetic controls. An additional 47 age- and sex-matched non-diabetic individuals served as controls. All participants underwent resting echocardiography (MW, GLS), DSTE, CAVI assessment, and biomarker measurement (BNP, troponin, galectin-3). <b>Results</b>: Compared to non-diabetics, diabetic patients had significantly higher TRVmax (2.21 vs. 2.05 m/s), LAVI (39.70 vs. 33.50 mL/m²), E/e' (8.64 vs. 7.59), CAVI (8.51 vs. 7.82 m/s), BNP (91.50 vs. 35.10 pg/mL), and troponin (3.94 vs. 2.43 ng/mL) (all <i>p</i> < 0.01), while galectin-3 levels showed no significant difference between groups. Differences were more pronounced between DBCM and No-DBCM diabetic groups. Multivariate analysis identified BNP (OR 5.45), TRVmax (OR 8.56), and CAVI (OR 1.91) as independent predictors of DBCM. <b>Conclusions</b>: DSTE and CAVI, alongside BNP and echocardiographic parameters, may provide valuable noninvasive tools for the early detection of DBCM in diabetic patients presenting with otherwise unexplained dyspnea, potentially enabling earlier intervention and improved outcomes. This is clinically important guiding an efficient management of an increasing number of diabetic patients presented with unexplained dyspnea.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172906","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":"Allogeneic NKG2D CAR-T Cell Therapy: A Promising Approach for Treating Solid Tumors.","authors":"Sabir A Mukhametshin, Elvina M Gilyazova, Damir R Davletshin, Irina A Ganeeva, Ekaterina A Zmievskaya, Vitaly V Chasov, Alexsei V Petukhov, Aigul Kh Valiullina, Sheila Spada, Emil R Bulatov","doi":"10.3390/biomedicines13092314","DOIUrl":"10.3390/biomedicines13092314","url":null,"abstract":"<p><p>Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their highly personalized nature limits scalability, increases costs, and delays timely treatment. Allogeneic CAR-T cells generated from healthy donors provide an \"off-the-shelf\" alternative but face two critical immune barriers: graft-versus-host disease (GvHD), caused by donor T-cell receptor (TCR) recognition of host tissues, and host-versus-graft rejection, mediated by recipient immune responses against donor HLA molecules. Recent advances in genome engineering, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, allow precise modification of donor T cells to overcome these limitations. For example, TRAC gene knockout eliminates TCR expression, preventing GvHD, while disruption of HLA molecules reduces immunogenicity without impairing cytotoxicity. Beyond hematologic cancers, CRISPR-edited allogeneic CAR-T cells targeting the NKG2D receptor have shown promise in preclinical studies and early-phase trials. NKG2D CAR-T cells recognize stress ligands (MICA/B, ULBP1-6) expressed on over 80% of diverse solid tumors, including pancreatic and ovarian cancers, thereby broadening therapeutic applicability. Nevertheless, the genomic editing process carries risks of off-target effects, including potential disruption of tumor suppressor genes and oncogenes, underscoring the need for stringent safety and quality control. This review examines the distinguishing features of allogeneic versus autologous CAR-T therapy, with a particular focus on NKG2D-based allogeneic CAR-T approaches for solid tumors. We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172630","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":"Human Stem Cells in Disease Modelling and Treatment: Bridging the Gap Between Bench and Bedside.","authors":"Alvaro Plaza Reyes, Sofia M Calado","doi":"10.3390/biomedicines13092313","DOIUrl":"10.3390/biomedicines13092313","url":null,"abstract":"<p><p>Human stem cell research is entering a stage where disease modeling, translational applications, and clinical therapies are increasingly connected. This editorial provides an overview of the contributions included in this Special Issue, titled \"Human Stem Cells in Disease Modelling and Treatment\", placing them within the wider landscape of stem cell science. We summarize advances in ovarian stem cells for infertility, mesenchymal stem cells for neurodegeneration, pluripotent stem cell-derived cardiovascular and kidney organoids, adipose-derived stem cells, and emerging immunomodulatory and neural progenitor approaches. These studies illustrate the breadth of stem cell research and its potential to inform clinical practice. At the same time, challenges remain in reproducibility, safety, scalability, and ethical oversight. Looking forward, collaborative work and harmonized global standards will be important to bring laboratory findings into therapies that are safe, effective, and accessible. This editorial closes the first edition of the Special Issue with a reflection on current progress and directions for the future.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172908","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":"Comparative Efficacy of Platelet-Rich Plasma, Autologous Serum, and Artificial Tears in Dry Eye Disease: A Systematic Review and Meta-Analysis.","authors":"Alexandra Laura Mederle, Diana Andrei, Laura Andreea Ghenciu, Emil Robert Stoicescu, Roxana Iacob, Ovidiu Alin Haţegan","doi":"10.3390/biomedicines13092316","DOIUrl":"10.3390/biomedicines13092316","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Dry eye disease (DED) is a prevalent, complex disorder with a major impact on patients' quality of life. While artificial tears (AT) are still the first-line treatment, their effectiveness is often limited in moderate-to-severe cases. Autologous serum (AS) and platelet-rich plasma (PRP) are now recognized as viable biologic treatments due to their regenerative and anti-inflammatory characteristics. This systematic review and meta-analysis sought to assess and compare the clinical efficacy of PRP, AS, and AT in the treatment of DED, with a focus on comparative studies. <b>Methods</b>: A comprehensive search of PubMed, Scopus, and Google Scholar was conducted until June 2025 for studies directly comparing PRP, AS, and AT. Eligible trials included patients with DED who reported results such as the Schirmer test, tear break-up time (TBUT), and Ocular Surface Disease Index (OSDI). The risk of bias was calculated using ROB 2 for randomized trials and ROBINS-I for non-randomized studies. Meta-analyses were carried out using standardized mean differences (SMDs) and 95% confidence intervals (CIs). <b>Results</b>: Seventeen studies were included in the systematic review. Both PRP and AS demonstrated greater improvements in OSDI, TBUT, and Schirmer test scores compared to AT. PRP showed a trend toward better outcomes than AS, especially in studies using injectable PRP. However, substantial heterogeneity and methodological variability were noted. <b>Conclusions</b>: Comparative research suggests that PRP and AS are more effective than AT in treating DED. Direct comparisons of PRP and AS yield varied results, with the route of delivery impacting outcomes. Given the heterogeneity of current protocols, further standardized, long-term trials are required to confirm the optimal delivery method and ensure safety.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172960","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":"Mammographic Calcifications in Lung Transplant Recipients: Prevalence and Evolution.","authors":"Jonathan Saenger, Jasmin Happe, Caroline Maier, Bjarne Kerber, Ela Uenal, Denise Bos, Thomas Frauenfelder, Andreas Boss","doi":"10.3390/biomedicines13092318","DOIUrl":"10.3390/biomedicines13092318","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the prevalence and progression of macrocalcifications or sporadic scattered microcalcifications, breast arterial calcifications (BAC) and grouped microcalcifications in women undergoing lung transplantation (LTX). <b>Materials and Methods:</b> In this retrospective single-center cohort study, 176 adult female patients who underwent mammography between 2008 and 2025 were included: 82 LTX recipients and 94 age-matched controls. Mammographic findings were assessed using standardized BI-RADS criteria and a visual BAC scoring system. Clinical and demographic data were extracted from electronic medical records. Multivariable logistic regression and cumulative incidence analysis were used to evaluate associations and progression patterns. Interobserver agreement was assessed using Fleiss' kappa. <b>Results:</b> BAC and grouped microcalcifications were significantly more prevalent in the LTX group in the last mammography (BAC: OR 6.57, 95% CI 2.34-20.7; microcalcifications: OR 14.6, 95% CI 3.93-73.9; both <i>p</i> < 0.001). Cumulative incidence analysis showed accelerated progression of BAC and grouped microcalcifications in LTX recipients (<i>p</i> ≤ 0.01), while macrocalcifications or sporadic scattered microcalcification progression did not differ significantly. BAC was often more extensive and potentially mimicked malignant findings. Interobserver agreement was highest for the four-level BAC scoring system (κ = 0.61), followed by BAC presence (κ = 0.59) and macrocalcifications (κ = 0.51), while grouped microcalcifications showed only fair agreement (κ = 0.33). <b>Conclusions:</b> Lung transplant recipients demonstrate significantly higher prevalence and faster progression of BAC and grouped microcalcifications compared to controls, complicating mammographic interpretation. Given their elevated risk of aggressive malignancies and diagnostic overlap between benign and suspicious calcifications, transplant recipients may benefit from tailored screening strategies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173067","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":"Localization and Expression of Renin-Angiotensin System Receptors in Lung from Transplant Patients: A Case-Control Study.","authors":"Andresa Thomé Silveira, Lucas Sagrillo Fagundes, Juliane Flor, Isabel Amaral Martins, Laura Bastos Otero, Laura Tibola Marques da Silva, Lorenzo Santana Maciel, Sarah Eller, Giuliano Rizzotto Guimarães, Fabíola Adelia Perin, Márcia Rosângela Wink, Katya Rigatto","doi":"10.3390/biomedicines13092312","DOIUrl":"10.3390/biomedicines13092312","url":null,"abstract":"<p><p><b>Objective</b>: We aimed to assess the expression and localization of renin-angiotensin system (RAS) receptors in lung tissue and the plasma concentration of related peptides in IPF patients. <b>Materials and Methods</b>: This case-control study involved 19 patients from southern Brazil undergoing lung resection or transplantation. Plasma levels of Angiotensin I, II, A, 1-7, Alamandine were measured via liquid chromatography-tandem mass spectrometry. Lung tissue expression and localization of angiotensin type 1 (AT1), Mas, and Mas-related G-protein-coupled receptor D (MrgD) receptors were evaluated using Western blot and immunohistochemistry. Clinical data and the 6-min walk test were analyzed to correlate receptor expression with lung function and oxygen dependence. <b>Results</b>: IPF patients showed reduced forced vital capacity (FVC) at 49 ± 13% and forced expiratory volume (FEV1) at 51 ± 14%, with a 60% increase in oxygen dependence. Plasma peptide concentrations were similar between the groups, except for Angiotensin I, which was significantly higher in the control group. In IPF lungs, AT1 and Mas receptors were expressed 2.31 and 2.13 times more, respectively, while MrgD expression was lower. Mas receptors were mostly found in bronchiole areas, whereas MrgD was predominant in the lung parenchyma. <b>Conclusions</b>: This study indicates that the RAS operates independently within tissue, in addition to its systemic functions, highlighting distinct differences between tissue and plasma RAS activities. The distinct roles of MrgD and Mas receptors in lung structure and function could be pivotal for new therapies, potentially leading to more effective IPF treatments.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172827","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":"The Role of Antifibrotic Therapy in Pulmonary Fibrosis and Lung Cancer: A Multicenter Retrospective Analysis.","authors":"Francesco Rocco Bertuccio, Nicola Baio, Fabio Perrotta, Donato Lacedonia, Vito D'Agnano, Andrea Bianco, Giulia Scioscia, Pasquale Tondo, Maria Pia Foschino Barbaro, Chandra Bortolotto, Angelo Guido Corsico, Giulia Maria Stella","doi":"10.3390/biomedicines13092310","DOIUrl":"10.3390/biomedicines13092310","url":null,"abstract":"<p><p><b>Background</b>: Patients with fibrotic interstitial lung disease (ILD) are at increased risk of lung cancer, yet the impact of antifibrotic therapy on oncologic outcomes remains unclear. Objective: This study aimed to explore associations between antifibrotic therapy and overall survival (OS) and acute exacerbations of ILD (AE-ILD) in patients with fibrotic ILD who develop lung cancer. <b>Methods</b>: We retrospectively analyzed 61 patients from multiple Italian centers: 35 received antifibrotic therapy (pirfenidone or nintedanib) and 26 did not. Outcomes included OS from cancer diagnosis and post-treatment AE-ILD. <b>Results</b>: Mean OS was 17.9 months in the antifibrotic group and 33.2 months in the non-antifibrotic group; no adjusted survival analyses were possible due to missing censoring data, and these descriptive values should not be overinterpreted. AE-ILD occurred in 11.4% of antifibrotic-treated patients and 11.5% of those without antifibrotics. PD-L1 expression was detected in 24.1% vs. 21.8% of tumors in the two groups, and autoantibody positivity was observed in 22.8% vs. 30.7%, respectively, reflecting differences in ILD subtypes. <b>Conclusions</b>: In this heterogeneous real-world cohort, antifibrotic therapy was not associated with increased AE-ILD risk, and descriptive OS comparisons showed no clear survival advantage. These exploratory findings warrant confirmation in larger, prospective studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173235","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":"IgG4-Related Orbital Disease vs. Idiopathic Orbital Inflammation: Clinical Features, Therapy and Outcomes in a Central-European Retrospective Single-Center Cohort.","authors":"Alexander Lukas Rattunde, Vitus André Knecht, Eckart Bertelmann","doi":"10.3390/biomedicines13092311","DOIUrl":"10.3390/biomedicines13092311","url":null,"abstract":"<p><p><b>Objective:</b> IgG4-Related Orbital Disease (IgG4-ROD) is an incompletely understood differential of idiopathic orbital inflammatory syndrome (IOIS). Accurate separation guides therapy and prognosis. This retrospective study also profiles its clinical features, therapy needs, and compares them with IOIS. <b>Methodology:</b> Fifty-four patients were biopsied between January 2016 and December 2023, comprising 18 who were diagnosed with IgG4-ROD (4 definite, 14 probable) and 36 with IOIS. Mean follow-up was 21.7 ± 26.2 months for IgG4-ROD versus 7.5 ± 10.3 months for IOIS. <b>Results:</b> Patients with IgG4-ROD were older than those with IOIS (mean 61.8 vs. 49.9 years). Gender distribution was balanced. The lacrimal gland (66.7% vs. 61.6%; <i>p</i> = 0.690) and extra-ocular muscles (55.6% vs. 30.6%; <i>p</i> = 0.076) were frequently involved in both entities, whereas paranasal sinus infiltration was significantly associated with IgG4-ROD (<i>p</i> = 0.003). Common shared symptoms (<i>p</i> > 0.05) included eyelid swelling (83.3% vs. 86.1%), exophthalmos (50% vs. 36.1%), and motility restriction (22.2% vs. 25%). Relative afferent pupillary defect (<i>p</i> = 0.042), chemosis (<i>p</i> = 0.02), and systemic disease (<i>p</i> = 0.005) were more prevalent in IgG4-ROD. During ≥ 6-month follow-up (<i>n</i> = 7), only 28.6% of IgG4-ROD patients achieved sustained remission; Kaplan-Meier analysis yielded a mean time to first event of 926 days. Additional steroid-sparing therapy was required more often in IgG4-ROD than in IOIS (<i>p</i> = 0.002). <b>Conclusion:</b> IgG4-ROD and IOIS share clinical features but differ in key aspects such as associated diseases, therapy requirements, and disease control. Understanding these differences is crucial for targeted diagnostics and individualized treatment strategies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173013","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":"Key Common Genes with LTF and MMP9 Between Sepsis and Relapsed B-Cell Lineage Acute Lymphoblastic Leukemia in Children.","authors":"Ying-Ping Xiao, Yu-Cai Cheng, Chun Chen, Hong-Man Xue, Mo Yang, Chao Lin","doi":"10.3390/biomedicines13092307","DOIUrl":"10.3390/biomedicines13092307","url":null,"abstract":"<p><p><b>Background:</b> Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the shared genes between pediatric sepsis and relapsed B-ALL. This study aims to further elucidate the more comprehensive and novel common genetic factors and molecular pathways between the two diseases. <b>Methods:</b> Gene expression datasets pertaining to pediatric sepsis (GSE13904, GSE80496) and relapsed B-ALL (GSE3910, GSE28460) were retrieved from the Gene Expression Omnibus database for this retrospective analysis. The initial analysis identified differentially expressed genes common to both pediatric sepsis and relapsed B-ALL. Subsequent investigations employed three complementary approaches: protein-protein interaction networks, molecular complex detection (MCODE) clustering functions, and support vector machine recursive feature elimination model to separately identify the diagnostic biomarkers for each condition. Importantly, key common genes were identified by overlapping the diagnostic genes for pediatric sepsis and relapsed B-ALL. Further characterization involved comprehensive functional analysis through the Metascape platform, construction of transcription factor (TF)-mRNA-microRNA (miRNA) networks, drug prediction, and molecular docking to explore their biological significance and potential therapeutic targets. <b>Results:</b> Comparative analysis of pediatric sepsis-related and relapsed B-ALL-related datasets revealed two shared genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), exhibiting diagnostic significance and consistent upregulation in both disease groups. Transcriptional regulatory network analysis identified specificity protein 1 (SP1) as the principal transcription factor capable of coregulating LTF and MMP9 expression. In addition, molecular docking demonstrated high-affinity interactions between curcumin and MMP9 (-7.18 kcal/mol) as well as reserpine and LTF (-5.4 kcal/mol), suggesting their potential therapeutic utility for clinical evaluation. <b>Conclusions:</b> These findings elucidate the molecular pathogenesis involving LTF and MMP9 in pediatric sepsis and relapsed B-ALL, providing novel insights for clinical diagnosis and therapeutic development.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173243","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}