BiomedicinesPub Date : 2025-06-30DOI: 10.3390/biomedicines13071591
Ana Paucarmayta, Hannah Taitz, Latoya McGlorthan, Yovanni Casablanca, G Larry Maxwell, Kathleen M Darcy, Viqar Syed
{"title":"RETRACTED: Paucarmayta et al. Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro. <i>Biomedicines</i> 2020, <i>8</i>, 73.","authors":"Ana Paucarmayta, Hannah Taitz, Latoya McGlorthan, Yovanni Casablanca, G Larry Maxwell, Kathleen M Darcy, Viqar Syed","doi":"10.3390/biomedicines13071591","DOIUrl":"10.3390/biomedicines13071591","url":null,"abstract":"<p><p>The journal retracts the article, \"Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro\" [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551852","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061504
Sivasree Ravindran, Sok Kuan Wong, Nur-Vaizura Mohamad, Kok-Yong Chin
{"title":"A Review of the Relationship Between Insulin and Bone Health.","authors":"Sivasree Ravindran, Sok Kuan Wong, Nur-Vaizura Mohamad, Kok-Yong Chin","doi":"10.3390/biomedicines13061504","DOIUrl":"10.3390/biomedicines13061504","url":null,"abstract":"<p><p>Insulin, a key hormone primarily involved in glucose metabolism, has emerged as a crucial modulator of bone metabolism. Increasing evidence suggests that insulin influences bone health, but its precise mechanism of action remains unestablished. This review explores the intricate relationship between insulin and bone health, as well as elucidating the mechanism of action involved. Animal models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) demonstrated distinct skeletal alterations, largely attributed to differences in insulin availability and associated metabolic dysfunction. Insulin deficiency in T1DM was associated with the deterioration of trabecular and cortical bone, whereas insulin resistance in T2DM primarily compromised trabecular bone quality. The route, frequency, and duration of insulin administration have been shown to influence bone-related outcomes. Studies involving insulin receptor silencing have suggested that insulin signalling is essential for normal bone development and maintenance. In humans, inconsistent findings on the effects of circulating insulin levels and insulin resistance on bone health were mainly attributed to heterogeneity in age, gender, metabolic status, study designs, population characteristics, and assessment methods. This review also highlights current knowledge gaps and underscores the need for longitudinal studies and mechanistic research. A clearer understanding of the insulin-bone axis may guide the development of targeted strategies to mitigate skeletal complications in individuals with diabetes mellitus.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494113","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061507
Aleksandra Kubas, Ewa Małecka-Wojciesko
{"title":"Malignancies in Celiac Disease-A Hidden Threat with Diagnostic Pitfalls.","authors":"Aleksandra Kubas, Ewa Małecka-Wojciesko","doi":"10.3390/biomedicines13061507","DOIUrl":"10.3390/biomedicines13061507","url":null,"abstract":"<p><p>Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1-STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance-particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494242","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061508
Elizabeth Kim, Kevin Zhang, Miski Abdi, Wei Tse Li, Ruomin Xin, Jessica Wang-Rodriguez, Weg M Ongkeko
{"title":"Evaluating Genomic and Clinical Risk Factors for Alzheimer's Disease in Individuals with Hypertension.","authors":"Elizabeth Kim, Kevin Zhang, Miski Abdi, Wei Tse Li, Ruomin Xin, Jessica Wang-Rodriguez, Weg M Ongkeko","doi":"10.3390/biomedicines13061508","DOIUrl":"10.3390/biomedicines13061508","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Alzheimer's disease (AD) is a progressive neurodegenerative condition whose growing prevalence has become an increasingly important public health concern as the population ages. The lack of a definitive cure elevates the importance of identifying risk factors that are crucial for prevention efforts. Hypertension (HTN) and obesity have emerged as two highly widespread, interrelated conditions that have independently been associated with AD risk. Despite extensive research into AD pathology, the impact of obesity in a hypertensive population is not well explored. This study aims to investigate how obesity and blood pressure control within a hypertensive population may interact with genomic risk and environmental factors to influence AD incidence. <b>Methods:</b> A retrospective cohort of matched AD and normal patients diagnosed with HTN and taking anti-HTN drugs (<i>n</i> = 1862) from the All of Us database was analyzed. In this hypertensive cohort, obesity was significantly associated with increased AD risk. Genome-wide association studies (GWASs) were conducted on hypertensive AD individuals (<i>n</i> = 1030) and identified six single nucleotide variants (SNVs) that were associated with AD development in this population. <b>Results:</b> Obesity and Area Deprivation Index, a measure of socioeconomic status, were significantly associated with elevated AD risk within the hypertensive cohort. GWAS analysis identified six SNVs significantly associated with AD development among the hypertensive cohort. <b>Conclusions:</b> Our findings suggest that among hypertensive individuals, comorbid obesity and the Area Deprivation Index confer greater AD risk. These results highlight the critical need for obesity prevention and management strategies as part of Alzheimer's risk reduction efforts.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494176","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":"Pyridostigmine Mitigates Methotrexate-Induced Liver Fibrosis in Rats: Association with Changes in BMP-9, SIRT1, and Endoglin Expression.","authors":"Mehmet Ulusan, Mumin Alper Erdogan, Ozkan Simsek, Hilal Ustundag, Zafer Dogan, Bertug Bekir Ciftci, Mesih Kocamuftuoglu, Imdat Orhan, Oytun Erbas","doi":"10.3390/biomedicines13061502","DOIUrl":"10.3390/biomedicines13061502","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. <b>Methods:</b> Thirty-six female Wistar albino rats randomly assigned to three groups: control (<i>n</i> = 12), MTX + saline (<i>n</i> = 12), and MTX + pyridostigmine (<i>n</i> = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. <b>Results:</b> Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (<i>p</i> < 0.05) and cytokeratin-18 levels (<i>p</i> < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (<i>p</i> < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (<i>p</i> < 0.05), bone morphogenetic protein-9 (<i>p</i> < 0.001), and endoglin levels (<i>p</i> < 0.05), as well as increased sirtuin 1 level (<i>p</i> < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. <b>Conclusions:</b> Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494207","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061505
Marco La Verde, Marco Torella, Irene Iavarone, Rossella Molitierno, Antonio Cerillo, Margherita Casillo, Maria Maddalena Marrapodi, Mario Fordellone, Liliana Mariani, Chiara Melito, Barbara Gardella, Mattia Dominoni
{"title":"Vaginal Cleansing and Post-Cesarean Infectious Morbidity? Updated Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Marco La Verde, Marco Torella, Irene Iavarone, Rossella Molitierno, Antonio Cerillo, Margherita Casillo, Maria Maddalena Marrapodi, Mario Fordellone, Liliana Mariani, Chiara Melito, Barbara Gardella, Mattia Dominoni","doi":"10.3390/biomedicines13061505","DOIUrl":"10.3390/biomedicines13061505","url":null,"abstract":"<p><p><b>Background</b>: Endometritis, maternal fever and wound infection represent the most frequent post-cesarean complications. The aim of the present research was to evaluate the incidence of post-cesarean infections after vaginal cleansing. <b>Materials and methods</b>: The databases analyzed were MEDLINE, Scopus, EMBASE, CENTRAL, Google Scholar, Clinicaltrials.gov and the Register of Controlled Trials. No language or geographical restrictions were applied. We included only randomized controlled trials that analyzed various vaginal antiseptic solutions to reduce postpartum endometritis. The terms employed were as follows: vaginal solution, cesarean section, endometritis, wound infection, chlorhexidine, povidone, metronidazole, cetrimide, and pregnancy. The PICO categorization was as follows: P-population: pregnant women; I-intervention: vaginal antiseptic; C-control: hands-off or routine care; O-outcome: post-cesarean endometritis, wound infection and postoperative fever; S-study design: randomized controlled trials. <b>Results</b>: A total of 32 articles, including 13,853 participants, were selected. The vaginal cleansing group showed a low incidence of endometritis. The chlorhexidine group had an OR of 0.56 (95% CI 0.45-0.70, <i>p</i> = 0.010). The povidone group had an OR of 0.47 (95% CI 0.37-0.59, <i>p</i> = 0.002). Considering maternal fever, 2598 patients from 5 studies in the chlorhexidine group were analyzed, alongside 6965 patients from 18 trials in the povidone group. The povidone group presented an Odds ratio of 0.47 (95% CI 0.38-0.57, <i>p</i> = 0.0001). A reduction in wound infection incidence was observed in the povidone group (OR = 0.59, 95% CI = 0.42-0.82, <i>p</i> < 0.05). <b>Conclusions</b>: Vaginal cleansing before cesarean section, particularly with povidone solutions, reduces the incidence of postoperative endometritis and maternal fever.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494282","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061506
Olga Dubljević, Miodrag Dragoj, Milica Potrebić Stefanović, Maja Srbovan, Miloš Stanojlović, Željko Pavković
{"title":"Genotype-Based Housing as a Potential Confounder in Studies Using Transgenic Mouse Models-Insight from the A53T Mouse Model of Parkinson's Disease.","authors":"Olga Dubljević, Miodrag Dragoj, Milica Potrebić Stefanović, Maja Srbovan, Miloš Stanojlović, Željko Pavković","doi":"10.3390/biomedicines13061506","DOIUrl":"10.3390/biomedicines13061506","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Environmental factors, including the differences in genotype-based housing (GbH), can act as confounding variables in studies using transgenic mouse models, potentially influencing experimental outcomes and limiting their reproducibility and translational value. Despite the widespread use of transgenic models in preclinical studies, the extent to which housing conditions can affect the behavioral and molecular parameters of interest remains poorly understood. This study aims to investigate how different GbH conditions influence visuo-spatial memory and gene expression in the A53T mouse model (JAX006823) of Parkinson's disease (PD) during the pre-motor phase. <b>Methods</b>: A53T+ transgenic male mice and their non-transgenic littermates (A53T-) were housed in either mixed-genotype (MGH) or single-genotype (SGH) environments from postnatal day (PND) 30, with C57BL/6J mice serving as the controls. A behavioral assessment using the Novel Object Recognition and Object Location Tests was conducted at PND 180, followed by a qPCR analysis of <i>Iba1</i>, <i>Gfapα</i>, <i>Bdnf</i>, <i>Tnfα</i>, <i>Il-1β</i>, and <i>Il-6</i> expression in the medial prefrontal cortex and the hippocampus. <b>Results</b>: The variations in GbH influenced behavior and mRNA expression differently in the A53T+ and A53T- animals. Specifically, the A53T- mice in SGH environments displayed behavioral and molecular profiles similar to the C57BL/6J controls, while the same was not evident in the MGH environments. In the A53T+ mice, the mRNA expression of <i>Iba1, Gfapα, Bdnf,</i> and <i>Tnfα</i> was sensitive to variations in GbH, while memory impairment was not. <b>Conclusions</b>: This study highlights the importance of considering environmental factors in studies using transgenic animal models. The obtained data suggests that GbH can influence the parameters of interest in preclinical research, implicating the need for the optimization of future study designs.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494099","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}
BiomedicinesPub Date : 2025-06-19DOI: 10.3390/biomedicines13061503
Panagiota-Angeliki Galliou, Niti Argyri, Papaioannou Maria, George Koliakos, Nikolaos A Papanikolaou
{"title":"MSC1 Cells Suppress Colorectal Cancer Cell Growth via Metabolic Reprogramming, Laminin-Integrin Adhesion Signaling, Oxidative Stress Resistance, and a Tumor-Suppressive Secretome.","authors":"Panagiota-Angeliki Galliou, Niti Argyri, Papaioannou Maria, George Koliakos, Nikolaos A Papanikolaou","doi":"10.3390/biomedicines13061503","DOIUrl":"10.3390/biomedicines13061503","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Mesenchymal stem cells (MSCs) possess immunomodulatory properties, tumor-homing, and low immunogenicity, making them attractive for cell-based cancer therapies, but their role in colorectal cancer (CRC) remains controversial. The MSC1 phenotype, a pro-inflammatory, tumor-suppressive state induced by short-term, low-dose LPS activation via TLR4, has shown therapeutic promise but remains poorly characterized in CRC. We aimed to elucidate MSC1's tumor-suppressive mechanisms and validate its activity against CRC cells using an integrated bioinformatics and in vitro approach. <b>Methods:</b> We constructed a high-confidence protein-protein interaction (PPI) network in Wharton's jelly-derived MSCs (WJ-MSCs) following TLR4 activation to uncover enriched signaling pathways, transcriptional regulators, and secreted factors. Functional and transcriptional enrichment analyses pinpointed key mechanisms. We then co-cultured MSC1 cells with CRC cells to assess effects on proliferation and metabolism. <b>Results:</b> Network analysis revealed six tumor-suppressive mechanisms of MSC1 cells: (i) Metabolic reprogramming via enhanced glucose and lipid uptake, phosphoinositide signaling, and membrane/protein recycling, (ii) Robust antioxidant defenses, including SOS signaling and system xc⁻, (iii) Extracellular matrix stabilization and laminin-111-integrin-mediated adhesion, (iv) Secretome with direct anti-cancer effects, (v) Regulation of survival and cancer-associated fibroblasts (CAFs) formation inhibition through balanced proliferation, apoptosis, and epigenetic signals, (vi) Controlled pro-inflammatory signaling with anti-inflammatory feedback. In vitro, MSC1 cells significantly suppressed CRC cell proliferation and metabolic activity versus controls. <b>Conclusions:</b> This study provides the first mechanistic map of MSC1's tumor-suppressive functions in CRC, extending beyond immunomodulation to include metabolic competition, ECM stabilization, and anti-cancer secretome activity. These findings establish MSC1 cells as a novel therapeutic strategy for CRC in cell-based cancer therapies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494225","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}
BiomedicinesPub Date : 2025-06-18DOI: 10.3390/biomedicines13061501
Corina Andreea Rotarescu, Ion Maruntelu, Ion Rotarescu, Alexandra-Elena Constantinescu, Ileana Constantinescu
{"title":"Analysis of Tacrolimus Clearance in Patients with Kidney Transplants from Romania.","authors":"Corina Andreea Rotarescu, Ion Maruntelu, Ion Rotarescu, Alexandra-Elena Constantinescu, Ileana Constantinescu","doi":"10.3390/biomedicines13061501","DOIUrl":"10.3390/biomedicines13061501","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Tacrolimus is a key immunosuppressant in kidney transplantation, but its high interindividual pharmacokinetic variability complicates dosing. This study aimed to develop a population pharmacokinetic model and identify the factors explaining variability to optimize tacrolimus therapy in Romanian kidney transplant recipients. <b>Methods</b>: The study included 106 kidney transplant recipients treated at Fundeni Clinical Institute (2022-2024). Tacrolimus blood levels were measured using immunoassays, while gene polymorphisms of CYP3A4, CYP3A5, and ABCB1 were identified by real-time polymerase chain reaction. <b>Results</b>: Patients with CYP3A4*1/*1.001 impact clearance (RSE = 11.8%), while hematocrit was a significant covariate for intercompartmental clearance (RSE = 6.14%). <b>Conclusions</b>: Incorporating CYP3A4*1/*1.001 genotype and hematocrit into dosing strategies can improve therapeutic drug monitoring and personalize immunosuppressive therapy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494125","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}
BiomedicinesPub Date : 2025-06-18DOI: 10.3390/biomedicines13061494
Iulian Tătaru, Simona Moldovanu, Oana-Maria Dragostin, Carmen Lidia Chiţescu, Alexandra-Simona Zamfir, Ionut Dragostin, Liliana Strat, Carmen Lăcrămioara Zamfir
{"title":"Auto Machine Learning and Convolutional Neural Network in Diabetes Mellitus Research-The Role of Histopathological Images in Designing and Exploring Experimental Models.","authors":"Iulian Tătaru, Simona Moldovanu, Oana-Maria Dragostin, Carmen Lidia Chiţescu, Alexandra-Simona Zamfir, Ionut Dragostin, Liliana Strat, Carmen Lăcrămioara Zamfir","doi":"10.3390/biomedicines13061494","DOIUrl":"10.3390/biomedicines13061494","url":null,"abstract":"<p><p>Histopathological images represent a valuable data source for pathologists, who can provide clinicians with essential landmarks for complex pathologies. The development of sophisticated computational models for histopathological images has received significant attention in recent years, but most of them rely on free datasets. <b>Materials and Methods:</b> Motivated by this drawback, the authors created an original histopathological image dataset that resulted from an animal experimental model, acquiring images from normal female rats/rats with experimentally induced diabetes mellitus (DM)/rats who received an antidiabetic therapy with a synthetic compound (AD_SC). Images were acquired from vaginal, uterine, and ovarian samples from both MD and AD_DC specimens. The experiment received the approval of the Medical Ethics Committee of the \"Gr. T. Popa\" University of Medicine and Pharmacy, Iași, Romania (Approval No. 169/22.03.2022). The novelty of the study consists of the following aspects. The first is the use of a diabetes-induced animal model to evaluate the impact of an antidiabetic therapy with a synthetic compound in female rats, focusing on three distinct organs of the reproductive system (vagina, ovary, and uterus), to provide a more comprehensive understanding of how diabetes affects female reproductive health as a whole. The second comprises image classification with a custom-built convolutional neural network (CB-CNN), the extraction of textural features (contrast, entropy, energy, and homogeneity), and their classification with PyCaret Auto Machine Learning (AutoML). <b>Results:</b> Experimental findings indicate that uterine tissue, both for MD and AD_DC, can be diagnosed with an accuracy of 94.5% and 85.8%, respectively. The Linear Discriminant Analysis (LDA) classifier features indicate a high accuracy of 86.3% when supplied with features extracted from vaginal tissue. <b>Conclusions:</b> Our research underscores the efficacy of classifying with two AI algorithms, CNN and machine learning.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494154","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}