Biomedicines最新文献

{"title":"RETRACTED: Jabbar et al. Sinapic Acid Attenuate Liver Injury by Modulating Antioxidant Activity and Inflammatory Cytokines in Thioacetamide-Induced Liver Cirrhosis in Rats. <i>Biomedicines</i> 2023, <i>11</i>, 1447.","authors":"Ahmed A J Jabbar, Zaenah Zuhair Alamri, Mahmood Ameen Abdulla, Ahmed S AlRashdi, Soran Kayfi Najmaldin, Mustafa AbdulMonam Zainel","doi":"10.3390/biomedicines13040862","DOIUrl":"https://doi.org/10.3390/biomedicines13040862","url":null,"abstract":"<p><p>The journal retracts the article titled \"Sinapic Acid Attenuate Liver Injury by Modulating Antioxidant Activity and Inflammatory Cytokines in Thioacetamide-Induced Liver Cirrhosis in Rats\" [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence.","authors":"Jimi Olaghere, David A Williams, Jeremy Farrar, Hildegard Büning, Cecelia Calhoun, Tony Ho, Maneesha S Inamdar, David Liu, Julie Makani, Kwasi Nyarko, Sol Ruiz, John Tisdale, Joseph M McCune, Esther Boadi, Reagan-Udall Foundation For The Fda","doi":"10.3390/biomedicines13030758","DOIUrl":"10.3390/biomedicines13030758","url":null,"abstract":"<p><p>On 4 September 2024, the Reagan-Udall Foundation for the FDA (FDA Foundation) in collaboration with the Food and Drug Administration (FDA) and the Gates Foundation hosted a workshop titled \"Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence\". The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-income countries (LMICs), with sickle cell disease (SCD) serving as the model disorder for the discussions. Although there has been significant progress in gene therapy, such as breakthroughs in clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies and FDA-approved therapies, access to these therapies remain limited in underresourced regions. The workshop addressed critical challenges, including the high cost of therapies, regulatory gaps and barriers and ethical concerns regarding informed consent and public engagement in LMICs. This paper highlights the critical discussion points from the workshop with a focus on exploring strategies for global regulatory convergence, the role of international collaborations and the potential pathways to making gene therapies affordable and accessible to all.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727899","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":"Comparison of Inflammatory Biomarkers in Females with and Without Patellofemoral Pain and Associations with Patella Position, Hip and Knee Kinematics, and Pain.","authors":"Lori A Bolgla, Sharad Purohit, Daniel C Hannah, David Monte Hunter","doi":"10.3390/biomedicines13030761","DOIUrl":"10.3390/biomedicines13030761","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patellofemoral pain (PFP) is believed to be a precursor to knee osteoarthritis (OA). The primary purpose of this study was to compare matrix metalloproteinase-9 (MMP-9) levels in young adult females with and without PFP. The secondary purpose was to determine the associations between MMP-9, patella position, hip and knee kinematics, and pain in females with PFP. <b>Methods</b>: Plasma was analyzed for MMP-9. Patellar position was measured using diagnostic ultrasound as the degree of offset (RAB angle) from the deepest aspect of the femoral trochlear groove to the inferior pole of the patella. A positive RAB angle suggested patella lateralization. Hip and knee kinematics during a single-leg squat were measured using 2-dimensional motion analysis and quantified as the dynamic valgus index (DVI), a combined measure of hip and knee motion. A higher DVI suggests increased valgus loading at the patellofemoral joint. Pain was measured using a 10 cm visual analog scale. <b>Results</b>: Females with PFP had significantly higher levels of MMP-9 than controls (72.7 vs. 58.0 ng/mL, <i>p</i> = 0.03). Females with PFP had a significant positive association between MMP-9 and patella lateralization (<i>r</i> = 0.38, <i>p</i> = 0.04), suggesting that greater patellar lateralization may contribute to increased joint inflammation. A significant inverse association was observed between MMP-9 and the DVI (<i>r</i> = -0.50, <i>p</i> = 0.007), indicating that individuals with higher inflammatory marker levels may adopt movement patterns that reduce valgus loading. <b>Conclusions</b>: The significant association between MMP-9 and patella lateralization suggested a potential link between patella alignment and joint inflammation, which may contribute to early joint degeneration. The inverse association between MMP-9 levels and the DVI suggested that subjects with higher MMP-9 levels adjusted their movement pattern as a compensatory mechanism to reduce knee valgus stress to reduce joint degeneration.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728065","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":"Ethanol Induces Craniofacial Defects in Bmp Mutants Independent of <i>nkx2.3</i> by Elevating Cranial Neural Crest Cell Apoptosis.","authors":"Hieu D L Vo, C Ben Lovely","doi":"10.3390/biomedicines13030755","DOIUrl":"10.3390/biomedicines13030755","url":null,"abstract":"<p><p><b>Background:</b> Craniofacial malformations lie at the heart of fetal alcohol spectrum disorders (FASDs). While there is growing evidence for a genetic component in FASDs, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. The bone morphogenetic protein (Bmp) signaling pathway-dependent endoderm pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like <i>nkx2.3</i>, may mediate the impact of ethanol on Bmp mutants. <b>Methods:</b> We use an ethanol exposure paradigm with <i>nkx2.3</i> knockdown approaches to test if <i>nkx2.3</i> loss sensitizes Bmp mutants to ethanol-induced facial defects. We combine morphometric approaches with immunofluorescence and a hybridization chain reaction to examine the cellular mechanisms underlying Bmp-ethanol interactions. <b>Results:</b> We show that Bmp-ethanol interactions alter the morphology of the endodermal pouches, independent of <i>nkx2.3</i> gene expression. Knockdown of <i>nkx2.3</i> does not sensitize wild-type or Bmp mutants to ethanol-induced facial defects. However, we did observe a significant increase in CNCC apoptosis in ethanol-treated Bmp mutants, suggesting an ethanol sensitive, Bmp-dependent signaling pathway driving tissue interactions at the heart of FASDs. <b>Conclusions:</b> Collectively, our work builds on the mechanistic understanding of ethanol-sensitive genes and lays the groundwork for complex multi-tissue signaling events that have yet to be explored. Ultimately, our work provides a mechanistic paradigm of ethanol-induced facial defects and connects ethanol exposure with complex tissue signaling events that drive development.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728079","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":"Systemic Inflammatory Markers as Prognostic Factors in Oral Squamous Cell Carcinoma of the Tongue.","authors":"Maria Giulia Cristofaro, Francesco Ferragina, Federico Tolino, Ida Barca","doi":"10.3390/biomedicines13030754","DOIUrl":"10.3390/biomedicines13030754","url":null,"abstract":"<p><p><b>Background</b>: Oral tongue squamous cell carcinoma (OTSCC) is a common disease that can cause occult metastasis (OM). <b>Methods</b>: This study aims to investigate the role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) in predicting the presence of neck OM in early-stage OTSCC. We reprocessed the pre-treatment blood data to calculate the NLR and the PLR on patients treated for OTSCC. We used a logistic regression model and the ROC curve to estimate the probability of metastases in cervical lymph nodes using data from pre-surgery blood tests. <b>Results</b>: During the period under review, 113 patients were treated for OTSCC; however, only 74 met the inclusion criteria and were, therefore, enrolled in the study. Twenty-five patients (35.3%) had lymph node metastases, and 46 (64.7%) did not. Without the NLR influence, the probability of metastasis is less than 50% (β0 = -1.058). A higher NLR value means a higher chance of metastasis. This is shown by the positive value of the NLR level coefficient (β1 = 0.135) and the ROC curve (AUC = 0.83). <b>Conclusions</b>: Our study showed a statistical correlation between high pre-treatment NLR values and neck OM in patients with OTSCC. These results may help to identify which patients are at risk of developing OM and then choose the right treatment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728187","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 Hospital Frailty Risk Score as a Predictor of Mortality, Complications, and Resource Utilization in Heart Failure: Implications for Managing Critically Ill Patients.","authors":"Nahush Bansal, Eun Seo Kwak, Abdel-Rhman Mohamed, Vaishnavi Aradhyula, Mohanad Qwaider, Alborz Sherafati, Ragheb Assaly, Ehab Eltahawy","doi":"10.3390/biomedicines13030760","DOIUrl":"10.3390/biomedicines13030760","url":null,"abstract":"<p><p><b>Background:</b> Frailty, with a high prevalence of 40-80% in heart failure, may have a significant bearing on outcomes in patients. This study utilizes the Hospital Frailty Risk Score (HFRS), a validated tool derived from the administrative International Classification of Diseases, 10th Revision, Clinical Modifications (ICD-10-CM) codes, in investigating the mortality, morbidity, and healthcare resource utilization among heart failure hospitalizations using the Nationwide Inpatient Sample (NIS). <b>Methods:</b> A retrospective analysis of the 2021 NIS database was assessed to identify adult patients hospitalized with heart failure. These patients were stratified by the HFRS into three groups: low frailty (LF: <5), intermediate frailty (IF: 5-15), and high frailty (HF: >15). The outcomes analyzed included inpatient mortality, length of stay (LOS), hospitalization charges, and complications including cardiogenic shock, cardiac arrest, acute kidney injury, and acute respiratory failure. These outcomes were adjusted for age, race, gender, the Charlson comorbidity score, hospital location, region, and teaching status. Multivariate logistic and linear regression analyses were used to assess the association between frailty and clinical outcomes. STATA/MP 18.0 was used for statistical analysis. <b>Results:</b> Among 1,198,988 heart failure admissions, 47.5% patients were in the LF group, whereas the IF and HF groups had 51.1% and 1.4% patients, respectively. Compared to the LF group, the IF group showed a 4-fold higher (adjusted OR = 4.60, <i>p</i> < 0.01), and the HF group had an 11-fold higher (adjusted OR 10.90, <i>p</i> < 0.01) mortality. Frail patients were more likely to have a longer length of stay (4.24 days, 7.18 days, and 12.1 days in the LF, IF, and HF groups) and higher hospitalization charges (USD 49,081, USD 84,472, and USD 129,516 in the LF, IF, and HF groups). Complications were also noticed to be significantly (<i>p</i> < 0.01) higher with increasing frailty from the LF to HF groups. These included cardiogenic shock (1.65% vs. 4.78% vs. 6.82%), cardiac arrest (0.37% vs. 1.61% vs. 3.16%), acute kidney injury (19.2% vs. 54.9% vs. 74.6%), and acute respiratory failure (29.6% vs. 51.2% vs. 60.3%). <b>Conclusions:</b> This study demonstrates the application of HFRS in a national dataset as a predictor of outcome and resource utilization measures in heart failure admissions. Stratifying patients based on HFRS can help in holistic assessment, aid prognostication, and guide targeted interventions in heart failure.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728203","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 Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses.","authors":"Bingyi Song, Youjia Qiu, Zilan Wang, Yuchen Tao, Menghan Wang, Aojie Duan, Minjia Xie, Ziqian Yin, Zhouqing Chen, Chao Ma, Zhong Wang","doi":"10.3390/biomedicines13030753","DOIUrl":"10.3390/biomedicines13030753","url":null,"abstract":"<p><p><b>Background:</b> The gut microbiome (GM) has been reported to play a role in traumatic brain injury (TBI). To investigate the causal relationship between GMs, inflammatory mediators, and TBI, a comprehensive Mendelian randomization (MR) analysis was conducted. <b>Methods:</b> We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM and TBI. To assess the potential causal associations between GM and TBI, we employed the inverse-variance-weighted, MR-Egger, and weighted median methods. Mediation analysis was used to assess the possible mediating factors. Several sensitivity analyses methods were implemented to verify the stability of the results. Additionally, we utilized FUMA GWAS to map single-nucleotide polymorphisms to genes and conduct transcriptomic MR analysis. <b>Results:</b> We identified potential causal relationships between nine bacterial taxa and TBI. Notably, class <i>Methanobacteria</i>, family <i>Methanobacteriaceae</i>, and order <i>Methanobacteriales</i> (<i>p</i> = 0.0003) maintained a robust positive correlation with TBI. This causal association passed false discovery rate (FDR) correction (FDR < 0.05). Genetically determined 1 inflammatory protein, 30 immune cells and 3 inflammatory factors were significantly causally related to TBI. None of them mediated the relationship between GMs and TBI. The outcome of the sensitivity analysis corroborated the findings. Regarding the mapped genes of significant GMs, genes such as <i>CLK4</i>, <i>MTRF1</i>, <i>NAA16</i>, <i>SH3BP5</i>, and <i>ZNF354A</i> in class <i>Methanobacteria</i> showed a significant causal correlation with TBI. <b>Conclusions:</b> Our study reveals the potential causal effects of nine GMs, especially <i>Methanogens</i> on TBI, and there was no link between TBI and GM through inflammatory protein, immune cells, and inflammatory factors, which may offer fresh insights into TBI biomarkers and therapeutic targets through specific GMs.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728195","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":"Navigating Glioma Complexity: The Role of Abnormal Signaling Pathways in Shaping Future Therapies.","authors":"Qiang Chen, Jin Jin, Pian Li, Xiuping Wang, Qianyan Wang","doi":"10.3390/biomedicines13030759","DOIUrl":"10.3390/biomedicines13030759","url":null,"abstract":"<p><p>Gliomas are a type of highly heterogeneous and invasive central nervous system tumor. Traditional treatment methods have limited efficacy, and the prognosis for patients remains poor. Recent studies have revealed the crucial roles of several abnormal signaling pathways in the pathogenesis of gliomas, including the Receptor Tyrosine Kinase/Rat Sarcoma Virus Oncogene/Phosphatidylinositol-3-Kinase (RTK/RAS/PI3K) pathway, the Wingless-Related Integration Site/β-Catenin (Wnt/β-Catenin) pathway, the Hippo/YAP (Hippo/Yes-associated protein) pathway, and the Slit/Robo (Slit Guidance Ligands/Roundabout) signaling pathway. These pathways play extremely vital roles in tumor proliferation, invasion, and treatment resistance. This article comprehensively and systematically reviews the molecular mechanisms of these signaling pathways, deeply summarizing the research progress of various treatment strategies, including targeted inhibitors, gene therapy, and nanomedicine against them. Moreover, the combination of targeted therapy and personalized treatment regimens is expected to overcome the current treatment bottleneck and provide a more favorable survival prognosis for glioblastoma patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727464","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":"Investigation into the Use of Surufatinib and Donafenib as Novel Multi-Kinase Inhibitors Therapeutic Agents in Managing Advanced Differentiated Thyroid Cancer: A Systematic Review.","authors":"Danut Dejeu, Paula Dejeu, Anita Muresan, Paula Bradea, Viorel Dejeu","doi":"10.3390/biomedicines13030752","DOIUrl":"10.3390/biomedicines13030752","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Differentiated thyroid cancer is the predominant form of endocrine cancer, with most cases being treatable. However, some patients develop resistance to traditional treatments. This review examines the use of the new multi-kinase inhibitors surufatinib and sonafenib, which target pathways related to angiogenesis and tumor growth in these patients. <b>Methods:</b> An extensive search of the literature was performed to find research involving these drugs in treating differentiated thyroid cancer. Four relevant studies were found, including two each for surufatinib and donafenib. Information regarding the research design, participant details, treatment methods, results on effectiveness, and side effects was collected and analyzed. <b>Results:</b> Surufatinib showed encouraging results, with response rates between 23.2% and 60% and progression-free survival times as long as 11.1 months. Donafenib also demonstrated improved progression-free survival times (12.9 months) compared to a placebo (6.4 months) and had response rates as high as 23.3%. Both drugs were well tolerated, with the most frequent side effects being hypertension and hand-foot syndrome. <b>Conclusions:</b> Both urufatinib and donafenib offer substantial benefits for patients with advanced differentiated thyroid cancer and have acceptable safety profiles. These results support their potential inclusion in treatment strategies for resistant cases, and further investigation of their clinical application is recommended.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728132","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":"Inhibition of the Renin-Angiotensin System Improves Hemodynamic Function of the Diabetic Rat Heart by Restoring Intracellular Calcium Regulation.","authors":"Krisztina Anna Paulik, Tamás Ivanics, Gábor A Dunay, Ágnes Fülöp, Margit Kerék, Klára Takács, Zoltán Benyó, Zsuzsanna Miklós","doi":"10.3390/biomedicines13030757","DOIUrl":"10.3390/biomedicines13030757","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Disrupted intracellular calcium (Ca²⁺_i) regulation and renin-angiotensin system (RAS) activation are pathogenetic factors in diabetic cardiomyopathy, a major complication of type 1 (T1D) and type 2 (T2D) diabetes. This study explored their potential link in diabetic rat hearts. <b>Methods:</b> Experiments were conducted on T1D and T2D Sprague-Dawley rats induced by streptozotocin and fructose-rich diet, respectively. In T1D, rats were treated with Enalapril (Ena) or Losartan (Los) for six weeks, whereas T2D animals received high-dose (HD) or low-dose (LD) Ena for 8 weeks. Heart function was assessed via echocardiography, Ca²⁺_i transients by Indo-1 fluorometry in Langendorff-perfused hearts, and key Ca²⁺_i cycling proteins by Western blot. Data: mean ± SD. <b>Results:</b> Diabetic hearts exhibited reduced contractile performance that was improved by RAS inhibition both in vivo (ejection fraction (%): T1D model: Control: 79 ± 7, T1D: 54 ± 11, T1D + Ena: 65 ± 10, T1D + Los: 69 ± 10, <i>n</i> = 18, 18, 15, 10; T2D model: Control: 73 ± 8, T2D: 52 ± 6, T2D + LDEna: 62 ± 8, T2D + HDEna: 76 ± 8, <i>n</i> = 9, 8, 6, 7) and ex vivo (+dPressure/dt_max (mmHg/s): T1D model: Control: 2532 ± 341, T1D: 2192 ± 208, T1D + Ena: 2523 ± 485, T1D + Los: 2643 ± 455; T2D model: Control: 2514 ± 197, T2D: 1930 ± 291, T2D + LDEna: 2311 ± 289, T2D + HDEna: 2614 ± 268). Analysis of Ca²⁺_i transients showed impaired Ca²⁺_i release and removal dynamics and increased diastolic Ca²⁺_i levels in both models that were restored by Ena and Los treatments. We observed a decrease in sarcoendoplasmic reticulum Ca²⁺-ATPase2a (SERCA2a) expression, accompanied by a compensatory increase in 16Ser-phosphorylated phospholamban (P-PLB) in T2D that was prevented by both LD and HD Ena (expression level (% of Control): SERCA2a: T2D: 36 ± 32, T2D + LDEna: 112 ± 32, T2D + HDEna: 106 ± 30; P-PLB: T2D: 557 ± 156, T2D + LDEna: 129 ± 38, T2D + HDEna: 108 ± 42; <i>n</i> = 4, 4, 4). <b>Conclusions:</b> The study highlights the critical role of RAS activation, most likely occurring at the tissue level, in disrupting Ca²⁺_i homeostasis in diabetic cardiomyopathy. RAS inhibition with Ena or Los mitigates these disturbances independent of blood pressure effects, underlining their importance in managing diabetic heart failure.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727956","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}