Biomedicines最新文献

{"title":"Astilbin Alleviates Radiation-Induced Pulmonary Fibrosis via <i>circ</i>PRKCE Targeting the TGF-β/Smad7 Pathway to Inhibit Epithelial-Mesenchymal Transition.","authors":"Zhiling Shi, Jing Liu, Jing Qin, Xian Liang, Xue Ou, Tingting Zhang, Xueting Yan, Qianxin Hu, Weimei Huang, Kai Hu","doi":"10.3390/biomedicines13030689","DOIUrl":"10.3390/biomedicines13030689","url":null,"abstract":"<p><p><b>Purpose:</b> This study aimed to clarify the protective effect of astilbin (AST) on radiation-induced pulmonary fibrosis (RIPF) and explore its underlying molecular mechanism, focusing on non-coding RNAs. <b>Methods:</b> Mouse lung epithelial cells (MLE-12 and TC-1) and C57BL/6J mice were used to establish in vitro radiation injury models and in vivo RIPF models, respectively. Cell viability, apoptosis, the epithelial-to-mesenchymal transition (EMT), and fibrosis-related markers were assessed using cell-counting kit-8 assays, Western blotting, immunohistochemistry, and histological staining. High-throughput sequencing identified differentially expressed circRNAs. The mechanistic studies included RNA-FISH, a dual-luciferase reporter assay, an RNA immunoprecipitation (RIP) assay, and loss-of-function experiments. <b>Results:</b> AST significantly alleviated radiation-induced apoptosis and EMT in vitro, as well as RIPF in vivo. AST treatment reduced collagen deposition, fibrosis-related protein expression, and EMT marker changes. High-throughput sequencing revealed that AST upregulated <i>circPRKCE</i>, a non-coding RNA that functions through a ceRNA mechanism by binding to miR-15b-5p, thereby promoting Smad7 expression and suppressing the TGF-β/Smad7 pathway. Knockdown of <i>circPRKCE</i> abolished AST's protective effects, confirming its pivotal role in mediating AST's anti-fibrotic activity. <b>Conclusions:</b> This study demonstrates that Astilbin alleviates radiation-induced pulmonary fibrosis via <i>circPRKCE</i> targeting the TGF-β/Smad7 pathway to inhibit EMT, suggesting AST as a potential therapeutic agent for managing this severe complication of radiotherapy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727826","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 New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide.","authors":"Loredana Vesci, Giulia Martinelli, Yongqiang Liu, Luca Tagliavento, Mario Dell'Agli, Yunfei Wu, Sara Soldi, Valeria Sagheddu, Stefano Piazza, Enrico Sangiovanni, Francesco Meneguzzo","doi":"10.3390/biomedicines13030686","DOIUrl":"10.3390/biomedicines13030686","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Minimal hepatic encephalopathy (MHE) is a clinical condition characterized by neurological impairments, including brain inflammation, arising from the accumulation of toxic metabolites associated with liver dysfunction and leaky gut. This study investigated the pharmacological activity of a new phytocomplex extracted from red orange by-products (AL0042) using hydrodynamic cavitation and consisting of a mixture of pectin, polyphenols, and essential oils. <b>Methods</b>: Preliminary in vitro studies evaluated the impact on the epithelial integrity (TEER) of enterocytes challenged by a pro-inflammatory cocktail. The effect of AL0042 was then evaluated in a model of thioacetamide (TAA)-treated mice that mimics MHE. A group of 8-10-week-old male C57BL/6 mice was intraperitoneally injected with TAA to establish the MHE model. The intervention group received TAA along with AL0042 (20 mg/kg, administered orally once daily for 7 days). At the end of the treatment, the rotarod test was conducted to evaluate motor ability, along with the evaluation of blood biochemical, liver, and brain parameters. <b>Results</b>: In vitro, AL0042 (250 μg/mL) partially recovered the TEER values, although anti-inflammatory mechanisms played a negligible role. In vivo, compared with the control group, the test group showed significant behavioral differences, together with alterations in plasma ammonia, serum TNF-α, ALT, AST, corticosterone levels, and SOD activity. Moreover, histological data confirmed the anti-inflammatory effect at liver and brain level. <b>Conclusions</b>: AL0042 treatment revealed a significant therapeutic effect on the TAA-induced MHE mouse model, curbing oxidative stress and peripheral and central inflammation, thus suggesting that its pharmacological activity deserves to be further investigated in clinical studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727855","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":"Characterization of Sublingual Microvascular Tortuosity in Steady-State Physiology and Septic Shock.","authors":"Athanasios Chalkias, Nikolaos Papagiannakis, Konstantina Katsifa, Antonios Destounis, Athanasios Gravos, Sofia Kanakaki, Georgios Karapiperis, Faidra Koufaki, Athanasios Prekates, Paraskevi Tselioti","doi":"10.3390/biomedicines13030691","DOIUrl":"10.3390/biomedicines13030691","url":null,"abstract":"<p><p><b>Background:</b> The characteristics of hemodynamic coherence in healthy states and disease remain unknown. Capillary tortuosity is a morphologic variant of microcirculatory vessels, but its effects have generally not been considered in the assessment of tissue perfusion and oxygenation. We investigated the role of sublingual capillary tortuosity in the hemodynamic coherence of anesthetized adult individuals with steady-state physiology (ASA 1) and patients with septic shock requiring emergency abdominal surgery (ASA 4E and 5E). <b>Methods:</b> Sublingual macro and microcirculatory variables, oxygen transport, metabolic parameters, and the capillary tortuosity score (CTS) were assessed. <b>Results:</b> Mean (SD) CTS was 0.55 (0.76) and 3.31 (0.86) in the steady-state and septic shock group, respectively (<i>p</i> < 0.001). In patients with septic shock, CTS was significantly associated with alveolar-to-arterial oxygen gradient (r = 0.658, <i>p</i> = 0.015) and oxygen debt (r = -0.769, <i>p</i> = 0.002). Significant differences were also observed in Consensus Proportion of Perfused Vessels (PPV; <i>p</i> < 0.001), Consensus PPV (small) (<i>p</i> < 0.001), Microvascular Flow Index (<i>p</i> < 0.001), vessel diameter (<i>p</i> < 0.001) and length (<i>p</i> < 0.001), wall shear stress (<i>p</i> < 0.001), lactate (<i>p</i> < 0.001), oxygen extraction ratio (<i>p</i> = 0.001), arterial oxygen content (<i>p</i> < 0.001), venous oxygen content (<i>p</i> < 0.001), oxygen delivery (<i>p</i> < 0.001), oxygen consumption (<i>p</i> < 0.001), and oxygen debt (<i>p</i> = 0.002) between the two groups. <b>Conclusions:</b> Sublingual tortuosity was essentially absent in individuals with steady-state physiology. In contrast, it was significantly increased and associated with Alveolar-to-arterial oxygen gradient and oxygen debt in critically ill patients with septic shock.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728056","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":"Carbetocin Is More Effective in Stabilizing Hemodynamic Parameters Compared to Oxytocin During Cesarean Section.","authors":"Edyta Zagrodnik, Maciej Ziętek, Tomasz Machałowski, Barbara Dołęgowska, Małgorzata Szczuko","doi":"10.3390/biomedicines13030685","DOIUrl":"10.3390/biomedicines13030685","url":null,"abstract":"<p><p><b>Background/Objectives</b>: First-line uterotonics include carbetocin and oxytocin, which act on the oxytocin receptor with varying potencies. <b>Methods</b>: In 70 pregnant Caucasian women who delivered by cesarean section, the effects of oxytocin and carbetocin on heart rate and blood pressure were compared. The pregnant women were divided into two groups: the OXY group, which received intravenous oxytocin 5 IU on an even day of the month, and the CARBE group, which received intravenous carbetocin 100 µg on an odd day of the month. Blood pressure and heart rate were measured noninvasively every 3 min from the beginning of cesarean section until the lower uterine incision, and then at 1, 2, and 3 min after the fetus and placenta were removed and the uterotonic drugs were discontinued. Subsequent measurements were taken at 3 min intervals until the end of the cesarean procedure. <b>Results</b>: After the administration of uterotonic drugs, a significant decrease in systolic blood pressure was observed only in the group receiving oxytocin at the first (<i>p</i> < 0.0001) and second minute after drug administration (<i>p</i> < 0.0001). Diastolic arterial pressure was significantly different in the study groups at the sixth minute after oxytocin and carbetocin administration (<i>p</i> = 0.004). Mean arterial pressure values were significantly different in the two study groups at the first and sixth minute after drug administration (<i>p</i> = 0.006; <i>p</i> = 0.014). With regard to heart rate, significant differences between the groups were found at 6 min after uterotonic drug administration (<i>p</i> = 0.019). <b>Conclusions</b>: Blood pressure and heart rate variability are significantly higher after oxytocin than after carbetocin administration in women delivering by cesarean section.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727950","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":"Developing an IPF Prognostic Model and Screening for Key Genes Based on Cold Exposure-Related Genes Using Bioinformatics Approaches.","authors":"Peiyao Luo, Quankuan Gu, Jianpeng Wang, Xianglin Meng, Mingyan Zhao","doi":"10.3390/biomedicines13030690","DOIUrl":"10.3390/biomedicines13030690","url":null,"abstract":"<p><p><b>Background:</b> Cold exposure has an impact on various respiratory diseases. However, its relationship with idiopathic pulmonary fibrosis (IPF) remains to be elucidated. In this study, bioinformatics methods were utilized to explore the potential link between cold exposure and IPF. <b>Methods:</b> Cold exposure-related genes (CERGs) were identified using RNA-Seq data from mice exposed to cold versus room temperature conditions, along with cross-species orthologous gene conversion. Consensus clustering analysis was performed based on the CERGs. A prognostic model was established using univariate and multivariate risk analyses, as well as Lasso-Cox analysis. Differential analysis, WGCNA, and Lasso-Cox methods were employed to screen for signature genes. <b>Results:</b> This study identified 151 CERGs. Clustering analysis based on these CERGs revealed that IPF patients could be divided into two subgroups with differing severity levels. Significant differences were observed between these two subgroups in terms of hypoxia score, EMT score, GAP score, immune infiltration patterns, and mortality rates. A nine-gene prognostic model for IPF was established based on the CERG (AUC: 1 year: 0.81, 3 years: 0.79, 5 years: 0.91), which outperformed the GAP score (AUC: 1 year: 0.66, 3 years: 0.75, 5 years: 0.72) in prognostic accuracy. IPF patients were classified into high-risk and low-risk groups based on the RiskScore from the prognostic model, with significant differences observed between these groups in hypoxia score, EMT score, GAP score, immune infiltration patterns, and mortality rates. Ultimately, six high-risk signature genes associated with cold exposure in IPF were identified: GASK1B, HRK1, HTRA1, KCNN4, MMP9, and SPP1. <b>Conclusions:</b> This study suggests that cold exposure may be a potential environmental factor contributing to the progression of IPF. The prognostic model built upon cold exposure-related genes provides an effective tool for assessing the severity of IPF patients. Meanwhile, GASK1B, HRK1, HTRA1, KCNN4, MMP9, and SPP1 hold promise as potential biomarkers and therapeutic targets for IPF.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726972","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":"Theoretical Models and Simulations of Gene Delivery with Polyurethane: The Importance of Polyurethane as a Vector in Personalized Therapy.","authors":"Roxana Maria Jeleriu, Roxana-Karin Hajaj, Iuliana-Anamaria Trăilă, Mihaela Zaharie, Maria Puiu","doi":"10.3390/biomedicines13030692","DOIUrl":"10.3390/biomedicines13030692","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Advancements in personalized medicine have revolutionized drug delivery, enabling tailored treatments based on genetic and molecular profiles. Non-viral vectors, such as polyurethane (PU)-based systems, offer promising alternatives for gene therapy. This study develops mathematical models to analyze PU degradation, DNA/RNA release kinetics, and cellular interactions, optimizing their application in personalized therapy. <b>Methods</b>: This theoretical study utilized mathematical modeling and numerical simulations to analyze PU-based gene delivery, focusing on diffusion, degradation, and cellular uptake. Implemented in Python 3.9, it employed differential equation solvers and adsorption/internalization models to predict vector behavior and optimize delivery efficiency. <b>Results</b>: This study demonstrated that PU degrades in biological environments following first-order kinetics, ensuring a controlled and predictable release of genetic material. The Higuchi diffusion model confirmed a gradual, sustained DNA/RNA release, essential for efficient gene delivery. Simulations of PU adsorption onto cellular membranes using the Langmuir model showed saturation-dependent binding, while the endocytosis model revealed a balance between uptake and degradation. These findings highlight PU's potential as a versatile gene delivery vector, offering controlled biodegradability, optimized release profiles, and effective cellular interaction. <b>Conclusions</b>: Our results confirm that PU-based vectors enable controlled biodegradability, sustained DNA/RNA release, and efficient cellular uptake. Mathematical modeling provides a framework for improving PU's properties, enhancing transport efficiency and therapeutic potential in personalized medicine and gene therapy applications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727957","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":"Basic-Clinical Analysis of Parathyroid Cancer.","authors":"Lucas Fuenzalida, Sebastián Indo, Héctor R Contreras, Daniel Rappoport, Patricio Cabané","doi":"10.3390/biomedicines13030687","DOIUrl":"10.3390/biomedicines13030687","url":null,"abstract":"<p><p>Parathyroid cancer (PC) presents clinically as a case of hyperparathyroidism associated with local compression symptoms. The definitive diagnosis of PC is complex as it requires unequivocal criteria of invasion in postoperative biopsy. Given the difficulty in confirming the diagnosis of PC, attempts have been made to address this problem through the search for biomarkers, mainly using immunohistochemistry. Within this theme, the phenomenon of epithelial-mesenchymal transition and cancer stem cell markers have been scarcely studied; this could eventually help discriminate between a diagnosis of parathyroid adenoma or carcinoma. On the other hand, identification of oncogenes and tumor suppressing genes, as well as epigenetic markers such as miRNAs, lncRNAs, and circRNAs all play a crucial role in tumorigenesis and have enormous potential as diagnostic tools. Furthermore, proteomic-based and inflammatory markers have also been described as diagnostic aids for this uncommon neoplasm. This review presents a clinical approach to the disease, as well as providing a state-of-the-art analysis of basic biomarkers in diagnosis and future projections in this field.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727928","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":"Novel Insights into CKMB, Myoglobin, and Troponin I Levels as Predictors of COVID-19 Severity and Hospitalization Outcomes.","authors":"Aida-Isabela Adamescu, Cătălin Tilișcan, Laurențiu Mihăiță Stratan, Nicoleta Mihai, Oana-Alexandra Ganea, Sebastian Ciobanu, Adrian Gabriel Marinescu, Victoria Aramă, Ștefan Sorin Aramă","doi":"10.3390/biomedicines13030672","DOIUrl":"10.3390/biomedicines13030672","url":null,"abstract":"<p><p><b>Background</b>: COVID-19 has largely become an endemic disease in many regions, with sporadic outbreaks, with some areas where the disease shows a seasonal pattern like the influenza virus. The focus has shifted towards managing mild and moderate forms of disease through outpatient care, aiming to prevent healthcare system overload. Consequently, identifying markers that could be used in stratifying the risk and the prognostic assessment has become crucial. Cardiovascular implications of COVID-19 are a critical area of research due to their significant impact on disease severity, mortality, and morbidity. <b>Methods</b>: We conducted a retrospective, observational study and included 472 patients, diagnosed with COVID-19, all of whom were admitted to Prof. Dr. Matei Bals National Institute of Infectious Disease, Bucharest, Romania. Levels of cardiac biomarkers like creatine kinase (CK), creatine kinase-myocardial band (CKMB), myoglobin, troponins, and NT-pro-BNP were measured and analyzed in relation to clinical presentation and outcomes. <b>Results</b>: We combined CKMB, myoglobin, and troponin I to predict hospital length of stay (LOS). Our model significantly predicted LOS (F = 12.537, <i>p</i> = 0.0001), with higher levels associated with prolonged stays (β = 0.166, <i>p</i> = 0.000). Logistic regression demonstrated that the combination of elevated CKMB and myoglobin levels significantly increased the odds of a longer LOS (OR = 1.679, <i>p</i> = 0.000). Furthermore, we found significant correlations with acute respiratory failure (<i>p</i> = 0.001), severe forms of disease (<i>p</i> = 0.000), and the development of complications during hospitalization (<i>p</i> = 0.027). <b>Conclusions</b>: These findings emphasize the value of combining cardiac biomarkers to stratify risk and predict hospital outcomes in COVID-19 patients. Routine cardiac monitoring and targeted management strategies could decrease the risk of complications, reducing the LOS. Our findings highlight the potential of cardiac biomarkers as prognostic tools to stratify risk, guide clinical interventions, and improve outcomes in COVID-19 patients.</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/PMC11940227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727951","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 Development of a Nomogram Predictive Model for Intracardiac Thrombosis Risk: A Study Based on Risk Factors in Patients with Acute Myocardial Infarction.","authors":"Xiaowei Huo, Zizhu Lian, Peizhu Dang, Yongjian Zhang","doi":"10.3390/biomedicines13030679","DOIUrl":"10.3390/biomedicines13030679","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Intracardiac thrombosis (ICT) is a serious complication in acute myocardial infarction (AMI) patients. This study aimed to identify potential risk factors of ICT in AMI patients, providing valuable insights for clinical management. <b>Methods</b>: A case-control study was conducted involving consecutive AMI patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University between January 2019 and December 2022. Binary logistic regression identified independent risk factors of ICT and a nomogram prediction model was constructed and validated for accuracy. <b>Conclusions</b>: A total of 7341 patients with ICT and 74 without ICT were included. Multivariate logistic regression identified male gender, acute anterior wall myocardial infarction (AWMI), ventricular aneurysm, and lower prothrombin activity as independent risk factors of ICT in AMI patients. A nomogram based on these factors demonstrated excellent performance (AUC: 0.910, 95% CI: 0.877-0.943, <i>p</i> < 0.001), with calibration and sensitivity analyses confirming its robustness. This nomogram provides an accurate tool for predicting ICT risk, facilitating personalized management and early intervention in AMI patients.</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/PMC11940212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728199","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":"HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.","authors":"Elias Kouroumalis, Ioannis Tsomidis, Argyro Voumvouraki","doi":"10.3390/biomedicines13030683","DOIUrl":"10.3390/biomedicines13030683","url":null,"abstract":"<p><p>Iron overload can lead to increased deposition of iron and cause organ damage in the liver, the pancreas, the heart and the synovium. Iron overload disorders are due to either genetic or acquired abnormalities such as excess transfusions or chronic liver diseases. The most common genetic disease of iron deposition is classic hemochromatosis (HH) type 1, which is caused by mutations of <i>HFE</i>. Other rare forms of HH include type 2A with mutations at the gene <i>hemojuvelin</i> or type 2B with mutations in <i>HAMP</i> that encodes hepcidin. HH type 3, is caused by mutations of the gene that encodes transferrin receptor 2. Mutations of <i>SLC40A1</i> which encodes ferroportin cause either HH type 4A or HH type 4B. In the present review, an overview of iron metabolism including absorption by enterocytes and regulation of iron by macrophages, liver sinusoidal endothelial cells (LSECs) and hepatocyte production of hepcidin is presented. Hereditary Hemochromatosis and the current pathogenetic model are analyzed. Finally, a new hypothesis based on published data was suggested. The Kupffer cell is the primary defect in <i>HFE</i> hemochromatosis (and possibly in types 2 and 3), while the hepcidin-relative deficiency, which is the common underlying abnormality in the three types of HH, is a secondary consequence.</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/PMC11940282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727462","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}