BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051201
Dmitri Artemiev, Christophe Valmaggia, Scott Tschuppert, Konstantin Kotliar, Cengiz Türksever, Margarita G Todorova
{"title":"Retinal Vessel Flicker Light Responsiveness and Its Relation to Analysis Protocols and Static and Metabolic Data in Healthy Subjects.","authors":"Dmitri Artemiev, Christophe Valmaggia, Scott Tschuppert, Konstantin Kotliar, Cengiz Türksever, Margarita G Todorova","doi":"10.3390/biomedicines13051201","DOIUrl":"https://doi.org/10.3390/biomedicines13051201","url":null,"abstract":"<p><p><b>Background:</b> The aim of this study was to assess the agreement between different analysis protocols for the determination of retinal vessel dilation response to flicker light (FL) and its relation to static and metabolic parameters of retinal vessels in healthy subjects. <b>Methods</b>: In total, 24 right eyes of 24 healthy controls (mean age: 36.04 ± SD 14.4 years) who underwent dynamic and static retinal diameter and oxygen saturation measurements on a Retinal Vessel Analyzer (RVA, Imedos, Jena, Germany) were included. Using repeated video analyses, responses to FL were measured with RVA. These measurements were conducted at three specific retinal locations: within the superotemporal area-within a distance of less than one optic disk (OD) diameter to optic nerve head (ONH) (group 1); greater than one OD diameter to ONH (group 2); and areas near the ONH within the VesselMap region (group 3). For comparability, the static and oxygen saturation parameters were also calculated in the superotemporal peripapillary area using the VesselMap tool of the RVA and were evaluated in relation to the corresponding dynamic area (group 3). <b>Results</b>: In all groups, the vascular FL response of arteries was less pronounced compared to venules (<i>p</i> = 0.0014). Even though FL responses (mean ± SD: FL-A; FL-V) in group 1 were more pronounced (3.36 ± 2.31; 4.42 ± 1.69) compared to those in group 2 (2.97 ± 2.40; 4.08 ± 1.55) and group 3 (2.84 ± 2.29; 4.21 ± 2.03), they did not reach statistically significant values. The mean flicker response of venules (VDil) in all groups showed negative correlations to the corresponding static parameter: central retinal venous equivalent (CRV) (<i>r</i> = -0.0437; <i>p</i> = 0.015). The mean flicker response of arteries (ADil) in all groups showed negative correlations to the corresponding metabolic parameter: arterio-venous oxygen extraction fraction (<i>r</i> = -0.101; <i>p</i> = 0.041). <b>Conclusions</b>: Our study confirms that the flicker light response, despite slight variations in its duration and location, allows for reliable measurements, proving the Retinal Vessel Analyzer to be a valuable diagnostic tool. Furthermore, we were able to highlight the relationship between the dynamic and metabolic components of retinal supply, which enables early diagnosis concerning the development of diseases within this spectrum.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156502","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}
BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051206
Branimir Plavša, Najda Rudman, Flemming Pociot, Olga Gornik
{"title":"Altered IgG <i>N</i>-Glycosylation at Onset of Type 1 Diabetes in Children Is Predominantly Driven by Changes in the Fab <i>N</i>-Glycans.","authors":"Branimir Plavša, Najda Rudman, Flemming Pociot, Olga Gornik","doi":"10.3390/biomedicines13051206","DOIUrl":"https://doi.org/10.3390/biomedicines13051206","url":null,"abstract":"<p><p><b>Background</b>: <i>N</i>-glycosylation is a post-translational modification involving the attachment of oligosaccharides to proteins and is known to influence immunoglobulin G (IgG) effector functions and even antigen binding. IgG contains an evolutionarily conserved <i>N</i>-glycosylation site in its fragment crystallizable (Fc) region, while during V-D-J recombination and somatic hypermutation processes it can also obtain <i>N</i>-glycosylation sites in its antigen binding fragment (Fab). Our previous study demonstrated altered IgG <i>N</i>-glycosylation in children at type 1 diabetes (T1D) onset, with the most prominent changes involving sialylated glycans, hypothesized to mainly come from the Fab region, however, the analytical method used could not distinguish between Fc and Fab. <b>Methods</b>: IgG was isolated from plasma from 118 children with T1D and 98 healthy controls from the Danish Registry of Childhood and Adolescent Diabetes. Isolated IgG was cleaved into Fc and Fab fragments using IdeS enzyme. <i>N</i>-glycans were enzymatically released from each fragment, fluorescently labelled with procainamide, and analyzed separately using the UPLC-MS method. Structural annotation of resulting chromatograms was performed using MS/MS. <b>Results</b>: T1D related <i>N</i>-glycosylation changes were more pronounced in the Fab glycans compared to Fc glycans, with five Fab glycans (Man5, Man7, FA2BG1S1, A2G2S2, FA2BG2S1) being significantly altered compared to only one in the Fc region (FA2[3]BG1). Comparing Fc and Fab glycosylation overall reveals stark differences in the types of glycans on each region, with a more diverse and complex repertoire being present in the Fab region. <b>Conclusions</b>: These findings suggest that <i>N</i>-glycosylation changes in early onset T1D predominantly originate from the Fab region, underscoring their potential role in modulating (auto)immunity and highlighting distinct glycosylation patterns between Fc and Fab.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156356","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}
BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051200
Lincheng Duan, Jingyi Yang, Junxin Zhao, Zhuoyang Chen, Hong Yang, Dingjun Cai
{"title":"Evaluating the Causal Role of Genetically Inferred Immune Cells and Inflammatory Cytokines on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.","authors":"Lincheng Duan, Jingyi Yang, Junxin Zhao, Zhuoyang Chen, Hong Yang, Dingjun Cai","doi":"10.3390/biomedicines13051200","DOIUrl":"https://doi.org/10.3390/biomedicines13051200","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted and diverse disorder with an ambiguous etiology. Recent evidence indicates that immune system impairment and inflammatory mechanisms are pivotal to the initiation and advancement of ME/CFS. Nonetheless, the causal relationships among these factors remain inadequately comprehended. <b>Methods</b>: This study investigated the causative contributions of immunological dysfunction and inflammatory variables in ME/CFS utilizing genome-wide association study (GWAS) data. We employed Mendelian randomization (MR) to investigate associations between 91 inflammatory cytokines, 731 immune cell characteristics, and the risk of ME/CFS. Summary statistics for immune cell traits and inflammatory cytokines were sourced from European GWAS cohorts (n = 3757 and n = 14,824, respectively), while ME/CFS data were obtained from the UK Biobank (n = 462,933, including 2076 cases). We predominantly employed the inverse variance weighted (IVW) approach, complemented by MR-Egger, weighted median, BWMR, and MR-RAPS tests to guarantee robust and precise outcomes. <b>Results</b>: The study revealed significant causal links between various inflammatory factors, immune cell characteristics, and the risk of ME/CFS. Increased CXCL5 and CCL20 levels were significantly linked to a higher risk of ME/CFS, while elevated TNF levels were inversely related to ME/CFS risk. Furthermore, 13 immune cell characteristics were identified as having substantial causal associations with the likelihood of ME/CFS. These data are supportive of the causality that immune system dysfunction and inflammatory variables play a pivotal role in the development of ME/CFS. <b>Conclusions</b>: This study provides new insights into the causal role of immune system dysfunction in the development of ME/CFS, contributing to a deeper understanding of its underlying mechanisms. These results offer a foundation for identifying diagnostic biomarkers and developing targeted therapeutic strategies. Future research should validate these findings using multi-center cohort studies and further investigate the mechanisms behind key factors to enable the development of personalized treatment approaches.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156446","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}
BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051205
Shuo Zhang, Changqing Tong, Na Cao, Dong Tian, Linshan Du, Ya Xu, Weiguang Wang, Zijie Chen, Shuangqing Zhai
{"title":"Hippocampal Transcriptome Analysis in a Mouse Model of Chronic Unpredictable Stress Insomnia.","authors":"Shuo Zhang, Changqing Tong, Na Cao, Dong Tian, Linshan Du, Ya Xu, Weiguang Wang, Zijie Chen, Shuangqing Zhai","doi":"10.3390/biomedicines13051205","DOIUrl":"https://doi.org/10.3390/biomedicines13051205","url":null,"abstract":"<p><p><b>Background</b>: This study aimed to develop a model for understanding stress-induced sleep disturbances and to explore the potential interactions between sleep disturbances and mood disturbances. <b>Methods</b>: The chronic unpredictable mild stress (CUMS) group was established using the CUMS method, while the CUMS+Noise group was subjected to an additional 8-h exposure to noise in conjunction with the CUMS protocol. Each group was tested for anxiety and depressive-like behavior using the open-field, elevated plus maze, tail suspension, and forced swimming tests in male C57BL/6J mice. Subsequently, we assessed sleep status using sleep recordings and a standardized scoring system alongside the pentobarbital sodium-induced sleep test. <b>Results</b>: The mice in both model groups exhibited anxiety-like behavior. Sleep disturbances observed in the CUMS+Noise group were characterized by disruptions in sleep duration and circadian rhythm. This observation was supported by a marked reduction in multiple sleep time intervals and single sleep duration, as well as a significant increase in sleep duration at the final time interval of ZT23-24. To further investigate the potential mechanisms of interaction, we conducted an analysis of hub genes present in the hippocampal sequencing data utilizing weighted gene co-expression network analysis (WGCNA). Pearson correlation analysis revealed a significant association between the hub genes <i>Alb</i>, <i>P2rx1</i>, and <i>Npsr1</i> and key phenotypic traits. However, PCR experiments indicated that only <i>Alb</i> showed a significant difference, which aligns with the sequencing results. <b>Conclusions</b>: Albumin is a crucial transporter protein for thyroid hormones and plays a vital role in their metabolism. The interaction between sleep disorders and anxiety-like behavior may be closely linked to the dysfunctional transportation of thyroid hormones by albumin.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156187","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}
BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051207
Weronika Szybiak-Skora, Wojciech Cyna, Katarzyna Lacka
{"title":"New Insights in the Diagnostic Potential of Sex Hormone-Binding Globulin (SHBG)-Clinical Approach.","authors":"Weronika Szybiak-Skora, Wojciech Cyna, Katarzyna Lacka","doi":"10.3390/biomedicines13051207","DOIUrl":"https://doi.org/10.3390/biomedicines13051207","url":null,"abstract":"<p><p>SHBG is a glycoprotein that not only controls serum sex hormone levels but is also strongly correlated with metabolic syndrome, cardiovascular risk, thyroid function, gynecological conditions, and even the process of carcinogenesis. Synthesis of SHBG is controlled by many factors related to obesity, lipogenesis, inflammatory status, and genetic predisposition. By influencing the bioavailability of sex hormones, SHBG regulates their effects not only on the reproductive system, but also cardiomyocytes, vascular epithelium, and more. In this review, we aim to gather and summarize current knowledge on the physiology of SHBG and its association with cardiovascular disease, metabolic syndrome, DM 2, thyroid function, PCOS, hypogonadism, infertility, and its correlations with oral contraception. What is more, genetic alterations are mentioned to highlight SHBG as a potential new diagnostic marker. Furthermore, we assess the clinical usefulness of this parameter in the diagnosis and treatment of patients suffering from the above-specified conditions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156311","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":"Increased STAT3 Phosphorylation in CD4<sup>+</sup> T-Cells of Treated Patients with Chronic Lymphocytic Leukemia and Changes in Circulating Regulatory T-Cell Subsets Relative to Tumor Mass Distribution Value and Disease Duration.","authors":"Mojca Dreisinger, Zlatko Roškar, Aleš Goropevšek, Andreja Zakelšek, Sara Čurič, Nada Živko, Sebastjan Bevc, Evgenija Homšak","doi":"10.3390/biomedicines13051204","DOIUrl":"https://doi.org/10.3390/biomedicines13051204","url":null,"abstract":"<p><p><b>Introduction</b>: In mouse models of chronic lymphocytic leukemia (CLL), an effective anti-leukemia immune response was obtained by depleting a specific regulatory T-cell (Treg) subset. While STAT5 signaling could alter the homeostasis of naïve (nTreg) and activated (aTreg) subsets, which are capable of suppressing also CLL patients' responses to microbial antigens, perturbed STAT3 signaling could drive CXCR5 expression in circulating T-follicular regulatory cells (Tfr) and their entry into the lymph node/tumor microenvironment. <b>Materials and Methods</b>: By using phospho-specific flow cytometry, we monitored STAT signaling/phosphorylation (pSTAT), in vitro responses to Sars-Cov2-antigen-specific stimulation, and circulating Treg subsets in relation to Binet stage and total tumor mass/tumor distribution (TTM/TD) scoring in 62 patients with CLL. <b>Results</b>: The percentage of CXCR5<sup>+</sup> Treg significantly increased in patients with Binet stage B disease, and Tfr-like subsets were associated with higher TTM and lower TD. The pSTAT3 levels in CD4<sup>+</sup> T-cells were only significantly increased in patients undergoing therapy. Lower nTreg percentages correlated with increased disease duration, and an increased aTreg/nTreg ratio correlated with SARS-CoV-2-antigen-induced STAT5 signaling responses. <b>Conclusions</b>: The results show increased amounts of circulating CXCR5<sup>+</sup> Tfr-like subsets in patients with extensive lymph node involvement and augmented STAT3 signaling in patients on therapy. While STAT5 responses may drive nTreg differentiation into aTreg, nTreg decline is associated with increased disease duration.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156253","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}
BiomedicinesPub Date : 2025-05-15DOI: 10.3390/biomedicines13051208
Tina Zavidić, Emina Babarović, Vedrana Drvar, Božena Ćurko-Cofek, Gordana Laškarin
{"title":"Patients with Higher Pulse Wave Velocity Are More Likely to Develop a More Severe Form of Knee Osteoarthritis: Implications for Cardiovascular Risk.","authors":"Tina Zavidić, Emina Babarović, Vedrana Drvar, Božena Ćurko-Cofek, Gordana Laškarin","doi":"10.3390/biomedicines13051208","DOIUrl":"https://doi.org/10.3390/biomedicines13051208","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Knee osteoarthritis (KOA) is a progressive degenerative joint disease characterised by low-grade inflammation and is associated with increased cardiovascular (CV) risk and arterial stiffness. Pulse wave velocity (PWV) is a quantitative measure of arterial stiffness and an important tool for detecting subclinical arterial calcification and CV risk. This study aimed to determine whether PWV can distinguish radiographically mild KOA (Kellgren-Lawrence grades 1-2) from severe KAO (Kellgren-Lawrence grades 3-4) in terms of CV risk factors. <b>Methods</b>: A total of 223 postmenopausal women with KOA participated in this cross-sectional study. Assessments included anthropometry, laboratory analyses, blood pressure and PWV measurements, a 6 min walk test, pain evaluation using a visual analogue scale (VAS), and completion of the International Physical Activity Questionnaire (IPAQ). <b>Results</b>: PWV was significantly higher in the severe KOA group (10.53 m/s vs. 8.78 m/s, <i>p</i> < 0.001). A cut-off value of 8.4 m/s effectively distinguished between severe and mild forms of KOA (AUC = 0.798, <i>p</i> = 0.001). OA grade, pain, age, waist circumference, WHR, SCORE 2/SCORE 2OP, systolic blood pressure, serum glucose, HbA1c, uric acid, creatinine, and erythrocyte sedimentation rate were increased in the group with PWV > 8.4 m/s, compared to the group with PWV ≤ 8.4 m/s. Conversely, eGFR, the 6 min walk test and physical activity of patients were reduced in the group with PWV > 8.4 m/s. A patient with a PWV > 8.4 m/s has a 1.77 times higher chance of developing a more severe form of the disease than a patient with a lower PWV. <b>Conclusions</b>: Patients with a higher PWV are more likely to develop a more severe form of KOA, which is associated with increased cardiovascular risk.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156534","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}
BiomedicinesPub Date : 2025-05-14DOI: 10.3390/biomedicines13051198
Mauro Francesco Pio Maiorano, Brigida Anna Maiorano, Gennaro Cormio, Vera Loizzi
{"title":"Mucinous Ovarian Carcinoma: Integrating Molecular Stratification into Surgical and Therapeutic Management.","authors":"Mauro Francesco Pio Maiorano, Brigida Anna Maiorano, Gennaro Cormio, Vera Loizzi","doi":"10.3390/biomedicines13051198","DOIUrl":"https://doi.org/10.3390/biomedicines13051198","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features-including frequent KRAS mutations and HER2 amplifications-and exhibits limited sensitivity to platinum-based chemotherapy. These differences highlight the need for individualized treatment strategies guided by molecular and histological profiling. This review aims to integrate current evidence on the clinical management of MOC with emerging insights into its molecular biology, with a focus on how these factors influence surgical decision-making, fertility preservation, and adjuvant therapy selection. <b>Methods</b>: We performed a comprehensive narrative review of the literature, synthesizing findings from retrospective cohorts, molecular studies, and clinical guidelines relevant to the surgical, reproductive, and therapeutic management of MOC. <b>Results</b>: Histologic subtype-expansile versus infiltrative-plays a critical role in guiding lymphadenectomy as lymph node metastases are rare (<1%) in expansile tumors but occur in up to 23% of infiltrative cases. Complete surgical staging remains essential for accurate prognostication, yet tailored approaches may reduce overtreatment in low-risk patients. Fertility-sparing surgery (FSS) appears safe in FIGO stage IA expansile MOC, with favorable reproductive outcomes, while higher-stage or infiltrative cases warrant caution. Given MOC's chemoresistance, the role of adjuvant therapy in early-stage disease remains debated. Targeted strategies, including MEK inhibitors and HER2-directed therapies, are under investigation and may benefit selected molecular subgroups. <b>Conclusions</b>: MOC requires a nuanced, biomarker-informed approach. This review advocates for personalized, evidence-based management supported by multidisciplinary evaluation while underscoring the urgent need for prospective studies and biomarker-driven clinical trials.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156367","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}
BiomedicinesPub Date : 2025-05-14DOI: 10.3390/biomedicines13051196
Jurica Novak, Olga B Tseilikman, Vladislav A Shatilov, Maxim S Zhukov, Vadim A Shevyrin, Zuhra R Khismatullina, Albina M Fedorova, Georgiy N Patrikyan, Timur L Khaibullin, Vadim E Tseilikman
{"title":"Resveratrol and Its Metabolite as Potential Allosteric Regulators of Monoamine Oxidase A Activity in the Brain and Liver Under Chronic Predator Stress.","authors":"Jurica Novak, Olga B Tseilikman, Vladislav A Shatilov, Maxim S Zhukov, Vadim A Shevyrin, Zuhra R Khismatullina, Albina M Fedorova, Georgiy N Patrikyan, Timur L Khaibullin, Vadim E Tseilikman","doi":"10.3390/biomedicines13051196","DOIUrl":"https://doi.org/10.3390/biomedicines13051196","url":null,"abstract":"<p><p><b>Background</b>: Resveratrol has been shown to modulate stress-related anxiety by reducing brain monoamine oxidase A (MAO-A) activity. However, the molecular mechanism underlying this neurochemical effect remains unknown. In this study, we employed in silico approaches to investigate the binding affinity of resveratrol and its predominant blood metabolite, resveratrol glucuronide, to specific sites on MAO-A. <b>Methods</b>: For the in silico analysis, we employed molecular docking and molecular dynamics simulations. Within the liver-brain axis, we investigated the role of hepatic MAO-A in the development of anxiety. The activity of whole-brain MAO-A was compared with its activity in specific brain regions, including the amygdala, hippocampus, and prefrontal cortex. <b>Results</b>: Our findings suggest the presence of an allosteric site on the enzyme that accommodates these compounds. Furthermore, in vivo experiments demonstrated that high-dose resveratrol suppresses MAO activity not only in the brain but also in the liver of stress-exposed rats. The in vivo results are interpreted in the context of an allosteric site on MAO-A in both the brain and liver, which may mediate the interaction with resveratrol and its metabolite. <b>Conclusions</b>: The primary outcomes of the study include the identification of the role of hepatic MAO-A in the development of anxiety-like behavior, as well as the determination of resveratrol dose ranges at which it functions as an allosteric modulator of MAO-A activity.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156485","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}
BiomedicinesPub Date : 2025-05-14DOI: 10.3390/biomedicines13051193
Oumaima Laghzali, Shahriar Shalikar, Siqin Liu, Sandra Lehmann, Joao Dos Santos Periquito, Andreas Pohlmann, Sonia Waiczies, Lucie Carrier, Hsin-Jung Yang, Thoralf Niendorf, Min-Chi Ku
{"title":"Cardiac Phase-Resolved T<sub>2</sub><sup>*</sup> Magnetic Resonance Imaging Reveals Differences Between Normal Hearts and a Humanized Mouse Model of Hypertrophic Cardiomyopathy.","authors":"Oumaima Laghzali, Shahriar Shalikar, Siqin Liu, Sandra Lehmann, Joao Dos Santos Periquito, Andreas Pohlmann, Sonia Waiczies, Lucie Carrier, Hsin-Jung Yang, Thoralf Niendorf, Min-Chi Ku","doi":"10.3390/biomedicines13051193","DOIUrl":"https://doi.org/10.3390/biomedicines13051193","url":null,"abstract":"<p><p><b>Background/Objectives</b>: While T<sub>2</sub><sup>*</sup> mapping effectively assesses cerebral blood oxygenation, its utility for capturing cardiac phase-dependent myocardial changes in hypertrophic cardiomyopathy (HCM) is underexplored. This study investigates T<sub>2</sub><sup>*</sup> dynamics in an HCM mouse model, to validate T<sub>2</sub><sup>*</sup> as a clinically relevant biomarker for improved HCM diagnosis and treatment monitoring. <b>Methods</b>: A cardiac-specific <i>Mybpc3</i> genetic mouse model, closely mirroring human HCM, was used with 12 young mice (6-11 weeks old), including both male and female wild-type (WT) and <i>Mybpc3</i>-KI (HCM) groups. The cardiac function was assessed using self-gated multi-slice 2D CINE imaging. To investigate myocardial T<sub>2</sub><sup>*</sup> variations across the cardiac cycle, multi-gradient echo (MGE) imaging was employed. This approach used retrospective gating and continuous acquisition synchronization with pulse oximetry at 9.4 T small animal MRI. <b>Results</b>: <i>Mybpc3</i>-KI mice demonstrated left-ventricular (LV) hypertrophy compared to WT (HCM = 50.08 ± 4.68 µm/g vs. WT = 45.80 ± 20.07 µm/g, <i>p</i> < 0.01) and reduced ejection fraction (HCM = 38.55 ± 5.39% vs. WT= 72.53 ± 3.95%, <i>p</i> < 0.01). Myocardial T<sub>2</sub><sup>*</sup> was significantly elevated in HCM across all cardiac phases (HCM = 12.14 ± 1.54 ms vs. WT = 7.93 ± 1.57 ms, <i>p</i> = 0.002). Strong correlations were observed between myocardial T<sub>2</sub><sup>*</sup> and LV mass (rho = 0.88, <i>p</i> = 0.03). <b>Conclusions</b>: T<sub>2</sub><sup>*</sup> was elevated in HCM with increased LV mass, highlighting the potential of T<sub>2</sub><sup>*</sup> MRI as a sensitive biomarker for distinguishing healthy mice from those with HCM and revealing possible myocardial abnormalities.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156272","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}