Biomedicines最新文献

{"title":"Tumor-Promoted Changes in Pediatric Brain Histology Can Be Distinguished from Normal Parenchyma by Desorption Electrospray Ionization Mass Spectrometry Imaging.","authors":"Ana L Seidinger, Felipe L T Silva, Mayara F Euzébio, Anna C Krieger, João Meidanis, Junier M Gutierrez, Thais M S Bezerra, Luciano Queiroz, Alex A Rosini Silva, Iva L Hoffmann, Camila M M Daiggi, Helder Tedeschi, Marcos N Eberlin, Livia S Eberlin, José A Yunes, Andreia M Porcari, Izilda A Cardinalli","doi":"10.3390/biomedicines12112593","DOIUrl":"10.3390/biomedicines12112593","url":null,"abstract":"<p><p><b>Background:</b> Central nervous system (CNS) tumors are the second most frequent type of neoplasm in childhood and adolescence, after leukemia. Despite the incorporation of molecular classification and improvement of protocols combining chemotherapy, surgery, and radiotherapy, CNS tumors are still the most lethal neoplasm in this age group. Mass spectrometry imaging (MSI) is a powerful tool to map the distribution of molecular species in tissue sections. Among MSI techniques, desorption electrospray ionization (DESI-MSI) has been demonstrated to enable reliable agreement with the pathological evaluation of different adult cancer types, along with an acceptable time scale for intraoperative use. <b>Methods:</b> In the present work, we aimed to investigate the chemical profile obtained by DESI-MSI as an intraoperative surgical management tool by profiling 162 pediatric brain biopsies and reporting the results according to the histopathology and molecular profile of the tumors. <b>Results:</b> The 2D chemical images obtained by DESI-MSI allowed us to distinguish tumor-transformed tissue from non-tumor tissue with an accuracy of 96.8% in the training set and 94.3% in the validation set after statistical modeling of our data using Lasso. In addition, high-grade and low-grade tumors also displayed a distinct chemical profile when analyzed by DESI-MSI. We also provided evidence that the chemical profile of brain tumors obtained by DESI-MSI correlates with methylation-based molecular classes and specific immunophenotypes found in brain biopsies. <b>Conclusions:</b> The results presented herein support the incorporation of DESI-MSI analysis as an intraoperative assistive tool in prospective clinical trials for pediatric brain tumors management in the near future.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725631","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":"CART (Cocaine- and Amphetamine-Regulated Transcript): A New Identified Intrafollicular Mediator in Ovulation Induction Protocols.","authors":"Charalampos Voros, Despoina Mavrogianni, Sofoklis Stavros, Myrto Papamentzelopoulou, Evangelia Dimitroulia, Dimitrios Doumplis, Dimitris Mathiopoulos, Dimitrios Loutradis","doi":"10.3390/biomedicines12112598","DOIUrl":"10.3390/biomedicines12112598","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study investigates the relationship between cocaine- and amphetamine-regulated transcript (CART) expression, leptin, and hormone profiles-specifically progesterone, testosterone, androstenedione, estradiol, follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG)-across four distinct ovulation induction protocols (HMG, HMG/hCG, rFSH, and rFSH/hCG). It also investigates the relationship between follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphisms, CART expression, and in vitro fertilization (IVF) results, with the goal of better understanding how CART and FSHR polymorphisms affect ovarian response and oocyte quality.</p><p><strong>Methods: </strong>Data were obtained from 94 women who underwent controlled ovarian stimulation (COS) as part of their IVF therapy. Hormone levels, CART expression, and FSHR polymorphisms were measured across all four ovulation induction procedures. Statistical studies were undertaken to investigate the relationships between CART expression, hormone levels, and IVF results.</p><p><strong>Results: </strong>The study found no significant difference in body mass index (BMI) amongst the four stimulation procedures (<i>p</i>-values varied from 0.244 to 0.909). CART expression did not show a significant correlation with hormone levels throughout the whole cohort (progesterone, testosterone, androstenedione, FSH, hCG, and estradiol; <i>p</i> > 0.05). However, CART levels were adversely linked with the number of follicles > 12 mm (r = -0.251, <i>p</i> = 0.018), total oocyte count (r = -0.247, <i>p</i> = 0.019), and oocyte maturity (r = -0.212, <i>p</i> = 0.048). Furthermore, there was a strong negative connection between CART expression and thyroid hormone T3 (r = -0.319, <i>p</i> = 0.048). Among FSHR polymorphisms, the SER/SER genotype was related to greater CART levels (mean 4.198 ± 2.257) than the SER/ASN and ASN/ASN genotypes (<i>p</i> = 0.031).</p><p><strong>Conclusions: </strong>These data indicate that CART expression and FSHR polymorphisms may influence ovarian response and oocyte quality in IVF patients, possibly acting as biomarkers for evaluating ovarian outcomes in various ovulation induction procedures.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725690","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":"Possible Potentiating Effects of Combined Administration of Alcohol, Caffeine, and Nicotine on In Vivo Dopamine Release in Addiction-Related Circuits Within the CNS of Rats.","authors":"Carmen Costas-Ferreira, Martiño Barreiro-Chapela, Rafael Durán, Lilian R Ferreira Faro","doi":"10.3390/biomedicines12112591","DOIUrl":"10.3390/biomedicines12112591","url":null,"abstract":"<p><strong>Background: </strong>Studies that assess the effects of the interaction of psychoactive substances on dopamine release, the key neurotransmitter in the neurochemical and behavioral effects related to drug consumption, are crucial to understand both their roles and the dysfunctions they produce in the central nervous system.</p><p><strong>Objective: </strong>We evaluated the effects of individual and combined administration of the three most widely consumed psychoactive substances in the world, ethanol, caffeine, and nicotine, on dopaminergic neurotransmission in three brain regions of rats related to addiction: the prefrontal cortex (PFC), the nucleus accumbens (NAcc), and the dorsal striatum.</p><p><strong>Methods: </strong>The dopamine levels were measured in vivo by cerebral microdialysis associated with HPLC-ED.</p><p><strong>Results: </strong>We observed that local administration of a single concentration of caffeine (5 mM) or nicotine (5 mM) significantly increased the dopamine levels in all three areas studied, while ethanol (300 mM) increased them in the NAcc and striatum. Perfusion of nicotine + caffeine produced a synergistic effect in both the NAcc and striatum, with increases in the in vivo dopamine release greater than the sum of the effects of both substances. When administering the combination of nicotine + caffeine + ethanol, we observed an additive effect in the NAcc, while in the PFC we observed a synergistic effect.</p><p><strong>Conclusions: </strong>Our results support the stimulating effects of caffeine, nicotine, and ethanol on the brain reward system. In addition, we also observed that the administration of different mixtures of these substances produces synergistic and additive effects on the release of dopamine in the mesocortical and nigrostriatal systems.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725762","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":"Connexins and Aging-Associated Respiratory Disorders: The Role in Intercellular Communications.","authors":"Tatiana Zubareva, Ekaterina Mironova, Anna Panfilova, Yulia Krylova, Gianluigi Mazzoccoli, Maria Greta Pia Marasco, Igor Kvetnoy, Peter Yablonsky","doi":"10.3390/biomedicines12112599","DOIUrl":"10.3390/biomedicines12112599","url":null,"abstract":"<p><p>This article reviews the contemporary understanding of the functional role of connexins in intercellular communications, their involvement in maintaining cellular and tissue homeostasis, and in aging-associated respiratory disease pathogenesis. Connexins are discussed as potential therapeutic targets. The review particularly focuses on the involvement of gap junction connexins and hemichannels in the transfer of calcium ions, metabolite molecules, ATP, and mitochondria through the cell membrane. Various disorders in the regulation of intercellular communication can heavily contribute to the pathogenesis of multiple diseases, including respiratory system diseases. A deeper understanding of molecular mechanisms underlying the activities of various connexins in gap junction channels will enable the prospective development of therapeutic approaches by either inhibiting or stimulating the activities of a certain connexin, while considering its critical functions in intercellular communications on the whole.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725529","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":"A Systematic Identification of RNA-Binding Proteins (RBPs) Driving Aberrant Splicing in Cancer.","authors":"Cesar Lobato-Fernandez, Marian Gimeno, Ane San Martín, Ana Anorbe, Angel Rubio, Juan A Ferrer-Bonsoms","doi":"10.3390/biomedicines12112592","DOIUrl":"10.3390/biomedicines12112592","url":null,"abstract":"<p><strong>Background: </strong>Alternative Splicing (AS) is a post-transcriptional process that allows a single RNA to produce different mRNA variants and, in some cases, multiple proteins. Various processes, many yet to be discovered, regulate AS. This study focuses on regulation by RNA-binding proteins (RBPs), which are not only crucial for splicing regulation but also linked to cancer prognosis and are emerging as therapeutic targets for cancer treatment. CLIP-seq experiments help identify where RBPs bind on nascent transcripts, potentially revealing changes in splicing status that suggest causal relationships. Selecting specific RBPs for CLIP-seq experiments is often driven by a priori hypotheses.</p><p><strong>Results: </strong>We developed an algorithm to detect RBPs likely related to splicing changes between conditions by integrating several CLIP-seq databases and a differential splicing detection algorithm. This work refines a previous study by improving splicing event prediction, testing different enrichment statistics, and performing additional validation experiments. The new method provides more accurate predictions and is included in the Bioconductor package EventPointer 3.14. We tested the algorithm in four experiments involving knockdowns of seven different RBPs. The algorithm accurately assessed the statistical significance of these RBPs using only splicing alterations. Additionally, we applied the algorithm to study sixteen cancer types from The Cancer Genome Atlas (TCGA) and three from TARGET. We identified relationships between RBPs and various cancer types, including alterations in CREBBP and MBNL2 in adenocarcinomas of the lung, liver, prostate, rectum, stomach, and colon. Some of these findings are validated in the literature, while others are novel.</p><p><strong>Conclusions: </strong>The developed algorithm enhances the ability to predict and understand RBP-related splicing changes, offering more accurate predictions and novel insights into cancer-related splicing alterations. This work highlights the potential of RBPs as therapeutic targets and contributes to the broader understanding of their roles in cancer biology.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725523","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":"A Review of Limbic System-Associated Membrane Protein in Tumorigenesis.","authors":"Kayleigh Wittmann Sinopole, Kevin Babcock, Albert Dobi, Gyorgy Petrovics","doi":"10.3390/biomedicines12112590","DOIUrl":"10.3390/biomedicines12112590","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose of review: &lt;/strong&gt;This review aims to describe the role of limbic system-associated membrane protein (LSAMP) in normal- and pathophysiology, and its potential implications in oncogenesis. We have summarized research articles reporting the role of LSAMP in the development of a variety of malignancies, such as clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. We also examine the current understanding of how defects in LSAMP gene function may contribute to oncogenesis. Finally, this review discusses the implications of future LSAMP research and clinical applications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Recent findings: &lt;/strong&gt;LSAMP has been originally described as a surface adhesion glycoprotein expressed on cortical and subcortical neuronal somas and dendrites during the development of the limbic system. It is categorized as part of the IgLON immunoglobulin superfamily of cell-adhesion molecules and is involved in regulating neurite outgrowth and neural synapse generation. LSAMP is both aberrantly expressed and implicated in the development of neuropsychiatric disorders due to its role in the formation of specific neuronal connections within the brain. Additionally, LSAMP has been shown to support brain plasticity via the formation of neuronal synapses and is involved in modulating the hypothalamus in anxiogenic environments. In murine studies, the loss of LSAMP expression was associated with decreased sensitivity to amphetamine, increased sensitivity to benzodiazepines, increased hyperactivity in new environments, abnormal social behavior, decreased aggressive behavior, and decreased anxiety. Findings have suggested that LSAMP plays a role in attuning serotonergic activity as well as GABA activity. Given its importance to limbic system development, LSAMP has also been studied in the context of suicide. In malignancies, LSAMP may play a significant role as a putative tumor suppressor, the loss of which leads to more aggressive phenotypes and mortality from metastatic disease. Loss of the LSAMP gene facilitates epithelial-mesenchymal transition, or EMT, where epithelial cells lose adhesion and gain the motile properties associated with mesenchymal cells. Additionally, LSAMP and the function of the RTK pathway have been implicated in tumorigenesis through the modulation of RTK expression in cell membranes and the activation of second messenger pathways and β-catenin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;Beyond its many roles in the limbic system, LSAMP functions as a putative tumor suppressor protein. Loss of the LSAMP gene is thought to facilitate epithelial-mesenchymal transition, or EMT, where cells lose adhesion and migrate to distant organs. LSAMP's role in modulating RTK activity and downstream ERK and Akt pathways adds to a large body of data investigating RTK expression in oncogenesis. The characteristics of LSAMP defects and their as","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725563","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":"Methods for Identifying Epilepsy Surgery Targets Using Invasive EEG: A Systematic Review.","authors":"Karla Ivankovic, Alessandro Principe, Riccardo Zucca, Mara Dierssen, Rodrigo Rocamora","doi":"10.3390/biomedicines12112597","DOIUrl":"10.3390/biomedicines12112597","url":null,"abstract":"<p><strong>Background: </strong>The pre-surgical evaluation for drug-resistant epilepsy achieves seizure freedom in only 50-60% of patients. Efforts to identify quantitative intracranial EEG (qEEG) biomarkers of epileptogenicity are needed. This review summarizes and evaluates the design of qEEG studies, discusses barriers to biomarker adoption, and proposes refinements of qEEG study protocols.</p><p><strong>Methods: </strong>We included exploratory and prediction prognostic studies from MEDLINE and Scopus published between 2017 and 2023 that investigated qEEG markers for identifying the epileptogenic network as the surgical target. Cohort parameters, ground truth references, and analytical approaches were extracted.</p><p><strong>Results: </strong>Out of 1789 search results, 128 studies were included. The study designs were highly heterogeneous. Half of the studies included a non-consecutive cohort, with sample sizes ranging from 2 to 166 patients (median of 16). The most common minimum follow-up was one year, and the seizure onset zone was the most common ground truth. Prediction studies were heterogeneous in their analytical approaches, and only 25 studies validated the marker through post-surgical outcome prediction. Outcome prediction performance decreased in larger cohorts. Conversely, longer follow-up periods correlated with higher prediction accuracy, and connectivity-based approaches yielded better predictions. The data and code were available in only 9% of studies.</p><p><strong>Conclusions: </strong>To enhance the validation qEEG markers, we propose standardizing study designs to resemble clinical trials. This includes using a consecutive cohort with long-term follow-up, validating against surgical resection as ground truth, and evaluating markers through post-surgical outcome prediction. These considerations would improve the reliability and clinical adoption of qEEG markers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725743","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":"Peripheral Eosinophil Count May Be the Prognostic Factor for Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Treatment.","authors":"Wojciech Ciesielski, Izabela Kupryś-Lipińska, Anna Kumor-Kisielewska, Oliwia Grząsiak, Julia Borodacz, Sebastian Niedźwiecki, Piotr Hogendorf, Adam Durczyński, Janusz Strzelczyk, Alicja Majos","doi":"10.3390/biomedicines12112596","DOIUrl":"10.3390/biomedicines12112596","url":null,"abstract":"<p><p>(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and <0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I-III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I-III, EOS < 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS < 0.1 G/l group: 5.0 months. EOS < 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, <i>p</i> = 0.035 and HR = 1.57, <i>p</i> = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725759","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":"Effects of Mediterranean Diet on Endothelial Reactivity in Individuals with High Cardiometabolic Risk: A Randomized Controlled Parallel-Group Preliminary Trial.","authors":"Roberta Lupoli, Ilenia Calcaterra, Pasquale Ambrosino, Rosalba Giacco, Marilena Vitale, Giuseppe Della Pepa, Angela Albarosa Rivellese, Gabriella Iannuzzo, Lutgarda Bozzetto, Matteo Di Minno","doi":"10.3390/biomedicines12112595","DOIUrl":"10.3390/biomedicines12112595","url":null,"abstract":"<p><strong>Background: </strong>Endothelial dysfunction is recognized as an early modification involved in the pathogenesis of vascular diseases. Evidence suggests that the Mediterranean Diet (MD) is associated with endothelial function improvement and, in turn, plays an important role in atherosclerosis development and progression.</p><p><strong>Objectives: </strong>To evaluate both acute and sustained effects of the MD on endothelial function in patients with high cardiometabolic risk.</p><p><strong>Methods: </strong>A total of 25 subjects were randomly assigned to either the MD group or the Control Diet (CD) group according to a single-blind, parallel-group study design. Endothelial function was evaluated through non-invasive flow-mediated dilation (FMD) measurements at baseline (T0) and after 8 weeks (Tw8) of the MD or CD intervention, under both 12 h fast condition (fasting) and 2 h post-meal resembling the assigned diet (2 h). Assessments were conducted by a blinded sonographer.</p><p><strong>Results: </strong>FMD at T0-fasting was similar between MD and CD groups (6.11% ± 0.67 vs. 7.90% ± 1.65; <i>p</i> = 0.266). A significant difference in FMD between MD and CD groups was observed at T0-2h (12.14% ± 1.93 vs. 4.01% ± 1.03; <i>p</i> = 0.004), T8w-fasting (9.76% ± 1.18 vs. 5.03% ± 0.89; <i>p</i> = 0.008), and T8w-2h (8.99% ± 1.22 vs. 3.86% ± 0.52; <i>p</i> = 0.003). Oral glucose insulin sensitivity (OGIS) at T0 correlated with FMD percent changes from T0-fasting to T0-2h (r = 0.414, <i>p</i> = 0.044). After adjusting for age, gender, and OGIS, MD was an independent predictor of percent changes in FMD from T0-fasting to T0-2h (β: -0.582, <i>p</i> = 0.003), from T0-fasting to T8w-fasting (β: -0.498, <i>p</i> = 0.013), and from T0-fasting to T8w-2h (β: -0.479, <i>p</i> = 0.018).</p><p><strong>Conclusions: </strong>Adherence to the MD may improve endothelial function in both the short- and medium-term among patients at high cardiometabolic risk.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725598","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":"Rituximab Administration to Treat Nephrotic Syndrome in Children: 2-Year Follow-Up.","authors":"Dmytro Ivanov, Lutz T Weber, Elena Levtchenko, Liudmyla Vakulenko, Mariia Ivanova, Iryna Zavalna, Yelizaveta Lagodych, Ninel Boiko","doi":"10.3390/biomedicines12112600","DOIUrl":"10.3390/biomedicines12112600","url":null,"abstract":"<p><strong>Background: </strong>Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children's quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments.</p><p><strong>Objective: </strong>This study aims to evaluate the long-term efficacy and safety of rituximab administration in children with SSNS, encompassing FRNS and SDNS, and SRNS over a two-year follow-up period, facilitating individualized management.</p><p><strong>Methods: </strong>We conducted an open-label, multicenter, randomized, and patient-oriented study (RICHNESS), involving children aged 3-18 with SRNS (18) and SSNS (11) undergoing 2 years continuous RTX therapy. The primary outcome was complete/partial remission (CR/PR), as defined by IPNA/KDIGO guidelines, at 6, 12, 18, and 24 months on RTX; secondary outcomes included adverse events. Key endpoints included the estimated glomerular filtration rate (eGFR), the albumin-to-creatinine ratio (ACR), CD20 levels, IgG levels, and the incidence of infections. Kidney biopsies were performed in 94% of SRNS patients. RTX was administered every 6-9 months, depending on CD20 levels, IgG levels, and the presence of infections. The eGFR and ACR were assessed every 6 months.</p><p><strong>Results: </strong>Some 31 children were selected for RTX treatment. Overall, 2 experienced severe allergic reactions, leading to their exclusion from the final analysis of 29 children. In the SSNS group, all children achieved and maintained complete remission within 2 years. Remission rates in the SRNS group ranged from 39% (RR 0.78; 95% CI: 16.4-61.4%, NNT 9) at the 6th month to 72% (RR 1.44; 95% CI: 51.5-92.9%) over the 2-year follow-up period due to continuous RTX therapy. The median duration of RTX use was 26.1 months, with a median cumulative dose of 1820 mg/m². Adverse reactions and complications were presented by mild infusion-related reactions in 3 children (10.3%), severe allergic reactions in 2 children (6.2%), hypogammaglobulinemia in 7 children (24%), infections in 3 children (10.3%), severe destructive pneumonia in 1 child, recurrent respiratory infections in 2 children, and neutropenia in 1 child (3.44%).</p><p><strong>Conclusions: </strong>RTX was tolerated well, and proved highly effective as a steroid-sparing agent, offering potential in terms of stopping relapses and minimizing steroid-related side effects. It also demonstrated efficacy in slowing progression in SRNS, indicating potential for use in ACR reduction and renal function restoration, but requires careful use given potential severe allergic reactions and infectious complications. Further studies should focus on long-term cost-effectiveness and deferred side effects.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725586","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}