IF 5.1 2区生物学

Cells Pub Date : 2025-05-12 DOI: 10.3390/cells14100704

Alessia Peserico, Barbara Barboni, Chiara Camerano Spelta Rapini, Chiara Di Berardino, Giulia Capacchietti, Angelo Canciello, Fani Konstantinidou, Marisa Donato, Liborio Stuppia, Valentina Gatta

{"title":"Transcriptomic Profile of Early Antral Follicles: Predictive Somatic Gene Markers of Oocyte Maturation Outcome.","authors":"Alessia Peserico, Barbara Barboni, Chiara Camerano Spelta Rapini, Chiara Di Berardino, Giulia Capacchietti, Angelo Canciello, Fani Konstantinidou, Marisa Donato, Liborio Stuppia, Valentina Gatta","doi":"10.3390/cells14100704","DOIUrl":"10.3390/cells14100704","url":null,"abstract":"Early antral follicles (EAfs) offer oocyte potential in Assisted Reproductive Technology (ART), but most fail to mature under current in vitro maturation (IVM) protocols. This study examines transcriptomic profiles of the follicular wall (FW) compartment during IVM in ovine EAfs using a 3D follicle-enclosed oocyte (FEO) culture to identify somatic gene markers predicting oocyte maturation success. Differentially expressed genes (DEGs) were identified across three comparisons: pre- vs. post-hCG in FW enclosing mature/fertilizable (1) or immature (2) oocytes, and post-hCG between FW supporting successful vs. failed maturation (3). Network analysis highlighted key modulated and HUB genes. Two DEG categories emerged: genes regulating meiosis resumption and genes defining follicular signatures linked to oocyte competence. Meiosis resumption involved ECM remodeling, hypoxia, and relaxin signaling activation, while proliferative and metabolic pathways were downregulated. MMP13 and EGFR regulated the ECM pathway, working for meiosis resumption, while TGFB1 predicted failure. Oocyte competence involves ECM activation and the suppression of stress and cell cycle pathways, with ITIH4 being conducive to central HUB tuning inflammation and angiogenesis-dependent maturation. This study reveals molecular mechanisms behind follicle maturation, identifying transcriptomic signatures for FW releasing mature/fertilizable and incompetent oocytes. It confirms known biomarkers and uncovers new regulators, offering tools to assess follicle quality, improve IVF-oocyte selection, and enhance fertility preservation.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Effect of Variants in Serotonin Transporter Gene in Women with Alcohol Use Disorder. 女性酒精使用障碍患者血清素转运基因变异的分子效应

IF 5.1 2区生物学

Cells Pub Date : 2025-05-12 DOI: 10.3390/cells14100699

Monika Rychel, Aleksandra Suchanecka, Jolanta Chmielowiec, Krzysztof Chmielowiec, Jacek Różański, Jolanta Masiak, Anna Grzywacz, Agnieszka Boroń

{"title":"Molecular Effect of Variants in Serotonin Transporter Gene in Women with Alcohol Use Disorder.","authors":"Monika Rychel, Aleksandra Suchanecka, Jolanta Chmielowiec, Krzysztof Chmielowiec, Jacek Różański, Jolanta Masiak, Anna Grzywacz, Agnieszka Boroń","doi":"10.3390/cells14100699","DOIUrl":"10.3390/cells14100699","url":null,"abstract":"The dysregulation of the serotonin system has been implicated in the pathophysiology of alcohol use disorders. Meta-analytic evidence suggests a significant correlation between genetic variation in the serotonin transporter gene and the risk of alcohol dependence. Hence, we aimed to analyse the association between 5-HTTLPR polymorphism and alcohol use disorder in a group of women and to perform an interaction analysis of 5-HTTLPR variants, personality traits, and AUD. The study group comprised 213 female volunteers; 101 were diagnosed with alcohol addiction, and 112 were not dependent on any substance or behaviour. The 5-HTTLPR variants were identified by PCR, and the resulting products were separated electrophoretically. When comparing the AUD group with the controls, we observed significant differences in the distribution of 5-HTTLPR genotypes (p = 0.0230) and alleles (p = 0.0046). We also observed a significant impact of the 5-HTTLPR genotype (p = 0.0001) on the Neuroticism and Extraversion (p = 0.0037) scales. Additionally, there was a statistically significant impact of 5-HTTLPR genotype interaction and alcohol dependency or lack of it on the Neuroticism scale (p < 0.0001). The observed interaction suggests that the effect of the 5-HTTLPR on neuroticism may be exacerbated or attenuated in the presence of alcohol addiction. Further investigation is needed to elucidate the precise nature of this interaction. Still, it potentially indicates a gene-environment interaction where the genetic predisposition conferred by the 5-HTTLPR polymorphism interacts with the environmental stressor of alcohol dependence to influence neuroticism.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic and Phenotypic Characterization of CHO 4BGD Cells with Quad Knockout and Overexpression of Two Housekeeping Genes That Allow for Metabolic Selection and Extended Fed-Batch Culturing. CHO 4BGD细胞的基因组和表型特征与四敲除和两个管理基因的过表达，允许代谢选择和延长饲料批量培养。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-11 DOI: 10.3390/cells14100692

Nadezhda Alexandrovna Orlova, Maria Valerievna Sinegubova, Denis Eduardovich Kolesov, Yulia Alexandrovna Khodak, Victor Vyacheslavovich Tatarskiy, Ivan Ivanovich Vorobiev

{"title":"Genomic and Phenotypic Characterization of CHO 4BGD Cells with Quad Knockout and Overexpression of Two Housekeeping Genes That Allow for Metabolic Selection and Extended Fed-Batch Culturing.","authors":"Nadezhda Alexandrovna Orlova, Maria Valerievna Sinegubova, Denis Eduardovich Kolesov, Yulia Alexandrovna Khodak, Victor Vyacheslavovich Tatarskiy, Ivan Ivanovich Vorobiev","doi":"10.3390/cells14100692","DOIUrl":"10.3390/cells14100692","url":null,"abstract":"Re-engineering of CHO cells using genome editing and the overexpression of multiple helper genes is the central track for obtaining better cell lines for the production of biopharmaceuticals. Using two subsequent rounds of genome editing of the CHO S cells, we have developed the cell line CHO 4BGD with four knockouts of two pro-apoptotic genes bak1 and bax, and two common selection markers genes-glul (GS) and dhfr, and additional copies of genes bcl-2 and beclin-1 used for enhancement of macroautophagy. The NGS sequencing of 4BGD cells revealed that all eight targeted alleles were successfully disrupted. Two edited loci out of eight contained large inserts of non-relevant DNA. Further data analysis shows that cells have no off-target DNA editing events, and all known CHO genes are preserved. The cells obtained are completely resistant to the induction of apoptosis, and they are suitable for the generation of stably transfected cell lines with the dhfr selection marker. They also properly undergo the target gene amplification. The 4BGD-derived clonal cell line that secretes the monoclonal antibody retains the ability for prolonged fed-batch culturing. The method of obtaining multiply edited CHO cells using the multiplex CRISPR/Cas9 editing and simultaneous stable transfection of plasmids, coding for the housekeeping genes, is suitable for the rapid generation of massively edited CHO cells.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cooperative Role of Carbonic Anhydrase IX/XII in Driving Tumor Invasion and Metastasis: A Novel Targeted Therapeutic Strategy. 碳酸酐酶IX/XII在驱动肿瘤侵袭和转移中的协同作用：一种新的靶向治疗策略

IF 5.1 2区生物学

Cells Pub Date : 2025-05-11 DOI: 10.3390/cells14100693

Hanyu Yang, Rui Chen, Xiang Zheng, Yufan Luo, Mingxuan Yao, Famin Ke, Xiurong Guo, Xiaoyan Liu, Qiuyu Liu

{"title":"Cooperative Role of Carbonic Anhydrase IX/XII in Driving Tumor Invasion and Metastasis: A Novel Targeted Therapeutic Strategy.","authors":"Hanyu Yang, Rui Chen, Xiang Zheng, Yufan Luo, Mingxuan Yao, Famin Ke, Xiurong Guo, Xiaoyan Liu, Qiuyu Liu","doi":"10.3390/cells14100693","DOIUrl":"10.3390/cells14100693","url":null,"abstract":"Cancer invasion and metastasis are critical factors that influence patient prognosis. Carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) are key regulators of hypoxia and pH homeostasis in the tumor microenvironment (TME). It has been verified that both CA IX and CA XII play significant roles in promoting tumor metastasis in recent years, but most of the literature tends to treat them as separate entities rather than exploring their synergistic effects. This review provides a comprehensive overview of the roles of CA IX and CA XII in tumor invasion and metastasis, along with their clinical applications, including their spatial distribution characteristics, molecular mechanisms that facilitate tumor metastasis, and their potential for clinical translation. Moreover, this review incorporates the classical tumor core-invasive front model to propose a metabolic coupling model of CA IX and CA XII, offering a fresh perspective on precision therapies that target tumor metabolism. By emphasizing the metabolic coupling between these two molecules, this review offers new insights distinct from previous studies and highlights the clinical therapeutic potential of simultaneously targeting both during treatment. It sheds new light on future research and clinical applications, aiming to enhance the prognosis of cancer patients through innovative therapeutic strategies.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Identification of Opioid Receptors and Peptide Precursors in Human DRG Neurons Expressing Pain-Signaling Molecules Confirms Their Potential as Analgesic Targets. 人类DRG神经元中表达疼痛信号分子的阿片受体和肽前体的鉴定证实了它们作为镇痛靶点的潜力。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-11 DOI: 10.3390/cells14100694

Shaaban A Mousa, Mohammed Shaqura, Sascha Tafelski, Jan David Wandrey, Özgür Celik, Sascha Treskatsch, Michael Schäfer

{"title":"The Identification of Opioid Receptors and Peptide Precursors in Human DRG Neurons Expressing Pain-Signaling Molecules Confirms Their Potential as Analgesic Targets.","authors":"Shaaban A Mousa, Mohammed Shaqura, Sascha Tafelski, Jan David Wandrey, Özgür Celik, Sascha Treskatsch, Michael Schäfer","doi":"10.3390/cells14100694","DOIUrl":"10.3390/cells14100694","url":null,"abstract":"The presence and function of the opioidergic system in sensory dorsal root ganglia (DRG) was demonstrated in various animal models of pain. To endorse recent functional and transcriptional evidence of opioid receptors in human DRG, this study compared morphological and transcriptional evidence in human and rat DRG using immunofluorescence confocal microscopy and mRNA transcript analysis. Specifically, it examined the neuronal expression of mu (MOR), delta (DOR), and kappa (KOR) opioid receptors, opioid peptide precursors (POMC, PENK, and PDYN), and key pain-signaling molecules. The results demonstrate abundant immunoreactivity in human DRG for key pain transduction receptors, including the thermosensitive ion channels TRPV1, TRPV4 and TRPA1, mechanosensitive PIEZO1 and PIEZO2, and the nociceptive-specific Nav1.8. They colocalized with calcitonin gene-related peptide (CGRP), a marker for peptidergic sensory neurons. Within this same subpopulation, we identified MOR, DOR, and KOR, while their ligand precursors were less abundant. Notably, the mRNA transcripts of MOR and PENK in human DRG were highest among the opioid-related genes; however, they were considerably lower than those of key pain-signaling molecules. These findings were corroborated by functional evidence in demonstrating the fentanyl-induced inhibition of voltage-gated calcium currents in rat DRG, which was antagonized by naloxone. The immunohistochemical and transcriptional demonstration of opioid receptors and their endogenous ligands in both human and rat DRG support recent electrophysiologic and in situ hybridization evidence in human DRG and confirms their potential as analgesic targets. This peripherally targeted approach has the advantage of mitigating central opioid-related side effects, endorsing the potential of future translational pain research from rodent models to humans.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes. 胰岛细胞功能中的Ryanodine受体：钙信号、激素分泌和糖尿病。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-10 DOI: 10.3390/cells14100690

Md Shahidul Islam

{"title":"Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.","authors":"Md Shahidul Islam","doi":"10.3390/cells14100690","DOIUrl":"10.3390/cells14100690","url":null,"abstract":"Ryanodine receptors (RyRs) are large intracellular Ca2+ release channels primarily found in muscle and nerve cells and also present at low levels in pancreatic islet endocrine cells. This review examines the role of RyRs in islet cell function, focusing on calcium signaling and hormone secretion, while addressing the ongoing debate regarding their significance due to their limited expression. We explore conflicting experimental results and their potential causes, synthesizing current knowledge on RyR isoforms in islet cells, particularly in beta and delta cells. The review discusses how RyR-mediated calcium-induced calcium release enhances, rather than drives, glucose-stimulated insulin secretion. We examine the phosphorylation-dependent regulation of beta-cell RyRs, the concept of \"leaky ryanodine receptors\", and the roles of RyRs in endoplasmic reticulum stress, apoptosis, store-operated calcium entry, and beta-cell electrical activity. The relationship between RyR dysfunction and the development of impaired insulin secretion in diabetes is assessed, noting their limited role in human diabetes pathogenesis given the disease's polygenic nature. We highlight the established role of RyR-mediated CICR in the mechanism of action of common type 2 diabetes treatments, such as glucagon-like peptide-1, which enhances insulin secretion. By integrating findings from electrophysiological, molecular, and clinical studies, this review provides a balanced perspective on RyRs in islet cell physiology and pathology, emphasizing their significance in both normal insulin secretion and current diabetes therapies.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells. 免疫蛋白酶体抑制抑制T辅助性17细胞的分化，但不影响其存活。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-10 DOI: 10.3390/cells14100689

Franziska Oliveri, Dennis Mink, Tony Muchamuel, Michael Basler

{"title":"Immunoproteasome Inhibition Impairs Differentiation but Not Survival of T Helper 17 Cells.","authors":"Franziska Oliveri, Dennis Mink, Tony Muchamuel, Michael Basler","doi":"10.3390/cells14100689","DOIUrl":"10.3390/cells14100689","url":null,"abstract":"Autoimmune and inflammatory diseases are characterized by aberrant immune responses. The immunoproteasome was proposed as a target for such Th cell-mediated diseases due to its role in the activation, differentiation and function of T cells. Even though many studies demonstrated reductions in Th17 cells upon immunoproteasome inhibition, it is still unclear if the differentiation or survival of these cells is affected. Therefore, this study used DSS-induced colitis and house dust mite airway inflammation mouse models to investigate the effect of immunoproteasome inhibition on Th17 cells and Tregs at different time points. Th17 cells were almost abolished when immunoproteasome inhibition was applied continuously in DSS-induced colitis. In contrast, immunoproteasome inhibition did not decrease levels of already differentiated Th17 cells and did not enhance Treg induction. Dendritic cells were barely affected by immunoproteasome inhibition. Moreover, immunoproteasome inhibition reduced T cell activation in vitro and in vivo, suggesting impaired activation as the underlying mechanism for reduced Th17 differentiation. In conclusion, immunoproteasome inhibition reduces Th17 differentiation by impairing the activation of naïve T cells, but it does not affect the survival of already-differentiated Th17 cells and Tregs.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of SNAP-Tag Based Nanobodies as Secondary Antibody Mimics for Indirect Immunofluorescence Assays. 基于snap标签的纳米小体作为间接免疫荧光检测的二抗模拟物的开发。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-10 DOI: 10.3390/cells14100691

Wenjie Sheng, Chaoyu Zhang, T M Mohiuddin, Marwah Al-Rawe, Roland Schmitz, Marcus Niebert, Lutz Konrad, Steffen Wagner, Felix Zeppernick, Ivo Meinhold-Heerlein, Ahmad Fawzi Hussain

{"title":"Development of SNAP-Tag Based Nanobodies as Secondary Antibody Mimics for Indirect Immunofluorescence Assays.","authors":"Wenjie Sheng, Chaoyu Zhang, T M Mohiuddin, Marwah Al-Rawe, Roland Schmitz, Marcus Niebert, Lutz Konrad, Steffen Wagner, Felix Zeppernick, Ivo Meinhold-Heerlein, Ahmad Fawzi Hussain","doi":"10.3390/cells14100691","DOIUrl":"10.3390/cells14100691","url":null,"abstract":"The immunofluorescence assay is widely used for cellular biology and diagnosis applications. Such an antigen-antibody detection system enables the assessment and visualization of the expression and localization of target proteins. In the classical indirect immunofluorescence assay, secondary antibodies are conjugated to fluorophores. However, conventional secondary antibodies have limited applications due to their large size (150 kDa). Moreover, as animal-derived products, secondary antibodies are associated with ethical concerns and batch-to-batch variability. In this study, we developed fluorescence-labeled recombinant nanobodies as secondary antibodies by utilizing previously established anti-mouse and anti-rabbit IgG secondary nanobodies in combination with the self-labeling SNAP-tag. Nanobodies, which are significantly smaller (15 kDa), are capable to detect primary antibodies produced in mice and rabbits. The SNAP-tag (20 kDa) enables site-specific binding of various O6-benzylguanine (BG)-modified fluorophores to the recombinant nanobodies. These recombinant nanobodies were produced using mammalian cell expression system, and their specific binding to mouse or rabbit antibodies was validated using flow cytometry and multi-color fluorescence microscopy. The low cost, easy of expression, purification and site-specific conjugation procedures for these anti-mouse and anti-rabbit IgG secondary nanobodies make them an attractive alternative to traditional secondary antibodies for indirect immunofluorescence assays.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinoid X Receptor as a Therapeutic Target to Treat Neurological Disorders Associated with α-Synucleinopathy. 类视黄醇X受体作为治疗α-突触核蛋白病相关神经系统疾病的治疗靶点。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100685

Assylbek Zhylkibayev, Christopher R Starr, M Iqbal Hossain, Sandeep Kumar, Shaida A Andrabi, Maria B Grant, Venkatram R Atigadda, Marina S Gorbatyuk, Oleg S Gorbatyuk

{"title":"Retinoid X Receptor as a Therapeutic Target to Treat Neurological Disorders Associated with α-Synucleinopathy.","authors":"Assylbek Zhylkibayev, Christopher R Starr, M Iqbal Hossain, Sandeep Kumar, Shaida A Andrabi, Maria B Grant, Venkatram R Atigadda, Marina S Gorbatyuk, Oleg S Gorbatyuk","doi":"10.3390/cells14100685","DOIUrl":"10.3390/cells14100685","url":null,"abstract":"This study investigated the therapeutic potential of the nuclear retinoid X receptor (RXR) in mitigating the progression of alpha-synucleinopathies (αSNPs), particularly in Parkinson's disease (PD). PD-like pathology in mice was successfully induced through the co-delivery of AAV expressing human α-synuclein (αS) and αS preformed fibrils (PFFs) into the substantia nigra pars compacta (SNpc). Significant increases in Lewy body (LB)-like inclusions, loss of tyrosine hydroxylase-positive (TH+) neurons, and reductions in dopamine (DA) levels in the striatum were observed. Additionally, diminished levels of PPARα and NURR1-proteins essential for neuronal survival-along with elevated expression of IBA1 and GFAP, markers of microglial activation and astrocytic gliosis, respectively, are associated with the pathogenesis of Parkinson's disease. AAV-mediated overexpression of human RXRα demonstrated preservation of TH+ neurons, prevention of DA decline, and attenuation of αS accumulation. Furthermore, RXR-treated PD brains showed a reduced number of GFAP+ and Iba1+ cells, decreased GFAP+ and IBA1+ immunoreactivity, and fewer and less widespread LB-like aggregates. RXR overexpression also enhanced the production of PPARα and NURR1. These findings suggest that RXRα upregulation promotes neuroprotection by mitigating αSNPs and chronic neuroinflammation, a major contributor to PD progression. This research underscores the therapeutic potential of targeting nuclear receptors, such as RXR, in neurodegenerative diseases like PD.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Muscle Regeneration with Small Extracellular Vesicles from Adipose Tissue-Derived Stem Cells-A Review. 脂肪组织源性干细胞细胞外小泡靶向肌肉再生研究进展

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100683

Lucas Fornari Laurindo, Enzo Pereira de Lima, Adriano Cressoni Araújo, Victória Dogani Rodrigues, Jefferson Aparecido Dias, Marcos Barbosa Tavares Filho, Debora Aparecida Pires de Campos Zuccari, Lívia Fornari Laurindo, Maria Angélica Miglino, Eduardo Federighi Baisi Chagas, Claudemir Gregório Mendes, Rosa Direito, Vítor Engrácia Valenti, Sandra Maria Barbalho

{"title":"Targeting Muscle Regeneration with Small Extracellular Vesicles from Adipose Tissue-Derived Stem Cells-A Review.","authors":"Lucas Fornari Laurindo, Enzo Pereira de Lima, Adriano Cressoni Araújo, Victória Dogani Rodrigues, Jefferson Aparecido Dias, Marcos Barbosa Tavares Filho, Debora Aparecida Pires de Campos Zuccari, Lívia Fornari Laurindo, Maria Angélica Miglino, Eduardo Federighi Baisi Chagas, Claudemir Gregório Mendes, Rosa Direito, Vítor Engrácia Valenti, Sandra Maria Barbalho","doi":"10.3390/cells14100683","DOIUrl":"10.3390/cells14100683","url":null,"abstract":"Extracellular vesicles (EVs) are membrane-bound structures released by cells carrying diverse biomolecules involved in intercellular communication. Small EVs are abundant in body fluids, playing a key role in cell signaling. Their natural occurrence and therapeutic potential, especially in the context of muscular disorders, make them a significant area of research. Sarcopenia, characterized by progressive muscle fiber loss, represents a pathological state in which EVs could offer therapeutic benefits, reducing morbidity and mortality. Recent studies have proposed an interplay between adipose tissue (AT) and skeletal muscle regarding sarcopenia pathology. AT dysregulation, as seen in obesity, contributes to skeletal muscle loss in a multifactorial way. While AT-derived stem cell (ATDSC) small EVs have been implicated in musculoskeletal homeostasis, their precise action in muscle regeneration remains incompletely understood. In this context, ATDSC-derived small EVs can stimulate skeletal muscle regeneration through improved proliferation and migration of muscle cells, enhancement of muscular perfusion, improvement of tendon and nerve regeneration, stimulation of angiogenesis, and promotion of myogenic differentiation. However, they can also increase skeletal muscle loss. Notably, this is the first comprehensive review to systematically examine the role of ATDSC-derived small EVs in sarcopenia.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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