Biology subjects

Rong, X.

Publications and source records attributed to Rong, X..

7 recordsLinked to original sources

bioRxiv2025

Human umbilical cord mesenchymal stromal cells ameliorate ovarian damage and restore function in Premature Ovarian Insufficiency rat model

Premature ovarian insufficiency (POI) is a debilitating condition characterized by infertility and systemic health decline, with limited effective therapeutic options. This study explores the therapeutic potential of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in a cyclophosphamide (CTX)-induced rat model of POI. The POI rats were administered low or high doses of hUC-MSCs via tail vein transplantation. Ovarian function was evaluated through monitoring of the estrous cycle, serum hormone analysis, ovarian histomorphology, follicle counting, and mating assays. Immunohistochemistry was employed to assess the expression of proteins related to apoptosis and angiogenesis. Additionally, in vitro co-culture assays were conducted to evaluate the immunomodulatory capacity of hUC-MSCs. The results indicated that hUC-MSC transplantation restored estrous cyclicity, normalized hormone levels, increased follicle counts, and improved pregnancy outcomes in a dose-dependent manner. Histological analysis indicated a reduction in atretic follicles and an enhancement of ovarian structure. Mechanistically, hUC-MSCs were found to attenuate apoptosis by modulating the expression of Bcl-2 and Caspase-3 and to promote angiogenesis through the upregulation of VEGF. In vitro, hUC-MSCs demonstrated significant immunomodulatory effects, including the suppression of pro-inflammatory cytokine secretion and the promotion of regulatory T cell expression. In conclusion, hUC-MSCs effectively ameliorate CTX-induced ovarian damage, highlighting their promise as a regenerative therapy for POI.

cell biology↗

bioRxiv2025

CD300LG is a receptor for triglyceride-rich lipoproteins that facilitates postprandial lipid clearance

Circulating triglycerides are principally transported by triglyceride-rich lipoprotein particles (TRLs) including very-low-density-lipoproteins (VLDL) and chylomicrons and require the activity of lipoprotein lipase for appropriate lipid processing and cellular uptake. Despite known genetic links between CD300LG variants and altered lipid profiles, the functional role of CD300LG in lipid metabolism remains unclear. In this study, we identify CD300LG as a crucial receptor for TRLs. Human genetic analyses reveal that reduced CD300LG protein levels are causally linked with CAD risk and increased number, diameter, and TAG concentration of TRLs. In mice, CD300LG deficiency results in postprandial hypertriglyceridemia independent of changes in VLDL secretion, intestinal lipid absorption, or lipoprotein lipase activity. Mechanistically, CD300LG acts as a receptor for TRLs through a direct interaction with ApoA4 to facilitate TRL clearance at the microvascular endothelium. These findings elucidate new functions for both CD300LG and ApoA4 and advance our general understanding of triglyceride metabolism.

physiology↗

bioRxiv2025

Mapping Anhedonia-Related Damage Network: Insights for TMS Treatment

BackgroundMany studies have explored anhedonia-related functional connectivity (FC), but the findings remain inconsistent. There is a gap in identifying a consistent anhedonia-related damage network and applying it to TMS treatment. MethodsWe systematically reviewed studies on anhedonia-related functional connectivity and identified anhedonia-related brain damage locations. Using a novel functional connectivity network mapping approach applied to a large normative connectome dataset, we mapped these damage locations to anhedonia-related damage networks. Subsequently, transcriptomic analysis was conducted to uncover underlying molecular mechanisms. Additionally, we investigated the application of the anhedonia-related damage network in transcranial magnetic stimulation (TMS) treatment, focusing on changes in FC within this network following TMS treatment and its association with anhedonia improvement, as well as predicting TMS treatment efficacy based on baseline FC within the anhedonia-related damage network. ResultsA total of eight experiments from seven studies using the nucleus accumbens (NAc) as the seed were eligible for functional connectivity network mapping analysis. This study identified an anhedonia-related damage network, primarily characterized by disrupted functional connectivity between the NAc and the default mode network. Transcriptomic analysis revealed gene enrichment associated with synaptic signaling, neuronal development, ion transport, and actin cytoskeleton regulation. TMS treatment increased NAc functional connectivity within the anhedonia-related damage network in the response group, with these changes correlating with improvements in anhedonia. Furthermore, baseline NAc FC within this network demonstrated predictive potential for TMS treatment efficacy. ConclusionThe anhedonia-related damage network was identified, emphasizing its underlying mechanisms and predictive value for TMS in treating anhedonia.

neuroscience↗

bioRxiv2024

Chronic alcohol exposure induces cerebral microbleeds by TGF-β1/Smad signaling pathway mediated remodeling of cerebral small vessels

BackgroundLong-term heavy drinking is a major risk factor for cerebral microbleeds(CMBs), which are increasingly gaining attention as a pathological phenotype of cerebral small vessel diseases(CSVD). Under pathological conditions, remodeling of the extracellular matrix(ECM) on the walls of small vessels causes disarray in the structure and function of these vessels, leading to cerebral small vessel sclerosis and consequent rupture and bleeding. This can result in cognitive and emotional disorders, abnormal gait and increased risk of falling. However, the mechanisms underlying how long-term alcohol consumption leads to CMBs and decline in motor function remain unknown. MethodsWe constructed a chronic alcohol exposure mouse model and measured the deposition of ECMs on the small vessels in motor-related brain regions. The presence of microbleeds was confirmed through Prussian blue staining and Magnetic Resonance Imaging. We also extracted primary cerebral microvascular smooth muscle cells (CMVSMCs) from the newborn mice and explored the effects of alcohol on the phenotypic transformation and substance synthesis function. Additionally, we conducted interventional experiments on the cell and animal models with an anti-fibrotic drugs Pirfenidone(PFD). ResultsWe found that mice with long-term alcohol exposure showed decreased motor function. In their motor-related brain regions, such as the motor cortex(MC), thalamus/basal ganglia(Tha/BG), and cerebellum(CB), we observed microbleeds. On the small vessels in these areas, we detected excessive deposited ECM proteins. In vitro experiments with primary CMVSMCs revealed that after alcohol treatment, the cells underwent a transformation into fibroblast-like phenotypes, and excessive production of the aforementioned ECM proteins, which is regulated by upstream TGF{beta}1/Smad signaling pathway. Additionally, PFD applied on cell and animal models could reverse the above processes to some extent. ConclusionsOur study found that the remodeling of ECM accompanied by activation of TGF-{beta}1/Smad signaling pathway may be involved in alcohol-induced CMBs. It could be a potential therapeutic target for CMBs or CSVD.

molecular biology↗

bioRxiv2021

pVHL regulates protein stability of TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation

The Wnt/{beta}-catenin signaling pathway plays key roles in development and adult tissue homeostasis by controlling cell proliferation and cell fate decisions. In this pathway, transcription factors TCF/LEFs are the key components to repress target gene expression by recruiting co-repressors or to activate target gene expression by recruiting {beta}-catenin when the Wnt signals are absent or present, respectively. While progress has been made in our understanding of Wnt signaling regulation, the underlying mechanism that regulates the protein stability of the TCF/LEF family is far less clear. Here, we show that von Hippel-Lindau protein (pVHL), which is the substrate recognition component in an E3 ubiquitin ligase complex, controls TCF/LEF protein stability. Unexpectedly, pVHL directly binds to TCF/LEFs and promotes their proteasomal degradation independent of E3 ubiquitin ligase activity. Knockout of vhl in zebrafish embryos leads to a reduction of dorsal habenular neurons and this effect is upstream of dorsal habenular neurons phenotype in tcf7l2-null mutants. Our study uncovers a previously unknown mechanism for the protein stability regulation of the TCF/LEF transcription factors and demonstrates that pVHL contains a 26S proteasome binding domain that drives ubiquitin-independent proteasomal degradation. These findings provide new insights into the ubiquitin-independent actions of pVHL and uncover novel mechanistical regulation of Wnt/{beta}-catenin signaling.

cell biology↗

bioRxiv2019

The Lands cycle modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle

Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analyses of primary myocytes from lean insulin-sensitive (LN) and obese insulin-resistant (OB) individuals revealed several species of lysophospholipids (lyso-PL) that were differentially-abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lyso-PC/PC, concomitant with greater insulin sensitivity in vivo and insulin-stimulated skeletal muscle glucose uptake ex vivo. Absence of LPCAT3 reduced phospholipid packing of the cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.

physiology↗

bioRxiv2019

The rs6505162 C>A polymorphism in the miRNA-423 gene exhibits a protective element of coronary artery in a southern Chinese population with Kawasaki disease

BackgroundManifesting as acute rash, fever and vasculitis, belonging to autoimmune syndrome, Kawasaki disease(KD) is prone to occur in infants and young children. Males and females is affected by KD at a ratio of 1.4 to 1.7: 1. KD is known to own many common clinical manifestations and complications, like coronary artery lesion(CAL) and coronary artery aneurysm(CAA). Polymorphisms of the rs6505162 locus in the miRNA-423 gene are associated with enhancive susceptibility to coronary artery disease and the alterations of the four cytokines IL-4., IL-10, IL-21, IL-22 in the early stages of diabetes. However, no researcher has reported whether rs6505162 is related to KD susceptibility or no. Therefore, we carried out the trial concentrating on the connection between miRNA-423 rs6505162 C>A polymorphism and KD susceptibility.\n\nMethodsTo obtain the genotypes of rs6505162 in objects enrolled by 532 KD children and 623 control, we applied Taqman real-time PCR and all statistical analyses was carried out by SAS.\n\nResultsThe comparison between all cases and all controls hinted that the rs6505162C>A polymorphism has no relationship with KD susceptibility. Nevertheless, a subgroup analysis revealed that the CA/AA genotypes of rs6505162 could reduce the occurrence of CAA (Adjusted age and gender odds ratio=1.30, 95%CI=1.02-1.67, P=0.037) and CAL (Adjusted OR=1.56, 95%CI=1.19-2.03, P=0.001)in KD patients.\n\nConclusionOur final results stated clearly that miRNA-423 rs6505162 polymorphism appears to be a protective element of CAL and CAA in southern Chinese suffers with KD.

genetics↗