Background: Premature ovarian insufficiency (POI) is a refractory disease that severely affects female fertility. The PERK/eIF-2α/ATF4/CHOP pathway is one of the classical pathways involved in the unfolded protein response to endoplasmic reticulum stress by regulating protein synthesis and promoting apoptosis. This study aimed to investigate the functional role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in the POI animal model through the PERK/eIF-2α/ATF4/CHOP pathway.
View Article and Find Full Text PDFIntroduction: Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental disorders characterized by impaired social interactions and stereotypic behaviors. Current clinical care is palliative at the most and there remains huge unmet medical need to fully address the core symptoms of ASD. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are emerging as a promising candidate for ASD treatment, but the precise mechanism remains controversial.
View Article and Find Full Text PDFBackground: Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number.
Methods: MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, = 2), chorionic villi-derived MSCs (CMMSCs, = 2), amniotic membrane-derived MSCs (AMMSCs, = 3), and umbilical cord-derived MSCs (UCMSCs, = 3).
The efficacy of human amniotic mesenchymal stem cell (hAMSC) ovarian injection in improving ovarian function in primary ovarian insufficiency (POI) patients has been shown in some reports. However, the safety and efficacy of hAMSC vein injection remains unclear. In this study, we evaluated the safety and efficacy of hAMSC intravenous injection in cynomolgus macaques and SD rats and provided evidence for clinical trials.
View Article and Find Full Text PDFBipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood.
View Article and Find Full Text PDFNav1.5 channel is crucial for the proliferation and migration of breast cancer cells. In this study, we investigated the anticancer effect of JZTX-14, a natural peptide considered an effective antagonist of Nav1.
View Article and Find Full Text PDFThe key signaling networks regulating bone marrow mesenchymal stem cells (BMSCs) are poorly defined. Lgr4, which belongs to the leucine-rich repeat-containing G protein-coupled receptor (LGR) family, is widely expressed in multiple tissues from early embryogenesis to adulthood. We investigated whether Lgr4 functions in BMSCs and in osteogenesis, adipogenesis, and skeletal myoblasts, using mice with a β-geo gene trap inserted into the Lgr4 gene.
View Article and Find Full Text PDFTumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL) regulates multiple physiological or pathological functions, including osteoclast differentiation and osteoporosis. TNFRSF11A (also called RANK) is considered to be the sole receptor for RANKL. Herein we report that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL.
View Article and Find Full Text PDFExcessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems.
View Article and Find Full Text PDFThe G protein-coupled receptor TGR5 is a membrane receptor for bile acids. Its agonism increases energy expenditure and controls blood glucose through secretion of glucagon-like peptide-1 in enteroendocrine cells. In this study, we explored the therapeutic potential of WB403, a small compound activating TGR5 which was identified by combining TGR5 targeted luciferase assay and active GLP-1 assay, in treating type 2 diabetes.
View Article and Find Full Text PDFReceptor activator of NF-κB ligand (RANKL) stimulation leads to the activation of mitogen-activated protein kinase (MAPK)/AP-1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) signaling pathways in osteoclastogenesis. Targeting these pathways has been an encouraging strategy for bone-related diseases, such as postmenopausal osteoporosis. In this study, we examined the effects of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on osteoclastogenesis.
View Article and Find Full Text PDFActivation of NF-κB and MAPK/activator protein 1 (AP-1) signaling pathways by receptor activator NF-κB ligand (RANKL) is essential for osteoclast activity. Targeting NF-κB and MAPK/AP-1 signaling to modulate osteoclast activity has been a promising strategy for osteoclast-related diseases. In this study we examined the effects of maslinic acid (MA), a pentacyclic triterpene acid that is widely present in dietary plants, on RANKL-induced osteoclastogenesis, osteoclast function, and signaling pathways by in vitro and in vivo assay systems.
View Article and Find Full Text PDFSG2NA is a member of the striatin protein family. In human and mouse, the SG2NA gene encodes two major protein isoforms: SG2NA alpha and SG2NA beta. The functions of these proteins, except for acting as the regulatory subunits for PP-2A, remain largely unknown.
View Article and Find Full Text PDFIt is well established that the protein serine/threonine phosphatase 2A (PP2A) plays very important roles in many different cellular processes, including cell proliferation and differentiation, gene expression, neurotransmission, apoptosis, and aging. PP2A consists of three heterogenic subunits: the scaffold subunit A, the catalytic subunit C, and the regulatory subunit B. While both the scaffold and the catalytic subunits contain only two forms, at least four families of the regulatory subunits, B, B', B'', and B''' have been identified.
View Article and Find Full Text PDFObjective: To explore the relationship between the RANTES, TGFbeta1 and amount of mast cells (MC) surrounding the implanted tumors.
Method: Pieces of Walker 256 carcinosarcoma were implanted in the liver of 40 male Wistar rats and the formed intrahepatic implanted tumors were then divided into 3 groups: group without MC infiltration, group with little MC infiltration and group with MC infiltration; 8 normal rats served as control group. The sera of rats in the different groups were tested by ELISA to find the serum RANTES content of the tumor bearing rats, then the chemotactic activity of the serum RANTES of different tumor bearing groups vs peritoneal MC of normal rats was tested by the microBoyden chamber.