Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats.
View Article and Find Full Text PDFAs the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C.
View Article and Find Full Text PDFDendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive.
View Article and Find Full Text PDFThe suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length.
View Article and Find Full Text PDFBackground: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research.
View Article and Find Full Text PDFThe communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment.
View Article and Find Full Text PDFBackground: The pancreatic islet microcirculation adapts its metabolism to cope with limited oxygen availability and nutrient delivery. In diabetes, the balance between oxygen delivery and consumption is impaired. Insulin has been proven to exert complex actions promoting the maintenance of homeostasis of the pancreas under glucotoxicity.
View Article and Find Full Text PDFBackground: Surgical treatment is the primary intervention for cataracts. Extracapsular cataract extraction (ECCE) is a routine surgery for cataracts, phacoemulsification (PE) is another procedure with a small incision and injury area. This study investigated the comparison of the effects of these two procedures on the patient's visual acuity.
View Article and Find Full Text PDFChildhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood.
View Article and Find Full Text PDFPrimary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure.
View Article and Find Full Text PDFCyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted.
View Article and Find Full Text PDFBackground: The phytocannabinoid cannabidiol (CBD) exhibits anxiolytic activity and has been promoted as a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense.
Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.
Background: In recent years, increasing discovery of the extremely important regulatory effects of circular RNAs on biological development, angiogenesis, tumor genesis, and development, as well as stem cell proliferation and differentiation has provided new opportunities for investigating regulation mechanism in angiogenesis.
Objectives: This study explored the expression of circ 001839 in renal ischemia-reperfusion injury (RI-RI) rats and whether its upstream microRNA-432-3p (miR-432-3p) affects inflammation in both RI-RI rats and NRK52E cells.
Methods: Rat model of RI-RI was made, and circ 001839 was identified by the gene-chip analysis in RI-RI rats.
The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses.
View Article and Find Full Text PDFLack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein.
View Article and Find Full Text PDFDynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied.
View Article and Find Full Text PDFPrimary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy.
View Article and Find Full Text PDFSichuan Da Xue Xue Bao Yi Xue Ban
January 2021
Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway.
View Article and Find Full Text PDFIonic liquids (ILs) as green alternatives for volatile organic solvents are increasingly used in commercial applications. It is necessary to explore the cytotoxic mechanism of ILs to reduce the risk to human health. For this purpose, cell viability, apoptosis, cytochrome P450 3A4 (CYP3A4), glucose transporter type 2 (GLUT2), and microRNA-122 (miR-122) gene expression in HepG2 cells was evaluated after IL exposure.
View Article and Find Full Text PDFThe primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly.
View Article and Find Full Text PDFIt is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo.
View Article and Find Full Text PDFOxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis.
View Article and Find Full Text PDFOxidative stress is involved in the onset and progression of many human diseases. Activators of the Keap1/Nrf2/ARE pathway effectively inhibit the progression of oxidative stress-induced diseases. Herein, a small library of diterpenoids was established by means of phytochemical isolation, and chemical modification on naturally occurring molecules.
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