Abstract Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron‐mediated Fenton reactions. It has been reported iron deficiency had implicated in the pathogenesis intervertebral disc degeneration (IVDD) by activating apoptosis. However, role ferroptosis process IVDD not illuminated. Here, we demonstrate involvement pathogenesis. Our vitro models show changes protein levels marker enhanced level during oxidative stress. Safranin O...

Abstract The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis nucleus pulposus (NP) cells. Oxidative stress a significant cause IVDD. Whether mitophagy induced by strong oxidative in IVDD remains to be determined. This study aimed investigate relationship between and better understand vivo vitro. To this end, we obtained primary NP cells from human subsequently exposed them TBHP. We observed that cells, suppressed found were protected against...

Abstract High dose and long‐term steroid treatment can alter antioxidative ability decrease the viability function of osteoblasts, leading to osteoporosis osteonecrosis. Ferroptosis, a new type cell death characterized by excessive lipid peroxidation due downregulation GPX4 system X c− , is involved in glucocorticoid‐induced osteoporosis. Endothelial cell‐secreted exosomes (EC‐Exos) are important mediators cell‐to‐cell communication many physiological pathological processes. However, effect...

Microglia and macrophages are the largest component of inflammatory infiltrate in glioblastoma (GBM). However, whether there differences their representation activity prognostically-favorable isocitrate dehydrogenase (IDH)-mutated compared to -wild type GBMs is unknown. Studies on human specimens untreated IDH-mutant rare given they comprise 10% all often present at lower grades, receiving treatments prior dedifferentiation that can drastically alter microglia macrophage phenotypes. We were...

Musculoskeletal tissue degeneration impairs the life quality and motor function of many people, especially seniors athletes. Tendinopathy is one most common diseases associated with musculoskeletal degeneration, representing a major global healthcare burden that affects both athletes general population, clinical presentation long-term recurring chronic pain decreased tolerance to activity. The cellular molecular mechanisms at basis disease process remain elusive. Here, we use single-cell...

Mitochondrial unfold protein response (UPR mt ) can induce mitophagy to protect cell from protein.However, how UPR induces is not yet clear.Herein, Sesn2 was considered be a key molecule that communicated and in the intervertebral disc.Silencing of able reverse protective effects Nicotinamide riboside (NR) on nucleus pulposus (NP) cells inhibit induced by .UPR upregulated through Eif2ak4/eIF2α/Atf4, further mitophagy.Sesn2 promoted translocation cytosolic Parkin Sqstm1 defective mitochondria...

Apoptosis of annulus fibrosus (AF) is observed widely in intervertebral disc degeneration (IVDD) which causes weaken tension the disc. Previous studies reported that apoptosis AF induced mainly by oxidative stress. SIRT2 a major regulator mitochondria to mediate ROS production. However, mechanism IVDD remains unclear. Here, expression was detected cells exposed tert-Butyl hydroperoxide (TBHP) western blotting. Autophagic flux and were assessed blotting, flow cytometry immunofluorescence...

Hypoxia has been associated with multiple sclerosis (MS) and is an important area of research. can exacerbate inflammation via the prolylhydroxylase pathway. Inflammation also trigger hypoxia by damaging mitochondria endothelial cells to impair blood flow regulation. We hypothesize that there a “hypoxia–inflammation cycle” in MS which plays role disease progression. Therapies break this cycle may be interesting exploration for treatment MS.

Long-term and high dose glucocorticoid treatment can cause decreased viability function of osteoblasts, which leads to osteoporosis osteonecrosis. In this study, we investigated the role mechanism action HIF-1α in glucocorticoid-induced osteogenic inhibition MC3T3-E1 cells. Our results showed that protein expression was reduced when cells were exposed dexamethasone (Dex) at varying concentrations ranging from 10-9 10-6 M. PDK1 also after treatment. treated with receptor antagonist RU486...

By rejuvenating the deficient activity of myeloid cells in glioblastoma, niacin improves treatment otherwise incurable brain tumors.

N6-methyladenosine (m6A) is required for differentiation of human bone marrow mesenchymal stem cells (hBMSCs). However, its intrinsic mechanisms are largely unknown. To identify the possible role m6A binding protein YTHDF1 in hBMSCs osteogenesis vivo, we constructed Ythdf1 KO mice and showed that depletion would result decreased mass vivo. Both deletion mouse BMSCs shRNA-mediated knockdown prevented osteogenic vitro. Using methylated RNA immunoprecipitation (Me-RIP) sequencing...

Abstract Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPR mt ) take part various aging-related diseases. Our research intents to explore the role underlying mechanism UPR IVDD. Nucleus pulposus (NP) cells were exposed IL-1β nicotinamide riboside (NR) served as inducer treat NP cells. Detection ATP, NAD + NADH used determine function mitochondria. MRI, Safranin...

Knee osteoarthritis is a common degenerative joint disease involving multiple pathological processes, including energy metabolism, cartilage repair, and osteogenesis. To investigate the alterations in critical metabolic pathways differential proteins patients through metabolomic proteomic analyses to explore potential mechanisms underlying synovial osteogenesis during progression. Metabolomics was used analyze metabolites fluid synovium of (osteoarthritis group: 10; control 10), whereas...

Abstract Disconnection procedures in epilepsy surgery have become an important tool for the management of multifocal drug-resistant epilepsy. In this chapter, we will review their indications, describe technical procedures, and outcome data literature. Among curative approaches, anterior quadrant disconnection, posterior (PQ) functional hemispherectomy can be performed patients whose epileptic focus resides one hemisphere or quadrant. Seizure freedom rates from these range 50 to 81%...

Abstract Hypoxia (low oxygen) is associated with many brain disorders as well inflammation, but the lack of widely available technology has limited our ability to study hypoxia in human brain. Multiple sclerosis (MS) a poorly understood neurological disease significant inflammatory component which may cause hypoxia. We hypothesized that if were occur, there should be reduced microvascular hemoglobin saturation (S t O 2 ). In this study, we aimed determine S can detected MS using frequency...

We investigated the feasibility of using frequency-domain near-infrared spectroscopy (fdNIRS) to study brain oxygenation in first few hours stroke onset. The OxiplexTS(®) fdNIRS system was used this study. Using a standard probing protocol based on surface landmarks, we measured tHb and [Formula: see text] healthy volunteers, cadavers, acute patients within 9 h onset 3 days later. obtained measurements from 11 controls, 5 patients. values were significantly lower cadavers compared controls...

Abstract Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects MS are needed. The experimental autoimmune encephalomyelitis (EAE) model was used to determine the extent inflammation-associated central nervous system pathology. High-resolution magnetic resonance imaging (MRI) and atlas-based volumetric analysis were performed measure brain regional...

Exosomes are major mediators of cell-to-cell communication, and involved in many physiological pathological processes. Recently, the roles exosomes osteoarthritis (OA) their therapeutic potential have received increasing attention. derived from vascular endothelial cells been confirmed to participate occurrence development numerous diseases; however, effects OA not reported. Here, we demonstrated secreted by OA. Through vivo vitro experiments, that decreased ability chondrocytes resist...

Background: Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus is a major origin knee osteoarthritis common threat to athletic ability, but its cellular mechanism remains elusive. Methods: We built cell atlas 12 healthy or degenerated human meniscus samples from inner outer meniscal zones 8 patients using scRNA-seq investigate microenvironment homeostasis changes in process verified findings with immunofluorescent imaging. Results: identified...

Osteosarcoma (OS) accounts for a large proportion of the types bone tumors that are newly diagnosed, and is relatively common tumor. However, there still no effective treatments this affliction. One interesting avenue related to mitochondrial NDUFA4L2 protein, which encoded by nuclear gene known be critical mediator in regulation cell survival. Thus, study, we aimed investigate effect upon metastasis epithelial–mesenchymal transition OS. We found protein expression was upregulated hypoxic...