Post-stroke cognitive impairment (PSCI) is characterized by progressive cognitive decline following ischemic stroke, and recent studies have suggested that natural compounds may offer therapeutic benefits; however, the effects and mechanisms of Betulin in PSCI remain unclear. Male C57BL/6 mice were subjected to ischemic stroke surgery to induce PSCI and treated with Betulin (50 mg/kg/day) for 3 weeks, followed by assessments of cognitive impairment, pathological changes, and the production of pro-inflammatory cytokines. Network pharmacology and RNA sequencing were performed to explore potential mechanisms. In vitro, BV2 microglia were stimulated with lipopolysaccharide to examine the anti-inflammatory effects of Betulin. Betulin improved cognitive performance, reduced microglial activation, and attenuated neuroinflammation, as evidenced by decreased levels of TNF-α, IL-1β, and IL-6. Mechanistically, the epidermal growth factor receptor (EGFR)/JAK2/STAT3 pathway was identified as a key pathway potentially involved in these effects. Further experiments with EGFR point-mutation constructs indicated that disrupting the Betulin-EGFR interaction attenuated the inhibitory effect of Betulin on the EGFR/JAK2/STAT3 pathway. Collectively, these findings suggest that Betulin mitigates microglia-driven neuroinflammation by targeting EGFR and may represent a potential therapeutic candidate for PSCI.

Spinal cord injury (SCI) is accompanied by a significant microglia-associated inflammatory response that is associated with secondary tissue damage and poorer functional outcomes. Serum and glucocorticoid-regulated kinase 1 (SGK1) has been implicated in the regulation of cell survival and neuronal excitability in various diseases. However, the role and cell-specific mechanism of SGK1 in SCI remain to be elucidated. In this study, we observed that SGK1 was predominantly expressed in microglia located at the lesion margin during the early phase of SCI in a mouse contusion model. Inhibition of SGK1 by GSK650394 has been shown to promote neural repair while simultaneously suppressing neuroinflammation and mitochondrial oxidative stress. Mechanistically, the inhibition of SGK1 results in a reduction of FoxO1 phosphorylation and the promotion of nuclear import, consequently inducing microglial mitophagy and promoting mitochondrial homeostasis, leading to the suppression of absent in melanoma 2 (AIM2) related pyroptosis and the conversion of microglia into a neuroprotective M2 phenotype. In particular, AIM2 overexpression or deletion effectively interfered with the influence of SGK1-FoxO1 on the modulation of SCI. In conclusion, the present findings provide a potential therapeutic strategy for the treatment of SCI.

The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy (1H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment. GluCEST, GABACEST and 1H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression. GluCEST, GABACEST and 1H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism. CEST imaging combined with 1H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer’s disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms.

Traumatic optic neuropathy (TON) is a prevalent form of optic neuropathy, which is a significant cause of irreversible blindness. To date, effective therapeutic interventions for TON are lacking, highlighting the urgent need for the development of new therapeutic drugs. In this study, a compound library comprising 480 Food and Drug Administration (FDA)-approved drugs was screened to identify potentially effective therapeutic drugs for TON. We reported that dimercaprol (DMP), an FDA-approved drug, can reduce L-Glutamic acid (Glu) and hydrogen peroxide (H2O2)-induced injury in a retinal cell line (R28 cell). Our findings further demonstrated that intracellular reactive oxygen species (ROS) and acrolein, a lipid peroxide, are major contributors to apoptosis-induced cell death in vitro. A series of functional assays revealed that DMP can inhibit apoptosis-induced by Glu via scavenging of intracellular ROS and acrolein in R28 cells and primary cortical neurones. Notably, DMP inhibited retinal ganglion cell complex (GCC) thinning and retinal ganglion cell (RGC) loss resulting from optic nerve crush (ONC) injury in vivo. Moreover, DMP effectively eliminated ONC-induced acrolein in the retina and inhibited RGC apoptosis in vivo. In conclusion, intracellular ROS and acrolein play significant roles in RGC loss in TON, and DMP effectively inhibits RGC apoptosis-induced by the oxidative stress pathway in vitro and in vivo. Therefore, DMP has emerged as a potential new therapeutic drug against TON.

Lycium barbarum is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. The therapeutic effect of Lycium barbarum on intervertebral disc degeneration (IVDD) has not been conclusively established. In our study, we investigated the mechanisms of Lycium barbarum extract (LBE) using Network pharmacology and bioinformatic analyses. In vitro experiments, the levels of ferroptosis were assessed using Western blot analysis and detection kits for MDA, Ferric iron and GSH. Transmission electron microscopy and Mitotracker were used to detect mitochondrial morphology. Immunofluorescence and Western blot were employed to detect the levels of mitophagy and lysosomal permeability. In vivo experiments, X-ray imaging, morphological staining, and immunohistochemical staining were used to assess the degree of intervertebral disc degeneration. As a result of the intersection between target genes of complex compounds and disease-related genes, 61 overlapping genes were identified, with PTGS2 ranking as the top overlapping gene. Molecular docking revealed that six compounds were highly stable in the Cys41 active site pocket of PTGS2. Moreover, LBE exhibited potential therapeutic effects through inhibiting mitochondrial dysfunction and ferroptosis. Besides, LBE can reduce lysosomal membrane permeability and enhance mitophagy caused by oxidative stress via regulating phosphatidylinositol metabolism. The administration of LBE in vivo can effectively slow the progression of intervertebral disc degeneration. The findings of this study suggest that LBE exhibits maybe a potential therapeutic candidate for intervertebral disc degeneration.

Background: Ischemia stroke is the leading cause of death and long-term disability. Sanhua Decoction (SHD), a classic Chinese herbal prescription, has been used for ischemic stroke for about thousands of years. Here, we aim to investigate the neuroprotective effects of SHD on cerebral ischemia/reperfusion (CIR) injury rat models. Methods: The male Sprague-Dawley rats (body weight, 250-280 g; age, 7-8 weeks) were randomly divided into sham group, CIR group, and SHD group and were further divided into subgroups according to different time points at 6 h, 1, 3, 7, 14, 21, and 28 d, respectively. The SHD group received intragastric administration of SHD at 10 g kg(-1) d(-1). The focal CIR models were induced by middle cerebral artery occlusion according to Longa's method, while sham group had the same operation without suture insertion. Neurological deficit score (NDS) was evaluated using the Longa's scale. BrdU, doublecortin (DCX), and glial fibrillary acidic protein (GFAP) were used to label proliferation, migration, and differentiation of nerve cells before being observed by immunofluorescence. The expression of reelin, total tau (t-tau), and phosphorylated tau (p-tau) were evaluated by western blot and RT-qPCR. Results: SHD can significantly improve NDS at 1, 3, 7, and 14 d (p < 0.05), increase the number of BrdU positive and BrdU/DCX positive cells in subventricular zone at 3, 7, and 14 d (p < 0.05), upregulate BrdU/GFAP positive cells in the ischemic penumbra at 28 d after CIR (p < 0.05), and reduce p-tau level at 1, 3, 7, and 14 d (p < 0.05). There was no significant difference on reelin and t-tau level between three groups at each time points after CIR. Conclusions: SHD exerts neuroprotection probably by regulating p-tau level and promoting the proliferation, migration, and differentiation of endogenous neural stem cells, accompanying with neurobehavioral recovery.

Ginseng is a kind of traditional Chinese medicine. It is widely believed that ginseng can improve cognitive function, but its clinical efficacy is still controversial. This study aimed to systematically evaluate the effects of ginseng on cognitive function improvement. This is a systematic review and meta-analysis of the randomized controlled trials (RCTs). Searching PubMed, Web of Science, the Cochrane Library, and Medline databases to collect RCTs of ginseng on the effects of human cognitive function. The time range is from the establishment of the database to December 2023. The main intervention in the trials was ginseng preparation. The Cochrane risk-of-bias tool 2.0 (RoB2.0) and Jadad scale were used to assess the risk of bias and evaluate the quality of the included articles. After data extraction, meta-analysis was performed using Stata 17.0 software. A total of 15 RCTs were included, and 671 patients were analyzed. The subjects included healthy people, patients of cognitive impairment, schizophrenia, hospitalized, and Alzheimer's disease. The intervention measures were mainly ginseng preparations. The meta-analysis results indicated that ginseng has a significant effect on memory improvement (SMD = 0.19, 95%CI: 0.02-0.36, p < 0.05), especially at high doses (SMD = 0.33, 95%CI: 0.04-0.61, p < 0.05). Ginseng did not have a positive effect on overall cognition, attention, and executive function (SMD = 0.06, 95%CI: -0.64-0.77, p = 0.86; SMD = 0.06, 95%CI: -0.12 to 0.23, p = 0.54; SMD = -0.03, 95%CI: -0.28 to 0.21, p = 0.79). Ginseng has some positive effects on cognitive improvement, especially on memory improvement. But in the future, more high-quality studies are needed to determine the effects of ginseng on cognitive function. Trial Registration: Prospero: CRD42024514231.

To summarize the emergency nursing experience of a patient with massive hemoptysis after lung transplantation undergoing rigid bronchoscopy assisted by extracorporeal membrane oxygenation. For patients with massive hemoptysis without symptoms,a comprehensive emergency plan was adopted,including safe and quick transport,extracorporeal membrane oxygenation care,bedside rigid bronchoscopy management,and monitoring of patient bleeding and thrombosis. After 12 days of active treatment and care,the patient recovered and was discharged from the hospital.

Background Pyroptosis, a lytic form of programmed cell death initiated by inflammasomes, has been reported to be closely associated with tumor proliferation, invasion and metastasis. However, the roles of pyroptosis genes (PGs) in low-grade glioma (LGG) remain unclear. Methods We obtained information for 1,681 samples, including the mRNA expression profiles of LGGs and normal brain tissues and the relevant corresponding clinical information from two public datasets, TCGA and GTEx, and identified 45 differentially expressed pyroptosis genes (DEPGs). Among these DEPGs, nine hub pyroptosis genes (HPGs) were identified and used to construct a genetic risk scoring model. A total of 476 patients, selected as the training group, were divided into low-risk and high-risk groups according to the risk score. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves verified the accuracy of the model, and a nomogram combining the risk score and clinicopathological characteristics was used to predict the overall survival (OS) of LGG patients. In addition, a cohort from the Gene Expression Omnibus (GEO) database was selected as a validation group to verify the stability of the model. qRT-PCR was used to analyze the gene expression levels of nine HPGs in paracancerous and tumor tissues from 10 LGG patients. Results Survival analysis showed that, compared with patients in the low-risk group, patients in the high-risk group had a poorer prognosis. A risk score model combining PG expression levels with clinical features was considered an independent risk factor. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched among the DEPGs and that immune activity was increased in the high-risk group. Conclusion In summary, we successfully constructed a model to predict the prognosis of LGG patients, which will help to promote individualized treatment and provide potential new targets for immunotherapy.

Oxidative stress-induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)-induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

Osteoarthritis (OA) is a chronic injury of joints, which is characterized by the destruction and degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA. Linalool is a natural compound with anti-inflammatory effects in various diseases. However, the anti-inflammatory effect of linalool in the development of osteoarthritis remains unclear. This study aimed to investigate the anti-inflammatory effect of linalool on IL-1β-induced mouse chondrocytes, as well as its protective effect on joints in a mouse model of OA. Mouse chondrocytes were co-treated with 10 ng/mL IL-1β and different concentration gradients of linalool. These in vitro experiments demonstrated that linalool could inhibit the expression of Interleukin-1β (IL-1β)-induced inflammatory factors, such as nitric oxide synthase, cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Furthermore, linalool reduced the catabolism of the extracellular matrix (ECM) by inhibiting the expression of matrix metalloproteinase-13 (MMP-13) and thrombospondin motif-5 (ADAMTS5) while upregulating the expression of type II collagen (COL II) and aggrecan. Regarding the mechanism of OA, it was observed that linalool inhibited the signal transduction of nuclear factor kappa B (NF-κB) by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in chondrocytes. The inhibitory effect of linalool on the development of OA was demonstrated by the mouse DMM model experiment. The results suggested that linalool may be a potential drug for the treatment of OA.

In this study, we investigate the association of serum calcium with coagulopathy and hemorrhagic progression contusion (HPC) in patients with traumatic intraparenchymal hemorrhage (tIPH), and further explore the interaction and mediation effect between serum calcium and coagulopathy on HPC. We conducted retrospective analyses of patients with tIPH admitted to the First Affiliated Hospital of Wenzhou Medical University between January 2016 to December 2019. The clinical data, coagulation parameters, and serum calcium levels were collected for further analysis. Multi-variate logistic regression analysis was applied to identify the association of serum calcium level with coagulopathy and HPC. Causal mediation analysis (CMA) and additive interaction model were used to estimate the interaction and mediation effect between serum calcium as well as coagulopathy on HPC. Additionally, we repeated the analysis using corrected calcium. A total of 473 patients were included in this study. Of these, 54 (11.4%) patients had hypocalcemia at admission, 105 (22.2%) presented with coagulopathy, and 187 (39.5%) experienced HPC. Admission serum calcium level in patients presented with coagulopathy and HPC were 8.84 (interquartile range [IQR]: 8.44-9.40] and 8.92 (IQR: 8.48-9.40) mg/dL respectively, which were significantly lower than that of patients without coagulopathy (9.10 [IQR: 8.68-9.88] and 9.12 [IQR: 8.72-9.89] mg/dL; all p < 0.001). Multi-variate logistic regression analysis identified that hypocalcemia emerged as an independent risk factor for coagulopathy and HPC. However, no significant interaction was detected between hypocalcemia and coagulopathy. CMA showed that the mediator coagulopathy explained 24.4% (95% confidence interval: 4.7-65.0%; p = 0.006) of the association between hypocalcemia and HPC. Moreover, comparable results were held using corrected calcium, as well. Admission serum calcium level is associated with the HPC for patients with tIPH and this relationship is partially mediated by coagulopathy, but no significant interaction is detected. Further studies are needed to validate the findings and explore its mechanisms.

-OBJECTIVE: This study aimed to investigate whether surgical resection of multifidus in rats could generate a reliable model of intervertebral disc degeneration (IVDD).-METHODS: Instability of the lumbar spine in Sprague- Dawley rats was induced by multifidus resection. Long-issimus changes were examined by hematoxylin and eosin staining and immunohistochemistry. Specific protein and mRNA changes in the nucleus pulposus (NP) were quan-tified by Western blot and reverse transcription- polymerase chain reaction. Bone alterations were assessed using X-ray imaging, and disc changes were evaluated by hematoxylin and eosin staining, immunoflu-orescence, and immunohistochemistry.-RESULTS: Fat infiltration and increased tumor necrosis factor -a expression in the longissimus were detected following surgery. Reverse transcription-polymerase chain reaction and Western blot results demonstrated that the inflammation and catabolism in the NP were increased after the surgical intervention. Moreover, X-ray imaging showed that the disc height had decreased and bone spurs had formed at the vertebral rims. Histological analyses further revealed degeneration of the annulus fibrosus, endplate, and NP. Furthermore, in contrast to the sham group, the collagen II expression was reduced, while matrix metalloproteinase-13 was increased in the surgery group.-CONCLUSIONS: Surgical resection of the multifidus in rats resulted in a reproducible IVDD model. Because the present procedure does not impart direct injury to the intervertebral disc, it can better imitate the pathological states in humans. Therefore, our rat multifidus resection model might help us further understand the intrinsic path-ophysiology of IVDD.

Ginseng has been used for the treatment of aging and memory impairment for thousands of years. Several studies have found that ginsenoside Rg1, as one of the main active components of ginseng, could potentially improve cognitive function in several different animal models. A preclinical systematic review to evaluate the efficacy and mechanisms of ginsenoside Rg1 for ameliorating cognitive impairments in Alzheimer’s disease is reported here. We searched six databases from their inceptions to January 2019. Thirty-two studies were selected, which included a total of 1,643 animals. According to various cognitive behavioral tests, the results of the meta-analyses showed that ginsenoside Rg1 significantly improved cognitive behavioral impairments in most Alzheimer’s disease models (P < 0.05), but there were no significant effects in animals with neuronal degeneration induced by chronic stress or in SAMP8 transgenic mice. The potential mechanisms included antioxidant and anti-inflammatory effects, amelioration of Alzheimer’s disease-related pathology, synapse protection, and up-regulation of nerve cells via multiple signaling pathways.

Intravenous immunoglobulin (IVIg) has been used for neuromyelitis optica spectrum disorder (NMOSD) patients to prevent relapses in several studies. However, efficacy of the rescue treatment of IVIG was just assessed in a small sample research. The aim of this study is to investigate the efficacy of IVIG in NMOSD as a rescue treatment and whether it could reduce the relapse rate. We retrospectively reviewed patients with NMOSD in the First and Second Affiliated Hospital of Wenzhou Medical University. Clinical parameters were extracted from the medical records, such as expanded disability scale score (EDSS) and time to next relapse. Thirty-one events of 20 NMOSD patients were included in the intravenous methylprednisolone (IVMT) + IVIG group and 72 events of 39 patients in the IVMT group. IVMT therapy combined with IVIG could improve the neurological disability when discharged (p < 0.001), whereas patients first attacked did not show a similar trend. Patients who were treated with IVMT + IVIG (17.39 ± 2.75 months) show a longer time to next relapse compared to patients who were treated with IVMT (9.50 ± 0.79 months) (log rank test p = 0.002), especially in relapsed patients or anti-aquaporin-4 antibody (AQP4-Ab) seropositive patients. IVIG might be helpful for NMOSD patients as the rescue treatment and might bring a longer remission, especially for patients with relapse and AQP4-ab seropositive patients.

Bone marrow mesenchymal stem cells (BMMSCs)-based therapy has emerged as a promising novel therapy for Traumatic Brain Injury (TBI). However, the therapeutic quantity of viable implanted BMMSCs necessary to initiate efficacy is still undetermined. Increased oxidative stress following TBI, which leads to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathway, has been implicated in accounting for the diminished graft survival and therapeutic effect. To prove this assertion, we silenced the expression of NADPH subunits (p22-phox, p47-phox, and p67-phox) and small GTPase Rac1 in BMMSCs using shRNA. Our results showed that silencing these proteins significantly reduced oxidative stress and cell death/apoptosis, and promoted implanted BMMSCs proliferation after TBI. The most significant result was however seen with Rac1 silencing, which demonstrated decreased expression of apoptotic proteins, enhanced in vitro survival ratio, reduction in TBI lesional volume and significant improvement in neurological function post shRac1-BMMSCs transplantation. Additionally, two RNA-seq hub genes (VEGFA and MMP-2) were identified to play critical roles in shRac1-mediated cell survival. In summary, we propose that knockdown of Rac1 gene could significantly boost cell survival and promote the recovery of neurological functions after BMMSCs transplantation in TBI mice.

Ginseng has been used for the treatment of aging and memory impairment for thousands of years. Several studies have found that ginsenoside Rg1, as one of the main active components of ginseng, could potentially improve cognitive function in several different animal models. A preclinical systematic review to evaluate the efficacy and mechanisms of ginsenoside Rg1 for ameliorating cognitive impairments in Alzheimer's disease is reported here. We searched six databases from their inceptions to January 2019. Thirty-two studies were selected, which included a total of 1,643 animals. According to various cognitive behavioral tests, the results of the meta-analyses showed that ginsenoside Rg1 significantly improved cognitive behavioral impairments in most Alzheimer's disease models (P < 0.05), but there were no significant effects in animals with neuronal degeneration induced by chronic stress or in SAMP8 transgenic mice. The potential mechanisms included antioxidant and anti-inflammatory effects, amelioration of Alzheimer's disease-related pathology, synapse protection, and up-regulation of nerve cells via multiple signaling pathways.

Diabetes (DB) is a risk factor for osteoarthritis progression. High glucose (HG) is one of the key pathological features of DB and has been demonstrated to induce apoptosis and senescence in chondrocytes. Autophagy is an endogenous mechanism that can protect cells against apoptosis and senescence. The effects of HG on autophagy in cells including chondrocytes have been studied; however, the results have been inconsistent. The current study aimed to elucidate the underlying mechanisms, which could be associated with the contrasting outcomes. The present study revealed that HG can induce apoptosis and senescence in chondrocytes, in addition to regulating autophagy dynamically. The present study demonstrated that HG can cause oxidative stress in chondrocytes and suppress the AMPK pathway in a dose-dependent manner. Elimination of oxidative stress by Acetylcysteine, also called N-acetyl cysteine (NAC), downregulated autophagy and alleviated HG-stimulated apoptosis and senescence, while activation of the AMPK signaling pathway by AICAR not only upregulated autophagy but also alleviated HG-stimulated apoptosis and senescence. A combined treatment of NAC and AICAR was superior to treatment with either NAC or AICAR. The study has demonstrated that HG can suppress autophagy through the AMPK pathway and induce autophagy via oxidative stress in chondrocytes.

Damaged deoxyribonucleic acid (DNA) is a primary pathologic factor for osteoarthritis (OA); however, the mechanism by which DNA damage drives OA is unclear. Previous research demonstrated that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) participates in DNA damage response. As a result, the current study aimed at exploring the role STING, which is the major effector in the cGAS-STING signaling casacde, in OA progress in vitro, as well as in vivo. In this study, the expression of STING was evaluated in the human and mouse OA tissues, and in chondrocytes exposed to interleukin-1 beta (IL-1β). The influences of STING on the metabolism of the extracellular matrix (ECM), apoptosis, and senescence, were assessed in STING overexpressing and knocking-down chondrocytes. Moreover, the NF-κB-signaling casacde and its role in the regulatory effects of STING on ECM metabolism, apoptosis, and senescence were explored. The STING knockdown lentivirus was intra-articularly injected to evaluate its therapeutic impact on OA in mice in vivo. The results showed that the expression of STING was remarkably elevated in the human and mouse OA tissues and in chondrocytes exposed to IL-1β. Overexpression of STING promoted the expression of MMP13, as well as ADAMTS5, but suppressed the expression of Aggrecan, as well as Collagen II; it also enhanced apoptosis and senescence in chondrocytes exposed to and those untreated with IL-1β. The mechanistic study showed that STING activated NF-κB signaling cascade, whereas the blockage of NF-κB signaling attenuated STING-induced apoptosis and senescence, and ameliorated STING-induced ECM metabolism imbalance. In in vivo study, it was demonstrated that STING knockdown alleviated destabilization of the medial meniscus-induced OA development in mice. In conclusion, STING promotes OA by activating the NF-κB signaling cascade, whereas suppression of STING may provide a novel approach for OA therapy.