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Background: Lipid metabolism disorder, as one major complication in patients with chronic kidney disease (CKD), is tied to an increased risk for cardiovascular disease (CVD). Traditional lipid-lowering statins have been found to have limited benefit for the final CVD outcome of CKD patients. Therefore, the purpose of this study was to investigate the effect of microinflammation on CVD in statin-treated CKD patients., Methods: We retrospectively analysed statin-treated CKD patients from January 2013 to September 2020. Machine learning algorithms were employed to develop models of low-density lipoprotein (LDL) levels and CVD indices. A fivefold cross-validation method was employed against the problem of overfitting. The accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were acquired for evaluation. The Gini impurity index of the predictors for the random forest (RF) model was ranked to perform an analysis of importance., Results: The RF algorithm performed best for both the LDL and CVD models, with accuracies of 82.27% and 74.15%, respectively, and is therefore the most suitable method for clinical data processing. The Gini impurity ranking of the LDL model revealed that hypersensitive C-reactive protein (hs-CRP) was highly relevant, whereas statin use and sex had the least important effects on the outcomes of both the LDL and CVD models. hs-CRP was the strongest predictor of CVD events., Conclusion: Microinflammation is closely associated with potential CVD events in CKD patients, suggesting that therapeutic strategies against microinflammation should be implemented to prevent CVD events in CKD patients treated by statin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Jiang, Wang, Liu, Huang, Huang, Jin, Zhao, Wang, Ruan, Liu and Ma.)

Type-2 diabetes (T2D) is a common metabolic disorder, which causes several physiological and pathological complications. Spleen is regarded as an important organ, which regulates immune system and iron metabolism in the body. Precious few studies have been conducted to explore the pathological and deleterious roles of diabetes on spleen. In our current study, we have explored and confirmed the pathological effects of diabetes on spleen in db/db experimental mice model. In our current study, 0.5 mg/kg fibroblast growth factor 1 (FGF1) dose was intraperitoneally administrated to db/db mice. We found that diabetes evidently induced spleen enlargement and fibrosis progression in the db/db mice. Additionally, our studies demonstrate that iron has hugely deposited in the spleen in db/db mice. Several studies have documented that diabetes largely disrupts the inflammatory cells distribution, immune homeostasis, proliferation and oxidative stress with the down-regulation of anti-inflammatory cytokines and antioxidant activities. Moreover, we have observed that FGF1 administration significantly reversed the deleterious effect of diabetes on spleen enlargement and dysfunction. In summary, these substantial findings clearly demonstrate that diabetes plays deleterious roles in maintaining the spleen structure and functions. Therefore, our investigations suggest that FGF1 can effectively prevent diabetes-mediated splenomegaly progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alcoholic liver disease (ALD) has become one of the leading causes of death in the world. Berbamine (BM), a natural product mainly derived from Berberis vulgaris L, possesses multiple bioactivities as a traditional medicine. However, the protective effect of BM on ALD remains unknown. In this study, we investigated the effect of BM on ethanol-induced hepatic injury in mice and its underlying mechanism. It was shown that BM at 0.3125-40 μmol·L -1 had no effect on macrophages and hepatocytes proliferation. BM at 5-20 μmol·L -1 significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1β and IL-6 mRNA expression in RAW264.7 cells. Moreover, BM treatment significantly inhibited LPS-induced p65 and STAT3 phosphorylation in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg -1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels in ethanol-fed mice. Oil red O staining results showed that BM administration ameliorated hepatic lipid accumulation in ethanol-fed mice. Preventions of ethanol-induced hepatic injury by BM were reflected by markedly decreased serum and hepatic triglyceride (TG) and total cholesterol (TC) contents. Real-time PCR results showed that BM treatment significantly inhibited pro-inflammatory cytokines mRNA expression in ethanol-fed mouse liver. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 phosphorylation levels in liver. In addition, BM treatment significantly inhibited ERK phosphorylation but not JNK and p38 of MAPK pathway. Taken together, our results demonstrate a beneficial effect of BM on ethanol-induced liver injury via a mechanism associated with inactivation of NF-κB, STAT3 and ERK pathway, which gives insight into the further evaluation of the therapeutic potential of BM for ALD., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.

To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. 73 patients were enrolled. Age among five groups was statistically different (P = 0.032). Alanine aminotransferase (ALT) (P = 0.033) and aspartate aminotransferase (AST) (P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT (r = 0.697, P = 0.025), AST (r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI. [ABSTRACT FROM AUTHOR]

Objectives Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD. Methods An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc. Key findings Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model. Conclusions Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD. [ABSTRACT FROM AUTHOR]

In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double‐edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme‐linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI‐induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3‐methyladenine partially abolished VPA‐induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI‐induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI. Cover Image for this issue: doi: 10.1111/jnc.14755. [ABSTRACT FROM AUTHOR]

Summary: Aims: To examine whether early rise of neutrophil‐to‐lymphocyte ratio (NLR) after patient hospitalization correlates with 30‐day mortality in patients with spontaneous intracerebral hemorrhage (ICH). Methods: This retrospective study included all patients receiving treatment for spontaneous ICH between January 2015 and September 2016 at the Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences in Shanghai, China. NLR was determined at admission (T1), at 24‐48 hours (T2) and 5‐7 days (T3). NLR and clinicopathologic features were compared between those who survived for >30 days vs not. Multivariate regression was used to identify risk factors for 30‐day mortality. Results: A total of 275 subjects were included in the analysis: 235 survived for at least 30 days; the remaining 40 subjects died within 30 days. The patients who died within 30 days had higher ICH score, larger ICH volume, and lower GCS score (all P < 0.05). In comparison with the baseline (NLRT1), NLR at 24‐48 hours (NLRT2) and 5‐7 days (NLRT3) was significantly higher in patients who died within 30 days (P < 0.05), but not in patients surviving for >30 days. In the multivariate analysis, the 30‐day mortality was associated with both NLRT2 (OR 1.112, 95%CI 1.032‐1.199, P = 0.006) and NLRT3 (OR 1.163, 95%CI 1.067‐1.268, P = 0.001). Spearman correlation analysis showed that both NLRT2 and NLRT3 correlated inversely with GCS score and positively with ICH score and ICH volume at the baseline. Conclusions: Early rise of NLR predicts 30‐day mortality in patients with spontaneous ICH. [ABSTRACT FROM AUTHOR]

Furin, a member of the mammalian proprotein convertases family, can promote the proteolytic maturation of proproteins. It is known that furin is predominantly present in certain cell types of human atherosclerotic lesions and neointima in animal models, including vascular smooth muscle cells, endothelial cells and mononuclear inflammatory cells. Evidence suggests that furin participates in the initiation and progression of atherosclerosis through regulation of lipid and cholesterol metabolism, inflammatory response, blood pressure and the formation of atherosclerotic lesions. This review provides a panorama of the roles of furin in atherosclerosis and the insights into the prevention and treatment of atherosclerosis and cardiovascular disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • We have verified through different experiments in vivo and in vitro that novel ERK inhibitor PD0325901 an play a good role in the occurrence and development of OA by inhibiting the MAPK/NF-κ B/NLRP3 signaling pathway. Osteoarthritis (OA), a degenerative disease affecting the joint, is characterized by degradation of the joint edge, cartilage injury, and subchondral bone hyperplasia. Treatment of early subchondral bone loss in OA can inhibit subsequent articular degeneration and improve the prognosis of OA. PD0325901, a specific inhibitor of ERK, is widely used in oncology and has potential as a therapeutic agent for osteoarthritis In this study, we investigated the biological function of PD0325901 in bone marrow monocytes/macrophages (BMMs)treated with RANKL and found that it inhibited osteoclast differentiation in vitro in a time- and dose-dependent manner. PD0325901 restrained the expression of osteoclast marker genes, such as c-Fos and NFATc1 induced by RANKL. We tested the biological effects of PD035901 on ATDC5 cells stimulated by IL-1β and found that it had protective effects on ATDC5 cells. In animal studies, we used a destabilization of the medial meniscus (DMM) model and injected 5 mg/kg or 10 mg/kg of PD0325901 compound into each experimental group of mice. We found that PD0325901 significantly reduced osteochondral pathological changes in post-OA subchondral bone destruction.Finally, we found that PD0325901 down-regulated the pyroptosis level in chondrocytes to rescue cartilage degeneration. Therefore, PD0325901 is expected to be a new generation alternative therapy for OA. [ABSTRACT FROM AUTHOR]

Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fluocinolone acetonide (FA) is commonly used as a steroidal anti-inflammatory drug. We recently found that in dental pulp cells (DPCs) FA has osteo-/odonto-inductive as well as anti-inflammatory effects. However, the mechanism by which FA induces these effects in DPCs is poorly understood.Experimental Approach: The effect of FA on the mineralization of DPCs during inflammatory conditions and the underlying mechanism were investigated by real-time PCR, Western blot, EMSA, histochemical staining, immunostaining and pathway blockade assays.Key Results: FA significantly inhibited the inflammatory response in LPS-treated DPCs not only by down-regulating the expression of pro-inflammation-related genes, but also by up-regulating the expression of the anti-inflammatory gene PPAR-γ and mineralization-related genes. Moreover, histochemical staining and immunostaining showed that FA could partially restore the expressions of alkaline phosphatase, osteocalcin and dentin sialophosphoprotein (DSPP) and mineralization in LPS-stimulated DPCs. Real-time PCR and Western blot analysis revealed that FA up-regulated DSPP and runt-related transcription factor 2 expression by inhibiting the expression of phosphorylated-NF-κB P65 and activating activator protein-1 (AP-1) (p-c-Jun and Fra-1). These results were further confirmed through EMSA, by detection of NF-κB DNA-binding activity and pathway blockade assays using a NF-κB pathway inhibitor, AP-1 pathway inhibitor and glucocorticoid receptor antagonist.Conclusions and Implications: Inflammation induced by LPS suppresses the mineralization process in DPCs. FA partially restored this osteo-/odonto-genesis process in LPS-treated DPCs and had an anti-inflammatory effect through inhibition of the NF-κB pathway and activation of the AP-1 pathway. Hence, FA is a potential new treatment for inflammation-associated bone/teeth diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is widely accepted to be a multistep pathophysiological process associated with several other processes such as angiogenesis and inflammatory response. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs (more than 200 nucleotides in length) and can regulate gene expression at the transcriptional and post-transcriptional levels. Recent studies suggest that lncRNA-H19 plays important roles in the regulation of angiogenesis, adipocyte differentiation, lipid metabolism, inflammatory response, cellular proliferation and apoptosis. In this review, we primarily discuss the roles of lncRNA-H19 in atherosclerosis-related pathophysiological processes and the potential mechanisms by which lncRNA-H19 regulates the development of atherosclerosis, to help provide a better understanding of the biological functions of lncRNA-H19 in atherosclerosis. [ABSTRACT FROM AUTHOR]

• Activating cIAP1 and subsequently blocking the phosphorylation pathway of RIP1 ameliorates the pathogenesis of OA. • TNF-α exacerbated the inflammatory response resulting in an imbalance in the metabolism and decomposition process of chondrocytes. • AZD8330 may inhibit chondrocyte necrosis and ECM degradation through cIAP1. • AZD8330′s strong effectiveness in preventing the development of OA in DMM mice. Osteoarthritis (OA) is a prevalent degenerative joint disease [1]. It has come to light that AZD8330 can suppress the generation of proinflammatory factors and deter the inflammatory response [2]. Given that inflammation is a primary causative factor in OA, it is posited that AZD8330 might exhibit superior efficacy in OA management. In this study, we investigated the potential of intraperitoneal injection of AZD8330 to retard the progression of osteoarthritis in a murine model with surgically induced medial meniscus destruction (DMM). Concurrently, we employed ATDC5 cartilage cells to dissect the mechanism through which AZD8330 inhibits the TNF-α-induced NF-κB signaling pathway via modulation of RIP1. The findings revealed that AZD8330 mitigated cartilage degradation and the inflammatory response, leading to a substantial reduction in OARSI scores among DMM mice treated with AZD8330. Mechanistically, AZD8330 functioned as a suppressor of the TNF-α-induced NF-κB/p65 signaling pathway by facilitating the phosphorylation activation of cIAP1-mediated RIP1. The combination of data from both in vivo and in vitro experiments supports the conclusion that AZD8330 can attenuate chondrocyte degradation, thereby alleviating OA, by regulating the NF-κB/P65 signaling pathway through modulation of RIP1 activity. Consequently, the utilization of AZD8330 may hold potential in the prophylaxis of osteoarthritis. Our investigation delineates the role of AZD8330 in the regulation of inflammation in the context of OA treatment. Furthermore, we have unveiled that the inhibitory impact of AZD8330 on OA may hinge upon the activation of cIAP1, which in turn downregulates RIP1, thereby restraining the NF-κB/P65 signaling pathway. This study lends credence to the notion that AZD8330 may be a promising contender for osteoarthritis therapy. Our study provides compelling evidence attesting to the capacity of AZD8330 in managing inflammation within the realm of OA treatment. Likewise, our study has elucidated that the attenuation of OA by AZD8330 relies on the activation of cIAP1 to inhibit RIP1, consequently suppressing the NF-κB signaling pathway. On the strength of our present study, we may have identified a viable drug candidate for OA treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Osteoarthritis (OA) is a disabling joint disease characterized by cartilage degeneration. Reactive oxygen species (ROS)-induced oxidative stress is an important cause of early chondrocyte death. For this reason, we investigated PD184352, a small molecule inhibitor with potential anti-inflammatory and antioxidant activity. We evaluated the protective effect of PD184352 against destabilized medial meniscus (DMM)-induced OA in mice. The knee joints of the PD184352-treated group had higher Nrf2 expression and milder cartilage damage. Moreover, in in vitro experiments, PD184352 suppressed IL-1β-induced NO, iNOS, PGE2 production, and attenuated pyroptosis. PD184352 treatment promoted antioxidant protein expression and reduced the accumulation of ROS by activating the Nrf2/HO-1 axis. Finally, the anti-inflammatory and antioxidant effects of PD184352 were shown to be partially dependent on Nrf2 activation. Our study reveals the potential role of PD184352 as an antioxidant and provides a new strategy for OA treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study focused on the role of chondrocytes and osteoclasts in the development of osteoarthritis. • AZ-628 slows chondrocyte necroptosis and inflammatory development by reducing RIP3 activity and phosphorylation. • AZ-628 blocks autophagy, MAPK/NF-κB signaling to reduce RANKL-induced osteoclast differentiation, decreasing bone remodeling. • In the DMM mice, AZ-628 reversed bone matrix loss and prevented bone loss owing to joint disease and cartilage deterioration. As a degenerative disease, the pathogenesis and treatment of osteoarthritis (OA) are still being studied. The prevailing view is that articular cartilage dysfunction plays an essential role in the development of osteoarthritis. Similarly, dynamic bone remodeling dramatically influences the development of osteoarthritis. The inflammatory response is caused by the overexpression of inflammatory factors, among which tumor necrosis factor-α is one of the main causes of OA, and its sources include the secretion of chondrocytes themselves and osteoclast secretion of subchondral bone. Moreover, TNF-α-induced activation of RIP1, RIP3, and MLKL has been shown to play an important role in cell necroptosis and inflammatory responses. In vitro , AZ-628 alleviates chondrocyte inflammation and necroptosis by inhibiting the NF-κB signaling pathway and RIP3 activation instead of RIP1 activation. AZ-628 also reduces osteoclast activity, proliferation and differentiation, and release of inflammatory substances by inhibiting autophagy, MAPK, and NF-κB pathways. Similarly, the in vivo study demonstrated that AZ-628 could inhibit chondrocyte breakdown and lower osteoclast formation and bone resorption, thereby slowing down subchondral bone changes induced by dynamic bone remodeling and reversing the progression of osteoarthritis in mice. The results of this study indicate that AZ-628 could be used to treat OA by inhibiting chondrocyte necroptosis and regulating osteoclast formation. [ABSTRACT FROM AUTHOR]