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In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-κB pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases. Delivery of anti-inflammatory microRNA (miRNA) could be beneficial for inflammatory diseases such as rheumatoid arthritis (RA). Here the authors show that a fluorinated polyamidoamine dendrimer nanoparticle delivers miR-23b to affected RA joints and reduces inflammation, joint damage and synovial cell influx. [ABSTRACT FROM AUTHOR]

To verify the role of PI3K-AKT-GSK3β pathway during manganese (Mn)-induced cell death, apoptosis, related indicators were investigated. SH-SY5Y cells were directly exposed to different concentrations of MnCl2. Then, cell viability, apoptosis, necrosis rate, and cell cycle were detected by MTT, FITC Annexin V Apoptosis Detection Kit with PI and PI staining. Then, in two intervention groups, cells were preconditioned with agonist (PQQ) and suppressant (LY294002). The cell viability decreased with a dose-response relationship (p < 0.05), while apoptosis and necrosis increased (p < 0.05). The ratio of G0/G1 and G2/M also decreased, but the percentage of S phase increased (p < 0.05). During above process, PI3K-AKT-GSK3β pathway was involved by regulating the expression of PI3K, AKT, p-AKT, and GSK3β (p < 0.05). For further research, cell cycle and apoptosis were detected pretreatment with PQQ and LY294002 before Mn exposure. The result showed cell ability, apoptosis, and necrosis rate changed obviously compared with non-pretreated group (p < 0.05). The variance of G0/G1 and G2/M ratio and percentage of S phase were also different, especially in 2.0 mM (p < 0.05). Mn can cause apoptosis and necrosis, varying cell cycle of SH-SY5Y cells, which could be changed by PQQ and LY294002 by regulating PI3K-AKT-GSK3β pathway. [ABSTRACT FROM AUTHOR]

Synovium-derived mesenchymal stem cells (SMSCs) can migrate to the site of destroyed condylar cartilage and differentiate into chondrocytes to repair temporomandibular joint (TMJ) damage. Interleukin (IL)-1β-induced IL-6 secretion has been shown to inhibit the chondrogenic potential of SMSCs. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) has recently been shown to be closely related to the inflammation induced by IL-1β. However, the relationship between SAHA and IL-6 secretion induced by IL-1β in SMSCs remains unclear. In this study, we evaluated the relationships between IL-1β and IL-6 in synovial specimens from patients with TMD and in model rats with osteoarthritis (OA). We found that IL-1β and IL-6 were positively correlated and that IL-6 expression in SMSCs increased with IL-1β stimulation in vitro. Moreover, microtubule affinity-regulating kinase 4 (MARK4) was significantly upregulated in IL-1β-stimulated SMSCs and in the synovium of rats with OA. MARK4 knockdown inhibited IL-6 secretion and nuclear factor (NF)-κB pathway activation in IL-1β-stimulated SMSCs. SAHA attenuated IL-6 secretion in IL-1β-induced SMSCs through NF-κB pathway inhibition, and MARK4 was also downregulated in SAHA-treated SMSCs. However, inhibition of the NF-κB pathway did not suppress MARK4 expression. Thus, these results showed that SAHA attenuated IL-6 secretion in IL-1β-induced SMSCs through inhibition of the MARK4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence.A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence.1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05).Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence.Methods: To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence.A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence.1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05).Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence.Results: To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence.A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence.1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05).Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence.Conclusion: To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence.A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence.1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05).Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence. [ABSTRACT FROM AUTHOR]