N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats.

AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1ß), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1ß expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1ß expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.

[Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis]. / 基于HMGB1/NF-κB/NLRP3è½´æŽ¢è®¨è¤ªé»‘ç´ å¯¹æ°§è¯±å¯¼è§†ç½‘è†œç— å˜çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS: Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Socioeconomic status influences on bone mineral density in American men: findings from NHANES 2011-2020.

The association between socioeconomic status (SES) and bone mineral density (BMD) in men remains controversial. We showed that SES was positively associated with BMD in American men. Confounding factors like race/ethnicity and age could affect the association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES), 2011-2020, this article aims to investigate the association of SES (poverty income ratio (PIR) and education level) with the BMD in American men. METHODS: We evaluated the association of SES with BMD in 4446 men aged ≥ 20 years (mean age, 41.0 ± 13.4 years) from the NHANES 2011-2020. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine. We used multivariate linear regression models to examine the relationship between SES and total spine BMD, adjusted for a large range of confounding factors. RESULTS: Compared with other PIR quarters, individuals in the highest quarter of PIR were more likely to be older and white and had fewer smoking or drinking behaviors. After adjusting for race/ethnicity, age, drinking and smoking behavior, body mass index (BMI), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, and blood urea nitrogen, PIR was positively correlated with total spine BMD (ß = 0.004 95% CI: 0.001-0.007, P = 0.006). Individuals with the highest degree (college degree or above) had a 0.057 g/cm2 greater BMD than that of the lowest degree (less than 9th grade) (ß = 0.057 95% CI: 0.037-0.077, P < 0.001). CONCLUSIONS: Our study indicates that SES was positively associated with the lumbar BMD among American men. Clinicians, healthcare providers, and policymakers should consider the unequal SES of men when implementing osteoporosis prevention and treatment strategies.

Prevalence and treatment rate of osteoporosis in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis.

PURPOSE: Due to age and gender, patients awaiting total knee or hip arthroplasty (TKA/THA) are at a higher risk of osteoporosis. In joint arthroplasty, low bone mineral density (BMD) is a risk factor for implant osseointegration, durability, and prosthesis complications. This study aims to investigate the prevalence and treatment rate of osteoporosis in patients undergoing total joint arthroplasty (TJA). METHODS: We applied a comprehensive literature search through PubMed, Cochrane Library, and EMBASE from inception to July 10, 2021, for studies investigating the prevalence and treatment rate of osteoporosis in TJA patients. The aggregated prevalence was calculated with the random-effects model, and the heterogeneity between studies was checked by Cochran's Q test and quantified by the I2 statistic. We performed subgroup analyses and meta-regression analyses to determine the source of heterogeneity. Publication bias was assessed by a funnel plot and verified by Egger's test. Anti-osteoporosis treatment for TJA patients was described qualitatively and quantitatively. RESULTS: Of 4561 citations identified by the search strategy, 11 studies including 3462 patients were eligible for inclusion. The pooled prevalence of osteoporosis and osteopenia in TJA patients was 24.8% (95%CI: 14.1-37.2%) and 38.5% (95%CI: 29.3-48.0%), respectively. The prevalence of osteoporosis/osteopenia in TJA patients was 64.0% (95%CI: 45.8-80.3%). In terms of gender, the pooled prevalence of osteoporosis in males, females, and postmenopausal females were 5.5% (95%CI: 1.5-11.4%), 29.0% (95%CI: 18.3-41.1%), and 38.3% (95%CI: 13.2-67.1%), respectively. The treatment rate of osteoporosis in TJA patients was 32.9% (95%CI: 15.2-53.1%) by a random-effects model. CONCLUSIONS: Osteoporosis is highly prevalent in patients undergoing TJA, especially in postmenopausal females. However, the treatment rate of osteoporosis is low. Considering the possibility of surgical complications, clinicians should strengthen their awareness of pre-operative BMD assessment and manage osteoporosis in high-risk patients.