CX3C chemokine ligand 1 (CX3CL1) belongs to the CX3C chemokine family and is involved in various disease processes. However, its role in intervertebral disc degeneration (IDD) remains to be elucidated. In the present study, western blotting, reverse transcription-quantitative PCR and ELISA assays were used to assess target gene expression. In addition, immunofluorescence and TUNEL staining were used to assess macrophage infiltration, monocyte migration and apoptosis. The present study aimed to reveal if and how CX3CL1 regulates IDD progression by exploring its effect on macrophage polarization and apoptosis of human nucleus pulposus cells (HNPCs). The data showed that CX3CL1 bound to CX3C motif chemokine receptor 1 (CX3CR1) promoted the M2 phenotype polarization via JAK2/STAT3 signaling, followed by increasing the secretion of anti-inflammatory cytokines from HNPCs. In addition, HNPC-derived CX3CL1 promoted M2 macrophage-derived C-C motif chemokine ligand 17 release thereby reducing the apoptosis of HNPCs. In clinic, the reduction of mRNA and protein levels CX3CL1 in degenerative nucleus pulposus tissues (NPs) was measured. Increased M1 macrophages and pro-inflammatory cytokines were found in NPs of IDD patients with low CX3CL1 expression. Collectively, these findings suggested that the CX3CL1/CX3CR1 axis alleviates IDD by reducing inflammation and apoptosis of HNPCs via macrophages. Therefore, targeting CX3CL1/CX3CR1 axis is expected to produce a new therapeutic approach for IDD.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007–2010, 2017–2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (−0.40 [−0.45, −0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

Thyroid dysfunction is a common thyroid disorder in our life and its symptoms are non‐specific, therefore the diagnosis of thyroid dysfunction is important for patients. Albumin (ALB) can carry thyroid hormones to their sites of action as a way to achieve rapid delivery of thyroid hormones to the tissues. The purpose of this study was to investigate the relationship between serum ALB levels and total triiodothyronine (TT3) in adults.

Sulfiredoxin-1 (SRX1) is a conserved endogenous antioxidative protein, which is involved in the response to cellular damage caused by oxidative stress. Oxidative stress and inflammation are the primary pathological changes in spinal cord injuries (SCI). The aim of present study was to explore the roles of SRX1 in SCI. Using reverse transcription-quantitative PCR and western blotting, the present study discovered that the expression levels of SRX1 were downregulated in the spinal cord tissues of SCI model rats. Massive irregular cavities and decreased Nissl bodies were observed in the model group compared with the sham group. Thus, to determine the underlying mechanisms, neuron-like PC12 cells were cultured in vitro. Western blotting analysis indicated that SRX1 expression levels were downregulated following the exposure of cells to lipopolysaccharide (LPS). Following the transfection with the SRX1 overexpression plasmid and stimulation with LPS, the results of the Cell Counting Kit-8 assay indicated that the cell viability was increased compared with LPS stimulation alone. Furthermore, the expression levels of proinflammatory cytokines secreted by LPS-treated PC12 cells were downregulated following SRX1 overexpression. Increased malondialdehyde content, decreased superoxide dismutase activity and reactive oxygen species production were also identified in PC12 cells treated with LPS using commercial detection kits, whereas the overexpression of SRX1 partially reversed the effects caused by LPS stimulation. The aforementioned results were further verified by determining the expression levels of antioxidative proteins using western blotting analysis. In addition, nuclear factor erythroid-2-related factor 2 (NRF2), a transcription factor known to regulate SRX1, was indicated to participate in the protective effect of SRX1 against oxidative stress. Inhibition of NRF2 further downregulated the expression levels of SRX1, NAD(P)H dehydrogenase quinone 1 and heme oxygenase-1 in the presence of LPS, while activation of NRF2 reversed the effects of LPS on the expression levels of these proteins. In conclusion, the results of the present study indicated that the anti-inflammatory and antioxidative effects of SRX1 may depend on NRF2, providing evidence that SRX1 may serve as a novel molecular target to exert a neuroprotective effect in SCI.

STUDY DESIGN:In vitro studies of the role of 17β-estradiol (E2) and its possible targets in intervertebral disc degeneration (IDD).OBJECTIVE:To define the regulatory role of E2 in IDD and the potential mechanisms.SUMMARY OF BACKGROUND DATA:IDD has intricate etiology that is influenced by multiple risk factors. However, the underlying molecular mechanisms of occurrence and progression of IDD are not well elucidated. The degradation of extracellular matrix (ECM) has been extensively observed in IDD. E2 was found to inhibit ECM degradation in human nuleus pulposus cells (HNPCs), but the molecular mechanism remained to be determined.METHODS:Western blot and qPCR was performed to quantify the expression of target proteins in HNPCs. Luciferase reporter gene assay was applied to detect the effects of E2 and forkhead box O-3 (FOXO3) on matrix metalloproteinases (MMP)-3 promoter activity. Chromatin immunoprecipitation assay analyzed the binding of FOXO3 to MMP-3 and the effect of E2 on this process.RESULTS:We identified the upregulation of collagen II and aggrecan by E2 independent of time and concentration. And E2 downregulated MMP-3 expression in human nucleus pulposus cells. The phosphorylation of FOXO3 led to the reduction of MMP-3 promoter activity. Furthermore, 17β-estradiol-induced the activation of PI3K/Akt pathway is required for FOXO3 phosphorylated.CONCLUSION:E2 prevents the degradation of ECM by upregulating collagen II and aggrecan expression via reducing MMP-3 expression in HNPCs, and PI3K/Akt/FOXO3 pathway is dispensable for MMP-3 downregulated. Therefore, E2 protects against IDD by preventing ECM degradation.LEVEL OF EVIDENCE:3.