Transcription factor Brachyury, a protein containing 435 amino acids, has been widely investigated and reported in notochord differentiation and nucleus pulposus development. The crucial functions and underlying mechanisms by Brachyury are discussed in this paper, which suggests Brachyury can be developed into a potential novel target for the therapy of intervertebral disc degeneration.
Objective: Damage to Schwann cells play a crucial role in diabetic peripheral neuropathy (DPN) . To observe whether HMGB1 inhibitor (Glycyrrhizic acid, GA) can prevent diabetic Schwann cells damage and its potential mechanisms. Methods: RSC96 cells were divided into 5 groups: NG group (5.6 mmol/L) and HG group (25.0 mmol/L) , HG+GA (1μM) group, HG+GA (10μM) , HG+GA (100μM) . Small interfering RNA was used to knock out HMGB1. CCK8 assay was used to detect the proliferation of RSC96 cells. The levels of inflammatory factors were determined by ELISA. The mRNA expression of NGF and neuritin-1 was detected by qRT-PCR. The expression levels of NSE, cleaved-caspase-3, RAGE, p38MAPK, ERK, JNK and NF-κBp65 in cells were measured by western blot. Results: GA at the concentration of μM for 24h had significant inhibitory effect on HMGB1 synthesis and secretion (P<0.05) . Schwann cell viability in high glucose was restored due to GA and siHMGB1 (P<0.05) . GA intervention and siHMGB1 potently prevented inflammatory substance generation (TNF-α, IL-1β, IL-6, MCP-1 and ICAM-1) , alleviated the neurotrophic factor reduction (NGF and neuritin-1) , and suppressed cellular apoptosis related protein activation (cleaved caspase-3) in Schwann cells exposed to high glucose ambience (P<0.05) . Moreover, we found that RAGE expression, p38MAPK phosphorylation and nuclear NF-κBp65 expression in high glucose-stimulated Schwann cells was reversed by GA or siRNA interference with HMGB1 (P<0.05) . Conclusions: GA and siHMGB1 can not only inhibit HMGB1 expression in Schwann cells exposed to high glucose, but also enhance cell viability. GA and siHMGB1 restored neurotrophic factors level and reduce cleaved caspase-3 expression in Schwann cell due to its anti-inflammatory ability, which may be related to the inhibition of RAGE/p38MAPK/nuclear NF-κBp65 pathway. HMGB1 may implicate in Schwann cells lesion in high glucose milieu and HMGB1 inhibition protects Schwann cells from high glucose induced cytotoxicity. Funding National Natural Science Foundation of China Grant Award (81700723)
Aim: To analyze the relationship between serum Elabela (ELA) levels and type 2 diabetic retinopathy (DR) . Methods: A total of 81 patients with type 2 diabetes were collected. According to the stages of diabetic retinopathy, the patients were divided into three groups: group 1: no diabetic retinopathy stage, group 2: non-proliferative diabetic retinopathy (NPDR) and group 3: proliferative diabetic retinopathy (PDR) , with 27 patients in each group. Serum ELA levels were detected by ELISA. Relevant clinical datas were recorded and analyzed. Results: There were no statistical significance in age, BMI, FPG, HbA1c, t-chol, TG, LDL-C, HDL-C among 3 groups (all P> 0.05) . The duration of diabetes in group 1 was significantly shorter than that in groups 2 and 3 (all P<0.05) , and there were significant differences in SBP, DBP, eGFR and Cre in groups 3 compared with those in groups 1 and 2 (P<0.05) . From group 1 to group 3, the levels of ELA decreased gradually, with statistical significance among the three groups (P<0.05) . Correlation analysis showed that serum ELA levels were negatively correlated with the course of diabetes, DR, SBP, Cre (P<0.05) , and positively correlated with eGFR (P<0.05) . Stepwise multiple linear regression analysis showed that the most relevant variables for ELA were age, BMI and DR (P=0.005; P = 0.000; P = 0.001) . According to ROC curve analysis, the sensitivity and specificity of ELA in the diagnosis of diabetic retinopathy were 59.3%, 83.3%, and the area under the curve was 0.753 (95%CI: 0.638, 0.869, P=0.000) . Conclusions: With the progressive of diabetic retinopathy, the level of serum ELA decreases gradually. ELA may be a potential clinical predictor and therapeutic target of diabetic retinopathy. Disclosure W.Gu: None. M.Shi: None. Y.Chen: None. Y.Liu: None. J.Song: None. H.Zhang: None. Funding National Natural Science Foundation of China Grant Award (81200595/81400807/81700723) , Six High-peak Talents Project of Jiangsu Province (WSN-101) , Research Project of Jiangsu 333 engineering (BRA2016232) and Research Project of Jiangsu Provincial Commission of Health and Family Planning (F201549/H201667) , and International Science and Technology Cooperation Project of Huaian (HAC201707) .
Background/Aims: C1q/TNF-related protein 9 (CTRP9) as a member of CTRP super family, participates in the regulation of glycolipid metabolism. However information regarding the role of CTRP9 in gestational diabetes mellitus (GDM) is scarce. The current study aims to ascertain the relationship between serum CTRP9 levels and GDM. Methods: A total of 35 GDM patients and 37 normal pregnant women were enrolled in our study. Serum CTRP9 levels were measured via enzyme-linked immunosorbent assay (ELISA) . Fasting insulin (FINS) , IL-6, Leptin, MCP-1, TNF-α and IL-1β were quantified using Luminex-xMAP technology. Anthropometric data and biochemical parameters were also obtained or measured. Results: The results showed that fasting plasma glucose (FPG) , one hour plasma glucose (1-h PG) , 2 hour plasma glucose (2-h PG) , FINS, IL-6, Leptin, TNF-α and CTRP9 during GDM group were significantly higher than the control group. In addition, serum CTRP9 levels had a significantly positive correlation with FPG (r = 0.559, P < 0.001) , 1h-PG (r = 0.539, P <0.0) , 2h-PG (r = 0.378, P = 0.001) , FINS (r = 0.253, P = 0.032) , HOMA-IR (r = 0.382, P = 0.001) , IL-6 (r = 0.283, P = 0.016) , and TNF-α (r = 0.266, P = 0.024) . Furthermore, binary logistic regression demonstrated that HOMA-IR and CTRP9 were independent risk factors for GDM. The AUC-ROC indicated that the diagnostic efficiency of combined CTRP9 and HOMA-IR was much higher than a single index. Conclusions: The high level of serum CTRP9 is an independent risk factor for GDM. Moreover, the combination of serum CTRP9 and HOMA-IR were more efficient in diagnosing GDM. Key words: Gestational diabetes mellitus, CTRP9, insulin resistance Disclosure H. Zhang: None.
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