ABSTRACT
Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Subject(s)
Animals , Rats , Interleukin-17 , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord Injuries/drug therapy , T-Lymphocytes, Regulatory , Receptors, Antigen, T-Cell, gamma-delta/immunologyABSTRACT
Ocular choristoma is composed of ectopic tissues with normal structures. The pathogenesis still remains uncertain. Histopathologically, it is a dense connective tissue mixed with epidermal appendages, smooth muscle cells, mature adipose tissue, lacrimal glands, lymph nodes, skeletal muscle fibers, cartilage and bone. Because of its low incidence, most of published literature are case reports. The clinical manifestations are non-specific and we need to distinguish it from other ocular masses. The choice of surgical resection depends on the ocular symptoms, the effect on appearance, and the need for clinical confirmation. This paper reviews the epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis and treatment of ocular choristoma.
ABSTRACT
The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer’s disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ1-42. In conclusion, spinosin reduced Aβ1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/ APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.
ABSTRACT
Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.
ABSTRACT
Objective To compare the endocrine and metabolic parameters between patients suffering from polycystic ovary syndrome (PCOS) with or without subclinical hypothyroidism.Methods One hundred and fifty-six PCOS patients and 47 healthy controls were enrolled.Height,weight,waist circumference,and hip circumference were measured and recorded.Fasting blood samples were collected for measuring luteinizing hormone (LH),follicular stimulating hormone (FSH),total testosterone,prolactin,estrogen,sex hormone binding globulin (SHBG),thyroidstimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),blood glucose,serum insulin,triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol (HDL-C).Body mass index,waist-to-hip ratio,LH-to-FSH ratio,and free androgen index (FAI) were calculated.Homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-β) were assessed.All patients underwent ultrasound for diagnosing polycystic ovary.All the patients were subdivided into two groups in terms of TSH value:subclinical hypothyroidism group with TSH level ≥4.2 μIU/ml and non-subclinical hypothyroidism group with TSH level＜4.2 μIU/ml.The differences in endocrine and metabolic parameters were compared between two subgroups.Results Compared with healthy controls,the PCOS patients had significantly higher body mass index,waist-to-hip ratio,LH,LH-to-FSH ratio,total testosterone,FAI,TSH,and lower SHBG (all P＜0.05).The other indexes were not different between two groups (P＞0.05).24.4％ PCOS patients were diagnosed as cases of subclinical hypothyroidism.TSH,prolactin,and triglycerides levels were higher in PCOS patients with subclinical hypothyroidism than those without (P＜0.01).Whereas estrogen,FT3,FT4 were significantly lower(P＜0.01).The differences of other parameters were not significant between two groups(P＞0.05).The results of correlation analysis and TSH quartiles showed no significant linear correlation between TSH and sex hormones,lipids,insulin resistance indices (P＞0.05).Conclusions The incidence of subclinical hypothyroidism in all PCOS patients is 24.4％.Prolactin and triglycerides levels were higher in PCOS patients with subclinical hypothyroidism than those without.Whereas estrogen,FT3,FT4 were significantly lower.
ABSTRACT
BACKGROUND:Receptor-interacting protein 140-knockout mice are lean and resistant to high fat diet-induced obesity due to an increase in mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. OBJECTIVE:To study the expression level of receptor-interacting protein 140 mRNA in adipose tissue of high fat diet-induced obese mice and the correlation with insulin resistance. METHODS:Male C57BL/6J mice were randomly divided into control group and high fat diet group, and fed for 14 weeks separately. The mice of the two groups were weighed. Mice in high fat diet group whose body weight were 20%higher than average weight of control mice were selected as obese mice. RESULTS AND CONCLUSION:A total of 12 mice in high fat diet group were recruited into the obesity group. The levels of triglycerides, total cholesterol, fast blood glucose and fast insulin in obesity group were significantly higher than those of control group (P0.05).
ABSTRACT
Objective To investigate the association of gene polymorphism of cytotoxic T lymphocyte-associated antigen 4（CTLA-4） with autoimmune thyroid diseases. Methods The A／G transition polymorphism at position 49（exon 1，codon 17） of the CTLA-4 gene was determined by polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP）method in 122 autoimmune thyroid diseases patients which included 87 Graves’ disease （GD） patients and 35 Hashimoto's thyroiditis（HT） patients， as well as 84 control subjects. We detected their thyroid function by ELISA technique， and the thyroid autoimmune antibodies （TGAb，TPOAb） by indirect immunofluorescent technique. Results The strong association of the CTLA-4／G49 allele with AITDs was seen in our study（66.4％ vs 36.9％ P＜0.0001）. The G allele in GD patients was significantly increased compared with control subjects（69.5％ vs 36.9％， P＜0.0001）. In HT patients， the frequency of G allele was also higher than control subjects（58.6％ vs 36.9％，P＜0.01）， and there was no significant difference between HT and GD groups. When GD and HT subjects were stratified with respect to sex， neither female nor male patients demonstrated evident association of G49 allele with gender.Conclusions The polymorphism of CTLA-4 gene （exon 1 condon 17 position 49）confers susceptibility to AITDs. This association is independent of sex.
ABSTRACT
Objective To investigate the association of cytotoxic T lymphocyte associated antigen 4(CTLA 4) gene polymorphism with type 1 diabetes in Chinese Han population.Methods The A/G phenotype at position 49 of the CTLA 4 gene exon 1 was determined by polymerase chain reaction restriction fragment length polymorphism(PCR RFLP)method in 33 typical type 1 diabetes patients,57 latent autoimmune diabetes in adults(LADA) patients and 84 healthy control subjects of Chinese Han.Results The frequency of the CTLA 4/G 49 phenotype was significantly higher in type 1 diabetes patients than in control subjects(55.6% vs 36.9%, respectively, P =0.0005),but there was no significant difference between typical type 1 DM and LADA groups. Neither the presence nor the absence of G 49 allele influenced the occurrence of islet autoantibody(ICA) and glutamate decarboxylase antibody(GADAb).Conclusion The polymorphism of CTLA 4 gene exon1 confers susceptibility to type 1 diabetes. This association is independent of ICA and GADAb.