Evaluation of serum Epstein-Barr virus envelope glycoproteins antibodies and their association with systemic autoimmune diseases.

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.

Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1.

BACKGROUND: In recent years, studies have found that the occurrence and development of diabetic cardiomyopathy (DCM) is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1 (PARP-1) activity. PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress, the inflammatory response, apoptosis and myocardial fibrosis. AIM: To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats, further clarified the protective effect of liraglutide on the heart, and provided a new option for the treatment of DCM. METHODS: Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group (n = 10) and a model group (n = 30), which were fed an ordinary diet and a high-sugar and high-fat diet, respectively. After successful modeling, the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group (further divided into a high-dose group and a low-dose group). The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention. Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles. Intact heart tissue was dissected, and its weight was used to calculate the heart weight index. Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry. RESULTS: The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group, and those in the intervention group were decreased compared with those in the model group, with a more obvious decrease observed in the high-dose group (P < 0.05). In the model group, myocardial fibers were disordered, and inflammatory cells and interstitial fibrosis were observed. The cardiomyopathy of rats in the intervention group was improved to different degrees, the myocardial fibers were arranged neatly, and the myocardial cells were clearly striated; the improvement was more obvious in the high-dose group. Compared with the normal control group, the expression of PARP-1 in myocardial tissue of the model group was increased, and the difference was statistically significant (P < 0.05). After liraglutide intervention, compared with the model group, the expression of PARP-1 in myocardial tissue was decreased, and the reduction was more obvious in the high-dose group (P < 0.05) but still higher than that in the normal control group. CONCLUSION: Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

[Experimental study of repairing rabbit femur defect with NPP/C-HA/ rhBMP-2].

PURPOSE: To investigate the osteogenic effect of nano-grade pearl powder(NPP)/chitosan-hyaluronic acid (C-HA)/recombinant human bone morphology protein-2 (rhBMP-2) artificial bone. METHODS: A bone defect model with a diameter of 7 mm and a height of 10 mm was made at the distal end of the femur. NPP/C-HA stent containing rhBMP-2 was prepared according to the shape of the defect. No material was implanted in the defect as blank group. NPP/C-HA was used as the control group, NPP/C-HA/rhBMP-2 was implanted into the experimental group. At 4 weeks, 8 weeks, and 12 weeks, the bone effects of each component were detected by cone-beam CT(CBCT), H-E and Masson staining. Serum ALP activity and OCN in tissues to determine the osteogenic differentiation and osteogenesis maturity were detected. SPSS 18.0 software package was used for statistical analysis. RESULTS: At 12 weeks, the defect was completely repaired in the experimental group. No immunological side effects such as inflammation and rejection were observed. At 8 and 12 weeks, CBCT showed that the experimental group had a higher CT value (Hounsfield units, HU) compared with the control group and the blank group(P<0.05). H-E and Masson staining showed that the experimental group had obvious new bone formation compared with the control group and the blank group at 8 weeks and 12 weeks, and ALP activity of the experimental group was significantly different from the control group and the blank group at 8 weeks. OCN immunohistochemical scoring of the experimental group was significantly different from the control group and the blank group(P<0.05). CONCLUSIONS: NPP/C-HA/rhBMP-2 has good tissue fusion, osteoinductivity, osteoconductivity and osteogenicity, which is expected to provide more effective treatment for bone repair.

Aberrant DNA Methylation Involved in Obese Women with Systemic Insulin Resistance.

BACKGROUND: Epigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray. METHODS: The genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student's t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women. RESULTS: Relative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes. CONCLUSION: Based on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.