Pediatric body mass index trajectories and the risk of hypertension among adolescents in China: a retrospective cohort study.

BACKGROUND: The impact of pediatric body mass index (BMI) trajectories on the risk of adolescent hypertension (HTN) determined by three separate visits remains unclear. This longitudinal study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes. METHODS: Based on the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou, China, a total of 24,426 participants who had initial normal blood pressure (BP) and had at least four BMI measurements during 2012-2020 were included. HTN was defined as simultaneously having three separate visits of elevated BP in 2020. Latent class growth models were used to explore sex-specific BMI trajectories, whose associations with HTN and HTN subtypes were further examined by logistic regression. RESULTS: The incidence of HTN determined through three separate visits was 3.34%. Four trajectories were identified for both sexes: low BMI increasing, medium BMI increasing, high BMI increasing, and highest BMI increasing. Compared to the medium BMI increasing group, the odds ratio (95% confidential interval) for developing adolescent HTN of the low, high, and highest BMI increasing groups among boys were 0.54 (0.39, 0.75), 1.90 (1.44, 2.51), and 2.89 (1.90, 4.39), respectively; and the corresponding values for girls were 0.66 (0.48, 0.90), 2.30 (1.72, 3.09), and 4.71 (3.06, 7.26). Similar gradually elevated associations between different trajectories with isolated systolic hypertension, systolic and diastolic hypertension were observed. CONCLUSION: Current results emphasized the adverse effects of stable high BMI on HTN and the benefits of maintaining normal weight throughout childhood.

Selenium Supplementation Protects Against Arsenic-Trioxide-Induced Cardiotoxicity Via Reducing Oxidative Stress and Inflammation Through Increasing NAD+ Pool.

Arsenic is an environmental contaminant, and accumulating evidence has indicated that exposure to arsenic can cause various diseases, especially cardiotoxicity. Selenium (Se) exerts a vital role in the regulation of multiple physiological activities. Recently, several studies highlighted that Se treatment can effectively antagonize the toxic effects induced by arsenic. However, the exact underlying effect and mechanism of Se on Arsenic-induced cardiotoxicity has not been explored. In the current study, the arsenic trioxide (ATO)-triggered heart damage mice model was used to explore whether Se exerts protective roles in ATO-related cardiotoxicity and its potential mechanism. Our data showed that Se treatment significantly alleviated ATO-mediated cardiotoxicity evidenced by increased weight, decreased myocardial damage markers, and improved heart functions in mice. Furthermore, we demonstrated that Se remarkably inhibited ATO-mediated oxidative stress and inflammatory responses in heart tissues. Mechanistically, we showed that Se upregulated the levels of NAD+ in cardiomyocytes of the mice challenged by ATO, and this effect involved in the activation of the NAD+ biosynthesis through the salvage pathway. Collectively, our findings demonstrated that Se protected against ATO-mediated cardiotoxicity by antioxidant and anti-inflammatory effects via increasing the NAD+ pool in mice.

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.

Selenium Attenuates Doxorubicin-Induced Cardiotoxicity Through Nrf2-NLRP3 Pathway.

Selenium (Se), an essential nutrient for humans, has been reported to possess cardioprotective effect. However, the protective effects of Se against doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanism are rarely reported. In this study, we sought to explore whether Se protected against DOX-induced cardiotoxicity by inhibiting Nrf2-NLRP3 pathway. We found that Se treatment effectively alleviated DOX-induced myocardial dysfunctions, decreasing plasma markers associated with myocardial injury. Moreover, Se treatment significantly inhibited DOX-induced oxidative damages and pro-inflammatory cytokine expression in heart tissues. Furthermore, Se treatment markedly promoted the expression of Nrf2 and prevented the activation of NLRP3 inflammasome. Importantly, suppression of Nrf2 abolished the cardioprotective effects of Se and diminished the inhibition of Se on NLRP3 inflammasome. Collectively, our study demonstrated that Se might protect against DOX-induced cardiotoxicity via regulating Nrf2-NLRP3 pathway. Se supplementation may be a potential therapeutic strategy to protect against DOX-induced cardiac injury.

Comparison of China Reference with Different National and International References: The Prevalence of High Blood Pressure in 695,302 Children and Adolescents in a Metropolis of Yangtze River Delta, China.

OBJECTIVES: This study aimed to compare performances of China reference and different national references on high blood pressure (HBP). METHODS: A cross-sectional study including 695,302 children and adolescents aged 7 to 17 years in Suzhou, China, was conducted to determine the prevalence of HBP based on U.S., international, Europe, and China references in 2016. RESULTS: Different percentiles of height and blood pressure were found among four references. Referring to U.S. reference, the prevalence of HBP was the highest with 26.0%, followed by International reference with 20.0%, Europe reference with 19.5%, and China reference with 19.2%. McNemar tests indicated statistically significant differences between HBP prevalence comparing China reference with the other 3 references (P < 0.001). The area under the curve was 0.947, 0.851, and 0.949 for U.S., international, and Europe reference, respectively. U.S. reference showed the highest sensitivity (98.2%), but the lowest specificity (91.2%), and Europe reference showed the highest kappa value (0.893). CONCLUSIONS: The prevalence of HBP varied among these four references, and the appropriate choice of reference would be important to recognize high-risk children and judge the trends of HBP prevalence in the targeted population.

[Effects of extracellular matrix PDMS stiffness on proliferation and osteogenic differentiation of dental pulp stem cells].

PURPOSE: To investigate the effects of extracellular matrix stiffness on proliferation and osteogenic differentiation of dental pulp stem cells (DPSCs) in polydimethylsiloxane (PDMS)-based cell culture substrate model. METHODS: The premolars removed during orthodontic treatment in Changzhou NO.2 People's Hospital were collected for DPSCs culture. PDMS matrix membranes were prepared, and divided into three groups according to the different stiffness degrees, group A (binder/hardener: 10∶1; 135 kPa), group B (binder/hardener: 20∶1; 54 kPa), and group C (binder/hardener: 30∶1; 16 kPa). Group free from PDMS was set as control group. Thereafter, DPSCs cells were cultured on PDMS matrix, and various indexes were detected. The proliferation rate of DPSCs was detected by CCK-8, the osteogenic differentiation of DPSCs was detected by alizarin red staining, and the protein expression levels of osteocalcin(OCN), RUNX2, Wnt1 and ß-catenin were detected by Western blot. The data were processed with SPSS 22.0 software package. RESULTS: Alizarin red staining showed that DPSCs cells in group A had obvious morphological changes, and the cell arrangement showed obvious orientation, its morphology gradually changed from polygon and spindle shape to square shape, and calcified nodules were also observed. The number of calcified nodules among four groups were the most in the group A, followed by group B and group C, which was the lowest in control group, with significant difference (P<0.05). The cell proliferation rate and the expression of OCN, RUNX2, Wnt1 and ß-catenin were the highest in group A, followed by group B and group C, which was the lowest in control group, with significant difference(P<0.05). CONCLUSIONS: The extracellular matrix with high stiffness may promote the proliferation and osteogenic differentiation of DPSCs by activating Wnt/ß-catenin signaling pathway, which may provide a theoretical basis for periodontal tissue engineering.

Does underweight amplify the relationship between short-term particulate matter exposure and blood pressure in children and adolescents: a large cross-sectional study in a metropolis of China.

Overweight/obesity modified the effects of ambient particulate matter (PM) exposure on blood pressure (BP). This study aims to assess whether interaction of underweight and short-term PM exposure on BP exists in Chinese children. A cross-sectional analysis including 144,513 children aged 6 to 17 years in 2016 Health Promotion Program for Children and Adolescents of Suzhou, China, was performed. Daily concentrations of inhalable PM (PM10) and fine PM (PM2.5) were extracted from air monitoring stations close to students' schools. We applied generalized linear mixed-effects models to estimate the interactions. Estimated changes (95% confidence intervals (CIs)) of systolic BP (SBP), diastolic BP (DBP), and odds ratios (ORs) (95% CIs) for prevalence of HBP were calculated. Significant interactions between PM and underweight on BP and prevalence of high BP (HBP) were observed. For example, at lag 6, the ORs (95% CIs) for HBP by each 10 µg/m3 changes of PM2.5 were 1.066 (1.039, 1.093) and 1.036 (1.028, 1.043) among underweight and normal weight subjects, respectively; these values for PM10 were 1.048 (1.031, 1.065) and 1.025 (1.021, 1.030). At lag 5, the increases of SBP for PM2.5 were 0.32 (95% CI 0.22, 0.43) mmHg and 0.23 (95% CI 0.29, 0.26) mmHg, while changes of DBP were 0.27 (95% CI 0.18, 0.35) mmHg and 0.19 (95% CI 0.16, 0.21) mmHg among underweight and normal weight subjects, respectively. Stratified analyses demonstrated that these interactions were only obtained in males. Effects of short-term PM exposure on BP and prevalence of HBP are enhanced in underweight children and adolescents.

Association between decreased HDL levels and cognitive deficits in patients with bipolar disorder: a pilot study.

BACKGROUND: Cognitive deficits are common in patients with bipolar disorder (BD). Abnormal high density lipoprotein (HDL) levels have been implicated in cognitive deficits associated with ageing and neurodegenerative disorders. The present study aimed to investigate serum HDL levels, cognitive deficits and their association in patients with BD. METHODS: Thirty-seven patients with BD and 37 gender- and age-matched healthy controls (HCs) were recruited in a case-control study. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum HDL levels were measured using enzymatic colourimetry. RESULTS: There was no difference in serum HDL levels between patients with BD and HCs after adjusting for gender, age, education and body mass index (BMI). Cognitive test scores in patients with BD were significantly lower than those in HCs except for the visuospatial/constructional index after adjusting for confounding variables. Serum HDL levels were positively correlated with RBANS total score and language score in patients with BD. Stepwise multiple regression analysis showed that serum HDL levels were significantly correlated with RBANS total score and subscale scores on immediate memory and language in patients with BD after adjusting for confounding factors. CONCLUSIONS: Our findings suggest that patients with BD had poorer cognitive performance than HCs except for the visuospatial/constructional domain, and decreased serum HDL levels were correlated with cognitive deficits, especially in immediate memory and language domains in patients with BD.

Short-term effects of ambient particulate matter on blood pressure among children and adolescents:A cross-sectional study in a city of Yangtze River delta, China.

Several studies have demonstrated associations between short-term exposure to particulate matter (PM) and blood pressure (BP) among various adults groups, but evidence in children and adolescents is still rare. In 2016, a cross-sectional survey was conducted among 194 104 participants aged 6-17 years in Suzhou, China. Daily concentrations of particulate matters with an aerodynamic diameter of ≤10 µg/m3 (PM10) and aerodynamic diameter ≤2.5 µg/m3 (PM2.5) on 0-6 days preceding BP examination were collected from nearby air monitoring stations. Using generalized linear mixed-effects models, short-term effects of PM on personal BP were estimated. A 10 µg/m3 increment in the 0-6 day mean of PM2.5 was significantly associated with elevation of 0.20 mmHg [95% confidence interval (95% CI) 0.16-0.23] in systolic BP (SBP), 0.49 mmHg (95% CI 0.45-0.53) in diastolic BP (DBP), respectively. Similarly, 0.14 mmHg (95% CI 0.12-0.16) higher SBP and 0.32 mmHg (95% CI 0.30-0.34) higher DBP were found for each 10 µg/m3 increase in 0-6 day mean of PM10. More apparent associations were observed in females than in males. Odds ratio (95%CI) of for PM2.5 exposure at 0-6 d mean was 1.06 (1.03-1.08) in females, while it was 1.01 (0.99-1.03) in males. Participants with young ages, underweight and obesity were also associated with increased susceptibility to PM-induced BP effects. Short-term exposure in PM was significantly associated with elevated BP in children, indicating a need to control PM levels and protect children from PM exposure in China.

Prevalence of high blood pressure and high normal blood pressure among 7- to 17-year-old children and adolescents in developed regions, China from 2014 to 2017: using new national blood pressure reference for Chinese children and adolescents.

As the first blood pressure (BP) reference considering influence of height in China, national blood pressure reference for Chinese han children and adolescents aged 7 to 17 years (CCBP) was issued in 2017. The current study aimed to observe the short-term trends in BP and prevalence of high blood pressure (HBP) and high normal blood pressure (HNBP) using this CCBP reference in Suzhou, China. Data of children and adolescents aged 7 to 17 years were collected from 2014 to 2017. Total population of 2014 to 2017 were 617,383, 684,453, 695,302, and 774,605, respectively, and proportions of males were 54.1%, 54.0%, 53.9%, and 53.8%, respectively. P-trend tests were conducted to examine the trends of BP among different age, region, body mass index, and socioeconomic status groups for each gender. Multivariate logistic regression analyses found secular decreases in prevalence of HBP and HNBP, after adjustment for potential confounders. Compared with that in 2014, the odds ratios (95% confidence intervals) for total study population were 0.936 (0.928, 0.944) in 2015, 0.879 (0.872, 0.887) in 2016, and 0.934 (0.926, 0.941) in 2017. In conclusion, prevalence of HBP and HNBP decreased among children and adolescents in developed regions of China from 2014 to 2017, and a slight rise were found in 2017.

The short-term effects of outdoor temperature on blood pressure among children and adolescents: finding from a large sample cross-sectional study in Suzhou, China.

Although several studies have demonstrated a short-term association between outdoor temperature and blood pressure (BP) among various adult groups, evidence among children and adolescents is lacking. One hundred ninety-four thousand one hundred four participants from 2016 Health Promotion Program for Children and Adolescents (HPPCA) were analyzed through generalized linear mixed-effects models to estimate the short-term effects of two outdoor temperature variables (average and minimum temperature) on participants' BP. Decreasing outdoor temperature was associated with significant increases in systolic BP (SBP), diastolic BP (DBP), and prevalence of hypertension during lag 0 through lag 6. Additionally, daily minimum temperature showed a more apparent association with participants' BP. The estimated increases (95% confidence interval) in SBP and DBP at lag 0 were 0.82 (0.72, 0.92) mmHg and 2.28 (2.20, 2.35) mmHg for a 1 °C decrease in daily minimum temperature, while those values were 0.11 (0.10, 0.12) mmHg and 0.25 (0.24, 0.26) mmHg for a 1 °C decrease in daily average temperature, respectively. The effects of temperature on BP were stronger among female, as well as those with young age and low body mass index. It demonstrated that short-term decreases in outdoor temperature were significantly associated with rises in BP among children and adolescents. This founding has some implications for clinical management and research of BP. Meanwhile, public health intervention should be designed to reduce the exposure to cold temperature for protecting children and adolescents' BP.

Tumor necrosis factor gene polymorphisms are associated with silicosis: a systemic review and meta-analysis.

Studies investigating association between tumor necrosis factor (TNF) gene polymorphisms and silicosis susceptibility report conflicting results. The aim of this meta-analysis was to assess association between TNF gene polymorphisms and silicosis susceptibility. A systematic literature search was conducted to find relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Finally, a total of 12 articles, involving 1990 silicosis patients and 1898 healthy controls were included in the meta-analysis. Overall, meta-analysis revealed a significant association between the TNF -308A allele and silicosis (OR = 1.348, 95%CI = 1.156-1.570, P<0.001). A significant association of AA+AG genotype of the TNF -308 A/G polymorphism with susceptibility to silicosis was also found (OR = 1.466, 95%CI = 1.226-1.753, P<0.001). After stratification by ethnicity, significant associations were detected under the genetic models (A allele and AA+AG genotype) for TNF -308A/G polymorphisms in the Asian population (P<0.05). Similarly, meta-analysis of the TNF -238A/G polymorphism revealed the same pattern as that shown by meta-analysis of TNF -308A/G. The meta-analysis suggests that the TNF -308A/G and -238A/G polymorphisms are associated with susceptibility to silicosis, especially in Asians.

Effect of Diallyl Trisulfide on Ischemic Tissue Injury and Revascularization in a Diabetic Mouse Model.

BACKGROUND AND OBJECTIVE: Allitridin [diallyl trisulfide (DATS)] is an extract from garlic (Allium sativum) that putatively improves endothelial function and is protective against cardiovascular diseases. Endothelial dysfunction after tissue ischemia in diabetic patients is partially due to poor angiogenic response. This study investigated whether DATS may improve angiogenesis in a diabetic mouse model with hind limb ischemia. METHODS: Streptozotocin was administered by intraperitoneal injection to establish the model of diabetes in male C57BL/6 mice. After 14 days, nondiabetic and diabetic mice (n = 24, each) underwent unilateral hind limb ischemia by femoral artery ligation. The mice were apportioned to 4 groups: nondiabetic treated (or not) with DATS and diabetic treated (or not) with DATS. DATS treatment consisted of a single daily intraperitoneal injection of 500 µg·kg·d for 14 days, beginning on the day of induced ischemia. Ischemia was scored by standard criteria. Blood perfusion was determined using thermal infrared imaging. Tissue capillary density and oxidative stress levels were measured by immunohistochemistry and immunofluorescence, respectively. Serum lipids were measured by enzymatic colorimetric assay. Fasting serum insulin was detected using an insulin enzyme-linked immunosorbent assay kit. Nitric oxide (NO) metabolites and protein carbonyls in tissues were determined by enzyme-linked immunosorbent assay. Targeted protein concentrations were measured by western blotting. RESULTS: At 14 days after ligation, the ischemic skeletal muscle of the streptozotocin-induced diabetic mice had lower levels of endothelial NO synthase, phosphorylated endothelial NO synthase, and vascular endothelial growth factor compared with nondiabetic group. In addition, the hind limb blood perfusion, capillary density, and NO bioactivity were lower in the diabetic group, whereas oxidative stress and protein carbonyl levels were higher. These changes were ameliorated by DATS treatment. CONCLUSIONS: DATS treatment of diabetic mice promoted revascularization in ischemic tissue.

Effects of resting heart rate on blood pressure and hypertension in Chinese children: findings from blood pressure surveillance program.

The purpose of this study was to analyze the association between resting heart rate (RHR) and prevalence of hypertension in Chinese children and to identify if this association was mediated by body mass index (BMI). The data of 5445 children who participated in the Blood Pressure Surveillance Program (2011-2017) were analyzed in this study. Children were divided into four groups according to quartiles of RHR in boys and girls, respectively. Compared to those in the first quartile, boys and girls in the fourth quartile were 3.06 (95% CI 2.12, 4.41) and 4.94 (95% CI 3.21, 7.61) times more likely to have hypertension, respectively. Meanwhile, every 10 beats per minute (bpm) increase in RHR was associated with a 41% (95% CI 1.27, 1.56) and 66% (95% CI 1.49, 1.85) greater risk of hypertension in boys and girls, respectively. There were no significant interactions between RHR and BMI on the prevalence of hypertension. This study confirms the existence of a relationship between elevated RHR and increased risk of hypertension in children, independent of BMI. An elevated RHR could be considered as a risk factor for the risk assessment of hypertension, no matter from a clinical setting or a public health perspective.

Association of elevated resting pulse rate with increased risk of hypertension development in children: A prospective study in Suzhou, China.

BACKGROUND: Elevated resting heart rate (RHR) or resting pulse rate (RPR) is associated with increased risk of hypertension development. However, information is limited to adults. The purpose of this study is to analyze this association among Chinese children in a prospective design. METHODS: A total of 4861 children who participated in the Blood Pressure Surveillance Program (2011-2017) were selected in this research. To investigate the association between RPR and hypertension development, children were divided into 4 groups according to the quartiles of RPR at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression model. RESULTS: Over a mean follow-up of 3.0 ±â€Š0.1 years, there were 384 cases of incident hypertension. Compared to boys and girls in the 1st quartile, those in the 4th quartile were 1.73 (95% CI 1.13, 2.65), 2.22 (95% CI 1.43, 3.45) times more likely to have hypertension, respectively. Every 10 bpm increase in RPR was associated with a 26% greater risk of hypertension development in boys (OR: 1.26; 95% CI 1.10, 1.44), while this risk was 1.28 (95% CI 1.13, 1.44) in girls. Baseline blood pressure (BP) and body mass index (BMI) did not have significant interactions with RPR on risk of hypertension development. CONCLUSION: This study confirms the relationship between elevated RPR and increased risk of hypertension development in children, independent of confounders including baseline BP and BMI. An elevated RPR could be considered as a risk factor for the assessment of hypertension, no matter from a clinical setting or a public health perspective.

Relation of body mass index (BMI) to the prevalence of hypertension in children: A 3years' school-based prospective study in Suzhou, China.

BACKGROUND: The prevalence of hypertension has been increasing in children and adolescents in China, which is considered to be accompanied with the epidemic of childhood overweight and obesity, but limited prospective studies have investigated the effect of body mass index (BMI) change on blood pressure among children, especially in China. METHODS: This school-based prospective study compared the blood pressure and prevalence of hypertension in students with different patterns of change in BMI between two periods (childhood and adolescence). 5465 children were followed-up since 2011(childhood) in Suzhou, China and had weight, height and blood pressure measured in 2011(childhood) and 2014(adolescence). RESULTS: Those who changed from being overweight in childhood to having normal BMI in adolescence had similar mean blood pressures to those who had a normal BMI at both two periods. In contrast, those who were overweight at both two periods or who had a normal BMI in childhood and were overweight in adolescence had higher blood pressure in adolescence than those who had a normal BMI at both two periods. Compared with students who had a normal BMI at both periods, those with combination of abnormal BMI in childhood and adolescence have higher ORs of hypertension (4.83 in boys, 3.44 in girls and 3.73 in total). CONCLUSION: These results suggest that obesity is a key determinant of blood pressure during childhood, and weight reduction may have important beneficial effects on blood pressure.

Roles of A20 in autoimmune diseases.

A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings.

The roles of Egr-2 in autoimmune diseases.

Being a member of the early growth response (Egr) family of transcription factors, Egr-2 is expressed in a variety of cell types of the immune system. Recent findings imply that Egr-2 is important in the development and function of T helper (Th) 17 cell, regulatory T (Treg) cell, as well as dendritic cell (DC). Although these cells perform significantly in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and systemic sclerosis, the roles of Egr-2 in the pathogenesis of autoimmune diseases can not be neglected. In this article, we will discuss recent findings about the important roles of Egr-2 in immune cells and the possible pathological roles of Egr-2 in autoimmune diseases.

[Effect of overexpressed VEGF165 and TGFß1 on the regeneration of dentin-like tissue in rat].

PURPOSE: To transfect recombinant vectors pcDNA3.1hisA-VEGF165 and pcDNA3.1hisA-TGFß1 in Chinese hamster ovary cell (CHO) and investigate the effect of released VEGF165 and TGFß1 proteins by CHO on the regeneration of dentin-like tissues. METHODS: The recombinant plasmids pcDNA3.1hisA-VEGF165 and pcDNA3.1hisA-TGFß1 were transfected in CHO via liposome. After screen culture by G418, stable transfected CHO cell line was established. The levels of VEGF165 and TGFß1 were evaluated by RT - PCR and ELISA. Then the cells were seeded on collagen membranes. The bilateral maxillary first molars of 24 Wistar rats were selected as experimental teeth and the collagen membranes were separately planted over the holes of artificial dental pulp exposure. The cavities were filled with ChemFlex finally. After 8 weeks, specimens from 24 rats were collected and dyed with toluidine blue. Statistical analysis was performed with SPSS 17.0 software package. RESULTS: The results of RT-PCR and ELISA showed that CHO stably expressed VEGF165 and TGFß1 mRNAs and proteins after transfection and selection. The result of toluidine blue staining showed that in the group of CHO transfected with pcDNA3.1hisA-VEGF165, the blood capillaries were congestive and inflammatory cells infiltrated obviously under the mechanically exposed pulpal site, but no hard tissue regenerated. In the group of CHO transfected with pcDNA3.1hisA-TGFß1, a spot of colored mineralization pellets under the mechanically exposed pulpal site surrounded with hyperplastic fibroblast were observed, no tubular dentin and sporadic inflammatory cells were detected. In the group of CHO transfected with pcDNA3.1hisA-VEGF165 and pcDNA3.1hisA-TGFß1, generous colored mineralization pellets almost closed the mechanically exposed pulpal site and columnar odontoblast were arranged orderly, no regular dentin bridge was detected. The hard tissue was not detected in the control group. CONCLUSIONS: TGFß1 could promote the formation of mineralization pellets in vivo, and VEGF165 and TGFß1 could promote the formation of mineralization pellets better. Supported by Science and Technology Development Foundation of Shandong Province (2010G0020230) and Natural Science Foundation of Shandong Province (Y2006C47).

[The effect of CD137-CD137 ligand interaction on the expression of nuclear factor of activated T cells c1 in apolipoprotein E-deficient mice atherosclerotic plaque model].

OBJECTIVE: To investigate the effects of CD137-CD137L interaction on the nuclear factor of activated T cells c1 (NFATc1) in apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Atherosclerotic plaque model was produced by rapid perivascular carotid collar placement in ApoE(-/-) mice. In vivo, the expression of NFATc1 in mice plaque and lymphocytes was detected by immunohistochemical and flow cytometry, respectively. In vitro, the NFATc1 mRNA and protein expressions in cultured lymphocytes of ApoE(-/-) mice were measured by RT-PCR and flow cytometry, respectively. RESULTS: In vivo, after stimulating CD137-CD137L signal pathway, the expression of NFATc1 was significantly upregulated in the atherosclerotic plaques and lymphocytes. In vitro, the mRNA and protein expressions of NFATc1 in cultured leukocytes of ApoE(-/-) mice were also significantly increased, the maximal effect appeared post 20 µg/ml anti-CD137 mAb-stimulation and reached maximum at 24 h at any concentrations. Anti-CD137L mAb significantly downregulated the mRNA and protein expressions of NFATc1 in lymphocytes of ApoE(-/-) mice, maximal effect appeared at 20 µg/ml anti-CD137L mAb and reached minimum at 24 h. CONCLUSION: CD137-CD137L interactions can modulate the expression of NFATc1 in this ApoE(-/-) mice atherosclerotic plaque model.