The Mediating Role of Physical Activity Self-Efficacy in Predicting Moderate-Intensity Physical Activity in Pregnant People at High Risk for Gestational Diabetes.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common medical complication in pregnancy. Moderate-intensity physical activity during pregnancy can lower the risk of GDM. However, the relationship between moderate-intensity physical activity and correlated factors among pregnant people at high risk for GDM remains unknown. METHODS: A cross-sectional study was conducted in China. Two hundred fifty-two participants completed the Pregnancy Physical Activity Questionnaire, Pregnancy Physical Activity Self-Efficacy Scale, Physical Activity Knowledge Questionnaire, Physical Activity Social Support Scale, 7-item Generalized Anxiety Disorder Scale, Edinburgh Postnatal Depression Scale, and a sociodemographic data sheet. Structural equation modeling was used to explore the direct and indirect associations between the study variables. RESULTS: A total of 51.6% of the participants did not meet the current physical activity guidelines. Only physical activity self-efficacy was significantly correlated with moderate-intensity physical activity. Physical activity self-efficacy mediated the relationship between moderate-intensity physical activity and knowledge of physical activity, social support for physical activity, and anxiety symptoms. Furthermore, knowledge of physical activity was also associated with improved moderate-intensity physical activity mediated by reduced anxiety symptoms and increased physical activity self-efficacy. CONCLUSION: Our study revealed a high prevalence of not meeting current physical activity guidelines among pregnant people at high risk for GDM. Physical activity self-efficacy played an important mediating role in predicting moderate-intensity physical activity. Future studies should focus on enhancing self-efficacy to improve moderate-intensity physical activity for pregnant people at high risk for GDM.

Development and feasibility of a theory-guided and evidence-based physical activity intervention in pregnant women with high risk for gestational diabetes mellitus: a pilot clinical trial.

BACKGROUND: Physical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention. RESULTS: The validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful. CONCLUSIONS: The developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study. TRIAL REGISTRATION: The study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR).

A self-efficacy-enhancing physical activity intervention in women with high-risk factors for gestational diabetes mellitus: study protocol for a randomized clinical trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Evidence has demonstrated that moderate-intensity physical activity may reduce the risk of gestational diabetes. However, women at risk of GDM spend most of their time performing sedentary behaviors. Although researchers identified self-efficacy as a mediator to overcome physical activity barriers, exercise intervention during pregnancy based on self-efficacy theory has not been discussed so far. Furthermore, there is conflicting evidence regarding the effects of a physical exercise intervention on the incidence of GDM and other maternal or neonatal outcomes in women at higher risk for GDM. METHODS/DESIGN: A single-center, parallel, randomized controlled trial will be conducted in a maternal-child health care center. A total of 244 pregnant women at high risk for GDM will be randomized into a study group receiving a self-efficacy-enhancing physical activity intervention or a control group receiving the usual care. The intervention will consist of four group sessions and everyday reminders by WeChat (Tencent, Shenzhen, China). The program will begin at approximately 13-14+6 gestational weeks and end at 36+6 gestational weeks. The primary outcomes will include the incidence of GDM, blood sugar values, and physical activity. The secondary outcomes will include physical activity self-efficacy, gestational weight gain, maternal outcomes, and neonatal outcomes. DISCUSSION: The findings of this research will contribute toward understanding the effects of a self-efficacy theory-oriented physical activity program on the incidence of GDM, blood sugar values, physical activity level, gestational weight gain, physical activity self-efficacy, maternal outcomes, and neonatal outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry (CHiCTR) ChiCTR2200056355 . Registered on February 4, 2022.

Shewanella jiangmenensis sp. nov., isolated from aquaculture water.

A Gram-stain-negative and facultatively anaerobic bacterial strain designated as JM162201T was isolated from aquaculture water for farming Pacific white shrimp (Litopenaeus vannamei). The genome size of strain JM162201T was 4,436,316 bp, and the genomic DNA G + C content was 55.0%. Phylogenetic analysis based on 16S rRNA gene sequences and genomes showed that strain JM162201T belonged to the genus Shewanella and was closely related to Shewanella litorisediminis SMK1-12T (97.1%), Shewanella khirikhana TH2012T (97.0%), and Shewanella amazonensis SB2BT (96.0%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain JM162201T and three reference type strains were below the recognized thresholds of 95.0-96.0% (for ANI) and 70.0% (for dDDH) for species delineation. Growth occurred at 10-40 °C (optimum, 30 °C), at pH 4.0-10.0 (optimum, 7.0-8.0), and in 0-6.0% NaCl (w/v, optimum, 0-0.1%). The major cellular fatty acids of strain JM162201T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C17:1 ω8c, iso-C15:0, C16:0, and C15:0. The predominant quinones were MK7, Q-7, and Q-8. The major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Based on the polyphasic taxonomical analyses, strain JM162201T represents a novel species of the genus Shewanella, for which the name Shewanella jiangmenensis sp. nov. is proposed, with the type strain JM162201T (= GDMCC 1.2006T = KCTC 82340T).

Attenuation of virulence in multiple serotypes (M1, M3, and M28) of Group A Streptococcus after the loss of secreted esterase.

INTRODUCTION: Group A Streptococcus (GAS) can produce streptococcal secreted esterase (Sse), which inhibits neutrophil recruitment to the site of infection and is crucial for GAS pathogenesis. As an effective esterase, Sse hydrolyzes the sn-2 ester bond of human platelet-activating factor, inactivating it and abolishing its ability to recruit neutrophils. OBJECTIVES: The purpose of this study was to investigate the effects of sse deletion on the virulence of multiple serotypes of GAS. METHODS: Isogenic strains that lack the sse gene (Δsse) were derived from the parent strains MGAS5005 (serotype M1, CovRS mutant), MGAS2221 (serotype M1, wild-type CovRS), MGAS315 (serotype M3, CovRS mutant) and MGAS6180 (serotype M28, wild-type CovRS) and were used to study the differences in virulence and pathogenicity of GAS serotypes. RESULTS: In a subcutaneous infection model, mice infected with MGAS5005Δsse exhibited higher survival rates but decreased dissemination to the organs compared with mice infected with MGAS5005. When mice were infected with the four Δsse mutants, the MPO activity and IFN-γ, TNF-α, IL-2 and IL-6 levels increased, but the skin lesion sizes decreased. In an intraperitoneal infection model, the absence of Sse significantly reduced the virulence of GAS, leading to increased mouse survival rates and decreased GAS burdens in the organs in most of the challenge experiments. In addition, the numbers of the four Δsse mutants were greatly reduced 60 min after incubation with isolated rat neutrophils. CONCLUSION: Our results suggest that Sse participates in the pathogenesis of multiple GAS serotypes (MGAS5005, MGAS2221, MGAS315 and MGAS6180), particularly the hypervirulent CovS mutant strains MGAS5005 and MGAS315. These strain differences were positively correlated with the virulence of the serotype.

Immunization With a Secreted Esterase Protects Mice Against Multiple Serotypes (M1, M3, and M28) of Group A Streptococcus.

Streptococcal secreted esterase (Sse) is a platelet-activating factor acetylhydrolase that is critical for Group A Streptococcus (GAS) skin invasion and innate immune evasion. There are two Sse variant complexes that share >98% identity within each complex but display about 37% variation between the complexes in amino acid sequences. Sse immunization protects mice against lethal infection and skin invasion in subcutaneous infection with the hypervirulent CovRS mutant strain, MGAS5005. However, it is not known whether Sse immunization provides significant protection against infection of GAS with functional CovRS and whether immunization with Sse of one variant complex provides protection against infection of GAS that produces Sse of another variant complex. This study was designed to address these questions. Mice were immunized with recombinant Sse of M1 GAS (SseM1) and challenged with MGAS5005 (serotype M1, CovS mutant, and Sse of variant complex I), MGAS315 (M3, CovS mutant, and Sse of variant complex I), MGAS2221 (M1, wild-type CovRS, and Sse of variant complex I), and MGAS6180 (M28, wild-type CovRS, and Sse of variant complex II). SseM1 immunization significantly increased survival rates of mice in subcutaneous MGAS5005 and intraperitoneal MGAS6180 challenges and showed consistently higher or longer survival in the other challenges. Immunized mice had smaller skin lesion and higher neutrophil responses in subcutaneous infections and lower GAS burdens in spleen, liver, and kidney in most of the challenge experiments than control mice. SseM1 immunization enhanced proinflammatory responses. These data suggest that Sse immunization has a broad benefit against GAS infections that can vary in extent from strain to strain and that the benefit may be due to the immunization-enhanced proinflammatory responses. In particular, immunization with SseM1 can provide protection against M28 GAS infection even though its Sse and SseM1 have significant variations.

Active and passive immunizations with HtsA, a streptococcal heme transporter protein, protect mice from subcutaneous group A Streptococcus infection.

BACKGROUND/PURPOSE: HtsA (Streptococcus heme transporter A) is the lipoprotein component of the streptococcal heme ABC transporter (HtsABC). The aim of this study is to investigate whether the HtsA protein has immunoprotective effect against group A Streptococcus (GAS) infection in mice. METHODS: The HtsA protein was purified by sequential chromatography on Ni-sepharose, DEAE-sepharose and Phenyl-sepharose, CD-1 mice were actively immunized with ALUM (control) or HtsA/ALUM, and passively immunized with control or anti-HtsA serum. Mice were challenged with GAS after immunization, and the survival rate, skin lesion size and systemic GAS dissemination were determined. RESULTS: The HtsA gene was cloned, and the recombinant protein HtsA was successfully purified. HtsA has a strong antigenicity, and active immunization with the HtsA protein significantly protected mice against lethal subcutaneous GAS infection, inhibited invasion of the skin by GAS, and reduced GAS systemic dissemination in blood and organs. In addition, passive immunization with anti-HtsA serum also significantly protected mice against subcutaneous GAS infection, and inhibited invasion of the skin by GAS. CONCLUSION: The results showed that both active and passive immunization with the HtsA protein protected mice against subcutaneous GAS infection, suggesting that HtsA may be a candidate of GAS vaccine to protect against GAS infection.

Naringin suppresses the growth and motility of hypertrophic scar fibroblasts by inhibiting the kinase activity of Akt.

Hypertrophy is a very common pathologic phenomenon of scar hyperplasia after human skin injury and wound healing. In this article, we first proved that naringin could inhibit the proliferation of fibroblasts by MTT experiments. Flow cytometry indicated that naringin could block the cell cycle and promote apoptosis. Transwell experiments showed that naringin could inhibit the motility activity of fibroblasts. We also found that naringin specifically inhibits the kinase activity of Akt and the phosphorylation of Akt in hypertrophic scar fibroblasts by Kinase-Glo, western blot and real-time PCR assays. Subsequently, western blots and real-time PCR indicated that naringin can inhibit phosphorylation of Akt and downstream proteins of Akt. Our data demonstrated that naringin inhibits the development of hypertrophic scars, at least to a certain extent, by its inhibition of Aktp-Ser473/Thr308.

The Heme Transporter HtsABC of Group A Streptococcus Contributes to Virulence and Innate Immune Evasion in Murine Skin Infections.

Group A Streptococcus (GAS) requires iron for growth, and heme is an important source of iron for GAS. Streptococcus heme transporter A (HtsA) is the lipoprotein component of the GAS heme-specific ABC transporter (HtsABC). The objective of this study is to examine the contribution of HtsABC to virulence and host interaction of hypervirulent M1T1 GAS using an isogenic htsA deletion mutant (ΔhtsA). The htsA deletion exhibited a significantly increased survival rate, reduced skin lesion size, and reduced systemic GAS dissemination in comparison to the wild type strain. The htsA deletion also decreased the GAS adhesion rate to Hep-2 cells, the survival in human blood and rat neutrophils, and increased the production of cytokine IL-1ß, IL-6, and TNF-α levels in air pouch exudate of a mouse model of subcutaneous infection. Complementation of ΔhtsA restored the wild type phenotype. These findings support that the htsA gene is required for GAS virulence and that the htsA deletion augments host innate immune responses.

Overexpression of microRNA-26a protects against deficient ß-cell function via targeting phosphatase with tensin homology in mouse models of type 2 diabetes.

The prevalence of type 2 diabetes mellitus (T2DM) increased rapidly in the world. The development of ß-cell dysfunction is the quintessential defects in T2DM patients However, the pathogenesis of ß-cell dysfunction is still unclear. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of ß-cell dysfunction and T2DM. Here, we investigated the mechanisms by which miR-26a regulate ß-cell function and insulin signaling pathway in high fat diet (HFD) fed and db/db T2DM mice model. The expression of miR-26a was down-regulated dramatically in the serum and islets of both HFD and db/db mice model. miR-26a overexpression protected against HFD-induced diabetes and maintained prolonged normoglycemic time in HFD fed mice. Overexpression of miR-26a improved ß-cell dysfunction in T2DM mice. Further, we identified that PTEN is a direct target gene of miR-26a. Overexpression of miR-26a significantly inhibited the luciferase activity of hPTEN 3'-UTR, while the effect of miR-26a disappeared when the miR-26a potential binding site within the PTEN 3'-UTR was mutated. Overexpression of miR-26a reduced both the mRNA and protein levels of PTEN in vitro and in vivo. We also found that miR-26a overexpression increased the expression of p-Akt and p-FoxO-1, while the effect of miR-26a was blocked by PTEN overexpression. In conclusion, our data indicated that miR-26a potentially contributes to the ß-cell dysfunction in T2DM, and miR-26a may be a new therapeutic strategy against T2DM.

Streptococcal heme binding protein (Shp) promotes virulence and contributes to the pathogenesis of group A Streptococcus infection.

Streptococcal heme binding protein (Shp) is involved in the process of heme acquisition in group A Streptococcus (GAS). However, no research thus far has examined the contribution of Shp to the virulence of GAS. To this end, we generated an isogenic strain lacking the shp gene (Δshp) and its complemented strain (Δshp-c) using the parent strain MGAS5005 (WT). Deletion of shp increased survival rates and neutrophil recruitment and reduced skin lesion sizes and GAS loads in the blood and the liver, lung, kidney and spleen in subcutaneous infections of mice. These results indicate that Shp significantly contributes to the skin and systemic invasion of GAS. The growth of the Δshp mutant was significantly slower than MGAS5005 and Δshp-c than in non-immune human blood and in incubation with isolated rat neutrophils. Microarray transcriptional analyses found no alteration in expression of virulence genes, indicating that the phenotype of the Δshp mutant was directly linked to the lack of Shp. The findings indicate that Shp significantly contributes to GAS skin invasion, systemic infection and virulence and that these contributions of Shp are mediated by the effects of Shp on systemic GAS growth and neutrophil responses.

Immunization with Streptococcal Heme Binding Protein (Shp) Protects Mice Against Group A Streptococcus Infection.

Streptococcal heme binding protein (Shp) is a surface protein of the heme acquisition system that is an essential iron nutrient in Group A Streptococcus (GAS). Here, we tested whether Shp immunization protects mice from subcutaneous infection. Mice were immunized subcutaneously with recombinant Shp and then challenged with GAS. The protective effects against GAS challenge were evaluated two weeks after the last immunization. Immunization with Shp elicited a robust IgG response, resulting in high anti-Shp IgG titers in the serum. Immunized mice had a higher survival rate and smaller skin lesions than adjuvant control mice. Furthermore, immunized mice had lower GAS numbers at the skin lesions and in the liver, spleen and lung. Histological analysis with Gram staining showed that GAS invaded the surrounding area of the inoculation sites in the skin in control mice, but not in immunized mice. Thus, Shp immunization enhances GAS clearance and reduces GAS skin invasion and systemic dissemination. These findings indicate that Shp is a protective antigen.

miRNA-34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a fast progressing vascular disease characterized by uncontrolled cell proliferation of pulmonary artery smooth muscle cells (PASMCs). Some studies have suggested that PAH and cancers share an apoptosis-resistant state, featuring excessive cell proliferation. The miR-34 family consists of tumour-suppressive miRNAs, and its reduced expression has been reported in numerous cancers; however, its role in hypoxia-induced PAH has not been previously studied. MATERIALS AND METHODS: miR-34 family expression was evaluated in a rat model with hypoxia and in cultured hypoxic PASMCs, using real-time quantitative PCR (RT-qPCR). Function of miR-34 family was assessed by transfecting miR-34 mimics and inhibitors. Dual luciferase reporter gene assays, RT-qPCR and Western blotting were performed to validate target genes of miR-34. RESULTS: Significant down-regulation of miR-34a in hypoxic lung tissue, pulmonary artery and PASMCs was identified and then effects of miR-34a in modulating cell proliferation in human pulmonary artery smooth muscle cells (hPASMCs) was investigated in vitro. Reduction of miR-34a levels in hPASMCs caused increased proliferation and these effects were reversed by overexpression of miR-34a. miR-34a overexpression down-regulated platelet-derived growth factor receptor alpha (PDGFRA) expression, which is a key factor in PAH development. These results suggest that miR-34a is a potential regulator of proliferation in PASMCs, and that it could be used as a novel treatment strategy in PAH.

Arsenic induced overexpression of inflammatory cytokines based on the human urothelial cell model in vitro and urinary secretion of individuals chronically exposed to arsenic.

Chronic persistent inflammation could play an important role in the pathogenesis of some malignancies, and inflammation is a critical factor for bladder cancer development. In this study, we measured urine levels of transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α), and IL-8 in arsenic exposure workers and expressions of inflammatory cytokines in human urothelial cells in vivo and in vitro. We found the concentrations of IL-8, TNF-α, and TGF-α presented in urine were significantly elevated in the high urinary arsenic workers compared with the low urinary arsenic workers. Multiple regression analysis showed that the urinary IL-8 level was significantly positively associated with urinary iAs concentration after adjusting for the confounding effects of age, employed years, body mass index (BMI), smoking, alcohol, and seafood consumption in recent 3 days. Urinary TNF-α and TGF-α levels were also significantly positively associated with urinary iAs concentration, and SMI. TGF-α level was negatively associated with age after adjusting for the confounding effects. Consistent with the results in vivo, mRNA expressions of TNF-α, TGF-α, and IL-8 and protein expressions of TGF-α, TGF-ß1, and IL-8 were significantly elevated in SV-HUC-1 cells after exposure to lower concentrations of arsenite for 24h as compared to the control group. These data indicated that arsenic increased the secretion of inflammatory factors and IL-8, TNF-α, and TGF-α expression may be a useful biomarker of the effect of arsenic exposure.

Urinary VEGF and PGE2 levels and the association with arsenical metabolites in copper-smelting workers.

OBJECTIVES: To examine vascular endothelial growth factor (VEGF) and PGE2 levels in urine from the copper smelting workers exposed to arsenic and analyse the relationships between urinary VEGF or PGE2 level and arsenical metabolites. METHODS: The study was conducted in a group of 106 copper-smelting male workers. Information about each subject was obtained by questionnaire, inorganic As (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), VEGF and prostaglandin E2 (PGE2) in urine were determined. Standing height, body weight, and blood pressure were measured. RESULTS: According to the urine arsenic levels, participants were separated into three groups: Group 1: urine total arsenic <35 mg/L, Group 2: 35-100 mg/L, and Group 3: >100 mg/L. The median levels of urinary VEGF and PGE2 in Groups 1, 2 and 3 were 10.57 and 1032.0 pg/mL, 24.39 and 1060.9 pg/mL, and 49.0 and 1330.4 pg/mL, respectively. Urinary VEGF levels were positive associated with arsenical metabolites (iAs, MMA, DMA and TAs). Additionally, urinary VEGF and PGE2 levels were all correlated positively with the urinary MMA% (r=0.221, p=0.026 and r=0.206, p=0.037). While urinary VEGF was negatively with DMA% and secondary methylation index (r=-0.242, p=0.014 and r=-0.214, p=0.030, respectively). CONCLUSIONS: Urinary VEGF and PGE2 levels increased in arsenic exposure copper smelting workers, and urinary VEGF levels are well associated with the urinary arsenicals. This finding may provide useful information for developing measurement, prevention and treatment of damage induced by arsenic in the future.

Thermal-induced formation of a three-dimensional nanoplasmonic sensor from Ag nanocubes with high stability and reusability.

Nanoplasmonic sensors based on the localized surface plasmon resonance (LSPR) of noble metal nanoparticles have many advantages, such as real-time detection, no need for reagent labelling, and no use of complicated equipment. However, the nanoplasmonic sensors with two dimensional structures usually suffer from a low LSPR signal and thus low sensitivity due to the low density of the nanoparticles. In addition, complicated surface functionalization is always required to suppress the non-specific binding of the analyst to the substrate of the sensor, because the two types of surface, that is, metal and substrate surfaces, are simultaneously exposed to the reaction medium. To overcome these problems, an innovative thermal-induced method has been proposed in the present work, to construct three dimensional (3D) nanostructure of Ag nanocubes on both surfaces of the substrate by using the unique amphiphilic property of 2-diethylaminoethanethiol. The prepared nanoplasmonic sensor is highly sensitive due to the high density of 3D structure of the nanoparticles and the low non-specific binding since only one type of surface is exposed. To enhance the stability of the sensor, a thin SiO2 overlayer was formed on the surface without using an additional coupling agent. Furthermore, the Ni(II)-nitriloacetic acid (Ni(II)-NTA) complex was covalently bound on the surface, so that the regeneration and reuse of the sensor becomes easy. Therefore, the easy fabrication, high stability, and good reusability of this 3D LSPR sensor makes our method competitive for the development of nanoplasmonic sensors.

Maize purple plant pigment protects against fluoride-induced oxidative damage of liver and kidney in rats.

Anthocyanins are polyphenols and well known for their biological antioxidative benefits. Maize purple plant pigment (MPPP) extracted and separated from maize purple plant is rich in anthocyanins. In the present study, MPPP was used to alleviate the adverse effects generated by fluoride on liver and kidney in rats. The results showed that the ultrastructure of the liver and kidney in fluoride treated rats displayed shrinkage of nuclear and cell volume, swollen mitochondria and endoplasmic reticulum and vacuols formation in the liver and kidney cells. MPPP significantly attenuated these fluoride-induced pathological changes. The MDA levels in serum and liver tissue of fluoride alone treated group were significantly higher than those of the control group (p < 0.05). The presence of 5 g/kg MPPP in the diet reduced the elevation of MDA levels in blood and liver, and increased the SOD and GSH-Px activities in kidney and GSH level in liver and kidney compared with the fluoride alone treated group (p < 0.05). In addition, MPPP alleviated the decrease of Bcl-2 protein expression and the increase of Bax protein expression induced by fluoride. This study demonstrated the protective role of MPPP against fluoride-induced oxidative stress in liver and kidney of rats.

Progress in development of Group A Streptococcus vaccines.

Streptococcus pyogenes or Group A Streptococcus (GAS) is a major Gram-positive human pathogen that causes diverse human diseases with a high morbidity and mortality worldwide. The development of an effective GAS vaccine is hindered by the occurrence of many unique GAS serotypes, the complexity of the global epidemiology of GAS infections, and safety concerns over the cross-reactivity of some antigen-specific antibodies with human tissues and proteins. Although no licensed GAS vaccine is available, a number of candidate vaccines have been or are being evaluated in laboratory or in clinical trials. This minireview provides brief information on the progress and difficulty in the development of GAS vaccines.

JNK and NADPH oxidase involved in fluoride-induced oxidative stress in BV-2 microglia cells.

Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF- α , IL-1 ß inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2(·-) and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells.

Arsenic induces the expressions of angiogenesis-related factors through PI3K and MAPK pathways in SV-HUC-1 human uroepithelial cells.

Arsenic, a well-established human carcinogen, can cause various types of cancers, including bladder cancer. Angiogenesis is a key event for tumor initiation. In this study, several important angiogenesis related factors, including cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α), were up-regulated and PI3K/AKT and MAPK signal pathways were activated in human uroepithelial cell line (SV-HUC-1) treated with NaAsO2 (0, 1, 2, 4, 8 or 10µM) for 24h. Arsenite-induced HIF-1α, VEGF and COX-2 expressions were decreased by PI3K inhibitors. Blockage of the ERK1/2, p38 and JNK down-regulated the VEGF level, while ERK1/2 and p38 inhibitors were more effective than JNK in attenuating arsenite-induced COX-2 expression. HIF-1α expression was only decreased by ERK1/2 inhibitor. It was found that superoxide (O2(-)) generation was involved in arsenite-induced the activation of MAPK and PI3K pathways, which led to the HIF-1α, COX-2 and VEGF overexpressions. In conclusion, arsenite-induced COX-2, VEGF and HIF-1α expressions, mediated partially by reactive oxygen species (ROS), were regulated by MAPK and PI3K/AKT signaling pathways in human uroepithelial cells.