Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials.

Dietary astaxanthin supplementation has been demonstrated to have many beneficial and health-promoting effects. The purpose of this systematic review and meta-analysis was to assess the effect of astaxanthin supplementation on fatigue, cognition, and exercise efficiency. A total of 11 randomized controlled trials (RCTs) with 346 healthy participants were included. The random effects model and pooled standardized mean difference (SMDs) were used according to Hedge's g for the meta-analysis, and a meta-regression was also conducted. The results of the two existing studies showed a positive trend for astaxanthin in subjective fatigue relief. The effects of astaxanthin supplementation for 8-12 weeks on cognitive accuracy were marginally significant (SMD: .12; 95% CI: -.02-.26) and on reaction time was not significant (SMD: -.08; 95% CI: -.26 to .10). Remarkably, astaxanthin supplementation combined with regular training could enhance the fat oxidation (SMD: 2.56; 95% CI: 1.24-3.89), and significantly improve the physical performance (SMD: .62; 95% CI: .17-1.06). The subgroup analysis further showed significantly greater benefits when performing the aerobic exercises performance (SMD: .45; 95% CI: .13-.76), when the dose was ≥ 20 mg (SMD: .37; 95% CI: .11-.63), and when the supplementation duration was > 12 weeks (SMD: .66; 95% CI: .13-.63). We conclude that astaxanthin supplementation could significantly enhance aerobic exercise efficiency, especially at higher doses and for longer durations. Further studies based on large sample sizes are imperatively warranted.

Astaxanthin could regulate the gut-kidney axis to mitigate kidney injury in high-fat diet/streptozotocin-induced diabetic mice.

Accumulating evidences have shown the beneficial effects of astaxanthin (AST) supplementation on metabolic diseases prevention and treatment. The goal of present study was to reveal the favorable interactions among AST supplementation, gut microbiota, and kidneys in vivo, so as to attenuate kidney impairment in diabetic mice. Twenty C57BL/6J mice were assigned to a normal control group and a diabetic model group induced by a high-fat diet plus low-dose streptozotocin, and then the diabetic mice were fed with a high-fat diet without or with AST [0.01% (AST_a) or 0.02% (AST_b)] for 12 weeks. When compared to the diabetes kidney disease (DKD) group, AST supplementation delayed the renal pathological progression, reduced fasting blood glucose (AST_b: 1.53-fold, p<0.05), repressed levels of lipopolysaccharide (LPS; AST_a: 1.24-fold, p=0.008; AST_b: 1.43-fold, p<0.001) and TMAO (AST_a: 1.51-fold, p=0.001; AST_b: 1.40-fold, p=0.003), inhibited IL-6 (AST_a: 1.40-fold, p=0.004; AST_b: 1.57-fold, p=0.001) and reactive oxygen species (ROS; AST_a: 1.30-fold, p=0.004; AST_b: 1.53-fold, p<0.001), as well as regulated the Sirt1/PGC-1α/NFκB p65 signaling pathway. Moreover, the results of 16S rRNA gene-based Illumina deep sequencing in each group revealed that dietary AST supplementation also favorably modulated the gut microbiota compared with the DKD group, as evidenced by the inhibition of the harmful bacteria Clostridium_sensu_stricto_1, Romboutsia, and Coriobacteriaceae_UCG-002, and the enhancement of the probiotics such as Lachnospiraceae_NK4A136_group, Roseburia, and Ruminococcaceae. Taken together, dietary AST supplementation could protect kidneys against inflammation and oxidative stress by adjusting the gut-kidney axis in diabetic mice.

[Cypermethrin induced liver oxidative DNA damage via the JNK/c-Jun pathway].

OBJECTIVE: To clarify the adverse effect of cypermethrin(CYP) on the liver and explore the underlying role of the MAPK pathway. METHODS: Twenty-four Sprague-Dawley(SD) rats were exposed to 0, 5, 10 and 20 mg/(kg·d) ß-CYP by gavage for 31 days. Histomorphological and ultrastructural changes were evaluated by the hematoxylin & eosin(HE) staining and transmission electron microscope(TEM). Levels of MDA and 8-OHdG were detected by ELISA. Expressions of p-JNK and γ-H2A. X were assessed by IHC and IF respectively. RT-PCR was performed to examine mRNA levels of GPx1, GPx4, SOD1, and SOD2 in rat testes. Western blot was conducted to determine protein expressions of GPx1, SOD2, CAT, γ-H2A. X, and the MAPK pathway-associated proteins in rat testes. RESULTS: After ß-CYP exposure, the histomorphology and ultrastructures of rat livers were abnormally altered, as evidenced by hepatic sinusoidal dilation, hepatic plate space formation, mitochondrial crest fracture, etc. Moreover, ß-CYP induced mRNA levels of GPx1, GPx4, SOD1 and SOD2, as well as protein expressions of GPx1 and SOD2 in the liver. Compared to the control, GPx1 and SOD2 protein expressions were decreased by 57.9% and 50.0%(P<0.05), whereas the MDA level was increased by 56.2%(P<0.05) in the high-dose group. Additionally, the JNK/c-Jun pathway, one of MAPK pathways, in the liver was activated by ß-CYP, as shown by the increase of JNK and c-Jun phosphorylation, and protein expressions of p-JNK and p-c-Jun in the high-dose group were elevated by 47.7% and 46.5%(P<0.05) in comparison to the control, but the ERK and p38 pathways were not affected after ß-CYP exposure. Furthermore, ß-CYP promoted 8-OHdG and γ-H2A. X expressions in the liver. Compared to the control, γ-H2A. X protein expression in the mid-and high-dose group was upregulated by 16.9% and 33.9%(P<0.05), respectively. CONCLUSION: Cypermethrin had detrimental effects on the liver. CYP not only directly altered liver histomorphology and ultrastructures, but also caused oxidative stress, which activated the JNK/c-Jun pathway, finally inducing the DNA damage.

JNK and Jag1/Notch2 co-regulate CXCL16 to facilitate cypermethrin-induced kidney damage.

Cypermethrin (CYP), a widely-used composite pyrethroid pesticide, has underlying nephrotoxic effects. To elucidate potential roles of the MAPK pathway, the Jag/Notch pathway, and miRNAs in CYP-mediated kidney lesion, Sprague-Dawley rats and glomerular mesangial cells were used in this work. Results displayed that ß-CYP abnormally altered renal histomorphology and ultrastructures, induced renal DNA damage, and impaired renal functions, as evidenced by the increase in plasma levels of Cys-C and ß2-Mg. ß-CYP activated the JNK/c-Jun pathway by inducing ROS and oxidative stress. Meanwhile, ß-CYP changed the miRNA expression profile, miR-21-5p showing the most significant increase. Moreover, the Jag1/Notch2/Hes1 pathway was directly targeted by miR-21-5p, the mRNA and protein expression of Jag1, Notch2, and Hes1 being declined in vivo and in vitro. The chemokine CXCL16 was induced by ß-CYP, accompanied by the inflammatory factor production and inflammatory cell infiltration in kidneys. The specific JNK inhibitor, Jag1 overexpression, Hes1 overexpression, bidirectional Co-IP, ChIP, and CXCL16 silencing demonstrated that CXCL16 co-regulated by the JNK/c-Jun and Jag1/Notch2/Hes1 pathways elicited renal inflammation. Collectively, our findings indicate that ß-CYP is of nephrotoxicity and it not only directly changes renal histomorphology and ultrastructures, but induces CXCL16 to trigger renal inflammation via the JNK/c-Jun and Jag1/Notch2/Hes1 pathways, finally synergistically contributing to kidney damage.

Intronic miR-140-5p contributes to beta-cypermethrin-mediated testosterone decline.

Beta-cypermethrin (ß-CYP), a widely-used pyrethroid pesticide, is considered to have anti-androgenic effects and could impair male reproduction. To ascertain whether MAPK pathways, DNA methyltransferases (DNMTs), and miRNAs played pleiotropic roles in ß-CYP-mediated testicular dysfunction, Sprague-Dawley rats and Leydig cells were employed in this study. Results showed that plasma testosterone levels were declined, testicular histomorphology and ultrastructures were abnormally altered, and Leydig cell functions were damaged after ß-CYP exposure. JNK and p38/MAPK pathways were inactivated, accompanied by the decrease in c-Jun and Sp1 expressions. Specific activators/inhibitors of MAPK pathways and Co-IP demonstrated that DNMT3α was synergistically regulated by JNK/p38 pathways. The activity, mRNA and protein expressions of DNMT3α were all reduced by ß-CYP. ß-CYP induced expressions of intronic miR-140-5p and its host gene Wwp2, and then overexpressed miR-140-5p suppressed steroidogenic StAR, P450scc, and 3ß-HSD by directly targeting SF-1. SF-1 silencing/overexpression, ChIP, and qPCR indicated that SF-1 modulated positively StAR, P450scc, and 3ß-HSD expressions by directly binding to their promoter regions. Intriguingly, 5α-reductase expressions were downregulated after ß-CYP exposure. Collectively, ß-CYP has the anti-androgenic feature and the DNMT3α/miR-140-5p/SF-1 cascade co-regulated by JNK/p38 functions critically in ß-CYP-caused testosterone declines. The downregulation of 5α-reductases may be a potential compensatory mechanism of the organism.

Efficacy of Tai Chi on Patients With Chronic Kidney Disease.

Previous systematic reviews elucidate the efficacy of Tai Chi on the rehabilitation and treatment for various chronic diseases. Yet, no consensus has been reached on its efficacy and safety from those with chronic kidney disease (CKD). Therefore, we conducted a systematic review to critically summarize what is already known about the prevailing benefits of Tai Chi for CKD patients. There was no evidence that Tai Chi had adverse effects on CKD patients. Long-term Tai Chi exercises could improve quality of life, cardiorespiratory fitness, and physical motor function for the end-stage renal disease (ERSD) patients undergoing dialysis. Regular Tai Chi exercises might exert modest influences in delaying CKD progression for mild-moderate CKD patients. However, there is insufficient evidence to demonstrate positive effects of Tai Chi exercises on bone health of the ESRD patients. Accordingly, rigorously designed, longer-term studies of Tai Chi are warranted to identify its efficacy on CKD patients across different stages, especially targeting potential mechanisms in terms of Tai Chi altering biological gene profile expressions.

Factors promoting shared decision-making in renal replacement therapy for patients with end-stage kidney disease: systematic review and qualitative meta-synthesis.

PURPOSE: Shared decision-making (SDM) about the type of renal replacement therapy to use is a matter of great importance involving patients, their families, and health treatment teams. This review aims to synthesize the volume of qualitative work explaining the factors influencing SDM regarding renal replacement therapy. METHODS: A systematic review and qualitative meta-synthesis approach recommended by JBI was used, six databases were searched. Studies were qualitative or mixed research published since 2000, with a primary focus on patient experiences, perceptions and practices regarding which method to choose for renal replacement therapy in End-Stage Kidney Disease (ESKD) patients. All themes were analyzed and compared to the established connectedness. RESULTS: A total of 1313 patients were enrolled in 32 studies focusing on factors associated with SDM regarding renal replacement therapy were included. All quality evaluations of the literature were medium to high. Four common themes were identified in our synthesis: (1) patient personal reasons, (2) family-related factors, (3) health care professional-related factors, and (4) social factors influence. CONCLUSION: The model proposes pathways that could be explored further in future qualitative and quantitative studies and suggests that patients' beliefs, emotions, and awareness should be targeted alongside patients' decision-making practices to increase the efficacy of interventions. The majority of studies included in this review focus on older patients, and all report patients' perspectives. Further research is required to understand the family member perspectives on SMD of renal replacement therapy.

PKCα mediated by the PI3K/Akt-FOXA1 cascade facilitates cypermethrin-induced hyperthyroidism.

Cypermethrin (CYP), a broad-spectrum pyrethroid insecticide is extensively used. CYP is also considered as a potential endocrine disruptor with the thyroid-disturbing property. Protein kinase C alpha (PKCα) is a pleiotropic signal transduction molecule that functions crucially in thyroid hormone (TH) homeostasis and thyroid functions. To explore underlying roles of PKCα in CYP-mediated disturbance of TH homeostasis, Sprague-Dawley rats and rat thyroid cells were used in this study. Results showed that ß-CYP stimulated TH biosynthesis, as shown by the increase in plasma levels of TT4, FT4, TT3, FT3, and TSH. After ß-CYP treatment, expressions of PKCα, three miRNAs (miR-17-5p, miR-330-3p, and miR-331-3p), thyroid transcription factor TTF-1, and thyroid-specific proteins (TSHr, TPO, and Tg) were significantly increased, while expressions of PI3K p110α, p-Akt, FOXA1, and thyroid transcription factors (TTF-2 and Pax8) were decreased. Further studies found that ß-CYP induced PKCα translation by the miR-330-3p-targeted PI3K/Akt-FOXA1 cascade and then PKCα positively regulated TTF-1 to promote TPO and Tg expressions, which in turn facilitated TH biosynthesis. Likewise, PKCα positively modulated TSHr expressions to strengthen the TSH/TSHr signal in the HPT axis, thereby synergistically contributing to TH biosynthesis. Moreover, ß-CYP also disturbed TH biotransformation and biotransport by inducing DIO1 and inhibiting DIO3 in thyroids and TTR expressions in livers. Taken together, ß-CYP has the thyroid-disturbing effect and could promote TH biosynthesis, and PKCα plays vital roles in ß-CYP-caused hyperthyroidism.

miR-142-5p/DAX1-dependent regulation of P450c17 contributes to triclosan-mediated testosterone suppression.

Triclosan (TCS) is a potent antibacterial and antifungal compound that is extensively used in various daily products. TCS is also considered as an underlying endocrine disruptor and has anti-androgenic effects. In our previous work, we found that TCS suppressed testicular steroidogenesis via the miR-6321/JNK/Nur77 cascade, but roles of the abnormal expression of miR-142-5p and P450c17 in this molecular event were still unknown. Therefore, to verify the hypothesis that miR-142-5p and P450c17 might significantly function in other manner in testosterone decline after TCS exposure, Sprague-Dawley rats and the rat Leydig cell line were used in this study. Results showed that after TCS exposure, testicular histomorphology was abnormally changed and testosterone level was declined. Overexpressed miR-142-5p by TCS directly targeted the JAK1/STAT1 pathway. Bidirectional Co-IP assays and the use of STAT1 activator demonstrated that STAT1 could interact with and regulate Sp1. The activity, mRNA level, and protein expression of DNMT1 and DNMT3ß were all decreased after TCS treatment. Sp1 silencing, ChIP, and qPCR assays showed that Sp1 regulated DNMT1 expressions by directly binding to the promoter region of DNMT1. Though the DNA methylation status of the DAX1 promoter was not affected, TCS induced the transcription and translation of DAX1 by DNMT1, in turn leading to the inhibition of steroidogenic P450c17. Taken together, TCS-induced miR-142-5p inhibits P450c17 by the JAK1/STAT1 pathway and downstream Sp1/DNMT1/DAX1 cascade, finally facilitating the decrease in testosterone levels.

MicroRNA-3064-5p sponged by MALAT1 suppresses angiogenesis in human hepatocellular carcinoma by targeting the FOXA1/CD24/Src pathway.

Angiogenesis is critical for the development, progression, and metastasis of hepatocellular carcinoma (HCC), but the roles of miR-3064-5p in HCC angiogenesis are still unknown. In this study, the roles of miR-3064-5p in HCC angiogenesis were studied in 192 HCC patients, xenograft mouse models, and HCC cell lines. The results showed that miR-3064-5p expression was significantly decreased in HCC tissues and cells, and downregulated miR-3064-5p was associated with upregulated angiogenic potential of HCC. MiR-3064-5p inhibited proangiogenic VEGFA and angiogenin expressions but induced antiangiogenic endostatin and MMP12 expressions, finally leading to suppression of HCC angiogenesis, as shown by the decline in intratumoral microvessel density (MVD). Moreover, miR-3064-5p was inversely correlated with lncRNA MALAT1 and FOXA1. FOXA1 bound to and interacted with CD24 and then regulated Src phosphorylation. MiR-3064-5p played an antiangiogenic role by inhibiting the FOXA1/CD24/Src pathway, whereas oncogenic MALAT1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-3064-5p to alleviate the suppressive effect on the FOXA1 pathway. HCC patients with high miR-3064-5p, low MALAT1, or low FOXA1 expression had a better prognosis with longer overall survival and recurrence-free survival. In univariate and multivariate analyses, miR-3064-5p was identified as the independent prognostic predicator for HCC progression and patient survival. Taken together, miR-3064-5p exerts an antiangiogenic role by targeting the FOXA1/CD24/Src pathway but oncogenic lncRNA MALAT1 acts as a ceRNA to sponge miR-3064-5p. MiR-3064-5p is of great clinical significance and is a novel prognostic indicator and an attractive therapeutic target for HCC.

Relationships of social support, health-promoting lifestyles, glycemic control, and bone turnover among adults with type 2 diabetes.

AIM: There is increasing evidence that hyperglycemia, oxidative stress, and the accumulation of advanced glycation end products in type 2 diabetes mellitus (T2DM) can lead to the deterioration of bone remodeling. The purpose of this study was to explore relationships of social support, health-promoting lifestyles, glycated hemoglobin (HbA1c) levels, and serum bone turnover markers (BTMs, including procollagen type I amino-terminal propeptide [PINP] and ß-isomerised carboxy-terminal cross-linking telopeptide of type I collagen [ß-CTX]) among individuals with T2DM. METHODS: A total of 175 subjects were recruited by convenience sampling and divided into three groups based on their HbA1c levels. Statistical strategies of Spearman's correlation coefficient and multiple linear regression were used in this cross-sectional study. RESULTS: There was a positive association between PINP and ß-CTX, whereas the HbA1c level was inversely correlated with BTMs. Moreover, scores of both PINP and ß-CTX were different in genders, males having lower levels of BTMs than females after adjustment for weight. Furthermore, both social support and health-promoting lifestyles were negatively correlated with HbA1c levels, whereas they did not significantly relate to declines in PINP and ß-CTX. CONCLUSION: High HbA1c levels detrimentally influence bone formation and bone resorption, and males with T2DM might be more susceptible to osteoporosis because of their relatively lower levels of BTMs. However, social support and health-promoting lifestyles could contribute to better glycemic control.

Triclosan Suppresses Testicular Steroidogenesis via the miR-6321/JNK/ Nur77 Cascade.

BACKGROUND/AIMS: Triclosan (TCS), a broad-spectrum antibacterial and antifungal compound and an endocrine disruptor, has anti-androgenic properties and could adversely affect male reproduction and fertility. METHODS: To elucidate the underlying roles of miRNAs and the MAPK pathway in TCS-mediated repression of testicular steroidogenesis, Sprague-Dawley male rats were dosed daily with TCS for 31 days, and TM3 cells were exposed to TCS for 24 h after the pretreatments with the activator of JNK, Nur77 siRNA, or recombinant lentivirus vector for Nur77. Tissues and/or cells were analyzed by several techniques including transmission electron microscopy, lentivirus production, overexpression, gene silencing, luciferase reporter assay, chromatin immunoprecipitation, western blot, and real-time PCR. RESULTS: TCS caused histopathologic alterations in the testis and reduced plasma LH and testicular testosterone. TCS induced miR-6321 expression, which in turn depressed its target gene, Map3k1. The inhibition of Map3k1 subsequently inactivated its downstream JNK/c-Jun pathway. ChIP and qPCR assays confirmed that c-Jun directly bound to the Nur77 DNA promoter regions to regulate Nur77 expression. The knockdown and overexpression of Nur77 demonstrated that the JNK/c-Jun-mediated decline in the transcription and translation of Nur77 resulted in the depression of steroidogenic proteins including SRB1, StAR, and 3ß-HSD. Intriguingly, the protein expressions of 5α-Reductases (SRD5A1 and SRD5A2) were also downregulated after TCS exposure. CONCLUSION: Taken together, the miR-6321/Map3k1-regulated JNK/c-Jun/ Nur77 cascade contributes to TCS-caused suppression of testicular steroidogenesis, and the decrease in 5α-Reductase expressions may be the compensatory mechanism.

Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes.

Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP.

Di-(2-ethylhexyl) phthalate inhibits testosterone level through disturbed hypothalamic-pituitary-testis axis and ERK-mediated 5α-Reductase 2.

Di-(2-ethylhexyl) phthalate (DEHP) has reproductive toxicity and can affect male reproductive development. In order to clarify adverse effects of DEHP on testicular physiology and testosterone production, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30days; TM3 cells (mouse Leydig cell line) were treated with DEHP for 24h after pretreatment with vitamin C or U0126. Results indicated that the hypothalamic-pituitary-testis (HPT) axis was disturbed and serum testosterone, LH and FSH levels were decreased following DEHP exposure. Histomorphological changes of rat testes were also observed, such as deformed seminiferous tubules, aggregated chromatin, multiple vacuoles, swollen mitochondria, apoptotic germ cells and Sertoli cells, as well as increased Leydig cell numbers. Moreover, DEHP caused oxidative stress in vivo and in vitro and then induced the ERK pathway, which was required to mediate 5α-Reductase 2 and scavenger receptor class B-1 (SRB1) levels. However, levels of steroidogenic acute regulatory protein (StAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), P450 17α-hydroxylase/17.20 lyase (P450c17), and P450 side-chain cleavage enzyme (P450scc) were not significantly altered after DEHP exposure. Taken together, DEHP-disturbed HPT axis and induced 5α-Reductase 2 contribute to the reduction of serum testosterone level. The activated ERK pathway is required to modulate expressions of 5α-Reductase 2 and SRB1.

Reliability and Validity of a Chinese Version of the Stroke Action Test: A New Instrument for Assessment of Stroke Knowledge and Response.

BACKGROUND: The public's cognition of stroke and responses to stroke symptoms are important to prevent complications and decrease the mortality when stroke occurs. The aim of study was to develop and validate the Chinese version of the Stroke Action Test (C-STAT) in a Chinese population. METHODS: This study was rigorously implemented with the published guideline for the translation, adaptation and validation of instruments for the cross-cultural use in healthcare care research. A cross-sectional study was performed among 328 stroke patients and family members in the Department of Neurology in the Second Hospital of Lanzhou University, Gansu province, China in 2014. RESULTS: The Chinese version of the instrument showed favorable content equivalence with the source version. Values of Cronbach's alpha and test-retest reliability of the C-STAT were 0.88 and 0.86, respectively. Principal component analysis supported four-factor solutions of the C-STAT. Criterion-related validity showed that the C-STAT was a significant predictor of the 7-item stroke symptom scores (R = 0.77; t = 21.74, P< 0.001). CONCLUSION: The C-STAT is an intelligible and brief psychometrical tool to assess individuals' knowledge of the appropriate responses to stroke symptoms in Chinese populations. It could also be used by health care providers to assess educational programs on stroke prevention.

p53-dependent apoptosis contributes to di-(2-ethylhexyl) phthalate-induced hepatotoxicity.

Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread non-occupational human exposure through multiple routes and media. DEHP has various deleterious effects including hepatotoxicity. p53 protein is a central sensor in cell apoptosis. In order to clarify the roles of p53 in DEHP-induced hepatotoxicity, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30 days; BRL cells (rat liver cell line) were treated with DEHP for 24 h after pretreatment with NAC or small interfering RNA (siRNA). Results indicated that after exposure to DEHP, hepatic histological changes such as hepatocyte edema, vacuolation and hepatic sinusoidal dilation, and increased apoptosis index were observed. In the liver, DEHP induced oxidative stress and DNA damage, which activated p53 in vivo and in vitro. Pretreatment with NAC significantly reduced ROS level and p53 expression in BRL cells. The suppressed Mdm2 also contributed to p53 accumulation. Activated p53 mediated hepatocyte apoptosis via the intrinsic mitochondrial pathway, inhibiting anti-apoptotic Bcl-2 and Bcl-xL and inducing pro-apoptotic Bax, cytochrome c and caspases. In p53-silenced BRL cells, hepatocyte apoptosis mediated by p53 was attenuated. PCNA protein level was upregulated after p53 gene silencing. However, the Fas/FasL apoptotic pathway did not exhibit activated signs in DEHP-caused hepatotoxicity. Taken together, DEHP-caused oxidative stress and Mdm2 downregulation contribute to p53 activation. The p53-dependent apoptotic pathway plays critical and indispensable roles in DEHP-induced hepatotoxicity, while the Fas/FasL pathway does not involve in this molecular event.

The PI3K/Akt and ERK pathways elevate thyroid hormone receptor ß1 and TRH receptor to decrease thyroid hormones after exposure to PCB153 and p,p'-DDE.

PCBs and DDT cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. To test the hypothesis that the PI3K/Akt and MAPK pathways would play significant roles in TH imbalance caused by PCBs and DDT, Sprague-Dawley rats were dosed with PCB153 and p,p'-DDE intraperitoneally for 5 consecutive days, and human thyroid follicular epithelial (Nthy-ori 3-1 cell line) were treated with PCB153 and p,p'-DDE for different time. Results showed that serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were decreased, whereas serum free triiodothyronine (FT3) and thyrotropin releasing hormone (TRH) were not changed. The PI3K/Akt and ERK pathways were activated in vivo and in vitro after the treatment with PCB153 and p,p'-DDE. Moreover, TH receptor ß1 (TRß1) was elevated after the activation of the PI3K/Akt pathway and was depressed after the inhibition of the PI3K/Akt pathway; TRH receptor (TRHr) was increased after the activation of the ERK pathway and was decreased after the inhibition of the ERK pathway. Though TH receptor α1 (TRα1) level was increased in the hypothalamus, TRα1 and TSHr were not influenced by the status of signaling pathways in in vitro study. Taken together, after exposure to PCB153 and p,p'-DDE, activated PI3K/Akt and ERK pathways disrupt the hypothalamic-pituitary-thyroid (HPT) axis via TRß1 and TRHr and then decrease TH levels, and that would be a potential mechanism by which PCBs and DDT disturb TH homeostasis.

PCB153 and p,p'-DDE disorder thyroid hormones via thyroglobulin, deiodinase 2, transthyretin, hepatic enzymes and receptors.

Polychlorinated biphenyls (PCBs) and DDT are widespread environmental persistent organic pollutants that have various adverse effects on reproduction, development and endocrine function. In order to elucidate effects of PCBs and DDT on thyroid hormone homeostasis, Sprague-Dawley rats were dosed with PCB153 and p,p'-DDE intraperitoneally (ip) for five consecutive days and sacrificed within 24 h after the last dose. Results indicated that after combined exposure to PCB153 and p,p'-DDE, total thyroxine , free thyroxine, total triiodothyronine, and thyroid-stimulating hormone in serum were decreased, whereas free triiodothyronine and thyrotropin-releasing hormone were not affected. Thyroglobulin and transthyretin levels in serum were significantly reduced. mRNA expression of deiodinases 2 (D2) was also suppressed, while D1 and D3 levels were not significantly influenced after combined exposure. PCB153 and p,p'-DDE induced hepatic enzymes, UDPGTs, CYP1A1, CYP2B1, and CYP3A1 mRNA expressions being significantly elevated. Moreover, TRα1, TRß1, and TRHr expressions in the hypothalamus displayed increasing trends after combined exposure to PCB153 and p,p'-DDE. Taken together, observed results indicate that PCB153 and p,p'-DDE could disorder thyroid hormone homeostasis via thyroglobulin, deiodinase 2, transthyretin, hepatic enzymes, and hormone receptors.

The effects of an educational self-efficacy intervention on osteoporosis prevention and diabetes self-management among adults with type 2 diabetes mellitus.

BACKGROUND: Prevalence of osteoporosis (OP) is high among Chinese adults with diabetes. Assessment of OP and fracture risk as well as patient education should be included as part of the management of diabetes. PURPOSE: The purpose of this pilot study was to test the effectiveness of an educational self-efficacy intervention on knowledge about OP, dietary calcium intake, the importance of physical activity (PA), and glycemic control among Chinese adults with type 2 diabetes residing in Wuhan, China. METHOD: A quasi-experimental design with repeated measures was employed. Participants were assigned to either the intervention (n = 23) or the control group (n = 23). Intervention participants attended 6 weekly 1-hr educational sessions comprising presentations, demonstration, and discussions. Control participants received standard care. Data were collected via questionnaires at pre- and postintervention and at 3-month follow-up, and blood was drawn at preintervention and 3-month follow-up. RESULTS: Participants in the intervention group had significant improvement in OP knowledge, F(2, 43) = 11.504, p < .001; OP self-efficacy, F(2, 43) = 6.915, p = .003; dietary calcium intake, F(2, 43) = 7.856, p = .002; level of PA, F(2, 43) = 4.787, p = .011; diabetes self-care activities, F(2, 43) = 14.009, p < .001; diabetes self-efficacy, F(2, 43) = 19.722, p < .001; and glycemic control (A1C level; t = 2.809, p = .010) compared to the control group at the 3-month follow-up. CONCLUSION: The results demonstrate the effectiveness of OP prevention education based on self-efficacy theory among Chinese adults with type 2 diabetes.