By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.
Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC) products and is ubiquitous as a substitute; however, its toxicity due to exposure remains to be determined. This study investigated the oxidative damage induced by DINP and the induced production of the pro-inflammation cytokines interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). Oral exposure to DINP induced oxidative damage and inflammatory responses in liver and kidney tissues through the accumulation of ROS, which may be an underlying mechanism for its toxicity. These changes may contribute to hepatic and renal histopathological alterations. Our data suggest that oxidative stress is involved in DINP-induced toxicity and that the co-administration of melatonin exerts a protective effect against DINP-induced toxicity.
BackgroundCadmium (Cd) is classified as a human carcinogen probably associated with epigenetic changes. DNA methylation is one of epigenetic mechanisms by which cells control gene expression. Therefore, the present study genome-widely screened the methylation-altered genes in the liver of rats previously exposed to low-dose Cd.Methodology Principal FindingsRats were exposed to Cd at 20 nmol/kg every other day for 4 weeks and gene methylation was analyzed at the 48th week with methylated DNA immunoprecipitation-CpG island microarray. Among the 1629 altered genes, there were 675 genes whose promoter CpG islands (CGIs) were hypermethylated, 899 genes whose promoter CGIs were hypomethylated, and 55 genes whose promoter CGIs were mixed with hyper- and hypo-methylation. Caspase-8 gene promoter CGIs and TNF gene promoter CGIs were hypermethylated and hypomethylated, respectively, along with a low apoptosis rate in Cd-treated rat livers. To link the aberrant methylation of caspase-8 and TNF genes to the low apoptosis induced by low-dose Cd, mice were given chronic exposure to low-dose Cd with and without methylation inhibitor (5-aza-2′-deoxyctidene, 5-aza). At the 48th week after Cd exposure, livers from Cd-treated mice displayed the increased caspase-8 CGI methylation and decreased caspase-8 protein expression, along with significant increases in cell proliferation and overexpression of TGF-β1 and cytokeratin 8/18 (the latter is a new marker of mouse liver preneoplastic lesions), all which were prevented by 5-aza treatment.Conclusion/SignificanceThese results suggest that Cd-induced global gene hypermethylation, most likely caspase-8 gene promoter hypermethylation that down-regulated its expression, leading to the decreased hepatic apoptosis and increased preneoplastic lesions.
Macroporous calcium phosphate cements (CPCs) were developed using genipin-crosslinked gelatin microspheres (GMs) with two weight ratios (2.5 wt% and 5 wt%). The initial setting time of the composite was prolonged by GMs. After GMs/CPCs were soaked in phosphate-buffered saline (PBS) for several weeks, macropores appeared as a result of the degradation of GMs. The presence of GMs accelerated the setting reaction and improved the structure of the composite. The compressive strength increased up to 12 MPa (2.5 wt% GMs/CPCs) and 14 MPa (5 wt% GMs/CPCs) after one week of PBS soaking, then gradually decreased to 9 MPa (2.5 wt% GMs/CPCs) and 7 MPa (5 wt% GMs/CPCs) after three weeks of soaking, and further to 6 MPa (2.5 wt% GMs/CPCs) and 2 MPa (5 wt% GMs/CPCs) after five weeks of soaking. CPCs with 2.5 wt% GMs were the most favorable composite in the tested samples. Cell experiments showed that rat osteoblasts displayed normal morphologies when exposed to the 2.5 wt% GMs/CPCs, and proliferation of the cells was also enhanced. An in vivo study showed that new bone tissue was able to grow into the pores that resulted from GM degradation. This study suggests that the new composite could be a promising candidate for use as a bone substitute under non-compression-loaded circumstances.
Chronic lymphocytic thyroiditis (CLT) is a common autoimmune disorder. The possible pathogenic role and mechanism of dibutyl phthalate (DBP) in CLT is still controversial. Experiments were conducted after 35-days of oral exposure to the three concentrations of DBP or saline, and three immunizations with thyroglobulin (TG). Healthy female Wistar rats were randomly divided into ten exposure groups (n = 8 each): (A) saline control, (B) 0.5 mg/kg/d DBP, (C) 5 mg/kg/d DBP, (D) 50 mg/kg/d DBP, (E) TG-immunized group, (F) TG- combined with 0.5 mg/kg/d DBP, (G) TG- combined with 5 mg/kg/d DBP, (H) TG- combined with 50 mg/kg/d DBP, (I) TG- combined with 50 mg/kg/d DBP plus 100 mg/kg/d vitamin C; (J) 100 mg/kg/d vitamin C. We showed that oral exposure DBP can aggravate CLT in rats. This deterioration was concomitant with increased thyroid auto antibodies, Th1/Th2 imbalance and Th17 immune response, activated pro-inflammatory and apoptosis pathways, and increased thyroid dysfunction in rats. Our results also suggested that DBP could promote oxidative damage. The study also found that vitamin C reduced the levels of oxidative stress and alleviated CLT. In short, the study showed that DBP exacerbated CLT through oxidative stress.
Objective
The relationship between physical activity (PA) and the risk of frailty has not reached a conclusive result. This systematic review with meta-analysis aimed to evaluate the effect of PA on the onset of frailty in the community-dwelling middle and older age adults by pooling data from cohort studies.
Methods
A systematic literature search was performed via PubMed, Embase, and Web of Science up to June 01, 2021. Pooled adjusted effect estimates (ES) with 95% confidence interval (CI) were calculated by using the random-effect model and by comparing the highest with lowest levels of PA. Heterogeneity was tested using the I2 statistic and Q-test. The quality of evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Results
A total of ten cohort studies with 14 records were selected, and the GRADE approach classified the quality of evidence as low. In comparison with the lowest level of PA, the highest level of PA was associated with 41% decreased odds of frailty (ES: 0.59, 95% CI: 0.51–0.67; I2 = 70.0%, P-heterogeneity < 0.001) after pooling results from included studies. In stratified analysis by frailty assessment approach, the highest level of PA was significantly associated with 37% (ES 0.63, 95% CI: 0.52–0.77, 49% (ES: 0.51, 95% CI: 0.41–0.63), and 30% (ES: 0.70, 95% CI: 0.65–0.75) reduced odds of frailty when pooling studies using criteria of physical frailty, multidimensional model, and accumulation of disability, respectively. Stratified analyses further by PA indicators and PA assessment tools yielded similar protective effects in any subgroups.
Conclusions
This study with moderate-certainty evidence shows that a higher level of PA was associated with lower odds of frailty, and the benefits of PA for frailty prevention were independent of frailty assessment tools, PA indicators, and PA assessment methods. Findings from this study may help implement active exercise strategies to prevent frailty.
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