PAH exposure is associated with enhanced risk for pediatric dyslipidemia through serum SOD reduction

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked to abnormal lipid metabolism, but evidence regarding PAHs as risk factors for dyslipidemia is lacking. Objective: To investigate the respective role and interaction of PAH exposure and antioxidant consumption in the risk for pediatric dyslipidemia. Methods: We measured the concentrations of serum lipids, superoxide dismutase (SOD) and urinary hydroxylated PAHs (OH-PAHs) in 403 children, of which 203 were from an e-waste-exposed area (Guiyu) and 200 were from a reference area (Haojiang). Biological interactions were calculated by additive models. Results: Guiyu children had higher serum triglyceride concentration and dyslipidemia incidence, and lower serum concentration of high-density lipoprotein (HDL) than Haojiang children. Elevated OH-PAH concentration, and concomitant SOD reduction, were both associated with lower HDL concentration and higher hypo-HDL risk (S3OH-Phes: B for lgHDL = 0.048, P <0.01; OR for hypo-HDL = 3.708, 95% CI: 1.200, 11.453; SOD: BT3 for lgHDL = 0.061, P <0.01; ORT3 for hypo-HDL = 0.168, 95% CI: 0.030, 0.941; all were adjusted for confounders). Biological interaction between phenanthrol exposure and SOD reduction was linked to dyslipidemia risk (RERI = 2.783, AP = 0.498, S = 2.537). Children with both risk factors (higher S3OH-Phes and lower SOD) had 5.594times (95% CI: 1.119, 27.958) the dyslipidemia risk than children with neither risk factors (lower S3OH-Phes and higher SOD). Conclusion: High PAH exposure combined with SOD reduction is recommended for predicting elevated risk for pediatric dyslipidemia. Risk assessment of PAH-related dyslipidemia should take antioxidant concentration into consideration

Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma

Abstract Background N6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear. Methods The related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups. Results The m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC. Conclusion A comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments

Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood–brain barrier dysfunction

Abstract Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently, especially in warfarin-associated intracerebral hemorrhage (W-ICH). In the present study, we employ the warfarin-associated intracerebral hemorrhage (W-ICH) rat model, to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage, hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage. Methods In the present study, we tested whether glibenclamide, a common hypoglycemic drug, could attenuate hematoma expansion in a rat model of W-ICH. Hematoma expansion was evaluated using magnetic resonance imaging; brain injury was evaluated by brain edema and neuronal death; and functional outcome was evaluated by neurological scores. Then blood–brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein. Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH, thus mitigating brain edema and neuronal death and promoting neurological function recovery, which may benefit from alleviating blood–brain barrier disruption by suppressing matrix metallopeptidase-9. Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH

Efficacy of Mobile Health in Patients With Low Back Pain: Systematic Review and Meta-analysis of Randomized Controlled Trials

BackgroundLow back pain is one of the most common health problems and a main cause of disability, which imposes a great burden on patients. Mobile health (mHealth) affects many aspects of people’s lives, and it has progressed rapidly, showing promise as an effective intervention for patients with low back pain. However, the efficacy of mHealth interventions for patients with low back pain remains unclear; thus, further exploration is necessary. ObjectiveThe purpose of this study was to evaluate the efficacy of mHealth interventions in patients with low back pain compared to usual care. MethodsThis was a systematic review and meta-analysis of randomized controlled trials designed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) statement standard. We searched for studies published in English before October 2020 in the PubMed, EMBASE, Web of Science, and Cochrane Library databases. Two researchers independently scanned the literature, extracted data, and assessed the methodological quality of the included studies. Bias risks were assessed using the Cochrane Collaboration tool. We used RevMan 5.4 software to perform the meta-analysis. ResultsA total of 9 studies with 792 participants met the inclusion criteria. The simultaneous use of mHealth and usual care showed a better reduction in pain intensity than usual care alone, as measured by the numeric rating scale (mean difference [MD] –0.85, 95% CI –1.29 to –0.40; P<.001), and larger efficacy in reducing disability, as measured by the Rolland-Morris Disability Questionnaire (MD –1.54, 95% CI –2.35 to –0.73; P<.001). Subgroup analyses showed that compared with usual care, mHealth using telephone calls significantly reduced pain intensity (MD –1.12, 95% CI –1.71 to –0.53; P<.001) and disability score (MD –1.68, 95% CI –2.74 to –0.63; P<.001). However, without the use of telephone calls, mHealth had no obvious advantage over usual care in improving pain intensity (MD –0.48, 95% CI –1.16 to 0.20; P=.16) and the disability score (MD –0.41, 95% CI –1.88 to 1.05; P=.58). The group that received a more sensitive feedback intervention showed a significantly reduced disability score (MD –4.30, 95% CI –6.95 to –1.69; P=.001). ConclusionsThe use of simultaneous mHealth and usual care interventions has better efficacy than usual care alone in reducing pain intensity and disability in patients with low back pain. Moreover, the results of subgroup analysis revealed that mHealth using telephone calls might play a positive role in improving pain intensity and disability in patients with low back pain

SATB1 Overexpression Regulates the Development and Progression in Bladder Cancer through EMT

The global gene regulator Special AT-rich sequence-binding protein-1 (SATB1) has been reported to induce EMT-like changes and be associated with poor clinical outcome in several cancers. This study aims to evaluate whether SATB1 affects the biological behaviors of bladder transitional cell carcinoma (BTCC) and further elucidate if this effect works through an epithelial-mesenchymal transition (EMT) pathway. The expression of SATB1, E-cadherin (epithelial markers), vimentin (mesenchymal markers) in BTCC tissues and adjacent noncancerous tissues, as well as in two cell lines of bladder cancer were investigated. Whether the SATB1 expression is associated with clinicopathological factors or not was statistically analyzed. Cell invasion and migration, cell cycle, cell proliferation and apoptosis were evaluated in SATB1 knockdown and overexpressed cell lines. Our results showed that the expression of SATB1 was remarkably up-regulated both in BTCC tissues and in bladder cancer cell lines with high potential of metastasis. The results were also associated with EMT markers and poor prognosis of BTCC patients. Moreover, SATB1 induced EMT processes through downregulation of E-cadherin, upregulation of E-cadherin repressors (Snail, Slug and vimentin). SATB1 also promoted cell cycle progression, cell proliferation, cell invasion and cell migration, but did not alter cell survival. In conclusion, our results suggest that SATB1 plays a crucial role in the progression of bladder cancer by regulating genes controlling EMT processes. Further, it may be a novel therapeutic target for aggressive bladder cancers

Increased expression of immediate early response gene 3 protein promotes aggressive progression and predicts poor prognosis in human bladder cancer

Abstract Background Immediate early response gene 3 (IER3) is a stress-inducible gene, which exerts diverse effects in regulating cell apoptosis and cell cycle. Growing evidence shows that IER3 functions either as an oncogene or a tumor suppressor in various human cancers with a cancer type-dependent manner. However, the involvement of IER3 in human bladder cancer (BCa) has not been elucidated. In the current study, we aimed to investigate the expression pattern and the clinical significance of IER3 in BCa. Methods We performed immunohistochemistry analysis to examine the subcellular localization and the expression levels of IER3 protein in 88 BCa specimens obtained from Department of Pathology in Massachusetts General Hospital. The associations of IER3 protein expression with various clinicopathological features and patients’ overall survival were statistically evaluated. Results IER3 protein was mainly expressed in the cytoplasm in bladder cancer cell. Of 88 BCa tissue specimens, 39 (44.3%) showed high expression of IER3 protein and 49 (55.7%) showed low expression. High IER3 protein expression was significantly associated with high pathologic nodal stage (p = 0.018). Kaplan-Meier analysis revealed that the overall survival of BCa patients with overexpression of IER3 protein was shorter than that with low expression (p < 0.01). Multivariate analysis by Cox regression further identified IER3 as an independent prognostic factor of BCa patients (p = 0.010). Conclusions Our findings suggest for the first time that the increased expression of IER3 protein may promote the aggressive progression of BCa. Importantly, IER3 may be a potential prognostic marker for BCa patients

The SATB1-overexpressing cells and SATB1-knockdown cells are established.

<p>The SATB1 expression of BIU-87 cells and T24 cells transfected with pcDNA3.1-SATB1 and pGenesil2-SATB1-shRNA were examined by qRT-PCR and western blot (A and B; **P < 0.001). Non-transfected BIU-87 cells were used as control group. T24 cells treated with pGenesil2 control vector which does not target any specific gene were used as the control groups. Immunofluorescence analysis was performed to detect the SATB1staining in each cell groups. Immunofluorescence images at 200×magnification (C and D). Error bars indicate s.e.m., n = 3 experiments.</p