Effect of Accessory Renal Arteries on Essential Hypertension and Related Mechanisms.

BACKGROUND: This case-control study aimed to determine whether there were differences between patients with essential hypertension with accessory renal arteries (ARAs) and those without ARAs. METHODS AND RESULTS: The enrolled patients with essential hypertension were divided into the ARA group (n=200) and control group without ARAs (n=238). After propensity matching, 394 patients (197 in each of the 2 groups), were included. The 24-hour BP (4.33/2.43 mm Hg) and daytime BP (4.48/2.61 mm Hg) of patients in the ARA group were significantly higher than those of the control group (P<0.05). The flow-mediated dilation was lower in the ARA group (5.98±2.70 versus 5.18±2.66; P<0.05). In correlation analysis, the horizontal plasma aldosterone concentration had the highest correlation with 24-hour, daytime, and nighttime systolic BP (r=0.263, 0.247, and 0.243, respectively; P<0.05) and diastolic BP (r=0.325, 0.298, and 0.317, respectively; P<0.05). As for multivariate regression analysis, plasma aldosterone concentration was a significant risk factor for elevated 24-hour, daytime, and nighttime systolic BP (ß=0.249 [95% CI, 0.150-0.349], 0.228 [95% CI, 0.128-0.329], and 0.282 [95% CI, 0.187-0.377], respectively; P<0.05) and elevated diastolic BP (ß=0.289 [95% CI, 0.192-0.385], 0.256 [95% CI, 0.158-0.353], and 0.335 [95% CI, 0.243-0.427], respectively; P<0.05). Direct renin concentration was also a risk factor for 24-hour and daytime BPs, whereas heart rate was a risk factor correlated with 24-hour, daytime, and nighttime diastolic BP (all P<0.05). For the mixed-effects model for repeated measures, the results were similar to results of the multivariate regression analysis (all P<0.05). CONCLUSIONS: ARAs could contribute a higher BP of patients with essential hypertension and might promote the development of essential hypertension. The mechanism might be related to overactivation of the renin-angiotensin-aldosterone system and sympathetic nervous system.

Association of Preablation Plasma Corin Levels With Atrial Fibrillation Recurrence After Catheter Ablation: A Prospective Observational Study.

BACKGROUND: We assessed the impact of pre- and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: This prospective, single-center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre- and postprocedure corin concentrations were 539.14 (329.24-702.08) and 607.37 (364.50-753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36-489.28) and 489.12 (315.66-629.05) pg/mL (both P<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282-1.655]; P<0.0001). CONCLUSIONS: Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.

Correlation Between the Peripheral Neuropathy and Levels of hs-CRP, IL-1ß and IL-6 in Senile Parkinson's Disease Patients.

This study was carried out to investigate the correlation between the onset of peripheral neuropathy and levels of hypersensitive C-reactive protein (hs-CRP), interleukin 1ß (IL-1ß) and IL-6 in senile Parkinson's disease (PD) patients. For this purpose, a total of 60 PD patients and 60 age-matched healthy subjects were enrolled in this study and received the assessment for peripheral nerves by using the quantified method. Besides, levels of hs-CRP, IL-1ß and IL-6 in serum were determined to analyze the correlation between the clinical features, including the severity of PD and cognitive decline, and the levels of hs-CRP, IL-1ß and IL-6. Results showed that PD patients had more cases of peripheral neuropathy than those in the healthy control group. Levels of hs-CRP, IL-1ß and IL-6 in the serum of PD patients were much higher than those in the healthy control (P<0.05). Besides, PD patients had lower scores of MMSE and MoCA but higher CNPI scores when compared to the healthy control group. As a result, we found that the severity of peripheral neuropathy was in a positive correlation with the levels of hs-CRP, IL-1ß and IL-6. It was concluded that PD patients generally have peripheral neuropathy that may correlate with the increases in the levels of hs-CRP, IL-1ß and IL-6, and early intervention may mitigate the development and progression of peripheral neuropathy.

Attenuation of experimental osteoarthritis with human adipose-derived mesenchymal stem cell therapy: inhibition of the pyroptosis in chondrocytes.

AIM: To explore the role and mechanism of human adipose-derived mesenchymal stem cells (hAD-MSCs) in the treatment of osteoarthritis (OA). METHODS: OA hulth model of Sprague Dawley (SD) rats and 20 ng/ml TNF-α treated chondrocytes were used as models of OA in vivo and in vitro, respectively. hAD-MSCs were administrated in the articular cavity by injection in vivo and co-cultured with chondrocytes using transwell in vitro. Haematoxylin and eosin staining and Safranin-O/Fast green staining were performed to detect tissue destruction and histopathology. Scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructure of chondrocytes. The pyroptosis signaling pathway-related proteins were detected by immunohistochemistry, immunofluorescence, qRT-PCR and Western blot. And small interference technology was used to study the mechanism in depth. RESULTS: hAD-MSCs could delay the development of rat OA, improve the pathological changes of joints, inhibit the expression of NLRP3, Caspase1, GSDMD and TNFR1. In vitro, the expression of pyroptosis signal proteins in chondrocytes was significantly elevated when stimulated with TNF-α, the level of inflammatory factors such as IL-1ß, IL-18 was increased, and the cell morphology was significantly destroyed. While co-cultured with hAD-MSCs, these syndromes were reversed. Knockout of TNFR1 also returned the upregulation of pyroptosis signals which caused by TNF-α. CONCLUSION: These results demonstrated that hAD-MSCs could inhibit pyroptosis signaling pathway of chondrocytes induced by TNF-α, which have raised our understanding of the role of hAD-MSCs as promising therapy for the management of OA.

A novel command generation method for SSVEP-based BCI by introducing SSVEP blocking response.

Increasing the number of commands in a steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) by increasing the number of visual stimuli has been widely studied. This paper proposes a novel BCI paradigm based on SSVEP and SSVEP blocking responses (defined as the disappearance or attenuation of the ongoing SSVEP) to increase the number of BCI commands with limited visual stimuli, in which the duration of SSVEP blocking response can be voluntarily controlled by users. Besides, this paper also proposes a frequency-specific threshold method and a unified threshold method to identify SSVEP blocking response. The paradigm includes a frequency recognition phase and an SSVEP blocking response identification phase. Filter bank canonical correlation analysis is used to detect the stimulation frequency, and the proposed threshold method is used to identify the SSVEP blocking response and calculate the blocking duration. The experimental results show that the two proposed threshold methods can effectively identify the SSVEP blocking response with different blocking duration and alternative stimulation frequencies. When there are Nf stimulation frequencies, the number of commands can be increased to Nf×Nt using the proposed paradigm, where Nt blocking durations correspond to each stimulus. This study demonstrates that the proposed paradigm based on SSVEP and SSVEP blocking responses is effective in increasing the number of BCI commands and has great potential for practical applications.

The Correlation of Fibroblast Growth Factor 23 with Cardiac Remodeling in Essential Hypertension with Normal Renal Function.

BACKGROUND: Fibroblast growth factor 23 (FGF23), a glycoprotein-regulating calcium and phosphorus homeostasis, has been linked to cardiovascular diseases. We aimed to evaluate the correlation of FGF23 levels and cardiac remodeling (left atrial [LA] enlargement and left ventricular hypertrophy [LVH]) in essential hypertension (EH) with normal renal function and explore the diagnostic values of FGF23 and B-type natriuretic peptide (BNP) in cardiac remodeling. METHODS AND RESULTS: We enrolled 40 healthy control subjects (group I) and 146 EH patients (group II). Plasma FGF23 concentration was measured in all subjects. In this study, FGF23 level was significantly higher in group II (660.77 [446.26, 1,001.72]) pg/mL compared with the controls (73.23 [52.92, 103.69]) pg/mL (p < 0.001). Logistic regression analysis revealed that FGF23 was independently correlated to LVH and LA enlargement. Receiver operating characteristic (ROC) curve indicated FGF23 had an optimal cutoff of 834.63 pg/mL for LVH (area under ROC curve [AUC], 0.913; 95% CI: 0.863-0.963) and 497.06 pg/mL for LA enlargement (AUC, 0.694; 95% CI: 0.612-0.768). The DeLong test was performed to compare AUCs of FGF23 and BNP, and the AUC of FGF23 (0.913) was statistically higher compared to AUC of BNP (0.661) (DeLong test: p < 0.001) in the diagnosis of LVH. CONCLUSION: Plasma FGF23 level elevated in EH, increased with the progress of cardiac remodeling, and was independently related to LVH and LA enlargement. The diagnostic value of FGF23 in cardiac remodeling, especially for LVH, was superior to BNP.

Cohort study of THRIVE predicting adverse outcomes in acute ischemic stroke of the anterior circulation and posterior circulation after 3 months and 1 year of follow-up.

PURPOSE: To evaluate the difference of Totaled Health Risks In Vascular Events (THRIVE) in predicting adverse outcomes in acute ischemic stroke (AIS) of the anterior circulation and posterior circulation at 3-month and 1-year follow-up. METHODS: A total of 858 patients with AIS were followed up for 3 months and 1 year, and their data prospectively collected. The occurrence of death or moderate to severe disability (modified Rankin Scale ≥ 3 points) was regarded as the endpoint. MedCalc software was used to create the THRIVE receiver operating characteristic curve. The area under the curve (AUC) was calculated to compare the THRIVE scale in predicting adverse outcomes in AIS of the anterior and posterior circulation and compare the differences. RESULTS: At 3-month follow-up, the AUC of THRIVE was 0.685 (95% CI 0.644-0.724) for AIS of the anterior circulation and 0.709 (95% CI 0.647-0.765) for AIS of the posterior circulation. The area difference between them was 0.0235 (95% CI -0.0728-0.120, P = 0.6330[>0.05]). The AUC of THRIVE for AIS in the anterior circulation at 1 year was 0.701 (95% CI 0.660-0.740), and that for AIS in the posterior circulation at 1 year was 0.747 (95% CI 0.687-0.800). The area difference between them was 0.0458 (95% CI -0.0489-0.140, P = 0.3436 [>0.05]). The difference was not statistically significant. CONCLUSION: THRIVE can well predict the short-term and long-term adverse prognosis of AIS in the anterior and posterior circulation and has the same predictive effect.

Correction: Yuan et al. Sub-Micromolar Methylmercury Exposure Promotes Premature Differentiation of Murine Embryonic Neural Precursor at the Expense of Their Proliferation. Toxics 2018, 6, 61.

In the original article [...].

Cohort study on the prognosis of acute cerebral infarction in different circulatory systems at 1-year follow-up.

BACKGROUND: To evaluate the prognosis of acute cerebral infarction at 1-year follow-up in different circulation infarctions. METHODS: Clinical data of 858 consecutive patients with acute cerebral infarction were collected. Of the 858 cases, 21 (2.45%) were lost to follow-up and 837 completed follow-up and thus were enrolled in this study. At 1-year follow-up, death or moderate-to-severe dysfunction (modified Rankin Scale (mRS) ≥ 3 points) was regarded as the poor prognostic endpoint. Univariate analysis and multivariate logistic stepwise regression analysis were performed to assess the prognosis. The prediction probability of indicators was obtained for the multivariate model, and the receiver operating characteristic curve was delineated to calculate the area under the curve (AUC) to predict the fitness of the model. RESULTS: The older the age, the greater the probability of a poor prognosis. Patients with previous diabetes and cerebral infarction had a poor prognosis. The higher the National Institutes of Health Stroke Scale and mRS scores and the lower the Barthel index at admission, the worse the prognosis of the patients. The longer the hospital stay, the worse the prognosis of the patients. The prognosis of different circulation infarctions was different. The AUC of the multivariate model was AUC = 0.893, and the 95% confidence interval was 0.870-0.913, indicating a good fit. The prognosis of anterior circulation infarction (ACI) was worse than that of posterior circulation infarction (PCI) (P < 0.05). The prognosis of patients with ACI and PCI was not significantly different from that of patients with ACI or PCI alone (P > 0.05). CONCLUSIONS: Diabetes, the Barthel index at admission and previous cerebral infarction are poor prognostic factors of acute cerebral infarction. The prognosis of ACI is worse than that of PCI. Different factors affect the prognosis of different circulatory system infarctions.

Single-Nucleotide Polymorphisms in the 3' Untranslated Region of CORIN Associated With Cardiovascular Diseases in a Chinese Han Population: A Case-Control Study.

Background: Corin is a transmembrane serine protease that activates pro-forms of atrial and brain natriuretic peptides. Numerous studies have indicated that corin played an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of CORIN and CVDs. The aims of this study were to investigate the associations of three SNPs (rs3749585, rs4695253, and rs12641823) in the 3'UTR of CORIN with CVDs and to find the seed regions of microRNAs (miRNAs) that bind to SNPs of CORIN. Methods and Results: A case-control study (n = 3,537) was performed in a Han population of northeastern China. CVDs included essential hypertension (EH), atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Genotyping was performed using high-resolution melt analysis. In the EH-control study, rs3749585T was significantly associated with the risk of EH after adjusting for sex and age in allelic (p adj = 0.049; OR: 1.113) and dominant (p adj = 0.015, OR: 1.233) models. Rs4695253T was significantly associated with the risk of EH in the recessive model after adjusting for sex and age (p adj = 0.005, OR: 2.084). Rs3749585T was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM, and CAD (dominant: p adj = 0.009, OR: 0.762; additive: p adj = 0.048, OR: 0.873). In the HF-control study and CAD-control study, none of the three SNPs was associated with HF and CAD after adjusting for covariates in any models (p adj > 0.05). The levels of high-density lipoprotein (HDL) in rs4695253CC+CT were lower than the levels of HDL in rs4695253TT (42.47 ± 10.30 vs. 48.0 ± 10.24 mg/dl, p adj = 0.008). The levels of total cholesterol (TC) in rs4695253CC+CT were lower than the levels of TC in rs4695253TT (164.01 ± 49.15 vs. 180.81 ± 43.92 mg/dl, p adj = 0.036). Luciferase assay revealed that the relative luciferase activity of rs3749585CC-transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585TT (p < 0.001). A significant decrease in the relative luciferase activity of rs3749585TT reporter was observed as compared with rs3749585CC reporter in the presence of miR-1323 or miR-548o-3p (p = 0.017 and 0.012, respectively). Conclusions: We found significant associations between rs3749585T and rs4695253T and EH, between rs4695253T and the levels of TC and HDL, and between rs3749585T and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.

Value of Barthel, PLAN and NIHSS scores for predicting the death of patients with acute ischemic stroke during their 5-year follow-up.

OBJECTIVE: This study aimed to investigate the value of Barthel, PLAN, and NIHSS scores for predicting death in the 5-year follow-up after patients with AIS are discharged and find a simple and convenient predictive scale. METHODS: Data were prospectively collected from 678 patients with AIS. Patients' death after 5 years of follow-up was considered the final event. The predictors of death were examined through single-factor and multivariate analysis. The receiver operating characteristic curve (ROC) of the patients' Barthel, PLAN, and NIHSS scores was drawn, and the area under the curve (AUC) was calculated. Differences in the predictive power of the three scales were compared using MedCalc. The goodness of fit between predictive and actual models was evaluated with the Hosmer-Lemeshow method. RESULTS: Multivariate analysis suggested that the BI score was an independent predictor of death from AIS in the 5-year follow-up. The Barthel, PLAN, and NIHSS scale scores predicted the 5-year mortality AUC values of AIS were 0.687 [95% CI, (0.649-0.722)], 0.621 [95% CI, (0.583-0.659)], 0.637 [95% CI, (0.599-0.674)], the Hosmer-Lemeshow test revealed P > 0.05, indicating that the three models had a good fit. In pairwise comparison, the AUC value of the BI score was significantly greater than that of the NIHSS scores (Pc = 0.0189). BI and PLAN scores were very close to statistical significance (Pc = 0.0513). However, PLAN and NIHSS scores had no significant differences (Pc = 1.7493). CONCLUSION: Simple BI scores had a high predictive value for the death of Chinese patients with AIS within 5 years.

1α,25-Dihydroxyvitamin D3 Supplementation during Pregnancy Is Associated with Allergic Rhinitis in the Offspring by Modulating Immunity.

BACKGROUND: Maternal supplementation with 1α,25-dihydroxyvitamin D3 (VD3) has immunologic effects on the developing fetus through multiple pathways. This study was aimed at investigating the effects of VD3 supplementation on immune dysregulation in the offspring during allergic rhinitis. METHODS: Different doses of VD3 as well as control were given to pregnant female mice. Ovalbumin (OVA) challenge and aluminum hydroxide gel in sterile saline were used to induce allergic rhinitis in offspring mice. Nasal lavage fluids (NLF) were collected, and eosinophils were counted in NLF 24 hours after the OVA challenge. Th1, Th2, Th17, and Treg subtype-relevant cytokines, including IFN-γ, IL-4, IL-10, IL-17, TGF-ß, and OVA-IgE levels from the blood and NLF of offspring mice, were detected by the enzyme-linked immunosorbent assay (ELISA) method. The Treg subtype was analyzed by flow cytometry. Treg cells were purified from offspring and were adoptively transferred to OVA-sensitized allogenic offspring mice. The outcomes were assessed in allogenic offspring. RESULTS: Our data showed that VD3 supplementation significantly decreased the number of eosinophils, basophils, and lymphocytes in the peripheral blood and NLF. The proportion of CD4+CD25+FoxP3+Tregs had a positive correlation with VD3 in a dose-dependent manner. The levels of serum IgE, IL-4, and IL-17 were decreased while the expressions of IFN-γ, IL-10, and TGF-ß were significantly enhanced in VD3 supplementation groups. Adoptive transfer CD4+CD25+FoxP3+Tregs of VD3 supplementation groups promoted Th1 and suppressed Th2 responses in the offspring during allergic rhinitis. CONCLUSION: Our findings indicated that low dose VD3 supply in pregnant mice's diet suppressed Th2 and Th17 responses in allergic rhinitis by elevating the Th1 subtype and the proportion of CD4+CD25+FoxP3+Tregs in offspring. It suggested that low dose VD3 supply may have the potential to act as a new therapeutic strategy for allergic rhinitis.

Nrf2 exerts mixed inflammation and glucose metabolism regulatory effects on murine RAW264.7 macrophages.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that mediates a broad range of cellular antioxidative, detoxification and anti-inflammatory effects. However, the precise mechanism by which Nrf2 regulates inflammation and metabolism in macrophages remains controversial and unclear. To further clarify the roles of Nrf2 in inflammation and glucose metabolism regulation, retrovirus-mediated knockdown of Nrf2 was performed in murine RAW264.7 macrophages, and the cells were stimulated with 100 ng/mL lipopolysaccharide for 24 h for M1 activation. qPCR and western blotting results indicated that Nrf2 knockdown significantly enhanced expression of the inflammatory genes Il1a and Il1b in unstimulated macrophages and increased expression of the inflammatory genes Il1a, Il1b, Il6, Il10, Ccl2, Ccl22, and CD38 but decreased that of Tnfa and Tgfb1 in M1 macrophages. Nrf2 knockdown also significantly elevated IL6 and IL10 secretion by M1 macrophages. Western blotting showed that Nrf2 knockdown reduced iNOS protein levels in resting macrophages and enhanced CD38 protein levels in both resting and M1 macrophages. The differential regulation of these macrophage inflammation and polarization markers by Nrf2 reveals multiple roles for Nrf2 in regulating inflammation in macrophages. Moreover, Nrf2 knockdown increased the Glu4 protein level and decreased AKT and GSK3ß protein phosphorylation in M1 macrophages, suggesting multiple roles for Nrf2 in regulating glucose metabolism in macrophages. Overall, our results are the first to demonstrate mixed inflammation and glucose metabolism regulatory effects of Nrf2 in macrophages that may occur independent of its classic function in redox regulation. These findings support the potential of Nrf2 as a therapeutic target for the prevention and treatment of inflammation- and obesity-associated syndromes, including diabetes and atherosclerosis.

Sub-Micromolar Methylmercury Exposure Promotes Premature Differentiation of Murine Embryonic Neural Precursor at the Expense of Their Proliferation.

Methylmercury (MeHg) is a ubiquitous environmental pollutant that is known to be neurotoxic, particularly during fetal development. However, the mechanisms responsible for MeHg-induced changes in adult neuronal function, when their exposure occurred primarily during fetal development, are not yet understood. We hypothesized that fetal MeHg exposure could affect neural precursor development leading to long-term neurotoxic effects. Primary cortical precursor cultures obtained from embryonic day 12 were exposed to 0 nM, 0.25 nM, 0.5 nM, 2.5 nM, and 5 nM MeHg for 48 or 72 h. Total Hg accumulated in the harvested cells in a dose-dependent manner. Not all of the concentrations tested in the study affected cell viability. Intriguingly, we observed that cortical precursor exposed to 0.25 nM MeHg showed increased neuronal differentiation, while its proliferation was inhibited. Reduced neuronal differentiation, however, was observed in the higher dose groups. Our results suggest that sub-nanomolar MeHg exposure may deplete the pool of neural precursors by increasing premature neuronal differentiation, which can lead to long-term neurological effects in adulthood as opposed to the higher MeHg doses that cause more immediate toxicity during infant development.

Magnetic suspension dynamic calibration device of measurement system for dynamic characteristics of sliding bearings.

A measurement system error is a key factor that disturbs the identification precision of sliding bearing's dynamic characteristic coefficients. The transfer process and influence rule of errors from a measurement system to dynamic characteristic coefficients are analyzed by solving the dynamic characteristic measurement model. In order to ensure that the identification errors are no more than 40%, the amplitude error and phase error of the transfer function of the measurement system should be controlled within 10% and 1°, respectively. A novel magnetic suspension calibration method of the measurement system, which generates a vibration through a noncontact electromagnetic force rather than a traditional contact force, is proposed. A magnetic dynamic calibration device is developed. The experiment results show that the device can make dynamic calibration at different frequencies successfully, which is favorable to improve the controllability of the calibration process and the stability of calibration results.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation­specific PCR, semi­quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3­methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.

Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P < 0.05) of that of untransfected control cells. The impacts of Nrf2 knockdown (NK) on the antioxidant system, inflammatory response, and glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2αS51, p-nuclear factor-κB p65S276, and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKTS473, and p-GSK3α/ßY279/Y216, which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and insulin-resistant phenotype that includes impaired lipogenesis and gluconeogenesis in the liver. These apparently paradoxical observations led us to evaluate the impact of Nrf2 in liver cells in the absence of any influence from the systemic environment, including changes in the secretion of adipokines and proinflammatory cytokines by adipose tissues. In the present study, Nrf2 knockdown was sufficient to induce fundamental changes in the glucose metabolism of AML12 hepatocytes in addition to its classical cytoprotective functions. We also discuss similarities and differences between our in vitro study and previous in vivo studies, which may be helpful to dissect and better understand in vivo data that represents the culmination of both local and systemic alterations.

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma.

This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.

Dynamic Calibration and Verification Device of Measurement System for Dynamic Characteristic Coefficients of Sliding Bearing.

The identification accuracy of dynamic characteristics coefficients is difficult to guarantee because of the errors of the measurement system itself. A novel dynamic calibration method of measurement system for dynamic characteristics coefficients is proposed in this paper to eliminate the errors of the measurement system itself. Compared with the calibration method of suspension quality, this novel calibration method is different because the verification device is a spring-mass system, which can simulate the dynamic characteristics of sliding bearing. The verification device is built, and the calibration experiment is implemented in a wide frequency range, in which the bearing stiffness is simulated by the disc springs. The experimental results show that the amplitude errors of this measurement system are small in the frequency range of 10 Hz-100 Hz, and the phase errors increase along with the increasing of frequency. It is preliminarily verified by the simulated experiment of dynamic characteristics coefficients identification in the frequency range of 10 Hz-30 Hz that the calibration data in this frequency range can support the dynamic characteristics test of sliding bearing in this frequency range well. The bearing experiments in greater frequency ranges need higher manufacturing and installation precision of calibration device. Besides, the processes of calibration experiments should be improved.

Enhanced penetration of exogenous EPCs into brains of APP/PS1 transgenic mice.

The aim of this study was to investigate the repair function of exogenous Endothelial progenitor cells (EPCs) for brain microvascular damage of the APP/PS1 transgenic mouse model of Alzheimer's disease (AD). This study used a density-gradient centrifugation method to isolate mononuclear cells (MNCs) from mouse bone marrow, which were subsequently seeded and cultured. Cells were characterized by morphology and detection of the surface markers CD34 and CD133 at different time points by immunofluorescence (IF) and flow cytometry (FCM). Then, EPCs were transfected with GFP adenoviral vectors (GFP-EPCs). Wild-type (WT) and APP/PS1 transgenic mice both received GFP-EPCs injection through the tail vein, and using a PBS buffer injection as the control. Seven days later, the animals' brain tissue was isolated. Expression of GFP was detected by quantitative polymerase chain reaction (qPCR) and western-blot (WB), while the fluorescence of GFP within the brains of mice was observed under a fluorescence microscope. Higher mRNA and protein expression of GFP, accompanied with increased green fluorescence, were detected in the brain of GFP-EPCs-injected APP/PS1 mice, as compared with GFP-EPCs-injected WT mice. The results show that the APP/PS1 transgenic mouse model of AD exhibited enhanced penetration of exogenous EPCs into brains than the WT mice.