Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo

Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague–Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction.     

Change of Th17 Lymphocytes and Treg/Th17 in Typical and Atypical Optic Neuritis

Background

Typical and atypical optic neuritis (ON) are two clinical types of autoimmune inflammatory diseases of the optic nerve that causes acute vision loss, and are difficult to distinguish in their early stages. The disturbance in the balance of Th17 and Treg lymphocytes is thought to play an essential role in these autoimmune inflammatory diseases.

Objectives

To detect the clinical relevance of Th17 and Treg in peripheral blood and the ratio of Treg/Th17 in patients with typical and atypical ON. To determine whether analysis of Th17 and Treg lymphocytes will provides insights into the different disease phenotypes of typical and atypical ON.

Methods

We studied a consecutive series of patients aged 14–70 years who presented to our neurological department with typical ON (n = 30) or atypical ON (n = 33) within 4 weeks of their acute attacks. Routine clinical tests and ophthalmological examination were performed in all patients. Blood samples were collected from untreated patients and from gender- and age-matched healthy controls (n = 30). The proportion of peripheral blood Th17 cells and Treg cells was determined by flow cytometry.

Results

Patients with atypical ON had a higher proportion of Th17 cells than patients with typical ON (3.61±1.56 vs 2.55±1.74, P<0.01) or controls (1.45±0.86, P<0.01). The proportion of Th17 cells in patients with typical ON was also markedly higher than in controls (P<0.01). The mean percentage of Treg cells in atypical ON (6.31±2.11) and typical ON (6.80±2.00) were significantly lower when compared to controls (8.29±2.32, both P<0.01). No significant difference in Treg frequency was observed between typical ON and atypical ON (p>0.05).

Conclusions

The frequency of Th17 cells is higher in atypical ON than typical ON, and patients with atypical ON have a greater imbalance of pro-inflammatory and regulatory cells than patients with typical ON when compared with controls. These changes are indicative of distinct pathological mechanisms and may provide useful information to distinguish typical and atypical ON.     

Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis

Introduction

In response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson''s disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.

Methods

We conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.

Results

Eleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).

Conclusions

Results of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.     

Decreased TUSC3 Promotes Pancreatic Cancer Proliferation,Invasion and Metastasis

Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-κB activity, TUSC3 expression was found to be reversely correlated with NF-κB activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-κB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.     

Acute Effects of Particulate Air Pollution on the Incidence of Coronary Heart Disease in Shanghai,China

Introduction

Evidence based on ecological studies in China suggests that short-term exposure to particulate matter (PM) is associated with cardiovascular mortality. However, there is less evidence of PM-related morbidity for coronary heart disease (CHD) in China. This study aims to investigate the relationship between acute PM exposure and CHD incidence in people aged above 40 in Shanghai.

Methods

Daily CHD events during 2005–2012 were identified from outpatient and emergency department visits. Daily average concentrations for particulate matter with aerodynamic diameter less than 10 microns (PM₁₀) were collected over the 8-year period. Particulate matter with aerodynamic diameter less than 2.5 microns (PM_2.5) were measured from 2009 to 2012. Analyses were performed using quasi-poisson regression models adjusting for confounders, including long-term trend, seasonality, day of the week, public holiday and meteorological factors. The effects were also examined by gender and age group (41–65 years, and >65 years).

Results

There were 619928 CHD outpatient and emergency department visits. The average concentrations of PM₁₀ and PM_2.5 were 81.7μg/m³ and 38.6μg/m³, respectively. Elevated exposure to PM₁₀ and PM_2.5 was related with increased risk of CHD outpatients and emergency department visits in a short time course. A 10 μg/m³ increase in the 2-day PM₁₀ and PM_2.5 was associated with increase of 0.23% (95% CI: 0.12%, 0.34%) and 0.74% (95% CI: 0.44%, 1.04%) in CHD morbidity, respectively. The associations appeared to be more evident in the male and the elderly.

Conclusion

Short-term exposure to high levels of PM₁₀ and PM_2.5 was associated with increased risk of CHD outpatient and emergency department visits. Season, gender and age were effect modifiers of their association.     

RY10-4 Inhibits the Proliferation of Human Hepatocellular Cancer HepG2 Cells by Inducing Apoptosis In Vitro and In Vivo

This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer.     

The Relationship between Nonalcoholic Fatty Liver Disease and Retinopathy in NHANES III

BackgroundNonalcoholic fatty liver disease (NAFLD), an emerging multisystem disease, has the similar pathogenesis with diabetes and is prevalent in diabetes. This study investigated whether NAFLD is associated with retinopathy in individuals with diabetes and without diabetes.MethodsThe association between NAFLD and retinopathy was investigated in 5963 participants aged 40 years and older who participated in the NHANES III, a nationally representative, population-based and cross-sectional study. NAFLD was detected via ultrasonography, and fundus photographs were obtained to grade retinopathy patterns. We performed multivariate logistic regression analysis to investigate the relationship between the presence of retinopathy and NAFLD and diabetes.ResultsAfter adjusting for multiple covariates, NAFLD population had no evidence of retinopathy increase in population without diabetes (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.48 to 1.26). In addition, NAFLD in individuals with diabetes was not significantly associated with retinopathy (OR: 0.77; 95% CI: 0.47 to 1.26), independent of age, gender, ethnicity, waist circumference, serum high-density lipoprotein (HDL) cholesterol, serum triglycerides, systolic blood pressure, and glycated hemoglobin.ConclusionsIn the US general population, NAFLD is not a precipitating factor of retinopathy in population with or without diabetes.     

Identification and Severity Determination of Wheat Stripe Rust and Wheat Leaf Rust Based on Hyperspectral Data Acquired Using a Black-Paper-Based Measuring Method

It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R²) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies.     

Intensified plant N and C pool with more available nitrogen under experimental warming in an alpine meadow ecosystem

Nitrogen (N) availability is projected to increase in a warming climate. But whether the more available N is immobilized by microbes (thus stimulates soil carbon (C) decomposition), or is absorbed by plants (thus intensifies C uptake) remains unknown in the alpine meadow ecosystem. Infrared heaters were used to simulate climate warming with a paired experimental design. Soil ammonification, nitrification, and net mineralization were obtained by in situ incubation in a permafrost region of the Qinghai‐Tibet Plateau (QTP). Available N significantly increased due to the stimulation of net nitrification and mineralization in 0–30 cm soil layer. Microbes immobilized N in the end of growing season in both warming and control plots. The magnitude of immobilized N was lower in the warming plots. The root N concentration significantly reduced, but root N pool intensified due to the significant increase in root biomass in the warming treatment. Our results suggest that a warming‐induced increase in biomass is the major N sink and will continue to stimulate plant growth until plant N saturation, which could sustain the positive warming effect on ecosystem productivity.