Pass-Transistor Logic Circuits Based on Wafer-Scale 2D Semiconductors.

2D semiconductors, such as molybdenum disulfide (MoS2 ), have attracted tremendous attention in constructing advanced monolithic integrated circuits (ICs) for future flexible and energy-efficient electronics. However, the development of large-scale ICs based on 2D materials is still in its early stage, mainly due to the non-uniformity of the individual devices and little investigation of device and circuit-level optimization. Herein, a 4-inch high-quality monolayer MoS2 film is successfully synthesized, which is then used to fabricate top-gated (TG) MoS2 field-effect transistors with wafer-scale uniformity. Some basic circuits such as static random access memory and ring oscillators are examined. A pass-transistor logic configuration based on pseudo-NMOS is then employed to design more complex MoS2 logic circuits, which are successfully fabricated with proper logic functions tested. These preliminary integration efforts show the promising potential of wafer-scale 2D semiconductors for application in complex ICs.

Oridonin induces apoptosis in HGC-27 cells by activating the JNK signaling pathway.

Gastric cancer (GC) is a very common type of cancer. Although current treatment modalities include surgical resection and chemotherapy, many patients are either not eligible for radical resection or have a poor response to chemotherapy. Due to the complex features of the disease, there is a need for complementary therapy. In the present study, the effects of oridonin on cell proliferation, invasion and apoptosis were assessed in the HGC-27 cell line using the Cell Counting Kit-8 assay, real-time cell analysis, and an Annexin V-FITC/propidium iodide (PI) detection kit, respectively. The effect of oridonin on apoptosis, through the JNK pathway, was also investigated using western blotting. The present study demonstrated that oridonin can suppress cell viability and inhibit cell proliferation by inducing G2/M arrest. Oridonin also induced caspase-dependent apoptosis in cells by activating the phosphorylated-JNK/C-JUN pathway. These results demonstrate the potential of oridonin as a potential therapeutic compound for the treatment of GC.

Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1.

BACKGROUND: Arachidonic acid (AA) metabolic enzymes including cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1) and cytochrome P450 (CYP) 4A11 play important roles in glioma angiogenesis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. METHODS: A homology model of human CYP4A11 was constructed using SYBYL-X 2.0. Structure-based virtual screening against COX-2, mPGES-1 and CYP4A11was performed using the Surflex-Dock of the SYBYL suite. The candidates were further evaluated their antiangiogenic activities in a zebrafish embryo and rabbit corneal angiogenesis model. Laser doppler analysis was used to measure tumor perfusion. The expression of CD31 and α-SMA was measured by immunofluorescence. Western blot was used to measure the expression of HIF-1, Akt and p-Akt. The gene expression of FGF-2, G-CSF, PDGF, TGF-ß, Tie-2, VEGF, lncRNA NEAT1 and miR-194-5p were determined using qPCR. The production of FGF-2, TGF-ß and VEGF were analyzed using ELISA. Bioinformatic analysis and luciferase reporter assays confirmed the interaction between lncRNA NEAT1 and miR-194-5p. RESULTS: The nearly 36,043 compounds from the Traditional Chinese Medicine (TCM) database were screened against COX-2, mPGES-1 and CYP4A11 3D models, and the 17 top flavonoids were identified. In zebrafish screening, isoliquiritigenin (ISL) exhibited the most potent antiangiogenic activities with the EC50 values of 5.9 µM. Conversely, the antiangiogenic effects of ISL in the zebrafish and rabbit corneal models were partly reversed by 20-hydroxyeicosatetraenoic acid (20-HETE) or prostaglandin E2 (PGE2). ISL normalized glioma vasculature and improved the efficacy of temozolomide therapy in the rat C6 glioma model. Inhibition of COX-2, mPGES-1 and CYP4A by ISL decreased FGF-2, TGF-ß and VEGF production in the C6 and U87 glioma cells with p-Akt downregulation, which was reversed by Akt overexpression. Furthermore, ISL downregulated lncRNA NEAT1 but upregulated miR-194-5p in the U87 glioma cell. Importantly, lncRNA NEAT1 overexpression reversed ISL-mediated increase in miR-194-5p expression, and thereby attenuated FGF-2, TGF-ß and VEGF production. CONCLUSIONS: Reprogramming COX-2, mPGES-1 and CYP4A mediated-AA metabolism in glioma by flavonoid ISL inhibits the angiogenic Akt- FGF-2/TGF-ß/VEGF signaling through ceRNA effect of miR-194-5p and lncRNA NEAT1, and may serve as a novel therapeutic strategy for human glioma.

Cardiovascular Benefits of Fish-Oil Supplementation Against Fine Particulate Air Pollution in China.

BACKGROUND: Few studies have evaluated the health benefits of omega-3 fatty acid supplementation against fine particulate matter (aerodynamic diameter <2.5 µm [PM2.5]) exposure in highly polluted areas. OBJECTIVES: The authors sought to evaluate whether dietary fish-oil supplementation protects cardiovascular health against PM2.5 exposure in China. METHODS: This is a randomized, double-blinded, and placebo-controlled trial among 65 healthy college students in Shanghai, China. Participants were randomly assigned to either the placebo group or the intervention group with dietary fish-oil supplementation of 2.5 g/day from September 2017 to January 2018, and received 4 rounds of health examinations in the last 2 months of treatments. Fixed-site PM2.5 concentrations on campus were measured in real time. The authors measured blood pressure and 18 biomarkers of systematic inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism, and neuroendocrine stress response. Acute effects of PM2.5 on these outcomes were evaluated within each group using linear mixed-effect models. RESULTS: The average PM2.5 level was 38 µg/m3 during the study period. Compared with the placebo group, the fish-oil group showed relatively stable levels of most biomarkers in response to changes in PM2.5 exposure. Between-group differences associated with PM2.5 exposure varied by biomarkers and by lags of exposure. The authors observed beneficial effects of fish-oil supplementation on 5 biomarkers of blood inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response in the fish-oil group at a false discovery rate of <0.05. CONCLUSIONS: This trial shows that omega-3 fatty acid supplementation is associated with short-term subclinical cardiovascular benefits against PM2.5 exposure among healthy young adults in China. (Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution; NCT03255187).

Ginsenosides and ginsenosidases in the pathobiology of ginseng-Cylindrocarpon destructans (Zinss) Scholten.

To investigate the role that ginsenosides (and some of their metabolites) play in interactions between plants and phytopathogenic fungi (e.g. Cylindrocarpon destructans (Zinss) Scholten), we systematically determined the anti-fungal activities of six major ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1), along with the metabolites of ginsenoside Rb1 (Gypenoside XVII (G-XVII) and F2), against the ginseng root pathogen C. destructans (Zinss) Scholten and non-ginseng pathogens Fusarium graminearum Schw., Exserohilum turcicum (Pass.) Leonard et Suggs, Phytophthora megasperma Drech. and Pyricularia oryzae Cav. Our results showed that the growth of both ginseng pathogens and non-pathogens could be inhibited by using the proto-panaxatriol (PPT) ginsenosides Re and Rg1. In addition, the growth of the non-pathogens could also be inhibited by using proto-panaxadiol (PPD) ginsenosides Rb1, Rb2, Rc and Rd, whereas the growth of ginseng pathogen C. destructans (Zinss) Scholten was enhanced by ginsenosides Rb1 and Rb2. In contrast, ginsenoside G-XVII and F2 strongly inhibited the hyphal growth of both C. destructans (Zinss) Scholten and the non-pathogens tested. Furthermore, addition of sucrose to the media increased the growth of C. destructans (Zinss) Scholten, whereas glucose did not affect the growth. Moreover, C. destructans (Zinss) Scholten and all four non-pathogens were able to deglycosylate PPD ginsenosides using a similar transformation pathway, albeit with different sensitivities. We also discussed the anti-fungal structure-activity relationships of the ginsenosides. Our results suggest that the pathogenicity of C. destructans (Zinss) Scholten against ginseng root is independent of its ability to deglycosylate ginsenosides.

[Post-stroke unilateral spatial neglect treated with acupuncture and rehabilitation: a randomized controlled trial].

OBJECTIVE: To observe the impacts on post-stroke unilateral spatial neglect treated with acupuncture for "regaining consciousness, benefiting marrow and opening orifices" and rehabilitation. METHODS: Forty patients of post-stroke unilateral spatial neglect were randomized into an observation group and a control group, 20 cases in each one. In the observation group, acupuncture was applied to the acupoints for "regaining consciousness, benefiting marrow and opening orifices", named Baihui (GV 20), Sishencong (EX-HN 1), Benshen (GB 13), Shenting (GV 24), and the bilateral yuan-primary points and luo-connecting points of the heart meridian, pericardium meridian and kidney meridian, as well as the acupoints along the affected meridians. Additionally, the rehabilitation was provided. In the control group, acupuncture at the acupoints along the affected meridians and rehabilitation were adopted. The treatment was given once a day, 5 times a week. After 8 weeks of treatment the evaluation was made. the indexes of unilateral spatial neglect such as line bisection test, the score of the mini-mental state examination (MMSE), the score of simple Fugl-Meyer motor function assessment and the modified Barthel indexes were adopted for the assessment of the severity of unilateral spatial neglect, cognitive function, motor function, and the activities of daily living. RESULTS: After treatment, the indexes of unilateral spatial neglect (line bisection test, line cancellation test, clock-drawing test and copying drawing test), MMSE score, the simple Fugl-Meyer motor function assessment and modified Barthel indexes were all improved as compared with those before treatment in the two groups (all P<0.01). The improvements in the observation group were more obvious than those in the control group (P<0.05, P<0.01). CONCLUSION: The combination of acupuncture treatment for "regaining consciousness, benefiting marrow and opening orifices" and rehabilitation much more effectively alleviates the severity of post-stroke unilateral spatial neglect and improves the motor function and the activities of daily living in the patients.

Enteral supplementation of alanyl-glutamine attenuates the up-regulation of beta-defensin-2 protein in lung injury induced by intestinal ischemia reperfusion in rats.

BACKGROUND: Beta-defensin-2 (BD-2), an endogenous antimicrobial peptide, plays a key role in immune response against microbial invasion. This study aimed to observe the effect of Alanyl-Glutamine (Ala-Gln) on BD-2 protein expression in pulmonary tissues after intestinal ischemia reperfusion (IIR) in rats and to investigate its correlations to pulmonary inflammatory and oxidative injury. METHODS: Rats in IIR and the two treatment groups were subjected to intestine ischemia for 60 min and those in the treatment groups were administered orally with Ala-Gln or alanine (Ala) respectively. Lung tissues were harvested to detect the BD-2 protein expression. Concentrations of Tumor necrosis factor (TNF)-α and malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity in lung tissues were determined simultaneously. RESULTS: Ala-Gln attenuated the up-regulation of BD-2 expression (p < 0.05) and TNF-α (p < 0.05), MDA (p < 0.05) levels, as well as the reduction of SOD activity (p < 0.05) in lung tissues after IIR. But Ala did not exert significant effects. BD-2 protein in lung tissues was positively correlated to local TNF-α level (p < 0.01) and MDA concentration (p < 0.01) with statistical significance. CONCLUSION: Ala-Gln can relieve the IIR-induced up-regulation of BD-2 protein expression in the lung of rats, which involves anti-inflammation and anti-oxidation mechanisms.

Sweetened beverages, coffee, and tea and depression risk among older US adults.

Sweetened beverages, coffee, and tea are the most consumed non-alcoholic beverages and may have important health consequences. We prospectively evaluated the consumption of various types of beverages assessed in 1995-1996 in relation to self-reported depression diagnosis after 2000 among 263,923 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions. The OR (95% CI) comparing ≥4 cans/cups per day with none were 1.30 (95%CI: 1.17-1.44) for soft drinks, 1.38 (1.15-1.65) for fruit drinks, and 0.91 (0.84-0.98) for coffee (all P for trend<0.0001). Null associations were observed for iced-tea and hot tea. In stratified analyses by drinkers of primarily diet versus regular beverages, the ORs were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft drinks, 1.51 (1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit drinks, and 1.25 (1.10-1.41) for diet versus 0.94 (0.83-1.08) for regular sweetened iced-tea. Finally, compared to nondrinkers, drinking coffee or tea without any sweetener was associated with a lower risk for depression, adding artificial sweeteners, but not sugar or honey, was associated with higher risks. Frequent consumption of sweetened beverages, especially diet drinks, may increase depression risk among older adults, whereas coffee consumption may lower the risk.

Dietary fat intake, pesticide use, and Parkinson's disease.

BACKGROUND: Dietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides. METHODS: We conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor α-linolenic acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with α-linolenic acid (0.81, 0.68-0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p-interaction = 0.02). CONCLUSIONS: PUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD.

Caffeine intake, smoking, and risk of Parkinson disease in men and women.

The authors prospectively examined whether caffeine intake was associated with lower risk of Parkinson disease (PD) in both men and women among 304,980 participants in the National Institutes of Health-AARP Diet and Health Study and whether smoking affected this relation. Multivariate odds ratios and 95% confidence intervals were derived from logistic regression models. Higher caffeine intake as assessed in 1995-1996 was monotonically associated with lower PD risk (diagnosed in 2000-2006) in both men and women. After adjustment for age, race, and physical activity, the odds ratio comparing the highest quintile of caffeine intake with the lowest was 0.75 (95% confidence interval: 0.60, 0.94; P(trend) = 0.005) for men and 0.60 (95% confidence interval: 0.39, 0.91; P(trend) = 0.005) for women. Further adjustment for duration of smoking and analyses carried out among never smokers showed similar results. A joint analysis with smoking suggested that smoking and caffeine may act independently in relation to PD risk. Finally, the authors conducted a meta-analysis of prospective studies and confirmed that caffeine intake was inversely associated with PD risk in both men and women. These findings suggest no gender difference in the relation between caffeine and PD.

Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee.

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)<5×10(-8) in GWAIS, and OR = 0.41, P = 3×10(-8) in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients.

Multivitamins, individual vitamin and mineral supplements, and risk of diabetes among older U.S. adults.

OBJECTIVE: Understanding the relationship between multivitamin use and diabetes risk is important given the wide use of multivitamin supplements among U.S. adults. RESEARCH DESIGN AND METHODS: We prospectively examined supplemental use of multivitamins and individual vitamins and minerals assessed in 1995-1996 in relation to self-reported diabetes diagnosed after 2000 among 232,007 participants in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Multivitamin use was assessed by a food-frequency questionnaire at baseline. Odds ratios (ORs) and 95% CIs were calculated by logistic regression models, adjusted for potential confounders. In total, 14,130 cases of diabetes diagnosed after 2000 were included in the analysis. RESULTS: Frequent use of any multivitamins was not associated with risk of diabetes after adjustment for potential confounders and uses of individual supplements. Compared with nonusers of any multivitamins, the multivariate ORs among users were 1.07 (95% CI 0.94-1.21) for taking vitamins less than once per week, 0.97 (0.88-1.06) for one to three times per week, 0.92 (0.84-1.00) for four to six times per week, and 1.02 (0.98-1.06) for seven or more times per week (P for trend = 0.64). Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements. The multivariate ORs comparing daily users with nonusers were 0.91 (0.86-0.97) for vitamin C supplements and 0.85 (0.80-0.90) for calcium supplements. Use of vitamin E or other individual vitamin and mineral supplements were not associated with diabetes risk. CONCLUSIONS: In this large cohort of U.S. older adults, multivitamin use was not associated with diabetes risk. The findings of lower diabetes risk among frequent users of vitamin C or calcium supplements warrant further evaluations.

Multivitamin use and telomere length in women.

BACKGROUND: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation. OBJECTIVE: The objective was to examine whether multivitamin use is associated with longer telomeres in women. DESIGN: We performed a cross-sectional analysis of data from 586 early participants (age 35-74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction. RESULTS: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins. CONCLUSION: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.

Dietary iron intake and risk of Parkinson's disease.

Dietary iron is the most important source of iron stores. Several case-control studies have described the association of high dietary iron and Parkinson's disease, but prospective data are lacking. The authors prospectively followed 47,406 men and 76,947 women from the United States who provided information through a mailed questionnaire on their diet, medical history, and lifestyle practices between 1984 and 2000. The authors documented 422 new cases of Parkinson's disease. Total iron intake was not associated with an increased risk of Parkinson's disease (relative risk (RR) = 1.10, 95% confidence interval (CI): 0.74, 1.65; P(trend) = 0.84), but dietary nonheme iron intake from food was associated with a 30% increased risk of Parkinson's disease (RR = 1.27, 95% CI: 0.92, 1.76; P(trend) = 0.02). A secondary analysis revealed that Parkinson's disease risk was significantly increased among individuals with high nonheme iron and low vitamin C intakes (RR = 1.92, 95% CI: 1.14, 3.32; P(trend) = 0.002). Supplemental iron intake was associated with a borderline increase in Parkinson's disease risk among men. Although the authors' prospective data did not support an association between total iron intake (dietary and supplemental) and risk of Parkinson's disease, a 30% increased risk was associated with a diet rich in nonheme iron. This increase in risk was present in those who had low vitamin C intake.

Recreational physical activity and risk of Parkinson's disease.

The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men > or = 23 metabolic equivalent task-hours/week [MET-h/wk], women > or = 18.5 MET-h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men > or = 16 MET-h/wk, women > or = 11.5 MET-h/wk) to the lowest (0 MET-h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow-up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD.

The effect of acupuncture on plasma endothelin content in cerebral infarction patients--a clinical study.

OBJECTIVE: To observe the effect of acupuncture on content of plasma endothelin in cerebral infarction patients. METHODS: The plasma endothelin content in cerebral infarction patients was observed before and after acupuncture, which was compared with that of the medication group and the healthy subjects. RESULTS: Before treatment, the content of plasma endothelin in cerebral infarction patients was significantly higher than that of the healthy subjects (P<0.01); after acupuncture treatment, the content greatly decreased (P<0.01), and there was a statistically significant difference between the acupuncture group and the medication group (P<0.05). CONCLUSION: Acupuncture may decrease the content of plasma endothelin in the cerebral infarction patients, improve the vascular elasticity, and improve the cerebral circulation of blood.

A prospective study of night shift work, sleep duration, and risk of Parkinson's disease.

The authors prospectively investigated whether working rotating night shifts was associated with the risk of Parkinson's disease among 84,794 female nurses who reported years of night shift work in 1988 (the US Nurses' Health Study). After 975,912 person-years of follow-up (1988-2000), 181 incident Parkinson's disease cases were documented. Compared with nurses who never worked rotating night shifts, those with 15 years or more of night shift work had a 50% lower risk of Parkinson's disease after adjustment for age and smoking (95% confidence interval: 0.26, 0.97; p(trend) = 0.01). Sleep duration was positively associated with Parkinson's disease risk: The relative risk was 1.84 (95% confidence interval: 0.99, 3.42) when comparing nurses who reported 9 or more hours of sleep per day with those who slept 6 hours or less (p(trend) = 0.005). These data suggest that working night shifts may be protective against Parkinson's disease or that low tolerance for night shift work is an early marker of Parkinson's disease. Conversely, habitual longer sleep duration may be an earlier marker of Parkinson's disease. Because of the novelty and the exploratory nature of these findings, confirmation is needed.

Therapeutic effects and molecular mechanisms of Ginkgo biloba extract on liver fibrosis in rats.

Oxidative stress can be implicated as a cause of liver fibrosis. In this sense, Ginkgo Biloba Extract (EGB), an antioxidant, may be beneficial in restraining liver fibrosis. The aim of this study was to evaluate the effects of EGB on experimental liver fibrosis. Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) twice a week for 8 weeks. Three groups of rats received EGB (0.25, 0.5 and 1.0 g/kg, respectively) by stomach everyday. CCl4 administration induced liver fibrosis, which was inhibited by EGB in a dose-dependent manner. The histopathologic score of fibrosis, liver function and the levels of plasma hyaluronic acid (HA) and laminin (LN) were significantly improved in rats treated with CCl4 + EGB, compared with those treated with CCl4 only (p < 0.01 or p < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were notably elevated, while malondialdehyde (MDA) content was significantly decreased in the rats treated with CCl4 + EGB (p < 0.01 or p < 0.05). Inhibition of hepatic stellate cell (HSC) activation and nuclear factor kappaBP65 (NF-kappaBP65) expression was demonstrated in the livers of EGB-treated rats. The activation of NF-kappaB was significantly suppressed in EGB-treated rats determined by electrophoretic mobility shift assay (EMSA). Furthermore, EGB reduced expressions of transforming growth factor-beta1 (TGF-beta1) and collagen I mRNA. In conclusion, EGB is able to ameliorate liver injury and prevent rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on HSC activation and the expression of TGF-beta1.

Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice.

The effects of isoliensinine (IL), a bisbenzylisoquinoline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn., on bleomycin (BLM)-induced pulmonary fibrosis in mice were investigated. Seventy-two male Kungming mice were divided randomly into eight groups as BLM-IL10, BLM-IL20, BLM-IL40, BLM-Sal, Sal-IL10, Sal-IL20, Sal-IL40 and Sal-Sal groups. BLM (0.1 mg in 0.05 ml saline per animal, once) or saline (0.05 ml per animal, once) was applied intratracheally, and IL (10, 20, 40 mg/kg) or saline was administered orally 3 times per day in the appropriate groups. Animals were sacrificed 14 days after intratracheal treatment. Lung tissue and serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta 1 (TGF-beta (1)) were determined by biochemical measurements and immunohistochemistry. BLM treatment resulted in a significant increase of the hydroxyproline content and an obvious lung histological injury as compared to the Sal-Sal group. Administration of IL remarkably suppressed the increase in hydroxyproline content and abated the lung histological injury induced by BLM. There was a decrease in SOD activity and an increase in MDA level in lung tissue and serum in the BLM-Sal group (p < 0.01 , p < 0.01, vs. Sal-Sal group, respectively). And IL could obviously enhance the SOD activity and decrease the MDA level in a concentration-dependent manner. Moreover, IL also significantly inhibited the overexpression of TNF-alpha and TGF-beta (1) induced by BLM. These results indicated that IL possessed a significant inhibitory effect on BLM-induced pulmonary fibrosis, probably due to its antioxidant and/or anti-inflammatory activities and inhibitory overexpressing TNF-alpha and TGF-beta (1) induced by BLM.