Chronic alpha-linolenic acid treatment alleviates age-associated neuropathology: Roles of PERK/eIF2α signaling pathway.

Aging is a principal risk factor for neurodegenerative diseases and especially shares similar pathologic mechanisms to Alzheimer's disease (AD). Amyloid-ß (Aß) plaques deposition and neurofibrillary tangles (NFTs) are the prominent age-dependent pathologies implicated in the cognitive deficits. Accumulation of mis-folded proteins in the endoplasmic reticulum triggers a cellular stress response called the unfolded protein response (UPR), the activation of which is increased in AD patients. However, the UPR relates to the pathological hallmarks of aging is still elusive. In this study, we report that long-term supplement of α-linolenic acid (ALA), starting before the onset of disease symptoms (6month-old), prevents the age-related memory deficits during natural aging. The amelioration of the memory impairment is associated with a decrease in UPR related markers [glucose regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), eukaryotic Initiation Factor 2α (eIF2α)]. ALA suppressed the PERK/eIF2α signaling, which may be responsible for multifaceted memory-deteriorating and neurodegenerative mechanisms, including inhibition of Aß production by suppressing ß-site APP-cleaving enzyme 1 (BACE1) expression, enhancement of cAMP response element binding protein (CREB) function via down-regulating activating transcription factor 4 (ATF4), and suppression of Tau phosphorylation by inhibiting glycogen synthase kinase 3ß (GSK-3ß) pathway. Taken together, our findings provide new insights into the link between ALA and PERK/eIF2α signaling, which could contribute to a better understanding of an ALA-mediated protective effect in aging-associated neuropathology.

Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague-Dawley rats.

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage.

Intensive blood pressure control on arterial stiffness among older patients with hypertension.

BACKGROUND: Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. METHODS: The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60-80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes. RESULTS: The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8-73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7-110.1 cm/s) in the standard treatment group (P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s-1·year-1vs. 36.7 cm·s-1·year-1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70-80 years or with SBP <140 mmHg. CONCLUSION: Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; No. NCT03015311.

Achieved systolic blood pressure and cardiovascular outcomes in 60-80-year-old patients: the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial.

AIMS: Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, data is missing on patients who had target-achieved (TA). This study aims to show the cardiovascular effect of maintaining SBP at intensive levels. METHODS: The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60-80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg). This secondary analysis assessed data in patients who achieved a mean SBP within target values. The association of mean achieved SBP and cardiovascular events was examined using a cubic spline function. RESULTS: In total, 3053 patients (72.0%) in the intensive-treatment group and 3427 (80.3%) in the standard-treatment group had an SBP target achieved, with mean follow-up SBP values of 124.2 mmHg and 137.4 mmHg, respectively. Throughout the median 3.38-year follow-up, the cardiovascular risk was significantly lower in the TA intensive-treatment group than in the TA standard-treatment group [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.46-0.80; P < 0.001]. In the intensive-treatment group, patients failing to achieve SBP targets presented higher cardiovascular risk than those TA patients (HR 2.04, 95% CI 1.44-2.88; P < 0.001). A J-shaped relationship was observed between the mean achieved SBP and risk of cardiovascular events, with the lowest risk at an SBP of 126.9 mmHg. CONCLUSIONS: Maintaining SBP at <130 mmHg offers additional cardiovascular benefits among young-older patients with hypertension. REGISTRATION: ClinicalTrials.gov: NCT03015311.

This present study is a secondary analysis that investigated the association between mean achieved BP in the two treatment groups (SBP target, 110 to <130 vs. 130 to <150 mmHg) and their cardiovascular outcomes in the STEP study (60­80-year-old patients with hypertension).Patients achieving a target in the intensive-treatment group have better cardiovascular outcome than patients achieving a target in the standard treatment arm, supporting the cardiovascular benefits of maintaining SBP <130 mmHg.J-shaped relationships were observed between mean achieved SBP and cardiovascular outcomes (with the nadir around 130 mmHg), but not for stroke.

Procyanidins extracted from the lotus seedpod ameliorate scopolamine-induced memory impairment in mice.

The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) in mice. The capacities of memory and learning were evaluated by the Morris water maze and the step-down avoidance test. LSPC (50, 100, 150 mg/kg BW, p.o.) significantly reversed scopolamine-induced learning and memory impairments in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. In the step-down avoidance test, LSPC (50, 100, 150 mg/kg BW, p.o.) treatment significantly reduced the number of errors and shortened latency compared with that of scopolamine. In addition, LSPC was also found to inhibit acetyl cholinesterase (AChE) activity. These results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by AD and aging.

Seroprevalence of antibodies for pertussis and diphtheria among people leaving or entering China: a cross-sectional study.

INTRODUCTION: Despite high population immunity, pertussis remains one of the leading causes of vaccine-preventable deaths worldwide. The aim of this study was to determine the seroprevalence of IgG antibodies to pertussis toxin (PT) and diphtheria among the adult male population leaving or entering China. METHODOLOGY: Blood samples were obtained from 240 Chinese and 207 African healthy adults that were leaving and entering China, respectively. Serum IgG antibodies against PT (anti-PT IgG) and diphtheria were determined. RESULTS: The mean concentration of anti-PT IgG antibodies was 13.82 IU/mL and 18.11 IU/mL for the leaving and entering populations, respectively. None of the studied Chinese leaving China were seropositive for pertussis. Of the 240 subjects leaving China, 209 (87.1%) had anti-diphtheria antibody concentrations of ≥ 0.1 IU/mL and 31 (12.9%) had antibody concentrations between 0.01 and 0.099 IU/mL. Eleven (5.31%) of the studied Africans entering China had anti-PT IgG antibodies higher than 30 IU/mL and thus were considered seropositive for pertussis. Of the 207 Africans entering China, antibody concentrations of ≥ 0.1 IU/mL were found in 164 subjects (79.2%) while 43 (20.8%) had antibody concentrations between 0.01 and 0.099 IU/mL. CONCLUSIONS: Almost all Chinese adult men leaving China and most African men entering China have very low serum antibody levels of pertussis. Furthermore, the antibody level of diphtheria among these two populations was low among adults. A larger population study is needed to determine whether booster vaccinations against pertussis and diphtheria should be considered for adults in China and also for Africans entering China.

[Analysis of impact factors on children's neurobehavioral functions by answertree].

OBJECTIVE: To explore the latent neurobehavioral function impairments by traffic exhausts and other factors on the children. METHODS: Two primary schools were chosen according to the air quality report in Beijing. School B is located at seriously exhausts polluted area while school A is at less polluted area. All children in grade three and grade four were selected as our objects. The survey was conducted based on the agreement of the children's parents. NES was employed to measure the children's neurobehavioral functions while the 24 hour NO2 and SO2 personal exposure levels, Zinc Protoporphyrin (ZZP) and CO levels in expiration gas were measured. Then, Answertree was used. RESULTS: It is indicated that neurobehavioral functions of children were associated with the education level of children's mothers, children's personal COHb levels and personal SO2 exposure levels. CONCLUSION: The children, whose mothers' education level were middle, with high personal COHb levels and SO2 exposure levels were the high risk population.

[Advancements of the studies on the relationships between air temperature and solar activity with diseases].

Varieties of air temperature and solar activity have a close correlation with human health. The megatemperature mainly results in the increased incidence of cerebrovascular disorder (CVD). It is related to the regulatory mechanism of homeothermism. In the hypothermy environment, obvious increment of human's blood viscosity was observed, which may induce the cerebral infarction, myocardial infarct or coronary heart disease. Not only have solar activities a close relationship with the incidences of plague and epidemic cerebrospinal meningitis, but also high correlation with onco-genesis and infant natality and mortality. UV-A and UV-B may cause skin destructions. The measures and further study on lessening hazards of climate change were discussed in this article.

Procyanidins extracted from the lotus seedpod ameliorate age-related antioxidant deficit in aged rats.

The alleviative effect of procyanidins extracted from the lotus seedpod (LSPC) on oxidative stress in various tissues was evaluated by determining the activities of the antioxidant enzymes and the content of reduced glutathione (GSH) in heart, liver, lung, kidney, skeletal muscle, and serum in aged rats. Aging led to antioxidant deficit in various tissues in this study, which is confirmed by remarkable increased lipid peroxidation, whereas the change patterns of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and GSH were diverse in various tissues of aged rats. LSPC treatment (50 and 100 mg/kg body weight) modified the activity of SOD, CAT, and GPx as well as GSH content alteration in these tissues, which reversed the age-related antioxidant deficit in aged rats. However, the regulatory patterns on the activities of these enzymes and GSH content by LSPC treatment were different according to the tissues in aged rats.

Memory impairment in cognitively impaired aged rats associated with decreased hippocampal CREB phosphorylation: reversal by procyanidins extracted from the lotus seedpod.

The major purpose of this study was to determine the effects of procyanidins extracted from the lotus seedpod on cAMP-response element-binding protein phosphorylation in hippocampus and cerebral cortex in cognitively impaired aged rats. Based on Morris water maze, aged unimpaired and aged impaired rats were chosen from aged rats. Comparing with young and aged unimpaired animals, aged impaired rats exhibited significant reduction in hippocampal but not cortical cAMP-response element-binding phosphorylation states as well as brain-derived neurotrophic factor messenger RNA and protein expressions, which were accompanied by decreased phosphorylation states of hippocampal extracellular signal-related kinase (42/44) and calcium calmodulin kinase IV. Lotus seedpod supplementation (50 and 100 mg/kg body weight intragastric administration) for 7 weeks significantly reversed all these declines happened in hippocampus except calcium calmodulin kinase IV phosphorylation levels. These results suggested that lotus seedpod might enhance cAMP-response element-binding-dependent transcription through the activation of extracellular signal-related kinase signalling pathway, which might contribute to its ameliorative effects on cognitive deficits in aged impaired animals.

Comparison of risk factors associated with hypertension subtypes by classification tree method in Tongshan County of Jiangsu Province, China.

BACKGROUND: There are only a very limited number of studies relating to risk factors for hypertension in rural populations in China. There are even fewer studies comparing various hypertension subtypes. METHODS: A cross-sectional investigation was carried out in a representative sample of 20,390 subjects drawn from among 1,180,000 adult residents of Tongshan County of Jiangsu Province, China. The impact of risk factors including demographic, socioeconomic, dietary, and behavioral, on three hypertension subtypes, namely, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH), was analyzed by applying statistical tests and a classification tree. RESULTS: ISH was the predominant untreated hypertension subtype (13.68 +/- 0.24%) in the adults of Tongshan County, followed by SDH (11.70 +/- 0.23%) and IDH (6.24 +/- 0.17%). Age, number of cigarettes smoked daily, and the types of vitamins taken varied among the ISH, IDH, and SDH classification trees. Low socioeconomic status was associated with an increased risk for ISH and SDH. Light alcohol intake was associated with higher risk for ISH, but with lower risks for IDH and SDH. Light cigarette smoking was associated with higher ISH risk but lower SDH risk. The intake of appropriate amounts of fish, shrimp, or meat lowered the risks for ISH and IDH. The intake of appropriate amounts of seafood, eggs, milk, or fruit lowered the risks for all hypertension subtypes. Interestingly, an excessive preference for sweet or salty foods was associated with a higher risk for all the subtypes. CONCLUSIONS: In Tongshan County, there was a considerable prevalence of hypertension of various subtypes, each associated with distinctive and complex risk factors. This suggests that there is a need for testing more diverse prevention measures, tailored to specific subtypes.

Rejuvenation of antioxidant and cholinergic systems contributes to the effect of procyanidins extracted from the lotus seedpod ameliorating memory impairment in cognitively impaired aged rats.

The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments in cognitively impaired aged rats. Based on Morris water maze performance compared with young female rats, aged unimpaired (AU) and aged impaired (AI) rats were chosen from aged female rats. LSPC supplementation (50, 100 mg/kg BW, p.o.) for 7 weeks significantly improved learning and memory impairments in AI animals in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. Aged rats had significantly declined antioxidant defense capacities and significantly increased lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex than young rats. Further, AI group had higher protein oxidation level compared with AU group. LSPC (50, 100 mg/kg BW, p.o.) significantly reversed the decline of antioxidant defense capacities and significantly reduced lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex of AI rats. In addition, LSPC significantly restored acetylcholine (ACh) contents and acetylcholinesterase (AChE) activities in hippocampus and cerebral cortex of AI animals. The results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by Alzheimer's disease and aging.