MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3ß.

This study aims to investigate the effects and underlying mechanisms of overexpression microRNA-9-5p (miR-9-5p) on the Aß-induced mouse hippocampal neuron cell line HT22. Different concentrations of Aß25-35 (10, 20, 40, 80, and 160 µM) treatment were used to establish AD model in HT22 cells. The CCK-8 assay was used to measure the cell viability. The mRNA expression levels of miR-9-5p and glycogen synthase kinase-3ß (GSK-3ß) were determined by RT-qPCR. HT22 cell apoptosis was analyzed flow cytometry. MiR-9-5p was down-regulated in Aß25-35-induced HT22 cells. GSK-3ß is a functional target for miR-9-5p. MiR-9-5p overexpression inhibited Aß25-35-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress by regulating GSK-3ß expression in HT22 cells. Furthermore, through targeting GSK-3ß, overexpression of miR-9-5p partly activated nuclear factor Nrf2/Keap1 signaling, including part increases of Nrf2, HO-1, SOD-1, GCLC expression and slight decrease of Keap1 expression. Our results showed miR-9-5p may play a powerful role in the pathogenesis of AD.

Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau.

OBJECTIVE: Several environmental factors including hypoxia have been reported to contribute to oxidative stress in individuals living in the highlands. However, little is known about the role of oxidized low-density lipoprotein (ox-LDL) among community-dwelling elderly in the Qinghai-Tibet plateau. METHODS: The study population comprised 168 community-dwelling elderly subjects aged 60 years or older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan County, located 3000 to 3200 m above sea level, 30 km northwest of Xining, Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody-based enzyme-linked immunosorbent assay. RESULTS: Mean ox-LDL level was higher among Tibetan elderly than Han elderly (Tibetan, 79.0 ± 29.6 U/L; Han, 62.8 ± 23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL levels (≥70 U/L) were significantly associated with a homeostasis model assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after adjusting for age, sex, and ethnicity. CONCLUSIONS: Our findings support the hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders compared with those among Han elderly. As ox-LDL levels can affect insulin resistance and arteriosclerosis, further research is needed to determine how oxidative stress influences the health situation among elderly individuals at high altitudes.

Prochloraz induced alterations in the expression of mRNA in the reproductive system of male offspring mice.

Prochloraz is a widely used fungicide worldwide. It is classified as an endocrine disrupting pesticide that affects the reproductive system. This study aimed to examine the impact of exposure to prochloraz of male mice on the reproductive system of their offspring male mice. Male father mice were intragastrically administered different dosages of prochloraz (group MA: 0 mg/kg/day; MB: 53.33 mg/kg/day; MD:160 mg/kg/day). Then, the testicular average weight of male offspring in the dose groups was found to be significantly lower than those in the control group (MB:0.312g, MD:0.294g, and MA:0.355 g; P < 0.05). Additionally, the testicular coefficient index in the MB and MD groups was also lower than that of the control group. Secondly,we observed that there were significantly different expressed genes clustered in groups B and D, in contrast to the control. Finally, the findings demonstrated a significant alteration in the response of male mice reproductive relative genes to prochloraz invasion. Two genes (Mt-nd6 and Slc12a4) were found to be involved in the regulation of sperm mitochondria function and six genes (Greb1, Esrrb, Catsperb, Mospd2, Sohlh1 and Specc1) were closely linked to sperm functions and estrogen response. The study revealed a significant impact of prochloraz on the reproductive system of male mice, thereby supporting further investigation into the reproductive toxicological effects of the drug.

[Echinococcosis prevalence in elderly population from Haiyan County of Qinghai Province].

Echinococcus infection in elderly population (60-87 years old) was investigated by serological assay, medical imaging and epidemiology history in August, 2008. A total of 234 subjects from different nationalities were examined. Seven cases were serologically positive for echinococcosis and confirmed by medical imaging. Out of 30 suspected sera-positive cases, 3 were positive by medical imaging. There were 10 confirmed echinococcosis cases with a positive rate of 4.3%. There was significant difference on the prevalence among different towns (P < 0.05), but no significant statistical difference on the prevalence among nationalities, careers and sex. The prevalence in females (4.8%) was higher than that of males (3.6%).

Is it possible to reverse frailty in patients with chronic obstructive pulmonary disease?

In recent years, frailty has attracted increasing attention from clinicians and health care workers. The influence of frailty on the elderly, especially those with chronic diseases of the respiratory system, is highly significant. Frailty is particularly more common in patients with chronic obstructive pulmonary disease (COPD). Frailty and COPD share many risk factors and pathophysiological mechanisms. As a comprehensive interventional method for chronic respiratory diseases, pulmonary rehabilitation is an important basic measure for the management of patients with COPD. Frailty in these patients can be reversed using pulmonary rehabilitation by targeting five components of the frailty phenotype at the entry point. The present review discusses the benefits of pulmonary rehabilitation in patients with COPD complicated by frailty and provides a theoretical basis for pulmonary rehabilitation treatment in this population. In addition, the timing of pulmonary rehabilitation is also addressed, with the prefrail stage being the "golden" period. The implementation of pulmonary rehabilitation must vary among individuals, and individualized treatment strategies will help maximize benefits.

[Clinical study on effect of fluoxetine combined with Chinese medicine or tibetan drugs in treating senile depression in plateau district].

OBJECTIVE: To compare the ettect and side-ettect of fluoxetine and combination of fluoxetine and Chinese or Tibetan medicine in treating senile depression in plateau district. Methods Ninety patients with diagnosis of senile depression conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were randomly divided into three groups and treated with fluoxetine (group A), fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao pill (group C), respectively, 30 cases in each group. Therapeutic effects were evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom scale (TESS) after 6 weeks treatment. RESULTS: There was no significant difference in the therapeutic effects between the three groups. The adverse reaction in Group B and C was less than that in Group A (P<0.01). Conclusion Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients with senile depression in plateau area against the adverse reaction of fluoxetine.

Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

OBJECTIVES: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. DESIGN: Cross-sectional epidemiological study on Tibetan highlanders. PARTICIPANTS: We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). MAIN OUTCOME MEASURE: Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. RESULTS: The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. CONCLUSIONS: Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing.

Is it possible to reverse frailty in patients with chronic obstructive pulmonary disease?

In recent years, frailty has attracted increasing attention from clinicians and health care workers. The influence of frailty on the elderly, especially those with chronic diseases of the respiratory system, is highly significant. Frailty is particularly more common in patients with chronic obstructive pulmonary disease (COPD). Frailty and COPD share many risk factors and pathophysiological mechanisms. As a comprehensive interventional method for chronic respiratory diseases, pulmonary rehabilitation is an important basic measure for the management of patients with COPD. Frailty in these patients can be reversed using pulmonary rehabilitation by targeting five components of the frailty phenotype at the entry point. The present review discusses the benefits of pulmonary rehabilitation in patients with COPD complicated by frailty and provides a theoretical basis for pulmonary rehabilitation treatment in this population. In addition, the timing of pulmonary rehabilitation is also addressed, with the prefrail stage being the "golden" period. The implementation of pulmonary rehabilitation must vary among individuals, and individualized treatment strategies will help maximize benefits.

Comprehensive geriatric assessment of elderly highlanders in Qinghai, China I: activities of daily living, quality of life and metabolic syndrome.

AIM: To reveal the comparison of comprehensive geriatric functions of elderly highlanders in Qinghai Plateau in China among three different ethnic groups. METHODS: Activities of daily living (ADL), screening-based depression, quality of life (QOL) and checking-up of metabolic syndrome including community-based oral glucose tolerance test were assessed in 393 community-dwelling elderly subjects aged 60 years or more (247 Han elderly subjects, 49 Mongolian ones and 97 Tibetan ones). RESULTS: Tibetan elderly highlanders were more disabled in ADL, but had higher QOL than Han elderly ones in Qinghai Plateau. Blood pressure measurements, rate of hypertension and hemoglobin concentrations in Tibetan elderly highlanders were lower than Han ones. Rates of diabetes and impaired glucose tolerance in elderly highlanders were relatively lower than other Asian elderly lowlanders. CONCLUSION: Prevalence of metabolic syndrome in elderly highlanders in Qinghai was still not high, however, we should pay attention to its tendency related with socialglobalism in the near future. Further investigation on physiological adaptability to hypoxic environment and human ageing phenomena in a global context may open a new research frontier for ageing science.

Comprehensive geriatric assessment of elderly highlanders in Qinghai, China II: the association of polycythemia with lifestyle-related diseases among the three ethnicities.

AIM: The objective of this study is to disclose the association of polycythemia with lifestyle-related diseases (hypertension, obesity and glucose intolerance) among the three ethnicities in Qinghai, China. METHODS: The subjects were 393 elderly people (247 Han, 97 Tibetan and 49 Mongolian) aged 60 years and more living in Qinghai (3000 m a.s.l.) in China. The associated factors with polycythemia were analyzed in the subjects. Excessive polycythemia was defined as hemoglobin concentration over 20 mg/dL. RESULTS: Polycythemia was associated with men, hypoxemia, obesity and high diastolic blood pressure (DBP) in the elderly in Qinghai. Male sex was associated with polycythemia in all ethnicities. Obesity was associated with Han and Tibetan men. Glucose intolerance and activities of daily living were not directly associated with polycythemia after adjustment for sex. There were 7.9% with excessive polycythemia. Independently-associated factors for excessive polycythemia were male sex, body mass index of 25 or more, SpO(2) of less than 85%, DBP of 85 mmHg or more and Han ethnicity (vs Tibetan) by multiple logistic regression. CONCLUSION: There was a close association of polycythemia with diastolic hypertension and obesity in lifestyle-related diseases in high-altitude elderly people. Han people had a higher hemoglobin concentration after adjustment of lifestyle-related diseases compared with Tibetan people. The difference of hemoglobin concentration may be due to Tibetans undergoing a much longer period of adaptation than Han people. Further study is needed to disclose the association between the difference of hypoxic adaptation, lifestyle-related diseases and chronic mountain sickness for their prevention.

Comprehensive geriatric assessment of elderly highlanders in Qinghai, China, III: oxidative stress and aging in Tibetan and Han elderly highlanders.

BACKGROUND: Although there are several factors which may contribute to oxidative stress at high altitude, little is known about the association between oxidative stress and aging in the community-dwelling elderly in the Tibetan Plateau. METHODS: Reactive oxygen species (ROS) and comprehensive geriatric functions were examined among 235 community-dwelling elderly subjects aged 60 years or more (146 Hans and 89 Tibetans). As a marker of ROS, the levels of reactive oxygen metabolites (ROM) were measured using the d-ROM test. RESULTS: The rate of dependence of basic activities of daily living (basic ADL) among Tibetan elderly highlanders was significantly higher than that among Han elderly highlanders. The d-ROM level was higher among the Tibetan elderly than those among the Han elderly (Tibetan 465.6 +/- 97.9 Carr U, Han 415.3 +/- 72.0 Carr U, P = 0.003). The ROM level was higher among women than those among men. Stepwise multiple regression analysis showed that being Tibetan, female, and oxygen saturation were independent predictors of increasing d-ROM level (Tibetan beta, 0.241; female beta, 0.206; oxygen saturation beta, 0.218). The high levels of ROM (d-ROM >500 Carr U) were significantly associated with dependence of basic ADL after adjustment for age, sex and ethnicity (odds ratio = 2.51, P = 0.028). CONCLUSION: The findings of this study imply the possibility that ROS is higher among Tibetan elderly highlanders than that of Han, which related to the geriatric items. Further studies are needed to show the impact of oxidative stress on the aging of highlanders.

Comprehensive geriatric assessment of elderly highlanders in Qinghai, China IV: comparison of food diversity and its relation to health of Han and Tibetan elderly.

AIM: To examine the association between food diversity and health status of Han and Tibetan elderly highlanders in Qinghai Plateau, China. METHODS: The study population consisted of 240 community-dwelling elderly subjects aged 60 years or more (176 Han elderly subjects, 64 Tibetan ones). Food diversity was determined using an 11-item Food Diversity Score Kyoto (FDSK-11). Subjects were interviewed on health status including activities of daily living (ADL), screening-based depression and quality of life (QOL). Blood chemical investigation was carried out in association with food diversity. RESULTS: ADL was significantly lower in both Han and Tibetan elderly with lower food diversity than those with higher diversity. In Han elderly with lower food diversity, QOL was significantly lower in the items of subjective sense of health, relationship with family and subjective happiness, but not significant in Tibetan elderly. A close association was found between lower food diversity and lower financial satisfaction in both Han and Tibetan subjects. No association was found between food diversity and age or body mass index. Higher food diversity was associated with lower blood glucose level in Han elderly subjects, but the opposite association was found in Tibetan ones. CONCLUSION: Food diversity was associated with ADL and QOL in highlanders in Qinghai, China. Food assessment is very important as a useful indicator to establish the actual condition of diet and its relation to health status of community-dwelling elderly as well as the change of economic background in the Qinghai highlands.