UFMylation is associated with LPS-induced inflammatory response in goat endometrial epithelial cells.

The endometrium plays an important role in the defence against invading pathogens, although the mechanisms are not clear. UFMylation is a recently discovered novel ubiquitination-like modification system that plays a pivotal role in inflammation and the immune response. The purpose of this study was to investigate the effects of UFMylation on lipopolysaccharide (LPS)-induced inflammatory responses in immortalized goat endometrial epithelial cells (gEECs). Ubiquitin-fold modifier conjugating enzyme 1 (UFM1) and DDRGK domain containing 1 (DDRGK1) were mainly localized in the luminal epithelium and glandular epithelium of mouse and goat endometrial tissues. The expression levels of UFM1, ubiquitin-like modifier activating enzyme 5 (UBA5), UFM1 specific ligase 1 (UFL1) and DDRGK1, as key components of the UFMylation system, were significantly activated by 5 µg/mL LPS-induced inflammatory response in gEECs for 6 hr. Meanwhile, the expression levels of interleukin-6 (IL-6) were significantly upregulated, and tumour necrosis factor-α (TNF-α) was significantly down-regulated after overexpression of UFM1 in gEECs. Additionally, we observed UFM1 and DDRGK1 were markedly increased on LPS-stimulated mouse endometritis in vivo. In conclusion, the current study demonstrated that UFMylation was significantly activated by LPS and might be involved in regulating inflammatory response in gEECs.

Progesterone-induced RNA Hand2os1 regulates decidualization in mice uteri.

Decidualization is a critical process for successful embryo implantation and subsequent placenta formation. The characterization and physiological function of lncRNA during decidualization remain largely unknown. In the present study, we conducted RNA-sequencing analysis to compare gene expression between decidua of days 6 and 8, and normal pregnant endometrium (day 4). A total of 2332 high-confidence putative lncRNA transcripts were expressed. Functional clustering analysis of cis and trans lncRNA targets showed that differentially expressed lncRNAs may regulate multiple gene ontology terms and pathways that have important functions in decidualization. Subsequent analyses using qRT-PCR validated that eight of all lncRNAs were differentially regulated in mice uteri during decidualization, both in vivo and in vitro. Furthermore, we showed that differentially expressed lncRNA of Hand2os1 was specifically detected in stromal cells on days 2 to 5 of pregnancy and was strongly upregulated in decidual cells on days 6-8 of pregnancy. Similarly, Hand2os1 expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. In uterine stromal cells, P4 was able to significantly upregulate the expression of Hand2os1, but upregulation was impeded by RU486, whereas E2 appeared to have no regulating effect on Hand2os1 expression. Concurrently, Hand2os1 significantly promoted the decidual process in vitro and dramatically increased decidualization markers Prl8a2 and Prl3c1. Our results provide a valuable catalog for better understanding of the functional roles of lncRNAs in pregnant mouse uteri, as it relates to decidualization.

Endoplasmic reticulum stress is involved in lipopolysaccharide-induced inflammatory response and apoptosis in goat endometrial stromal cells.

Endoplasmic reticulum (ER) stress is involved in regulating cell metabolism, apoptosis, autophagy, and survival. However, there is not enough information about the role of ER stress in lipopolysaccharide (LPS)-induced apoptosis and inflammatory cytokine secretion in the uterus. In this study, we found that LPS induced apoptosis and inflammation in goat endometrial stromal cells (ESCs). LPS treatment inhibited cell viability and cell proliferation. In addition, the genes associated with proliferation, such as proliferating cell nuclear antigen and MKI67, were affected by LPS treatment. Moreover, LPS increased the secretion of interleukin (IL)-1ß and IL-8, promoting the levels of MYD88, caspase1, and TRL4. The 4-phenylbutyric acid pretreatment inhibited the expression of unfolded protein response proteins and the secretion of inflammatory cytokines in LPS-treated cells. However, blockage of inositol-requiring enzyme 1 and activating transcription factor 6 did not significantly reduce apoptosis and inflammatory cytokine secretion. Collectively, ER stress involved in LPS-induced apoptosis and inflammatory cytokine increased in goat ESCs. This study provides new insight into the function of ER stress in the pathological process.

CREBZF regulates testosterone production in mouse Leydig cells.

CREBZF, including the two isoforms SMILE (long isoform of CREBZF) and Zhangfei (short isoform of CREBZF), has been identified as a novel transcriptional coregulator of a variety of nuclear receptors. Our previous studies found that SMILE is expressed in the mouse uterine luminal and glandular epithelium and is upregulated by estrogen. In the present study, CREBZF was age-dependently and -specifically expressed in mouse interstitial Leydig cells during sexual maturation. The expression pattern of CREBZF exhibited an age-related increase, and SMILE was the dominant isoform in the mouse testis. Although hCG did not affect CREBZF expression, CREBZF silencing significantly inhibited hCG-stimulated testosterone production in primary Leydig cells and MLTC-1 cells. Meanwhile, the serum concentration of testosterone was significantly decreased after microinjection of lentiviral-mediated shRNA-CREBZF into the mature mouse testis. In addition, CREBZF silencing markedly decreased P450c17, 17ß-HSD, and 3ß-HSD expression following hCG stimulation in primary Leydig cells, and this inhibitory effect was obviously reversed by overexpression of CREBZF. Furthermore, CREBZF significantly upregulated the mRNA levels of Nr4a1 and Nr5a1, which are the essential orphan nuclear receptors for steroidogenic gene expression. Together our data indicate that CREBZF promotes hCG-induced testosterone production in mouse Leydig cells by affecting Nr4a1 and Nr5a1 expression levels and subsequently increasing the expression of steroidogenic genes such as 3ß-HSD, 17ß-HSD, and P450c17, suggesting a potential important role of CREBZF in testicular testosterone synthesis.

Ambient air pollution, smog episodes and mortality in Jinan, China.

We aimed to assess the acute effects of ambient air pollution and weather conditions on mortality in the context of Chinese smog episodes. A total of 209,321 deaths were recorded in Jinan, a large city in eastern China, during 2011-15. The mean concentrations of daily particulate matter ≤10 µm (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were 169 µg/m3, 100 µg/m3, 77 µg/m3, and 54 µg/m3, respectively. Increases of 10 µg/m3 in PM10, PM2.5, SO2 and NO2 were associated with 1.11% (95% CI 0.96-1.26%), 0.71% (95% CI 0.60-0.82%), 1.69% (95% CI 1.56-1.83%), and 3.12% (95% CI 2.72-3.53%) increases in daily non-accidental mortality rates, respectively. Moreover, the risk estimates for these 4 pollutants were higher in association with respiratory and cardiovascular mortality. The effects of all the evaluated pollutants on mortality were greater in winter than in summer. Smog episodes were associated with a 5.87% (95% CI 0.16-11.58%) increase in the rate of overall mortality. This study highlights the effect of exposure to air pollution on the rate of mortality in China.

The impact of temperature extremes on mortality: a time-series study in Jinan, China.

OBJECTIVE: To investigate the relationship between temperature extremes and daily number of deaths in Jinan, a temperate city in northern China. METHODS: Data ondaily number of deaths and meteorological variables over the period of 2011-2014 were collected. Cold spells or heat waves were defined as ≥3 consecutive days with mean temperature ≤5th percentile or ≥95th percentile, respectively. We applied a time-series adjusted Poisson regression to assess the effects of extreme temperature on deaths. RESULTS: There were 152 150 non-accidental deaths over the study period in Jinan, among which 87 607 people died of cardiovascular disease, 11 690 of respiratory disease, 33 001 of stroke and 6624 of chronic obstrutive pulmonary disease (COPD). Cold spells significantly increased the risk of deaths due to non-accidental mortality (RR 1.08, 95% CI 1.06 to 1.11), cardiovascular disease (RR 1.06, 95% CI 1.03 to 1.10), respiratory disease (RR 1.19, 95% CI 1.11 to 1.27), stroke (RR 1.11, 95% CI 1.06 to 1.17) and COPD (RR 1.27, 95% CI 1.16 to 1.38). Heat waves significantly increased the risk of deaths due to non-accidental mortality (RR 1.02, 95% CI 1.00 to 1.05), cardiovascular disease (RR 1.03, 95% CI 1.00 to 1.06) and stroke (RR 1.06, 95% CI 1.00 to 1.13). The elderly were more vulnerable during heat wave exposure; however, vulnerability to cold spell was the same for the whole population regardless of age and gender. CONCLUSIONS: Both cold spells and heat waves have increased the risk of death in Jinan, China.

Impact of heat waves on nonaccidental deaths in Jinan, China, and associated risk factors.

An ecological study and a case-crossover analysis were conducted to evaluate the impact of heat waves on nonaccidental deaths, and to identify contributing factors of population vulnerability to heat-related deaths in Jinan, China. Daily death data and meteorological data were collected for summer months (June to August) of 2012-2013. Excess mortality was calculated and multivariate linear regression models were used to assess the increased risk of heat waves on deaths. Univariate and multivariate logistic regression models were performed to estimate the odd ratios (ORs) of risk factors and their 95 % confidence intervals (CIs). Overall, heat waves were related to 24.88 % excess deaths of total nonaccidental deaths and 31.33 % excess deaths of circulatory diseases, with an OR of 16.07 (95 % CI 8.80-23.33) for total nonaccidental deaths and 12.46 (95 % CI 7.39-17.53) for deaths of circulatory diseases. The case-crossover analysis indicated that older people were more likely to die during heat waves (OR = 1.233, 95 % CI 1.076-1.413) and more deaths occurred outside a hospital during heat waves (OR = 1.142, 95 % CI 1.006-1.296). In conclusion, heat waves have caused excess deaths and significantly increased the risk of circulatory deaths. The risk factors identified in our study have implications for public health interventions to reduce heat-related mortality during extreme heat events.

[Heat vulnerability assessment in Jinan city: a comparison between residents living in urban centers and urban-fringe areas].

OBJECTIVE: To find out the differences in regional characteristics of heat vulnerability between people living in urban centers and urban-fringe areas of Jinan city so as to provide basis for the development of adaptation measures to heat. METHODS: A cross-sectional survey on heat vulnerability was conducted in urban center and urban-fringe areas of Jinan city, using a self-designed questionnaire among 801 residents at the age of 16 years or older in August 2013. Data of 23 indicators related to heat vulnerability were collected and aggregated to 7 dimensions:health and medical insurance, social networks, heat perception and adaptive behavior, economic status, resources, living environment and working environment. An index score was calculated using a balanced weighted average approach for each dimension, ranging from 0 to 1, with the closer to 1 as greater vulnerability. RESULTS: The scores on heat perception and adaptive behavior, economic status, resources and working environment dimensions for urban-fringe areas were 0.42,0.63,0.55 and 0.62, statistically significantly higher than the urban center area of 0.41,0.51,0.26 and 0.41. Scores of living environment, social networks and health/medical insurance dimensions for urban center area were 0.57,0.49 and 0.31, which were all higher than the urban-fringe areas of 0.50,0.46 and 0.25, with differences statistically significant. CONCLUSION: Residents living in the urban center might be more vulnerable to heat in terms of living environment, health/medical insurance and social networks while residents living in the urban-fringe areas might more be vulnerable in terms of heat perception and adaptive behavior, economic status, life resources and working environment. These facts indicated that heat vulnerability among residents could be quite different, even at a fine geographic sale. We would thus suggest that intervention strategies on protecting people from heat, should be more targeted.

[Analysis of epidemiological characteristics of acute pesticide poisoning during 2007-2013 in Jinan, China].

OBJECTIVE: To investigate the epidemiological characteristics of acute pesticide poisoning in Jinan, China and to provide effective proposals for the prevention and control of pesticide poisoning. METHODS: Reported cases of acute pesticide poisoning from 2007 to 2013 in Jinan were collected and subjected to statistical analysis using SPSS 17. RESULTS: A total of 4852 cases of acute pesticide poisoning were reported from 2007 to 2013 in Jinan. The fatality rate was 14.10%. The incidence of non-occupational poisoning accounted for 94.23% (4 572/4 852). The incidence of occupational poisoning showed a decreasing trend from 2007 to 2013, with most cases poisoned by insecticides (236 cases, accounting for 82.86% of all cases of occupational poisoning). Among non-occupational poisoning cases, fatality rate was higher in cases aged 60 years or over than in those under 60 years; fatality rate was higher among male cases (16.11%) than among female cases (13.79%); herbicides had a significantly higher lethal rate (22.25%) than insecticides (14.02%) (P < 0.05). CONCLUSION: More attention should be paid to acute pesticide poisoning in Jinan, and effective management measures should be taken immediately.

Perceptions of heat risk to health: a qualitative study of professional bus drivers and their managers in Jinan, China.

Summer extreme heat threatens the health of individuals, especially persons who are involved in outdoor activities. Ensuring the normal function of a city, bus drivers are among those who participate in outdoor physical activities and are exposed to excessive heat in hot summer weather. This qualitative study was performed to explore professional bus drivers' in-depth views of extreme heat risks to their health, and ultimately develop targeted advice and policy interventions for city bus drivers. An interview-based study was performed among professional bus drivers in Jinan, China, including four focus groups with professional bus drivers (n = 37) and three interviews with their managers (n = 14). Five central themes or categories from the bus driver interviews were found: concerns about summer heat; health effects related to extreme heat; adaptive measures; barriers in implementing these adaptive measures; and suggested interventions. The beneficial role of cooling facilities (particularly air-conditioning) during extreme heat are addressed. The barriers not only impede the implementation of behavioral adaptive measures but also enhance the negative attitudes of bus drivers towards their effectiveness. The responsibilities of managers in promoting preventive actions are addressed.