Inhibition of leucine-rich repeats and calponin homology domain containing 1 accelerates microglia-mediated neuroinflammation in a rat traumatic spinal cord injury model.

BACKGROUND: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. METHODS: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. RESULTS: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. CONCLUSION: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.

Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006-2015.

BACKGROUND: The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. METHODS: A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran's I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. RESULTS: A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran's I index varied from 0.23 to 0.44 with all P-value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion (DIC)(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval (CI): 6.7-13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI: 13.7-32.7%) for every 1-standard-deviation increase in education year. CONCLUSIONS: There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.

The Higher the Children's Achievements, the Better the Elderly Health? Evidence From China.

Health, an important indicator for measuring the elderly's life and wellbeing, is an important part of positive and healthy aging. Children's achievements are closely linked to their parents' health. However, existing literature does not cover how children's achievements impact the health of their elderly parents. Data were derived from the 2014 Chinese Longitudinal Aging Social Survey; this study includes 6,793 elderly people ages 60 and older as samples. A multiple linear regression model was used to analyze the correlation between children's achievements and their elderly parents' health statuses in China. The results show that the higher the children's income and education, the better their health of their elderly parents. Living patterns, children' financial support to their parents, and social capital play a mediating role in the relationship between children and their elderly parents. These findings provide further insight into potential factors associated with the children's achievements and elderly health.

[Safety and immunological effect of domestic split influenza virus vaccine].

OBJECTIVE: To evaluate the safety and immunological effect of domestic split influenza virus vaccine. METHODS: All 606 subjects were divided into three groups by under 6, 16-60 and above 60 years old. Each age group was divided as study group (n = 213), control group 1 (n = 195) and control group 2 (n= 198) by Table of Random Number, one domestic vaccine and two imported vaccines were respectively inoculated in three group people. The differences of clinical side effect rate, antibody positive rate, protective rate and geometric mean titer (GMT) of these three vaccines were compared by using the statistical software with statistical significance of P < 0.05. RESULTS: The side effect rate of study group, control group 1 and control group 2 was 3.76% (8/213), 4.10% (8/195), and 3.54% (7/198), respectively without statistical significance(chi2 = 0.87, P =0.93). The positive seroconversion rates of H1N1, H3N2 and B in these three groups were respectively 89.2% (190/213), 63.4% (135/213), 86.4% (184/213), 88.7% (173/195), 61.5% (120/195), 87.2% (170/195), 87.9% (174/198), 61.6% (122/198) and 84.8% (168/198). There were no statistical significance in the total positive seroconversion rate of each antibody type (chi2(H1N1) = 0.94, P(H1N1) = 0.63; chi2(H3N2) = 0.94, P(H3N2) = 0.63; chi2(B) = 0.75, P(B) = 0.69). The average growth multiple of H1N1, H3N2 and B in these three groups were 10.7, 7.3, 8.4, 10.5, 6.3, 8.3, 10.2, 7.1, 8.8 times. There were no statistical significances in the GMT growth multiple of each antibody type (F(H1N1) = 0.35, P(H1N1) = 0.70; F(H3N2) = 2.22, P(H3N2) = 0.11; F(B) = 1.51, P(B) = 0.35). The antibody protective rates of H1N1, H3N2 and B were 100% (213/213), 70.0% (149/213), 95.3% (203/213), 100% (195/195), 66.7% (130/195), 97.9% (191/195), 99.5% (197/198), 66.2% (131/198), 96.5% (191/198) respectively. There was no statistical difference among the three vaccines (chi2(H1N1) = 2.04, P(H1N1) = 0.36; chi2(H3N2) = 0.74, P(H3N2) = 0.69; chi2(B) = 0.42, P(B) = 0.82). CONCLUSION: The domestic influenza split vaccine might be suitable for colony vaccination for its having clinical safety and immunological effect.

Histone deacetylase inhibitor, Romidepsin (FK228) inhibits endometrial cancer cell growth through augmentation of p53-p21 pathway.

OBJECTIVE: Romidepsin (FK228), a Histone Deacetylase (HDAC) inhibitor, has been used for anti-cancer therapies. However, the anti-cancer effect of FK228 and its underlying mechanism in endometrial carcinoma (EC) have not been studied. The aime of this study was to investigate the anti-cancer effects of FK228 and the associated mechanism(s) in EC. METHODS: Ishikawa and HEC-1-A endometrial cancer cells were treated with 8nM concentration of FK228 and cell growth was measured by XTT assay. The cell cycle distribution and cell death were measured by flow cytometry, immunofluorescence, respectively. The mNRA and protein expressions were analyzed by quantitative RT-PCR and western blot, respectively. RESULTS: Based on assays carried out in EC cell lines, it was observed that FK228 inhibited EC cell proliferation in a dose and time-dependent manner. Furthermore, following treatment with FK228 for 48h, there were significant induction of apoptosis and cell cycle arrest at G0/G1 phase in EC cells. Moreover, FK228 treatment significantly increased the mRNA and protein expressions of p53, p21, cleaved caspases such as 3, 7 and 8 and PARP. Further, FK228 treatment increased the levels of acetylated histone H3 and H4 that confirms the HDAC inhibition. CONCLUSION: In conclusion, FK228 inhibits EC tumor cell proliferation and induces apoptosis by activation caspase/PARP via the induction of p53/p21 signaling cascades, suggesting that FK228 is a potential therapeutic agent for EC.