Nano-selenium attenuates nickel-induced testosterone synthesis disturbance through inhibition of MAPK pathways in Sprague-Dawley rats.

The aim of this study was to investigate the protective effects of Nano-Se against Ni-induced testosterone synthesis disorder in rats and determine the underlying protective mechanism. Sprague-Dawley rats were co-treated with Ni (5.0 mg/kg, i.p.) and Nano-Se (0.5, 1.0, and 2.0 mg/kg, oral gavage) for 14 days after which various endpoints were evaluated. The Ni-induced abnormal pathological changes and elevated 8-OHdG levels in the testes were attenuated by Nano-Se administration. Importantly, decreased serum testosterone levels in the Ni-treated rats were significantly restored by Nano-Se treatment, particularly at 1.0 and 2.0 mg/kg. Furthermore, the mRNA and protein levels of testosterone synthetase were increased by Nano-Se compared to the Ni group, whereas phosphorylated protein expression levels of mitogen-activated protein kinase (MAPK) pathways were suppressed by Nano-Se administration in the Ni-treated rats. Overall, the results suggest that Nano-Se may ameliorate the Ni-induced testosterone synthesis disturbance via the inhibition of ERK1/2, p38, and JNK MAPK pathways.

Ameliorative effects of nano-selenium against NiSO4-induced apoptosis in rat testes.

Nickel (Ni) is a common environmental pollutant, which has toxic effects on reproductive system. Nowadays, nano-selenium (Nano-Se) has aroused great attention due to its unique antioxidant effect, excellent biological activities and low toxicity. The aim of this study was to explore the protective effects of Nano-Se on NiSO4-induced testicular injury and apoptosis in rat testes. Nickel sulfate (NiSO4) (5 mg/kg b.w.) was administered intraperitoneally and Nano-Se (0.5, 1, and 2 mg Se/kg b.w., respectively) was given by oral gavage in male Sprague-Dawley rats. Histological changes in the testes were determined by H&E staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and immunohistochemistry were performed to evaluate the apoptosis in testes. Expression levels of mitochondrial apoptosis-related genes and proteins were analyzed by RT-qPCR and Western blot. The results showed that Nano-Se improved lesions of testicular tissue induced by NiSO4. Nano-Se significantly alleviated NiSO4-induced apoptosis in rat testes, as well as significantly downregulated the Bak, cytochrome c, caspase-9 and caspase-3 and upregulated Bcl-2 expression levels, all of which were involved in mitochondria-mediated apoptosis. Altogether, we concluded that Nano-Se may potentially exert protective effects on NiSO4-induced testicular injury and attenuate apoptosis, at least partly, via regulating mitochondrial apoptosis pathways in rat testes.

Competitive endogenous RNA (ceRNA) regulation network of lncRNA-miRNA-mRNA during the process of the nickel-induced steroidogenesis disturbance in rat Leydig cells.

Nickel (Ni) is a ubiquitous environmental pollutant, which can disrupt the production of steroid in rat Leydig cells. Steroidogenesis can be affected by non-coding RNAs (ncRNAs), which operate in normal physiological processes. To date, however, very few studies have focused on whether ncRNAs are involved in Ni-induced steroidogenesis disturbance. The present study was designed to investigate the impact of NiSO4 on the regulation of RNA networks including long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA in rat Leydig cells. After treatment with 1000 µmol/L NiSO4 for 24 h, 372 lncRNAs, 27 miRNAs (fold change>2, p < .05) and 3666 mRNAs (fold change>2, p < .01, and FDR < 0.01) were identified to be markedly altered by high-throughput sequencing analysis in rat Leydig cells. Functional analysis showed that the differentially expressed mRNAs were annotated into some steroid-related pathways. A dysregulated competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA was constructed based on bioinformatic analysis. Furthermore, a ceRNA network related to steroidogenesis was selected to analyze further and after the validation by qRT-PCR. The LOC102549726/miR-760-3p/Atf6, LOC102549726/miR-760-3p/Ets1, LOC102549726/miR-760-3p/Sik1 and AABR07037489.1/miR-708-5p/MAPK14 ceRNA networks were eventually confirmed. Collectively, our study provided a systematic perspective on the potential role of ncRNAs in steroidogenesis disturbance induced by Ni in rat Leydig cells.

Long-Term Epidemiological Dynamics of Japanese Encephalitis Infection in Gansu Province, China: A Spatial and Temporal Analysis.

The incidence of Japanese encephalitis (JE) has greatly declined in China. However, JE incidence has significantly increased in Gansu in recent years, on the top of ranks among all provinces in China. To explore the spatial spread and resurgence of JE transmission in Gansu in the past 60 years, we collected yearly data on reported JE in each county (1958-2017) and monthly data on JE cases (1968-2017), respectively. We grouped the dataset into six categories, each consisting of a 10-year period between 1958 and 2017. Spatial cluster analysis was applied to identify the potential space-time clusters of JE incidence, and logistic regression models were used to identify the spatial and temporal dispersion of JE. Japanese encephalitis incidence in Gansu showed an upward trend from 1970 to 1977 and peaked in 1974, then declined, and fluctuated over the study period until an outbreak again in 2017. Japanese encephalitis incidence for the first 30-year period (1958-1987) peaked in September each year and thereafter peaked in July and August during 1988-2017. Spatial cluster analysis showed the geographical range of JE transmission fluctuated over the past 60 years. The high-incidence clusters of JE were primarily concentrated in the southeast of Gansu. We found significant space-time clustering characteristics of JE in Gansu, and the geographical range of notified JE cases has significantly expanded over recent years. The potential rebound of JE transmission occurred in 2016-2017 should be placed on the top priority of government work during the control and prevention of JE in Gansu, China.