Store-operated calcium entry-associated regulatory factor regulates airway inflammation and airway remodeling in asthma mice models.

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

Acute toxicity and health effect of perfluoroisobutyronitrile on mice: a promising substitute gas-insulating medium to SF6.

Perfluoroisobutyronitrile (C4F7N) is a new eco-friendly gas insulation medium that has potential to replace the most greenhouse gas sulfur hexafluoride (SF6) used in power industry. In order to ensure the engineering application safety, an in-depth assessment of the acute inhalation toxicity of C4F7N gas mixture is required. This article revealed gender differences in male and female mice after exposure to C4F7N and the physiological recovery characteristics of surviving mice by means of 4 h acute inhalation toxicity tests, hematological determinations and histopathological examination. Comparative analysis on the toxicity of C4F7N on mice and rats is also evaluated. We find that the LC50 of C4F7N for male and female mice is 1175 ppm (4 h), 1380 ppm (4 h) and female ones are more tolerant to C4F7N. Mice that exposed to 1000 ppm C4F7N for 4 h could survive and return to their normal state after the 14-day observation period without irreversible damage. The toxic effect duration of C4F7N on rats is longer than that of mice. Relevant results revealed the acute inhalation toxicity of C4F7N systematically and provided fundamental reference for inhalation safety protection and engineering application.

Assessment on the toxicity and application risk of C4F7N: A new SF6 alternative gas.

C4F7N (fluorinated nitrile) gas mixture has been utilized as the gas insulating medium to replace the most greenhouse gas SF6 (sulphur hexafluoride). Nowadays, there are few reports on the toxicity mechanism of C4F7N and studies on the application risk of C4F7N is insufficient. In this paper, we carried out acute toxicity tests for C4F7N gas systematically. The changes of vital signs of rats after exposure to C4F7N were analyzed and the influence of C4F7N on the main organs of rats was revealed for the first time. It was found that rats developed symptoms of respiratory rate decrease, respiratory mucosa damage, movement systems impairment and abnormal blood cell count after exposure to C4F7N. Pathological section results showed that 1.5% C4F7N could damage the lung, kidney, intestine and brain tissues of rats to a certain extent, but has little influence to the eye, skin, heart and liver. The LC50 (rat, 4 h) of C4F7N gas is in the range of 15,000 ppm (1.5%) and 20,000 ppm (2%). Relevant research results not only reveal the acute toxicity mechanism of C4F7N, but also provide important reference for the safety protection of scientific researcher, equipment production, engineering operation and maintenance personnel.

Neuropeptide Y knockdown in the dorsomedial hypothalamus improved basal and obesity-induced decrease in bone mass density.

OBJECTIVE: Neuropeptide Y (NPY) has been shown to have a prominent role in the control of bone formation through the regulation of osteoblast activity. We aimed to investigate the role of hypothalamus-derived NPY in bone metabolism. METHODS: Accordingly, adeno-associated virus (AAV)-mediated RNA interference (RNAi) was utilized to downregulate NPY gene expression in rats fed regular chow (RC) or a high-fat diet (HF). The serum concentrations of glucose, insulin, corticosterone, osteocalcin, insulin-like growth factor (IGF-1), triglycerides (TC), and cholesterol (TG) and fat mass and bone mineral density (BMD) were measured to assess the effect of NPY knockdown on basal and obesity-induced BMD. Forkhead transcription factor (FoxO1) and activating transcription factor 4 (ATF4) were measured to explore the molecular mechanism of the effect of dorsomedial nucleus (DMH) NPY knockdown on bone formation. RESULTS: Our results showed that DMH NPY knockdown enhanced basal and the obesity-induced decrease in BMD and osteocalcin and promoted the phosphorylation of FoxO1 and reduced the expression of ATF4. CONCLUSION: Our data suggest that DMH NPY knockdown can alter bone metabolism.