Calcitriol Attenuates HRV-Induced Respiratory Injury through the AMPK-mTOR-ER Stress Signaling Pathway.

Human rhinovirus (HRV) infection is one of the main causes of respiratory injury. Recently, calcitriol has been reported to have protective effect against respiratory infections. In this paper, we aimed to explore the effects and mechanisms of calcitriol on HRV-induced respiratory infection. Participants including pediatric patients diagnosed with HRV-induced respiratory infection (n = 50) and paired healthy controls (n = 40) were recruited at the Weifang People's Hospital between May 2019 and May 2020. The serum 25(OH)D3 level was measured in participants using ELISA kit. The HRV-induced respiratory infection model in human nasal mucosal epithelial cells (hNECs) was adapted, in vitro. HRV infection was measured by real-time PCR analysis of HRV expression. After HRV infection and treatment with calcitriol, the changes of cell viability were detected by MTT assay, the expression of ER stress-induced apoptosis and AMPK-mTOR related proteins by western blot, and the cell apoptosis by flow cytometry assay. In order to confirm whether AMPK-mTOR signal pathway was involved in the ER stress-induced apoptosis of hNECs, cells were pretreated with compound C which was a AMPK inhibitor. The 25-(OH)D3 concentration in serum collected in HRV-infected children was lower than that in controls. In vitro experiments showed that HRV infection decreased cell viability, and this effect was reversed when treated with calcitriol. Additionally, HRV increased levels of apoptosis and ER stress markers (including cleaved-caspase3, Bax, CHOP, nATF6, and BiP), while calcitriol significantly reversed these effects. Furthermore, calcitriol played a protective role by increasing p-AMPK and decreasing p-mTOR level. However, the protective effects of calcitriol could be abolished by compound C. Calcitriol protected HRV-infected hNECs by inhibiting the ER stress-induced apoptosis through the AMPK-mTOR signaling pathway. These protective effects of calcitriol against HRV-induced respiratory infection may provide an experimental basis for the clinical application.

LncRNA PVT1 regulate expression of HIF1α via functioning as ceRNA for miR­199a­5p in non­small cell lung cancer under hypoxia.

Non­small cell lung cancer (NSCLC) represents one of the most important causes of cancer mortality in the world, and leads to the largest number of deaths in all kinds of lung cancer. Hypoxia has been confirmed to be a characteristic feature of NSCLC and has been shown to decrease the therapeutic efficacy of radiotherapy and some forms of chemotherapy. Previous studies revealed that many miRNAs have been proven to be involved in the molecular regulation of hypoxia and to affect the protein expression level of HIF­1α. Here, we demonstrated that miR­199a­5p downregulated HIF­1α expression and was involved in regulating the proliferation of NLSCS cell under hypoxia through downregulation of HIF­1α. Recently, PVT1 has been proposed to function as a molecular sponge by competitively binding miR­199a­5p using miRcode. In this study, we confirmed that PVT1 was overexpressed in the hypoxic lung cancer cells, and then we further demonstrated that PVT1 functioned as competing endogenous (ce)RNA for miR­199a­5p, upregulated expression of its endogenous targets HIF­1α and inhibited its function. Collectively, our study suggested that PVT1 promotes expression of HIF­1α in NSCLC by functioning as ceRNA of miR­199a­5p. These findings support the hypothesis that PVT1 is a vital potential target for hypoxia therapy.

Relationship of the expression levels of XIAP and p53 genes in hepatocellular carcinoma and the prognosis of patients.

In this study, we measured mRNA and protein expression levels of X-linked inhibitor of apoptosis protein (XIAP) and p53 in hepatocellular carcinoma (HCC) and analyzed their relationships to clinicopathological parameters and the prognosis of the patients. Samples were obtained from tumors and tumor-adjacent normal tissues from 70 patients with HCC who were hospitalized in Weifang People's Hospital from January 2009 to December 2011. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to detect the mRNA and protein expression levels, respectively. The clinical data of patients who were followed for 5 years from the day of the tumor-resection surgery were collected in detailed clinical histories. Statistical analyses were used to find relationships between the XIAP and p53 levels and the clinical variables and 5-year survival of patients. Our qPCR results showed that the mRNA expression levels of XIAP and p53 in HCC tumors were significantly higher than those in tumor-adjacent normal tissues. At the same time, IHC results showed that the positive expression rates of XIAP and p53 in HCC in tumors were 81.4% (57/70) and 72.9% (51/70), respectively and their high expression was related to invasion, metastasis and tumor staging. The overall 5-year survival rate of the patients was 15.7% (11/70). Single factor survival analysis showed that both XIAP and p53 were influencing factors of the overall survival rate of patients with HCC (P<0.01). In conclusion, high expression levels of XIAP and p53 are closely related to clinicopathological parameters of patients with HCC, especially related to invasion, metastasis and tumor staging. XIAP and p53 levels can be used as reference values to guide the treatment of HCC and estimate the prognosis.

Evaluation of variation in coagulation among children with Mycoplasma pneumoniae pneumonia: a case-control study.

Objective Acute organ embolism in children with Mycoplasma pneumoniae pneumonia (MPP) has been reported, but changes in coagulation are unclear. This study aimed to investigate changes in coagulation in children with MPP. Methods A total of 185 children with MMP (cases) and 117 healthy children (controls) were recruited. We measured prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and plasma fibrinogen (FIB) and D-dimer levels. Results Plasma FIB (3.39 ± 0.96 g/L vs 2.93 ± 0.6 6g/L, t = 4.50) and D-dimer (326.45 ± 95.62mg/L vs 263.93 ± 103.32mg/L, t=5.36) in MPP children were higher than controls and PT (9.54 ± 4.97S vs 11.48 ± 5.96S, t=3.05) and APTT (31.41 ± 12.01S vs 38.38 ± 11.72S, t=4.95) were shorter than controls. FIB, D-dimer, PT, and APTT were not different between the high IgM-titre and low-titre groups. The areas under the receiver operating characteristic curves in cases and controls for plasma FIB and D-dimer levels were 0.654 (95% confidence interval [CI], 0.593-0.716, P = 0.031) and 0.682 (95% CI, 0.619-0.744, P = 0.032), respectively. Conclusions Children with MPP have a higher risk of blood coagulation and thrombosis. Controlling these problems should be considered as soon as possible.

Ankrd7, a novel gene specifically expressed in Sertoli cells and its potential roles in Sertoli cell maturation.

The somatic Sertoli cells play an essential role in testis determination and spermatogenesis by providing nutrition and structural support. In the current study, we report on the novel Ankrd7 gene that contains five ankyrin repeat domains. This gene was specifically expressed in Sertoli cells and was regulated in a maturation-dependent manner. Its expression was restricted to testicular tissue, and its mRNA could be detected in testes at as early as 14 dpp (days post partum) using RT-PCR analysis. In both testicular tissue sections and in vitro cultured Sertoli cells, the Ankrd7 protein was localized to the nucleus of the Sertoli cell. Immuno-histochemistry and immunocytochemistry investigations showed that the protein was detectable in testicular tissues at 20 dpp, at which time Sertoli cells were gradually differentiating into their mature cellular form. These results suggest that Ankrd7 is probably involved in the process of Sertoli cell maturation and in spermatogenesis.

WITHDRAWN: Fem1b interacts with Ankrd37 in mouse testis and induces its degradation by ubiquitin-mediated proteolysis pathway.

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Photo-induced cold vapor generation with low molecular weight alcohol, aldehyde, or carboxylic acid for atomic fluorescence spectrometric determination of mercury.

With UV irradiation, Hg(2+) in aqueous solution can be converted into Hg(0) cold vapor by low molecular weight alcohols, aldehydes, or carboxylic acids, e.g., methanol, formaldehyde, acetaldehyde, glycol, 1,2-propanediol, glycerol, acetic acid, oxalic acid, or malonic acid. It was found that the presence of nano-TiO(2) more or less improved the efficiency of the photo-induced chemical/cold vapor generation (photo-CVG) with most of the organic reductants. The nano-TiO(2)-enhanced photo-CVG systems can be coupled to various analytical atomic spectrometric techniques for the determination of ultratrace mercury. In this work, we evaluated the application of this method to the atomic fluorescence spectrometric (AFS) determination of mercury in cold vapor mode. Under the optimized experimental conditions, the instrumental limits of detection (based on three times the standard deviation of 11 measurements of a blank solution) were around 0.02-0.04 microg L(-1), with linear dynamic ranges up to 15 microg L(-1). The interference of transition metals and the mechanism of the photo-CVG are briefly discussed. Real sample analysis using the photo-CVG-AFS method revealed that it was promising for water and geological analysis of ultralow levels of mercury.