Pan-Cancer analyses of Necroptosis-Related genes as a potential target to predict immunotherapeutic outcome.

Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan-cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.

The anticancer effect of EGFR-targeting artificial microRNA controlled by SLPI promoter in nasopharyngeal carcinoma.

BACKGROUND: This study intends to use artificial microRNA (recombinant adenovirus vector) targeting epidermal growth factor receptor (EGFR) to inhibit the overexpressed EGFR in nasopharyngeal carcinoma, thereby inhibiting the proliferation and metastasis of nasopharyngeal carcinoma. METHOD: The research group verified the expression of EGFR in nasopharyngeal carcinoma through databases, clinical tissues, and cellular pathways. The team first tested the transfection of the recombinant adenovirus by fluorescence microscopy. After adenovirus treatment with different multiplicity of infection (MOI), EGFR level and cell viability in cells were examined by Western blot and MTT assay. Next, the effects of adenovirus (Ad)-SLPI-EGFR on cell proliferation, migration, apoptosis, and related proteins were sequentially examined by EdU, scratch, Transwell, and Western blot. In vivo experiments were performed to evaluate the biological function of EGFR in nasopharyngeal carcinoma. RESULT: All three validation pathways showed the increase in EGFR expression in nasopharyngeal carcinoma. Transfection tests showed that the SLPI promoter was specific in CNE2 cells. With the increase in MOI, the inhibition of EGFR expression and cancer cell viability by Ad-SLPI-EGFR was enhanced. Meanwhile, Ad-SLPI-EGFR effectively reduced the proliferation and metastasis of CNE2 cells and affected the expression of related proteins. Furthermore, Ad-SLPI-EGFR inhibited the invasion and metastasis of nasopharyngeal carcinoma in vivo. CONCLUSION: Ad-SLPI-EGFR inhibits the expression of EGFR in nasopharyngeal carcinoma cells, and finally achieves the purpose of inhibiting the proliferation and metastasis of cancer cells, which may provide novel targeted intervention for the treatment of nasopharyngeal carcinoma.

Chlorogenic Acid Alleviates Allergic Inflammatory Responses Through Regulating Th1/Th2 Balance in Ovalbumin-Induced Allergic Rhinitis Mice.

BACKGROUND Allergic rhinitis (AR) is a prevalent atopic disorder caused by immune imbalance. Chlorogenic acid (CGA) has antibacterial, antiviral, antioxidative and immunoregulatory effects, but its role in anaphylactic disease remains unclear. The current study aimed to investigate the function of CGA in AR. MATERIAL AND METHODS AR mice models were induced with ovalbumin (OVA) by orally administrating the mice with 50 mg/kg (L-CGA), 100 mg/kg (M-CGA), or 200 mg/kg (H-CGA) of CGA. The number of nasal rubbings and sneezes was recorded. Afterward, the mice were sacrificed for the collection of blood, nasal lavage fluid (NALF), and nasal tissues. The cells in NALF were counted by hemocytometer and stained by Diff-Quick. Nasal mucosa was observed by H&E staining. ELISA testing was conducted for detecting the levels of anti-OVA antibodies and Th1/Th2-related cytokine. Quantitative real-time polymerase chain reaction experiments were conducted to determine mRNA expressions of Th1/Th2-related cytokines. RESULTS In the OVA-induced AR mice, CGA treatment reduced nasal rubbing and sneezing, and also suppressed the number of total cells, eosinophils, neutrophils, lymphocytes, macrophages, and epithelial cells in NALF. OVA-induced up-regulation of nasal mucosa thickness was inhibited by CGA, and the effects of OVA on IgE, IgG1, and IgG2a were reversed by CGA. The regulatory effects of OVA on mRNA expressions and levels of Th1/Th2-related cytokines were abolished by CGA treatment in AR mice. CONCLUSIONS CGA can alleviate allergic inflammatory responses through regulating Th1/Th2 balance in OVA-induced allergic rhinitis mice.

Actinidia chinensis Planch Root extract suppresses the growth and metastasis of hypopharyngeal carcinoma by inhibiting E2F Transcription Factor 1-mediated MNX1 antisense RNA 1.

Increasing evidence has shown that traditional Chinese medicines and their bioactive components exert an anti-tumor effect, representing a novel treatment strategy. Actinidia chinensis Planch Root extracts (acRoots) have been reported to repress cancer cell proliferation and metastasis. The effect of acRoots on hypopharyngeal carcinoma progression was explored in this study. Firstly, data from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and colony formation assays showed that incubation with accRoots reduced cell proliferation of hypopharyngeal carcinoma cells. Moreover, acRoots promoted the cell apoptosis of hypopharyngeal carcinoma. Secondly, cell migration and invasion of hypopharyngeal carcinoma cells were suppressed by acRoots. Thirdly, E2F1 (E2F Transcription Factor 1) and lncRNA MNX1-AS1 (MNX1 antisense RNA 1) were up-regulated in hypopharyngeal carcinoma tissues, and reduced in hypopharyngeal carcinoma cells post acRoots incubation. Overexpression of E2F1 attenuated acRoots-induced decrease in MNX1-AS1 in hypopharyngeal carcinoma cells. Lastly, administration with acRoots retarded in vivo hypopharyngeal carcinoma growth through down-regulation of E2F1-mediated MNX1-AS1. In conclusion, acRoots exerted tumor-suppressive role in hypopharyngeal carcinoma through inhibition of E2F1-mediated MNX1-AS1.

Analysis of effect of 1α-hydroxyvitamin D3 on benign paroxysmal positional vertigo and risk factors.

The purpose of this study was to investigate the curative effect of 1α-hydroxyvitamin D3 on the benign paroxysmal positional vertigo (BPPV). Fifty BPPV patients diagnosed in the ENT Department of Anzhen Hospital from October 2015 to December 2016 were randomly selected as the treatment group, and treated with 0.25 µg 1α-hydroxyvitamin D3 once per day, in addition to the routine diagnosis and treatment. Moreover, 50 BPPV patients in the same period were selected as the control group, and received the routine diagnosis and treatment. The detection results of bone mineral density (BMD) t-value, vitamin D3 and bone metabolic markers before and after treatment were compared, and statistical analysis was performed on the results. There were no differences in the general data between treatment group and control group. There were no statistically significant differences in the BMD and age distribution of males and females between treatment group and control group (P>0.05). The BMD of male BPPV patients in each age group in the treatment group was significantly increased after treatment, and the difference was statistically significant (P<0.05). Although the BMD of male BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The BMD of female BPPV patients in each age group in treatment group was increased after treatment, and the difference was statistically significant (P<0.05). Similarly, although the BMD of female BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The average BMD of female BPPV patients in each age group was significantly lower than that of male patients, and the difference was statistically significant (P<0.05) (Table II). The BMD t-value of patients in treatment group showed a decreasing trend with the increase of age (Fig. 1). The levels of 25-hydroxyvitamin D3 and bone metabolic markers in treatment group were significantly improved compared with those before treatment (P<0.05). Multivariate Logistic regression analysis was performed to identify whether the treatment of BPPV was effective or not as a dependent variable, and six items, including the sex (female), hypertension, diabetes mellitus, age (>50 years), 25-hydroxyvitamin D3 and osteopenia/osteoporosis, as the independent variables, and the results suggested that the level of 25-hydroxyvitamin D3 and osteopenia/osteoporosis are the clinical features of whether the BPPV treatment is effective (P<0.05). The results showed that the treatment of BPPV with 1α-hydroxyvitamin D3 can effectively improve the symptoms of patients, and the level of vitamin D3 and the occurrence of osteopenia/osteoporosis are the clinical indexes of whether the BPPV treatment is effective.