MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.

BACKGROUND: Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. PATIENTS AND METHODS: The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. RESULTS: A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. CONCLUSION: MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers.

Host Responses to Live-Attenuated ASFV (HLJ/18-7GD).

African swine fever (ASF) is a highly contagious and fatal disease caused by the African swine fever virus. Recently, the multigene family and CD2v gene-deleted ASF vaccine candidate HLJ/18-7GD was found to be safe and effective in laboratory and clinical trials. However, the immune-protective mechanisms underlying the effects of HLJ/18-7GD remain unclear. We assessed samples from pigs immunized with a single dose of 106 TCID50 HLJ/18-7GD. We found that pigs immunized with HLJ/18-7GD showed high levels of specific antibodies. T lymphocyte subsets (helper T cells (Th); cytotoxic T lymphocytes (CTL); double-positive T cells (DP-T cells)) were temporarily increased in peripheral blood mononuclear cells (PBMCs) after HLJ/18-7GD immunization. Once the HLJ/18-7GD-immunized pigs had been challenged with virulent HLJ/18, the percentage of Th, CTL, and DP-T cells increased significantly. PBMCs extracted from the pigs induced higher levels of CD8+ T cells after infection with the HLJ/18 strain in vitro. The levels of GM-CSF, IFN-γ, and TNF-α were upregulated at 7 days post-inoculation; this finding was contrary to the results obtained after HLJ/18 or HLJ/18ΔCD2v infection. The immune protection from HLJ/18-7GD resulted from many synergies, which could provide a theoretical basis for HLJ/18-7GD as a safe and effective ASF vaccine.

Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.

BACKGROUND: DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). METHODS: Multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways. RESULTS: We found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways. CONCLUSIONS: PLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.

MicroRNA-29a promotes the proliferation of human nasal epithelial cells and inhibits their apoptosis and promotes the development of allergic rhinitis by down-regulating FOS expression.

OBJECTIVE: To explore the regulation of microRNA-29a (miR-29a) on FOS in human nasal epithelial cells and its molecular mechanism, as well as the effects of miR-29a on the cell proliferation and apoptosis. METHODS: By cell transfection, gene silencing, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and TUNEL assay (for cell apoptosis), CCK-8 assay (for cell proliferation), dual-luciferase reporter gene assay and Western Blot, it was validated that miR-29a promoted the proliferation of human nasal epithelial cells and inhibited their apoptosis by down-regulating FOS expression in RPMI2650 and HNEpC cell lines. RESULTS: ①Compared with healthy controls, miR-29a expression was up-regulated and FOS mRNA expression was down-regulated in the nasal tissues from the patients with allergic rhinitis (AR). ②MiR-29a over-expression promoted the proliferation of RPMI2650 cells and HNEpC cells but inhibited their apoptosis. ③MiR-29a targeted at FOS. ④MiR-29a over-expression and FOS silencing both significantly promoted cell proliferation and inhibited cell apoptosis. After transfection with both miR-29a and FOS, there was a decrease in the proliferation but an increase in the apoptosis of cells.⑤MiR-29a promoted the proliferation of human nasal epithelial cells and inhibited their apoptosis by down-regulating FOS expression. CONCLUSION: MiR-29a-/FOS axis can be regarded as a potential marker and a new therapy for AR.

Regulatory effect of glutathione on treg/Th17 cell balance in allergic rhinitis patients through inhibiting intracellular autophagy.

BACKGROUND: Glutathione is a potential therapy for systemic lupus erythematosus, but its role in allergic rhinitis (AR) has not been determined. This report probed into the actions of glutathione in AR, so as to supplement evidence for a therapeutical countermeasure for AR. METHODS: In this study, peripheral blood mononuclear cells (PBMCs) of patients were extracted and processed with glutathione. PBMCs and nasal mucosa tissues were collected from AR mouse models treated with or without glutathione. The proportions of Th17/Treg cell markers and autophagy-related molecules in the nasal mucosa, PBMCs or Th17/Treg cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) or flow cytometry analysis, and serum contents of related factors were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was applied to observe the thickness of mouse mucosa. RESULTS: IL-17A, RORγt, Beclin1 and LC3-II/LC3-I levels were increased in AR patients, while Foxp3 and P62 were decreased. The serum contents of IL-17A and eosinophil cationic protein (ECP) in AR patients were elevated, but IL-10 level was reduced. In PBMCs of AR patients, the levels of IL-17A and LC3-II were increased, and the levels of Foxp3 and P62 were decreased, while these changes could be reversed by glutathione. In AR mouse models, glutathione could balance Th17/Treg cells, reduce autophagy, correct the levels of related cytokines in mouse serum, and shrunk mucosa thickness. CONCLUSION: Glutathione could rescue the imbalance of Treg/Th17 cells by suppressing intracellular autophagy, which might be beneficial to the treatment of AR patients.

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE. DESIGN AND METHODS: Using a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects. RESULTS: Compared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups. CONCLUSION: Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.

Juvenile exposure to bisphenol A promotes ovarian differentiation but suppresses its growth - Potential involvement of pituitary follicle-stimulating hormone.

Bisphenol A (BPA), a plastic monomer and plasticizer, is commonly used in plastics industry, and it has been well documented to be an estrogenic endocrine disrupter. In the present study, we investigated the effect of early (juvenile) exposure to BPA on the hypothalamic-pituitary-gonad (HPG) axis in the zebrafish. Estradiol (E2) and testosterone (T) were also included as positive and negative controls respectively. Juvenile zebrafish were exposed to BPA (1 and 10µM), E2 (10nM) and T (10nM) from 20 to 40 dpf (days post-fertilization), the period of sex/gonadal differentiation, followed by histological and expression analyses at 40 dpf. The ovary and hepatic proteomes were also analyzed by mass spectrometry. Our results showed that 20day exposure to BPA and E2 increased the ratio of females; however, they both significantly suppressed ovarian growth. Meanwhile, BPA and E2 significantly suppressed fshb but stimulated lhb expression in the pituitary. These effects did not seem to involve the hypothalamus because neither BPA nor E2 altered the expression of kiss1, kiss2, gnrh2 and gnrh3 in the hypothalamus. At the ovary level, BPA and E2 both decreased lhcgr expression. Interestingly, E2 and BPA displayed different effects in the liver. E2 induced a significant hepatic hypertrophy; however, BPA had no such effect. Analysis of hepatic proteomes revealed distinct protein profiles in the E2 group as compared with the others, especially fructose-bisphospahte aldolase B. These results indicated that BPA has estrogenic effects on female reproduction, but it does not mimic all E2 actions. Our data in the zebrafish suggest that sex differentiation involves estrogens and it is a sensitive window for evaluating estrogenic activities of compounds and their impacts on wildlife reproduction.

The prevalence and associated lifestyle risk factors of self-reported allergic rhinitis in Kazakh population of Fukang City.

This study is to analyze the prevalence and the associated lifestyle risk factors of self-reported allergic rhinitis (AR) in Kazakh population of Fukang City.A cross-sectional study was conducted using stratified random sampling method and 1689 Kazak people were surveyed. A standard questionnaire was used for face-to-face interview.The prevalence of self-reported AR of Kazakh population in Fukang City was 13.7%, and sneezing was the most common symptoms (54.6%) with no significant differences among age, sex, and weight. The incidence of asthma in Kazakh people was correlated with age, and the incidence of allergies in Kazakh people was correlated with weight. Skin pruritus was the most common symptom for allergy (42.7%). The AR incidence was correlated with sinusitis and asthma, and was mostly associated with carpet use. For diet, the AR incidence was positively correlated with meat and fruit, and negatively correlated with beans and milk.The prevalence of AR is high among Kazakh people in Fukang City, and its incidence is closely related with lifestyle risk factors such as carpet use and meat and fruit consumption.

MicroRNA-125b targeted STAT3 to inhibit laryngeal squamous cell carcinoma cell growth and motility.

A majority of studies have indicated that microRNA-125b (miR-125b) is aberrantly expressed in various types of cancer. However, there are no studies on the expression and function of miR-125b in human laryngeal squamous cell carcinoma (LSCC). In the present study, miR-125b expression in LSCC sample tissues, corresponding adjacent non-neoplastic tissues, LSCC cell lines and a normal human keratinocyte cell line was measured using the reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-125b mimics, the Cell Counting Kit-8, cell migration, cell invasion, western blotting and dual-luciferase reporter assays were performed on LSCC cell lines. According to the results, miR-125b was observed to be significantly downregulated in LSCC, and its expression was significantly associated with clinical stage and alcohol history. miR-125b was also observed to decrease cell growth, migration and invasion in LSCC cells by directly targeting signal transducer and activator of transcription 3. The results of the present study suggested that miR-125b may be a potential treatment target of LSCC in the future.

[Relationship between adult craniofacial structures and development of obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the influence of adult craniofacial structures on obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: This study compared the measurements of the height, body weight,neck circumference, the mallampati oropharyngeal score grading, thyromental distance, thyromental angle, lobule-mental distance, mental-lower lip distance of 50 patients with OSAHS with those of 50 controls. RESULT: Statistical findings showed that OSAHS patients were different from controls in the following ways: (1) higher neck circumference; (2) larger thyromental angle; (3) higher Mallampati scores; (4) higher body mass index; (5) shorter mental-lower lip distance. CONCLUSION: A crowded posterior oropharynx and a steep thyromental plane are associated with OSAHS. The adult craniofacial structures of bony and soft tissue determine the dimension of upper airway during sleep andpaly an important role in the development of OSAHS.