Abstract Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real‐time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa‐miR‐933 overexpression. hsa_circRNA_100533 binds to hsa‐miR‐933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533‐miR‐933‐GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.
Immunity against malaria depends on germinal center (GC)-derived antibody responses that are orchestrated by T follicular helper (TFH) cells. Emerging data show that the regulatory cytokine IL-10 plays an essential role in promoting GC B cell responses during both experimental malaria and virus infections. Here we investigated the cellular source and temporal role of IL-10, and whether IL-10 additionally signals to CD4 T-cells to support anti- Plasmodium humoral immunity. Distinct from reports of virus infection, we found that IL-10 was expressed by conventional, Foxp3-negative effector CD4 T cells and functioned in a B cell-intrinsic manner only during the first 96 hours of Plasmodium infection to support humoral immunity. The critical functions of IL-10 manifested only before the orchestration of GC responses and were primarily localized outside of B cell follicles. Mechanistically, our studies showed that the rapid and transient provision of IL-10 promoted B cell expression of anti-apoptotic factors, MHC class II, CD83, and cell-cell adhesion proteins that are essential for B cell survival and interaction with CD4 T cells. Together, our data reveal temporal features and mechanisms by which IL-10 critically supports humoral immunity during blood-stage Plasmodium infection, information that may be useful for developing new strategies designed to lessen the burden of malaria.
The methods of spectrophotometry,HPLC and voltammetry for the determination of food flavor enhancer,maltol and ethyl maltol were compared in this paper.The flavor enhancer,maltol and ethyl maltol,could be detected by HPLC method.The total amount of flavor enhancer was determined by spectrophotometric and voltammetric methods.Voltammetric method is simple,rapid,sensitive and cheap for directly determining flavor enhancer in beverages without any complicated and time-consuming separation process.
Lipoprotein (a) [Lp(a)] plays a crucial role in the pathogenesis of deep vein thrombosis (DVT). The purpose of this study was to investigate whether Lp(a) serum levels at admission could be a risk factor for DVT in Chinese patients with acute ischemic stroke (AIS). A total of 232 patients with AIS were included in the study. The patients were assessed for DVT using colour Doppler ultrasonography. We performed colour Doppler ultrasonography 15 days after the stroke and whenever clinically requested. The value of Lp(a) to predict the DVT was analyzed using logistic regression analysis after adjusting for the possible confounders. In our study, 44 out of the 232 patients (19.0%) were diagnosed with DVT at 15-day follow-up. Serum Lp(a) levels were higher in AIS with DVT than in those patients without DVT [656 (interquartile range, 521-898) mg/l vs. 253 (interquartile range, 143-440) mg/l; P<0.0001]. Increased risk of DVT associated with Lp(a) levels greater than or equal to 300 mg/l was found in the multivariate analysis [odds ratio 12.14, 95% confidence interval (CI): 3.08-42.09; P<0.0001]. Visible by the receiver operating characteristic, the optimal cutoff value of serum Lp(a) levels for predicting DVT was projected to be 420 mg/l, yielding a sensitivity of 88.5% and a specificity of 75.4%. With an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.94), Lp(a) exhibited greater discrimination in predicting DVT compared with Hs-CRP (AUC, 0.77; 95% CI, 0.69-0.85; P<0.01), HCY (AUC, 0.76; 95% CI, 0.68-0.84; P<0.01), and NIHSS score (AUC, 0.74; 95% CI, 0.66-0.82; P<0.001). Elevated serum Lp(a) levels were independent predictors of DVT in AIS patients in China, revealing the critical role played by Lp(a) in the pathogenesis of DVT.
The present study aims to evaluate the relation between PON1 L55M polymorphism and ischemic stroke by a meta-analysis method.English and Chinese databases were retrieved to find qualified studies; a random or fixed effects model was used to merge the odds ratio (OR); Q test was used to assess the heterogeneity among studies, and Egger's test and funnel plot were used for the assessment of publication bias.14 studies were included in the meta-analysis; in total populations, there was no association between PON1 gene L55M polymorphism and ischemic stroke in additive, dominant, and recessive model, respectively. Furthermore, we did not found associations between L55M and ischemic stroke in Asian or Caucasian population.Available evidences suggested that L55M polymorphism had no effect on the risk of ischemic stroke. However, this conclusion needs further validation by larger sample and well-designed studies.
Purpose The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs).
HER2 plays a critical role in tumourigenesis and is associated with poor prognosis of patients with HER2-positive breast cancers. Although anti-HER2 drugs are beneficial for treating breast cancer, de novo, or acquired resistance often develops. Epigenetic factors are increasingly targeted for therapy; however, such mechanisms that interact with HER2 signalling are poorly understood.RNA sequencing was performed to identify PHF8 targets downstream of HER2 signalling. CHIP-qPCR were used to investigate how PHF8 regulates HER2 transcription. ELISA determined cytokine secretion. Cell-based assay revealed a feed forward loop in HER2 signalling and then evaluated in vivo.We report the synergistic interplay between histone demethylase PHF8 and HER2 signalling. Specifically, PHF8 levels were elevated in HER2-positive breast cancers and upregulated by HER2. PHF8 functioned as a coactivator that regulated the expression of HER2, markers of the HER2-driven epithelial-to-mesenchymal transition and cytokines. The HER2-PHF8-IL-6 regulatory axis was active in cell lines and in newly established MMTV-Her2/MMTV-Cre/Phf8fl°x/fl°x mouse models, which revealed the oncogenic function of Phf8 in breast cancer for the first time. Further, the PHF8-IL-6 axis contributed to the resistance to trastuzumab in vitro and may play a critical role in the infiltration of T cells in HER2-driven breast cancers.These findings provided informative mechanistic insight into the potential application of PHF8 inhibitors to overcome resistance to anti-HER2 therapies.This work was supported by Carver Trust Young Investigator Award (01-224 to H.H.Q); and a Breast Cancer Research Award (to H.H.Q.).
Abstract Background: Sick euthyroid syndrome is frequent in children admitted with diabetic ketoacidosis (DKA). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children admitted for management of DKA. Methods: 194 children admitted for management of DKA were selected from hospital records. Children on thyroxine replacement or those with overt hypothyroidism or anti-TPO antibody positive were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done for all. Children were divided into a euthyroid group (n=88) and an euthyroid sick syndrome（ESS）group (n=106). Results: The ESS group had a higher WBC, PG, β-HB, TG, AG, and HbA1c and lower HCO3-, PA, and ALB levels compared with the euthyroid group (P<0.05). FT3 levels were significantly correlated to β-HB, HCO3-, AG, PA, and HbA1c. (r=-0.642, 0.681, -0.377, 0.581, -0.309, respectively; P<0.01) FT4 levels were significantly correlated to β-HB, HCO3-, and ALB levels (r=-0.489, 0.338, 0.529, respectively; P<0.01). TSH levels were significantly affected by HCO3 – only (r=-0.28; P<0.01). HCO3 – level was the most important factor deciding adjudication to euthyroid or ESS group on logistic regression analysis (OR=0.844, P=0.004, 95%CI=0.751-0.948). Conclusions: Lower levels of free thyroid hormones and occurrence of ESS is associated with a higher degree of acidosis in children admitted with DKA. Lower levels of markers of nutrition such as serum albumin and pre-albumin levels are associated with lower levels of free thyroid hormone concentrations in children with DKA.
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