Methylation of ERß 5'-untranslated region attenuates its inhibitory effect on ERα gene transcription and promotes the initiation and progression of papillary thyroid cancer.

Normal thyroid tissue displays a prevalent expression of ERß than ERα, which drastically turns upside down in the initiation and progression of papillary thyroid cancer (PTC). The underlying molecular mechanism of this phenomenon remains unclear. Here, we demonstrated that ERα and ERß were coexpressed in human thyroid tissues and cells. ERα mRNA (A-1) and ERß mRNA (0N-1), transcribed from Promoter A of ERα gene and Promoter 0N of ERß gene, respectively, were the major mRNA isoforms which mainly contributed to total ERα mRNA and total ERß mRNA in human thyroid-derived cell lines and tissues. The expression levels of ERα mRNA (A-1) and total ERα mRNA were gradually increased, and those of ERß mRNA (0N-1) and total ERß mRNA were decreased by degree in the initiation and progression of PTC. No aberrant DNA methylation of ERα 5'-untranslated region was involved in its up-regulation; however, aberrant DNA methylation in Promoter 0N and Exon 0N of ERß gene was found to be involved in its down-regulation in the initiation and progression of PTC. ERß can repress ERα gene transcription via recruitment of NCoR and displacement of RNA polymerase II at the Sp1 site in ERα Promoter A-specific region in thyroid-derived cells. It is suggested that DNA methylation of CpG islands in Promoter 0N and Exon 0N of ERß gene leads to a decreased ERß gene expression, which attenuates its inhibitory effect on ERα gene transcription and results in an increased ERα gene expression, cell proliferation, initiation, and progression of PTC.

Prevalence and associated risk factors of Helicobacter pylori infection in the Wuwei cohort of north-western China.

OBJECTIVES: To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer. METHODS: Helicobacter pylori infection was analysed in 21 291 adults by 14 C-urea breath test, and H. pylori antibody were detected in 9183 serum samples by latex immunoturbidimetric method. The correlation of H. pylori infection with demographic-economic, lifestyle factors and medical history among the participants was determined by questionnaire. The antibodies against H. pylori urease, VacA and CagA in serum were determined by dot immunobinding assay. RESULTS: The infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P < 0.05). CONCLUSION: The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.

OBJECTIFS: Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée au 14 C, et des anticorps à H. pylori ont été détectés dans 9.183 échantillons de sérum par une méthode immuno-turbidimétrique au latex. La corrélation entre l'infection à H. pylori et les facteurs démographiques et économiques, le mode de vie et les antécédents médicaux des participants a été déterminée par un questionnaire. Les anticorps contre l'uréase de H. pylori, VacA et CagA dans le sérum ont été déterminés par un test dot par d'immuno-liaison. RÉSULTATS: Le taux d'infection à H. pylori était 53,0% et 90,1% des souches étaient du type I. Le taux d'infection à H. pylori est plus élevé chez les agriculteurs (OR = 1,34 ; IC95%: 1,19 à 1,50) et les personnes qui avaient un niveau d'instruction du premier cycle secondaire ou supérieur (OR = 1,10 ; IC95%: 01,06 à 01,15) et était plus faible chez les personnes âgées (OR = 0,86 ; IC95%: 0,83-0,90), les personnes à revenu élevé (OR = 0,93 ; IC95%: 0,90-0,95), les personnes ayant l'habitude de manger rapidement (OR = 0,93 ; IC9 %: 0,87-0,99) et les individus qui consommaient plus de fruits et de légumes (OR = 0,90 ; IC95%: 0,85-0,95). Les personnes ayant des antécédents de cholécystite/cholécystolithiase, d'hypertension et d'asthme avaient une corrélation négative avec l'infection à H. pylori (p <0,05 ). CONCLUSION: La prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

[Effects of UHRF1 on Estrogen Receptor and Proliferation, Invasion and Migration of BCPAP Cells in Thyroid Papillary Carcinoma].

OBJECTIVE: To investigate the effects of ubiquitin-like PDH and ring finger domain 1 (UHRF1) on the expression ratio of estrogen receptor (ER) α/ERß, and to explore the experimental mechanism of UHRF1 affecting the proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma. METHODS: The protein and mRNA expressions of UHRF1, ERα and ERß in normal thyroid Nthy-ori3-1 cells and thyroid papillary carcinoma BCPAP cells were detected by Western blot and qRT-PCR. BCPAP cells were treated with Scrambled siRNA and UHRF1 siRNA, respectively. The expressions of ER α and ER ß mRNAs were detected by qRT-PCR. MTT and Transwell were used to determine the proliferation, invasion and migration in each group of BCPAP cells. RESULTS: Compared with Nthy-ori3-1 cells, the expressions of UHRF1 and ERα proteins and mRNAs in BCPAP cells were significantly up-regulated ( P<0.05), while the expressions of ERß protein and mRNA were significantly down-regulated ( P<0.05). Compared with the control group and Scrambled siRNA group, the expression of ER α mRNA in BCPAP cells transfected with UHRF1 siRNA was significantly decreased ( P<0.05), while the expression of ER ß mRNA was significantly increased ( P<0.05). The proliferation, invasion and migration of BCPAP cells transfected with UHRF1 siRNA were significantly decreased ( P<0.05). CONCLUSION: UHRF1 upregulates ERα/ERß expression ratio and promotes proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma.

Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae.

Klebsiella pneumoniae is a major health threat. Vaccination and passive immunization are considered as alternative therapeutic strategies for managing Klebsiella infections. Lipopolysaccharide O antigens are attractive candidates because of the relatively small range of known O-antigen polysaccharide structures, but immunotherapeutic applications require a complete understanding of the structures found in clinical settings. Currently, the precise number of Klebsiella O antigens is unknown because available serological tests have limited resolution, and their association with defined chemical structures is sometimes uncertain. Molecular serotyping methods can evaluate clinical prevalence of O serotypes but require a full understanding of the genetic determinants for each O-antigen structure. This is problematic with Klebsiella pneumoniae because genes outside the main rfb (O-antigen biosynthesis) locus can have profound effects on the final structure. Here, we report two new loci encoding enzymes that modify a conserved polysaccharide backbone comprising disaccharide repeat units [→3)-α-d-Galp-(1→3)-ß-d-Galf-(1→] (O2a antigen). We identified in serotype O2aeh a three-component system that modifies completed O2a glycan in the periplasm by adding 1,2-linked α-Galp side-group residues. In serotype O2ac, a polysaccharide comprising disaccharide repeat units [→5)-ß-d-Galf-(1→3)-ß-d-GlcpNAc-(1→] (O2c antigen) is attached to the non-reducing termini of O2a-antigen chains. O2c-polysaccharide synthesis is dependent on a locus encoding three glycosyltransferase enzymes. The authentic O2aeh and O2c antigens were recapitulated in recombinant Escherichia coli hosts to establish the essential gene set for their synthesis. These findings now provide a complete understanding of the molecular genetic basis for the known variations in Klebsiella O-antigen carbohydrate structures based on the O2a backbone.

Tumor vaccines: Toward multidimensional anti-tumor therapies.

For decades, immunotherapies have offered hope for patients with advanced cancer. However, they show distinct benefits and limited clinical effects. Tumor vaccines have the potential to prime tumor-antigen-specific T cells and induce broad subsets of immune responses, ultimately eradicating tumor cells. Here, we classify tumor vaccines by their anti-tumor mechanisms, which include boosting the immune system, overcoming tumor immunosuppression, and modulating tumor angiogenesis. We focus on multidimensional tumor vaccine strategies using combinations of two or three of the above mechanisms, as these are superior to single-dimensional treatments. This review offers a perspective on tumor vaccine strategies and the future role of vaccine therapies in cancer treatment.

[Inhibitory effect of CMTM5 on xenografted human prostatic cancer in nude mice].

OBJECTIVE: To investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism. METHODS: We established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry. RESULTS: The tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group. CONCLUSION: CMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

Comprehensive analysis to identify DNA damage response-related lncRNA pairs as a prognostic and therapeutic biomarker in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. The identification of valuable predictive signatures to improve the prognosis of patients with GC is becoming a realistic prospect. DNA damage response-related long noncoding ribonucleic acids (drlncRNAs) play an important role in the development of cancers. However, their prognostic and therapeutic values remain sparse in gastric cancer (GC). METHODS: We obtained the transcriptome data and clinical information from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort. Co-expression network analyses were performed to discover functional modules using the igaph package. Subsequently, lncRNA pairs were identified by bioinformation analysis, and prognostic pairs were determined by univariate analysis, respectively. In addition, we utilized least absolute shrinkage and selection operator (LASSO) cox regression analysis to construct the risk model based on lncRNA pairs. Then, we distinguished between the high- or low- risk groups from patients with GC based on the optimal model. Finally, we reevaluated the association between risk score and overall survival, tumor immune microenvironment, specific tumor-infiltrating immune cells related biomarkers, and the sensitivity of chemotherapeutic agents. RESULTS: 32 drlncRNA pairs were obtained, and a 17-drlncRNA pairs signature was constructed to predict the overall survival of patients with GC. The ROC was 0.797, 0.812 and 0.821 at 1, 2, 3 years, respectively. After reclassifying these patients into different risk-groups, we could differentiate between them based on negative overall survival outcome, specialized tumor immune infiltration status, higher expressed immune cell related biomarkers, and a lower chemotherapeutics sensitivity. Compared with previous models, our model showed better performance with a higher ROC value. CONCLUSION: The prognostic and therapeutic signature established by novel lncRNA pairs could provide promising prediction value, and guide individual treatment strategies in the future.

The Association of Trefoil Factors with Gastric Cancer and Premalignant Lesions: A Cross-Sectional Population-Based Cohort Study.

BACKGROUND: A lack of research on the association of trefoil factors (TFF) with gastric cancer and premalignant lesions (PML) in the general population is an important obstacle to the application of TFFs for gastric cancer screening. We aimed to analyze the association of TFFs with gastric cancer and PMLs in a general population. METHODS: We evaluated 3,986 adults residing in Wuwei, China. We collected baseline characteristics and gastric cancer risk factors, including TFFs, endoscopic diagnosis, and pathologic information. Three logistic regression models were generated to analyze the association between TFFs and gastric cancer, as well as PMLs. Adjusted odds ratio (OR) and 95% confidence intervals (95% CI) were calculated to determine the strength of association. RESULTS: Compared with pepsinogen (PG) and anti-Helicobacter pylori immunoglobulin G antibody (Hp-IgG), TFFs had significant association with gastric cancer and PMLs after adjusting for biomarkers and risk factors (P < 0.05). The ORs (95% CI) for TFF1 (1.67; 1.27-2.20), TFF2 (2.66; 2.01-3.51), and TFF3 (1.32; 1.00-1.74) were larger than the ORs for PGI (0.79; 0.61-1.03), PGI/II (1.00; 0.76-1.31), and Hp-IgG (0.99; 0.73-1.35) in the gastric cancer group. In the intestinal metaplasia (IM) group, not only the TFF3 serum level was the highest, but also the OR (1.92; 1.64-2.25) was the highest. CONCLUSIONS: TFFs were associated with risk of gastric cancer and PMLs. IMPACT: Serum TFFs can improve the screening of high-risk populations for gastric cancer.

Risk factors in the development of gastric adenocarcinoma in the general population: A cross-sectional study of the Wuwei Cohort.

Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.

Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China; the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. AIMS: The aim of this meta-analysis was to assess the prevalence of comorbidities in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients and the risk of underlying diseases in severe patients compared to non-severe patients. METHODS: A literature search was conducted using the databases PubMed, EMBASE, and Web of Science through February 25, 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS: Seven studies were included in the meta-analysis, including 1 576 infected patients. The results showed the most prevalent clinical symptom was fever (91.3%, 95% CI: 86-97%), followed by cough (67.7%, 95% CI: 59-76%), fatigue (51.0%, 95% CI: 34-68%) and dyspnea (30.4%, 95% CI: 21-40%). The most prevalent comorbidities were hypertension (21.1%, 95% CI: 13.0-27.2%) and diabetes (9.7%, 95% CI: 7.2-12.2%), followed by cardiovascular disease (8.4%, 95% CI: 3.8-13.8%) and respiratory system disease (1.5%, 95% CI: 0.9-2.1%). When compared between severe and non-severe patients, the pooled OR of hypertension, respiratory system disease, and cardiovascular disease were 2.36 (95% CI: 1.46-3.83), 2.46 (95% CI: 1.76-3.44) and 3.42 (95% CI: 1.88-6.22) respectively. CONCLUSION: We assessed the prevalence of comorbidities in the COVID-19 patients and found that underlying disease, including hypertension, respiratory system disease and cardiovascular disease, may be risk factors for severe patients compared with non-severe patients.

New records of Celaenorrhinus pyrrha de Nicéville, 1889 and C. munda (Moore, 1884) from China (Lepidoptera, Hesperiidae).

Celaenorrhinus pyrrha de Nicéville, 1889, a rare species of Hesperiidae previously known to be distributed from northeastern India to Indochina, is reported from southwestern Yunnan and southwestern Chongqing, China. A 658 bp COI gene sequence of this species is published for the first time. Although Chongqing is obviously isolated from the main distribution range, morphological characters of the specimens from this locality do not indicate a subspecies differentiation. Another rare taxon, C. munda munda (Moore, 1884), is also recorded from China for the first time based upon a male specimen from Cuona County in the Tibet Autonomous Region. This is the second specimen of C. munda from China, over 100 years after the holotype of C. munda joka Evans, 1949. The genitalia of both species are illustrated and described. Some taxonomic notes and a distribution map are provided as well.