Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China

Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. MATERIAL AND METHODS: The female proband and her family members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). RESULTS: Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant diferences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. CONCLUSIONS: These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified

An investigation on normal school students’ learning burnout – A case study of English normal students

Learning burnout is a phenomenon in which students hold a negative attitude to curriculum learning, which manifests in aspects of physiology, psychology, behavior and interpersonal communication. China attaches great importance to higher education, colleges and universities shoulder the important task of training national modernization personnel. The problem of university students’ learning burnout has become a social phenomenon that cannot be ignored. Normal university students are one of the important groups of college students, and this phenomenon of learning burnout may also occur among them. English majors are the backbone of English teachers in primary and secondary schools in the future. The learning status of these groups affects the overall quality of teaching in normal colleges and universities and, more importantly, the quality of teachers in primary and secondary schools in the future. This paper first reviews the definition of learning burnout and the research methods of measurement. Subsequently, it investigates the learning burnout of English matriculation students by taking the first-year English majors of Jiangxi Normal University as an example. In this way, this research is hoped to promote the study on learning burnout not only among English normal students but also other normal students

DataSheet6_Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.xlsx

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.</p

Image2_Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.jpg

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.</p

Image1_Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.jpeg

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.</p

DataSheet4_Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.xlsx

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.</p

DataSheet2_Exploring the causal relationship between gastroesophageal reflux and oral lesions: A mendelian randomization study.CSV

Background: Clinical observations and retrospective studies have observed that patients with gastroesophageal reflux disease (GERD) have an increased probability of dental erosion, periodontitis and oral mucosal lesions and other common oral lesions. However, whether there is a genetic causal relationship between GERD and the occurrence of oral lesions has not been reported.Methods: In this study, we extracted instrumental variables from the largest published summary statistics of the oral lesion phenotype GWAS in UK Biobank (UKBB) and GERD GWAS. Then, we performed a causal inference analysis between GERD and common oral lesions by mendelian randomization (MR) analysis with the R package “TwoSampleMR”.Results: We observed a significant causal relationship between GERD and several common oral lesion phenotypes (painful gums, loose teeth, toothache, and mouth ulcers). GERD showed a positive correlation with the occurrence of these oral lesions. After removing outlier SNPs via the MR-PRESSO package, our conclusions were still robust.Conclusion: Our findings provide the first evidence for a genetic causal effect of GERD on oral lesion pathogenesis. For patients with confirmed GERD, attention should be paid to taking interventions to prevent the occurrence of oral lesions.</p