Correlation between sarcopenia and esophageal cancer: a narrative review.

BACKGROUND: In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people's attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. METHODS: A narrative review was performed in PubMed and Web of Science using the keywords ("esophageal cancer" or "esophageal neoplasm" or "neoplasm, esophageal" or "esophagus neoplasm" or "esophagus neoplasms" or "neoplasm, esophagus" or "neoplasms, esophagus" or "neoplasms, esophageal" or "cancer of esophagus" or "cancer of the esophagus" or "esophagus cancer" or "cancer, esophagus" or "cancers, esophagus" or "esophagus cancers" or "esophageal cancer" or "cancer, esophageal" or "cancers, esophageal" or "esophageal cancers") and ("sarcopenia" or "muscular atrophy" or "aging" or "senescence" or "biological aging" or "aging, biological" or "atrophies, muscular" or "atrophy, muscular" or "muscular atrophies" or "atrophy, muscle" or "atrophies, muscle" or "muscle atrophies"). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. RESULTS: The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). CONCLUSIONS: Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients.

CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer.

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system worldwide. To date, immune checkpoint inhibitors (including PD-1/PD-L1) have been applied to treat patients with bladder cancer in the clinic and achieved the promising outcome. Further improvement of the anticancer efficiency of these immune therapies is crucial for bladder cancer. Our previous RNA-seq data on CBX7 (GSE185630) suggested that CBX7 might repress PD-L1 expression and PD-1 checkpoint pathway in cancer. In this study, we revealed that CBX7 downregulated the expression of POU2F2 that indirectly repressed the PD-L1 in BC cells. Depletion of CBX7 resulted in resistance to PD-1 blockade in bladder cancer. Collectively, our results suggested that the CBX7/POU2F2/PD-L1 axis plays an important role in determining the antitumor effect of PD-1 blockade in bladder cancer.

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis.

Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H2O2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.

The prevalence of HLA-I LOH in Chinese pan-cancer patients and genomic features of patients harboring HLA-I LOH.

HLA-I LOH may facilitate immune evasion. However, large population studies on the prevalence of HLA-I LOH across different cancer types and in relation to mutational profiles are lacking, in particular, in the Chinese population. In this study, analysis was performed in 1504 advanced pan-cancer patients and 134 early-stage non-small-cell lung cancer patients using a 1021-gene panel. The consistency between the 1021-gene panel and whole-exome sequencing was evaluated in 45 samples, where concordant results were obtained in 95.6% (43/45) of the samples. Analytical results revealed that the prevalence of HLA-I LOH in tumor tissue presents considerable differences across cancer types. HLA-I LOH was relevant to genomic instability, reflected in higher tumor mutation burden level. HLA-I LOH occurs more frequently in MSS samples than in MSI-H samples. The alteration frequencies of p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway, and Nrf2 pathway in HLA-I LOH group were significantly higher than that in HLA-I stable group (p < .0001, p < .0001, p = .032, p = .013, p = .003, respectively). In DNA damage response pathways, alterations in the checkpoint factor pathway and Fanconi anemia pathway are enriched in HLA-I LOH group (p < .0001, p = .023, respectively). Besides, HLA-I LOH was accompanied by higher mutation rates of several tumor suppressors, including TP53 and LRP1B. These results may shed light on follow-up tumor immunology research.

Silencing of UAP1L1 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the malignant tumors with poor prognosis. UAP1L1 (UDP-N-acetylglucosamine-1-like-1) affects numerous biological processes, which is a key regulator of the development of malignant tumors. The biological function and molecular mechanism of UAP1L1 in ESCC were explored in this study. The relationship between UAP1L1 and ESCC was analyzed by immunohistochemical staining, revealing the high expression of UAP1L1 in ESCC. Importantly, the increased expression of UAP1L1 indicated the deterioration of patients' condition, which has clinical significance. Furthermore, the loss-of-function assays demonstrated that knockdown of UAP1L1 inhibited the progression of ESCC on suppressing proliferation, hindering migration, and enhancing apoptosis in vitro. Moreover, the apoptosis of ESCC cells was induced by knockdown of UAP1L1 via regulating a variety of apoptosis-related proteins, such as upregulation of Bax, CD40, CD40L, Fas, FasL, IGFBP-6, p21, p27, p53, and SMAC. Additionally, further investigation indicated that UAP1L1 by affecting the PI3K/Akt, CCND1, and MAPK promotes the progression of ESCC. In vivo xenograft model further confirmed that knockdown of UAP1L1 inhibited the development of ESCC. In conclusion, UAP1L1 was involved in the development and progression of ESCC, which may provide a powerful target for future molecular therapies.

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma.

Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis- trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA-mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA-related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty-one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA-mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan-Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22.

[Epidemiological survey of asthma among children aged 0-14 years in 2010 in urban Zhongshan, China].

OBJECTIVE: To investigate the prevalence, current treatment, and clinical characteristics of asthma, as well as the risk factors for this disease, among children aged 0-14 years in 2010 in urban Zhongshan, China. METHODS: A total of 10 336 children aged 0-14 years were selected from urban Zhongshan by cluster random sampling. The Third National Childhood Asthma Epidemiological Questionnaire 2010 was used to analyze the prevalence, current treatment, and clinical characteristics of childhood asthma, as well as the risk factors for this disease. RESULTS: Asthma was diagnosed in 179 cases (1.73%). The prevalence of asthma in male children was significantly higher than that in female children (2.25% vs 1.16%; P<0.01). Of the 179 patients, severe attacks were common in 104 cases (58.1%), 110 cases (61.5%) had slow onset, 102 cases (57.0%) had gradually relieved conditions, 61 cases (34.1%) suffered from asthma during seasonal transition, and 150 cases (83.8%) developed asthma due to respiratory tract infection. Among all asthmatic children, 71.5% had been treated with inhaled corticosteroids, and 71.5% had been treated with bronchodilator. The multivariate logistic regression analysis showed that a history of penicillin allergy, a family history of allergy, food allergy, eczema, allergic rhinitis, cesarean delivery, family mould, and perinatal passive smoking were independent risk factors for childhood asthma. CONCLUSIONS: The prevalence of childhood asthma in urban Zhongshan is on a high level, and is associated with gender. The treatment of asthma has been standardized, but still needs further improvement. The onset of asthma attack is influenced by various factors.

[Incidence of wheezing and chronic cough in children aged 3-14 years in rural and urban areas of Zhongshan, China: a questionnaire survey].

OBJECTIVE: To investigate the incidence of wheezing and chronic cough in children aged 3-14 years in different living areas of Zhongshan, China. METHODS: According to the unified program of the 2010 national epidemiological survey of asthmatic children aged 0-14 years, a questionnaire survey of the children aged 3-14 years in rural and urban areas of Zhongshan was conducted. RESULTS: A total of 15 763 children were included in the survey. Among all participants, 8 248 were from the urban area, and 7 515 from the rual area; 8 306 were boys, and 7 457 were girls. The percentage of children with a history of wheezing was significantly higher in the urban group than in the rural group (6.6% vs 3.2%; P<0.05), and it was significantly higher in boys than in girls for each group (P<0.05). The urban group had a significantly higher percentage of individuals who had wheezing in the past one year than the rural group (2.8% vs 1.5%; P<0.05), and this percentage was significantly higher in boys than in girls for each group (P<0.05). Compared with the rural group, the urban group had a significantly higher percentage of individuals who had chronic cough (duration 1 year) (7.9% vs 3.1%; P<0.05). The above indices were relatively high in children under 6 years of age, and all but the percentage of girls who had wheezing in the past one year in both rural and urban areas showed significant differences between all age groups. CONCLUSIONS: The incidence of wheezing and chronic cough varies with age, sex, and living area for children aged 3-14 years in Zhongshan, and it is relatively high under 6 years of age, in the urban area, and among boys.

Overexpressed FAM111B degrades GSDMA to promote esophageal cancer tumorigenesis and cisplatin resistance.

BACKGROUND: Chemotherapeutic agents such as cisplatin are commonly used in patients with clinically unresectable or recurrent esophageal cancer (ESCA). However, patients often develop resistance to cisplatin, which in turn leads to a poor prognosis. Studies have shown that FAM111B may be involved in the development of tumors as an oncogene or tumor suppressor gene. However, the pathological role and corresponding mechanism of FAM111B in ESCA are still unclear. METHODS: The GEPIA web tool, ENCORI Pan-Cancer Analysis Platform and UALCAN-TCGA database were used to study the expression of FAM111B in ESCA. CCK-8, angiogenesis, Transwell and xenograft assays were applied to explore the biological function of FAM111B in ESCA. Western blot, RT-qPCR, and RNA-seq analyses were applied to study the FAM111B/GSDMA axis in the progression of ESCA cells. CCK-8 and xenograft assays were used to study the role of the FAM111B/GSDMA axis in determining the sensitivity of ESCA to cisplatin. RESULTS: Our results demonstrated that FAM111B is highly expressed in ESCA tissues compared to normal tissues. We showed that FAM111B promotes the progression of ESCC cells by binding to GSDMA and that the trypsin protease domain is essential for the activity of FAM111B. Furthermore, we showed that the FAM111B/GSDMA axis regulates cisplatin sensitivity in ESCA. CONCLUSIONS: Overall, we identified a novel FAM111B/GSDMA axis regulating ESCA tumorigenesis and chemosensitivity, at least in ESCC cells.

Specific IgG4 production during house dust mite immunotherapy among age, gender and allergic disease populations.

BACKGROUND: Specific IgG4 induced by allergen-specific immunotherapy (SIT) is an immunological marker related to the appearance of clinical tolerance. But specific IgG4 levels in different age, gender and allergic disease populations have not been fully investigated. METHODS: This study involved 226 children and 109 adults with allergic rhinitis and/or asthma receiving a 156-week course of Dermatophagoides pteronyssinus (Der p) subcutaneous SIT. Symptom and medication scores, forced expiratory volume after 1 s (FEV(1)) and Der p-specific IgG4 levels at weeks 0, 5, 10, 25, 52, 104 and 156 were analyzed. RESULTS: Rhinitis symptom and medication scores and FEV(1) % predicted in children showed significantly greater improvement than in adults at week 104 and 156 (p < 0.05). Levels of Der p-specific IgG4 showed a significant increase after 10 weeks of subcutaneous SIT (p < 0.0001) and continued to increase during the 156-week SIT period. Before SIT, the initial Der p-specific IgG4 level was higher in children than adults (p = 0.0004). The increase ratio of Der p-specific IgG4 was higher in children than adults at 52 weeks (p < 0.001) and 104 weeks (p = 0.0156) of SIT, and was higher in rhinitis compared to asthma patients at 156 weeks of SIT (p = 0.0244). There was no difference between males and females at any time points. CONCLUSION: Children are more responsive to SIT, demonstrating clinical and FEV(1) improvement and producing higher levels of allergen-specific IgG4 during a shorter SIT period compared to adults. Rhinitis patients show a higher increase in specific IgG4 compared to patients with asthma symptoms. The increase of Der p-specific IgG4 reflects a specific response of the immune system towards the SIT vaccine being administrated.

Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma.

BACKGROUND: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients' immunotherapy stratification. METHOD: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. RESULT: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. CONCLUSION: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.

Immune characteristics associated with lymph node metastasis in early-stage NSCLC.

PURPOSE: Tumor metastasis significantly impacts the prognosis of non-small cell lung cancer (NSCLC) patients, with lymph node (LN) metastasis being the most common and early form of spread. With the development of adjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes（TDLN) in early-stage NSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but has potential benefits in adjuvant treatment. METHODS: We showed the remodeled immune environment in TDLNs through using TCR-seq to analyse 24 primary lung cancer tissues and 134 LNs from 24 lung cancer patients with or without LN metastasis. Additionally, we characterized the spatial profiling of immunocytes and tumor cells in TDLNs and primary tumor sites through using multi-IHC. RESULTS: We found the remodeled immune environment in TDLNs through analyzing primary lung cancer tissues and LNs from NSCLC patients with or without LN metastasis. Considering the intricate communication between tumor and immunocytes, we further subdivided TDLNs, revealing that metastasis-negative LNs from LN-metastatic patients (MNLN) exhibited greater immune activation, exhaustion, and memory in comparison to both metastasis-positive LNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN). CONCLUSIONS: Our data indicate that LN metastasis facilitated tumor-specific antigen presentation in TDLNs and induces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs through multiple mechanisms. These findings contribute to a comprehensive understanding of the immunological mechanisms through which LN metastasis influences tumor progression and plays a role in immunotherapy for NSCLC patients.

Body shape and risk of glaucoma: A Mendelian randomization.

Background: Body size (BS) is one of the risk factors for the development of many clinical diseases, but the relationship between BS and glaucoma is controversial. Herein, we try to use Mendelian randomization (MR) method to study BS causal association with glaucoma risk from the genetic level. Methods: The Body Size was determined through anthropometric traits (ATs), such as body mass index (BMI), waist-to-hip ratio adjusted by body mass index (WHRadjBMI), waist-to-hip ratio (WHR), and waist circumference (WC). Association of single nucleotide polymorphisms (SNPs) with each AT and glaucoma were determined individually from the aggregated data of the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the FinnGen study summary data (8,591 cases with glaucoma and 210,201 controls). To explore the role of BS and glaucoma, a two-sample MR analysis was performed on genome-wide association study (GWAS) data. Besides, three MR methods [inverse variance weighted (IVW), Weighted median, and MR-Egger regression] were used to get the whole causal estimate for multiple instrumental SNPs. Results: BMI (OR = 1.20; 95% CI = 1.02-1.41; P = 0.03) and WC (OR = 1.32; 95% CI =1.04-1.69; P = 0.03) were associated with a risk of glaucoma. Besides, genetically predicted WHRadjBMI (OR = 1.10; 95% CI = 0.88-1.35; P = 0.43) and WHR (OR = 1.22; 95% CI = 0.93-1,572; P = 0.14) were not associated with glaucoma. No heterogeneity and directional pleiotropy were detected. Conclusion: The data of this study revealed that increased BMI and WC are potential risk factors for glaucoma, and WHRadjBMI and WHR are not associated with the occurrence of glaucoma.

Immunogenic cell death related risk model to delineate ferroptosis pathway and predict immunotherapy response of patients with GBM.

Immunogenic cell death (ICD) is a type of cell death that leads to the regulation and activation of the immune response, which is marked by the exposure and delivery of damage-associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that high-risk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment.

[Risk factors for bronchial asthma in school children].

OBJECTIVE: To investigate the roles of the residential environment and eating habits in the pathogenesis of bronchial asthma in school children. METHODS: One hundred and twenty-nine children between 6-12 years who were diagnosed with asthma were enrolled. Two hundred and fifty-eight healthy age- and gender-matched children were used as the control group. A questionaire which included 23 factors related to respiratory tract anaphylactic diseases such as residential environment and eating habits were completed by the children's parents. RESULTS: Logistic regression analysis showed that 6 variances out of 16 agents of the residential environment, the experience of raising pets, the type of floor, the type of pillow, the type of quilts, the heating equipments and the house area, were entered into the regression equation; none of the 7 variances of eating inhabits was entered into it. CONCLUSIONS: The residential environment plays an impotent role in the pathogenesis of bronchial asthma in children. The incidence of bronchial asthma in children can be reduced by the improvement of the residential environment.

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/ß-Catenin/MYC.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/ß-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/ß-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/ß-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/ß-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

Autologous enzyme-linked immunosorbent facilitated antigen binding detects IgE-blocking activity based on direct competition between allergen-specific IgE and non-IgE.

Aim: To measure IgE-blocking activity induced by allergen immunotherapy (AIT) by an enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) assay based on autologous immunoglobulin competition. Methods: The developed ELIFAB assay was used to investigate the kinetics of IgE-blocking activity in 87 patients at multiple AIT treatment time points, in comparison to the changes in IgG4. Results: High ELIFAB response was observed until 2.5 months of AIT, then significantly decreased after 4 months and remained suppressed during the 3-year AIT period. After treatment cessation, the ELIFAB response was maintained at the level seen at the 4-6 month treatment time point, similar to IgG4, indicating sustained IgE-blocking activity related to IgG4. Conclusion: This ELIFAB assay measures the IgE-blocking activity for autologous allergen-specific IgE and non-IgE during and after immunotherapy. It is suited for measuring the sustained IgE-blocking activity induced by AIT.

Lay abstract Allergy is a serious health problem worldwide. Allergen immunotherapy is a controlled exposure to allergen with the aim of modulating the immune response and reducing symptoms. The immune modulation includes a shift from the production of allergy-inducing IgE antibodies to inhibiting IgG antibodies and the competition between these antibodies for allergen binding when exposed to allergen may be central to the effect of the treatment. The current study addressed several ways of monitoring the changes in IgE and IgG antibodies during house dust mite immunotherapy. A novel assay for monitoring the competitive binding of these antibodies to house dust mite allergen is introduced; it may be used to monitor the immunological changes induced by immunotherapy and help increase treatment compliance.

Novel mechanisms for osteogenic differentiation of human aortic valve interstitial cells.

OBJECTIVE: Aortic valve calcification is common in aging populations without effective pharmacologic interventions. Our previous in vitro data revealed a critical role for long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 as a positive regulator of osteogenic differentiation in aortic valve calcification pathogenesis. The current study sought to determine the mechanism by which metastasis-associated lung adenocarcinoma transcript 1 is regulated in aortic valve calcification. METHODS: The stability assay was used to examine the effect of human antigen R on metastasis-associated lung adenocarcinoma transcript 1 expression. Aortic valves from patients with aortic stenosis and normal controls were subjected to determination of RNA-binding protein human antigen R expression. Mineralized bone matrix formation was assessed by Alizarin Red staining. The interaction between metastasis-associated lung adenocarcinoma transcript 1 and miR-191-3p was confirmed via RNA pull-down, luciferase reporter, and RNA-binding protein immunoprecipitation assays. RESULTS: In cultured human aortic valvular interstitial cells, we found human antigen R enhanced metastasis-associated lung adenocarcinoma transcript 1 stability and thus increased its concentration. Moreover, human antigen R was significantly upregulated in human calcific aortic valves and valvular interstitial cells after osteogenic induction. Human antigen R partly relied on metastasis-associated lung adenocarcinoma transcript 1 to positively regulate osteogenic differentiation of valvular interstitial cells. Luciferase reporter assays validated human antigen R as the direct target of miR-191-3p. Metastasis-associated lung adenocarcinoma transcript 1 positively regulated the expression of human antigen R through sponging miR-191-3p. CONCLUSIONS: This study demonstrates the existence of a regulatory loop between metastasis-associated lung adenocarcinoma transcript 1 and human antigen R during osteogenic differentiation of valvular interstitial cells. Our findings provide novel mechanistic insights into a critical role of human antigen R in the aortic valve calcification progression and shed new light on RNA-binding protein-directed diagnostics and therapeutics in aortic valve calcification.

Clinical Outcomes And Cost-Effectiveness Of Different Staplers For Lung Lobectomy With Video-Assisted Thoracic Surgery.

PURPOSE: The aim of this study was to compare intra-operative adverse events (AE), post-operative outcomes, and costs of three different types of Echelon staplers (manual activated SC45A and electrical power-activated PSE45A & PSEE60A) used during video-assisted thoracic surgery (VATS) for lung lobectomy. PATIENTS AND METHODS: We carried out a retrospective chart review of patients undergoing VATS lobectomies using one of three staplers (SC45A, PSE45A, or PSEE60A) during a 2-year period at our institution. We compared intra-operative AEs, post-operative outcomes (drainage volume, chest tube duration, prolonged air leaks [PALs]), endoscopic product costs [ECs], and hospitalization costs [HCs]) amongst the three stapler groups. RESULTS: In all 204 peripheral lung cancer patients were included in the study (95 in the SC45A group, 72 in the PSE45A group, and 37 in the PSEE60A group). We observed intra-operative AEs in 6 patients of the SC45A group, in 4 of the PSE45A group, and in 1 of the PSEE60A group (P>0.05). Drainage volumes among the three groups were similar. The mean chest tube duration was shorter]st in the PSE45A group followed by those in the PSEE60A and SC45A groups (P<0.05). PALs were lowest in the PSE45A group and highest in the SC45A group (P<0.05). The mean EC in the PSEE60A group was significantly higher than those in the other two groups (P<0.05). We found no statistically significant differences in terms of HCs among groups. CONCLUSION: The three endoscopic staplers had similar incidences of intra-operative AEs when used for lobectomy with VATS. Use of the PSE45A stapler was associated with the shortest chest tube duration and least PALs, while use of the PSEE60A resulted in the highest EC rate.