Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis.

BACKGROUND: Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD. METHODS: The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis. RESULTS: Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the in vivo animal model and the in vitro cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(ITGB6), a hub and commonly upregulated gene, was upregulated in the in vitro models. CONCLUSION: ITGB6 may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Wilms' tumour gene 1 (WT1) enhances non-small cell lung cancer malignancy and is inhibited by microRNA-498-5p.

BACKGROUND: Wilms' tumour gene 1 (WT1) is clearly recognized as a tumour promoter in diversiform of human malignancies. Nevertheless, knowledge of its expression, functions and potential molecular mechanisms in non-small cell lung cancer (NSCLC) remains elusive. METHODS: Differential expression of WT1 mRNA and protein between NSCLC and normal tissues were assessed by analyzing RNA-seq data from Oncomine and protein data from Human Protein Atlas, respectively. Subsequently, prognosis significance and immune cell infiltration were analyzed by Kaplan-Meier plotter and CIBERSORT. 60 pairs of local NSCLC tissues were involved to validate WT1 expression by quantitative PCR (qPCR) and Western blot. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, transwell, dual luciferase reporter assays and in vivo xenograft tumour growth experiments were conducted to explore the function and mechanism of WT1 in NSCLC. RESULTS: Our solid data indicated that WT1 was increased in NSCLC tissues and cell lines in comparison with their matched controls. In particular, its upregulation correlated with worse prognosis and immune infiltration of the patients. Functional assays demonstrated that knockdown of WT1 inhibited NSCLC malignancy, including inhibiting cell proliferation, survival and invasion. Further exploration discovered that microRNA-498-5p (miR-498-5p) was the upstream suppressor of WT1 by directly targeting the 3' untranslated region (UTR) of WT1 mRNA. Moreover, expression of miR-498-5p was notably decreased and inversely correlated with WT1 in NSCLC tissues. Finally, we proved that miR-498-5p was a potent tumour suppressor in NSCLC by suppressing cell proliferation, survival and invasion, while WT1 restoration could in turn disrupt this suppression both in vitro and in vivo. CONCLUSION: The abnormal increase in WT1 contributes to the malignant properties of NSCLC cells, and miR-498-5p is a natural inhibitor of WT1. Our findings might facilitate the development of novel therapeutic strategies against NSCLC in the future.

[Research Progress of Klotho in Lung Neoplasms].

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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Exploring the Association Between PRC2 Genes Variants and Lung Cancer Risk in Chinese Han Population.

Background: Genetic susceptibilities play a large role in the pathogenesis of lung cancer (LC). The polycomb repressive complex 2 (PRC2) is a conserved chromatin-associated complex that represses gene expression and is crucial for proper organismal development and gene expression patterns. Despite PRC2 dysregulation has been observed in various human cancers, the relationship between PRC2 genes variants and lung cancer risk remains largely unexplored. Methods: To investigate the association between single nucleotide polymorphisms (SNPs) in PRC2 genes and the risk of developing LC, we genotyped blood genomic DNA from 270 LC patients and 452 healthy individuals of Chinese Han ethnicity using the TaqMan™ genotyping technique. Results: We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467-0.938, P < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4-0.947, P < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186-0.401, P < 0.001) were significantly associated with a reduced risk of LC. Stratified analysis revealed a protective effect of rs17171119 in both male and female patients, specifically those with lung adenocarcinoma (LUAD). Additionally, rs1391221 showed a protective effect in both the LUAD and lung squamous cell carcinoma (LUSC) groups, while rs1136258 exhibited a protective effect in both females and males, as well as in both LUAD and LUSC groups. Furthermore, analysis of The Cancer Genome Atlas (TCGA) dataset revealed expression levels of EED and RBBP4 in both LUAD and LUSC. Conclusion: This study provides evidence that allelic variants in EZH2, EED, and RBBP4 may act as protective factors against LC development and could serve as genetic markers associated with susceptibility to LC.

Epidemiological and demographic drivers of lung cancer mortality from 1990 to 2019: results from the global burden of disease study 2019.

Background: Understanding the effects of demographic drivers on lung cancer mortality trends is critical for lung cancer control. We have examined the drivers of lung cancer mortality at the global, regional, and national levels. Methods: Data on lung cancer death and mortality were extracted from the Global Burden of Disease (GBD) 2019. Estimated annual percentage change (EAPC) in the age-standardized mortality rate (ASMR) for lung cancer and all-cause mortality were calculated to measure temporal trends in lung cancer from 1990 to 2019. Decomposition analysis was used to analyze the contributions of epidemiological and demographic drivers to lung cancer mortality. Results: Despite a non-significant decrease in ASMR [EAPC = -0.31, 95% confidence interval (CI): -1.1 to 0.49], the number of deaths from lung cancer increased by 91.8% [95% uncertainty interval (UI): 74.5-109.0%] between 1990 and 2019. This increase was due to the changes in the number of deaths attributable to population aging (59.6%), population growth (56.7%), and non-GBD risks (3.49%) compared with 1990 data. Conversely, the number of lung cancer deaths due to GBD risks decreased by 19.8%, mainly due to tobacco (-12.66%), occupational risks (-3.52%), and air pollution (-3.47%). More lung cancer deaths (1.83%) were observed in most regions, which were due to high fasting plasma glucose levels. The temporal trend of lung cancer ASMR and the patterns of demographic drivers varied by region and gender. Significant associations were observed between the contributions of population growth, GBD risks and non-GBD risks (negative), population aging (positive), and ASMR in 1990, the sociodemographic index (SDI), and the human development index (HDI) in 2019. Conclusion: Population aging and population growth increased global lung cancer deaths from 1990 to 2019, despite a decrease in age-specific lung cancer death rates due to GBD risks in most regions. A tailored strategy is needed to reduce the increasing burden of lung cancer due to outpacing demographic drivers of epidemiological change globally and in most regions, taking into account region- or gender-specific risk patterns.

Effect of Arsenic Exposure and Cigarette Smoking on Total and Cause-Specific Mortality: An Occupational Cohort With 27 Follow-up Years.

BACKGROUND: The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies. METHODS: After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death. RESULTS: A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure. CONCLUSIONS: We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners.

The impact of low-dose CT on smoking behavior among non-smokers, former-smokers, and smokers: A population-based screening cohort in rural China.

BACKGROUND: Lung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported. METHODS: A baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression. RESULTS: From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes. CONCLUSIONS: The overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions.

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy cells. Recently, programmable endonucleases such as clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas) and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions, enabling their detection with deep next generation sequencing (NGS). However, the enrichment level achievable with these assays is limited by futile binding events and off-target cleavage. To overcome these shortcomings, we conceived a new assay (Programmable Enzyme-Assisted Selective Exponential Amplification, PASEA) that combines the cleavage of wild type alleles with concurrent polymerase amplification. While PASEA increases the numbers of both wild type and mutant alleles, the numbers of mutant alleles increase at much greater rates, allowing PASEA to achieve an unprecedented level of selective enrichment of targeted alleles. By combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification, we converted samples with 0.01% somatic mutant allele fractions (MAFs) to products with 70% MAFs in a single step within 20 min, enabling inexpensive, rapid genotyping with such as Sanger sequencers. Furthermore, PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA probes. Real-time PASEA' performance was proved equivalent to clinical amplification refractory mutation system (ARMS)-PCR and NGS when testing over hundred cancer patients' samples. This strategy has the potential to reduce the cost and time of cancer screening and genotyping, and to enable targeted therapies in resource-limited settings.