Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. Drug Metab. Dispos

ABSTRACT: Lung cancer is the leading cause of cancer death in many developed countries, includin

Risk of Chronic Kidney Disease in Pneumoconiosis: Results from a Retrospective Cohort Study (2008–2019)

Background: Pneumoconiosis has considerable comorbidities, most notably pulmonary and cardiovascular diseases. However, the relationship between pneumoconiosis and chronic kidney disease (CKD) is largely unknown. The present study aimed to use a retrospective cohort study design to further clarify the association between pneumoconiosis and subsequent CKD risk. Methods: This is a nationwide, population-based, retrospective cohort study that used data from Taiwan’s National Health Insurance Database. Between 2008 and 2018, 17,952 newly diagnosed patients were included in the pneumoconiosis cohort, while 71,808 individuals without pneumoconiosis were included in the comparison cohort, with a propensity score matching for age, gender, and date of pneumoconiosis diagnosis. The development of CKD was monitored until the end of 2019. The risk was assessed using Cox proportional hazard regression models. Results: After controlling for age, gender, and comorbidity, the overall incidence of CKD was 1.69-fold higher in the pneumoconiosis cohort than in the comparison cohort (19.71 vs. 11.76 per 1000 person-years, respectively, p p < 0.001). Conclusion: Patients with pneumoconiosis had a significantly higher risk of developing CKD than those without. Pneumoconiosis combined with hypertension, hyperglycemia, or hyperlipidemia would increase the risk even further. More studies are required to understand the possible pathophysiological mechanisms

Does chronic obstructive pulmonary disease with or without type 2 diabetes mellitus influence the risk of lung cancer? Result from a population-based cohort study.

BACKGROUND: Previous studies have suggested that chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. There are some evidence that people with diabetes are at a risk of developing many forms of cancer, but inconclusive with regard to lung cancer. The aim of this study was to evaluate whether COPD with or without type 2 diabetes mellitus (T2DM) influences the risk of developing lung cancer. METHODS: This is a retrospective cohort study consisting of 20,730 subjects newly diagnosed with COPD ("cases"). Their data was collected from the National Health Insurance system of Taiwan from 1998 to 2010. Among these patients, 5,820 patients had T2DM and 14,910 patients did not have T2DM. The retrospective matched control group consisted of 20,729 subjects without either COPD or T2DM. The control group was matched with the cases for sex, age, and index year (the year that the patient was diagnosed with COPD). The subjects were followed until the end of 2011. RESULTS: The findings of our study showed that the risk of lung cancer was higher in the COPD group than in the non-COPD group, with adjusted hazard ratio (HR) of 5.02 [95% confidence interval (CI) = 4.23-5.94] among total case group, adjusted HR was 5.38 (95% CI = 4.52-6.40) in the cohort without T2DM and adjusted HR was 4.05 (95% CI = 3.26-5.03) in the cohort with T2DM. We observed a significantly protective effect from lung cancer (adjusted HR = 0.75, 95% CI = 0.63-0.90) of diabetic cohort than non-diabetic cohort among patients with COPD. CONCLUSION: Patients with COPD had a significantly higher risk of developing lung cancer than healthy people. However, there was a protective effect of T2DM for lung cancer among patients with COPD. Further investigation may be needed to corroborate the mechanism or bring up reliable reasons

The Relationships Between Hemoglobin and Diabetes Factors (Insulin Resistance, Glucose Effectiveness, First- and Second-Phase Insulin Secretion) in Old Chinese

Summary: Background: Diabetes is characterized by increased insulin resistance (IR) and decreased insulin secretion. The roles of glucose effectiveness (GE), first- and second-phase insulin secretion (FPIS, SPIS) are often overlooked. We denote these factors as diabetic factors (DF). Hemoglobin (Hb) has been shown to be related to IR and FPIS, but not to SPIS and GE. The aims of this study are to investigate the relationships between Hb and DFs and to compare which one has the tightest correlation with Hb in old Chinese. Methods: We randomly enrolled 5109 men and 5851 women, whose age were over 65 years old. Subjects, who were obese or on medications, were excluded. Simple correlation was applied to evaluate the relationships between Hb and 4 DFs. To compare the relative tightness between each correlation lines, all the units of the DFs were transformed into percentage. Results: All the biochemistry data were higher in subjects with metabolic syndrome (MetS) in both genders, except for GE and HDL. Similar trends were also noted when dividing subjects into quartiles of Hb. The results of simple correlation showed that all the DFs are significantly related to Hb except for FPIS in women. The association between Hb and GE is negative. After transforming the different units into percentage, the relationships with Hb, from the highest to lowest, were IR, SPIS, GE and FPIS in both genders. Conclusion: Our data show that all DFs are almost related to Hb. IR has the tightest correlation with Hb in old Chinese. Keywords: hemoglobin, insulin resistance, glucose effectiveness, first-phase insulin secretion and second-phase insulin secretio

γ-glutamyl transpeptidase in men and alanine aminotransferase in women are the most suitable parameters among liver function tests for the prediction of metabolic syndrome in nonviral hepatitis and nonfatty liver in the elderly

Background/Aims: Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly. Patients and Methods: A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group. Results: Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan-Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women). Conclusion: Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly

Casticin Induces DNA Damage and Affects DNA Repair Associated Protein Expression in Human Lung Cancer A549 Cells

Casticin was obtained from natural plants, and it has been shown to exert biological functions; however, no report concerns the induction of DNA damage and repair in human lung cancer cells. The objective of this study was to investigate the effects and molecular mechanism of casticin on DNA damage and repair in human lung cancer A549 cells. Cell viability was determined by flow cytometric assay. The DNA damage was evaluated by 4’,6-diamidino-2-phenylindole (DAPI) staining and electrophoresis which included comet assay and DNA gel electrophoresis. The protein levels associated with DNA damage and repair were analyzed by western blotting. The expression and translocation of p-H2A.X were observed by confocal laser microscopy. Casticin reduced total viable cell number and induced DNA condensation, fragmentation, and damage in A549 cells. Furthermore, casticin increased p-ATM at 6 h and increased p-ATR and BRCA1 at 6–24 h treatment but decreased p-ATM at 24–48 h, as well as decreased p-ATR and BRCA1 at 48 h. Furthermore, casticin decreased p-p53 at 6–24 h but increased at 48 h. Casticin increased p-H2A.X and MDC1 at 6–48 h treatment. In addition, casticin increased PARP (cleavage) at 6, 24, and 48 h treatment, DNA-PKcs and MGMT at 48 h in A549 cells. Casticin induced the expressions and nuclear translocation of p-H2AX in A549 cells by confocal laser microscopy. Casticin reduced cell number through DNA damage and condensation in human lung cancer A549 cells

Bufalin Alters Gene Expressions Associated DNA Damage, Cell Cycle, and Apoptosis in Human Lung Cancer NCI-H460 Cells in Vitro

Lung cancer is the leading cause of cancer related death and there is no effective treatment to date. Bufalin has been shown effective in inducing apoptosis and DNA damage in lung cancer cells. However, the genetic mechanisms underlying these actions have not been elucidated yet. Cultured NCI-H460 cells were treated with or without 2 μM of bufalin for 24 h. The total RNA was extracted from each treatment for cDNA synthesis and labeling, microarray hybridization, and then followed by flour-labeled cDNA hybridized on chip. The localized concentrations of fluorescent molecules were detected and quantitated and analyzed by Expression Console software (Affymetrix) with default RMA parameters. The key genes involved and their possible interaction pathways were mapped by GeneGo software. About 165 apoptosis-related genes were affected. CASP9 was up-regulated by 5.51 fold and THAP1 by 2.75-fold while CCAR1 was down-regulated by 2.24 fold. 107 genes related to DNA damage/repair were affected. MDC1 was down-regulated by 2.22-fold, DDIT4 by 2.52 fold while GADD45B up-regulated by 3.72 fold. 201 genes related to cell cycles were affected. CCPG1 was down-regulated by 2.11 fold and CDCA7L by 2.71 fold. Many genes about apoptosis, cell cycle regulation and DNA repair are changed significantly following bufalin treatment in NCI-H460 cells. These changes provide an in depth understanding of cytotoxic mechanism of bufalin in genetic level and also offer many potentially useful biomarkers for diagnosis and treatment of lung cancer in future

Typhoon Disturbance and Forest Dynamics: Lessons from a Northwest Pacific Subtropical Forest

Abstract Strong tropical storms are known to affect forest structure, composition, and nutrient cycles in both tropical and temperate regions, although our understanding of these effects disproportionally comes from regions experiencing much lower cyclone frequency than many forests in the Northwest Pacific. We summarized the effects of typhoons on forest dynamics at Fushan Experimental Forest (FEF) in northeastern Taiwan, which averages 0.49 major typhoons annually, and compared their resistance and resilience to those of forests in other regions. Typhoons cause remarkably few tree falls at FEF; multiple typhoons in 1994 felled only 1.4% of canopy trees, demonstrating high structural resistance. The most important effect of typhoons in this ecosystem is defoliation, which maintains high understory light levels and enhances heterogeneity, sustaining diversity without large canopy gaps. The vulnerability of taller trees to being blown down has resulted in the short-stature FEF (mean canopy height is 10.2 m). As the FEF is P-limited and a large fraction of total annual P export occurs during typhoons, these storms may have the effect of reducing productivity over time. DIN and K+ export only remain elevated for days at FEF, in contrast to the several years observed in Puerto Rico. High resilience is also evident in the rapid recovery of leaf area following typhoons. Heavy defoliation and slow decomposition are among the processes responsible for the high resistance and resilience of FEF to typhoon disturbance. These key structural features may emerge in other forest ecosystems if the frequency of major storms increases with climate change