Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.

The Effects of Different Types of Sleep Disorder on Colorectal Cancer: A Nationwide Population-Based Cohort Study.

The impact of sleep disorders (SDs), particularly sleep apnea (SA), on the development of colorectal cancer (CRC) has been the subject of significant research. However, the potential contribution of other SDs to the incidence of CRC remains unexplored. The objective of this study was to examine the effects of SDs on the risk of developing CRC. This study assessed CRC risk among individuals diagnosed with SDs compared with age- and sex-matched unaffected individuals. A longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) encompassing 177,707 individuals diagnosed with SDs and 177,707 matched controls. Cox proportional hazard regression analysis was used to determine the relative increased risk of CRC in individuals with SDs and specific subgroups of SDs. The CRC incidences were 1.32-fold higher (95% CI 1.23-1.42) in the overall SD cohort, 1.17-fold higher (95% CI 0.82-1.68) in the SA cohort, 1.42-fold higher (95% CI 1.31-1.55) in the insomnia cohort, 1.27-fold higher (95% CI 1.17-1.38) in the sleep disturbance cohort, and 1.00-fold higher (95% CI 0.77-1.29) in the other SD cohort, after adjusting for age, sex, and comorbidities.

The Association between Statins and Liver Cancer Risk in Patients with Heart Failure: A Nationwide Population-Based Cohort Study.

Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20-0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26-0.44 and aHR 0.42, 95% CI: 0.28-0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF.

Protective Effects of Influenza Vaccine against Colorectal Cancer in Populations with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.

Chronic kidney disease (CKD) is associated with malignancy, including colorectal cancer, via the potential mechanism of chronic inflammation status. This study aimed to determine whether influenza vaccines can reduce the risk of colorectal cancer in patients with CKD. Our cohort study enrolled 12,985 patients older than 55 years with a diagnosis of CKD in Taiwan from the National Health Insurance Research Database at any time from 1 January 2001 to 31 December 2012. Patients enrolled in the study were divided into a vaccinated and an unvaccinated group. In this study, 7490 and 5495 patients were unvaccinated and vaccinated, respectively. A propensity score was utilized to reduce bias and adjust the results. Cox proportional hazards regression was used to estimate the correlation between the influenza vaccine and colorectal cancer in patients with CKD. The results showed that the influenza vaccine exerted a protective effect against colorectal cancer in populations with CKD. The incidence rate of colon cancer in the vaccinated group was significantly lower than in the unvaccinated group, with an adjusted hazard rate (HR) of 0.38 (95% CI: 0.30-0.48, p < 0.05). After the propensity score was adjusted for Charlson comorbidity index, age, sex, dyslipidemia, hypertension, diabetes, monthly income, and level of urbanization, the dose-dependent effect was found, and it revealed adjusted HRs of 0.74 (95% CI: 0.54-1.00, p < 0.05), 0.41 (95% CI: 0.30-0.57, p < 0.001), 0.16 (95% CI: 0.11-0.25, p < 0.001) for one, two to three, and four or more vaccinations, respectively. In summary, the influenza vaccine was found to be associated with a reduced risk of colorectal cancer in CKD patients. This study highlights the potential chemopreventive effect of influenza vaccination among patients with CKD. Future studies are required to determine whether the aforementioned relationship is a causal one.

Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.

Previous studies have indicated that influenza vaccination reduces the development of lung cancer. However, the protective effects of influenza vaccination on primary liver cancer in patients with chronic kidney disease (CKD) are unclear. This cohort study identified 12,985 patients aged at least 55 years who had received a diagnosis of CKD between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database of Taiwan. The patients were classified according to vaccination status. Propensity score matching was used to reduce selection bias. Cox proportional hazards regression analysis was used to evaluate the correlation between influenza vaccination and primary liver cancer in patients with CKD. The prevalence of primary liver cancer was lower in patients with CKD who had received an influenza vaccine (adjusted hazard ratio: 0.45, 95% confidence interval [CI]: 0.35−0.58, p < 0.001). The protective effects were observed regardless of sex, age, and comorbidities. Moreover, dose-dependent protective effects were observed. In the subgroup analysis, where the patients were classified by the number of vaccinations received, the adjusted hazard ratios for 1, 2−3, and ≥4 vaccinations were 0.86 (95% CI: 0.63−1.17), 0.45 (95% CI: 0.31−0.63), and 0.21 (95% CI: 0.14−0.33), respectively. In conclusion, influenza vaccination was associated with a lower incidence of liver cancer in patients with CKD.

Bottom-Up Templated and Oriented Crystallization for Inverted Triple-Cation Perovskite Solar Cells with Stabilized Nickel-Oxide Interface.

Inverted-structure perovskite solar cells (PSCs) are known for their superior device stability. However, based on nickel-oxide (NiOx ) substrate, disordered crystallization and bottom interface instability of perovskite film are still the main factors that compromise the power conversion efficiency (PCE) of PSCs. Here, 2D perovskite of thiomorpholine 1,1-dioxide lead iodide (Td2 PbI4 ) is introduced as a template to prepare 3D perovskite thin film with high crystal orientation and large grain size via a bottom-up growth method. By adding TdCl to the precursor solution, pre-crystallized 2D Td2 PbI4 seeds can accumulate at the bottom interface, lowering the barrier of nucleation, and templating the growth of 3D perovskite films with improved (100) orientation and reduced defects during crystallization. In addition, 2D Td2 PbI4 at the bottom interface also hinders the interfacial redox reaction and reduces the hole extraction barrier on the buried interface. Based on this, the Td-0.5 PSC achieves a PCE of 22.09% and an open-circuit voltage of 1.16 V. Moreover, Td-0.5 PSCs show extremely high stability, which retains 84% of its initial PCE after 500 h of continuous illumination under maximum power point operating conditions in N2 atmosphere. This work paves the way for performance improvement of inverted PSCs on NiOx substrate.

Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study.

Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan's National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38−0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66−1.25), 0.49 (0.34−0.71), and 0.25 (0.17−0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.

Prediction of Recurrent Atrial Tachyarrhythmia After Receiving Atrial Flutter Ablation in Patients With Prior Cardiac Surgery for Valvular Heart Disease.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL. Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence. Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence. Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Comparison of lesion characteristics between conventional and high-power short-duration ablation using contact force-sensing catheter in patients with paroxysmal atrial fibrillation.

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Role of Annual Influenza Vaccination against Lung Cancer in Type 2 Diabetic Patients from a Population-Based Cohort Study.

Type 2 diabetes mellitus (DM) patients are at a higher risk for developing lung cancer due to immune dysfunction and chronic inflammation. They also have increased morbidity and mortality related to influenza, and it is recommended that they receive an annual influenza vaccination. In this study, we evaluate whether influenza vaccination could reduce the incidence of lung cancer in DM patients. This cohort study included DM patients (≥55 years old) between 1 January 2002 and 31 December 2012 by using the Taiwan Health Insurance Database. Cox proportional hazard regression method was used to compare the relation between the influenza vaccination and lung cancer incidence after adjusting for potential confounders. Sub-group analyses were done according to vaccination status (unvaccinated, total number of vaccinations: 1, 2-3, ≥4) and evaluated the dose-dependent effects on lung cancer events. Among 22,252 eligible DM patients, 7860 (35.32%) received an influenza vaccination and 67.68% (14392) did not receive an influenza vaccination. Lung cancer incidence was significantly lower in the vaccinated group versus the unvaccinated group (adjusted HR 0.77; 95% CI 0.62-0.95, p < 0.05). Significant protective effects were observed among male sex (adjusted HR 0.72; 95% CI 0.55-0.94, p < 0.05) and 55-64 year (adjusted HR 0.61; 95% CI 0.40-0.94, p < 0.05) and ≥75 year (adjusted HR 0.63; 95% CI 0.42-0.92, p < 0.05) age groups, respectively. A dose-dependent protective effect was noted with a significant protective effect in those that received ≥4 vaccinations (adjusted HR 0.42; 95% CI 0.29-0.61, p < 0.001). In sub-group analysis, elder patients with ≥65 years of age were significantly protected from ≥4 vaccinations (adjusted HR 0.37; 95% CI 0.23-0.62, p < 0.001 in 65-74 years and adjusted HR 0.31; 95% CI 0.15-0.66, p = 0.002 in ≥75 years group, respectively). Male sex with ≥4 vaccinations had a significantly lower risk of lung cancer (adjusted HR 0.35; 95% CI 0.21-0.57, p < 0.001). Patients with comorbid conditions that received ≥4 vaccinations were also protected, and was especially significant among those with CCI ≥ 3 (adjusted HR 0.38; 95% CI 0.18-0.80, p = 0.009) as compared to 1 and 2-3 vaccination groups, including those with hypertension (adjusted HR 0.35; 95% CI 0.22-0.57, p < 0.001). This population-based cohort study demonstrated that annual influenza vaccination significantly reduced the lung cancer risk in DM patients and specifically demonstrates that a higher number of vaccinations is related with a more protective effect. Whether this is due to vaccine booster effects on anti-tumor immune regulation among DM patients still needs to be explored.

Application of noninvasive signal-averaged electrocardiogram analysis in predicting the requirement of epicardial ablation in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Signal-averaged electrocardiogram (SAECG) provides not only diagnostic information but also the prognostic implication of ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC). OBJECTIVE: This study aimed to validate the role of SAECG in identifying arrhythmogenic substrates requiring an epicardial approach in ARVC. METHODS: Ninety-one patients with a definite diagnosis of ARVC who underwent successful ablation for drug-refractory ventricular arrhythmia were enrolled and classified into 2 groups: group 1 who underwent successful ablation at the endocardium only and group 2 who underwent successful ablation requiring an additional epicardial approach. The baseline characteristics of patients and SAECG parameters were obtained for analysis. RESULTS: Male predominance, worse right ventricular (RV) function, higher incidence of syncope, and depolarization abnormality were observed in group 2. Moreover, the number of abnormal SAECG criteria was higher in group 2 than in group 1. After a multivariate analysis, the independent predictors of the requirement of epicardial ablation included the number of abnormal SAECG criteria (odds ratio 2.8, 95% confidence interval 1.4-5.4; P = .003) and presence of syncope (odds ratio 11.7; 95% confidence interval 2.7-50.4; P = .001). In addition, ≥2 abnormal SAECG criteria were associated with larger RV endocardial unipolar low-voltage zone (P < .001), larger RV endocardial/epicardial bipolar low-voltage zone/scar (P < .05), and longer RV endocardial/epicardial total activation time (P < .001 and P = .004, respectively). CONCLUSION: The number of abnormal SAECG criteria was correlated with the extent of diseased epicardial substrates and could be a potential surrogate marker for predicting the requirement of epicardial ablation in patients with ARVC.

Clinical efficacy of open-irrigated electrode cooled with half-normal saline for initially failed radiofrequency ablation of idiopathic outflow tract ventricular arrhythmias.

BACKGROUND: Acute failure of radiofrequency ablation (RFA) of ventricular arrhythmias (VAs) occur in 10%-20% of patients and is partly attributed to inadequate lesion depth acquired with standard ablation protocols. Half-normal saline (HNS)-irrigation is a promising strategy to improve the success rate of VA ablation. OBJECTIVE: This study investigated the efficacy of HNS-irrigated ablation after a failed standard plain normal saline solution (PNSS)-irrigated ablation on idiopathic outflow tract ventricular arrhythmia (OT-VA). METHOD: This is a prospective observational study of consecutive patients undergoing RFA of idiopathic OT-VA comparing the efficacy of additional HNS-irrigated ablation for failed standard PNSS-irrigated ablation. Acute failure was defined as persistence of spontaneous VA or persistent inducibility of the clinical VA. RESULTS: Out of 160 OT-VA cases (51 ± 15-year-old, 62 males), 31 underwent HNS irrigation after a failed standard PNSS-irrigated ablation. The HNS group had a significantly longer procedure time (60.06 ± 43.83 vs 37.51 ± 33.40 minutes; P = .013) and higher radiation exposure (31.45 ± 20.24 vs 17.22 ± 15.25 minutes; P = .001) than the PNSS group but provided an additional acute success in 21 of 31 (67.7%) patients. Over a follow-up duration of 7.8 ± 4.6 months, 24 recurrences were identified, including 8 (25.8%) in the HNS and 16 (12.4%) in the PNSS group, with lower freedom from recurrence in the HNS group (log rank P = .009). No major complication was observed. CONCLUSION: HNS-irrigated ablation after failed standard PNSS-irrigated ablation is safe and additionally improves acute ablation success by 67.7% for idiopathic OT-VA but with a higher rate of recurrence on follow-up. Whether the application of HNS as initial irrigant could result in better outcome requires further investigation.

Nicorandil prevents doxorubicin-induced human umbilical vein endothelial cell apoptosis.

Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with additional antioxidant properties. Doxorubicin (DOX) is an anticancer drug that exerts oxidation-mediated adverse cardiovascular effects. This study examined the effects of nicorandil on DOX-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and underlying intracellular signaling mechanisms. Cultured HUVECs were pretreated with nicorandil (0.1, 0.3, 1, 3, and 10 µM) for 12 h and then treated with DOX (1 µM) for 24 h. Cell viability and cytotoxicity were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. Cell apoptosis was examined using a caspase-3 activity assay, and DNA fragmentation was detected through TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining. Western blot analysis was conducted to determine the related protein expression. DOX markedly increased reactive oxygen species production, p53 expression, caspase-3 activity, cleaved caspase-3 levels, and TUNEL-positive cell numbers but reduced Bcl-2 expression and intracellular antioxidant enzyme levels; these effects were effectively antagonized through nicorandil (3 µM, 12 h) pretreatment, which resulted in HUVECs being protected from DOX-induced apoptosis. Activating transcription factor 3 (ATF3), a stress-induced transcription factor, was induced by nicorandil (3 µM). Furthermore, nicorandil (3 µM) enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. ATF3 short interfering RNA significantly attenuated nicorandil-mediated Nrf2 translocation, HO-1 expression, and inhibitory effects on DOX-stimulated reactive oxygen species production and cell apoptosis. In summary, nicorandil may protect HUVECs from DOX-induced apoptosis, in part through ATF3-mediated Nrf2/HO-1 signaling pathways, which potentially protect the vessels from severe DOX toxicity.

Electrophysiological and clinical characteristics of catheter ablation for isolated left side atrial tachycardia over a 10-year period.

AIMS: Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. METHODS: This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. RESULTS: A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. CONCLUSION: This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.

Cafestol Activates Nuclear Factor Erythroid-2 Related Factor 2 and Inhibits Urotensin II-Induced Cardiomyocyte Hypertrophy.

Through population-based studies, associations have been found between coffee drinking and numerous health benefits, including a reduced risk of cardiovascular disease. Active ingredients in coffee have therefore received considerable attention from researchers. A wide variety of effects have been attributed to cafestol, one of the major compounds in coffee beans. Because cardiac hypertrophy is an independent risk factor for cardiovascular events, this study examined whether cafestol inhibits urotensin II (U-II)-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed only to U-II (1 nM) or to U-II (1 nM) following 12-h pretreatment with cafestol (1-10 µ M). Cafestol (3-10 µ M) pretreatment significantly inhibited U-II-induced cardiomyocyte hypertrophy with an accompanying decrease in U-II-induced reactive oxygen species (ROS) production. Cafestol also inhibited U-II-induced phosphorylation of redox-sensitive extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor transactivation. In addition, cafestol pretreatment increased Src homology region 2 domains-containing phosphatase-2 (SHP-2) activity, suggesting that cafestol prevents ROS-induced SHP-2 inactivation. Moreover, nuclear factor erythroid-2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression were enhanced by cafestol. Addition of brusatol (a specific inhibitor of Nrf2) or Nrf2 siRNA significantly attenuated cafestol-mediated inhibitory effects on U-II-stimulated ROS production and cardiomyocyte hypertrophy. In summary, our data indicate that cafestol prevented U-II-induced cardiomycyte hypertrophy through Nrf2/HO-1 activation and inhibition of redox signaling, resulting in cardioprotective effects. These novel findings suggest that cafestol could be applied in pharmacological therapy for cardiac diseases.

Cafestol, a coffee diterpene, inhibits urotensin II-induced interleukin-8 expression in human umbilical vein endothelial cells.

Cafestol, a diterpene molecule found in the berries of Coffea arabica L. (Rubiaceae), has been shown to exercise anti-angiogenic and anti-tumorigenic effects. However, cafestol's cellular mechanism has yet to be fully investigated. We previously demonstrated that urotensin II enhanced interleukin-8 secretion by endothelial cells, thereby increasing endothelial cell proliferation. Urotensin II may also participate in angiogenesis and tumor infiltration by macrophages. However, the effects of cafestol on urotensin II-induced interleukin-8 expression and cellular proliferation have not been determined. Here, we showed that pretreatment with cafestol inhibited urotensin II-stimulated endothelial cell proliferation. Further experiments demonstrated that cafestol increased translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and expression of enhanced heme oxygenase-1. Moreover, cafestol inhibited expression of urotensin II-induced interleukin-8. Cafestol's inhibitory effects on interleukin-8 expression and cellular proliferation induced by urotensin II were significantly abrogated by heme oxygenase-1 silencing, suggesting it may be involved in mediating the effects of cafestol. This study reports that cafestol inhibits urotensin II-induced interleukin-8 expression and cell proliferation via Nrf2/heme oxygenase-1-dependent mechanism in endothelial cells. These findings provide novel insight into the signaling pathways that may be important in mediating the effects of cafestol.

Statins Dose-Dependently Exert Significant Chemopreventive Effects Against Various Cancers in Chronic Obstructive Pulmonary Disease Patients: A Population-Based Cohort Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012, were recruited. Each patient was followed to assess the following protective and risk factors for all cancers: age; sex; comorbidities (diabetes, hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]); urbanization level; monthly income; and nonstatin drug use. The index date of statins use was the date of COPD confirmation. Propensity scores (PSs) were derived using a logistic regression model to estimate the effect of statins by considering the covariates predicting intervention (statins) receipt. To examine the dose-response relationship, we categorized statin use into four groups in each cohort (<28 [statin nonusers], 28-90, 91-365, and >365 cumulative defined daily dose). RESULTS: After PS adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income, we analyzed the all-cancer risk. The adjusted hazard ratios (aHRs) for the all-cancer risk were lower among statin users than among statin nonusers (aHR = 0.46, 95% confidence interval: 0.43 to 0.50). The aHRs for the all-cancer risk were lower among patients using rosuvastatin, simvastatin, atorvastatin, pravastatin, and fluvastatin than among statin nonusers (aHRs = 0.42, 0.55, 0.59, 0.66, and 0.78, respectively). Sensitivity analysis indicated that statins dose-dependently reduced the all-cancer risk. CONCLUSION: Statins dose-dependently exert a significant chemopreventive effect against various cancers in COPD patients. In particular, rosuvastatin has the strongest chemopreventive effect.

Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. RESULTS: After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use). MATERIALS AND METHODS: The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users. CONCLUSIONS: Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.

Characterization of the interactions between protein and carbon black.

A considerable amount of studies have been conducted to investigate the interactions of biological fluids with nanoparticle surfaces, which exhibit a high affinity for proteins and particles. However, the mechanisms underlying these interactions have not been elucidated, particularly as they relate to human health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid (BALF) as models for protein-particle conjugates, we characterized the physicochemical modifications of carbon blacks (CB) with 23nm or 65nm in diameter after protein treatment. Adsorbed BALF-containing proteins were quantified and identified by pathways, biological analyses and protein classification. Significant modifications of the physicochemistry of CB were induced by the addition of BSA. Enzyme modulators and hydrolase predominately interacted with CB, with protein-to-CB interactions that were associated with the coagulation pathways. Additionally, our results revealed that an acute-phase response could be activated by these proteins. With regard to human health, the present study revealed that the CB can react with proteins (∼55kDa and 70kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs.

Visualizing long-term memory formation in two neurons of the Drosophila brain.

Long-term memory (LTM) depends on the synthesis of new proteins. Using a temperature-sensitive ribosome-inactivating toxin to acutely inhibit protein synthesis, we screened individual neurons making new proteins after olfactory associative conditioning in Drosophila. Surprisingly, LTM was impaired after inhibiting protein synthesis in two dorsal-anterior-lateral (DAL) neurons but not in the mushroom body (MB), which is considered the adult learning and memory center. Using a photoconvertible fluorescent protein KAEDE to report de novo protein synthesis, we have directly visualized cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not massed training. Memory retention was impaired by blocking neural output in DAL during retrieval but not during acquisition or consolidation. These findings suggest an extra-MB memory circuit in Drosophila: LTM consolidation (MB to DAL), storage (DAL), and retrieval (DAL to MB).