Factors influencing terminal cancer patients' autonomous DNR decision: a longitudinal statutory document and clinical database study.

OBJECTIVE: Much of our knowledge of patient autonomy of DNR (do-not-resuscitate) is derived from the cross-sectional questionnaire surveys. Using signatures on statutory documents and medical records, we analyzed longitudinal data to understand the fact of terminal cancer patients' autonomous DNR decision-making in Taiwan. METHODS: Using the medical information system database of one public medical center in Taiwan, we identified hospitalized cancer patients who died between Jan. 2017 and Dec. 2018, collected their demographic and clinical course data and records of their statutory DNR document types, letter of intent (DNR-LOI) signed by the patient personally and the consent form signed by their close relatives. RESULTS: We identified 1,338 signed DNR documents, 754 (56.35%) being DNR-LOI. Many patients had the first DNR order within their last week of life (40.81%). Signing the DNR-LOI was positively associated with being under the care of a family medicine physician prior to death at last hospitalization and having hospice palliative care and negatively associated with patient age ≥ 65 years, no formal education, having ≥ 3 children, having the first DNR order to death ≤ 29 days, and the last admission in an intensive care unit. CONCLUSIONS: A substantial proportion of terminal cancer patients did not sign DNR documents by themselves. It indicates they may not know their actual terminal conditions and lose the last chance to grasp time to express their life values and wishes. Medical staff involving cancer patient care may need further education on the legal and ethical issues revolving around patient autonomy and training on communicating end-of-life options with the patients. We suggest proactively discussing DNR decision issues with terminal cancer patients no later than when their estimated survival is close to 1 month.

Methyl-CpG Binding Domain Protein 2 Inhibits the Malignant Characteristic of Lung Adenocarcinoma through the Epigenetic Modulation of 10 to 11 Translocation 1 and miR-200s.

It has been reported that disorders of epigenetic modulation play a critical role in carcinogenesis. Methyl-CpG binding domain protein 2 (MBD2) is known to act as an epigenetic modulator in various types of tumors; however, the role of MBD2 in lung adenocarcinoma (LUAD) remains unclear. Herein, we demonstrated the down-regulation of MBD2 in LUAD compared with adjacent nontumor tissues. The down-regulation of MBD2 in LUAD was correlated with metastasis and poor survival. In addition, MBD2 inhibited tumor metastasis by maintaining the expression of the miR-200s, which suppressed the invasive properties of tumors. Also, MBD2 positively correlated with 5-hydroxymethylcytosine content in the promoter of miR-200s. The conventional view is that MBD2 acts as a transcriptional suppressor. However, the data revealed that MBD2 may act as a transcriptional activator by recruiting 10 to 11 translocation 1 (TET1) and forming a chromatin-remodeling complex. The MBD2-TET1 complex locates to the TET1 promoter and removes the methyl residues in this region, thereby activating TET1 transcription. TET1 also acted as a tumor suppressor in LUAD. Taken together, the data demonstrate the correlation between MBD2, miR-200s, and TET1, and tumor suppressive effect of MBD2 through up-regulation of TET1 and the miR-200s.

Prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwan.

BACKGROUND: To investigate the prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwanese general population. METHODS: From January 2009 to December 2011, consecutive asymptomatic subjects undergoing a health check-up were evaluated by colonoscopy. The colorectal diverticulosis was assessed, and a medical history and demographic data were obtained from each subject. Logistic regression analysis was conducted to search the risk factors of colorectal diverticulosis. RESULTS: Of the 1899 asymptomatic subjects, the prevalence of colorectal diverticulosis was 13.5%. On univariate logistic regression analysis, age over 60 years old, male, adenomatous polyp, current smoking and heavy alcohol consumption were significantly associated with diverticulosis. Multivariate logistic regression analysis revealed that age over 60 years old (relative risk [RR], 2.57; 95% confidence interval [CI], 1.64-6.47), adenomatous polyps (RR, 2.18; 95% CI, 1.18-4.61) and heavy alcohol consumption (RR, 1.82; 95% CI, 1.04-3.08) were independent predictors for colorectal diverticulosis. CONCLUSIONS: The prevalence of asymptomatic colorectal diverticulosis was 13.5% in Taiwan. Age over 60 years old, adenomatous polyp and heavy alcohol consumption may affect the risk of development of the disease.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. METHODS: Databases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). RESULTS: Analysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: -8.57 mg/dL; 95% confidence interval [CI]: -14.04 to -3.09 mg/dL, p = 0.002), HOMA-IR (WMD: -0.54; 95% CI: -0.78 to -0.30, p < 0.001), HbA1c (WMD: -0.25%; 95% CI: -0.43% to -0.07%, p = 0.006), and 2 h-PG (WMD: -18.42 mg/dL; 95% CI: -25.04 to -11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. CONCLUSION: Our meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

Case Report: Life-threatening pancytopenia with tislelizumab followed by cerebral infarction in a patient with lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs.

A real-world study of recombinant human endostatin combined with PD-1/PD-L1 blockade and chemotherapy for patients with advanced non-small cell lung cancer negative for actionable molecular biomarkers.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. To evaluate the real-world efficacy and safety of endostar combined with immune checkpoint inhibitor and chemotherapy (EIC) for advanced non-squamous non-small cell lung cancer patients negative for actionable molecular biomarkers (NSCLCnm), patients with advanced NSCLCnm hospitalized to Zhejiang Provincial People's Hospital from January 2020 to December 2022 were screened for eligibility. The included patients were analyzed for the objective response rate (ORR) and disease control rate (DCR). The pre- and posttreatment expression levels of serum tumor associated biomarkers, chemokines and subpopulations of immune cells in peripheral blood were compared. For the 31 patients with advanced NSCLCnm treated with EIC, the median follow-up and treatment cycles were 18.0 months and 4, respectively. The ORR and DCR were 38.7% and 90.3%, respectively. For those who received EIC as first-line treatment, the ORR and DCR were 63.2% and 94.7%, respectively. EIC significantly decreased expression levels of carcinoma antigen 125, carcinoma embryonic antigen and cytokeratin 19 (P<0.05) in patients who were partial remission or stable disease. Among the 31 patients, 27 (87.1%) experienced at least 1 treatment-related adverse events, and 13 (41.9%) had the treatment-related adverse events of grade 3 or higher. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.

Use of Coronary Computed Tomography Angiography to Screen Hospital Employees with Cardiovascular Risk Factors.

The objective of this study was to determine how coronary computed tomography angiography (CCTA) can be employed to detect coronary artery disease in hospital employees, enabling early treatment and minimizing damage. All employees of our hospital were assessed using the Framingham Risk Score. Those with a 10-year risk of myocardial infarction or death of >10% were offered CCTA; the Coronary Artery Disease Reporting and Data System (CAD-RADS) score was the outcome. A total of 3923 hospital employees were included, and the number who had received CCTA was 309. Among these 309, 31 (10.0%) had a CAD-RADS score of 3-5, with 10 of the 31 (32.3%) requiring further cardiac catheterization; 161 (52.1%) had a score of 1-2; and 117 (37.9%) had a score of 0. In the multivariate logistic regression, only age of ≥ 55 years (p < 0.05), hypertension (p < 0.05), and hyperlipidemia (p < 0.05) were discovered to be significant risk factors for a CAD-RADS score of 3-5. Thus, regular and adequate control of chronic diseases is critical for patients, and more studies are required to be confirmed if there are more significant risk factors.

Erosive esophagitis in asymptomatic subjects: risk factors.

INTRODUCTION: Asymptomatic erosive esophagitis is a common yet rarely reported disease. The purpose of this study is to investigate the prevalence of asymptomatic erosive esophagitis and to identify the risk factors for this disease. MATERIALS AND METHODS: In this study, we investigated 572 asymptomatic subjects undergoing health check-ups after upper gastrointestinal endoscopy. The severity of esophagitis was evaluated by the Los Angeles classification, and the independent risk factors for asymptomatic esophagitis were analyzed by the logistic regression method. RESULTS: The results showed the prevalence of erosive esophagitis in asymptomatic subjects was 12% (70/572). In all asymptomatic subjects, erosive esophagitis was grade A (71%) or B (29%). Univariate analysis revealed that male gender, high body mass index (BMI), and consumption of tobacco, alcohol, tea, spicy foods, and betel nut were associated with the development of erosive esophagitis. Multivariate analysis revealed that male gender (OR, 3.8, 95% CI, 1.5-9.3) and high BMI (BMI 25-30: OR, 2.3, 95% CI, 1.3-4.2; BMI >30: OR, 3.8, 95% CI, 1.3-10.9) were independent predictors of erosive esophagitis. CONCLUSION: Our data revealed male gender and high BMI are independent risk factors for asymptomatic erosive esophagitis.

Chronic fatigue of the small enterprise workers participating in an occupational health checkup center in southern Taiwan.

PURPOSE: There has been increasing interest in the occupational health of workers in small enterprises, especially in developing countries. This study examines the association between psychosocial job characteristics and fatigue, and attempts to identify risk factors for fatigue among workers of small enterprises in southern Taiwan. METHODS: A structured questionnaire was administered to workers receiving regular health examinations between August 2005 and January 2006. The questionnaire collected demographic information and data on working conditions, personal health status and life styles. It also collected information on psychosocial job characteristics, fatigue and psychological distress using three instruments. RESULTS: A total of 647 workers with mean age of 43.7 were completed. Probable fatigue was found in 34.6% of the sample. Fatigue was found by multiple logistic regressions to be associated with the lack of exercise, working in shifts, depression score and lack of social support at workplace. CONCLUSIONS: This study found associations between life style, psychosocial job characteristics and fatigue. Because the high prevalence of probable fatigue was found in such small enterprises, the authors suggest that a short interview with some quick questionnaires in health checkup for these small enterprise workers are helpful to early detect psychosocial and fatigue problems.

Chronic intermittent hypobaric hypoxia attenuates skeletal muscle ischemia-reperfusion injury in mice.

AIM: The aim of this study was to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against skeletal muscle ischemia-reperfusion (IR) injury and to determine the underlying mechanism. MAIN METHODS: C57BL/6 mice were randomly divided into 3 groups: skeletal muscle IR injury group (IR), CIHH pretreatment following IR group (IR + CIHH), and sham operation group (Sham). The skeletal muscle IR injury model was induced by the unilateral application of a tourniquet on a hind limb for 3 h and then releasing it for 24 h. CIHH pretreatment simulating a 5000-m altitude was applied 6 h per day for 28 days. The functional and morphological performance of IR-injured gastrocnemius muscle was evaluated using contraction force, H&E staining, and transmission electron microscopy. IR injury-induced CD68+ macrophage infiltration was assessed by immunofluorescence. TNFα levels in serum and muscle were measured by ELISA and western blotting, respectively. Apoptosis was examined by TUNEL staining and Cleaved Caspase-3 protein expression. KEY FINDINGS: Acute IR injury resulted in reduced contraction tension, morphological destruction, macrophage infiltration, increased TNFα levels, and apoptosis in gastrocnemius muscle. CIHH pretreatment significantly ameliorated contraction function and morphological performance in IR-injured skeletal muscle. In addition, CIHH pretreatment resulted in marked decreases in CD68+ macrophage infiltration, TNFα levels, and apoptosis. SIGNIFICANCE: These data demonstrated that CIHH has a protective effect against acute IR injury in skeletal muscle via inhibition of inflammation and apoptosis.

Prevalence and risk factors for colonization by extended-spectrum ß-lactamase-producing or ST 131 Escherichia coli among asymptomatic adults in community settings in Southern Taiwan.

Purpose: Fecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

Ginkgolide B inhibits carotid sinus baroreflex in anesthetized male rats.

The effects of ginkgolide B on the carotid sinus baroreflex (CSB) were studied in the perfused isolated carotid sinus of 30 anesthetized Sprague-Dawley male rats. The results were as follows. (1) By perfusing with ginkgolide B (0.1, 1, 10 µmol/L), the functional curve of the baroreflex was shifted to the right and upward. There was a marked decrease in peak slope (PS) and reflex decrease (RD) in mean arterial pressure (P<0.01), while the threshold pressure (TP), equilibrium pressure (EP) and saturation pressure (SP) were significantly increased (P<0.05, P<0.01). Among the functional parameters of CSB, the changes in PS, RD, TP, EP and SP were dose-dependent. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1 µmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium channel, completely abolished the above effects of ginkgolide B (1 µmol/L) on the CSB. These results suggest that ginkgolide B inhibits the CSB in anesthetized rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve endings.

The Prevalence and Risk Factors of Gastric Polyp in Asymptomatic Patients Receiving Health Examination.

BACKGROUND: To determine the risk factors and prevalence of asymptomatic gastric polyps in the general population of Taiwan. METHODS: Consecutive asymptomatic individuals completing a health examination during October 2015-March 2016 were enrolled in the study and subjected to upper GI endoscopy. Their demographic data and medical history were collected, and the prevalence of gastric polyps was calculated. The risk factors of gastric polyps were identified by analyzing these data through univariate and multivariate logistic regression. RESULTS: Gastric polyp prevalence in the study population was 29.8%. Age range of 45-60 years, current smoking, and lack of regular exercise were found to be significantly associated with gastric polyps, whereas age range of 45-60 years (relative risk [RR], 1.59; 95% confidence interval [CI], 1.06-2.40) and current smoking (RR, 1.63; 95% CI, 1.04-2.55) were found to be independent predictors for gastric polyps. CONCLUSIONS: In Taiwan, asymptomatic gastric polyps have a prevalence of 29.8%. Age range of 45-60 years and current smoking may increase the risk of asymptomatic gastric polyps.

Hydrogen sulfide facilitates carotid sinus baroreceptor activity in anesthetized male rats.

BACKGROUND: It has been reported that hydrogen sulfide (H(2)S) could relax vascular smooth muscle by direct activation of K(ATP) channels and hyperpolarization of the membrane potential. Recently, our study has shown that H(2)S facilitated carotid baroreflex. This study was conducted to investigate the effect of H(2)S on carotid baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. RESULTS: H(2)S (derived from NaHS) 25, 50 and 100 micromol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope (PS) and peak integral value of carotid sinus nerve charge (PIV) in a concentration-dependent manner. Pretreatment with glibenclamide (20 micromol/L), a K(ATP) channel blocker, the above effects of H(2)S on CBA were abolished. Pretreatment with Bay K8644 (an agonist of calcium channels, 500 nmol/L) eliminated the role of H(2)S on CBA. An inhibitor of cystathionine gamma-lyase (CSE), DL-propargylglycine (PPG, 200 micromol/L) inhibited CBA in male rats and shifted FCCB to the right and downward. CONCLUSIONS: Our results suggest that exogenous H(2)S exerts a facilitatory role on isolated CBA through opening K(ATP) channels and further closing the calcium channels in vascular smooth muscle. Endogenous H(2)S may activate CBA in vivo.

Factors related to incomplete flexible sigmoidoscopy among adult Chinese in Taiwan.

BACKGROUND: Sigmoidoscopy is effective in colorectal cancer screening, but incomplete examinations may overlook colonic pathologies and delay diagnosis. This study aimed to explore risk factors for incomplete insertions of flexible sigmoidoscopy among Taiwanese. METHODS: Healthy adults participating in health check-up in a tertiary medical center were invited for study. Subjects were recruited when they had fully consented and agreed to participate. Factors related to incomplete insertions of flexible sigmoidoscopy were evaluated and multivariate logistic regression was used to determine independent risk factors. A predictive model was generated by the risk factors identified. RESULTS: In total, 1,252 subjects (mean age, 53.9 13.1 years; age range, 2187 years; male/female,780/472) were enrolled, and 278 (22.2%) incomplete insertions were recorded. Multivariate analysis showed that female gender (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.562.73; p < 0.001), age >or= 60 years (OR, 1.68; 95% CI, 1.262.23; p < 0.001), inadequate bowel preparation (OR, 1.66; 95% CI, 1.212.16; p = 0.001), history of constipation (OR, 2.43; 95% CI, 1.045.69; p = 0.042), and body mass index (BMI) < 25 kg/m2 (OR, 1.41; 95% CI, 1.051.89; p = 0.024) were all independent risk factors. The probability of incomplete insertion was significantly associated with the sum of the aforementioned risk factors (p < 0.001). Compared with subjects with no risk factors, the risks of incomplete insertions increased significantly among subjects bearing 1 risk factor (OR, 2.57; 95% CI, 1.474.49; p = 0.001), 2 risk factors (OR, 4.41; 95% CI, 2.527.39; p < 0.001), 3 risk factors (OR, 6.40; 95% CI, 3.5611.52; p < 0.001) and >or= 4 risk factors (OR, 10.00; 95% CI, 3.8925.70; p < 0.001). CONCLUSION: Female sex, age >or= 60 years, BMI < 25 kg/m2, history of constipation, and inadequate bowel preparation were independent risk factors for incomplete insertion of flexible sigmoidoscopy. Subjects with multiple risk factors may consider alternative modalities for colonic examination.

Electrophysiological effects of hydrogen sulfide on guinea pig papillary muscles in vitro.

The cardiac electrophysiological effects of hydrogen sulfide (H2S) were examined in guinea pig papillary muscles in vitro using intracellular microelectrode technique. The results obtained were as follows: (1) the duration of action potential (APD) in the normal papillary muscles was decreased by NaHS (H(2)S donor, 50, 100, 200 micromol/L) in a concentration-dependent manner; (2) in partially depolarized papillary muscles, 100 micromol/L NaHS not only reduced APD, but also decreased the amplitude of action potential (APA), overshoot (OS) and maximal velocity of depolarization at phase 0 (V(max)); (3) pretreatment with ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide (20 micromol/L) partially blocked the effects of NaHS (100 micromol/L); (4) pretreatment with L-type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) also partially blocked the effects of NaHS (100 micromol/L); (5) pretreatment with Ca(2+)-free Krebs-Henseleit solution containing glibenclamide (20 micromol/L) completely blocked the effects of NaHS (100 micromol/L); (6) APD in the normal papillary muscles was increased by DL-propargylglycine (PPG, an inhibitor of cystathionine gamma-lyase, 200 micromol/L). All these results suggest that the electrophysiological effects of H(2)S on papillary muscles in our study are due to an increase in potassium efflux through the opening of K(ATP) channels and a decrease in calcium influx. Endogenous H(2)S may act as an important regulator in electrophysiological characters in papillary muscles.

Effect of resveratrol on baroreceptor activity of carotid sinus in anesthetized male rats.

This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 micromol x L(-1)) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol x L(-1)), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol x L(-1)) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol x L(-1)) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.

Anti-cancer effects of curcumin on lung cancer through the inhibition of EZH2 and NOTCH1.

Curcumin is potentially therapeutic for malignant diseases. The mechanisms of this effect might involve a combination of antioxidant, immunomodulatory, proapoptotic, and antiangiogenic activities. However, the exact mechanisms are not fully understood. In the present study, we provided evidences that curcumin suppressed the expression of enhancer of zeste homolog 2 (EZH2) in lung cancer cells both transcriptionally and post-transcriptionally. Curcumin inhibited the expression of EZH2 through microRNA (miR)-let 7c and miR-101. Curcumin decreased the expression of NOTCH1 through the inhibition of EZH2. There was a reciprocal regulation between EZH2 and NOTCH1 in lung cancer cells. These observations suggest that curcumin inhibits lung cancer growth and metastasis at least partly through the inhibition of EZH2 and NOTCH1.

Evidence for transcriptional interference in a dual-luciferase reporter system.

The dual-luciferase reporter assay is widely used for microRNA target identification and the functional validation of predicted targets. To determine whether curcumin regulates expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) by targeting its 3'untranslated region (3'UTR), two luciferase reporter systems containing exactly the same sequence of the EZH2 3'UTR were used to perform dual-luciferase reporter assays. Surprisingly, there were certain discrepancies between the luciferase activities derived from these two reporter constructs. We normalized luciferase activity to an internal control to determine the amount of the reporter construct successfully transfected into cells, induced a transcriptional block with flavopiridol, quantified renilla luciferase mRNA levels, and compared the absolute luciferase activity among the different groups. The results suggested that curcumin promoted the transcription of the luciferase genes located downstream of the simian vacuolating virus 40 (SV40) early enhancer/promoter, but not those located downstream of the human cytomegalovirus (CMV) immediate-early or the herpes simplex virus thymidine kinase (HSV-TK) promoters. These results explain the discrepancies between the two luciferase reporter systems. The current study underscores the importance of taking caution when interpreting the results of dual-luciferase reporter assays and provides strategies to overcome the potential pitfall accompanying dual-luciferase reporter systems.