Effectiveness of zinc supplementation on the incidence of oral mucositis during chemotherapy and radiation: A meta­analysis.

Oral mucositis (OM) is a commonly observed and debilitating side effect of chemotherapy and radiation therapy in patients with cancer, especially head and neck cancer. Although there is no proven therapy for the prevention and treatment of OM, zinc supplementation effectively decreases the incidence of OM. This paper provides a current and comprehensive meta-analysis of the efficacy of zinc compared with placebo/control in OM. A systematic literature review was conducted using MEDLINE and Central databases for randomized control trials (RCTs) comparing zinc supplementation (oral or rinse) with placebo/control in patients with various types of cancer undergoing chemotherapy, radiation therapy or combined chemo-radiation. The outcome was OM incidence, independent of the severity. A random-effects model was used to calculate the pooled risk ratio and subgroup analyses were performed. A total of 12 RCTs were included, containing information from 783 patients. A decrease in OM incidence was observed overall when all cancer therapies were considered. However, subgroup analyses showed that zinc did not significantly decrease the incidence of OM when studies were stratified by cancer therapy or scale/criteria used to assess OM. The results of the meta-analysis support the use of zinc supplementation in decreasing OM incidence in patients with cancer receiving chemotherapy or radiation therapy. However, the high heterogeneity between studies and the small number of studies are limitations of the meta-analysis.

Are E-Cigarette and Tea Cigarette Gifting Behaviors Associated with Tobacco Use and Failed Quit Attempts in China?

This study aims to investigate e-cigarette and tea cigarette gifting in China and their influencing factors, as well as to explore whether they were associated with tobacco use and cessation. Using a multistage sampling design, 1512 household heads from Guangdong and Shaanxi provinces were recruited for the study and filled out an online questionnaire about smoking status, social participation, e-cigarette, and tea cigarette gifting. Results showed that more than 30% and nearly 3% of participants had been gifted tea cigarettes and e-cigarettes, respectively. Marital status, province of residence, smoking status, and social participation were associated with gifting behaviors. Logistic regressions showed that receiving e-cigarettes (OR = 3.43, p < 0.05) and tea cigarettes (OR = 1.70, p < 0.01) were related to tobacco use. Smokers who have received e-cigarettes (OR = 9.85, p < 0.01) and tea cigarettes (OR = 1.92, p < 0.05) were also less likely to quit smoking.

The efficacy and safety of rivaroxaban in coronary artery disease patients with heart failure and sinus rhythm: a systematic review and meta-analysis.

PURPOSE: To explore the efficacy and safety of rivaroxaban in patients with coronary artery disease (CAD), heart failure (HF) and sinus rhythm (SR). METHODS: Comprehensive literature searches were conducted using the PubMed, Cochrane Library, Embase, CNKI and Wanfang databases from inception to February 2021. Randomized controlled trials (RCTs) focusing on the efficacy and safety of new oral anticoagulant (NOAC) therapy in CAD and HF patients in SR were eligible. Statistical analyses were performed using R Programming Language. RESULTS: Three RCTs included 10,658 adult patients treated with antiplatelet drugs with or without rivaroxaban were ultimately analysed. The average follow-up period was 20.4-24 months. Rivaroxaban had a favourable point estimate in myocardial infarction (MI) and stroke (MI rivaroxaban group (3.83%, 203/5306) vs. APT group (4.52%, 214/4731), RR = 0.78, 95% CI 0.65-0.94, P < 0.01, I2 = 0%), (stroke: rivaroxaban group (1.60%, 85/5306) vs. APT group (2.52%, 119/4731), RR = 0.64, 95% CI 0.49-0.85, P < 0.01, I2 = 12%) compared with the placebo. Rivaroxaban was comparable to the placebo for all-cause death and major bleeding (all-cause death: rivaroxaban group (12.27%, 688/5606) vs. APT group (14.59%, 737/5052), RR = 0.73, 95% CI 0.49-1.06, P > 0.05, I2 = 87%), (major bleeding: rivaroxaban group (1.52%, 85/5586) vs. APT group (1.37%, 69/5043), RR = 1.18, 95% CI 0.86-1.62, P > 0.05, I2 = 0%). CONCLUSIONS: In SR patients with CAD and HF, the rates of MI and stroke associated with rivaroxaban combined with APT were lower than those associated with APT alone, and the two treatments had similar rates of all-cause death and major bleeding.

Glucagon-Like Peptide-1 Analog Liraglutide Attenuates Pressure-Overload Induced Cardiac Hypertrophy and Apoptosis through Activating ATP Sensitive Potassium Channels.

PURPOSE: This study aimed to investigate whether inhibition of glucagon-like peptide-1 (GLP-1) on pressure overload induced cardiac hypertrophy and apoptosis is related to activation of ATP sensitive potassium (KATP) channels. METHODS: Male SD rats were randomly divided into five groups: sham, control (abdominal aortic constriction), GLP-1 analog liraglutide (0.3 mg/kg/twice day), KATP channel blocker glibenclamide (5 mg/kg/day), and liraglutide plus glibenclamide. RESULTS: Relative to the control on week 16, liraglutide upregulated protein and mRNA levels of KATP channel subunits Kir6.2/SUR2 and their expression in the myocardium, vascular smooth muscle, aortic endothelium, and cardiac microvasculature. Consistent with a reduction in aortic wall thickness (61.4 ± 7.6 vs. 75.0 ± 7.6 µm, p < 0.05), liraglutide enhanced maximal aortic endothelium-dependent relaxation in response to acetylcholine (71.9 ± 8.7 vs. 38.6 ± 4.8%, p < 0.05). Along with a reduction in heart to body weight ratio (2.6 ± 0.1 vs. 3.4 ± 0.4, mg/g, p < 0.05) by liraglutide, hypertrophied cardiomyocytes (371.0 ± 34.4 vs. 933.6 ± 156.6 µm2, p < 0.05) and apoptotic cells (17.5 ± 8.2 vs. 44.7 ± 7.9%, p < 0.05) were reduced. Expression of anti-apoptotic protein BCL-2 and contents of myocardial ATP were augmented, and expression of cleaved-caspase 3 and levels of serum Tn-I/-T were reduced. Echocardiography and hemodynamic measurement showed that cardiac systolic function was enhanced as evidenced by increased ejection fraction (88.4 ± 4.8 vs. 73.8 ± 5.1%, p < 0.05) and left ventricular systolic pressure (105.2 ± 10.8 vs. 82.7 ± 7.9 mmHg, p < 0.05), and diastolic function was preserved as shown by a reduction of ventricular end-diastolic pressure (-3.1 ± 2.9 vs. 6.7 ± 2.8 mmHg, p < 0.05). Furthermore, left ventricular internal diameter at end-diastole (5.8 ± 0.5 vs. 7.7 ± 0.6 mm, p < 0.05) and left ventricular internal diameter at end-systole (3.0 ± 0.6 vs. 4.7 ± 0.4 mm, p < 0.05) were improved. Dietary administration of glibenclamide alone did not alter all the parameters measured but significantly blocked liraglutide-exerted cardioprotection. CONCLUSION: Liraglutide ameliorates cardiac hypertrophy and apoptosis, potentially via activating KATP channel-mediated signaling pathway. These data suggest that liraglutide might be considered as an adjuvant therapy to treat patients with heart failure.

An Integrated Health Monitoring Method for Structural Fatigue Life Evaluation Using Limited Sensor Data.

A general framework for structural fatigue life evaluation under fatigue cyclic loading using limited sensor data is proposed in this paper. First, limited sensor data are measured from various sensors which are preset on the complex structure. Then the strain data at remote spots are used to obtain the strain responses at critical spots by the strain/stress reconstruction method based on empirical mode decomposition (REMD method). All the computations in this paper are directly performed in the time domain. After the local stress responses at critical spots are determined, fatigue life evaluation can be performed for structural health management and risk assessment. Fatigue life evaluation using the reconstructed stresses from remote strain gauge measurement data is also demonstrated with detailed error analysis. Following this, the proposed methodology is demonstrated using a three-dimensional frame structure and a simplified airfoil structure. Finally, several conclusions and future work are drawn based on the proposed study.

Fargesin as a potential ß1 adrenergic receptor antagonist protects the hearts against ischemia/reperfusion injury in rats via attenuating oxidative stress and apoptosis.

Fargesin displayed similar chromatographic retention peak to metoprolol in the cardiac muscle/cell membrane chromatography (CM/CMC) and ß1 adrenergic receptor/cell membrane chromatography (ß1AR/CMC) models. To provide more biological information about fargesin, we investigated the effects of fargesin on isoproterenol-(ISO-) induced cells injury in the high expression ß1 adrenergic receptor/Chinese hamster ovary-S (ß1AR/CHO-S) cells and occluding the left coronary artery- (LAD-) induced myocardial ischemia/reperfusion (MI/R) injury in rats. The results in vitro showed that ISO-induced canonical cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) levels were decreased by fargesin in ß1AR/CHO-S cells. Fargesin attenuated the serum creatine kinase (CK), lactate dehydrogenase (LDH), and improved histopathological changes of ischemic myocardium compared with the I/R rats. Similar results were obtained with Evans Blue/TTC staining, in which fargesin notably reduced infarct size. Moreover, compared with the I/R group, fargesin increased COX release and the activities of some endogenous antioxidative enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), but suppressed malondialdehyde (MDA), and intracellular ROS release. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated fargesin suppressed myocardial apoptosis, which may be related to inhibition of caspase-3 activity. Taken together, these results provided substantial evidences that fargesin as a potential ß1AR antagonist through cAMP/PKA pathway could protect against myocardial ischemia/reperfusion injury in rats. The underlining mechanism may be related to inhibiting oxidative stress and myocardial apoptosis.

Involvement of DDAH/ADMA pathway in the pathogenesis of rheumatoid arthritis in rats.

Endothelial dysfunction is the early stage of atherosclerosis, which is typically associated with rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is not only an independent predictor for endothelial dysfunction but also a proinflammatory mediator. It has been shown that the level of ADMA was elevated in patients with RA. In the present study, we investigated the potential effect of ADMA on inflammation process in collagen-induced arthritis (CIA) animal model and primary cultured fibroblast-like synoviocytes (FLS) exposed to tumor necrosis factor-α (TNF-α). In CIA rats, the plasma levels of inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß) and IL-6 were markedly increased, while the plasma levels of ADMA did not increase. The expression of dimethylarginine dimethylohydrolase2 (DDAH2), the key enzyme for ADMA degradation, was markedly reduced in inflamed joint synovium of CIA rats. Moreover, the expression of anti-inflammatory factor cortistatin (CST) was markedly decreased in joint synovium of CIA rats. Treatment of cultured FLS with TNF-α significantly increased the levels of ADMA, and decreased the expression of DDAH2 mRNA and protein accompany with an increase in the levels of IL-1ß and IL-6 and a reduction in the expression of CST mRNA and protein, and the effects of TNF-α were abolished by DDAH2 overexpression. Treatment of FLS with ADMA also significantly increased the levels of IL-1ß and IL-6, and reduced the expression of CST. These findings suggest that DDAH/ADMA participates in the pathogenesis of RA, and that the effect of DDAH/ADMA may be mediated by CST.

Tumor Cell Selective Cytotoxicity and Apoptosis Induction by an Herbal Preparation from Brucea javanica.

The plant Brucea javanica has shown impressive efficacy for treating various diseases including cancer. However, the mechanism by which B. javanica acts is poorly understood. We have established tissue culture assays to study the effects of B. javanica on cervical and several other cancer cells. Our results demonstrated that the aqueous extract from B. javanica is selectively toxic to cancer cells. Induction of apoptosis by B. javanica appears to be a possible mechanism by which it kills cancer cells. Interestingly, a significant increase of p53 protein level was observed in these apoptotic cells. Our studies indicated that both p53-dependent and p53-independent activities contributed to herb-induced cell death. These results imply that further studies with B. javanica may lead to the development of novel anti-cancer drugs.

An anti-DLK1 monoclonal antibody produced using ELISA and hybridoma techniques.

DLK1 is a newly identified prognostic factor associated with liver cancer survival. To prepare specific monoclonal antibody (MAb) against DLK1, cDNA of DLK1 was cloned by RT-PCR and inserted into prokaryotic expression vector pGEX-4T1, respectively. The fusion proteins were expressed in Escherichia coli. Monoclonal antibody against DLK1 was obtained with hybridoma technique and specific ELISA screening. Western blotting and immunohistochemistry assays showed that MAb 6D6 had specific binding ability with DLK1 protein in eukaryotic cells and cancer tissues. This MAb will be a helpful tool for the detection of DLK1 protein in the tissues and serum of liver cancer and other cancer patients.