hKLK alleviates myocardial fibrosis in mice with viral myocarditis.

Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-ß1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-ß1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-ß1 expression.

Fibrinogen and antithrombin III are associated with in-hospital mortality among critically ill patients with acute kidney injury.

OBJECTIVES: Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it's likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined. METHODS: Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan-Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII. RESULTS: A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan-Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII. CONCLUSION: Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.

Development and validation of a prognostic nomogram for adult patients with renal sarcoma: A retrospective study based on the SEER database.

Background: Renal sarcoma (RS) is rarely seen in clinical practice. The purpose of this study was to develop a prognostic nomogram model, which could predict the probability of overall survival (OS) and cancer-specific survival (CSS) in adult patients with RS. Methods: Patients diagnosed with RS were recruited from the SEER database between 2004 and 2015, and randomized to two cohorts: the training cohort and the validation cohort. Uni- and multivariate Cox regression analyses in the training cohort were used to screen independent prognostic factors for OS and CSS. Prognostic nomograms for OS and CSS were created separately for adult RS patients based on independent risk factors. The area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomograms. Results: A total of 232 eligible patients were recruited, including 162 in the training cohort and 70 in the validation cohort. Sex, histological type, SEER stage, and surgery were independent prognostic factors for OS, while histological type, SEER stage, surgery, chemotherapy were independent prognostic factors for CSS. Based on the above independent prognostic factors, prognostic nomograms for OS and CSS were created respectively. In the training cohort, the AUCs of the nomograms for OS and CSS were 0.742 and 0.733, respectively. In the validation cohort, the AUCs of the nomograms for OS and CSS were 0.837 and 0.758, respectively. The calibration curves of the nomograms showed high consistencies between the predicted and actual survival rates. Finally, the DCA demonstrated that the nomograms in the wide high-risk threshold had a higher net benefit than the SEER stage. Conclusion: A prognostic nomogram for renal sarcoma was created and validated for reliability and usefulness in our study, which assisted urologists in accurately assessing the prognosis of adult RS patients.

An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone.

Kurarinone is a major component found in the dried roots of Sophora flavescens Ait. that participates in vital pharmacological activities. Recombinant CYP450 supersomes and liver microsomes were used to study the metabolic profiles of kurarinone and its inhibitory actions against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes. 100 µM of kurarinone strongly inhibited more than 90% of UGT1A1, UGT1A6, CYP1A2, and CYP2C9. CYP1A2 and CYP2D6 played important roles in catalyzing the biotransformation of kurarinone. Moreover, metabolism of kurarinone considerably differs among species, and metabolic characteristics were similar between monkey and human. Kurarinone demonstrated moderate permeability at values of pH 4.0 and 7.4. Our findings offer a clearer idea to understand the pharmacological and toxicological mechanisms of kurarinone.

Chromium supplementation for adjuvant treatment of type 2 diabetes mellitus: Results from a pooled analysis.

SCOPE: We conducted a pooled analysis of randomized controlled trials to evaluate the effects of chromium supplementation on clinically relevant metabolic biomarkers in type 2 diabetes mellitus (T2DM) patients. METHODS AND RESULTS: Electronic searches were conducted and the bibliographies of located articles were searched, and 28 studies were suitable for statistical pooling. Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using fixed-effects or random-effects models. Statistical heterogeneity, publication bias, subgroup analyses, sensitivity analysis and meta-regression assessments were also assessed. Chromium reduced levels of fasting plasma glucose (WMD, -0.99 mmol/L; 95% CI, -1.72 to -0.25; p = 0.008), hemoglobin A1c (WMD, -0.54 %; 95% CI, -0.82 to -0.25; p = 0.0002), triglycerides (WMD, -11.71 mg/dL; 95% CI, -18.38 to -5.04; p = 0.0006). Chromium also increased levels of high-density lipoprotein cholesterol (WMD, 1.73 mg/dL; 95% CI, 0.50 to 2.96; p = 0.006). These results were robust in sensitivity analysis and were not dependent on the chromium dose and duration of supplementation. Subgroup analyses indicated that these notably favorable effects were presented in T2DM subjects ingesting chromium chloride and chromium picolinate formulations. CONCLUSION: Our pooled analysis suggested that chromium supplementation might be a candidate as an adjunct to pharmacological management in patients with T2DM.

Lack of efficacy of pomegranate supplementation for glucose management, insulin levels and sensitivity: evidence from a systematic review and meta-analysis.

BACKGROUND: The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans. METHODS: Comprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (≥18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta-regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations. RESULTS: Sixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, -0.6 mg/dL; 95% CI, -2.79 to 1.58; P=0.59), FBI (WMD, 0.29 µIU/mL; 95% CI, -1.16 to 1.75; P=0.70), HOMA-IR (WMD, -0.04; 95% CI, -0.53 to 0.46; P=0.88) or HbA1c (WMD, -0.11%; 95% CI, -0.39 to -0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis. CONCLUSION: Pomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results.

Generalized sidelobe canceller beamforming method for ultrasound imaging.

A modified generalized sidelobe canceller (IGSC) algorithm is proposed to enhance the resolution and robustness against the noise of the traditional generalized sidelobe canceller (GSC) and coherence factor combined method (GSC-CF). In the GSC algorithm, weighting vector is divided into adaptive and non-adaptive parts, while the non-adaptive part does not block all the desired signal. A modified steer vector of the IGSC algorithm is generated by the projection of the non-adaptive vector on the signal space constructed by the covariance matrix of received data. The blocking matrix is generated based on the orthogonal complementary space of the modified steer vector and the weighting vector is updated subsequently. The performance of IGSC was investigated by simulations and experiments. Through simulations, IGSC outperformed GSC-CF in terms of spatial resolution by 0.1 mm regardless there is noise or not, as well as the contrast ratio respect. The proposed IGSC can be further improved by combining with CF. The experimental results also validated the effectiveness of the proposed algorithm with dataset provided by the University of Michigan.

The effects of resveratrol intervention on risk markers of cardiovascular health in overweight and obese subjects: a pooled analysis of randomized controlled trials.

BACKGROUND: Potential effects of resveratrol consumption on cardiovascular disease risk factors and body weight in overweight/obese adults have not been fully elucidated. Our present analysis was to evaluate the effects of resveratrol consumption on risk markers related to cardiovascular health in overweight/obese Individuals. METHODS: Multiple literature databases were systematically searched, and 21 studies were included. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI), and heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. RESULTS: There were variations in reporting quality of included studies. Resveratrol intervention significantly lowered total cholesterol (WMD, -0.19 mmol/L; 95% CI, -0.32 to -0.06; P = 0.004), systolic blood pressure (WMD, -2.26 mmHg; 95% CI, -4.82 to -0.49; P = 0.02), and fasting glucose (WMD, -0.22 mmol/L; 95% CI, -0.42 to -0.03; P = 0.03). Heterogeneity was noted for these outcomes (35.6%, 38.7% and 71.4%, respectively). Our subgroup analysis showed significant reductions in total cholesterol, systolic blood pressure, diastolic blood pressure, glucose, and insulin in subjects ingesting higher dose of resveratrol (≥300 mg/day). CONCLUSION: Our finding provides evidence that daily resveratrol consumption might be a candidate as an adjunct to pharmacological management to better prevent and control cardiovascular disease in overweight/obese individuals.

Effects of Berries Consumption on Cardiovascular Risk Factors: A Meta-analysis with Trial Sequential Analysis of Randomized Controlled Trials.

The effects of berries consumption on cardiovascular disease (CVD) risk factors have not been systematically examined. Here, we aimed to conduct a meta-analysis with trial sequential analysis to estimate the effect of berries consumption on CVD risk factors. PubMed, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) that regarding the effects of berries consumption in either healthy participants or patients with CVD. Twenty-two eligible RCTs representing 1,251 subjects were enrolled. The pooled result showed that berries consumption significantly lowered the low density lipoprotein (LDL)-cholesterol [weighted mean difference (WMD), -0.21 mmol/L; 95% confidence interval (CI), -0.34 to -0.07; P = 0.003], systolic blood pressure (SBP) (WMD, -2.72 mmHg; 95% CI, -5.32 to -0.12; P = 0.04), fasting glucose (WMD, -0.10 mmol/L; 95% CI, -0.17 to -0.03; P = 0.004), body mass index (BMI) (WMD, -0.36 kg/m(2); 95% CI, -0.54 to -0.18, P < 0.00001), Hemoglobin A1c (HbA1c) (WMD, -0.20%; 95% CI, -0.39 to -0.01; P = 0.04) and tumor necrosis factor-α (TNF-α) (WMD, -0.99 ρg/mL; 95% CI, -1.96 to -0.02; P = 0.04). However, no significant changes were seen in other markers. The current evidence suggests that berries consumption might be utilized as a possible new effective and safe supplementary option to better prevent and control CVD in humans.