Characterization of SARS-COV-2 main protease inhibitory peptides from Ulva prolifera proteins

The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-silico proteolysis.Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all the peptides were non-cytotoxic.The hexapeptide(SSGFID)exhibited high M^(pro)inhibitory activity in molecular docking and its IC_(50)value was 139.40±0.82μmol/L in vitro according to fluorescence resonance energy transfer assay(FRET).Quantitative real-time(qRT-)PCR results show that SSGFID could stimulate the expression of mitosis-related factors,including nuclear factor-κB,cyclin D1,and cyclin-dependent kinase 4,to promote the proliferation of mice splenocytes.Stability study revealed that SSGFID showed resistance against pepsin and trypsin but lost D(Asp)after pretreatment at121℃ for 15 min.Besides,SSGFID was mainly transported through the Caco-2 cell monolayer by the peptide transporter PepT1 and passive-mediated transport during the transport study.Unfortunately,the peptide was also degraded by Caco-2 intracellular enzymes,and the transfer rate of intact peptide was4.2%.Furthermore,Lineweaver–Burk plots demonstrated that SSGFID possessed a mixed inhibitory characteristic with M^(pro).Our study indicated the potential of Ulva prolifera as antiviral and immuneenhancing functional food ingredients and nutraceuticals.

Value of N-Terminal Pro B-Type Natriuretic Peptide,High-Sensitivity C-Reactive Protein,and Homocysteine Levels in Predicting Cardiovascular Events in Chronic Heart Failure Patients After Discharge

Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.

Decrease of plasma N-terminal pro p-type natriuretic peptide as a predictor of clinical improvement after cardiac resynchronization therapy for heart failure

Background N-terminal pro β-type natriuretic peptide （NT pro BNP） has been shown to predict the prognosis and could guide the treatment of heart failure. We aimed to investigate the values of NT pro BNP in predicting the clinical response to cardiac resynchronization therapy （CRT）. Methods A total of 44 patients with chronic heart failure （34 male and 10 female, mean age of （58±13） years, New York Heart Association （NYHA） class 3.3±0.5, QRS duration （150±14） milliseconds） who underwent successful implantation of a CRT system were enrolled in this study. Pharmacotherapy remained stable during the first 3 months of follow-up. Plasma levels of NT pro BNP were evaluated before and 3 months after implantation. Clinical, echocardiographic and exercise parameters were monitored at each clinical visit after CRT implantation. Receiver operating characteristic analysis and a paired ttest were performed to analyze the data. Results After a mean of （16.3±5.5） months of follow-up, 11 nonresponders were identified. CRT resulted in a significant reduction in NT pro BNP （（1.70±1.28） vs （1.07±0.88） pmol/ml, P 〈0.001） in responders. Percentage change in NT pro BNP level （△BNP%） was a statistically significant predictor of long term clinical improvement at 3 months of follow-up. Conclusions △BNP% from baseline to 3 months of follow-up is a predictor of long term response to CRT. NT pro BNP may be a simple method for monitoring the effects of CRT.

Analyses of N‑Terminal Pro‑Brain Natriuretic Peptide,Cardiac Troponin T,and Creatine Kinase MB in Pericardial Fluid in Sudden Cardiac Death Caused by Ischemic Heart Disease

Background:Biochemical analyses of N‑terminal pro‑brain natriuretic peptide(NT‑proBNP),cardiac troponin T(cTnT),and creatine kinase MB(CK‑MB)have been reported to be valuable for the auxiliary diagnosis of sudden cardiac death(SCD)in previous forensic studies.Aims and Objectives:The present study aimed to evaluate the diagnostic efficiency of combined analyses of NT‑proBNP,cTnT and CK‑MB in the pericardial fluid for forensic diagnosis of SCD caused by ischemic heart disease.Materials and Methods:Levels of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid of 132 medicolegal autopsy cases were obtained through electrochemiluminescence method.Results:NT‑proBNP,cTnT,and CK‑MB levels were significantly elevated in SCD cases(P<0.05).Receiver‑operating characteristics(ROC)analysis showed that NT‑proBNP,cTnT,and CK‑MB have diagnostic value for the diagnosis of SCD:NT‑proBNP,cutoff value of 2236 pg/ml;cTnT,cutoff value of 199.51 ng/ml;CK‑MB:cutoff value of 2742.5 ng/ml,and the combined analyses of these three biomarkers have better diagnostic efficiency than each single biomarker alone.Moreover,the causes of SCD were sub‑divided into acute ischemic heart disease,acute myocardial infarction(AMI),and recurrent myocardial infarction subgroups for further analysis,which revealed that the ratio of cTnT/CK‑MB could be used to distinguish AMI with the cutoff value of 0.1085 estimated by ROC analysis.Conclusion:These observations suggested that the postmortem biochemical analyses of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid may assist to diagnose SCD in forensic practice,and the combined analyses of multiple biomarkers have better diagnostic efficiency than each single biomarker alone.On the basis of the postmortem biochemical analyses of NT‑proBNP,cTnT and CK‑MB,combining the ratio of cTnT/CK‑MB could be used to distinguish AMI.

Left atrial minimum volume by real-time three-dimensional echocardiography as an indicator of diastolic dysfunction

Background Left atrial （LA） maximum volume is becoming a prognostic biomarker for left ventricular （LV） diastolic dysfunction. However, we assessed LV diastolic function by measuring LA phasic volumes using real-time threedimensional echocardiography （RT3DE） in patients with stable coronary artery disease （CAD）. Methods Sixty-five stable CAD patients with normal LV ejection fraction （LVEF） were divided into three groups according to degree of coronary stenosis： control （n=15） with 〈50% stenosis as control group, mildS （n=25） with mild stenosis （50%- 70%） and severeS （n=25） with 〉70% stenosis. LA phasic volumes and function were evaluated and compared using RT3DE and two dimensional echocardiography （2DE）. N-terminal pro-B-type natriuretic peptide （NT-proBNP） levels were examined. The correlations of RT3DE-derived parameters with other conventional indices were analyzed. Results Significant correlations between RT3DE and 2DE for LA volume measurements were： control, r=0.93; mildS, 1=0.94; severeS, r=0.90 （all P 〈0.05）. Patients with severe coronary stenosis presented higher NT-proBNP level, indices of LA minimum volume and volume before atrial contraction, but lower LA total emptying fraction （LAEF） and LAEFpass^ve. Significant correlations of RT3DE derived LA volume indices with E/E＇ （r=0.695） and NF-proBNP （r=0.630） level were found. Conclusions RT3DE derived, LA indices correlate well with NT-proBNP level and may be superior to 2DE measurements for the evaluation of LV diastolic dysfunction. Enlargement of LA minimum volume in stable CAD patients without systolic dysfunction appears earlier and may be better correlated with LV diastolic function than that of LA maximum volume.