Peptide Characterization of Bovine Myocardium Hydrolysates and Its Ameliorative Effects on Doxorubicin-Induced Myocardial Injury in H9c2 Cells and in Mice.

The prevalence and mortality of heart disease have a persistent existence, and it is important to develop active substances with cardioprotective properties. It has been reported that peptides from animal heart hydrolysates possess cardioprotective activity, but those mechanisms and the sequence of peptides are still unrevealed. In the present study, the extracts of bovine myocardium were prepared by enzymatic hydrolysis (BHH-A) and water extraction (BHH-W). The cardioprotective function of peptides was verified in the DOX-induced H9c2 cells and myocardial injury mice. The mass spectrometry was used to contrast the differences of active ingredients between BHH-W and BHH-A. Results suggested that both BHH-A and BHH-W could increase the activity of antioxidant enzymes in cardiomyocytes and reduce the inflammatory level and apoptosis of myocardial cells. The improvement effects of BHH-A on myocardial injury in mice were better than those of BHH-W. The analysis of peptide composition demonstrated that the contents with N-segment hydrophobic amino acids were higher in the peptides identified in BHH-A. Hence, BHH-A could be used as a potential active substance to improve DOX-induced myocardial injury by reducing oxidative damage, inflammation, and cardiomyocyte apoptosis, and its activity may be related to the richness of small molecular peptides and hydrophobic amino acids.

Ultrasonographic study of female perineal body and its supportive function on pelvic floor.

Objectives: The study aimed to observe, measure the size and elastic value of perineal body (PB) and assess its association with levator hiatus. Methods: Datasets were acquired in 45 nulliparous, 66 POP women and 70 postpartum women using ultrasound. The PB was measured in depth, height, and Young's modulus. The datasets were compared to assess whether there are some differences in the morphology, dimension and elastography modulus of PB among women. Pearson correlation analysis was used to evaluate the association between the morphology measurements (ΔValsalva-rest[v-r]), tissue mechanical properties (ΔValsalva-rest[v-r]) of the PB and levator hiatus area (ΔValsalva-rest[v-r]) to preliminarily explore whether PB can influence levator hiatus. Results: Four representative manifestations of PB were presented in our study. Nulliparous women had smaller diameters and bigger Young's modulus while postpartum women had bigger diameters and smaller Young's modulus. POP and postpartum women had bigger levator hiatal distensibility and PB extensibility. There was no statistical association between PB measurements and levator hiatal area. Conclusion: It is feasible to observe the morphology of PB and assess the dimension and elastography modulus by high-frequency ultrasound. The manifestations and measurements of PB are influenced by parity and long-term increased abdominal pressure. Our study preliminarily shows that PB has little effect on levator hiatus area.

Diagnostic Value of cTnl, NT-pro BNP, and Combined Tests in Acute Myocardial Infarction Patients.

Objective: Acute myocardial infarction (AMI) is characterized by heart damage resulting from blocked blood flow. Prompt diagnosis is vital for timely treatment and saving lives. This study aimed to evaluate the diagnostic value of cTnl, NT-pro BNP, and a combined test in AMI patients. Methods: In this study, a retrospective observational design was employed, and we selected 221 patients with AMI admitted to our hospital within a 3-year period as the research subjects and included them in the AMI group. Additionally, 200 patients from the control group, who visited our hospital for physical examinations, were selected to compare the expressions of cardiac Troponin I (cTnl) and N-Terminal pro-B-type Natriuretic Peptide (NT-pro BNP) between the two groups. Receiver Operating Characteristic (ROC) curves were constructed to analyze the diagnostic value of cTnl combined with NT-pro BNP for AMI. Furthermore, AMI patients were categorized into four groups based on the New York Heart Association (NYHA) classification (grades I, II, III, and IV). The differences in cTnl, NT-pro BNP, and Left Ventricular Ejection Fraction (LVEF) were compared among the AMI patients with different cardiac function grades to analyze their correlation and diagnostic value in assessing the severity of AMI-related cardiac insufficiency. Results: The levels of cTnl and NT-pro BNP in AMI patients were significantly higher than those in the control group, and their combined detection effectively facilitated the diagnosis of AMI occurrence. Moreover, cTnl and NT-pro BNP concentrations increased with the severity of cardiac dysfunction (NYHA grades) and showed a notable negative correlation with LVEF. Furthermore, the combined testing of cTnl and NT-pro BNP demonstrated significant value in evaluating the severity of AMI in patients. Conclusions: The combined detection of cTnl and NT-pro BNP holds considerable application value in diagnosing AMI occurrence and assessing its severity.

Identification and Screening of Potential ACE2 Activating Peptides from Soybean Protein Isolate Hydrolysate against Ang II-Induced Endothelial Dysfunction.

Angiotensin-converting enzyme 2 (ACE2) is a counterregulator against ACE by converting angiotensin II (Ang II) to Ang-(1-7), and its down-regulation leads to endothelial dysfunction in the vascular system. In the present study, we investigated the effects of soybean protein isolate hydrolysate (SPIH) on Ang II-induced endothelial dysfunction with its underlying mechanisms via ACE2 activation in human umbilical vein endothelial cells (HUVECs). We further screened potential ACE2 activating peptides by peptidomics analysis combined with bioinformatics tools. Results showed that SPIH remarkably attenuated Ang II-induced cell migration from 129 to 92%, decreased the ROS level from 2.22-fold to 1.45-fold, and increased NO concentration from 31.4 ± 0.7 to 43.7 ± 0.1 µM in HUVECs. However, these beneficial effects were reversed by ACE2 inhibitor MLN-4760 to a certain extent, indicating the modulation of ACE2. Further results revealed that SPIH (1 mg/mL) significantly increased the expression and activity of ACE2 and two novel ACE2 activating peptides with different mechanisms were explored from SPIH. IVPQ and IAVPT (50 µM) enhanced ACE2 activity, and only IVPQ (50 µM) increased ACE2 protein expression in HUVECs. These findings furthered our understanding of the antihypertensive mechanism of SPIH mediating the ACE2 activation on vascular endothelium.

Tripeptide Leu-Ser-Trp Regulates the Vascular Endothelial Cells Phenotype Switching by Mediating the Vascular Smooth Muscle Cells-Derived Small Extracellular Vesicles Packaging of miR-145.

Tripeptide LSW, initially identified as a potent ACE inhibitory peptide from soybean protein, was recently reported to exert a protective effect against angiotensin II-induced endothelial dysfunction via extracellular vesicles (EVs). However, the molecular mechanisms, especially in lipid accumulation-induced atherosclerosis, still remain unclear. The study aimed to investigate whether the protective effects of LSW against endothelial dysfunction on vascular endothelial cells (VECs) was via vascular smooth muscle cells (VSMCs)-derived miRNA-145 packaged in EVs. The miRNA-145 was concentrated in EVs from LSW-treated VSMCs (LEVs), internalized into the HVUECs, and targeted the programmed cell death protein 4 (PDCD4) expression of HUVECs. Oxidized low-density lipoprotein (oxLDL) was applied to induce endothelial dysfunction in HUVECs; oxLDL-induced endothelial dysfunction in HUVECs was attenuated by PDCD4 knockout or LEVs incubation. The results of this study suggested a novel function of LSW as a regulator on the functional EVs from vascular cells in the oxLDL-induced atherosclerotic model.

The anti-inflammatory effect of vasoactive peptides from soybean protein hydrolysates by mediating serum extracellular vesicles-derived miRNA-19b/CYLD/TRAF6 axis in the vascular microenvironment of SHRs.

The excessive accumulation of angiotensin II (Ang II) in the vascular microenvironment promotes vascular dysfunction including vascular endothelial inflammation and remodeling. In the present study, a soybean protein hydrolysate enriching with vasoactive peptides was prepared and explored the anti-inflammatory effects on the aorta of spontaneous hypertensive rats (SHRs). The soybean-derived vasoactive peptide (SVP) significantly reduced the blood pressure and attenuated inflammation of the aorta in SHRs. Pathologically, the SVP improved the wall thickening and inflammatory cell infiltration of the aorta. Mechanistically, the SVP not only reduced the expression of miRNA-19b in the aorta but down-regulated the packaging of miRNA-19b in serum EVs. The miRNA-19b targeted the deubiquitinating enzyme cylindromatosis (CYLD) in the aorta and broke the ubiquitination balance of CYLD-TRAF6. These results caused a disorder of the TRAF6-mediated signaling pathway in the aorta, which resulted in upregulation of the expression of IL-6 and TNF-α in the aorta. This pathological process in SHRs was improved by the SVP hydrolysate gavage administration. These results reported a novel anti-inflammatory mechanism of SVP through the serum EVs mediating the miR-19b/CYLD/TRAF6 axis.

Efficacy of Bariatric Surgery in the Treatment of Women With Obesity and Polycystic Ovary Syndrome.

CONTEXT: The comparative effectiveness of drugs and surgical therapy for women with obesity and polycystic ovary syndrome (PCOS) has not been systematically compared. OBJECTIVE: We aimed to determine the difference in efficacy between drug and bariatric surgery therapy for women with obesity and PCOS. METHODS: This prospective nonrandomized trial enrolled 90 women aged 18 to 40 years with body mass index (BMI) ≥ 27.5 kg/m2 and waist circumference ≥ 85 cm and fulfilling the 2011 Chinese diagnostic criteria for PCOS; 81 subjects completed the study. In the drug group, patients were administered metformin and an oral contraceptive containing ethinyl-estradiol and cyproterone acetate for the first 6 months, and metformin alone for the second 6 months. In the surgical group, patients underwent laparoscopic sleeve gastrectomies. The follow-up period was 12 months. The main outcome was the complete remission of PCOS, requiring 6 consecutive regular menstruation cycles or spontaneous pregnancy. RESULTS: Median BMI at endpoint was 30.1 kg/m2 in the drug group and 23.7 kg/m2 in the surgical group; complete remission rate was 15% and 78%, respectively. Except endpoint BMI, no difference was observed in free androgen index, ovarian morphology, homeostasis model assessment for insulin resistance, and total weight loss between remission and nonremission patients. Logistic regression analyses also revealed that the final BMI was the major factor influencing the remission of PCOS. The cutoff points for the final BMI were 27.5 kg/m2 for the drug group and 26 kg/m2 for the surgical group. Overall, nearly 95% of patients with an endpoint BMI below the cutoff values achieved complete remission. CONCLUSION: Complete remission of PCOS in patients with obesity depends on the final BMI after weight loss. Thus, bariatric surgery should be prioritized for these patients.

Soybean-Derived Antihypertensive Peptide LSW (Leu-Ser-Trp) Antagonizes the Damage of Angiotensin II to Vascular Endothelial Cells through the Trans-vesicular Pathway.

An emerging inference is that vascular cells transfer their biological cargo to recipient cells by secretion of extracellular vesicles (EVs). This study explored the effects of EVs produced from VSMCs with Ang II (EVs-A) or LSW + Ang II on HUVECs. The EVs-A increase ROS production, activate inflammation, and upregulate the expression of adhesion molecules. Among the EVs-A, miR-22, miR-143, miR-144, and miR-155 were significantly downregulated, while VSMCs pre-incubated with LSW could produce improved EVs. RNA sequencing revealed differential expression of genes associated with endothelial dysfunction, including the TNF signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway, and fluid shear stress and atherosclerosis pathway. Finally, we found that LSW could improve endothelial function by repairing the expression of miRNAs in VSMCs. It also suggests a potential mechanism for the injury action of endogenous peptide Ang II and protective effects of exogenous peptide LSW on vascular endothelial cells.

Value of high-frequency two-dimensional ultrasound on evaluating puborectalis muscle.

PURPOSE: To explore the value of high-frequency two-dimensional (2D) ultrasound on demonstrating the morphology of puborectalis muscle and detect muscle avulsion. METHODS: High-frequency 2D ultrasound and tomographic ultrasound image (TUI) were peformed to demonstrate puborectalis muscle and detect muscle avulsion respectively among 158 women with or without significant pelvic organ prolapse (POP) (POP quantification grade 2 or higher). Mean values were compared using student's t test between women with or without avulsion defects. We performed Cohen's Kappa analysis to examine the test agreement between high-frequency 2D ultrasound and TUI mode. Pearson correlation analysis was performed to explore the relationship between the thickness of puborectalis muscle and the measurements of levator-urethra gap (LUG). RESULTS: The result of high-frequency 2D ultrasound in detecting muscle avulsion agreed well with TUI mode (Kappa 0.88, P < 0.05). Women with muscle avulsion had thinner muscles and larger LUG measurements than those with normal muscle insertion (P < 0.05). Pearson correlation analysis revealed the negative relationship between the thickness of puborectalis muscle and LUG measurements (r = - 0.73). CONCLUSION: The study confirmed that it was feasible to observe the morphology of puborectalis muscle and detect muscle avulsion by high-frequency 2D ultrasound.

Translabial Ultrasound Combined With Magnetic Resonance Imaging Assessing the Distensibility of Levator Ani Muscle With Unilateral High-Grade Tears.

OBJECTIVES: It is hypothesized that unilateral high-grade tears damage levator ani muscle (LAM) integrity and increase LAM distensibility. This study aimed to investigate how a unilateral high-grade tear caused overdistension of LAM and whether tear positions affect the degree of distension. METHODS: A total of 209 women were screened by translabial ultrasonography. Then, 18 nulliparous women with an intact LAM and 26 postpartum women with unilateral levator ani defects were recruited. The anteroposterior diameter (AP), coronal diameter (LR), and hiatal area (HA) of the minimum levator hiatus were recorded and compared for assessing the distensibility. All 44 subjects underwent magnetic resonance imaging for the diagnosis of levator ani defect and detection of tear positions. Within the software, 3-dimensional pelvic models were developed from magnetic resonance imaging scans for the direct visualization and measurements. RESULTS: Of the 26 postpartum women, 15 were diagnosed with unilateral high-grade tear (caudad in 9, cephalad in 6). The △AP, △LR, and △HA (Valsalva-rest) values of women with a unilateral high-grade tear were significantly larger than those of women with an intact LAM (P < 0.05). The △AP, △LR, and △HA (Valsalva-rest) values of cephalad tears were larger than those of women with caudad tears (P < 0.05). CONCLUSIONS: A unilateral high-grade tear caused the overdistension of LAM. It was validated that cephalad tears caused higher degree of LAM distension than caudad tears.

Assessment of female pelvic floor support to the urethra using 3D transperineal ultrasound.

INTRODUCTION AND HYPOTHESIS: To explore the feasibility of three-dimensional (3D) transperineal tomographic ultrasound in evaluating pelvic floor support of the urethra in women. METHODS: Three-dimensional transperineal ultrasound volume data sets of 50 women with stress urinary incontinence (SUI) and 25 women without SUI were obtained for analysis. Pelvic floor support of the urethra was evaluated by studying the relationship between the urethra and vagina in vaginal cross section and quantified by estimating the urethral depression (UD) rate. The extent of paravaginal support at level II was also evaluated in tomographic ultrasound imaging (TUI) mode in all participants. Two-sample t-test and Mann-Whitney U test were used for statistical analysis. RESULTS: The extent of paravaginal support at level II showed no difference between the two groups. Posterior depression of the urethra into the anterior vaginal wall was increased in SUI (P < 0.05). When the UD rate value was 0.53 (CI 85%) combined with three continuous "abnormal slices," the maximum Youden Index value (sensitivity 0.82, specificity 0.88) was obtained to screen dysfunctional support of the urethra. CONCLUSIONS: The pelvic floor support of the urethra can be evaluated indirectly by studying the relationship between the urethra and anterior vaginal wall in the vaginal cross section by TUI. The obvious posterior depression of the urethra into the anterior vaginal wall could be indirect evidence of a defect in the support of the urethra.

Efficacy and safety of once-weekly semaglutide for the treatment of type 2 diabetes.

INTRODUCTION: Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety. Glucagon-likepeptide1 (GLP-1) receptor analogues are appealing due to the improved glycemic control in a glucose-dependent manner, modest weight loss and low risk of hypoglycemia. Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1 analogue, is currently in the phase III clinical trial for the treatment of type 2 diabetes. This article aims to review the pharmacological and clinical profiles of semaglutide based on the available clinical data. Expert opinion: Semaglutide achieved greater reduction from baseline in HbA1c in comparison to placebo. The greater proportion of patients in semaglutide group than that in placebo group achieved target HbA1c <7.0% and <6.5%, respectively. Semaglutide is the second GLP-1 analogue contributing to the reduced bodyweight and improving obesity related complications. More importantly, semaglutide is beneficial to diabetic patients with high cardiovascular risk according to the recently completed phase III trial. The incidence of gastrointestinal adverse effects increased with semaglutide dose.

Empagliflozin/metformin fixed-dose combination: a review in patients with type 2 diabetes.

INTRODUCTION: Most patients with type 2 diabetes, who receive monotherapy, are unable to maintain glucose levels with the progress of disease. Therefore, combination therapy with two or more anti-diabetic agents of different classes is highly desired. Sodium glucose co-transporter 2 (SGLT2) inhibitors improve glycemic control through increasing urinary glucose excretion, which is independent of ß-cell function. In addition, they are generally well tolerated and associated with a low risk of hypoglycaemia. SGLT2 inhibitors as add-on therapy to metformin have an additive effect on glycemic control in patients with type 2 diabetes, and fixed-dose tablet is likely to reduce pill burden and then improve patients' adherence. Areas covered: This article reviews empagliflozin/metformin combination therapy for the treatment of type 2 diabetes. The clinical efficacy and tolerability of empagliflozin/metformin in patients with type 2 diabetes are discussed based on the available literature. Expert opinion: It was found that empagliflozin/metformin combination therapy could significantly improve glycemic control, body weight and blood pressure with a low risk of hypoglycaemia. In addition, the empagliflozin/metformin fixed-dose tablets, supported by bioequivalence studies, could reduce pill burden to further achieve the improved patients' adherence, better glycemic control and optimized cost-effectiveness.