Mechanistic Study of Novel Dipeptidyl Peptidase IV Inhibitory Peptides from Goat's Milk Based on Peptidomics and In Silico Analysis.

Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (<23 AA) were successfully identified by LC-MS/MS from goat milk hydrolysates (hydrolyzed by papaian plus proteinase K). Then, 105 potential DPP-IV inhibitory peptides were screened using PeptideRanker, the ToxinPred tool, Libdock, iDPPIV-SCM, and sequence characteristics. After ADME, physicochemical property evaluation, and a literature search, 12 candidates were efficiently selected and synthesized in vitro for functional validation. Two peptides (YPF and LLLP) were found to exert relatively high in vitro chemical system (IC50 = 368.54 ± 12.97 µM and 213.99 ± 0.64 µM) and in situ (IC50 = 159.46 ± 17.40 µM and 154.96 ± 8.41 µM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.

Distribution of LPRD in OSAHS Patients: Is There a Correlation?

Objective: Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) and Laryngopharyngeal Reflux Disease (LPRD) are interrelated medical conditions affecting the respiratory system. This article aimed to investigate the potential correlation between the two. Methods: This cross-sectional study was carried out on a total of 52 participants diagnosed with both OSAHS and LPRD. Clinical data of baseline demographics of year, sex, BMI, including clinical indicators such as AHI (Apnea Hypopnea Index), OSAHS severity grading, RFS (Reflux Finding Score), RSI (Reflux Symptom Index), and 24-hour pH level were collected. Statistical analysis was then conducted to evaluate the correlation between OSAHS and LPRD. Results: Among the 52 patients, the the average age was 43.3±11.6 years with a mean 24.7±2.9 kg/m2 BMI level. The mean duration of OSAHS was 4.1±1.7 years with mean 38.7±12 AHI scores and 30.8% mild OSAHS, 51.9% moderate OSAHS, and 17.3% severe OSAHS. Mean LPRD duration was 3.2±1.5 years with a mean 15.9±4.9 RFS score, mean 28.0±6.8 RSI score, and mean 3.9±0.8 24-hour pH level. There was a strong positive correlation between AHI scores and both the RFS score (r>0.9, P < .01) and RSI score (r>0.9, P < .01). While a strong negative correlation between AHI scores and 24-hour pH level was observed (r < -0.8, P < .01). And there was a strong positive correlation between OSAHS severity levels and both the RSF score (r>0.8, P < .01) and RSI score (r>0.79, P < .01). While a significant negative correlation between OSAHS severity and 24-hour pH level was detected (r < -0.7, P < .01). Conclusions: The findings of this cross-sectional study demonstrate a strong positive correlation between the severity of OSAHS, as indicated by AHI scores, and the severity of LPRD, as measured by RFS and RSI scores. A negative correlation was also observed between AHI scores and 24-hour pH level, indicating a connection between these two medical conditions.

One-Year Survival for Developing Acute Kidney Injury in Adult Patients with AMI Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

Objective: The incidence of cardiogenic shock cases treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been on the rise. Acute kidney injury (AKI) is a significant complication of cardiogenic shock and a frequent serious complication in patients requiring ECMO-supported therapy. AKI is strongly associated with unfavorable patient prognosis. However, there is a paucity of data on the influence of AKI on the prognosis of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who are receiving ECMO support, particularly with regard to long-term outcomes. Methods: This retrospective observational study included 103 patients in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2017 and June 2022. AKI was defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Cox regression and logistic regression were used to identify risk factors. Results: In this study, the incidence of AKI was 63.11%, with AKI stage 1, 2, and 3 accounting for 21.36%, 12.62%, and 29.13%, respectively. Patients with severe AKI had significantly higher in-hospital mortality (43.33% vs 27.40%, P < 0.001), 30-day mortality (60.00% vs 31.51%, P = 0.001), and 1-year mortality (63.67% vs 34.25%, P<0.001) than those without severe AKI. Furthermore, severe AKI significantly increased the risk of one-year mortality (HR 10.816, CI 3.118-37.512, P<0.001). Baseline serum creatinine, baseline platelet, and active cardiopulmonary resuscitation were independent predictors of one-year mortality. In addition, baseline white blood cell count, baseline aspartate aminotransferase, baseline alanine aminotransferase (ALT), baseline serum creatinine, preoperative lactate, and postoperative mean arterial pressure were independent risk factors of severe AKI during hospitalization. Conclusion: In patients with AMI-CS receiving ECMO support, AKI is highly prevalent. Development of severe AKI significantly increased the risk of one-year mortality.

Independent risk factors of acute kidney injury among patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: Acute kidney injury (AKI) is one of the most frequent complications in patients treated with extracorporeal membrane oxygenation (ECMO) support. The aim of this study was to investigate the risk factors of AKI in patients undergoing ECMO support. METHODS: We performed a retrospective cohort study which included 84 patients treated with ECMO support at intensive care unit in the People's Hospital of Guangxi Zhuang Autonomous Region from June 2019 to December 2020. AKI was defined as per the standard definition proposed by the Kidney Disease Improving Global Outcome (KDIGO). Independent risk factors for AKI were evaluated through multivariable logistic regression analysis with stepwise backward approach. RESULTS: Among the 84 adult patients, 53.6% presented AKI within 48 h after initiation of ECMO support. Three independent risk factors of AKI were identified. The final logistic regression model included: left ventricular ejection fraction (LVEF) before ECMO initiation (OR, 0.80; 95% CI, 0.70-0.90), sequential organ failure assessment (SOFA) score before ECMO initiation (OR, 1.41; 95% CI, 1.16-1.71), and serum lactate at 24 h after ECMO initiation (OR, 1.27; 95% CI, 1.09-1.47). The area under receiver operating characteristics of the model was 0.879. CONCLUSION: Severity of underlying disease, cardiac dysfunction before ECMO initiation and the blood lactate level at 24 h after ECMO initiation were independent risk factors of AKI in patients who received ECMO support.

Epidemiology and Serum Metabolic Characteristics of Acute Myocardial Infarction Patients in Chest Pain Centers.

BACKGROUND: We aimed to find a potential earlier diagnostic strategy for acute myocardial infarction (AMI) by investigating the epidemiology and serum metabolic characteristics of AMI patients in comparison with those of chest pain controls (CPCS). METHODS: We conducted this prospective, non-randomized, observational study of patients with acute chest pain symptoms presenting to the Emergency Rooms (ER) in The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Province, China from January 2015 to July 2016. We included a cohort of 45 patients with AMI together with 45 age- and sex-matched CPCS. The epidemiology of AMI was collected, and the phenotypic characteristics of the serum metabolite composition of AMI patients were determined using a combination of 1H nuclear magnetic resonance (NMR)-based metabolomics and clinical assays. RESULTS: The epidemiology showed that elderly AMI patients with chest pain syndrome presenting to ER have little awareness of their physical condition and compliance with medication. Significant serum metabolic differences observed between AMI patients and CPCS were highlighted by system differentiations in multiple metabolic pathways including anaerobic glycolysis, gluconeogenesis, tricarboxylic acid cycle (TCA cycle), protein biosynthesis, lipoprotein changes, choline and fatty acid metabolisms and intestinal microbial metabolism. CONCLUSION: The epidemiology and serum metabolic phenotypes observed here demonstrated that integration of metabolomics with other techniques could be useful for better understanding the biochemistry of AMI and for potential AMI molecular diagnosis. We should improve the general public's awareness of AMI, including early symptoms, risk factors, emergency responses, and treatments for related comorbidities.