Potential key targets and mechanism of the Mizuhopecten yessoensis derived ACE inhibitory peptide Asn-Cys-Trp (NCW) via network pharmacology and molecular docking

Mizuhopecten yessoensis-derived angiotensin converting enzyme (ACE) inhibitory peptide Asn-Cys-Trp (NCW) has been found that had a significantly in vivo antihypertensive effect. However, the special mechanism of peptide NCW for lowing blood pressure has not been fully elucidated. This study aimed to screen the key targets and elucidate the antihypertensive mechanism of based on the network pharmacology and molecular docking. A total of 70 potential antihypertensive targets of peptide NCW were identified, which were mainly enriched in Regulation of blood pressure, Positive regulation of smooth muscle cell proliferation, and other biological processes; Plasma membrane, Extracellular exosome, and other cellular components; Endopeptidase activity, Zinc ion binding, and other molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that lipid and atherosclerosis pathway, relaxin signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were the key pathways for peptide NCW to regulate the potential antihypertensive targets. Eleven potential key antihypertensive targets were screened via topology analysis of protein and protein interaction network, i.e., albumin (ALB), matrix metallopeptidase 9 (MMP9), MMP2, insulin like growth factor 1, AKT serine/threonine kinase 1 (IGF1), ACE, nitric oxide synthase 3 (NOS3), peroxisome proliferator activated receptor gamma (PPARG), epidermal growth factor receptor (EGFR), catalase (CAT), and renin (REN). In addition, molecular docking results showed that the peptide NCW had high affinities with these potential key antihypertensive targets, and hydrogen bonds were the key interaction forces between the peptide NCW and targets. This study provided a theoretical basis for the multi-target and multi-pathway prevention and improvement of hypertension with peptide NCW

Analysis of weighted co-regulatory networks in maize provides insights into new genes and regulatory mechanisms related to inositol phosphate metabolism

Sub-network 1 and 2 of “magenta2”, node annotation. (XLSX 10 kb

Synergistic Effects of Clopidogrel and Fufang Danshen Dripping Pills by Modulation of the Metabolism Target and Pharmacokinetics

Background and Objective. The aim was to evaluate the synergistic effects of clopidogrel and FDDP by modulating the metabolism target and the pharmacokinetics. Methods. The inhibition effect of FDDP on the CES1 was first investigated by the molecular simulation method, and the synergistic effects on the pharmacokinetics of CPGS were studied as follows: SD rats were treated with oral clopidogrel alone at a dosage of 30 mg/kg or the combination of clopidogrel and FDDP at dosages of 30 mg/kg and 324 mg/kg, respectively, for 21 days. The concentrations of CPGS in the blood plasma samples were determined and the calculated concentrations were used to determine the pharmacokinetic parameters. Results. 20 compounds in FDDP potentially interacted with CES1 target. The CPGS showed a two-compartment model pharmacokinetic profile. The concentration-time course of CPGS was not changed by FDDP, but FDDP decreased the peak plasma concentration and area under the curve of CPGS. Conclusion. The CES1’s activity could be partly inhibited by FDDP through the molecular simulation investigation. The concentration-time course of CPGS was altered slightly by FDDP. The results demonstrated the synergistic effects of clopidogrel and FDDP by modulating both the pharmacokinetics and the target metabolism

Risk factors of oncogenic HPV infection in HIV-positive men with anal condyloma acuminata in Shenzhen, Southeast China: a retrospective cohort study

BackgroundHuman immunodeficiency virus (HIV)-positive patients with anal condyloma acuminata (CA) present an increased risk of anal cancer progression associated with oncogenic human papillomavirus (HPV) infection. It is essential to explore determinants of anal infection by oncogenic HPV among HIV-positive patients with CA.MethodsA retrospective cohort study was performed in HIV-positive patients with CA between January 2019 to October 2021 in Shenzhen, Southeast China. Exfoliated cells were collected from CA lesions and the anal canal of HPV genotypes detected by fluorescence PCR. Unconditional logistic regression analysis was used to probe associations of independent variables with oncogenic HPV infection.ResultsAmong HIV-positive patients with CA, the most prevalent oncogenic genotypes were HPV52 (29.43%), HPV16 (28.93%), HPV59 (19.20%), and HPV18 (15.96%). Risk of oncogenic HPV infection increased with age at enrollment (COR: 1.04, 95% CI: 1.01–1.07, p = 0.022). In the multivariable analysis, age ≥ 35 years (AOR: 2.56, 95% CI: 1.20–5.70, p = 0.02) and history of syphilis (AOR: 3.46, 95% CI: 1.90–6.79, p < 0.01) were independent risk factors statistically associated with oncogenic HPV infection. History of syphilis (AOR: 1.72, 95% CI: 1.08–2.73, p < 0.02) was also an independent risk factor statistically associated with HPV16 or HPV18 infection.ConclusionIn clinical practice, HIV-positive CA patients aged ≥35 years or with a history of syphilis should carry out HR-HPV testing and even anal cancer-related examinations to prevent the occurrence of anal cancer

Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

Background/Aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism

The prognostic index PRIMA-PI combined with Ki67 as a better predictor of progression of disease within 24 months in follicular lymphoma

BackgroundProgression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction.MethodsThis study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital.ResultsThe multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient’s progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance.ConclusionAs such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value