Preclinical findings reveal the pharmacological targets of ferulic acid in the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is characterized by cellular damage and inflammation in lesioned brain tissue. Ferulic acid has been shown to have a melioration effect on neurological functions. However, the active pharmacological effects and the underlying mechanisms of ferulic acid against TBI remain unclear. On the basis of network pharmacology and molecular docking methodology, this study aimed to investigate the beneficial effects of ferulic acid in treating TBI, and characterized the detailed biotargets and mechanisms of these actions. The identified core targets were validated via in silico simulation. We identified 91 overlapping targets associated with ferulic acid and TBI. In-silico simulation analysis validated the putative core targets of tumor protein p53, mitogen-activated protein kinase (MAPK) 1, and estrogen receptor 1. The Gene Ontology-enriched annotations and findings were largely associated with cell proliferation, apoptosis, and inflammation in nerve cells. Additional Kyoto Encyclopedia of Genes and Genomes enrichment analysis unmasked the pharmacological pathways of ferulic acid in treating TBI, including the MAPK signaling pathway and hypoxia-inducible factor-1 signaling pathway. Bioinformatic analyses and findings provide a new preclinical strategy for revealing the core targets and network pathways of ferulic acid in treating TBI. Moreover, some bioinformatic findings were computationally validated in silico for exhibiting the neuroprotective action of ferulic acid against TBI.

Comparison of three nutritional screening tools for predicting mortality in maintenance hemodialysis patients.

OBJECTIVES: The aim of this study was to compare the effect of different nutritional screening tools on predicting the risk for mortality in patients on maintenance hemodialysis (MHD). METHODS: A cohort of 1025 patients on MHD were enrolled from eight hospitals. The malnutrition-inflammation score (MIS), objective score of nutrition on dialysis (OSND), and geriatric nutritional risk index (GNRI) were measured at baseline. All-cause mortality and cardiovascular (CV) mortality were the major study outcomes. RESULTS: The median follow-up duration was 28.1 mo. The MIS (per SD increase, hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.18-1.55), the OSND (per SD decrease, HR, 1.24; 95% CI, 1.09-1.42), and the GNRI (per SD decrease, HR, 1.26; 95% CI, 1.10-1.43) were significantly associated with the risk for all-cause mortality. More importantly, the mortality predictability of the MIS appears similar to the GNRI (P = 0.182) and greater than the OSND (MIS versus OSND: P = 0.001; GNRI versus OSND: P = 0.045). Similar results were found for CV mortality. CONCLUSIONS: Each of the three nutritional screening tools was significantly associated with an increased risk for all-cause and CV mortality. The mortality predictability of the MIS was similar to the GNRI and greater than the OSND.

Hyperhomocysteinemia predicts renal function decline: a prospective study in hypertensive adults.

Hyper-homocysteinemia (HHcy) is associated with microalbuminuria and glomerular injury in general and diabetic populations. However, HHcy's role in hypertensive patients was not studied. We investigated whether HHcy is an independent risk factor for renal function decline and development of chronic kidney disease (CKD) in hypertensive men and women. This was a community-based prospective cohort study of 2,387 hypertensive adults without CKD at baseline, with a mean follow-up of 4.4 years. Baseline and follow-up levels of plasma Hcy, folate, vitamin B12, blood pressure and other pertinent covariables were obtained. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/per 1.73 m(2) and an eGFR decline rate >1 ml/min/per 1.73 m(2)/year. There was a graded association between Hcy tertiles and eGFR decline. Subjects in the 3(rd) tertile of Hcy levels had an accelerated rate of eGFR decline and an increased risk of incident CKD, as compared with those in the 1st tertile, after adjusting for age, gender, baseline diabetes, SBP, BMI, smoking, dyslipidemia, eGFR, folate and vitamin B12 levels. In conclusion, in this prospective cohort of Chinese hypertensive adults, elevated baseline plasma Hcy can serve as an independent biomarker to predict renal function decline and incident CKD.

Enhanced anti-angiogenesis and anti-tumor activity of endostatin by chemical modification with polyethylene glycol and low molecular weight heparin.

Endostatin (ES), a potent endogenous angiogenesis inhibitor found in 1997 by O'Reilly, can effectively inhibit angiogenesis, inhibit the growth and metastasis of tumors. ES can also decrease drug resistance in long term and repeated treatment when it is used in combination with other chemotherapeutic agents. But there are still lots of obstacles on its clinical application, such as the need of a high dose to maintain its efficacy short half-life, poor stability, expensive, and some other shortcomings just like other protein drugs. Chemical modification on ES by polyethylene glycol (PEG) and low molecular weight heparin (LMWH) were successfully carried out in order to obtain a better ES derivative. Several classic experimental models were employed to study the bioactivity of ES and modified ES, including chicken chorioallantoic membrane (CAM) assay, corneal neovascularization (CNV) assay and Sarcoma 180 tumor bearing mice assay. The results showed that PEG-ES and LMWH-ES had better anti-angiogenesis and anti-tumor activity than ES, which indicates that LMWH was also a good protein modifier.

Characterization and secondary structure analysis of endostatin covalently modified by polyethylene glycol and low molecular weight heparin.

Endostatin (ES), as an angiogenesis inhibitor, has been approved by the State Food and Drug Administration (SFDA) in China for the treatment of patients with non-small-cell lung cancer. However, as a protein drug, there are a lot of obstacles on its clinical application, such as need of high dose to maintain its efficacy, expensive and poor stability, etc and limits its clinical use. In order to overcome these shortcomings, we chemically modified ES by polyethylene glycol and low molecular weight heparin (LMWH), respectively. The changes of the secondary structure of the modified products were studied by Fourier transform infrared spectroscopy and Circular dichroism spectra to obtain better ES derivatives. Our study demonstrated that the modified products have a better heat tolerance than ES towards. The result of secondary structure analysis suggests the percentage of beta-turn in whole protein is an important factor on the activity and heat stability and ES modified by LMWH can maintain higher activity and its secondary structure.