BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

Early bioprosthesis failure: report of three cases and literature review.

BACKGROUND: We experienced three rare early bioprosthesis failure (EBF) cases. In this study, we analyze the causes and discuss the coping strategy of EBF. METHODS: We reviewed all cases of EBF in patients who received a bioprosthesis replacement in Changhai Hospital between January 2001 and January 2014, and reviewed related articles that were published between 1994 and 2014, searching for keywords in PubMed such as "bioprosthesis," "heart valve prosthesis," "early failure," and "bioprosthesis failure." RESULTS: Only three cases were found in Changhai Hospital during this time period. The reasons for EBF in these 3 cases were: native valve attachment, early calcification caused by metabolic syndrome, and early valve thrombosis. Literature review identified an additional 14 cases. The reasons for EBF in these 14 cases were as follows: native valve attachment in 6 cases; metabolic abnormalities in 3 cases; early valve thrombosis in 2 cases; chronic inflammation in 2 cases; and improper operation in 1 case. CONCLUSIONS: EBF is a rare but serious complication. The cause of EBF is complex. Appropriate preventive measures should be developed according to the condition of the patient.

Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC-MS-Based Untargeted Metabolomics Study.

Background: Recurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies. Methods: We screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or <0.5, a t-test q-value <0.05, and variable importance in projection value of >1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways. Results: We identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q <0.05) were significantly lower during RH. The combination of these metabolites can serve as a reliable predictor biomarker for RH (area under the curve = 0.88). Regarding lipid metabolism, triglyceride was upregulated (P=0.003) and the O-Acylcarnitine was downregulated (q < 0.001). Besides, RH was accompanied by lower phenylalanine (q=0.003) and higher cortisone (q=0.005) levels. Conclusions: RH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed. Clinical Trial Registry: Chi CTR 1900026361, 2019-10-3.

Effects of vinpocetine and ozagrel on behavioral recovery of rats after global brain ischemia.

Brain ischemia leads to severe disruption of the nervous system and recovery is often prolonged. Rehabilitative post-ischemia pharmacological treatment may therefore be important for behavioral recovery, especially for cognition and motor behavior. The present study investigated the effects of combined vinpocetine and ozagrel administration on the behavioral recovery of rats from global brain ischemia. The results suggest that the combined treatment leads to significantly better improvement compared to single drug administration. We conclude that the combined use of vinpocetine and ozagrel may provide beneficial effects to patients suffering from brain ischemia.