Correlations between flavor and fermentation days and changes in quality-related physiochemical characteristics of fermented Aurantii Fructus.

The effects of different fermentation times (0, 1, 2, 3, 4, and 5 days) on the physicochemical properties and flavor components of fermented Aurantii Fructus (FAF) were evaluated. Component analysis identified 66 compounds in positive ion mode and 32 compounds in negative ion mode. Flash GC e-nose results showed that propanal, (+)-limonene and n-nonanal may be the flavor characteristic components that distinguish FAF with different fermentation days. Furthermore, we found that the change of total flavonoid content was closely related to colony growth vitality. The total flavonoid content of FAF gradually decreased from 3rd day and then increased from 5th day (3rd day: 0.766 ± 0.123 mg/100 g; 4th day: 0.464 ± 0.001 mg/100 g; 5th day: 0.850 ± 0.192 mg/100 g). Finally, according to antioxidant activity correlation analysis, meranzin, (+)-limonene and total flavonoids were found to be the key substances affecting the fermentation days of FAF. Overall, the optimal fermentation time for FAF was 4 days.

DNMT1 deregulation of SOCS3 axis drives cardiac fibroblast activation in diabetic cardiac fibrosis.

Cardiac fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Cardiac fibroblast activation is a key effector of cells resulting in diabetic cardiac fibrosis. However, the underlying mechanism of cardiac fibroblast activation and diabetic cardiac fibrosis remains unclear. Accumulating evidence suggests that DNA methylation alterations play a central role in cardiac fibroblast activation. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1)-mediated suppression of cytokine signaling 3 (SOCS3) promoter hypermethylation leads to downregulation of SOCS3 expression in diabetic cardiac fibrosis. High glucose-induced expression of DNMT1 was increased in cardiac fibroblasts, while the expression of SOCS3 was decreased. Downregulation of SOCS3 facilitated activation of STAT3 to promote cardiac fibroblast activation and collagen deposition. Genetic or pharmacological inactivation of DNMT1 reversed the activated phenotype of cardiac fibroblasts. Clinically, we observed a significant inverse correlation between DNMT1 and SOCS3 expression levels, and loss of SOCS3 expression or increased expression of DNMT1. Taken together, these findings identify DNMT1 silencing of SOCS3 axis as a driver of cardiac fibroblast activation in diabetic cardiac fibrosis. These results provide a scientific and new explanation of the underlying mechanism of diabetic cardiac fibrosis.

CTBP1­AS2 inhibits proliferation and induces autophagy in ox­LDL­stimulated vascular smooth muscle cells by regulating miR­195­5p/ATG14.

Atherosclerosis (AS) is a chronic progressive disease caused by injury and functional changes in vascular smooth muscle cells (VSMCs). Long non­coding RNAs (lncRNAs) are pivotal regulators in AS development. The present study aimed to explore the roles and molecular mechanisms of lncRNA CTBP1­AS2 in AS progression. A dual­luciferase reporter assay confirmed that miR­195­5p is a downstream target miRNA of lncRNA CTBP1­AS2 and miR­195­5p was increased in AS. The expression levels of miR­195­5p and CTBP1­AS2 in the serums of patients with AS and human aorta vascular smooth muscle cells was increased or decreased, respectively, following treatment with oxidized low­density lipoprotein (ox­LDL). Functional experiments showed that the overexpression of lncRNA CTBP1­AS2 inhibited the proliferation of HA­VSMCs and promoted their autophagy following ox­LDL treatment. This effect could be reversed by treatment with ROC­325, the inhibitor of autophagy, or miR­195­5p mimics. Autophagy related 14 (ATG14) was identified to be a target of miR­195­5p, and lncRNA CTBP1­AS2 promoted ATG14 expression by serving as a competing endogenous RNA of miR­195­5p. The present study revealed that lncRNA CTBP1­AS2 may serve a role in AS by inhibiting the proliferation and promoting the autophagy of VSMCs through ATG14 modulation via miR­195­5p. These data may provide a novel therapeutic target for AS.

Extralobar pulmonary sequestration in a 55-year-old man.

Pulmonary sequestration is a rare congenital lung malformation that more commonly occurs in the left lung, mainly near the lower mediastinum. It is rarely observed in patients with extralobar sequestration in adulthood. We report the case of a 55-year-old man with recurrent fever and cough lasting for about 1 month, who was admitted to our hospital. His past history was unremarkable. The final diagnosis of extralobar sequestration was dependent on three-dimensional computed tomography angiography (3D CTA), which showed an abnormal blood supply vessel to the consolidation from the aortic arch. The patient underwent a left pulmonary sequestration resection, and the pathological examination also verified the diagnosis postoperatively. 3D CTA images can provide an aberrant vessel anatomy map for the surgeon and play a decisive role in the detection of pulmonary sequestration.

Endostatin, an inhibitor of angiogenesis, decreases after bidirectional superior cavopulmonary anastamosis.

Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of hepatic venous effluent away from the pulmonary circulation after Glenn appears to play a significant role in the pathogenesis of PAVMs. Although the liver is known to produce factors that regulate vascular development, specific hepatic inhibitors of angiogenesis have not been described in the post-Glenn population. Endostatin, produced from its precursor collagen XVIII, is a potent inhibitor of angiogenesis produced by the liver. This study aimed to investigate the hypothesis that endostatin levels decrease in patients after Glenn. Levels of endostatin and its precursor, long-type collagen XVIII, were determined by enzyme-linked immunoassay and immunoprecipitation, respectively, for serum samples from 38 patients undergoing Glenn, total cavopulmonary anastomosis (Fontan), or biventricular repair of cardiac defects. Samples were obtained before surgery and 24 h afterward. In patients undergoing a bidirectional Glenn procedure, endostatin levels decreased after surgery (n = 17; 4.42 vs 3.34 ng/ml; p < 0.001), and long type-collagen XVIII levels increased by 200 % (n = 10; p = 0.0001). However, endostatin levels did not change after surgery in patients undergoing Fontan (n = 13) or biventricular repair (n = 8). In patients undergoing Fontan, long-type collagen XVIII increased by 18 % (p < 0.01), whereas in control subjects, the levels were unchanged. These data suggest that the diversion of hepatic blood flow away from the pulmonary circulation in patients after the Glenn procedure inhibits endostatin production from collagen XVIII, resulting in decreased circulating serum endostatin levels. A decrease in endostatin may promote angiogenesis. The mechanism whereby the pulmonary circulation processes endostatin and its potential role in the pathogenesis of PAVMs warrant further study.

Evolution of tricuspid regurgitation after mitral valve surgery for patients with moderate-or-less functional tricuspid regurgitation.

OBJECTIVES: The purpose of this study was to evaluate the impact of moderate-or-less functional tricuspid regurgitation (TR) treatment on the clinical outcome of patients with mitral valve (MV) surgery. METHODS: From October 2001 to January 2005, 167 patients in our hospital with MV surgery and without organic tricuspid valve (TV) disease or pulmonary hypertension (PH) showed moderate-or-less functional TR preoperatively, and 41.9% of these patients were treated with TR (group T), compared with 58.1% untreated with TR (group no-T). According to tricuspid annulus dimension (TAD)/body surface area (BSA), these 167 patients were further divided into another 2 groups (A and B): group A (70 patients) represented TAD/BSA ≤ 21 mm/m2 with 32 patients from group T and 38 from group no-T, and group B (97 patients) represented TAD/BSA > 21 mm/m2 with 38 patients from group T and 59 patients from group no-T. There was no statistical difference in preoperative and operative variables between the 2 groups. Meanwhile, among the 167 patients with MV surgery, 157 patients were replaced with MV and 10 patients were repaired with MV, and De Vega technique was constantly used for TR treatment. All the results were estimated by multivariate analysis. RESULTS: The median follow-up time was 63 months (25th and 75th percentiles are 53 and 94 months, respectively); 30-day mortality was 3% (1.4% in group T versus 4.1% in group no-T; P = .31). Adjusted 5-year survival was 70.7% (66.6%-80.4%) with 85.3% (83.0%-93.4%) in group T and 64.7% (33.7%-58.3%) in group no-T, P = .001. Among the 70 patients with TAD/BSA ≤ 21 mm/m2, patients who received treatment of moderate-or-less TR and those who did not showed similar secondary TR grade at postoperative period (0.5 ± 0.6 in group T versus 0.9 ± 0.9 in group no-T; P = .2) and follow-up (1.3 ± 1.1 in group T versus 1.8 ± 1.1 in group no-T; P = .06). In subgroup B (TAD/BSA > 21 mm/m2), patients who received tricuspid valvoplasty manifested more significantly improved outcome than patients without functional TR at postoperative period (0.8 ± 0.8 in group T versus 1.6 ± 1.3 in group no-T; P = .03) and follow-up (2.0 ± 1.2 in group T versus 3.0 ± 1.1 in group no-T; P = .005). The multivariate analysis identified TAD/BSA > 21 mm/m2 and preoperative atrial fibrillation (AF) as the risk factors for lower survival at follow-up period. CONCLUSIONS: Patients with MV surgery have better midterm outcome when they receive either more aggressive and effective surgical treatment for functional TR or moderate-or-less TR preoperatively. Indexed TAD (TAD/BSA > 21 mm/m2) is a more reliable surgical guideline for the treatment of TR. Preoperative tricuspid annulus dilation and AF might be predictors of late lower survival.

[Protective role of MMP-9 inhibitor batimastat in acute lung injury after cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), batimastat, in the lung injury induced by cardiopulmonary bypass (CPB) in dogs. METHODS: Thirty healthy mongrel puppies were randomly divided into 3 groups: control group, low-dose group [batimastat 10 mg/(kg.d) for 3 days before operation] and high-dose group [batimastat 30 mg/(kg.d) for 3 days before operation]. The off-pump puppies' model of acute lung injury was established, and hemodynamic and respiratory parameters were monitored. The preoperative and postoperative alveolar-arterial oxygen difference (A-aDO(2)) and respiratory index (RI) were calculated. From the beginning of surgery, blood samples were taken at the time 0, 60, 120, and 270 min. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 mRNA expressions were determined by RT-PCR. The myeloperoxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry. And MMP-9 activity was determined by Gelatin zymography. Light and electronic microscope were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken, weighed and baked to calculate the wet weight (W/D) index. RESULTS: After cardiopulmonary bypass, the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly, and lung injury was apparent. At 270 min, the MMP-9 plasma concentration of high-dose group (17.36 +/- 1.18) microg/L was significant reducing than control group (30.47 +/- 2.22) microg/L (P < 0.05). After operation, A-aDO(2) and RI of high-dose group were significantly improved than control group (P < 0.05). The W/D index of the high-dose group (2.8 +/- 0.48) was significantly lower than that of control group (4.7 +/- 0.6) (P < 0.05). And the pathological changes of lung tissue were significantly improved in the high-dose group. However, there was no significant difference in the MMP-9 mRNA expression in three groups. CONCLUSIONS: Batimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema.