Berberine inhibited carotid atherosclerosis through PI3K/AKTmTOR signaling pathway.

Atherosclerosis, a multifactorial vascular disease resulting from lipid metabolism disorders, features chronic inflammatory damage resulting from endothelial dysfunction, which usually affects multiple arteries. The carotid artery is a common site for clinical atherosclerosis evaluation. The aortic root is the standard site for quantifying atherosclerosis in mice. Due to the adverse reactions of first-line drugs, it is necessary to discover new drugs to prevent and treat atherosclerosis. Berberine (BBR) is one of the most promising natural products derived from herbal medicine Coptidis Rhizoma (Huanglian) that features significant anti-atherosclerosis properties. However, overall BBR mechanism against carotid atherosclerosis has not been clearly discovered. Our work aimed to investigate potential BBR mechanism in improving carotid atherosclerosis in ApoE knockout mice. Here, we proved that in ApoE -/- mice receiving high-fat diet for 12 weeks, BBR can reduce serum lipid levels, improve intimal hyperplasia, and antagonize carotid lipid accumulation, which may be achieved through regulating the PI3K/AKT/mTOR signaling pathway, regulating autophagy, promoting cell proliferation and inhibiting cell apoptosis. In summary, these data indicate that BBR can ameliorate carotid atherosclerosis. Therefore, it could be a promisingly therapeutic alternative for atherosclerosis.

Atherosclerosis prediction by microarray-based DNA methylation analysis.

Using a series of DNA methylation analysis, pathogenesis was investigated to identify the specific DNA methylation markers for diagnosing atherosclerosis. Firstly, with the chip platform of Illumina Human Methylation 450 BeadChip, a total of 1,458 CpGs, covering 971 differential methylated genes were extracted with stringent filtering criteria. Secondly, hierarchical clustering as a heat map was used to check on the dependability of differential methylated genes. Thirdly, the related GO terms and pathways were enriched by up- and down-methylated genes, respectively, after verifying the capacity of these differential methylated genes to distinguish between atherosclerosis and healthy controls. In total, 971 differential DNA methylated genes were identified (1,458 CpGs). Several important function regions were also identified, including cell adhesion, PI3K-Akt signaling pathway and transcription from RNA polymerase II promoter. This study indicates that patients with atherosclerosis have high levels of DNA methylation, which is promising for early diagnosis and treatment of atherosclerosis.

Overexpression of FNDC1 Relates to Poor Prognosis and Its Knockdown Impairs Cell Invasion and Migration in Gastric Cancer.

The distribution and content of fibronectin is closely related to the occurrence and development of tumors. Fibronectin is widely involved in cell migration, adhesion, proliferation, hemostasis, and tissue repair. Fibronectin type III domain containing 1, as a primary component of the structural domain of fibronectin, is closely related to the occurrence of some cancers. However, the molecular mechanism of fibronectin type III domain containing 1 in gastric cancer has not been elaborated. In this study, we analyzed the expression and prognosis of fibronectin type III domain containing 1 by collecting data from Oncomine and GEPIA database. The expression of fibronectin type III domain containing 1 in gastric cancer cells was detected by quantitative real-time polymerase chain reaction in vitro. After knockdown of fibronectin type III domain containing 1 by small interfering RNA, the proliferation, invasion, and migration of AGS (human gastric adenocarcinoma cell line) cells and the function of epithelial-mesenchymal transition were measured by Cell Counting Kit-8, colony formation, transwell, and Western blot. The results showed that fibronectin type III domain containing 1 was highly expressed in gastric cancer tissues and its overexpression was significantly correlated with the prognosis of gastric cancer. In vitro, experiments revealed that knockdown of fibronectin type III domain containing 1 could inhibit the proliferation, migration, and invasion of gastric cancer cells, possibly by changing the epithelial-mesenchymal transition pathway. The findings elaborated the biological role of fibronectin type III domain containing 1 in gastric cancer and potential mechanism of action, possibly providing a new insight for future clinical diagnosis or even molecular therapy.

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells.

Cantharidin (CTD), a component of Mylabris (blister beetle), is a traditional Chinese medicine that exerts an anticancer effect in multiple types of cancer cells. The aim of the present study was to investigate whether CTD exhibited anti-metastatic and inhibitory cell proliferation effects against human non-small cell lung cancer (NSCLC) A549 cells, and the possible underlying mechanism by which this occurs. The results of the present study demonstrated that CTD arrested proliferation, suppressed invasion and migration and induced apoptosis in A549 cells in vitro. Alterations of apoptosis-associated protein levels, including B-cell lymphoma-2 (Bcl-2), Bcl-associated X (Bax) and active caspase-3, were detected. Furthermore, the present study demonstrated that CTD activated autophagy through downregulation of p62 expression and upregulation of microtubule-associated proteins 1A/1B light chain 3B and Beclin-1 expression. Additionally, western blot analysis identified that CTD inhibited the phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine protein kinase (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway in NSCLC, demonstrating that the levels of phosphorylated (p-)Akt, p-mTOR, phosphorylated ribosomal p70S6 protein kinase (p-p70-S6K) and cyclin D1 were significantly decreased following treatment with CTD. In conclusion, the results of the present study indicated that CTD impeded cell growth and migration by inhibiting PI3K/Akt/mTOR signaling in NSCLC, and promoted autophagy and apoptosis. CTD exhibited anticancer activity against NSCLC in vitro, revealing it as a potential candidate for the treatment of NSCLC.

[Diagnosis of noncompaction of the ventricular myocardium by echocardiography].

OBJECTIVE: To evaluate the value of echocardiography in the diagnosis of noncompaction of the ventricular myocardium (NCVM) and to elucidate the echocardiographic characteristics of NCVM. METHODS: This study included 53 patients (28 boys and 25 girls), with an age for initial diagnosis of 15 days to 18 years, who were diagnosed with NCVM by echocardiography between May 2006 and May 2015. Transthoracic two-dimensional echocardiography and color Doppler were performed for qualitative diagnosis, and the end-diastolic non-compacted layer/compacted layer (N/C) ratio measured in the parasternal ventricular short-axis sectional view was selected as the criterion for quantitative diagnosis. RESULTS: The excessively prominent ventricular trabeculae and deep inter-trabecular recesses were all seen in 53 cases, and the blood flow in the cardiac chambers was connected to the inter-trabecular recesses. The areas involved in NCVM were mainly the apex (100%) and the middle segment of the left ventricular lateral wall (98%), followed by the middle segment of the left ventricular posterior wall (49%) and the middle segment of the left ventricular inferior wall (42%). In 53 children with NCVM, the N/C ratio was 4.3±1.9 (2.1-10.0). Cardiac insufficiency was found in 83% (44/53) of the children with NCVM, and the left ventricular ejection fraction for these children was (43±9)%. CONCLUSIONS: Echocardiography can be used in the qualitative and quantitative diagnosis of NCVM and in the evaluation of cardiac function. The apex and the middle segment of the left ventricular lateral wall are often involved in NCVM, accompanied by decrease in the left ventricular ejection fraction.

[The study of vascular lesion using ultrasound in children with a history of Kawasaki disease].

OBJECTIVE: To explore the endothelial function, carotid artery stiffness index and carotid intima-media thickness in children with a history of Kawasaki disease (KD). METHODS: A cohort of 204 children was studied, which comprised 51 patients with Kawasaki disease with coronary artery lesion (CAL group), 50 patients with Kawasaki disease with normal coronary arteries (normal coronary arteries group), and 103 healthy age matched children (control group). Their systemic blood pressure, fasting cholesterol concentrations, flow-mediated dilation (FMD) of the brachial artery, carotid artery stiffness index and carotid intima-media thickness (IMT) were compared. RESULTS: FMD of the brachial artery in CAL group (5.2% +/- 1.9%) and normal coronary arteries group (6.8% +/- 2.0%) were significantly lower than that of control group (13.2% +/- 4.1%, both P < 0. 01); carotid artery stiffness index in CAL group (4.0 +/- 0.6) was significantly greater than that of normal coronary arteries group (3.6 +/- 0.6) and control group (3.4 +/- 0.5, P = 0.05, P < 0.01); likewise, IMT in CAL group (0.447 mm +/- 0.024 mm) was significantly higher than that of normal coronary arteries group (0.426 mm +/- 0.016 mm) and control group (0.424 mm +/- 0.016 mm, both P < 0.01). In multiple linear regression analysis, age and patient grouping were significant determinants of carotid artery stiffness index, FMD and IMT. There were significant correlations between carotid artery stiffness index, FMD and IMT in both healthy group and KD group after adjustment of age. CONCLUSION: There were endothelial dysfunction and increased systemic arterial stiffness and IMT late after the acute phase of Kawasaki disease. flow-mediated dilation of the brachial artery, carotid artery stiffness index combined carotid intima-media thickness can evaluated completely the prognosis of vascular lesion in convalescence after KD.

Methodological study on real-time three-dimensional echo-cardiography and its application in the diagnosis of complex congenital heart disease.

BACKGROUND: Real-time three-dimensional echocardiography (RT-3DE) has made revolutionized improvements of cardiac imaging during the past few years. However, there is no standard examination method for RT-3DE so far. This study aimed to establish the diagnostic method of RT-3DE and evaluate its application in the diagnosis of complex congenital heart diseases (CHD). METHODS: Fifty patients with complex CHD were examined by RT-3DE with modes of Live 3DE and Full Volume. A series of novel volumetric views combined with Van Praagh sequential segmental approach were introduced to reveal the pathological morphology of the hearts, which were compared with the findings of two-dimensional echocardiography (2DE), angiography and cardiac surgery. RESULTS: In 50 patients, 190 image acquisitions of Full Volume were performed at several acoustic windows including subcostal, apical and parasternal regions. Among them, 94.2% (179/190) of image acquisitions were successful. Most sectional volumetric views could be clearly displayed in 92.6% of the successful image acquisitions. However, sectional volumetric views could not be clearly displayed in 7.4%, which was mainly due to poor perspective conditions of examination location, improper instrument multi-parameter setting and insufficient information of whole heart captured in Full Volume acquisitions. As compared with surgical findings and angiography, RT-3DE made correction to the diagnoses in 2 cases including 1 with corrected transposition of the great arteries and the other with single atrium and mitral cleft. The diagnoses initially made by 2DE for these 2 patients were double outlet right ventricle with transposition of the great arteries and complete atrio-ventricular septal defect. CONCLUSIONS: RT-3DE can clearly display the pathological morphology of complex CHD by a series of novel volumetric views combined with sequential segmental approach through providing more spatial informative cardiovascular structures, which provides a practical method for RT-3DE diagnosis.

Phylogenetic analysis of canine parvovirus VP2 gene in Taiwan.

Canine parvovirus (CPV) is a non-enveloped virus with a single-stranded DNA genome and causes infectious enteritis in dog. In this study, 36 isolates of CPV infection were obtained in Taichung, Taiwan from 2003 to 2004. Using primers that can distinguish subtypes of CPV, we amplified part of viral VP2 gene by polymerase chain reaction (PCR) and the PCR product was sequenced; results demonstrated that two isolates could be classified as type 2a of CPV and the others were type 2b. The complete coding region of VP2 gene of type 2b was also sequenced, and phylogenetic analysis of these DNA sequences revealed that our Taichung isolate was close to the V-120, FPV-314, 97-008, Taiwan 9, LCPV-T1, and T4 isolates; however, because of the degeneracy of codons, the amino acid sequences of Taichung isolate was similar to that of the 97-008 isolate from Japan. It is known that two important amino acid residues (Asn-426 in type 2a and Asp-426 in type 2b; Ile-555 in type 2a and Val-555 in type 2b) are the determinants for the discrimination of type 2a or type 2b. After scrutinizing the complete VP2 gene of our Taichung isolate, we found the VP2 protein of the Taichung isolate did possess this molecular feature of type 2b virus. Previous studies reported that type 2a virus was the major type in Taiwan; our finding showed that CPV type 2b was the predominant type in the middle part of Taiwan. Moreover, a unique Ala-489 in VP2 of our Taichung isolate was found, contrasting to a Val-489 in the VP2 of other strains.