The Potential of Melatonin to Treat Atherosclerosis by Targeting Mitochondria.

As a circadian rhythm hormone, melatonin is widely present in the body and has rich physiological functions. Compared to its prominent circadian role, melatonin has been extensively studied in many fields as an ancient antioxidant. In addition to being considered a potent antioxidant, melatonin has also been found to play an important role in mitochondrial homeostasis. Mitochondrial oxidative stress plays a crucial role in the occurrence and development of atherosclerosis. Therefore, the possible therapeutic value of melatonin as an antioxidant targeting mitochondria in atherosclerosis is worth exploring. The most widespread clinical applications of melatonin are in circadian rhythms and sleep, but the cardiovascular system may be the most promising area.

miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression.

The present study profiled differentially expressed microRNAs (miRs) in gastric cancer cell lines and then investigated miR-7 expression in gastric cancer tissue specimens and the effects of miR-7 on the growth, invasion and metastasis of gastric cancer cells and the underlying molecular events. A microRNA microarray was used to profile differentially expressed miRNAs in human gastric cancer cell lines relative to a normal stomach mucosal epithelial cell line. The miRNA miR-7 was selected for further investigation, which included real-time reverse-transcription PCR (qRT-PCR) analysis of miR-7 levels in different gastric cancer cell lines and tissues and distant non-tumor tissues from patient resections. Cell counting kit-8 (CCK-8), Transwell migration and invasion, and western blot assays were performed to assess tumor cell viability, invasion and gene expression, respectively, after miR-7 transfection. The miRNA microarray profiling revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b) and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) between gastric cancer and normal cell lines. The qRT-PCR analysis confirmed that reduced miR-7 expression occurred more frequently in poorly and moderately differentiated gastric cancer MGC-803, MKN-45 and SGC-7901 cell lines than in the well-differentiated gastric cancer NCI-N87 cell line, which was consistent with the results for gastric cancer tissues. Expression of miR-7 was downregulated in 86.9% (20/23) of the gastric cancer tissues compared with that in the distant non-tumor tissues. Restoration of miR-7 expression significantly inhibited tumor cell viability, invasiveness and migration when compared with the control cells. Luciferase assay confirmed the epidermal growth factor receptor (EGFR) as a target gene of mR-7, and expression of miR-7 significantly suppressed EGFR expression at both the mRNA and protein levels. The data from the present study demonstrated that reduced miR-7 expression contributes to gastric cancer development and progression. Further study will investigate miR-7 in the regulation of EGFR expression in vitro and in vivo.

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE(-/-) mice possibly via activated STAT3-mediated upregulation of tristetraprolin.

AIM: To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE(-/-) mice and the underlying mechanisms. METHODS: Male ApoE-KO mice were daily injected with LPS (25 µg, sc) or PBS for 4 weeks. The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP. After the animals were killed, blood, livers and aortas were collected for biochemical and histological analyses. For ex vivo experiments, the abdominal cavity macrophages were harvested from each treatment group of mice, and cultured with autologous serum, then treated with LPS. RESULTS: Chronic administration of LPS in ApoE(-/-) mice significantly increased the expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and MCP-1), increased infiltration of inflammatory cells, and enhanced the development of atherosclerosis. In LPS-challenged mice injected with rAAV-apoA-I-GFP, viral particles and human apoA-I were detected in the livers, total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased, TG and TC were slightly increased. Furthermore, overexpression of apoA-I significantly suppressed the expression of proinflammatory cytokines, reduced the infiltration of inflammatory cells, and decreased the extent of atherosclerotic lesions. Moreover, overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP), and phosphorylation of JAK2 and STAT3 in aortas. In ex vivo mouse macrophages, the serum from mice overexpressing apoA-I significantly increased the expression of TTP, accompanied by accelerated decay of mRNAs of the inflammatory cytokines. CONCLUSION: ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP.

[Assessment of left ventricular systolic and diastolic function by Doppler tissue imaging in patients with chronic heart failure].

OBJECTIVE: To investigate the application of pulsed-wave Doppler tissue imaging ( PW-DTI) in evaluating left ventricular systolic and diastolic function in patients with chronic heart failure (CHF). METHODS: Mitral annular velocities (MAV) were measured by PW-DTI in 35 patients with CHF and 25 healthy subjects. Traditional indices for evaluating the global left ventricular function by conventional echocardiography were also studied as a comparison. RESULTS: Peak systolic, peak early diastolic, peak late diastolic mitral annular velocities ( Sa, Ea, Aa), and Ea/Aa ratio progressively decreased in CHF patients compared with the healthy subjects (P <0.01 ). Sa of the mitral annulus correlated linearly with the left ventricle ejection fraction (LVEF) (r =0.890, P < 0.01). Compared with the healthy subjects, Ea in all 3 subgroups of diastolic dysfunction in the CHF group significantly decreased (P <0.01). Aa in 2 subgroups (pseudonormal filling and restrictive filling) decreased (P < 0.01 ) and the decreased Ea/Aa was found in the delayed relaxation and pseudonormal filling subgroups compared with the healthy subjects (P<0.001). CONCLUSION: MAV measured by PW-DTI can be used for assessing the left ventricular systolic and diastolic function in CHF patients.