Effects of Metabolic Syndrome with or without Obesity on Outcomes after Coronary Artery Bypass Graft. A Cohort and 5-Year Study

<div><p>Background</p><p>Metabolic syndrome (MetS) and obesity are risk factors for cardiovascular disease, however, it remains unclear about effects of MetS with or without obesity on perioperative and long-term morbidity and mortality after coronary artery bypass graft (CABG).</p><p>Methods</p><p>An observational cohort study was performed on 4,916 consecutive patients receiving isolated primary CABG in Fuwai hospital. Of all patients, 1238 patients met the inclusion criteria and were divided into three groups: control, MetS with obesity and MetS without obesity (n = 868, 76 and 294 respectively). The patient’s 5-year survival and major adverse cerebral and cardiovascular events (MACCE) were studied.</p><p>Results</p><p>Among all three groups, there were no significant differences in in-hospital postoperative complications, epinephrine use, stroke, ICU stay, ventilation time, atrial fibrillation, renal failure, coma, myocardial infarction, repeated revascularization, and long-term stroke. The patients in MetS without obesity group were not associated with increased perioperative or long-term morbidities and mortality. In contrast, the patients in MetS with obesity group were associated with significant increased perioperative complications including MACCE (30.26% vs. 20.75%, 16.7%, p = 0.0074) and mortality (11.84% vs. 3.74%, 3.11%, p = 0.0007) respectively. Patients in MetS with obesity group was associated with significantly increased long-term of MACCE (adjusted OR:2.040; 95%CI:1.196–3.481; P＜0.05) and 5-years of mortality (adjusted HR:4.659; 95%CI:1.966–11.042; P＜0.05).</p><p>Conclusions</p><p>Patients with metabolic syndrome and obesity are associated with significant increased perioperative and long-term complications and mortality, while metabolic syndrome without obesity do not worsen outcomes after CABG.</p></div

Kaplan-Meier for Mortality Rate Following-up Five Years.

<p>Kaplan-Meier for Mortality Rate Following-up Five Years.</p

Study Population Recruitment Summary.

<p>Study Population Recruitment Summary.</p

Multivariable-Adjusted Odd Ratio of Long-term MACCE.

<p>Multivariable-Adjusted Odd Ratio of Long-term MACCE.</p

Preoperative Medication Use in Patients Undergoing Cardiac Surgery.

<p>ACE: angiotensin-converting enzyme; AKI: acute kidney injury.</p

Overexpression of Mitochondria Mediator Gene <i>TRIAP1</i> by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma

<div><p>The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death <i>in vitro</i> and <i>in vivo</i>, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome <i>c</i> from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both <i>in vitro</i> and <i>in vivo</i>, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment.</p></div

TRIAP1 regulates apoptosis through controlling the release of cytochrome <i>c</i>.

<p><b>A</b> and <b>B</b>, Release of cytochrome <i>c</i> is increased upon TRIAP1 knockdown. Representative images of mitochondria, cytochrome <i>c</i> (<b>A</b>) and TRIAP1 (<b>B</b>) subcellular locations for CNE-2 (left panel) and SUNE-1 (right panel) cells transiently transfected with siSCR, siTRIAP1-1 or siTRIAP1-2 after staining with MitoTracker Red, cytochrome <i>c</i> or TRIAP1 primary antibodies. Scale bar, 10 μm. (<b>C</b>) Caspase-3/7 assay for cells with TRIAP1 knockdown. Each experiment was independently repeated at least three times. The data are presented as the mean ± s.d. Student’s <i>t</i>-test, * <i>P</i> < 0.05, ** <i>P</i> < 0.01.</p

TRIAP1 promotes NPC cell growth and inhibits apoptosis <i>in vivo</i>.

<p>(<b>A-C</b>) Representative images (<b>A</b>), tumor volume growth curves (<b>B</b>) and weight (<b>C</b>) of tumors developed in xenograft models subcutaneously injected with SUNE-1 cells stably expressing the empty vector or overexpressing TRIAP1. (<b>D</b>) Representative images (left panel) and quantification of the percentage (right panel) of Ki67-positive and TUNEL-positive cells in xenografts. Scale bar, 50 μm. (<b>E-G</b>) Representative images (<b>E</b>), tumor volume growth curves (<b>F</b>) and weight (<b>G</b>) of tumors developed in xenograft models subcutaneously injected with SUNE-1 cells stably expressing the scrambled control (SCR) or TRIAP1-specific shRNA (shTRIAP1). (<b>H</b>) Representative images (left panel) and quantification of percentage (right panel) of Ki67-positive and TUNEL-positive cells in xenografts. Scale bar, 20 μm. The data are presented as the mean ± s.d. Student’s <i>t</i>-test, * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.01.</p

TRIAP1 regulates mitochondrial fragmentation and membrane potential.

<p><b>A</b> and <b>B</b>, Representative images of mitochondria and TRIAP1 subcellular location for CNE-2 (left panel) and SUNE-1 (right panel) cells transiently transfected with an empty vector (upper panel) or TRIAP1 (lower panel) (<b>A</b>); or siSCR, siTRIAP1-1 or siTRIAP1-2 (<b>B</b>) after stained with MitoTracker Red and TRIAP1 primary antibody. Scale bar, 10 μm. (<b>C</b>) Representative dot plots (left panel) and quantification (right panel) of mitochondrial membrane potential of TIRAP1 knockdown in CNE-2 and SUNE-1 cells subjected to JC-1 staining. The percentage of cells with FL1-positive and FL2-negative signals represents depolarized mitochondrial cells. Each experiment was independently repeated at least three times. The data are presented as the mean ± s.d. Student’s <i>t</i>-test, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001.</p

TRIAP1 mediates the effects of miR-320b on NPC cell proliferation, mitochondrial fragmentation and apoptosis.

<p>(<b>A-F</b>) CNE-2 and SUNE-1 cells were co-transfected with a miR-320b mimic or miR-Ctrl and either the empty vector (Vector) or plasmid overexpressing TRIAP1. (<b>A</b>) MTT assay showing that recovery of TRIAP1 partially rescues the inhibitory effects of miR-320b on cell proliferation. (<b>B-F</b>) Flow cytometric analysis (<b>B-C</b>), caspase-3/7 (<b>D</b>) and immunofluorescent staining (<b>E-F</b>) assay showing that restoration of TRIAP1 reverses the promoting effects of miR-320b on mitochondrial fragmentation, apoptosis and cytochrome <i>c</i> release from mitochondria. Scale bar, 10 μm. Each experiment was independently repeated at least three times. The data are presented as the mean ± s.d. Student’s <i>t</i>-test, * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001.</p