A TagSNP in SIRT1 Gene Confers Susceptibility to Myocardial Infarction in a Chinese Han Population

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (P_c) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, P_c = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, P_c = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.     

Angiographic Lesion Complexity Score and In-Hospital Outcomes after Percutaneous Coronary Intervention

Objective

We devised a percutaneous coronary intervention (PCI) scoring system based on angiographic lesion complexity and assessed its association with in-hospital complications.

Background

Although PCI is finding increasing application in patients with coronary artery disease, lesion complexity can lead to in-hospital complications.

Methods

Data from 3692 PCI patients were scored based on lesion complexity, defined by bifurcation, chronic total occlusion, type C, and left main lesion, along with acute thrombus in the presence of ST-segment elevation myocardial infarction (1 point assigned for each variable).

Results

The patients’ mean age was 67.5 +/- 10.8 years; 79.8% were male. About half of the patients (50.3%) presented with an acute coronary syndrome, and 2218 (60.1%) underwent PCI for at least one complex lesion. The patients in the higher-risk score groups were older (p < 0.001) and had present or previous heart failure (p = 0.02 and p = 0.01, respectively). Higher-risk score groups had significantly higher in-hospital event rates for death, heart failure, and cardiogenic shock (from 0 to 4 risk score; 1.7%, 4.5%, 6.3%, 7.1%, 40%, p < 0.001); bleeding with a hemoglobin decrease of >3.0 g/dL (3.1%, 11.0%, 13.1%, 10.3%, 28.6%, p < 0.001); and postoperative myocardial infarction (1.5%, 3.1%, 3.8%, 3.8%, 10%, p = 0.004), respectively. The association with adverse outcomes persisted after adjustment for known clinical predictors (odds ratio 1.72, p < 0.001).

Conclusion

The complexity score was cumulatively associated with in-hospital mortality and complication rate and could be used for event prediction in PCI patients.     

Assessing Depression Related Severity and Functional Impairment: The Overall Depression Severity and Impairment Scale (ODSIS)

Background

The Overall Depression Severity and Impairment Scale (ODSIS) is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis.

Methods

From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive–compulsive disorder, and 371 non-clinical panelists). Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation.

Results

Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test–retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately.

Conclusions

This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity.     

Microencapsulation of Neuroblastoma Cells and Mesenchymal Stromal Cells in Collagen Microspheres: A 3D Model for Cancer Cell Niche Study

There is a growing trend for researchers to use in vitro 3D models in cancer studies, as they can better recapitulate the complex in vivo situation. And the fact that the progression and development of tumor are closely associated to its stromal microenvironment has been increasingly recognized. The establishment of such tumor supportive niche is vital in understanding tumor progress and metastasis. The mesenchymal origin of many cells residing in the cancer niche provides the rationale to include MSCs in mimicking the niche in neuroblastoma. Here we co-encapsulate and co-culture NBCs and MSCs in a 3D in vitro model and investigate the morphology, growth kinetics and matrix remodeling in the reconstituted stromal environment. Results showed that the incorporation of MSCs in the model lead to accelerated growth of cancer cells as well as recapitulation of at least partially the tumor microenvironment in vivo. The current study therefore demonstrates the feasibility for the collagen microsphere to act as a 3D in vitro cancer model for various topics in cancer studies.     

LC3B is indispensable for selective autophagy of p62 but not basal autophagy

Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.     

A dual functional fluorescent probe for glioma imaging mediated by Blood-brain barrier penetration and glioma cell targeting

Glioma is a huge threat for human being because it was hard to be completely removed owing to both the infiltrating growth of glioma cells and integrity of blood brain barrier. Thus effectively imaging the glioma cells may pave a way for surgical removing of glioma. In this study, a fluorescent probe, Cy3, was anchored onto the terminal of AS1411, a glioma cell targeting aptamer, and then TGN, a BBB targeting peptide, was conjugated with Cy3-AS1411 through a PEG linker. The production, named AsT, was characterized by gel electrophoresis, ¹H NMR and FTIR. In vitro cellular uptake and glioma spheroid uptake demonstrated the AsT could not only be uptaken by both glioma and endothelial cells, but also penetrate through endothelial cell monolayer and uptake by glioma spheroids. In vivo, AsT could effectively target to glioma with high intensity. In conclusion, AsT could be used as an effective glioma imaging probe.     

Syntheses of mucin-type <Emphasis Type="Italic">O</Emphasis>-glycopeptides and oligosaccharides using transglycosylation and reverse-hydrolysis activities of <Emphasis Type="Italic">Bifidobacterium</Emphasis> endo-α-<Emphasis Type="Italic">N</Emphasis>-acetylgalactosaminidase

Endo-α-N-acetylgalactosaminidase catalyzes the release of Galβ1-3GalNAc from the core 1-type O-glycan (Galβ1-3GalNAcα1-Ser/Thr) of mucin glycoproteins and synthetic p-nitrophenyl (pNP) α-linked substrates. Here, we report the enzymatic syntheses of core 1 disaccharide-containing glycopeptides using the transglycosylation activity of endo-α-N-acetylgalactosaminidase (EngBF) from Bifidobacterium longum. The enzyme directly transferred Galβ1-3GalNAc to serine or threonine residues of bioactive peptides such as PAMP-12, bradykinin, peptide-T and MUC1a when Galβ1-3GalNAcα1-pNP was used as a donor substrate. The enzyme was also found to catalyze the reverse-hydrolysis reaction. EngBF synthesized the core 1 disaccharide-containing oligosaccharides when the enzyme was incubated with either glucose or lactose and Galβ1-3GalNAc prepared from porcine gastric mucin using bifidobacterial cells expressing endo-α-N-acetylgalactosaminidase. Synthesized oligosaccharides are promising prebiotics for bifidobacteria.