The association of dimethylarginine dimethylaminohydrolase 1 gene polymorphism with type 2 diabetes: a cohort study

<p>Abstract</p> <p>Background</p> <p>Elevated plasma levels of asymmetric dimethylarginine (ADMA) has been reported to be associated with insulin resistance and micro/macrovascular diabetic complications, and may predict cardiovascular events in type 2 diabetic patients. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme eliminating ADMA in humans, but the effect of genetic variations in <it>DDAH1 </it>on type 2 diabetes and its long-term outcome are unknown.</p> <p>Methods</p> <p>From July 2006 to June 2009, we assessed the association between polymorphisms in <it>DDAH1 </it>and type 2 diabetes in 814 consecutive unrelated subjects, including 309 type 2 diabetic patients and 505 non-diabetic individuals. Six single nucleotide polymorphisms (SNPs) in <it>DDAH1</it>, rs233112, rs1498373, rs1498374, rs587843, rs1403956, and rs1241321 were analyzed. Plasma ADMA levels were determined by high performance liquid chromatography. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).</p> <p>Results</p> <p>Among the 6 SNPs, only rs1241321 was significantly associated with a decreased risk of type 2 diabetes (AA <it>vs </it>GG+AG, OR = 0.64, 95% CI 0.47-0.86, p = 0.004). The association remained unchanged after adjustment for plasma ADMA level. The fasting plasma glucose and log HOMA-IR tended to be lower in subjects carrying the homozygous AA genotype of rs1241321 compared with the GG+AG genotypes. Over a median follow-up period of 28.2 months, there were 44 all-cause mortality and 50 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction and stroke). Compared with the GG and AG genotypes, the AA genotype of rs1241321 was associated with reduced risk of MACE (HR = 0.31, 95% CI: 0.11-0.90, p = 0.03) and all-cause mortality (HR = 0.18, 95% CI: 0.04-0.80, p = 0.02) only in subgroup with type 2 diabetes. One common haplotype (GGCAGC) was found to be significantly associated with a decreased risk of type 2 diabetes (OR = 0.67, 95% CI = 0.46-0.98, p = 0.04).</p> <p>Conclusions</p> <p>Our results provide the first evidence that SNP rs1241321 in <it>DDAH1 </it>is associated with type 2 diabetes and its long-term outcome.</p

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Background/Aims: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice. Methods: ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. Results: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. Conclusion: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation

The Use of the ROS Scavenger Cysteine as a Surface Ligand of Metal Nanoclusters and Its Bactericidal Elimination Effect

The bactericidal effects of fluorescent metal nanoclusters have impeded their bacterial bioimaging applications due to the reactive oxygen species (ROS) generation that is induced by the nanoclusters in bacteria to cause bacterial death. Herein, an ROS scavenger of cysteine was exploited as a surface ligand to prepare cysteine-conjugated gold nanoclusters (Cys–AuNCs) and cysteine-conjugated silver nanoclusters (Cys–AgNCs) using a facile hydrothermal approach. The structural and optical characterizations demonstrated successful syntheses of Cys–AuNCs and Cys–AgNCs. With the same weight concentration, the bactericidal effect increased in the order of Cys–AuNCs, Cys–AgNCs, and silver nanoparticles (AgNPs), according to the results of the bacterial growth curves. Furthermore, based on the results of the standard colony-counting method, the Cys–AuNCs revealed the best biocompatibility compared to those of the Cys–AgNCs and AgNPs in Escherichia coli (E. coli). The superior biocompatibility of the Cys–AuNCs can be attributed to the use of the ligand of cysteine as an ROS scavenger to reduce ROS in E. coli. Electron paramagnetic resonance (EPR) analyses indicated that the use of the ROS scavenger cysteine as the surface ligand of the Cys–AuNCs eliminated the ROS production induced by the Cys–AuNCs in E. coli. The biocompatible Cys–AuNCs were also confirmed as a fluorescent probe using confocal microscopy. Highly biocompatible Cys–AuNCs could be a potential fluorescent probe in the application of bacterial bioimaging

An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/ thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of transGolgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria

[[alternative]]心臟病的細胞治療－從基礎至臨床

[[abstract]]Regenerative medicine is a term given to varied strategies of repairing or replacing damaged or diseased tissues or organs to restore, maintain, or enhance their function. As the average age of the population is rising with the increasing incidence of age-related degenerative conditions, a pressing need for the products of regenerative medicine is imminent. Regenerative medicine promises a more effective solution than current pharmaceutical and interventional therapy. By far the most well-known areas of regenerative medicine have been tissue engineering and cell therapy. Engineering complex organs ex vivo by knowledge from tissue engineering is still many years away, but the use of cells to rebuild diseased or damaged tissues by delivering a small number of cells may soon be used to treat some of the world most devastating diseases. In this review, we first examine the knowledge of regeneration and tissue stem cells. We provide the most updated information about cardiac stem cells, myocyte death and growth and regeneration in diseased and aging heart. Recent research demonstrates replacement and regeneration of functional cardiac muscle can be achieved by either implanting competent cells or stimulating proliferation of endogenous stem cells. We therefore explore the scientific advances, clinical trials and challenges ahead regarding cell therapy for myocardial regeneration. Our goal is not to provide detailed information about regenerative medicine, but rather, using heart repair as an example, to inform the readership about recent advances in this promising field and encourage their active participation in its further development

Relationship between the extent of aortic replacement and stent graft for acute DeBakey type I aortic dissection and outcomes: Results from a medical center in Taiwan.

BackgroundTotal arch replacement (TAR) and/or stent graft implantation has been proposed as the primary surgical treatment for acute DeBakey type I aortic dissection. However, the suggestion was based on excellent outcomes of high-volume or aortic centers. How about the real results in most places around the world? The purpose of this study was intended to compared in-hospital mortality, major complications, and aortic remodeling between TAR and/or stent graft implantation in a medical center of northern Taiwan.MethodsBetween January 2008 and August 2017, 156 patients with acute type I aortic dissection underwent surgery at our institution, including proximal aortic replacement only (Group I, n = 72), concomitant TAR (Group II, n = 23), concomitant TAR extended with stent grafting (Group III, n = 45), and proximal aortic replacement with descending aortic stent grafting (Group IV, n = 16).ResultsNo significant differences were found in underlying disease and preoperative presentations, including operative risk among four groups. Overall in-hospital mortality was 22.4% (13 patients in Group I, 9 in Group II, 12 in Group III, and 1 in Group IV). New-onset stroke occurred in 15 patients postoperatively (3 patients [5.2%] in Group I, 3 [21.4%] in Group II, and 9 [26.5%] in Group III after excluding 36 patients with documented preoperative cerebrovascular accident or cerebral malperfusion). Root reconstruction and TAR were significantly associated with in-hospital mortality. TAR was significantly associated with surgery-related stroke. Compared to those in Group I, true lumen expansion and false lumen shrinkage during 1-year aortic remodeling were significantly higher in Groups III and IV. Both TAR and descending aorta stent grafting were significantly associated with decreased risk of patent false lumen.ConclusionsProximal aortic replacement remains the preferred surgical strategy for acute type I aortic dissection, with lower mortality and neurological complications. Proximal descending aorta stent grafting may benefit aortic remodeling, even without TAR

Rapid Microwave-Assisted Synthesis of ZnIn₂S₄ Nanosheets for Highly Efficient Photocatalytic Hydrogen Production

In this study, a facile and rapid microwave-assisted synthesis method was used to synthesize In2S3 nanosheets, ZnS nanosheets, and ZnIn2S4 nanosheets with sulfur vacancies. The two-dimensional semiconductor photocatalysts of ZnIn2S4 nanosheets were characterized by XRD, FESEM, BET, TEM, XPS, UV–vis diffuse reflectance, and PL spectroscopy. The ZnIn2S4 with sulfur vacancies exhibited an evident energy bandgap value of 2.82 eV, as determined by UV–visible diffuse reflectance spectroscopy, and its energy band diagram was obtained through the combination of XPS and energy bandgap values. ZnIn2S4 nanosheets exhibited about 33.3 and 16.6 times higher photocatalytic hydrogen production than In2S3 nanosheets and ZnS nanosheets, respectively, under visible-light irradiation. Various factors, including materials, sacrificial reagents, and pH values, were used to evaluate the influence of ZnIn2S4 nanosheets on photocatalytic hydrogen production. In addition, the ZnIn2S4 nanosheets revealed the highest photocatalytic hydrogen production from seawater, which was about 209.4 and 106.7 times higher than that of In2S3 nanosheets and ZnS nanosheets, respectively. The presence of sulfur vacancies in ZnIn2S4 nanosheets offers promising opportunities for developing highly efficient and stable photocatalysts for photocatalytic hydrogen production from seawater under visible-light irradiation