Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling.

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

Anti-arrhythmic and anti-heart failure effects of low-level electrical stimulation on aortic root ventricular ganglionated plexi.

BACKGROUND: It remains uncertain whether low-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular GP (ARVGP). METHODS: Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. RESULTS: The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (p = .033 vs. drug group) after 1 week of treatment. The ventricular effective refractory period was prolonged from 139 ± 8 ms in the drug group to 166 ± 13 ms in the LL-ES group (p = .001). Compared to the drug group, the expressions of AT-1R, TGF-ß, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all p = .001). Moreover, in the LL-ES group, LVSV increased markedly from 13.16 ± 0.22 to 16.86 ± 0.27 mL, relative to that in the drug group (p = .001), and LVEF increased significantly from 38.48% ± 0.53% to 48.94% ± 0.57% during the same time frame (p = .001). CONCLUSION: Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of tachycardia-induced HF and its associated arrhythmia.

Prognosis of Neurological Improvement in Inpatient Acute Ischemic Stroke Survivors: A Propensity Score Matching Analysis.

OBJECTIVES: Stroke has become a national concern in China. Early prediction of stroke benefits patients and aids medical professionals in clinical decision making and rehabilitation plans to improve successful outcomes. To identify prediction factors influencing short-term outcomes in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: This was a hospital-based prospective observational study. Recovery of neurological improvement was represented by a percent reduction in the National Institutes of Health Stroke Scale (NIHSS) at discharge. We performed propensity score matching (PSM) to balance the NIHSS at admission and compared NIHSS scores before and after matching with PSM criteria. Finally, we assessed the prognosis of neurological improvement and patient-related variables. RESULTS: In the matched cohort, 92 pairs were matched by NIHSS admission after PSM. Modified Barthel Index, modified Rankin scale, NIHSS on admission, hypertension, sleep time, and Montreal Cognitive Assessment (MoCA) were statistically different between the two groups (P<0.05) before matching. Multivariable analysis identified two factors independently associated with neurological improvement: diabetes (P=0.030; adjusted odds ratio, 2.129; 95% confidence interval [CI] 1.078-4.026) and MoCA (P<0.001; adjusted odds ratio, 5.385; 95% CI 2.278-12.730). CONCLUSION: Consistent with previous studies, diabetes affected the short-term outcomes of AIS, while cognitive impairment had a negative effect on long-term AIS prognosis.Diabetes and early cognitive impairment have adverse effects on short-term prognosis after AIS.

A new photochromic Gd-MOF with photoswitchable bluish-white to greenish-yellow emission based on electron transfer.

Utilization of photochromism in photo-switchable white-light emitters (WLEs) is a challenging task. In an effort to achieve this, we have recently developed a new Gd-MOF using a photoactive pyridinium-based inner salt. The compound shows interesting photoswitchable bluish white light to greenish yellow light emission as a result of electron transfer, a phenomenon that has not been observed previously in photochromic crystal compounds.

Reversible Single-Crystal-to-Single-Crystal Transformation and Magnetic Change of Nonporous Copper(II) Complexes by the Chemisorption/Desorption of HCl and H2O.

Vapor-responsive magnetic materials are highly promising for applications as chemical switches or sensors. Compared with porous materials, nonporous species benefit in overcoming the intrinsic conflict between magnetic exchange and porosity but usually suffer from the powdering of single crystals, which hinders the understanding of the structural nature of vapor response and magnetic switch. Single-crystal-to-single-crystal (SCSC) transformation of nonporous compounds through the desorption/absorption of gaseous HCl is unprecedented. Reported here is a discrete nonporous copper(II) complex, (H3O)[K(15-crown-5)2][CuCl4], that exhibits reversible SCSC transformation and magnetic change by the chemisorption/desorption of HCl and H2O. Significant changes in the coordination number (4 ↔ 3), space group (P1̅ ↔ P21/c), color (green ↔ red), and magnetic behavior (antiferromagnetic ↔ paramagnetic) were found during the SCSC transformation.

Microparticles from Patients Undergoing Percutaneous Coronary Intervention Impair Vasodilatation by Uncoupling Endothelial Nitric Oxide Synthase.

OBJECTIVES: Percutaneous coronary interventions (PCIs) save countless acute myocardial infarction (AMI) patients. However, endothelial injury is still an inevitable complication. Circulating microparticles (MPs) play important roles in vascular dysfunction. Whether PCI affects function of MPs remains unclear. METHODS: MPs were obtained from AMI patients (n = 38) both preoperatively and 24 h after PCI, and healthy subjects (n = 20). MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs to determine the effects of MPs on phosphorylation of endothelial nitric oxide synthase (eNOS), caveolin-1 expression, eNOS association with heat shock protein 90 (Hsp90), generation of nitric oxide (NO) and superoxide anion (O2), and endothelial-dependent vasodilatation. RESULTS: Compared with healthy subjects, MP concentrations increased in AMI patients. Undergoing PCI had no further effect on MPs concentration, but it results in increased endothelial-derived MPs proportion and decreased platelet-derived MP ratio. MPs from AMI patients decreased eNOS phosphorylation at Ser1177, increased eNOS phosphorylation at T495 and caveolin-1 expression, decreased eNOS association with Hsp90, decreased NO production but increased (O2) generation, damaged endothelial-dependent vasodilatation. All of these effects of MPs were strengthened by PCI. CONCLUSIONS: PCI further enhances the vascular injury effect of MPs. Circulating MPs may be a potential therapeutic target for patients undergoing PCI.

A meta-analysis of association between cerebral microbleeds and cognitive impairment.

BACKGROUND: The clinical effect of cerebral microbleeds (CMBs) on cognition has been receiving much research attention, but results are often inconsistent. MATERIAL/METHODS: We searched PubMed, Embase, Web of Science, and some Chinese electronic databases. A total of 15 studies were included. RESULTS: Patients with CMBs had higher incidence of cognitive dysfunction (OR 3.14; 95% CI 1.66-5.92) and lower scores of cognitive function (SMD was -0.36 [-0.55, -0.18] in the MMSE group and -0.65 [-0.99, -0.32] in the MoCA [Montreal Cognitive Assessment] group). The results also indicated that a higher number of CMB lesions led to more severe cognitive dysfunction (SMD was -2.41 [-5.04, -0.21] in the mild group and -2.75 [-3.50, -2.01] in the severe group). We also found that cognitive performance was significantly impaired when CMBs were located in deep (-0.4 [-0.69, -0.11]), lobar regions (-0.50 [-0.92, -0.09]), basal ganglia (-0.72 [-1.03, -0.41]), and thalamus brain regions (-0.65 [-0.98, -0.32]). CONCLUSIONS: This meta-analysis showed that CMBs were associated with cognitive dysfunction according to higher number and different locations of CMBs. Future work should focus on long-term prognosis of continuing cognitive decline and specific treatments to reduce the formation of CMBs.

Inhibition of synaptophysin ubiquitination may improve the intelligent drop due to high glucose and hypoxia.

Synaptophysin (SYP) is a synaptic vesicle membrane protein and involved in the release of neurotransmitters, synaptic plasticity, and formation and recycling of synaptic vesicles. SYP may serve as a specific marker of synaptic proteins. Our results showed high glucose and hypoxia could significantly impair the intelligence and the SYP level was positively related to the degree of intelligence in animals. Ubiquitination may influence the SYP expression. In our study, an ubiquitination inhibitor (MG-132) was injected intraperitoneally. Results showed this could increase SYP expression in the brain to improve the intelligent drop due to high glucose and hypoxia in animals. SYP ubiquitination is closely associated with E3 ubiquitin ligase, a mammalian homologue of seven in absentia. In our study, lentivirus expressing siah shRNA was injected into the cerebral ventricle to down-regulate siah expression, and results showed the SYP expression in the brain increased markedly. In addition, we also found that VitK3 could increase the SYP expression in the brain to improve the intelligent drop due to high glucose and hypoxia.

Microbleeds and silent brain infarctions are differently associated with cognitive dysfunction in patients with advanced periventricular leukoaraiosis.

BACKGROUND: Leukoaraiosis, microbleeds, and silent brain infarctions are phenotypes of small vessel disease. Leukoaraiosis is the most prevalent, and advanced periventricular leukoaraiosis is regarded as a strong predictor of cognitive dysfunction. Microbleeds and silent brain infarctions sometimes coexist with leukoaraiosis. This study aims to analyze the effects of microbleeds and silent brain infarctions on cognitive function of patients with advanced periventricular leukoaraiosis. METHODS: 227 patients with advanced periventricular leukoaraiosis were divided into control, MB, SBI, and MB&SBI groups. The presence and locations of microbleeds and silent brain infarctions were evaluated. Mini-Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test and Verbal Fluency Test were performed. Chi-square test and ANOVA to compare the characteristics of four groups, multiple linear regressions to identify the risk factors for cognitive dysfunction. RESULTS: The scores in all four tests were lower in the MB and MB&SBI groups while only the scores in Clock Drawing Test and Verbal Fluency Test were lower in the SBI group than in the control group. Age and the presence of microbleeds were independent risk factors for the lower scores in all four tests, whereas the presence of silent brain infarctions was the only independent risk factor for the lower scores in Clock Drawing Test and Verbal Fluency Test. Lobar microbleeds had the most significant effect on cognitive function. CONCLUSION: Microbleeds and silent brain infarctions were associated differently with cognitive impairment of patients with advanced periventricular leukoaraiosis. The effect of lobar microbleeds was the most significant.

N-Heterocyclic carbene-palladium(II)-1-methylimidazole complex catalyzed Mizoroki-Heck reaction of aryl chlorides with styrenes.

A well-defined N-heterocyclic carbene-palladium(II)-1-methylimidazole [NHC-Pd(II)-Im] complex 1 was found to be an effective catalyst for the Mizoroki-Heck reaction of a variety of aryl chlorides with styrenes. Both activated and deactivated aryl chlorides work well to give the corresponding coupling products in good to excellent yields by using tetrabutylammonium bromide (TBAB) as the ionic liquid.

[Detection of cyclin D1 mRNA by reverse transcription-polymerase chain reaction in paraffin-embedded tissues and its diagnostic significance for mantle cell lymphoma].

OBJECTIVE: To investigate the feasibility of detecting cyclin D1 mRNA in paraffin-embedded tissues by reverse transcriptase polymerase chain reaction (RT-PCR) and competitive RT-PCR and its diagnostic and differential diagnostic significance for mantle cell lymphoma (MCL). METHODS: Paraffin-embedded samples of 36 cases of MCL, 71 cases of other small B-cell lymphomas and 20 cases of lymphoid reactive hyperplasia as control group were retrieved from archival materials. Cyclin D1 protein and its mRNA was detected by EnVision and RT-PCR and competitive RT-PCR in all samples. House-keeping gene PGK was choosen as internal control. RESULTS: (1) Cyclin D1 protein was expressed in 27 of the 38 MCL (71.1%). No cyclin D1 expression was found in the control group. (2) PGK was detected in 103 of the 116 cases (88.8%) and also detected in 34 of 36 MCL cases (94.7%). (3) cyclin D1 mRNA was detected in 34 nodal mantle cell lymphoma cases by RT-PCR in paraffin-embedded tissues. The positive rate of cyclin D1 mRNA was 94.4% in mantle cell lymphomas after exclusion of the 2 cases which were negative for both cyclin D1 mRNA and PGK. cyclin D1 mRNA was not detected in other nodal small B-cell lymphomas or lymphoid reactive hyperplasia, except 1 case of B-SLL. Sequencing analysis showed that sequences were identical to cyclin D1. (4) Cyclin D1 mRNA overexpression was detected in 27 cases of nodal mantle cell lymphoma by competitive RT-PCR in paraffin-embedded tissues. The positive rate of cyclin D1 mRNA overexpression was 75.0% in mantle cell lymphomas after exclusion of 2 cases which were negative for both cyclin D1 mRNA and PGK. cyclin D1 mRNA overexpression was not detected in other nodal small B-cell lymphomas or lymphoid reactive hyperplasia. CONCLUSION: RT-PCR and competitive RT-PCR detection of cyclin D1 mRNA overexpression could be used for the diagnosis and differential diagnosis of mantle cell lymphoma in paraffin-embedded blocks.

[Mutation of 5'noncoding region of the bcl-6 gene in diffuse large B cell lymphomas].

OBJECTIVE: To observe the mutation of 5'noncoding region of bcl-6 gene in diffuse large B cell lymphoma (DLBCL) and its effect on lymphoma pathogenesis. METHODS: 38 DLBCL, 2 reactive hyperplasias, 5 follicular lymphomas and 5 T cell lymphomas were chosen for PCR direct sequence analysis using two sets of primers in 5'noncoding region of the bcl-6 gene. RESULTS: No mutation was found in the marginal region of reactive hyperplasias, T cell lymphomas, and follicular lymphomas but detected in 1/2 of the follicular center cells, and 7/38 cases of DLBCL. The incidence is less than that seen in other reports. Basepairs substitution and point insertion were the main mutation types. CONCLUSIONS: The positive rate of mutation of 5'noncoding region of bcl-6 gene in DLBCL is 18.7%, less frequent than the published data of DLBCL reported in other countries. It may, in some extent, participate in the pathogenesis and progression of DLBCL.