TRIM27 protects against cardiac ischemia-reperfusion injury by suppression of apoptosis and inflammation via negatively regulating p53.

Myocardial ischemia/reperfusion (MI/R) has high morbidity and mortality worldwide, but the underlying mechanisms have not been entirely understood. TRIM27 is one of the Tri-domain proteins (TRIM) family proteins with crucial roles in numerous life processes. In the study, we attempted to explore the effects of heart-conditional knockout of TRIM27 (TRIM27cKO) on MI/R progression both in vivo and in vitro. Our results showed that TRIM27 was strongly decreased in murine hearts with MI/R injury and in cardiomyocytes with hypoxic reoxygenation (HR) treatment. TRIM27cKO could further accelerate the infarction size and cardiac dysfunction in MI/R mice. Function study demonstrated that heart-selective TRIM27 deletion significantly aggravated apoptosis in hearts of MI/R mice through enhancing Caspase-3 activities. Moreover, inflammatory response due to MI/R injury was remarkably exacerbated in TRIM27cKO mice by strengthening nuclear factor κB (NF-κB) activation. In addition, p53 expression levels were dramatically up-regulated in hearts of MI/R mice and cardiomyocytes with HR treatment, which were further aggravated by TRIM27cKO. Intriguingly, we found that TRIM27 could interact with p53 and promote its ubquitination. Of note, suppressing p53 remarkably ameliorated TRIM27cKO-intensified apoptotic cell death and inflammation in HR-treated cardiomyocytes. Taken together, all these findings revealed that TRIM27/p53 axis may be involved in MI/R progression, and thus could be a therapeutic target for this disease treatment.

PCBP2 promotes the development of glioma by regulating FHL3/TGF-ß/Smad signaling pathway.

The purpose of this study was to investigate the role of Poly (C)-binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor-ß (TGF-ß) pathway related proteins TGF-ß1, p-Smad2 and p-Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3-3'UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF-ß/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.

Association between ACE gene polymorphisms and Alzheimer's disease in Han population in Hebei Peninsula.

PURPOSE: This study aimed to detect the association between angiotensin I converting enzyme (ACE) gene polymorphisms (rs4343 and rs1800764) and Alzheimer's disease (AD) in Han population in Hebei Peninsular. METHODS: We recruited 113 AD patients and 142 healthy individuals in this case-control study. Differences of genotypes, alleles and haplotypes in two groups were analyzed by chi-square test. Besides, odds ratios (ORs) and 95% confidence intervals (CIs) were used to represent the relative risk of AD. At last, the analyses of linkage disequilibrium and haplotypes were done with HaploView software. RESULTS: In the analyses of genotypes and alleles of ACE polymorphisms (rs4343 and rs1800764) in AD, no obvious association was found between genotypes and alleles of rs4343 with the susceptibility of AD. In rs1800764 polymorphism, only C allele had significant association with AD susceptibility (P=0.035, OR=1.473, 95% CI=1.027-2.111), which suggested that rs1800764 C allele is the susceptible allele of AD. Linkage disequilibrium analysis between rs4343 and rs1800764 polymorphisms indicated there existed 3 haplotypes (A-T, A-C and G-C). A-C haplotype might associate with the susceptibility of AD (P=0.023, OR=2.591, 95% CI=1.111-6.043). CONCLUSION: Rs4343 polymorphism of ACE gene had no relationship with AD risk. C allele of rs1800764 could increase the susceptibility of AD. A-C haplotype of rs4343 and rs1800764 polymorphisms might increase the risk of AD, and the ORs was 2.591.

Conversion from MCI to AD in patients with the APOE ε4 genotype: Prediction by plasma HCY and serum BDNF.

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease (AD). Possession of the apolipoprotein E (APOE) ε4 genotype is a major predictor of progression to AD, particularly in patients with aMCI. However, the use of APOE genotyping in the diagnosis of aMCI that evolves into AD is limited due to its low sensitivity and specificity. In this study, we found that there was a notable increase in plasma homocysteine (HCY) and significant decrease in serum brain-derived neurotrophic factor (BDNF) in aMCI that converts to AD in patients with the APOE ε4 allele. Both plasma HCY and serum BDNF had higher positive predictive values and were more sensitive biomarkers of aMCI. Additionally, a testing strategy employing plasma HCY and serum BDNF revealed increases in sensitivity, specificity, and predictive ability compared with the use of either biomarker alone. The present study demonstrates that MCI that evolves into AD in patients with the APOE ε4 genotype may be predicted by plasma HCY and serum BDNF.

Marchiafava-Bignami disease with rare etiology: A case report.

A male, 62-year-old patient was admitted to hospital due to dizziness and gait disturbance for 10 days. The patient had fallen a few times due to the gait instability, which was associated with stiffness and memory loss. The patient had undergone cardiac carcinoma surgery three years previously and had no drinking history. Physical examination revealed that the patient was lucid when conscious but exhibited slurred speech, apathy and cognitive impairment. The finger-to-nose and rapid alternating movement tests showed the patient to be slightly clumsy. Magnetic resonance imaging revealed symmetric abnormal signals in the splenium of the corpus callosum, and the diagnosis was Marchiafava-Bignami disease (MBD). The patient recovered following the administration of vitamin B and other treatments. The patient had long-term appetite loss. A brain myelin metabolism disorder caused by long-term malnutrition and leading to demyelinating changes in the brain may have been the cause of the MBD of this patient. Clinicians should increase awareness of this disease and should not ignore the diagnosis of it, even when the patient lacks a drinking history. Early diagnosis and treatment can improve the prognosis of the patient.

Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimer's disease in patients with the apolipoprotein E ϵ4 genotype.

Possession of the apolipoprotein E (APOE) ϵ4 genotype is a major predictor of progression to Alzheimer's disease (AD), particularly in patients with mild cognitive impairment (MCI). However, the use of APOE genotyping in the diagnosis of MCI is limited due to its low sensitivity and specificity, which often results in a high false-positive rate. In this study, we found that there was a significant decrease in serum BDNF and notable increase in urine AD7c-NTP in MCI patients who harbored the APOE ϵ4 allele. Both serum BDNF and urine AD7c-NTP had higher positive predictive values and were more sensitive biomarkers of MCI. Additionally, a testing strategy employing serum BDNF and urine AD7c-NTP revealed increases in sensitivity, positive and negative predictive values, and predictive ability compared with the use of either biomarker alone, suggested that combinatorial detection might have great potential for translation to the clinic.

Amphiphilic phosphoprotein-controlled formation of amorphous calcium carbonate with hierarchical superstructure.

Amorphous calcium carbonate (ACC) plays important roles in biomineralization, and the phosphoproteins extracted from biogenic stable ACC can induce and stabilize synthetic ACC in vitro. Here, mineralization of square-shaped ACC plates with micrometer-sized channels has been reported in the presence of the amphiphilic phosphoprotein casein. Casein can be assumed to take a key role during ACC plate formation, where it serves as an effective stabilization agent for ACC and assembles spherical ACC particles into ACC plates. The stabilizing effect of casein arises from the electrostatic attraction between phosphate groups as well as carbonate groups (especially the former) and the calcium ions, preventing the transformation from unstable ACC to the more stable crystalline phase of CaCO(3). The assembling effect of casein mainly comes from the hydrophobic interaction between casein molecules bound on CaCO(3) particle surface. The inclusion of casein in ACC plates revealed by the thermogavimetric analysis confirms the proposed stabilizing and assembling mechanism. The ability to fabricate such novel hierarchical structured ACC holds the promise for creating more complex micro- and nanostructured materials by use of biological proteins with special structure.