Early Renal-Protective Effects of Remote Ischemic Preconditioning in Elderly Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI).

BACKGROUND With the wide clinical application of angiography, contrast-enhanced nephropathy (CIN) has become the third-leading cause of acute kidney injury (AKI). Remote ischemic preconditioning (RIPC) is a non-fatal ischemia-reperfusion injury that can provide protection against lethal ischemia-reperfusion. This study aimed to assess the effect of RIPC on CIN in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS Patients were randomly divided into 2 groups with 119 patients in each group treated with interventional therapy. Patients in the RIPC group received distal ischemic preconditioning 2 h before contrast exposure, while patients in the control group received a sham RIPC procedure. Incidence of CIN was the primary outcome. Changes in creatinine, NGAL, and KIM-1 after contrast administration were secondary outcomes. RESULTS CIN occurred in a total of 27 (12.3%) patients, including 12 (10.1%) in the RIPC group and 15 (15.1%) in the control group (P=0.329). RIPC treatment significantly reduced the levels of NGAL (P=0.024) and KIM-1 (P=0.007) at 12 h after contrast administration, suggesting RIPC treatment reduces sub-clinical renal damage. Subgroup analysis revealed that significant reduction of KIM-1 and NGAL by RIPC, mainly occurring in patients with a Mehran risk score of 6-10. CONCLUSIONS Although RIPC did not significantly reduce CIN incidence in elderly patients with NSTEMI, the application of more sensitive biomarkers - NGAL and KIM-1 - indicated a reduction of sub-clinical renal damage by RIPC, especially in the early stage of injury. As a simple and well-tolerated method, RIPC may be a potentially feasible option to prevent CIN.

Preparation and Macro-Micro Properties of SBS/REOB Modified-Rejuvenated Asphalt.

To solve the problem that waste oil residues cannot be utilized and to reuse the aged asphalt, suitable modifiers were selected to compound the aged asphalt with waste oil residues to study its performance. SBS/REOB modified-rejuvenated asphalt was prepared by a high-speed shearing mechanism with aged asphalt, Recycled Engine Oil Bottom (REOB), Styrenic Block Copolymers (SBS) modifier, and stabilizer. The effects of SBS content, REOB content, shear time, and shear rate on the conventional physical properties of asphalt were studied by orthogonal grey correlation analysis, and the optimum preparation scheme of SBS/REOB modified-rejuvenated asphalt was determined. The high and low temperature rheological properties of SBS/REOB modified-rejuvenated asphalt were studied using the Multiple Stress Creep Recover (MSCR) test and bending beam rheological (BBR) test. The mechanism of SBS/REOB on the modification and regeneration of aged asphalt was explored through four component tests and Fourier transforms infrared spectroscopy. The results show that the optimum preparation scheme is 4.5% SBS dosage, 9% REOB dosage, 50~60 min shear time, and 4500 r/min shear rate. The addition of SBS improves the elastic recovery performance and high temperature deformation resistance of REOB rejuvenated asphalt. At the same time, the S-value decreases and the m-value increases, which significantly improves the low temperature cracking resistance of REOB rejuvenated asphalt. The addition of REOB achieves component blending and regeneration of aged asphalt by supplementing the light components. After the addition of SBS absorbs the light component and swelling reaction occurs, the whole modification-regeneration process is mainly physical co-mixing and co-compatibility.

Abnormal Mitochondria-Endoplasmic Reticulum Communication Promotes Myocardial Infarction.

Myocardial infarction is characterized by cardiomyocyte death, and can be exacerbated by mitochondrial damage and endoplasmic reticulum injury. In the present study, we investigated whether communication between mitochondria and the endoplasmic reticulum contributes to cardiomyocyte death after myocardial infarction. Our data demonstrated that hypoxia treatment (mimicking myocardial infarction) promoted cardiomyocyte death by inducing the c-Jun N-terminal kinase (JNK) pathway. The activation of JNK under hypoxic conditions was dependent on overproduction of mitochondrial reactive oxygen species (mtROS) in cardiomyocytes, and mitochondrial division was identified as the upstream inducer of mtROS overproduction. Silencing mitochondrial division activators, such as B cell receptor associated protein 31 (BAP31) and mitochondrial fission 1 (Fis1), repressed mitochondrial division, thereby inhibiting mtROS overproduction and preventing JNK-induced cardiomyocyte death under hypoxic conditions. These data revealed that a novel death-inducing mechanism involving the BAP31/Fis1/mtROS/JNK axis promotes hypoxia-induced cardiomyocyte damage. Considering that BAP31 is localized within the endoplasmic reticulum and Fis1 is localized in mitochondria, abnormal mitochondria-endoplasmic reticulum communication may be a useful therapeutic target after myocardial infarction.

miR-146b-5p inhibits glioma migration and invasion by targeting MMP16.

miR-146b-5p is frequently down-regulated in solid tumours, including prostate cancer, pancreatic cancer, and glioblastoma. However, the tumour-suppressive effects of miR-146b-5p in malignant gliomas have not been investigated thoroughly. Here, we found that decreased miR-146b-5p expression was strongly correlated with chromosome 10q loss in gliomas, especially glioblastomas. The overexpression of miR-146b-5p in glioblastoma cell lines led to MMP16 mRNA silencing, MMP2 inactivation, and the inhibition of tumour cell migration and invasion. Our results suggest that the restoration of miR-146b-5p expression may be a feasible approach for inhibiting the migration and invasion of malignant gliomas.

Tumor-suppressive effects of miR-29c on gliomas.

Although miR-29c has been shown to be expressed less in various kinds of solid cancers, its expression pattern and tumor-suppressive effects in gliomas remain largely unknown. In this study, we detected miR-29c in 10 nontumoral brain tissues and 60 gliomas of various grades and found that its labeling indexes were significantly lower in gliomas (53.7% for the nontumoral brain tissues, and 18.9, 5.5, and 1.8% for the WHO grade I-II, grade III, and grade IV glioma groups, respectively). We then overexpressed miR-29c in the SNB19 glioblastoma cell line and found that it markedly downregulated the expression level of CDK6, and accordingly increased the percentage of the tumor cells in the G1 phase from 44.5 to 69.1% and decreased the colony formation efficiency from 81.1 to 51.5%. miR-29c overexpression also increased the percentage of apoptotic cells from 27.2 to 54.8%, and led to a more than 50% decrease in the migratory and invasive abilities of the tumor cells. Our study shows that miR-29c can effectively block the proliferation of glioblastoma cells by inducing G1 arrest, promote their apoptosis, and inhibit their migration and invasion. At least some of its tumor-suppressive effects are mediated by specifically downregulating the expression of CDK6. Therefore, miR-29c can be used as a tumor suppressor in the gene therapy of malignant gliomas.