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Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Genetic variations and the expression profile of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are involved in the invasion and metastasis of colorectal cancer. The gene profiles of TIMP2 and MMP were assayed from 333 colorectal cancer using polymerase chain reaction-restriction fragment length polymorphism. TIMP2-418*G/* G, TIMP2 303* G/* G and MMP9-1562*C/* C were more frequent in patients than in controls ( P = 0.020, P < 0.0001 and P < 0.044, respectively). Frequency of TIMP2-418* G/* G was higher in patients with metastasis than in those without metastasis, and that of TIMP2 303* G/* G was higher in patients with rectal cancer than in those with colon cancer ( P = 0.008 and P = 0.022, respectively). TIMP2-303* A/* A and MMP2-1575* G/* G were less frequent in patients than in controls ( P = 0.001 and P = 0.005, respectively). The TIMP2-418* G303* G haplotype was more frequent ( P < 0.0001) and MMP2-1575* G-735* C haplotype was less frequent in patients than in controls ( P = 0.005). Specific single-nucleotide polymorphism in TIMP2 and MMP appeared to be associated with tumorigenesis and biological behavior in colorectal cancer, which is expected be further verified in a larger cohort in the future. [ABSTRACT FROM AUTHOR]

Objective. The T cell co-stimulatory factors CD28 and CTLA-4 and their ligands CD80 and CD86 occur as receptors on T cells and antigen-presenting cells and also in soluble forms in the circulation. We determined the levels of soluble co-stimulatory molecules in patients with abdominal aortic aneurysm (AAA) and normal individuals. We further correlated these soluble co-stimulatory molecules to other clinical parameters of importance such as age of the patient, presence of hypertension, size of the aneurysm and levels of matrix metalloproteinases-9 and C-reactive protein. Design, setting, subjects. This case-control study was designed to quantify the circulating levels of soluble co-stimulatory molecules by an in-house enzyme linked immunosorbent assay. A total of 314 subjects participated in the study including 100 patients and 214 normal controls. The statistical analysis was performed by Mann–Whitney test and Spearman's correlation rank test. Results. Our results show increased plasma levels of sCD28, sCD86 ( P = 0.0001) and decreased plasma levels of sCTLA-4 ( P = 0.0018) in the patients compared with normal individuals. The levels of these factors were not related to the age of the patient, size of aneurysm or levels of C-reactive protein in plasma. There was, however, a significant inverse relationship between the concentrations of sCTLA-4 and sCD80 with matrix metalloproteinase-9. Conclusions. We suggest that soluble co-stimulatory molecules serve as biomarkers for the estimation of immune activation in AAA patients. [ABSTRACT FROM AUTHOR]