Diabetes is the most common metabolic disease with many chronic complications, and cognitive disorders are one of the common complications in patients with diabetes. Previous studies have showed that autophagy played important roles in the progression of metabolic syndrome, diabetes and other diseases. So we investigated whether aged diabetic mice are prone to be associated with the cognitive and affective disorders and whether Beclin-1-mediated autophagy might be involved in thepahological process. High-fat diet/streptozotocin (STZ) injection-induced diabetic C57 mice were adopted in this study. Cognitive disorders were detected by Morris water maze and fear conditional test. Affective disorders were detected by tail suspension test and forced swimming test. Magnetic resonance imaging was applied to observe changes of morphology and metabolism in the brain. The 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to assess metabolism changes in the brain of aged diabetic mice. Autophagy were evaluated by Beclin- 1, LC3II/I and P62, which were detected by western blot analysis and observed by electron microscopy. 1. Compared with control group, diabetes mice showed significantly decreasing abilities in spatial memory and conditioned fear memory (all P < 0.05), and increasing tendency of depression (P < 0.05). 2. MRI showed that the majority of elderly diabetic mice were associated with multiple cerebral small vessel disease. Some even showed hippocampal atrophy, ventricular dilatation and leukoaraiosis. 3. FDG-PET-CT discovered that the glucose metabolism in the amygdala and hippocampus was significantly decreased compared with normal aged mice (P < 0.05). 4. Electron microscopy found that, although autophagy bodies was not widespread, and there was no significant difference between the two groups, yet compared with normal aged mice, apparent cell edema, myelinated tow reduction and intracellular lipofuscin augmentation existed in elderly diabetic mice brain. 5. The level of p62 was increased in the STZ-induced diabetic mice hippocampus and striatum, and beclin1 protein expression were significantly decreased in diabetic mice hippocampus compared with normal aged mice (P < 0.05). There was a upward trend of the ratio of LC3II/I in hippocampus, cortex and striatum, but no statistically difference between the two groups. Compared with normal aged mice, diabetic aged mice were apt to cerebral small vessel disease and associated with cognitive and affective disorders, which may be related to the significantly reduced glucose metabolism in hippocampus and amygdala. Beclin1 mediated autophagy in hippocampus probably played an important role in cognitive and affective disorders of STZ-induced aged diabetic mice.

Introduction: Diabetic cardiomyopathy is characterized by an imbalance between myocyte death and regeneration mediated by the progressive loss of cardiac stem and progenitor cells (CSPCs) by apoptosis and necrosis due to the activation of oxidative stress with diabetes. In this study, we evaluated the beneficial effect of astragalus polysaccharides (APS) therapy on the protection of CSPCs through its antioxidative capacity in diabetic hearts. Materials and methods: Streptozotocin (STZ)-induced diabetic mice and heterozygous (SOD2+/-) knockout mice were employed and administered with APS. Ventricular CSPCs were isolated for oxidative evaluation. The abundance, apoptosis and proliferation, reactive oxygen species (ROS) formation, oxidative damage, and SOD2 protein levels and activities were evaluated in ventricular CSPCs. Results: We confirmed that APS increased the CSPC abundance, reduced the apoptosis of CSPCs, and enhanced the proliferation of CSPCs in both STZ-induced diabetic mice and nondiabetic SOD2+/- mice. In addition, therapy of APS enhanced SOD2 protein levels and enzyme activities, and inhibited ROS formation and oxidative damage of CSPCs from both STZ-induced diabetic mice and nondiabetic SOD2+/- mice. Conclusion: Our findings demonstrated the positive effect of APS on the rescue of CSPC preservation in diabetes, dependent on the inhibition of oxidative stress-mediated apoptosis.

Objective. Oxidant stress plays an important role in the development of diabetic cardiomyopathy. Previously we reported that Astragalus polysaccharides (APS) rescued heart dysfunction and cardinal pathological abnormalities in diabetic mice. In the current study, we determined whether the effect of APS on diabetic cardiomyopathy was associated with its impact on oxidant stress. Methods. Db/db diabetic mice were employed and administered with APS. The hematodynamics, cardiac ultra-structure, apoptosis, and ROS formation of myocardium were assessed. The cardiac protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and oxidation target genes (Gpx, SOD2, t/p-JNK, catalase, t/p-p38 MAPK, and t/p-ERK) were evaluated, respectively. Results. APS therapy improved hematodynamics and cardinal ultra-structure with reduced apoptosis and ROS formation in db/db hearts. In addition, APS therapy inhibited the protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and regulated the protein expression of oxidation target genes (enhancing Gpx, SOD2, and catalase, while reducing t/p-JNK, t/p-ERK, and t/p-p38 MAPK) in db/db hearts. Conclusion. Our findings suggest that APS has benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidant stress.

Objective: It is unclear how alterations in gray matter volume and white matter density affect elderly patients with irritable bowel syndrome (IBS). This study aimed to investigate the relationship between structural changes in the brain and psychological stress in elderly IBS patients.Methods: Eighteen IBS patients and 12 healthy controls underwent structural magnetic resonance imaging. Voxel‐based morphometry and diffusion tensor imaging analysis were used to identify abnormalities in cortical regions and white matter, respectively.Results: The IBS group showed a significant GMV reduction in the cingulate gyrus, occipital lobe, hippocampus, frontal lobe, medial frontal gyrus, superior frontal gyrus, and limbic lobe as well as a higher GMV in the insula, superior temporal gyrus, angular gyrus, and supramarginal gyrus. Diffusion tensor imaging indicated that the IBS group had lower fractional anisotropy in the corpus callosum, upper corona, fornix, internal capsule, and brainstem. Additionally, IBS patients showed higher mean diffusivity in the cingulate gyrus, corpus callosum, upper corona, internal capsule, external capsule, fornix, and superior longitudinal fasciculus.Conclusion: Structural changes in the brain play a role in the condition of elderly IBS patients. Psychological stress is an important factor for developing IBS via the hypothalamic‐pituitary‐adrenal axis.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db^−/− mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db^−/− mice’ carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db^−/− mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db^−/− mice’ cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db^−/− mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db^−/− mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery’ vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied.