Search

Hyperglycaemic memory refers to the damages occurred under early hyperglycaemic environment in organs of diabetic patients persisting after intensive glycaemic control. Mammalian sterile 20-like kinase 1 (Mst1) contributes to the development of diabetic cardiomyopathy. Here, we investigated the role of Mst1 in hyperglycaemic memory and test the effect of XMU-MP-1, a Mst1 inhibitor, on hyperglycaemic memory in hearts. Eight weeks after induction of type 1 diabetes by injection with streptozotocin (STZ) in mice, glycaemic control was obtained by means of insulin treatment and maintained for 4 additional weeks. In the diabetic mice, insulin treatment alone did not reduce phosphorylation of Mst1 or improve cardiac function. Treatment with XMU-MP-1 alone immediately after induction of diabetes for 12 weeks did not improve myocardial function in mice. But treatment with XMU-MP-1 for the later 4 weeks relieved myocardial dysfunction when glycaemic control was obtained by insulin treatment simultaneously. Mst1 deficiency and glycaemic control synergistically improved myocardial function and reduced apoptosis in myocardium of diabetic mice. Mechanistically, when Mst1 was deficient or inhibited by XMU-MP-1, AMPK was activated and mitochondrial dysfunction was attenuated. In vitro, treatment with AMPK activator reversed the detrimental effects of Mst1 overexpression in cultured cardiomyocytes. XMU-MP-1 might thus be envisaged as a complement for insulin treatment against diabetic cardiomyopathy.

Background and Purpose Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats. Experimental Approach Rats were injected with a single i.p. injection of STZ (60 mg·kg−1) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg−1·d−1 of 0.28 mol·L−1 NaHS, a donor of H2S) for 14 weeks. Key Results Treatment with H2S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H2S enhanced H2S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H2S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H2S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation. Conclusions and Implications Treatment with H2S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.

We aimed to evaluate the diagnostic accuracy of a combination of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) values in lesions that manifest with architectural distortion (AD) on mammography.All full-field digital mammography (FFDM) images obtained between August 2010 and January 2013 were reviewed retrospectively, and 57 lesions showing AD were included in the study. Two independent radiologists reviewed all mammograms and MRI data and recorded lesion characteristics according to the BI-RADS lexicon. The gold standard was histopathologic results from biopsies or surgical excisions and results of the two-year follow-up. Receiver operating characteristic curve analysis was carried out to define the most effective threshold ADC value to differentiate malignant from benign breast lesions. We investigated the sensitivity and specificity of FFDM, DCE-MRI, FFDM+DCE-MRI, and DCE-MRI+ADC.Of the 57 lesions analyzed, 28 were malignant and 29 were benign. The most effective threshold for the normalized ADC (nADC) was 0.61 with 93.1% sensitivity and 75.0% specificity. The sensitivity and specificity of DCE-MRI combined with nADC was 92.9% and 79.3%, respectively. DCE-MRI combined with nADC showed the highest specificity and equal sensitivity compared with other modalities, independent of the presentation of calcification.DCE-MRI combined with nADC values was more reliable than mammography in differentiating the nature of disease manifesting as primary AD on mammography.

Objective To describe the clinical characteristics and diagnostic features of giant lymph node hyperplasia or Castleman’s disease found in rare locations.

The peripheral neutrophils are one of the main inflammatory cells and significantly influence the damage of endothelium. Type 2 diabetes is a manifestation of an ongoing low-grade inflammation. In diabetes, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation were detected, which associated closely with adhesion molecules expressed on neutrophils and endothelial cells. To detect the expression of syndecan-1 on neutrophils in patients with type 2 diabetes mellitus, we recruited 29 patients with type 2 diabetes mellitus without any diabetic complication and 24 healthy subjects (controls). Expression of syndecan-1 was determined by flow cytometry, and potential correlations between syndecan-1 and clinical characteristics were analyzed. On neutrophils, percentage of positive syndecan-1 cells was significantly higher in subjects with diabetes (10.363 ± 1.689%) than that of the controls (3.775 ± 0.634%, P = 0.001). An association between body mass index (BMI) and percentage of positive syndecan-1 neutrophils was detected (r = 0.415, P = 0.025). When BMI was categorized into subgroups of ≤25 kg/m2 (n = 10) and >25 kg/m2 (n = 19), the average percentages of positive syndecan-1 neutrophils in patients with diabetes were 5.733 ± 1.842% and 12.642 ± 2.251%, respectively (t = −2.137, P = 0.042). A multiple regression analysis showed that BMI (β = 0.783, P < 0.000) was a significant predictor of positive syndecan-1 neutrophils in subjects with type 2 diabetes.

Summary Background Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a dismal prognosis. Despite intensive study on tumor biology, the underlying mechanisms of the unlimited proliferation and progressive local invasion are still poorly understood, and no effective treatment has been developed for GBM patients. Aims We determine the role of TRPM7 channels in the growth, migration, and infiltration of malignant glioma cells. Methods Using a combination of RT-PCR, Western blot, and patch-clamp techniques, we demonstrated the expression of functional TRPM7 channels of A172 cells, a human glioma cell line, as well as in human glioma tissues. Furthermore, we evaluated the role of TRPM7 in growth, migration, and infiltration of A172 cells with MTT and transwell migration and invasion assays. Results We showed the expression of functional TRPM7 channels in both A172 cells and human glioma tissues. Suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration, and invasion of A172 cells. Pharmacological inhibition of TRPM7 channel with 2-aminoethoxydiphenyl borate (2-APB) showed a similar effect as TRPM7-siRNA. Conclusion We demonstrate that human glioma cells express functional TRPM7 channel and that activation of this channel plays an important role in the proliferation, migration, and invasion of malignant glioma cells. TRPM7 channel may represent a novel and promising target for therapeutic intervention of malignant glioma.

Purpose: To describe a case of frosted branch angiitis in a patient with tuberculous meningitis.Methods: Case report.Results: A 27-year-old woman of tuberculous meningitis was referred to us complaining of blurred vision for 2 days. Prominent white sheathing of the retinal venules and, to a much lesser extent, arterioles, consistent with frosted branch angiitis were also observed in both eyes. And after treatment with systemic anti-tuberculosis medications and steroid, frosted branch angiitis showed resolution.Conclusions: Frosted branch angiitis can be caused by Mycobacterium tuberculosis. Systemic anti-tubercular therapy and steroids were effective.

The expression of hypoxia inducible factor-1 alpha (HIF-1alpha) and its relationship to apoptosis in tissues around cerebral bleeding loci was studied. The expression of HIF-1alpha and apoptosis in 37 samples of tissues around cerebral bleeding loci and 9 samples of normal cerebral tissues was assessed by immunohistochemical straining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling methods. In 37 tissue samples around cerebral bleeding loci, the positive rate of the HIF-1alpha expression was 40.6%. Especially in the patients with amount of bleeding60 ml, the positive rate (88.9%) of the HIF-1alpha expression was significantly higher than those with the amount of bleeding ranging from 30-45 ml or 45-60 ml (P0.05). The expression of HIF-1alpha was increased as the amount of bleeding and operative time increased (P0.05). There existed a positive correlation between HIF-1alpha labeling index and apoptosis index (n=12, r=0.56, P0.01). These results suggested that the expression of HIF-1alpha was closely related with the time of hemorrhage and the amount of bleeding, and could induce the apoptosis of neurons.

Heparan sulfate proteoglycans (HSPGs) are involved in the regulation of cell growth, apoptosis and lipid metabolism in vitro. Syndecans are the primary form of HSPGs. Syndecan-1 is involved in the processes of cell growth, differentiation, adhesion, wound healing and inflammation. Additionally, as a sinusoidal transmembrane HSPG facing the plasma compartment, syndecan-1 is a promising target to be involved in lipoprotein physiology. We aimed to examine the possible correlation of syndecan-1 and lipid profile in type 2 diabetes mellitus. In this study, serum syndecan-1 was detected by ELISA, and potential correlations between syndecan-1 and triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein a, apolipoprotein (apo) B, apoA1 and apoB/apoA1 were analyzed. Forty-one patients with type 2 diabetes and 31 age-matched, non-diabetic healthy subjects (controls) were enrolled. Syndecan-1 in patients with diabetes (26.15 ± 2.42 ng/ml) was significantly higher than that of the controls (16.85 ± 1.98 ng/ml, t = −2.98, P = 0.005). Serum syndecan-1 level correlated negatively with apoA1 (r = −0.46, P = 0.003). Multiple regression analysis showed that apoA1 (b = −0.43, P = 0.003) was a predictor of serum syndecan-1 levels in subjects with type 2 diabetes.

The new disease entity, hypokalemic flabbiness, is an endemic and epidemic hypokalemic paralytic disease found in recent twenty years mainly in certain rural districts in China where cotton is produced. We have carried out extensive investigations and deep-going research work on it for more than ten years. The following preliminary conclusions were drawn: (1) This disease does not belong to the group of well known hypokalemic paralysis of different origins (such as hypokalemic periodic paralysis and Cohn’s disease, etc.). It refers to a new clinical entity which was first discovered and described in China. Up to the present it has not yet been reported in medical literature abroad. (2) Its etiology is very closely related to the gossypol in the raw cotton seed oil usually taken by the inhabitants living in the endemic areas. (3) Pathologically and pathophysiologically, there are evidences of renal tubular damage and renal tubular acidosis, and the loss of body potassium is via kidney. Allergic reaction may presumably take part in the pathogenesis of this disease.