Hyperglycemia Aggravates the Cerebral Ischemia Injury via Protein O-GlcNAcylation.

BACKGROUND: At least one-third of Alzheimer's disease (AD) patients have cerebrovascular abnormalities, micro- and macro-infarctions, and ischemic white matter alterations. Stroke prognosis impacts AD development due to vascular disease. Hyperglycemia can readily produce vascular lesions and atherosclerosis, increasing the risk of cerebral ischemia. Our previous research has demonstrated that protein O-GlcNAcylation, a dynamic and reversible post-translational modification, provides protection against ischemic stroke. However, the role of O-GlcNAcylation in the exacerbation of cerebral ischemia injury due to hyperglycemia remains to be elucidated. OBJECTIVE: In this study, we explored the role and underlying mechanism of protein O-GlcNAcylation in the exacerbation of cerebral ischemia injury caused by hyperglycemia. METHODS: High glucose-cultured brain microvascular endothelial (bEnd3) cells were injured by oxygen-glucose deprivation. Cell viability was used as the assay result. Stroke outcomes and hemorrhagic transformation incidence were assessed in mice after middle cerebral artery occlusion under high glucose and streptozotocin-induced hyperglycemic conditions. Western blot estimated that O-GlcNAcylation influenced apoptosis levels in vitro and in vivo. RESULTS: In in vitro analyses showed that Thiamet-G induces upregulation of protein O-GlcNAcylation, which attenuates oxygen-glucose deprivation/R-induce injury in bEnd3 cells cultured under normal glucose conditions, while aggravated it under high glucose conditions. In in vivo analyses, Thiamet-G exacerbated cerebral ischemic injury and induced hemorrhagic transformation, accompanied by increased apoptosis. While blocking protein O-GlcNAcylation with 6-diazo-5-oxo-L-norleucine alleviated cerebral injury of ischemic stroke in different hyperglycemic mice. CONCLUSION: Overall, our study highlights the crucial role of O-GlcNAcylation in exacerbating cerebral ischemia injury under conditions of hyperglycemia. O-GlcNAcylation could potentially serve as a therapeutic target for ischemic stroke associated with AD.

[Analysis of the changes in bacterial types and drug sensitivity profiles of mycobacterial strains in Guangzhou over the last twelve years].

OBJECTIVE: To improve evidence-based care in the management of tuberculosis, we retrospectively analyzed the bacterial types and drug sensitivity test results of mycobacteria in Guangzhou over the past twelve years (from July 1998 to March 2010). METHODS: Over these twelve years, a total of 14 095 mycobacterial strains isolated from different samples were subjected to type identification and drug sensitivity tests according to the Standard Protocols of Laboratory Diagnostics for Tuberculosis by the Chinese Antituberculosis Association. Chi-square test was performed for statistical analyses for comparisons between groups. RESULTS: Of 14 095 strains of mycobacteria isolated, 10 844 strains (76.84%) were MTB, and 3251 strains (23.16%) were non-tuberculosis mycobacteria (NTM). Compared with the result of the fourth national survey of tuberculosis epidemiology, which showed 11.1% of NTM, the one of our study was significantly different (χ(2) = 69.79, P < 0.001). Drug sensitivity tests of MTB showed tolerance rates of 28.99% (2729/9413), 21.75% (2047/9413), 17.45% (1643/9413) and 11.53% (1085/9413) against isoniazid, rifampin, streptomycin and ethambutol, respectively. CONCLUSION: An increasing trend was observed in MTB drug tolerance against streptomycin, rifampin and isoniazid, whereas more and more NTM strains were isolated in recent years. These findings are worthy of note for clinicians.