Vulnerability for apoptosis in the hippocampal dentate gyrus of STZ-induced diabetic rats with cognitive impairment.

BACKGROUND: Hyperglycemia impaired hippocampal network via triggering suicide program of immanent neurons, this is regarded as an etiological factor for diabetic cognition deficits. AIM: To investigate the occurrence of apoptosis in the hippocampal dentate gyrus of streptozotocin (STZ)-induced diabetic rats with cognitive impairment and assess the gene and protein expression of the apoptotic proteins bax, bcl-2, and caspase-3. MATERIALS AND METHODS: Four weeks after the verification of STZ-induced diabetes, diabetic rats with and without cognitive decline subgroups were subsequently assigned according to Morris water maze test. The expression levels of apoptotic proteins were measured using real-time RT-PCR and western blotting, respectively. Neuronal apoptosis was detected by TUNEL staining and electron microscopy. RESULTS: In the dentate gyrus of the rats with cognitive decline, Bcl-2 exhibited lower gene and protein levels, whereas a higher expression of bax was detected contributing to a significant increase in their mean bax/bcl-2 ratio. However, caspase-3 was not activated. Statistically different numbers of TUNEL-staining cells and features of apoptosis were no found. CONCLUSIONS: The higher bax/bcl ratio probably represents neurons of dentate gyrus vulnerable to apoptosis in the diabetes with cognitive decline. However, the normal caspase-3 level suggests that apoptosis is not active in this illness phase.

PPARγ-mediated advanced glycation end products regulate neural stem cell proliferation but not neural differentiation through the BDNF-CREB pathway.

AIMS: To investigate the roles of PPARγ in advanced glycation end product (AGE)-mediated characteristics of neural stem cells (NSCs) and the molecular mechanisms of action. METHODS: We prepared pLentiLox3.7 lentiviral vectors expressing short hairpin RNA (shRNA) against PPARγ and transduced NSCs. MTT absorbance and cell counts were used to assay cell growth, and cell differentiation was analysed by confocal laser-scanning and western blots for the expression of MAP2/nestin. The protein and gene expression of the BDNF-CREB pathway components were examined by western blotting and real-time PCR. RESULTS: Immunoblot analysis indicated that shRNA delivered by lentiviral vectors silenced PPARγ expression in NSCs. The proliferation of NSCs and expression of BDNF pathway components dropped in AGE-BSA culture medium (400 mg/L and 200 mg/L) on Day 3 and Day 7, respectively (all P<0.001). PPARγ-silenced NSCs exhibited a significant increase in cell growth and expression of BDNF pathway components compared with NSCs incubated with AGE-BSA (all P<0.001). Immunocytochemistry and western blotting analysis showed that AGE-BSA (400 mg/L) induced a significant decrease in the expression of MAP2 both in NSCs and PPARγ-silenced NSCs, as standardised by nestin. There was no significant difference between NSCs and PPARγ-silenced NSCs in the presence of AGE-BSA. CONCLUSIONS: PPARγ plays roles in the AGE-mediated regulation of NSC proliferation but not neural differentiation through the BDNF-CREB pathway.

Meticillin-resistant Staphylococcus aureus isolated from foot ulcers in diabetic patients in a Chinese care hospital: risk factors for infection and prevalence.

A retrospective case-control study of 118 (male : female, 68 : 50) Chinese type 2 diabetic patients with foot ulcers (Wagner's grade 3-5) was conducted to determine the prevalence and risk factors for meticillin-resistant Staphylococcus aureus (MRSA) infection in relation to the original community or hospital parameters. Ulcer specimens were processed for Gram staining, aerobic culture and antimicrobial susceptibility testing. Staphylococcus species were tested for meticillin resistance using oxacillin. S. aureus was the most frequent pathogen (25.6 %) in diabetic patient specimens (160 isolates), and a high proportion of S. aureus isolates were MRSA (63.4 %). A high percentage of S. aureus isolates (65.4 %) satisfied the definition for hospital-associated MRSA (HA-MRSA) infection. The size of ulcers [adjusted odds ratio (OR) 1.61; 95 % confidence interval (CI) 1.22-2.12] and osteomyelitis (adjusted OR 18.51, 95 % CI 2.50-137.21) were independent predictors of MRSA infection. The HA-MRSA group had a significantly different distribution from the community-associated MRSA group with respect to age, history of diabetes and length of hospital stay (all P<0.001). Neuropathy, vascular disease (all P=0.049) and osteomyelitis (P=0.026) were the most common underlying conditions observed in the HA-MRSA group. This study contributes to the establishment of precautions against the emergence of MRSA including MRSA acquired from different sources among the Chinese population with diabetic foot ulcers based on their original or clinical parameters.