Interferon regulatory factor 8 protects against cerebral ischaemic-reperfusion injury.

Interferon regulatory factor 8 (IRF8), a transcriptional regulator in the IRF family, has been implicated in innate immunity, immune cell differentiation and tumour cell apoptosis. In the present study, we found that IRF8 is constitutively expressed in the brain and suppressed after cerebral ischaemia in a time-dependent manner. IRF8 knockout (IRF8-KO) mice, wild type (WT) mice, neuron-specific IRF8 transgenic (TG) mice and non-transgenic mice were used in a transient cerebral ischaemic model. The IRF8 knockout mice exhibited aggravated apoptosis, inflammation and oxidative injury in the ischaemic brain, eventually leading to poorer stroke outcomes, whereas neuron-specific IRF8 transgenic mice showed a marked inhibition of apoptosis and improved stroke outcomes. To model ischaemia/reperfusion conditions in vitro, primary cortical neurons were cultured and subjected to transient oxygen and glucose deprivation for 60 min. Similar to the in vivo study, IRF8 knockdown by Ad-shIRF8 resulted in increased apoptosis, whereas IRF8 over-expression by Ad-IRF8 significantly decreased neuronal apoptosis. These data indicate that IRF8 is strongly protective in ischaemic stroke by regulating neuronal apoptosis, the inflammatory response and oxidative stress. In the present study, we found that the transcriptional factor IRF8 plays a protective role in the cerebral ischaemic-reperfusion injury by attenuating neuronal apoptosis, oxidative stress and inflammation. Besides the known function of IRF8 in regulating the inflammatory gene expression, we first demonstrated that IRF8 can directly modulate apoptosis and oxidative stress by controlling the relative genes expression.

TRAF1 is a critical regulator of cerebral ischaemia-reperfusion injury and neuronal death.

Stroke is a leading global cause of mortality and disability. Less than 5% of patients are able to receive tissue plasminogen activator thrombolysis within the necessary timeframe. Focusing on the process of neuronal apoptosis in the penumbra, which lasts from hours to days after ischaemia, appears to be promising. Here we report that tumour necrosis factor receptor-associated factor 1 (TRAF1) expression is markedly induced in wild-type mice 6 h after stroke onset. Using genetic approaches, we demonstrate that increased neuronal TRAF1 leads to elevated neuronal death and enlarged ischaemic lesions, whereas TRAF1 deficiency is neuroprotective. In addition, TRAF1-mediated neuroapoptosis correlates with the activation of the JNK pro-death pathway and inhibition of the Akt cell survival pathway. Finally, TRAF1 is found to exert pro-apoptotic effects via direct interaction with ASK1. Thus, ASK1 positively and negatively regulates the JNK and Akt signalling pathways, respectively. Targeting the TRAF1/ASK1 pathway may provide feasible therapies for stroke long after onset.

Association of estrogen receptor alpha gene polymorphisms with bone mineral density: a meta-analysis.

BACKGROUND: A number of studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD), but previous studies of ESR-α gene XbaI (rs9340799) and PvuII (rs2234693) polymorphisms have been hampered by small sample size, regional restrictions and inconclusive results. Thus a meta-analysis is needed to assess their pooled effects. METHODS: This study reviewed all published articles indexed in Pubmed using the keywords in the title or abstract. All data were extracted independently by two reviewers using a standard form, the studies were meta-analyzed and minor discrepancies were resolved by authors' discussion. RESULTS: Twenty seven eligible studies involving 8467 women and 2032 men were identified. The XbaI and PvuII polymorphisms were significantly associated with BMD of the lumbar spine. XX and PP homozygotes had a protective effect in comparison with carriers of the x and p alleles, the effects were more significant in premenopausal women or Western women. At the femoral neck, the results were different. XX served as a protective factor in postmenopausal women, Western women, Western postmenopausal women, and men, while PP was likely to serve as a risk factor in Eastern women, Eastern postmenopausal women, and men. CONCLUSIONS: The XbaI polymorphism is correlated to BMD at diverse skeletal sites. PP had a protective role for the lumbar spine but might be a risk factor for the femoral neck.

1-[2,2-Bis(1,3-benzimidazol-1-ylmeth-yl)-3-bromo-prop-yl]-1,3-benzimidazole.

The title compound, C(26)H(23)BrN(6), has been synthesized as a potential ligand for the construction of metal-organic frameworks. The three benzimidazolyl groups present three potential coordination nodes. The dihedral angles between the benzimidazole ring systems are 74.03 (10), 66.49 (9) and 74.09 (9)°. The structure contains large voids, which contain highly disordered solvent mol-ecules that may be CH(3)CH(2)OH. Since the solvent mol-ecules could not be located, the PLATON/SQUEEZE procedure [Spek (2009 ▶). Acta Cryst. D65, 148-155] was used.

1,3,5,7-Tetra-bromo-adamantane.

In the pyramidal-shaped mol-ecule of the title compound, C(10)H(12)Br(4), the four terminal Br-C bond distances are nearly identical, ranging from 1.964 (4) to 1.974 (4) Å. The Br⋯Br distance of 3.6553 (7) Šindicates van der Waals contacts between mol-ecules in the crystal structure.

[Treatment of critically ill influenza A H1N1 patients in plateau region].

OBJECTIVE: To discuss the strategy of treatment of critically ill influenza A H1N1 patients in plateau region. METHODS: Four seriously ill and 4 critically ill patients suffering from influenza A H1N1 were admitted to the intensive care unit during October 10th through December 19th 2009. They were treated with antivirus drug, antibiotics, corticosteroid, measures to enhance immune function, fluid and electrolyte supplementation, symptomatic treatment, and mechanical ventilation. With their clinical data the distinguishing features in the treatment of these patients were analyzed. RESULTS: Oseltamivir as an antivirus drug, and moxifloxacin together with ceftriaxone or cefoperazone were given to all the patients. Fluid replacement was controlled to avoid over hydration. Corticosteroid was administered to 3 seriously ill patients and 3 critically ill patients. Methylprednisolone was given to 1 critically ill patient. gamma-globulin was given to 7 patients. Four patients underwent atraumatic mechanical ventilation with bi-level positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP) with good result. Owing to deterioration in respiratory function, traumatic mechanical ventilation was instituted in a critically ill patient, primarily with synchronized intermittent mandatory ventilation (SIMV)+pressure support ventilation (PSV)+high positive end expiratory pressure (PEEP). The condition of the patient was improved, and ventilation modality was changed to spontaneous respiration+PSV+low PEEP before weaning. Finally the patient was weaned from respirator successfully. All the 8 patients survived and discharged from the hospital. CONCLUSION: Short term, full dosage of corticosteroid should be given to seriously ill and critically ill influenza A H1N1 patients according to specification, and atraumatic mechanical ventilation should be installed early in the treatment.