A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway.

Stroke is a leading cause of disability and death in the worldwide. Therefore, prevention of stroke is critically important. Genistein, a natural phytoestrogen extracted from soybeans, has been found to be a potential neuroprotective agent for stroke prevention. However, the role of genistein and its underlying mechanism in ovariectomized rats has been rarely evaluated. In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. Seventy-two hours after reperfusion, the neurological function was evaluated by Garcia test, infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride staining; and neuronal damage and cell apoptosis were detected by Nissl and Tunel staining in the ischemic penumbra, respectively. In addition, Western blotting was used to detect the activity of PI3K-Akt-mTOR signal pathway in the ischemic penumbra in different groups. And we found that genistein treatment in ovariectomized rats significantly improved neurological outcomes, reduced infarct volumes, decreased neuronal damage and cell apoptosis, and increased the activity of PI3K-Akt-mTOR signal pathway. Our findings indicated that treatment genistein could alleviate neuronal apoptosis induced by cerebral ischemia in ovariectomized rats via promoting the activity of PI3K-Akt-mTOR signal pathway, which provides a new molecular mechanism for the neuroprotective effects of genistein against stroke.

Incidental extracerebral findings on brain nonenhanced magnetic resonance imaging: frequency, nondetection rate, and clinical importance.

PURPOSE: This study aims to elucidate the frequency, nondetection rate, and clinical importance of incidental extracerebral findings (IECFs) on brain nonenhanced magnetic resonance imaging (MRI). METHODS: A total of 8284 brain MRIs performed between January 1, 2015 and December 31, 2015 were evaluated for the presence of IECFs and the distribution of IECFs was analyzed. IECFs were categorized as E1 (clinically unimportant, e.g., sinus mucosal thickening); E2 (likely unimportant, e.g., pharyngeal mucosal symmetrical thickening); and E3 (potentially important, e.g., pharyngeal mucosal asymmetrical thickening). The nondetection rate was determined by comparing the results of the structured approach with the initial MRI reports. The medical records were examined for patients with E3 IECFs to assess clinical importance and outcome of these lesions. RESULTS: A total of 5992 IECFs were found in 4469 of the 8284 patients (54.0%). E1 findings constituted 82.2% (4924/5992) of all IECFs; E2 constituted 16.6% (995/5992) and E3 constituted 1.2% (73/5992). Overall IECFs and E1 findings were significantly more common in male patients (P < 0.05). Statistically significant difference was also seen between the different age groups (P < 0.001). The nondetection rate was 56.9% (3409/5992) for overall IECFs and 32.9% (24/73) for E3 IECFs. Of the 73 patients with E3 IECFs, 34 (46.6%) received final diagnosis and appropriate treatment during the study period. CONCLUSIONS: IECFs are prevalent in clinical patients on brain MR images with a nondetection rate of 32.9% for potentially important (E3) findings. The reporting of IECFs according to clinical importance is helpful for patients' management.

SIRT2 inhibition exacerbates neuroinflammation and blood-brain barrier disruption in experimental traumatic brain injury by enhancing NF-κB p65 acetylation and activation.

Sirtuin 2 (SIRT2) is a member of the sirtuin family of NAD(+) -dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI). We investigated the effects of SIRT2 inhibition on experimental TBI using the controlled cortical impact (CCI) injury model. Adult male mice underwent CCI or sham surgery. A selective brain-permeable SIRT2 inhibitor, AK-7, was administrated 30 min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with AK-7 (20 mg/kg), compared with the vehicle group, following TBI (p < 0.05 at 1 day and p < 0.05 at 3 days, respectively). Concomitantly, AK-7 administration greatly worsened neurobehavioral deficits on days 3 and 7 after CCI. Furthermore, blood-brain barrier disruption and matrix metalloproteinases (MMP)-9 activity increased following SIRT2 inhibition. AK-7 treatment increased TBI-induced microglial activation both in vivo and in vitro, accompanied by a large increase in the expression and release of inflammatory cytokines. Mechanistically, SIRT2 inhibition increased both K310 acetylation and nuclear translocation of NF-κB p65, leading to enhanced NF-κB activation and up-regulation of its target genes, including aquaporin 4 (AQP4), MMP-9, and pro-inflammatory cytokines. Together, these data demonstrate that SIRT2 inhibition exacerbates TBI by increasing NF-κB p65 acetylation and activation. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. SIRT2 is a member of the sirtuin family of NAD+-dependent protein deacetylases. Our study suggests that the SIRT2 inhibitor AK-7 exacerbates traumatic brain injury (TBI) via a potential mechanism involving increased acetylation and nuclear translocation of NF-κB p65, resulting in up-regulation of NF-κB target genes, including aquaporin 4 (AQP4), matrix metalloproteinase 9 (MMP-9), and pro-inflammatory cytokines. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2.

Cutaneous Rosai-Dorfman disease recurrence in infraorbital region.

Rosai-Dorfman disease (RDD), also named sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic, and benign disorder that classically presents as a painless massive bilateral cervical lymphadenopathy. In cases of extranodal presentations, such as cutaneous RDD, it may not involve the classic manifestation. The diagnosis is usually made by histopathologic analysis. Surgery is suggested in the cases of significant cosmetic deformity or when there is fatal or functional obstruction. We reported a case of extranodal RDD that recurred in the infraorbital region postoperatively.

[Effects of lysyl oxidase down-regulation on invasion, migration and E-cadherin protein expression of hypoxic lung cancer cells].

OBJECTIVE: To observe the effects of lysyl oxidase (LOX) down-regulation on invasion, migration and epithelial-mesenchymal transition phenotype molecule E-cadherin protein expression, induced by hypoxia in lung cancer NCI-H460 cells. METHODS: Small interfering RNA against human LOX gene (LOX siRNA) was used to transfect lung cancer cells under normoxia (19%O2). After a 24 h incubation, the cells were plated for 24 h in hypoxic incubator (0.5%O2). Real-time polymerase chain reaction (PCR) was performed to detect the LOX mRNA expression. The protein levels of LOX and E-cadherin were determined by Western blot. And invasion and migration capacities were detected by transwell chamber. RESULTS: Compared with NCI-H460 cells under normoxia (set to 1), hypoxia increased to the levels of LOX mRNA and protein expression up to 26.04 ± 1.78 and 5.57 ± 1.27 respectively (both P < 0.05). Compared with control siRNA group (set to 1), LOX mRNA and protein expression after LOX siRNA transfection were 0.24 ± 0.03 and 0.29 ± 0.03 respectively, cellular invasive and migratory capacities were 0.57 ± 0.03 and 0.49 ± 0.02 respectively, the protein expression of E-cadherin was 2.17 ± 0.21 (all P < 0.05). CONCLUSION: LOX down-regulation reduces invasion and migration potentials of hypoxic human lung cancer cell and potentiates the protein expression of E-cadherin.

[Association of gene polymorphisms in the DNA repair gene XPD with risk of non-Hodgkin's lymphoma].

This study was aimed to explore the relationship between the single nucleotide polymorphisms of XPD (G23591A, A35931C) and individual susceptibility to non-Hodgkin's lymphomas (NHL) in Shandong populations. XPD gene polymorphism in 309 cases of NHL and 305 healthy controls were detected using PCR-restriction fragment length polymorphism assay in a case-control molecular epidemiology study. The association between gene polymorphism and the risk of NHL were examined through comparing odds ratio (OR) and 95% confidence interval (CI) between two groups. The results showed that no significant association between the XPD (G23591A, A35931C) polymorphism and the risk of whole NHL was shown at first. In the further analysis, all NHL cases were divided into four groups: follicular lymphoma (FL) group, diffuse large B-cell lymphoma (DLBCL) group, T-cell lymphoma group and other B-cell lymphoma group. Frequencies of XPD 23591GA + AA genotypes were 16.3%, 18.0%, 10.5% and 18.4% in each subgroup respectively, while 12.5% in control. Individuals carrying GA + AA genotype had 1.43, 1.58, 0.89 and 1.50-fold risk of NHL sub groups as much as GG genotype, but no statistically significant difference between subgroups and control was found (p>0.05); frequencies of XPD 35931AC + CC genotypes were 15.2%, 15.8%, 18.4% and 12.5% in each subgroup, while 11.5% in control. Individuals carrying AC + CC genotype had 1.41, 1.48, 1.75 and 1.12-fold risk of NHL subgroup as much as AA genotype, but there were also no statistically significant difference between each subgroup and control (p>0.05). It is concluded that the gene polymorphism of XPD (G23591A, G935931C) does not associate with the risk of developing NHL in Shandong populations.