Levetiracetam attenuates diabetes-associated cognitive impairment and microglia polarization by suppressing neuroinflammation

Introduction: Cognitive impairment is a common complication and comorbidity of diabetes. However, the underlying mechanisms of diabetes-associated cognitive dysfunction are currently unclear. M1 microglia secretes pro-inflammatory factors and can be marked by CD16, iNOS, Iba1 and TNF-ɑ. The decline of M2 microglia in the diabetic rats indicates that high glucose promotes the differentiation of microglia into the M1 type to trigger neuroinflammatory responses. Moreover, there is a lack of strong evidence for treatments of diabetes-associated cognitive impairment in addition to controlling blood glucose.Methods: Diabetic rats were established by intraperitoneal injection of one dose of streptozotocin (60 mg/kg). Polarization transitions of microglia were induced by high glucose treatment in BV2 cells. Levetiracetam was orally administered to rats 72 h after streptozotocin injection for 12 weeks.Results: In STZ-induced diabetic rats, the results demonstrated that levetiracetam improved rat cognitive function (Morris water maze test) and hippocampus morphology (Hematoxylin-eosin staining), and the effect was more evident in the high-dose levetiracetam group. Microglia activation in the hippocampus was inhibited by levetiracetam treatment for 12 weeks. Serum levels of TNF-α, IL-1β, and IL-6 were reduced in the LEV-L and LEV-H groups, and IL-1β level was obviously reduced in the LEV-H group. In vitro, we found that levetiracetam 50 µM attenuated high-glucose induced microglial polarization by increasing IL-10 level and decreasing IL-1β and TNF-α levels. Moreover, levetiracetam 50 µM increased and decreased the proportion of CD206+/Iba1+ and iNOS+/Iba1+cells, respectively. Western blot analysis illustrated that LEV 50 µM downregulated the expression of MyD88 and TRAF6, and phosphorylation of TAK1, JNK, p38, and NF-κB p65. The effect of levetiracetam on the anti-polarization and expression of p-JNK and p-NF-κB p65 were partly reversed by anisomycin (p38 and JNK activators).Discussion: Together, our data suggest that levetiracetam attenuates streptozotocin-induced cognitive impairment by suppressing microglia activation. The in vitro findings also indicate that the levetiracetam inhibited the polarization of microglia via the JNK/MAPK/NF-κB signaling pathway

Effects of Herb-Partitioned Moxibustion on the miRNA Expression Profiles in Colon from Rats with DSS-Induced Ulcerative Colitis

Objective. This study explored the mechanism of herb-partitioned moxibustion (HM) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) from the miRNA perspective. Methods. Rats were randomly divided into 3 groups [normal control (NC) group, UC model (UC) group, and herb-partitioned moxibustion (UCHM) group]. The UC and UCHM groups were administered 4% DSS for 7 days. The UCHM group received HM at the Tianshu (bilateral, ST25). The effect of HM on UC was observed and the miRNA expression profile in the colon tissues was analyzed. Results. Compared with the UC group, the body weights were significantly higher in the UCHM group on day 14 (P<0.001); the macroscopic colon injury scores and microscopic histopathology scores in the UCHM group decreased (P<0.05); and there were 15 differentially expressed miRNAs in the UCHM group. The changes in miR-184 and miR-490-5p expression levels on the UC were reversed by HM intervention. Validation using qRT-PCR showed that two miRNAs expression trend was consistent with the sequencing results. Conclusion. HM at ST25 might regulate miR-184 and miR-490-5p expression, act on the transcription of their target genes to regulate inflammatory signaling pathways, and attenuate inflammation and tissue injury in the colons of rats with DSS-induced UC

Isolation and analysis of differentially expressed genes from peanut in response to challenge with Ralstonia solanacearum

Background: Bacterial wilt caused by Ralstonia solanacearum is the most devastating disease in peanut. Planting resistant peanut cultivars is deemed as the sole economically viable means for effective control of the disease. To understand the molecular mechanism underlying resistance and facilitate breeding process, differences in gene expression between seeds of Rihua 1 (a Virginia type peanut variety resistant to bacterial wilt) inoculated with the bacterial pathogen suspension (109 cfu ml-1) and seeds of the same cultivar treated with water (control), were studied using the GenefishingTM technology. Results: A total of 25 differentially expressed genes were isolated. Expression of genes encoding cyclophilin and ADP-ribosylation factor, respectively, were further studied by real time RTPCR, and full length cDNAs of both genes were obtained by rapid amplification of cDNA ends. Conclusions: The study provided candidate genes potentially useful for breeding peanut cultivars with both high yield and bacterial wilt resistance, although confirmation of their functions through transgenic studies is still needed

Mapping the history and current situation of research on John Cunningham virus – a bibliometric analysis

<p>Abstract</p> <p>Background</p> <p>John Cunningham virus (JCV) constitutes a family of polyoma viruses, which plays important roles in the progressive multifocal leukoencephalopathy (PML) and tumorigenesis. However, no bibliometric investigation has been reported to guide the researchers and potential readers.</p> <p>Methods</p> <p>Papers were collected from database Sci-expanded and Pubmed until May 22, 2008. The highly-productive authors, institutes and countries, highly-cited authors and journals were ranked. The highly-cited articles were subjected to co-citation and chronological analysis with highly-frequent MeSH words for co-occurrence analysis.</p> <p>Results</p> <p>Until now, 1785 articles about JCV were indexed in Sci-expanded and 1506 in Pubmed. The main document type was original article. USA, Japan and Italy were the largest three producers about JCV. Temple University published 128 papers and ranked the top, followed by University of Tokyo. Khalili K and Yogo Y became the core authors due to more than 20 documents produced. Journal of Neurovirology published more than 15 papers and ranked the top. Padgett BL and Berger JR were the first two highly-cited authors. Journal of Virology and Journal of Neurovirology respectively ranked to the first two highly-cited journals. These top highly-cited articles were divided into 5 aspects: (1) The correlation between JC virus and tumors; (2) Causal correlation of JCV with PML; (3) Polyoma virus infection and its related diseases in renal-allograft recipients; (4) Detection of JCV antibody, oncogene and its encoding protein; (5) Genetics and molecular biology of JCV. The MeSH/subheadings were classified into five groups: (1) JCV and virus infectious diseases; (2) JCV pathogenicity and pathological appearance of PML; (3) JCV isolation and detection; (4) Immunology of JCV and PML; (5) JCV genetics and tumors.</p> <p>Conclusion</p> <p>JCV investigation mainly focused on its isolation and detection, as well as its correlation with PML and tumors. Establishment of transgenic animal model using JCV T antigen would be a hopeful and useful project in the further study.</p

Roles of MAPK and Spindle Assembly Checkpoint in Spontaneous Activation and MIII Arrest of Rat Oocytes

Rat oocytes are well known to undergo spontaneous activation (SA) after leaving the oviduct, but the SA is abortive with oocytes being arrested in metaphase III (MIII) instead of forming pronuclei. This study was designed to investigate the mechanism causing SA and MIII arrest. Whereas few oocytes collected from SD rats at 13 h after hCG injection that showed 100% of mitogen-activated protein kinase (MAPK) activities activated spontaneously, all oocytes recovered 19 h post hCG with MAPK decreased to below 75% underwent SA during in vitro culture. During SA, MAPK first declined to below 45% and then increased again to 80%; the maturation-promoting factor (MPF) activity fluctuated similarly but always began to change ahead of the MAPK activity. In SA oocytes with 75% of MAPK activities, microtubules were disturbed with irregularly pulled chromosomes dispersed over the spindle and the spindle assembly checkpoint (SAC) was activated. When MAPK decreased to 45%, the spindle disintegrated and chromosomes surrounded by microtubules were scattered in the ooplasm. SA oocytes entered MIII and formed several spindle-like structures by 6 h of culture when the MAPK activity re-increased to above 80%. While SA oocytes showed one Ca2+ rise, Sr2+-activated oocytes showed several. Together, the results suggested that SA stimuli triggered SA in rat oocytes by inducing a premature MAPK inactivation, which led to disturbance of spindle microtubules. The microtubule disturbance impaired pulling of chromosomes to the spindle poles, caused spindle disintegration and activated SAC. The increased SAC activity reactivated MPF and thus MAPK, leading to MIII arrest