Miao Z.,Soochow University of China |
He Y.,Jilin University |
Xin N.,Soochow University of China |
Sun M.,Soochow University of China |
And 7 more authors.
Human Molecular Genetics | Year: 2015
Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRswere enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, whichwas accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke. © The Author 2015.
Ren L.,Soochow University of China |
Qian X.,Soochow University of China |
Zhai L.,Soochow University of China |
Sun M.,Soochow University of China |
And 3 more authors.
PLoS ONE | Year: 2014
Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1) deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO) mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets. © 2014 Ren et al.
Huang C.,Nantong University |
Wu J.,Suzhou Kowloon Hospital |
Liao R.,Nantong University |
Zhang W.,Nantong University
PLoS ONE | Year: 2012
Extracellular signal-regulated kinase 1/2 (ERK1/2) is a member of the mitogen-activated protein kinase family. It can mediate cell migration. Classical dopamine receptor-mediated ERK1/2 phosphorylation is widely studied in neurons. Here, we report that ERK1/2 phosphorylation is also modulated by putative phosphatidylinositol-linked D1-like receptors in cultured rat astrocytes. 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959), an agonist of the putative phosphatidylinositol-linked D1-like receptors, was found to enhance ERK1/2 phosphorylation, which then promoted the migration of cultured astrocytes. The SKF83959-induced ERK1/2 phosphorylation was found to be Ca2+-independent based on the following observations: i. chelating intracellular Ca2+ did not inhibit ERK1/2 phosphorylation and astrocyte migration; ii. blockage of the release of intracellular Ca2+ from the endoplasmic reticulum by an inhibitor of inositol 1,4,5-trisphosphate (IP3) receptor did not attenuate ERK1/2 phosphorylation. However, inhibition of phospholipase C (PLC), the upstream molecule of internal Ca2+ release, disabled SKF83959's ability to elevate the level of ERK1/2 phosphorylation. Both non-selective protein kinase C (PKC) inhibitor and PKCδ selective inhibitor prevented ERK1/2 phosphorylation increase and astrocyte migration, but PKCα inhibitor did not. This suggests that Ca2+-independent and diacylglycerol-dependent PKCδ acts downstream of putative phosphatidylinositol-linked D1-like receptor activation and mediates SKF83959-induced elevation of ERK1/2 phosphorylation in order to modulate astrocyte migration. In conclusion, our results demonstrate that SKF83959-induced increases in ERK1/2 phosphorylation and astrocyte migration are dependent on PLC-PKCδ signals. This might help us to further understand the functions of the putative phosphatidylinositol-linked D1-like receptors in the nervous system. © 2012 Huang et al.
Du G.,Soochow University of China |
Tu H.,Soochow University of China |
Li X.,Soochow University of China |
Pei A.,Soochow University of China |
And 7 more authors.
Neurochemical Research | Year: 2014
Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke. © 2013 Springer Science+Business Media New York.
Chen J.,Soochow University of China |
Li J.,Soochow University of China |
Li J.,Suzhou Kowloon Hospital |
Miao Z.,Soochow University of China |
And 2 more authors.
Journal of Neuroscience Research | Year: 2014
White matter tracts are composed of axons and myelinating oligodendrocytes. Oligodendrocytes are the myelinating cells in the central nervous system that allow formation of myelin and saltatory nerve conduction. Cerebral white matter is highly vulnerable to ischemic injury in adults and neonates. White matter injury in newborn brains results in cerebral palsy and cognitive disability. In this study, we found that XAV939, a small-molecular inhibitor that stimulated β-catenin degradation by stabilizing axin, protected against serum and glucose deprivation (SGD)-induced cell death in oligodentrocyte cell line OLN-93 cells in a concentration-dependent manner. We further showed that XAV939 reduced caspase-3 and caspase-8 levels and increased the expression of phosphorylated Akt in SGD-induced OLN-93 cells. Our data demonstrate that XAV939 protects against neonatal hypoxic/ischemic injury. In summary, our results demonstrate that XAV939 confers neuroprotection against SGD-induced injury in OLN-93 cells via its antiapoptotic activity and the loss of oligodendrocytes and neurons in neonatal hypoxic/ischemic injury. © 2014 Wiley Periodicals, Inc.
Shen F.-R.,Soochow University of China |
Shen F.-R.,Suzhou Kowloon Hospital |
Liu M.,Suzhou Kowloon Hospital |
Zhang X.,Suzhou Kowloon Hospital |
And 2 more authors.
International Journal of Gynecology and Obstetrics | Year: 2013
Objective To investigate factors associated with acute maternal morbidity and mortality in Kowloon Hospital, Suzhou, China. Methods Data from cases of near-miss and maternal death between January 2008 and December 2012 were reviewed retrospectively. Maternal characteristics and related factors were identified, and multiple regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results During the study period, there were 18 104 deliveries, 69 near-miss cases, and 3 maternal deaths. Women who had no health insurance (aOR, 4.55; 95% CI, 0.87-21.8), had fewer than 6 prenatal consultations (aOR, 6.76; 95% CI, 0.76-45.8), were part of a migrant population (aOR, 2.34; 95% CI, 0.45-24.9), or delayed seeking healthcare (aOR, 4.76; 95% CI, 0.89-13.6) had a greater risk of near-miss morbidity or death. Admission to intensive care (aOR, 6.75; 95% CI, 0.89-34.6) and blood transfusion within 30 min (aOR, 3.79; 95% CI, 0.65-8.67) were protective factors in disease progression. Conclusion The factors associated with maternal near-miss morbidity and mortality were closely related to health insurance and socioeconomic status, suggesting that the government should take an active role in the community in preventing morbidity and mortality in pregnancy.
Lu Y.,Suzhou Kowloon Hospital |
Jiang B.,Suzhou Kowloon Hospital |
Liu T.,Suzhou Kowloon Hospital
Journal of B.U.ON. | Year: 2016
Purpose: Laparoscopic total gastrectomy for advanced proximal gastric carcinoma is a complex and challenging procedure, limited to a few expert centers. This study analyzed the short- and long-term outcomes of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared with open gastrectomy. Methods: From January 2008 to January 2015, 61 patients underwent laparoscopic total gastrectomy for advanced proximal gastric carcinoma. They were matched and compared to 61 patients who underwent a conventional open operation. Short-term operative and postoperative outcomes as well as long-term outcomes, including overall survival and disease-free survival rates, were assessed. Results: Patients were well matched for several preoperative factors. Overall postoperative 30-day complication rates were significantly higher for the open group. No significant difference was seen in 5-year overall survival and 5-year disease-free survival between the open and laparoscopic groups. The same result was seen in subgroup analyses of TNM stage. Conclusion: This study shows ihefeasibility oflaparoscopic total gastrectomy for advanced proximal gastric carcinoma compared to open resection in regard to both short- and long-term outcomes. Laparoscopic surgery offers many advantages commonly attributed to laparoscopy and is well suited for proximal gastric carcinoma when performed by experienced surgeons.
PubMed | Suzhou Kowloon Hospital, Georgia Regents University, Guangji Hospital and Soochow University of China
Type: | Journal: Molecular neurobiology | Year: 2016
Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.
PubMed | Suzhou Kowloon Hospital
Type: Journal Article | Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology | Year: 2016
Laparoscopic total gastrectomy for advanced proximal gastric carcinoma is a complex and challenging procedure, limited to a few expert centers. This study analyzed the short- and long-term outcomes of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared with open gastrectomy.From January 2008 to January 2015, 61 patients underwent laparoscopic total gastrectomy for advanced proximal gastric carcinoma. They were matched and compared to 61 patients who underwent a conventional open operation. Short-term operative and postoperative outcomes as well as long-term outcomes, including overall survival and disease-free survival rates, were assessed.Patients were well matched for several preoperative factors. Overall postoperative 30-day complication rates were significantly higher for the open group. No significant difference was seen in 5-year overall survival and 5-year disease-free survival between the open and laparoscopic groups. The same result was seen in subgroup analyses of TNM stage.This study shows the feasibility of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared to open resection in regard to both short- and long-term outcomes. Laparoscopic surgery offers many advantages commonly attributed to laparoscopy and is well suited for proximal gastric carcinoma when performed by experienced surgeons.
PubMed | Suzhou Kowloon Hospital, Xuzhou Medical College, Emory University and Soochow University of China
Type: | Journal: Brain research | Year: 2016
5-hydroxymethylcytosine (5hmC) is considered as a novel DNA modification and plays an important role in cancer, stem cells, and developmental diseases. In this study, we demonstrated the existence of RNA 5hmC modification in mouse brain RNA by using a dot blot analysis method. Our data indicated that 5hmC modification in RNA samples was less than that in DNA samples. Further, we optimized the conditions for 5hmC detection in RNA samples such as DNase treatment, denature reagents, denature time, sample air-dry time, and the cross-linking time between RNA and membrane. Our results demonstrated that DNase treatment and denature reagents were two important factors that affected the 5hmC detection in RNA samples. By using the optimal conditions for RNA 5hmC detection, we found that the brainstem, the hippocampus, and the cerebellum had high levels of 5hmC modification and 5mC modification in RNA. Finally, we found that RNA 5hmC modification decreased in MPTP-induced Parkinsons disease model in mice. These suggest that 5hmC modification in RNA might play an important regulative role on protein or microRNA expression in these brain tissues. Because DNA 5hmC modification plays an important role in neural differentiation and development as well as neurological diseases, the significance of 5hmC modification in RNA in different neurological diseases needs further investigation. In summary, our study demonstrated for the first time the abundance of 5hmC modification in brain RNA by using a dot blot analysis method and proved that dot blot analysis is a useful method for 5hmC detection in RNA samples.