Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer＇s disease

The principal pathology of Alzheimer＇s disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques, which in turn induce neuroinflammation in the brain. Triptolide, a natural extract from the vine-like herb Tripterygium wilfordii Hook F, has potent anti-inflammatory and immunosuppressive efficacy. Therefore, we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer＇s disease. We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice （aged 4-4.5 months） for 45 days. Unbiased stereology analysis found that triptolide dose-dependent- ly reduced the total number of microglial cells, and transformed microglial cells into the resting state. Further, triptolide （5 μg/kg/d） also reduced the total number of hippocampal astrocytes. Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS 1 double transgenic mice with Alzheimer＇s disease.

Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells

AIM To find the mechanisms by which special AT-rich sequence-binding protein 2(SATB2) influences colorectal cancer(CRC) metastasis.METHODS Cell growth assay, colony-forming assay, cell adhesion assay and cell migration assay were used to evaluate the biological characteristics of CRC cells with gain or loss of SATB2. Sphere formation assay was used to detect the self-renewal ability of CRC cells. The m RNA expression of stem cell markers in CRC cells with upregulated or downregulated SATB2 expression was detected by quantitative real-time polymerase chain reaction. Chromatin immunoprecipitation(Ch IP) was used to verify the binding loci of SATB2 on genomic sequences of stem cell markers. The Cancer Genome Atlas(TCGA) database and our clinical samples wereanalyzed to find the correlation between SATB2 and some key stem cell markers.RESULTS Downregulation of SATB2 led to an aggressive phenotype in SW480 and DLD-1 cells, which was characterized by increased migration and invasion abilities. Overexpression of SATB2 suppressed the migration and invasion abilities in SW480 and SW620 cells. Using sequential sphere formation assay to detect the selfrenewal abilities of CRC cells, we found more secondary sphere formation but not primary sphere formation in SW480 and DLD-1 cells after SATB2 expression was knocked down. Moreover, most markers for stem cells such as CD133, CD44, AXIN2, MEIS2 and NANOG were increased in cells with SATB2 knockdown and decreased in cells with SATB2 overexpression. Ch IP assay showed that SATB2 bound to regulatory elements of CD133, CD44, MEIS2 and AXIN2 genes. Using TCGA database and our clinical samples, we found that SATB2 was correlated with some key stem cell markers including CD44 and CD24 in clinical tissues of CRC patients.CONCLUSION SATB2 can directly bind to the regulatory elements in the genetic loci of several stem cell markers and consequently inhibit the progression of CRC by negatively regulating stemness of CRC cells.

The effects of large doses of vitamin C and vitamin E on nerve injury, neurotrophic and oxidative stress in patients with acute craniocerebral injury

Objective:To study the effects of large doses of vitamin C and vitamin E on nerve injury,neurotrophic and oxidative stress in patients with acute craniocercbral injury.Methods:Patients with acute cranioccrebral trauma who were admitted to the Third People's Hospital of Zigong from April 2014 to December 2016 were selected as the subjects and were randomly divided into two groups.The control group received conventional treatment,and the intervention group received large doses of vitamin C and vitamin E combined with conventional treatment.On the yh day and 7th day after treatment,peripheral blood was collected and serum was isolated,then the contents of nerve injury index NSE,S 100B,NGB,UCH-L1,Tf,Ft and neurotrophic indexes NTF-α,BDNE NGF and IGF-I were determined by Enzyme-linked immunosorbent assay kit,and the contents of SOD,GPx,CAT,OH-,O2,MDA and AOPP were measured by radioactive immunoprecipitation kit.Results:3th day and 7th day after treatment,the contents of NSE,S100B,NGB,UCH-L1,Tf,Ft,NTF-α,BDNF,NGF,IGF-Ⅰ,OH-,O2-,MDA and AOPP in the intervention group were all significantly lower than those in the control group.The content of SOD,GPx and CAT in serum in the intervention group was significantly higher than that in the control group.Conclusions:High-dose vitamin C and vitamin E treatment can alleviate nerve injury,oxidative stress response,and improve neurotrophic state in patients with acute craniocerebral injury.

Curative effect of minimally invasive puncture and drainage assisted with alteplase on treatment of acute intracerebral hemorrhage

Objective: To investigate the different effects on evacuation of hematoma, the severity of nerve injury, inflammatory reaction and oxidative stress response in the treatment of acute intracerebral hemorrhage by using minimally invasive puncture and drainage assisted with alteplase or urokinase. <br> Methods:A total of 114 patients with acute intracerebral hemorrhage treated with minimally invasive puncture and drainage in our hospital from May 2012 to October 2015 were retrospectively analyzed and divided into alteplase group and urokinase group, which received adjuvant therapy with alteplase and urokinase, respectively. Before and after treatment, CT was used for scanning, and the volume of hematoma and edema and the distance of midline shift were examined. After treatment, serum was collected for detecting the contents of molecular markers of nerve injury, inflammatory reaction and oxidative stress response. <br> Results:On the 3rd day after treatment, the volume of hematoma and edema and the distance of midline shift in minimally invasive group were significantly lower than those of craniotomy group, and incidence of intracranial infection was lower than that of craniotomy group. There was no significant difference of rebleeding incidence compared to craniotomy group. The serum contents of osteopontin, S100β, glial fibrillary acidic protein, neuron-specific enolase, myelin basic protein, neuropeptide Y, ischemia modified albumin, tumor necrosis factor alpha, interleukin-1β, interleukin-6, interleukin-8, soluble intercellular adhesion molecule-1, high-mobility group protein 1, malonaldehyde, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine urine of patients from alteplase group were significantly lower than those of urokinase group. The content of total antioxidant capacity was obviously higher than that of urokinase group. <br> Conclusions: As for the effect on evacuation of hematoma and also the ameliorative effect on nerve injury, inflammatory reaction and oxidative stress response in treatment of acute intracerebral hemorrhage, minimally invasive puncture and drainage assisted with alteplase was superior to adjuvant therapy with urokinase.

Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study

The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.

The impact of crystal defects towards oxide semiconductor photoanode for photoelectrochemical water splitting

Photoelectrochemical (PEC) water oxidation for sustainable clean energy and fuel production is a potential solution to the demands of organic pollutant removal and growing energy consumption.Development of high performance photoanodes,which is a key component in the system,is one of the central topics in the area.The crystal defect is an old concept but fruiting new understanding witli promotive impact to the development of high performance photoanodes.In this review,we elucidated the typical defects involved in the photoanode with the position where they play the roles in the structure and how the properties of photoanode are influenced.In addition,we summarized the feasible protocols to maximize the pros but reduce the cons brought by having defects to the photoanode performance based on recent most prominent researcli advancements in the field.Finally,we briefly sketched the future perspective with the challenges of this topic when in the scenario of possible developments into practical applications.

Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer

The mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear.Here,using clinical samples from lung metastases of CRC patients,we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC.Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin,one member of the leucine-rich repeat and PDZ domain(LAP)family,was involved in the lung metastases.Erbin deletion in B cells suppressed lung metastasis of CRC in vivo.And,deletion of Erbin in B cells enhanced the killing effects of CD8+T cells on tumor cells.Mechanistically,Erbin knockout attenuated TGFp-mediated suppression of migration of CXCR5+lgA+cells and STAT6-mediated PD1 expression.Our study uncovered a key role of Erbin in regulating PD1+lgA+B cells in lung metastasis of CRC.Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice,suggesting the potential option for treatment of lung metastasis of CRC.

Emergence, Development, and Future of Cardio-Oncology in China

As the development of early detection and therapies advances in cancer patients, mortality rates attributed to cancer have declined. In the United States, there are approximately 15,5 million cancer survivors, and the number will grow to more than 20 million by 2026 （http：//www.cancer.org/cancer/news/news/ report-number-of-cancer-survivors-contint, es-to-grow）.

Adaptive multi-resolution Modularity for detecting communities in networks

Community structure is a common topological property of complex networks, which attracted much attention from various fields. Optimizing quality functions for community structures is a kind of popular strategy for community detection, such as Modularity optimization. Here, we introduce a general definition of Modularity, by which several classical(multi-resolution) Modularity can be derived, and then propose a kind of adaptive(multi-resolution) Modularity that can combine the advantages of different Modularity. By applying the Modularity to various synthetic and real-world networks, we study the behaviors of the methods, showing the validity and advantages of the multi-resolution Modularity in community detection. The adaptive Modularity, as a kind of multi-resolution method, can naturally solve the first-type limit of Modularity and detect communities at different scales;it can quicken the disconnecting of communities and delay the breakup of communities in heterogeneous networks;and thus it is expected to generate the stable community structures in networks more effectively and have stronger tolerance against the secondtype limit of Modularity.