OBJECTIVE:To study the protective effects of Polygonum hydropiper extract on acute gastric mucosal lesion (AGML)in rats. METHODS:48 rats were randomly divided into normal group(normal saline),model group(normal saline), positive group(ranitidine hydrochloride,0.05 g/kg),P. hydropiper extract low-dose,medium-dose and high-dose groups(2.7, 8.1,24.3 g/kg by crude drug),i.g. for consecutive 7 d,once a day. Except for normal group,other groups were given absolute ethyl alcohol to induce AGMI model after 1 h of last administration. 1.5 h after modeling,gastric mucosal lesion index of rats was calculated;the pathological changes of gastric tissue in rats were observed;nuclear factor E2 related factor 2(Nrf2)content and SOD activity in gastric tissue of rats were determined by ELISA. RESULTS:Compared with normal group,the gastric mucosa of model group was damaged obviously,there was blood capillary rupture in submucosa,gastric mucosal lesion index was increased significantly(P<0.01);Nrf2 content and SOD activity were significantly decreased in gastric tissue of rats(P<0.05 or P<0.01). Compared with model group,gastric mucosal lesion of rats was relieved to different extent;in positive group,P. hydropiper extract medium-dose and high-dose groups,gastric mucosal lesion index was decreased significantly(P<0.05),and Nrf2 content and SOD activity were increased significantly(P<0.05 or P<0.01). CONCLUSIONS:P. hydropiper extract has good protective effect on absolute ethyl alcohol-induce AGMI,the mechanism of which may be associated with raising Nrf2 content and enhancing SOD activity in gastric mucosal tissue.

PURPOSE: C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. METHODS: Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. RESULTS: Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. CONCLUSION Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.

Objective: To investigate the biological functions of protein phosphatase 2AC(PP2AC) in the brain, and to detect its spatio-temporal expression and its involvement in neurological disorders in the brains of mice and Alzheimer′s patients. Methods: Western blot was used to evaluate the expression level of PP2AC in different organs. Immunohistochemical staining was performed to detect the in situ expression levels of PP2AC in the brains of mice and patients, and the pathological changes were confirmed in the brains of patients with Alzheimer′s disease. Results: Among all the tested organs in adult mouse, the expression of PP2AC protein was the highest in the brain. From embryonic day 18.5 to postnatal 2-year-old mice, PP2AC exhibited spatio-temporal specific expression in the brains. Furthermore, an age-dependent increased expression in the cerebral cortex at both protein and RNA levels was observed. Compared to control group, PP2AC protein expression was lower in the frontal cortex of Alzheimer′s patients. Conclusions The spatio-temporal specific expression profiles of PP2AC in mouse brain implicate its biological significance. Its diminished expression in the frontal cortex of Alzheimer′s disease patients implies that PP2AC plays a potential role in the pathogenesis of Alzheimer′s disease.

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60^{+ /-} male mice at age of 4-6 months (young group, n=6) and 18-20 months (aged group, n=9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-β-Gal staining was utilized to detect the activity of senescence-associated β-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs.(1.12±0.09) mm, P<0.05], cardiomyocyte hypertrophy[(474.9±27.6) μm² vs.(358.8±48.7) μm², P<0.05] and interstitial fibrosis [ (38.24±7.58) ×10³μm² vs.(25.81±4.12)×10³μm^2, P<0.05], increased activity of SA-β-Gal (2.26±0.24 vs.0.25±0.05, P<0.01) and higher expression of p21 (P<0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-β-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.

OBJECTIVETo identify novel lncRNAs involved in cerebellar neurogenesis using neuronal specific Nbs1-deficient (Nbs1(CNS-del)) mouse model.

METHODSMicroarray analysis was performed to identify differentially expressed lncRNAs between Nbs1(CNS-ctr) and Nbs1(CNS-del) mice. Expression profiles of lncRNA Gm15577 and coding gene Negr1 in mice, primary cerebellar culture and cell lines were measured using RT-qPCR. Subcellular fractionation was performed to determine the subcellular localization of Gm15577.

RESULTSGm15577 was specifically expressed in mice cerebellum in a developmentally regulated manner, which could be abolished upon Nbs1-deficiency. Gm15577 was located in the intronic region of Negr1 in a reversed orientation. Gm15577 modulated the RNA expression of Negr1, Shh and β-catenin. NEGR1 had a distinct expression pattern between normal and medulloblastoma patients.

CONCLUSIONGm15577 may modulate cerebellar granule cell proliferation and differentiation by targeting Negr1, and their dysfunctions or abnormal expression may be related to tumorigenesis of medulloblastoma.

Animals ; Cell Differentiation ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cerebellar Neoplasms ; pathology ; Cerebellum ; cytology ; physiology ; Disease Models, Animal ; Humans ; Introns ; Medulloblastoma ; pathology ; Mice ; Mice, Knockout ; Neurogenesis ; Neurons ; physiology ; RNA, Long Noncoding ; metabolism

Objective: To analyze the research hotspots of domestic narrative nursing and explore its related research trends which provide reference and guidance for its application and development in China. Methods: Wanfang, CNKI, VIP, CBM and other databases were retrieved from inception until October 2018. Word frequency analysis and graph cluster analysis were performed on the main information using Excel, Bicomb, Ucinet, Netdraw and gCLUTO software. Results: A total of 649 articles were included. The result of visual analysis showed that the annual amount of publications showed an upward trend. The articles distributed abroad in many different journals which educational journals account mostly. The study regions were distributed in 34 provinces except Taiwan of China, Hainan, Tibet, and Macao Special Administrative Regions where mainly concentrated on East China and North China. The cooperation among authors and institutions both were not close; A total of 25 high-frequency key words were intercepted,and three hotspots of narrative nursing research in China were obtained,which respectively were: (1) The application of narrative medicine and the cultivation of narrative ability; (2) The application research of narrative therapy in humanistic care; (3) The application of narrative nursing in nursing practice. Conclusions Narrative nursing has attracted the attention of domestic scholars, but the depth and breadth of research still need to be improved. It is necessary to strengthen cooperation between inter-regional institutions, individuals and scientific research groups and pay attention to research hotspots in this field. Also,there is a need to conduct more high quality studies to verify the significance of narrative nursing.

Objective: To investigate the expression and potential role of heterogeneous nuclear ribonucleo-protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma. Methods: The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A-IP-qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells. Results: The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment. Conclusions HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up-regulated at transcriptional level but obviously down-regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin-proteasome pathway may account for the down-regulation of HNRNPA2B1 at protein level.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome