Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma

In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in 2024.We focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide.Most HCC cases develop in the context of liver cirrhosis.Among the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative stress.Over the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and leukemias.Specifically,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling pathways.It has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and metastasis.In addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy resistance.Finally,more studies finely investigated the influence of MTDH on CSCs.The CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their phenotype.Beyond their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.

基于GENE-8310的嵌入式TinyOs系统设计

无线传感器网络是当前国际上备受关注的、多学科高度交叉、知识高度集成的前沿热点研究技术,其核心技术Tinyos被誉为是"无线嵌入式系统"。在嵌入式开发板GENE-8310上移植Tinyos应用操作系统是一次技术上的新尝试,将GENE-8310作为无线传感器网络中的远程服务器,实现无线网络与有线网络的跨网段传输和远程网络监控将进一步推动无线传感器网络的技术的发展。

Downregulation of Astrocyte Elevated Gene-1 Expression Combined with All-Trans Retinoic Acid Inhibits Development of Vasculogenic Mimicry and Angiogenesis in Glioma

Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in glioma.Methods U87 glioma cells were transfected with AEG-1 shRNA lentiviral vectors(U87-siAEG-1)and incubated in a medium containing 20µmol/L ATRA.Matrigel-based tube formation assay was performed to evaluate VM formation,and the cell counting kit-8(CCK-8)assay was used to analyze the proliferation of glioma cells in vitro.Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to investigate the mRNA and protein expression of related genes,respectively.Glioma xenograft models were generated via subcutaneous implantation of glioma cells in nude mice.Tumor-bearing mice received an intraperitoneal injection of ATRA(10 mg/kg per day).Immunohistochemistry was used to evaluate the expression of related genes and the microvessel density(MVD)in glioma xenograft models.CD34/periodic acid-Schiff double staining was performed to detect VM channels in vivo.The volume and weight of tumors were measured,and a tumor growth curve was drawn to evaluate tumor growth.Results A combination of ATRA intervention and downregulation of AEG-1 expression significantly inhibited the proliferation of glioma cells in vitro and glioma VM formation in vitro and in vivo.It also significantly decreased MVD and inhibited tumor growth.Further,the expression levels of matrix metalloproteinase(MMP)-2,MMP-9,vascular endothelial-cadherin(VE-cadherin),and vascular endothelial growth factor(VEGF)in glioma significantly decreased in vivo and in vivo.Conclusion Hence,a combinatorial approach might be effective in treating glioma through regulating MMP-2,MMP-9,VEGF,and VE-cadherin expression.

Expression of hypoxia-inducible factor 1 alpha and oligodendrocyte lineage gene-1 in cultured brain slices after oxygen-glucose deprivation

Oligodendrocyte lineage gene-1 expressed in oligodendrocytes may trigger the repair of neuronal myelin impairment, and play a crucial role in myelin repair. Hypoxia-inducible factor la, a transcription factor, is of great significance in premature infants with hypoxic-ischemic brain damage There is little evidence of direct regulatory effects of hypoxia-inducible factor le on oligodendrocyte lineage gene-l. In this study, brain slices of Sprague-Dawley rats were cultured and subjected to oxygen-glucose deprivation. Then, slices were transfected with hypoxia-inducible factor la or oligodendrocyte lineage gene-1. The expression levels of hypoxia-inducible factor la and oligodendrocyte lineage gene-1 were significantly up-regulated in rat brains prior to transfection, as detected by immunohistochemical staining. Eight hours after transfection of slices with hypoxia-inducible factor la, oligodendrocyte lineage gene-1 expression was upregulated, and reached a peak 24 hours after transfection. Oligodendrocyte lineage gene-1 transfection induced no significant differences in hypoxia-inducible factor la levels in rat brain tissues with oxygen-glucose deprivation. These experimental findings indicate that hypoxia-inducible factor la can regulate oligodendrocyte lineage gene-1 expression in hypoxic brain tissue, thus repairing the neural impairment.

基于Celeron-M嵌入式平台的身份识别智能终端设计

利用基于嵌入式处理器Celeron-M的GENE-8310嵌入式开发板为硬件平台,集成RFID卡识别、二代身份证识别、说话人识别、人脸识别和指纹识别5种识别技术,实现了一个基于嵌入式系统的高安全性能的身份识别智能终端。该终端根据应用场合的安全要求选择不同的身份识别模式,可用于大型活动、会议和体育赛事的安检和公司的考勤中,具有重要的实际应用价值。

基于GENE8310的嵌入式多媒体网络通信系统设计

本文在嵌入式GENE8310开发平台上进行多媒体网络通信系统设计。文中在掌握了IntelECX规范的定义、发展和应用基础上,构建了GENE8310开发平台,运用软件解决了3个问题。一是摄像头的监控,包括远程控制、摄像信息的存储和远程传输;二是声音的控制,包括声音的录制、远程传送和播放;三是多媒体的管理。设计的开发平台能够实现与计算机有线和无线局域网的通信,系统除了能够实现无人区的视频监控,还能够实现语音信息的远程传送,从而实现广播的功能。

Oncolytic adenovirus-mediated MDA-7/IL-24 overexpression enhances antitumor activity in hepatocellular carcinoma cell lines

BACKGROUND: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells. We investigated the effect of the replication-competent oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24, both expressing human MDA-7/IL-24 on the hepatocellular carcinoma cell lines HepG2, Hep3B, SMMC-7721, HCCLM3, and the normal liver cell line L02. METHODS: Hepatocellular carcinoma cell lines and the normal liver cell line were infected with SG600-IL24 and Ad.IL-24. The mRNA and protein expression of MDA-7/IL-24 in infected cells was confirmed by RT-PCR, ELISA, and Western blotting. MTT assay was used to investigate the proliferation effect. Hoechst staining and Annexin-V and PI staining were performed to study the MDA-7/IL-24 gene expressed in HCC cell lines and the normal liver cell line. Flow cytometry was used to analyse the cell cycle. RESULTS: RT-PCR, ELISA and Western blotting confirmed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24. MTT and apoptosis detection indicated that SG600-IL24 induced growth suppression, promoted apoptosis, and blocked cancer cell lines in the G2/M phase in hepatocellular carcinoma cell lines but not in the normal liver cell line. CONCLUSIONS: SG600-IL24 selectively induces growth suppression and apoptosis in hepatocellular carcinoma cell lines in vitro but not in the normal liver cell line L02. Compared with Ad.IL-24, SG600-IL24 dramatically enhances antitumor activity in hepatocellular carcinoma cell lines. (Hepatobiliary Pancreat Dis Int 2010; 9:615-621)

Stem cells, a two-edged sword: Risks and potentials of regenerative medicine

The recent advancements in stem cell (SC) biology have led to the concept of regenerative medicine, which is based on the potential of SC for therapies aimed to facilitate the repair of degenerating or injured tissues. Nonetheless, prior to large scale clinical appli- cations, critical aspects need to be further addressed, including the long-term safety, tolerability, and efficacy of SC-based treatments. Most problematic among the risks of SC-based therapies, in addition to the pos- sible rejection or loss of function of the infused cells, is their potential neoplastic transformation. Indeed, SCs may be used to cure devastating diseases, but their specific properties of self-renewal and clonogenicity may render them prone to generate cancers. In this respect, ‘Stemness’ might be seen as a two-edged sword, its bright side being represented by normal SCs, its dark side by cancer SCs. A better understand- ing of SC biology will help fulfill the promise of regen- erative medicine aimed at curing human pathologies and fighting cancer from its roots.

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells

Objective:To prove whether astrocyte elevated gene-1(AEG-1) plays a role in high glucosestimulated Rho kinase activation and epithelial-mesenchymal transition(EMT) in human renal tubular epithelial(HK-2) cells.Methods:The protein levels of AEG-1,alpha-smooth muscle actin,E-cadherin and MYPT1 were determined by Western blot.Results:AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose.AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT.Conclusions:Our results show that AEG-1 acts a key role in high glucoseinduced activation of Rho kinase and EMT in HK-2 cells.

A novel mutation of SGK-1 gene in central serous chorioretinopathy

AIM: To investigate the association of serum glucocorticoid kinase gene-1(SGK-1) DNA variants with chronic central serous chorioretinopathy(CSC).METHODS: We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction amplification. SGK1 gene was sequenced by using Big Dye Terminator v3.1 cycle sequencing Kit(Applied Biosystems, Foster City, CA, USA). The SGK-1 gene and its variants were investigated in CSC patient group and control group.RESULTS: We identified a new polymorphism M32 V in two person in the patient group [Minor allele frequency(MAF) =0.009] on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK- 1 gene but not associated with CSC(P =0.68). An intrinsic rs1743966 is also not associated(P =0.28).CONCLUSION: The new polymorphism M32 V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.

Expression of Egr-1 in the liver of mice following hemorrhagic shock and resuscitation

Objective: To investigate the expression of early growth response gene-1(Egr-1) in the liver following hemorrhagic shock with or without resuscitation(HS or HSR). Methods: Mice were subjected to HS or HSR.Liver expression of Egr-1 mRNA was detected by Northern blotting.DNA binding activity of the Egr-1 protein in liver nuclear extracts(NE) was determined by electrophoretic mobility shift assay(EMSA).Western blot analysis was used to assess the induction of Egr-1 protein in the liver tissue,cytoplasma and NE. Results: Egr-1 mRNA was strongly expressed as early as 1 h after HS,and its level was decreased in the following 2.5 h but still higher than that in 1 h HS group.The Egr-1 DNA binding activity elevated in the liver NE of 2.5 h HS group and 2.5 h HS + 4 h R group,so did the Egr-1 protein in the liver and the liver NE of the same two groups.However,the maximal Egr-1 protein expression was found in the cytoplasma of liver following 2.5 h HS. Conclusion: Our data suggest that both Egr-1 mRNA and protein are strongly elevated and the binding activity of Egr-1 to its cognate DNA site is increased in the liver following HSR,indicating the increases of Egr-1 transcriptional and translational levels.This study provides evidence that Egr-1 gene is activated in the liver during HS and HSR.

Correlation of TSG-6 expression with apoptosis and collagen metabolism in pathological scar tissue

Objective: To study the correlation of tumor necrosis factor- stimulated gene-6 (TSG-6) expression with apoptosis and collagen metabolism in pathological scar tissue. Methods:Surgically removed pathological scar tissue and the normal skin tissue removed due to extremity trauma in Sichuan Provincial People's Hospital between June 2014 and February 2017 were selected to detect the mRNA expression of TSG-6 as well as the protein levels of apoptosis genes and collagen metabolism indexes. Results: TSG-6 mRNA expression as well as Smac, p53, Cyt-C, IGF-1 and bFGF protein levels in pathological scar tissue was significantly lower than those in normal skin tissue while Livin, PCNA, Col-I, Col-III and TGF-β1 protein levels were significantly higher than those in normal skin tissue;Livin, PCNA, Col-I, Col-III and TGF-β1 protein levels in pathological scar tissue with higher TSG-6 expression were lower than those in pathological scar tissue with lower TSG-6 expression while Smac, p53, Cyt-C, IGF-1 and bFGF protein levels were significantly higher than those in pathological scar tissue with lower TSG-6 expression. Conclusion: The low expression of TSG-6 in pathological scar tissue can inhibit apoptosis and promote collagen anabolism to accelerate scar formation.

新品信息

研扬推出第三代低功耗无风扇方案——嵌入式主板GENE-8310，研华更新ACP-7000&ACP-5260配置，大众工控推出一系列不同外壳、不同尺寸的平板电脑，艾讯科技推出低功耗无风扇嵌入式主板——SBC84400＆SBC-84401，MOXA发表新款的多串口通讯卡CP-118U……

Correlation of serum sLAG-3, PARP-1 and CA50 levels with oncogene expression in surgically removed lesions in patients with gastric cancer

Objective:To study the correlation of serum sLAG-3, PARP-1 and CA50 levels with oncogene expression in surgically removed lesions in patients with gastric cancer.Methods: A total of 98 patients who were diagnosed with gastric cancer in Zhouzhi County People's Hospital between June 2015 and March 2017 were selected as the gastric cancer group of the research, and 60 healthy volunteers who received physical examination during the same period were selected as control group of the research. The serum was collected from the two groups to determine sLAG-3, PARP-1 and CA50 levels;gastric cancer lesions and adjacent lesions were collected from gastric cancer group to determine the protein expression of PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2, CDC4, UHRF1, OCT4, Zeb-1 and c-jun.Results:Serum sLAG-3, PARP-1 and CA50 levels of gastric cancer group were significantly higher than those of control group, and the higher the TNM stage, the higher the serum sLAG-3, PARP-1 and CA50 levels;PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2 and CDC4 protein levels in gastric cancer lesions were significantly lower than those in adjacent lesions and negatively correlated with serum sLAG-3, PARP-1 and CA50 levels, while UHRF1, OCT4, Zeb-1 and c-jun protein levels in gastric cancer lesions were significantly higher than those in adjacent lesions and positively correlated with serum sLAG-3, PARP-1 and CA50 levels.Conclusions:The increase in serum sLAG-3, PARP-1 and CA50 levels in patients with gastric cancer is closely related to the pathological process of gastric cancer, deletion of tumor suppressor gene expression and increase of proto-oncogene expression.

研扬推出第三代低功耗无风扇方案

GENE-8310是研扬科技研制的第三代无风扇解决方案。比起以前的3.5寸单板电脑，CENE-8310在低功耗和高性能方面都有了更大的改进。我们相信，GENE-8310对于客户在低功耗控制下的优秀处理能力等更高需求方面都是最好的选择。GENE-8310的几个特殊功能体现在以下几个方面：极佳的性能和功耗的可控制性；支持多种显示模块；扩展性能。

Astrocyte elevated gene-1 induces breast cancer proliferation and invasion through upregulating HER2/neu expression

Background Astrocyte elevated gene-1 （AEG-1）, primarily identified as a late response gene induced by HIV-1 infection, plays multiple roles in the process of oncogenesis. This novel gene has been demonstrated to be involved in the several potent carcinogenic pathways, including PI3K/Akt pathway, nuclear factor （NF）-KB pathway, and Wnt/13-catenin pathway. Although the function of AEG-1 has been intensively investigated in recent years, the molecular mechanism underlying its oncogenic role is largely unknown. The aim of this research was to explore the potential function of AEG-1 in breast cancer development and progression. Methods AEG-1 was ectopically overexpressed in breast cancer MCF-7 cells and its biological effects on the proliferation and invasion of MCF-7 cells were studied by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and invasion assays. The expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis, was also determined. Results Overexpression of the AEG-1 promoted the proliferation and invasion ability of breast cancer cells, and upregulated the expression of HER2/neu, a crucial oncogene involving in breast cancer carcinogenesis. Conclusion AEG-1 might facilitate the proliferation and invasion of breast cancer cells by upregulating HER2/neu expression, which provides a potential target for breast cancer therapy.

Lipoxin A4 Ameliorates Lipopolysaccharide-lnduced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1

Background： Lipoxin A4 （LXA4） can alleviate lipopolysaccharide （LPS）-induced acute lung injury （ALl） and acute respiratory distress syndrome through promoting epithelial sodium channel （ENaC） expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. Methods： A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction （qRT-PCR） of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing ofA549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis ofA549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor （ALX） inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase （PI3K） inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression. Results： The A549 cell models of ALl were constrticted and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream- regulated gent- 1 （NDRG 1 ） was validated by real-time-PCR and Western blot. NDRG 1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG 1 expression induced by LXA4. NDRG I siRNA suppressed viability of LPS-treated A549 cells （treatment vs. control, 0.605± 0.063 vs. 0.878 ± 0.083, P = 0.040） and ENaC-α expression （treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008）. LY294002 inhibited NDRG 1 （treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P 0.001 ） and ENaC-α （treatment vs. control, 0.236 ± 0.021 vs. 0.814 ±0.025, P 〈 0.001 ） expressions and serum- and glucocorticoid-inducible kinase I phosphorylation （treatment vs. control, 0.442± 0.024 vs. 1.046 ± 0.082, P = 0.002）, indicating the PI3K signaling pathway was involved in regulating NDRG 1 expression induced by LXA4. Conclusion： Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.

Potential functions of esophageal cancer-related gene-4 in the cardiovascular system

Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the esophagus.It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor gene.Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell activation.Ecrg4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor suppression.Here,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.