INCREASED EXPRESSION OF PDGF AND C-MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXIA

The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known.The present study examined gene expression of platelet-derived growth factor(PDGF)-A and -B chain and proto-oncogene,c-myc,in lung tissue and pulmonary artery of rats exposed to hypoxia and compared to those levels of gene expression in normal rats.Normal lungs and pulmonary artery expressed PDGF-A chain transcript of 1.7 kb and PDGF-B chain transcript of 3.5 Kb.The c-myc transcript of 2.2 kb was expressed as well. After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and cmyc were elevated significantly compared with those of control rats.PDGF-A chain mRNA increased after hypoxia for 7 days,and then declined.These results suggest that activation of autocrine and/or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertensive rats.

INDUCTION OF C-MYC GENE AMPLIFICATION BY HYDROXYUREA AND ITS INHIBITION BY HOMOHARRINGTONINE

Induction of c-myc gene amplification in L1210 cells by hydroxyurea and its inhibition by homohar-ringtonine were investigated using the DNA-DNA molecular hybridization technique. When the cells were treated with hydroxyurea 1.0 mM for 16 hours, and incubated a further 16 hours in a drug-free medium, the c-myc gene amplified 23.5-fold. If homohar-ringtonine 50 μM was used at the same time as hydroxyurea, gene amplification did not occur. Cycloheximide, an inhibitor of protein biosynthesis, produced a similar effect. Our results indicated that a (or some) protein factor(s) might be involved in gene amplification. Detailed analysis showed that the synthesis of this protein factor(s) started 4 hours before the initiation of the S phase but did not continue in the S phase. It was also found that this protein factor(s) was very labile and began to degrade 2 hours after its appearance.

Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues

AIM: To investigate the possible roles of p53 and C-mycgenes in the primary hepatocellular carcinogenesis and therelationship between the liver hyperplastic nodule(LHN) andhepatocellular carcinoma(HCC).METHODS: The expression of p53 and C-myc genes wasdetected immunohist-ochemically in 73 and 60 cases of HCCand pericarcinomatous tissues, respectively .RESULTS: The positive expression of p53 in HCC wassignificantly higher than that in pericarcinomatous tissues(P＜0.05). In pericarcinomatous tissues, the p53 expressionwas observed only in LHN, but not in liver cirrhosis (LC) andnormal liver tissues. The positive expression rate of C-mycin HCC or LHN was significantly higher than that in LC ornormal liver tissues (P＜0.05 and P＜0.01), however, nosignificant difference was found between HCC and LHN(P＞0.05). The positive expression rate of p53 and C-myc inHCC was correlated with the histological differentiation, thatin the poorly differentiated was significantly higher than thatin well differentiated samples (P＜0.05).CONCLUSION: The overexpression of p53 and C-myc genesmight play a role in the carcinogenesis of HCC; And LHNseems a preneoplastic lesion related to hepatocarcinogenesis;No evidence supports that LC contribute directly to thehepatocarcinogenesis.

Proliferation and C-myc Gene Expression of Smooth Muscle Cells in Rabbit Carotid Artery after Stenting

Objectives To investigate theproliferation of smooth muscle cells (VSMCs) and theexpression of c-myc gene in rabbit carotid arieries af-ter stenting. Methods Platinium-Iridium stent wereimplanted into the right carotid arteries of 16 rabbitsunder vision. 7,14,30 and 90 days after the stentingprocedure, morphological changes of VSMCs were ob-served under light and transmission electron micro-scope. The c-myc gene expression was detected by insitu hybridization (ISH) and immunohistochemicalstaining. Results 7 days afer stenting, the pheno-type of VSMCs changed from contractile to syntheticphenotype; there were a number of proliferative VSM-Cs in the neointima. At 14 and 30 days, there weresynthetic and transitive VSMCs. At 90 days, the phe-notype of VSMCs recovered to contractile phenotype.The ultrastructure of typical synthetic phenotype ofVSMCs were round, containing a large amount ofrough endoplasmic reticulum and mitochondria. C-myc expression were positive both by ISH and im-munohistochemical staining. Conclusions C - mycgene expression increases and closely relates to VSM-Cs proliferation afer stenting. It may play an impor-tant role in the in-stent restenosis.

c-Myc、CDK12在胃癌组织中的表达及临床意义

目的 探讨胃癌组织中c-Myc、细胞周期蛋白依赖性激酶12(CDK12)表达及其与患者临床特征及预后的关系。方法 收集80例胃癌患者的胃癌组织和癌旁组织标本,采用免疫组化法检测标本中的c-Myc、CDK12表达水平。比较胃癌组织和癌旁组织中c-Myc、CDK12阳性表达情况;分析胃癌组织中c-Myc、CDK12阳性表达与患者临床病理特征的关系;分析c-Myc与CDK12阳性表达的相关性,胃癌组织中c-Myc、CDK12阳性表达与胃癌患者预后的关系。结果 胃癌组织中c-Myc、CDK12阳性表达率(77.5%、87.5%)均明显高于癌旁组织(13.8%、15.0%)(P<0.05)。不同年龄、性别、肿瘤最大直径患者胃癌组织中c-Myc、CDK12阳性表达率比较差异无统计学意义(P>0.05);中低分化、Ⅲ~Ⅳ期、侵犯浆膜、有淋巴结转移患者胃癌组织中c-Myc和CDK12阳性表达率分别为88.0%、87.0%、88.9%、90.0%和94.0%、92.6%、97.2%、100.0%,均明显高于高分化、Ⅰ~Ⅱ期、未侵犯浆膜、无淋巴结转移患者胃癌组织的60.0%、57.7%、68.2%、70.0%和76.7%、76.9%、79.5%、80.0%(P<0.05)。相关分析发现,c-Myc、CDK12在胃癌组织中的表达呈正相关性(r=0.487,P=0.016<0.05)。胃癌组织中c-Myc、CDK12阳性患者的3年生存率分别为19.4%、21.4%,均明显低于c-Myc、CDK12阴性患者的55.6%、70.0%(P<0.05)。结论 c-Myc、CDK12在胃癌组织中异常高表达,两者呈正相关性,并与肿瘤的TNM分期、分化程度、肿瘤侵袭深度及淋巴结转移有关,对患者的预后有明显影响,通过检测两者水平可能评估胃癌患者的预后。

胃癌模型大鼠胃黏膜组织Cyclin D1、c-Myc、CKIT的表达意义及其与胃癌病变程度的相关性

目的探讨胃癌模型大鼠胃黏膜组织细胞周期蛋白D1(cyclinD1)、c-Myc、CKIT的表达意义及其与胃癌病变程度的相关性。方法选择48只健康成年雌性大鼠,按照随机数字表法将其分为对照组、研究1组、研究2组、研究3组,每组各12只。研究1组、研究2组、研究3组均制备成胃癌模型。对照组给予等量0.9%氯化钠溶液,第24周处死取材;研究1组、研究2组、研究3组制备成胃癌大鼠后分别于第8、16、24周取材。分析各组大鼠一般情况及胃黏膜组织病理切片,采用蛋白质印迹法检测胃黏膜组织Cyclin D1、c-Myc、CKIT蛋白的表达,采用逆转录聚合酶链式反应(RT-PCR)法测定胃黏膜组织Cyclin D1、c-Myc、CKIT mRNA的表达,采用Spearman分析法测定胃黏膜组织Cyclin D1、c-Myc、CKIT表达与胃癌病变程度相关性。结果对照组大鼠胃黏膜完整正常,外膜层、肌层、黏膜下层、黏膜层等结构清晰,且无炎症细胞浸润;研究1组大鼠胃黏膜组织与对照组大鼠接近,不存在炎症细胞,且黏膜腺体结构基本正常;研究2组大鼠胃黏膜组织存在破损,细胞核变大,基底部部分腺体细胞形态异常,存在轻度异型性,为早期胃癌;研究3组大鼠胃黏膜组织增加破损,核质比变大,细胞形态不规则,部分腺体存在扩张,黏膜下层及肌层存在炎症细胞浸润,为胃癌进展期。研究1组、研究2组、研究3组胃黏膜组织Cyclin D1、c-Myc、CKIT蛋白均呈显著高于对照组,差异均有统计学意义(P<0.05),胃黏膜组织Cyclin D1、c-Myc、CKIT蛋白在研究1组、研究2组、研究3组中逐渐升高趋势。研究1组、研究2组、研究3组胃黏膜组织Cyclin D1、c-Myc、CKIT mRNA均呈显著高于对照组,差异均有统计学意义(P<0.05),胃黏膜组织Cyclin D1、c-Myc、CKIT mRNA在研究1组、研究2组、研究3组中逐渐升高趋势。采用Spearman相关性结果分析显示,胃黏膜组织Cyclin D1、c-Myc、CKIT表达与胃癌病变程度呈正相关(r=0.382、0.781、0.993,均P<0.001)。结论胃癌模型大鼠胃黏膜组织Cyclin D1、c-Myc、CKIT呈高表达,其与胃癌病变程度密切相关。

猫CDH1基因在过表达c-MYC成纤维细胞中的表达变化及生物信息学分析

[目的]试验旨在研究骨髓细胞瘤病毒癌基因同源物(myelocytomatosis viral oncogene homolog, c-MYC)对猫成纤维细胞的影响及其与E-钙黏蛋白(cadherin 1,CDH1)基因表达和分子特性的关系,为将其应用于猫肿瘤疾病防治和组织损伤修复提供依据。[方法]通过组织贴壁法对猫胎儿成纤维细胞进行分离培养,利用电转仪将PB-TRE-c-MYC质粒转染至细胞并观察细胞形态,利用实时荧光定量PCR检测CDH1基因的表达情况,并通过生物信息学软件分析CDH1蛋白的理化性质和结构特征。[结果]过表达c-MYC导致细胞形态发生变化,从间质细胞的长梭型向上皮细胞的鹅卵石状发生转变,且使上皮细胞标志基因CDH1的表达极显著上调(P<0.01)。生物信息学分析显示,猫CDH1蛋白有881个氨基酸,其中含量最多的是亮氨酸,定位于细胞膜,存在4个CA结构域,介导细胞与细胞的接触,属于亲水性的酸性蛋白,主要由无规则卷曲组成,可能存在由Sec易位子转运并被信号肽酶Ⅰ(Sec/SPⅠ)切割的信号肽位点。[结论]猫CDH1基因的表达可被外源性重编程因子c-MYC激活,其编码的钙黏蛋白可促进猫胎儿成纤维细胞的间质-上皮转化,以抑制细胞癌化。

华蟾素通过调控MYH9/USP7/c-MYC通路抑制急性髓系白血病细胞免疫逃逸

【目的】探讨华蟾素调控肌球蛋白重链9(MYH9)/泛素特异性蛋白酶7(USP7)/骨髓细胞瘤病毒癌基因(c-MYC)通路对急性髓系白血病(AML)细胞免疫逃逸的影响。【方法】(1)体内实验:建立裸鼠异种移植瘤模型,评估华蟾素对AML细胞在体内生长和免疫逃逸的影响。(2)体外实验:使用不同浓度的华蟾素处理人AML细胞株HL-60,细胞计数试剂盒8(CCK-8)法检测细胞活力,Transwell实验检测细胞侵袭能力。将HL-60细胞与活化的CD8^(+)T细胞共培养,流式细胞术检测CD8^(+)T细胞表面标志物CD25的表达,酶联免疫吸附分析(ELISA)检测共培养上清液中细胞因子[白细胞介素2(IL-2)和干扰素(IFN-γ)]的水平,CytoTox96非放射性细胞毒性分析评估CD8^(+)T细胞对HL-60细胞的毒性。Western Blot法检测MYH9、USP7和c-MYC的蛋白表达,免疫共沉淀(Co-IP)法检测MYH9、USP7和泛素化之间的相互作用。转染MYH9过表质粒,验证华蟾素在AML中的作用机制。【结果】华蟾素抑制裸鼠移植瘤生长,增强CD8^(+)T细胞抗肿瘤的能力。华蟾素浓度依赖性地抑制HL-60细胞活力、侵袭。华蟾素处理后上调CD8^(+)T细胞表面标志物CD25的表达,同时还上调IL-2和IFN-γ水平。华蟾素增强CD8^(+)T细胞对HL-60细胞的毒性。华蟾素抑制HL-60细胞MYH9、USP7和c-MYC的蛋白表达,MYH9通过募集USP7促进c-MYC去泛素化,华蟾素抑制MYH9介导的c-MYC去泛素化。【结论】华蟾素可通过抑制MYH9的表达进而减少去泛素化酶USP7对c-MYC的募集,促进c-MYC泛素化降解,从而抑制AML细胞免疫逃逸。

鳜弹状病毒N蛋白与鳜c-Myc互作调控谷氨酰胺代谢机制

为了研究鳜弹状病毒(SCRV)如何调控鳜c-Myc(Sc-c-Myc)进而调控谷氨酰胺代谢的分子机制,本研究通过免疫共沉淀联合蛋白质谱寻找可能与Sc-c-Myc互作的病毒蛋白,初步分析确定为核衣壳蛋白(N蛋白);Co-IP结果显示,SCRV的N蛋白与Sc-c-Myc存在相互作用。通过PCR扩增获得了带有Flag标签序列的SCRV-N基因的ORF片段,并构建了SCRV-N蛋白过表达载体pcDNA-N-Flag;将pcDNA-N-Flag质粒转染鳜脑组织细胞系(CPB细胞系),荧光共定位结果显示,Sc-c-Myc与SCRV-N在细胞质内存在共定位现象;通过逆转录实时定量PCR(RT-qPCR)和免疫印记(Western blot)检测转染pcDNA-N-Flag的CPB细胞系中Sc-c-Myc及谷氨酰胺代谢通路关键酶(GLS1、GDH和IDH2)的表达变化,发现Sc-c-Myc、GLS1的转录水平和蛋白水平均显著上调。综上表明,SCRV的N蛋白与Sc-c-Myc互作促进Sc-c-Myc的表达,进而调控宿主细胞谷氨酰胺代谢途径,为SCRV防控提供了新的靶点。

基于ERK介导C-Myc/PD-L1协同作用探讨参芪抑瘤方联合顺铂对H22肝癌荷瘤小鼠的抑瘤机制

目的:探讨参芪抑瘤方联合顺铂经ERK介导C-Myc/PD-L1相协途径对H22肝癌荷瘤小鼠的抑瘤作用及其机制。方法:60只SPF级雄性昆明小鼠,采用随机数字表法取10只小鼠作为空白组,其余50只小鼠复制H22肝癌荷瘤小鼠模型,模型复制成功后将模型小鼠随机分为模型组、顺铂组[2.5×10^(-3) g/(kg·3 d)]、参芪抑瘤方低[13.515 g/(kg·d)]、中[27.030 g/(kg·d)]、高剂量[54.060 g/(kg·d)]联合顺铂[2.5×10^(-3) g/(kg·3 d)]组,每组10只,治疗13 d,末次给药24 h后,麻醉处死小鼠,测定小鼠肿瘤抑制率和脾指数、胸腺指数;HE染色观察小鼠肿瘤组织病理学变化;ELISA试剂盒检测肿瘤组织匀浆液中EGF、IFN-γ含量;IHC法和Western blot法检测肿瘤组织中p-ERK1/2、C-Myc、PD-L1蛋白表达;RT-PCR法检测肿瘤组织中ERK、C-Myc、PD-L1mRNA表达水平。结果:与空白组相比,模型组小鼠平均体质量和脾脏指数均降低(P<0.05);与模型组相比,各治疗组肿瘤抑制效果明显,且参芪抑瘤方联合顺铂组以剂量依赖性方式抑制肝癌小鼠肿瘤生长,提高小鼠平均体质量和脾指数、胸腺指数,促进肿瘤细胞坏死,增加坏死面积,降低肿瘤组织中EGF和IFN-γ含量以及p-ERK1/2、C-Myc、PD-L1蛋白表达和ERK、C-Myc、PD-L1 mRNA表达(P<0.05);与顺铂组相比,参芪抑瘤方中、高剂量联合顺铂组治疗效果显著,差异具有统计学意义(P<0.05)。结论:参芪抑瘤方联合顺铂能有效抑制H22肝癌荷瘤小鼠的肿瘤生长,显著下调肿瘤组织中C-Myc与PD-L1蛋白表达,该机制可能通过调控ERK信号通路相关蛋白表达发挥抑瘤作用。

RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

Genetic dissection and validation of a major QTL for grain weight on chromosome 3B in bread wheat(Triticum aestivum L.)

Grain weight is one of the key components of wheat(Triticum aestivum L.)yield.Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs.A recombinant inbred line(RIL)population derived from a cross between W7268 and Chuanyu 12(CY12)was employed to detect quantitative trait loci(QTLs)for thousand-grain weight(TGW),grain length(GL),grain width(GW),and the ratio of grain length to width(GLW)in six environments.Seven major QTLs,QGl.cib-2D,QGw.cib-2D,QGw.cib-3B,QGw.cib-4B.1,QGlw.cib-2D.1,QTgw.cib-2D.1 and QTgw.cib-3B.1,were consistently identified in at least four environments and the best linear unbiased estimation(BLUE)datasets,and they explained 2.61 to 34.85%of the phenotypic variance.Significant interactions were detected between the two major TGW QTLs and three major GW loci.In addition,QTgw.cib-3B.1 and QGw.cib-3B were co-located,and the improved TGW at this locus was contributed by GW.Unlike other loci,QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike(GNS).They were further validated in advanced lines using Kompetitive Allele Specific PCR(KASP)markers,and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus.Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars.According to gene annotation,spatial expression patterns,ortholog analysis and sequence variation,the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted.Collectively,the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

在口腔表皮样癌细胞中c-myc对GS和GLS表达的调控以及对癌瘤生长的裸鼠体内实验研究

目的:用动物实验模型探讨人口腔表皮样癌细胞中c-myc与谷氨酰胺酶(GLS)、谷氨酰胺合成酶(GS)间的相关性。方法:免疫组化检测口腔癌临床样本中c-myc、GLS、GS表达。建立c-myc稳定高表达的KB细胞模型,并移植入裸鼠体内以建立裸鼠成瘤模型,细胞和裸鼠各分为3组(n=6),分别为正常对照组、空载体转染细胞组和c-myc过表达细胞组,观察肿瘤生长;免疫组化检测肿瘤中c-myc、 GLS、 GS的表达情况。结果:c-myc、 GLS、 GS在口腔癌临床样本中高表达;在c-myc高表达细胞模型中c-myc mRNA表达水平显著高于空载体对照组;在动物实验中,随着时间的延长,各组裸鼠成瘤模型均形成肿瘤,c-myc过表达组肿瘤体积及重量增加更为显著(P<0.01);c-myc过表达组瘤组织样本中GLS及GS表达显著高于空载体组和对照组(P<0.01)。结论:在口腔表皮样癌细胞中,c-myc高表达,并使GLS、GS表达升高。

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

Pangenome and multi-tissue gene atlas provide new insights into the domestication and highland adaptation of yaks

Background The genetic diversity of yak,a key domestic animal on the Qinghai-Tibetan Plateau(QTP),is a vital resource for domestication and breeding efforts.This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes.Results We discovered 290 Mb of nonreference sequences and 504 new genes.Our pangenome-wide presence and absence variation(PAV)analysis revealed 5,120 PAV-related genes,highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations.Principal component analysis(PCA)based on binary gene PAV data classified yaks into three new groups:wild,domestic,and Jinchuan.Moreover,we pro-posed a‘two-haplotype genomic hybridization model'for understanding the hybridization patterns among breeds by integrating gene frequency,heterozygosity,and gene PAV data.A gene PAV-GWAS identified a novel gene(Bos-Gru3G009179)that may be associated with the multirib trait in Jinchuan yaks.Furthermore,an integrated transcrip-tome and pangenome analysis highlighted the significant differences in the expression of core genes and the muta-tional burden of differentially expressed genes between yaks from high and low altitudes.Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed m RNAs and lnc RNAs(between high-and low-altitude regions),especially in the heart and lungs,when comparing high-and low-altitude adaptations.Conclusions The yak pangenome offers a comprehensive resource and new insights for functional genomic studies,supporting future biological research and breeding strategies.

AMME chromosomal region gene 1基因变异矮小相关综合征一例及文献复习

目的探讨1例身材矮小、面中部发育不全患儿的病因,以提高临床医师对特殊矮小综合征的认识。方法收集1例身材矮小、面中部发育不全患儿的临床资料,对患儿及父母行基因检测,并给予患儿常规治疗、随访。结果结合患儿特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征,结合文献复习总结AMMECR1基因变异矮小相关综合征特点。结论AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,临床主要表现为身材矮小、运动语言落后、肌张力减低、听力损失、面中部发育不全,部分存在心脏改变、腭裂、骨骼改变及椭圆形红细胞增多症、智力落后和肾钙质沉着症。该文报道1例AMMECR1基因新变异引起身材矮小、面中部发育不全患儿的病例资料,结合特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征。AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,本文初步概括其特点,并结合文献进行分析,以提高临床医师对AMMECR1基因变异矮小相关综合征的诊治。

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.