Immunogenicity and protective efficacy of recombinant M2e.Hsp70c(Hsp70_(359–610)) fusion protein against influenza virus infection in mice

New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.

Induction of Bone Matrix Protein Expression by Native Bone Matrix Proteins in C2C12 Culture

Objective To study the expression of bone matrix protein （BMP） induced by bovine bone morphogenetic proteins （BMPs） in vitro. Methods Type 1 collagen, osteopontin （OPN）, osteonectin （ON）, osteocalcin （OC）, and bone sialoprotein （BSP） were detected by immunohistochemistry in C2C12 cultured from day 1 to day 28. Results The signaling of bone matrix protein expression became weaker except for type I collagen, OC and BSP after 5 days. Fourteen days after culture, the positive signaling of type I collagen, OPN, ON, OC, and BSP was gradually declined, and could be detected significantly as compared with that of the negative control on day 28. BMP assay showed that the lkaline phosphatase （ALP） activity was higher in C2C12 culture than in the control during the 14-day culture. Also, total protein and DNA significantly increased during the 14-day culture. High levels of ALP were seen in preosteoblasts and osteoblsts in vivo and in differentiating osteoblasts in vitro. ALP was well recognized as a marker reflecting osteoblastic activity. Conclusion Native bovine BMP induces conversion of myoblasts into osteoblasts, produces type I collagen, and plays significantly role in osteoinduction and bone matrix mineralization of C2C 12 in vitro.

CHANGES OF NUCLEAR MATRIX PROTEIN AND ITS RELATIONSHIP WITH c-erbB-2 IN HUMAN COLON ADENOCARCINOMA

Objective： Nuclear matrix protein is tissue, cell-type specific, and tumor-relative. It plays an important role in the regulation of intranuclear processes. Some researches also showed that a c-erbB-2 promoter-specific DNA-binding nuclear matrix protein is present only in malignant human breast tissues and induces mitogenesis and cell surface expression of the c-erbB-2 protein in resting NIH/3T3 cells. But it is not clear that how it in colon adenocarcinomas. Methods： Two-dimensional gel electrophoretic method was used for NMP identification and immunohistochemistry was used for c-erbB-2 detection in 12 cases of colon adenocarcinomas and matched adjacent normal colon tissues. Results： 5 different nuclear matrix proteins （named C1-C5） were identified in 12 colon adenocarcinoma specimens, but not in the matched adjacent normal colon tissues; 3 nuclear matrix proteins （named N1-N3） were identified in all 12 matched adjacent normal colon tissues, but not in colon adenocarcinoma specimens. A nuclear matrix protein （named N4） was detected in all of 9 moderated-well differentiated adenocarcinomas and all 12 matched adjacent normal colon tissues, but not in 3 poor-differentiated adenocarcinomas. All of the 10 colon adenocarcinomas which had the nuclear matrix protein C4 were c-erbB-2 expression positive. Conclusion： The data suggest that there are specific nuclear matrix proteins in colon adenocarcinomas and its subtypes, which maybe valuable to serve as markers of colon adenocarcinomas in future. Nuclear matrix protein C4 probably is a c-erbB-2 promotor-specific nuclear matrix protein in colon adenocarcinomas, and may induce the expression of c-erbB-2.

Fitting evolutionary process of matrix protein 2 family from influenza A virus using analytical solution of differential equation

The evolution of protein family is a process along the time course, thus any mathematical methods that can describe a process over time could be possible to describe an evolutionary process. In our previously concept-initiated study, we attempted to use the differential equation to describe the evolution of hemagglutinins from influenza A viruses, and to discuss various issues related to the building of differential equation. In this study, we attempted not only to use the differential equation to describe the evolution of matrix protein 2 family from influenza A virus, but also to use the analytical solution to fit its evolutionary process. The results showed that the fitting was possible and workable. The fitted model parameters provided a way to further determine the evolutionary dynamics and kinetics, a way to more precisely predict the time of occurrence of mutation, and a way to figure out the interaction between protein family and its environment.

Anti-nuclear matrix protein 2+ juvenile dermatomyositis with severe skin ulcer and infection: A case report and literature review

BACKGROUND Juvenile dermatomyositis(JDM)is an idiopathic inflammatory myopathy that occurs in childhood.It is characterized by muscle weakness and a characteristic rash.Previous literature reports have rarely described JDM with severe skin ulcers and infections.CASE SUMMARY Herein,we describe a case of a 2-year-old female patient who suffered from JDM,whose myositis-specific autoantibodies were positive for anti-nuclear matrix protein 2 antibody,with progressively worsening skin ulcers and severe infections.The patient was treated with glucocorticoids and various immunosuppressants.Nevertheless,further progression of the disease and the combination of primary disease and severe infection in the later period were fatal.CONCLUSION In children,anti-nuclear matrix protein 2+JDM combined with skin ulcers often indicates severe disease.In such cases,personalized treatment for the primary disease and infection prevention and control are essential.

转H5禽流感病毒M2e基因烟草的研究

将禽流感病毒M2e与鸡IgG Fc的融合基因转入烟草植株,利用烟草生产禽流感抗原蛋白,探索利用植物作为生物反应器生产禽流感疫苗的可行性。将M2e-Fc融合基因克隆到植物表达载体pBI121中,与CaMV35s启动子相连,以烟草子叶作为外植体,利用农杆菌介导法将外源基因转入烟草中。对抗性植株进行了PCR、RT-PCR分析。结果表明,M2e基因已经导入到烟草中,在转录水平得到了表达。为进一步利用转基因植物生产禽流感疫苗进行了前期的探索工作。

禽流感病毒M2e基因与鸡IgG Fc基因在巴斯德毕赤酵母中的融合表达

【目的】得到融合蛋白M2e-Fc,并检测其免疫学特性,为研制禽流感通用疫苗奠定基础。【方法】根据禽流感病毒H5N1的M2e蛋白氨基酸序列设计2条长互补引物,通过重叠区互补扩增基因法扩增出目的基因M2e,然后与鸡IgGFc片段基因一起克隆入毕赤酵母表达质粒中,构建酵母表达载体。将阳性质粒线性化后电转化入感受态毕赤酵母X-33中,再经甲醇诱导后,通过Tricine-SDS-PAGE电泳及Western-blotting鉴定融合蛋白。之后用其免疫非免疫鸡,检验其免疫原性。【结果】成功构建了表达M2e和Fc融合蛋白的酵母表达载体pPICZαA-M2-Fc,并通过Zeocin筛选及PCR鉴定出了阳性重组子;阳性重组子经甲醇诱导后得到融合蛋白,Tricine-SDS-PAGE电泳及Western-blotting鉴定证实,融合蛋白得到正确表达,并且可以与M2e阳性血清反应。动物免疫试验证实,该融合蛋白可以诱导鸡产生抗M2e抗体,具有良好的免疫原性。【结论】融合蛋白M2e-Fc在巴斯德毕赤酵母表达系统中得到了成功表达,该融合蛋白具有较好的免疫原性,为后期进行其他免疫试验奠定了基础。

H9N2禽流感病毒M2 DNA疫苗初免-蛋白加强免疫的保护效果研究

流感病毒M2(基质蛋白2)是A型流感病毒的一个高度保守的蛋白。由于其免疫原性较弱,本研究采用M2 DNA疫苗初免-蛋白加强的策略来考察M2的免疫保护效果。制备A/Chicken/Jiangsu/07/2002(H9N2)流感病毒的M2 DNA疫苗以及经大肠杆菌表达的去除M2跨膜区的M2蛋白即sM2。以SPF级BALB/c小鼠为模型,电击法免疫M2 DNA疫苗,滴鼻法免疫sM2蛋白,免疫间隔三周,并于末次免疫后三周以致死量5LD50流感病毒H9N2攻击小鼠,通过检测小鼠存活率、体重丢失率、肺部病毒滴度及IgG抗体水平等指标来评价免疫的保护效果。实验结果表明,基于M2的疫苗采用DNA疫苗初免蛋白加强免疫二次的免疫程序能诱导较高的特异性抗体,明显减轻小鼠流感病症,提供完全的保护。

基于流感病毒HA柄部和M2e融合基因的DNA疫苗

由于流感病毒容易突变,流感通用疫苗的研究势在必行.流感病毒血凝素(HA)柄部和基质蛋白2的胞外域(M2e)都是流感病毒通用疫苗的重要候选靶点.通过重叠PCR的方法用A/PR/8/34(H1N1)(简称PR8)流感病毒的M2e或者4个甘氨酸取代HA的头部,分别获得HAM2e和HA4G,然后将两种重组基因插入真核表达载体pCAGGS-P7中,制得pHAM2e和pHA4G两种DNA疫苗.通过电击免疫的方法对小鼠分别免疫pHAM2e和pHA4G,免疫3次,每次免疫间隔2周.第3次免疫2周后用5LD50的同源流感病毒感染小鼠.结果表明HAM2e组和HA4G组的小鼠均产生了特异性抗体,HAM2e组比HA4G组具有更好的抗PR8流感病毒的能力,这提示可以用M2e替换HA头部用于疫苗研发.

Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer

BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

Retinoic Aacid Diminished the Expression of MMP-2 in Hyperoxia-exposed Premature Rat Lung Fibroblasts through Regulating Mitogen-activated Protein Kinases

This study examined the effects of retinoic acid （RA）, PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 （MMP-2） and metalloproteinase-2 （TIMP-2） in premature rat lung fibroblasts （LFs）. LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 （ERK1/2）, SP600125 （JNK1/2） and SB203580 （p38） respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that： （1） PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; （2） The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively （P0.01 or 0.05）, but did not change after treatment with PD98059 （P0.05）. Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia （P0.05）; （3） The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air （P0.05）, but decreased remarkably after hyperoxia （P0.01 or 0.05）. SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia （P0.01）. PD98059 exerted no effect on the expression of pro- and active MMP-2 （P0.05）. It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.

Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion

AIM： To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2＋ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase （MMP） production and adhesion ability of fibroblasts. METHODS： NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca^2＋ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction （RTPCR） were employed to detect the involvement of [Ca^2＋]i and NO/cGMP in MMP secretion. The involvement of NO/ cGMP-sensitive Ca^2＋ entry in adhesion was determined using matrigel-coated culture plates. RESULTS： 8-bromo-cGMP inhibited the thapsigargin-induced Ca^2＋ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 （1μmol/L）. A similar effect on the Ca^2＋ entry was observed in 3T3 cells in response to a NO donor, （±）-S-nitroso-N-acetylpenicillamine （SNAP）. The inhibitory effect of SNAP on the thapsigargin-induced Ca^2＋ entry was also observed, indicating NO/cGMP-regulated Ca^2＋ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca^2＋ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates.CONCLUSION： NO/cGMP sensitive store-operated Ca^2＋ entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion.

4种禽流感病毒M2e多肽的串联表达和小鼠口服免疫效果

为研制广谱性禽流感口服疫苗,将4种禽流感病毒特异的基质蛋白2胞外区(matrix protein 2ectodomain,M2e)多肽与黏膜免疫佐剂CTA1-DD串联,原核表达并纯化CTA1DD-AVI4M2e融合蛋白。以200μg融合蛋白CTA1DD-AVI4M2e口服免疫BALB/c小鼠,结果显示实验组肠液IgA抗体效价和血清IgG抗体效价比对照组显著升高,血清中特异性IgG抗体效价达约360倍。分割的3段肠样中:第1段浸出液IgA抗体效价约为360倍,第2段约为120倍,第3段约为9 720倍。结果表明,本研究制备的CTA1DDAVI4M2e具有显著口服免疫效果,为后续研究提供了基础。

结直肠癌组织中SPON2、MGP表达及临床意义

目的研究结直肠癌(CRC)组织中脊椎蛋白2(SPON2)、基质Gla蛋白(MGP)表达及与临床病理特征、预后的关系。方法选取2018年1月—2020年1月南京市第一医院普外科收治行手术治疗CRC患者94例。采用免疫组织化学法检测癌和癌旁组织中SPON2、MGP表达;分析SPON2、MGP表达与CRC患者临床病理特征及预后的关系;多因素Cox回归分析CRC患者预后影响因素。结果CRC癌及癌旁组织中SPON2阳性率分别为65.96%(62/94)和6.38%(6/94),MGP阳性率分别为63.83%(60/94)和8.51%(8/94),SPON2、MGP在CRC癌组织中的阳性率高于癌旁组织(χ^(2)=72.251、62.298,P均<0.001)。低分化程度、TNM分期Ⅲ期及有淋巴结转移患者SPON2、MGP阳性率分别高于高中分化、TNM分期I~Ⅱ期及无淋巴结转移患者(χ^(2)/P=9.694/0.002、10.883/0.001、14.100/<0.001,14.785/<0.001、9.731/0.002、12.739/<0.001)。SPON2阳性组、阴性组3年生存率分别为54.84%(34/62)和86.67%(26/30);MGP阳性组、阴性组3年生存率分别为53.33%(32/60)和87.50%(28/32)。SPON2阳性组、MGP阳性组3年累积生存率低于SPON2阴性组、MGP阴性组(χ^(2)=8.966、12.420,P=0.003、<0.001)。肿瘤TNM分期Ⅲ期、低分化程度、伴淋巴结转移、SPON2阳性、MGP阳性是影响CRC患者预后的独立危险因素[HR(95%CI)=1.768(1.226~2.551)、1.613(1.223~2.126)、1.600(1.167~2.194)、1.866(1.324~2.630)、1.315(1.151~1.503),均P<0.001]。结论CRC中SPON2、MGP表达升高,两者与CRC不良临床病理特征有关,是新的评估CRC患者预后的肿瘤标志物。

胰岛素样生长因子1对人RPE细胞分泌TGF-β2、MMP-2的影响及机制研究

目的研究胰岛素样生长因子1(IGF-1)对人视网膜色素上皮细胞(ARPE-19)表达转化生长因子β2(TGF-β2)、基质金属蛋白酶2(MMP-2)的影响,并探索其作用机制。方法ARPE-19细胞分别按不同浓度IGF-1和不同浓度LY294002培养6 h、12 h、24 h、48 h,采用CCK-8法检测细胞活力,确定IGF-1、LY294002的最佳作用浓度与时间。细胞划痕法检测细胞迁移活性。ELISA法检测细胞培养上清液中TGF-β2浓度。将ARPE-19细胞分为对照组、IGF-1组(80μg·L^(-1) IGF-1)、IGF-1+LY294002组(80μg·L^(-1) IGF-1+30 mmol·L^(-1) LY294002)、LY294002组(30 mmol·L^(-1) LY294002),使用无血清DMEM/F12培养基培养,对照组不做任何处理,分别采用RT-PCR、Western blot检测细胞中TGF-β2、MMP-2、磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)的mRNA和蛋白表达量。结果与0μg·L^(-1) IGF-1比较,80μg·L^(-1) IGF-1的细胞活力24 h变化显著(P<0.05),故确定其为IGF-1最佳作用浓度和时间。与0 mmol·L^(-1) LY294002比较,24 h的30 mmol·L^(-1) LY294002接近半数抑制浓度,故确定其为LY294002最佳作用时间和浓度。细胞划痕法检测结果显示,0μg·L^(-1) IGF-1组、40μg·L^(-1) IGF-1组、80μg·L^(-1) IGF-1组细胞迁移率整体比较及两两比较差异均有统计学意义(均为P<0.05)。ELISA检测结果显示,0μg·L^(-1) IGF-1组、40μg·L^(-1) IGF-1组、80μg·L^(-1) IGF-1组细胞上清液中TGF-β2浓度整体比较及两两比较差异均有统计学意义(均为P<0.05)。RT-PCR、Western blot检测结果显示,IGF-1、LY294002培养24 h,与对照组比较,IGF-1组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均升高,而LY294002组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均下降(均为P<0.05);与IGF-1组比较,IGF-1+LY294002组细胞中TGF-β2、MMP-2、PI3K、AKT的mRNA与蛋白表达水平均下降(均为P<0.05)。结论IGF-1能促进ARPE-19细胞增殖、迁移;IGF-1可能通过PI3K/AKT信号通路上调ARPE-19细胞中TGF-β2、MMP-2的表达,参与近视的发生与发展。

Nuclear localization of Sindbis virus nonstructural protein nsP2

In early infection, approximately 10% of nonstruc-tural protein nsP2 of Sindbis virus was transported into the nuclei of virus-infected BHK-21 cells. Nuclear nsP2 was dominantly associated with nuclear matrix. During the course of infection, increasing amounts of nsP2 accumulated in the nuclear fraction. A prominent accumulation of nuclear nsP2 occurred early in infection, from 1 h to 3 h postinfection. Meanwhile, a weak NTPase activity was found to be associated with the immunocomplexed nsP2. Nuclear localization of nsP2 and its possible role were discussed in relation to the inhibition of host macro-molecular synthesis.

2型糖尿病患者血清巨噬细胞炎症蛋白1α和基质金属蛋白酶9水平与甲状腺结节的相关性研究

目的探讨2型糖尿病(T_(2)DM)患者血清巨噬细胞炎症蛋白1α(MIP-1α)、基质金属蛋白酶9(MMP-9)水平与甲状腺结节的相关性。方法回顾性选取2021年10月至2023年3月于河北医科大学第三医院就诊的T_(2)DM患者154例,根据患者是否合并甲状腺结节分为甲状腺结节组(83例)和无甲状腺结节组(71例)。比较2组甲状腺功能、血糖、血脂、MIP-1α、MMP-9等指标。采用Logistic回归模型分析影响T_(2)DM患者出现甲状腺结节的因素;采用Pearson相关性检验分析T_(2)DM患者血清MIP-1α、MMP-9水平与其他因素的相关性;绘制受试者工作特征曲线分析血清MIP-1α、MMP-9水平对T_(2)DM患者出现甲状腺结节的预测价值。结果甲状腺结节组促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT_(3))、总甲状腺素(TT_(4))、稳态模型胰岛素抵抗指数(HOMA-IR)、稳态模型胰岛β细胞功能指数、空腹血糖、空腹胰岛素水平均高于无甲状腺结节组,胰岛素敏感指数(ISI)低于无甲状腺结节组(均P<0.05)。甲状腺结节组血清MIP-1α、MMP-9水平均高于无甲状腺结节组[(29±5)ng/L比(25±5)ng/L、(2.0±0.5)ng/L比(1.4±0.5)ng/L](均P<0.001)。Logistic回归分析结果显示,MIP-1α、MMP-9、TSH、TT_(3)、TT_(4)、空腹胰岛素、HOMA-IR和ISI均为T_(2)DM患者出现甲状腺结节的危险因素(均P<0.05)。Pearson相关性分析结果表明,T_(2)DM患者血清MIP-1α与MMP-9水平呈正相关(r=0.362,P<0.001)。血清MIP-1α、MMP-9水平与空腹胰岛素、TSH、HOMA-IR、TT_(3)、TT_(4)均呈正相关,与ISI呈负相关(均P<0.001)。MIP-1α、MMP-9水平联合检测预测T_(2)DM患者出现甲状腺结节的曲线下面积大于MIP-1α、MMP-9单独检测(均P<0.05)。结论血清MIP-1α、MMP-9水平与T_(2)DM患者出现甲状腺结节具有密切关系,对预测T_(2)DM患者甲状腺结节具有重要价值。

Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma

BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.

m^(6)A阅读蛋白YTHDF2在肿瘤中作用的研究进展

N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)修饰是真核生物最常见的RNA修饰类型之一,在多种生理过程和疾病进展中起着关键作用。YT521-B同源性域家族2(YT521-B homology domain family proteins 2,YTHDF2)是m^(6)A修饰的重要结合蛋白之一,影响mRNAs的翻译和稳定性,研究证实YTHDF2参与了肺癌、肝癌、急性髓系白血病等多种恶性肿瘤的发生发展,本文总结了YTHDF2在肿瘤发生发展中的调控机制,为基于YTHDF2的抗肿瘤研发提供新思路。

Expression and Significance of ECP, 25-(OH)D3 and M2 receptors in Children with Acute Attack of Asthma

Objective:To study the expression and significance of ECP, 25-(OH)D3 and M2 receptors in children with acute attack of asthma.Methods: Seventy children with bronchial asthma who first visited our hospital from September 2016 to September 2018 were divided into chronic persistence group, remission group and acute attack group. Thirty healthy children who underwent physical examination in our hospital were selected and divided into control group. The levels of ECP, 25-(OH) D3 and M2 receptors were analyzed by ELISA, and Pearson correlation analysis was performed.Results: Compared with the control group, the levels of ECP and M2 receptors in chronic persistence group, remission group and acute attack group increased, while the levels of 25-(OH)D3 decreased, with statistical difference (P<0.05). The levels of ECP and M2 receptors in acute attack group were higher than those in chronic persistence group, and the levels of 25-(OH)D3 were lower than those in chronic persistence group (P<0.05). The levels of ECP and M2 receptors in acute attack group were higher than those in remission group, and the levels of 25-(OH)D3 were lower than those in remission group (P<0.05). Compared with mild children, the levels of ECP and M2 receptors increased and 25-(OH)D3 decreased in moderate and severe children (P<0.05). Compared with moderate children, the levels of ECP and M2 receptors increased and 25-(OH)D3 decreased in severe children (P<0.05).There was a negative correlation between ECP and 25-(OH)D3 (r=-0.380, P=0.038);a negative correlation between 25-(OH)D3 and M2 receptor (r=-0.448,P=0.013);and a positive correlation between ECP and M2 receptor (r=0.450,P=0.013).Conclusions:The expression of ECP and M2 receptors increased during the acute attack of bronchial asthma in children, while the expression of 25-hydroxyvitamin D3 decreased during the acute attack of bronchial asthma in children. The correlation among ECP, 25-(OH) D3 and M2 receptors is significant in the clinical diagnosis of acute attack of bronchial asthma in children.