Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

PROTOS70卷烟机接装纸胶后刚性纠偏装置的研制

PROTOS70型卷烟机接装纸输送装置的稳定性较差,现有接装纸长短调整装置存在设计缺陷,是导致接装纸偏移、错牙,造成卷烟产品接装纸长短超标或翘边等缺陷的主要原因。通过分析和研究接装纸输送装置的结构和工作原理,确定在接装纸进入切纸鼓轮前的位置加一种纠偏定位装置,能够明显提高接装纸输送的稳定性。基于该种纠偏原理,设计研制出一种新型接装纸刚性纠偏装置。这项改进增强了设备工艺过程控制能力,使接装纸搓接缺陷发生频次较加装前减少了30.17次/周,废品质量降低了4.37 kg/周,提高了烟支产品的外观质量。

THE EXPRESSION OF PROTOONCOGENES IN HUMAN GASTRIC CANCER CELL LINES AND PRIMARY GASTRIC CANCERS DEFINED BY IN SITU HYBRIDIZATION

The expression of several protooncogenes was detected in three different differentiated gastric cancer cell lines (MKN28, MKN45, SGC7901) and 5 specimens from 5 human primary gastric cancers at cellular level by in situ hybridization. The data indicated that there were high levels of c-Ha-ras expression in both cell lines and tumor tissues as compared with control samples. But the transcripts of c-myc and c-erbB were rather low. The results suggested that Ha-ras be involved in or associated with the gastric cancer. There were another two interesting findings: (1) The levels of c-Ha-ras was different among the individual cancer cells within a single gastric cnacer. (2) Some inflammatory cells in the tumor tissuse and normal tissues adjacent to the cancer displayed high level of c-Ha-ras expression. Those two phenomena are worthwhile for further study.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

TCGA-based analysis of oncogenic signaling pathways underlying oral squamous cell carcinoma

Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.

基于Protos70的烟支硬度影响因素分析

烟支硬度由于受限于烟丝结构及吸丝成型,Protos70卷接机直接调控手段较少。为此,通过对影响烟支硬度的物料供给指标进行控制,设备参数进行优化。并对烟支紧头位置偏移、烟丝束在送丝轨道内的烟丝形态差异、烟支硬度与其他物理指标交互影响进行分析。根据分析结果,烟支紧头偏移区间介于[(8.5,21)~(34,46.5)]区域时将导致烟支硬度异常;当负压供给在118~147 mbar时,烟丝在送丝轨道内处于非均匀流时,硬度可控性好;烟支硬度与吸阻的离散程度呈高度线性正相关,与长度呈中度线性正相关。

Proto-oncogenes expression in the process of asthma airway remodeling

Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells. Pathologic studies showed there were smooth muscle thicken around bronchia and lymphocytes infiltration under mucosa or around bronchia smooth muscle. Conclusion: Proto-oncogenes expressed in airway of asthma in a guinea pig model, proto-oncogenes may have roles in the process of airway remodeling.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

一种用于PROTOS 2-2(MAX)接装纸胶带架的设计

为解决PROTOS 2-2(MAX)在生产新版玉溪和谐卷烟时接装纸搭接不上的问题,我们根据PROTOS 2-2的机器情况设计发明了一种接装纸搭接的胶带架,使新版玉溪和谐的接装纸可以顺利搭接。

PROTOS 2C卷烟机组SE胶水桶表层防凝结的设计及应用

PROTOS 2C卷烟机通过压缩空气向胶水桶内加压以保证连续不断向喷胶嘴供胶,但容易出现胶水桶内表层胶水产生胶皮和凝结成块,堵塞胶水管路及喷嘴的情况,针对这个问题,我们在继续使用原有压缩空气系统的情况下,在桶盖上原有安全阀位置处安装快插气管接头,接入或门型梭阀,使得压缩空气不向外界排出,不带走胶水水分,问题得到解决。目前已应用于卷包一车间10台PROTOS 2C卷接机组,应用效果良好。The PROTOS 2C cigarette machine pressurizes the glue bucket with compressed air to ensure continuous supply of glue to the spray nozzle. However, it is prone to the occurrence of glue on the surface of the glue bucket forming rubber skin and clumping, blocking the glue pipeline and nozzle. In response to this problem, we have installed a quick insertion air pipe joint at the original safety valve position on the bucket cover while continuing to use the original compressed air system, and connected it to a door type shuttle valve to prevent compressed air from being discharged to the outside and not taking away glue moisture, thus solving the problem. At present, it has been applied to 10 PROTOS 2C winding and splicing units in the first packaging workshop, and the application effect is good.

A COMPARISON OF THE PROTOONCOGENES BETWEEN THE HUMAN GASTRIC CANCEROUS AND NORMAL MUCOSAL TISSUES

The allelic distribution of EcoRI and BamHI fragments of ras family genes between the human primary gastric cancer tissues and the corresponding adjacent normal tissues did not show any differences. Three genotypes of BamHI restriction fragment length polymorphism of c-H-ras were revealed. No significant differences in the RFLPs were observed between normal individuals and gastric cancer patients. Four protooncogenes, c-H-ras, N-ras, c-myc and c-fos, were found to be transcriptionally active in the gastric cancer tissues in some cases examined. The comparison of the expression of these oncogenes between the malignant tissues and the corresponding normal tissues showed differential patterns. The expression of c-H-ras at cellular level was detected by in situ hybridization. The enhanced expression of c-H-ras in the gastric cancer cells was demonstrated, but the degree of the expression among the cancer cells was shown to be heterogeneous. In addition, the enhanced expression of c-H-ras was seen in the inflammatory cells.

PROTOS70卷接机组VE空气系统对烟丝成形的影响

PROTOS70卷烟机组是烟厂的主流生产设备机型,吸丝通道由上下风室及上下导轨共同组成,下风室小风机电机产生正压吹风,与上风室体高压风机产生的负压吸风相互作用,将烟丝吸附到吸丝带上。实际生产过程中,常常会因烟丝吸附不足产生烟支空头等问题。通过对供料成条机的小风机电机主动轮进行改进,有效增大正压风机风量供给,保证烟丝在向上运动过程中惯性、气室正压吹风,与风室体负压共同作用,使烟丝顺利且足量吸附到吸丝带。针对卷接机组之间的负压相互干扰的问题,尤其是停机对相邻设备造成负压波动的问题,探索技术解决方案。改进后,烟条成型效果显著增强,相关的空头、过轻、过重剔除率从0.5%下降到0.3%,取得了较好的经济效益。

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

Effects of Cadmium on Hepatocellular DNA Damage,Proto-Oncogene Expression and Apoptosis in Rats

Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.

Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review

BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

EXPRESSION OF CELLULAR ONCOGENES IN PRIMARY CELLS FROM HUMAN LEUKEMIAS

The expression of three protooncogenes (c-myc, c-fos, N-ras) in.the primary cells from 53 cases of leukemia as well as peripheral WBC from 8 normal individuals was studied. Semiquantitative analysis of mRNA levels of the protooncogenes was carried out by Quick-blot. The results showed that (1) c-myc oncogene was slightly expressed and Nras was marginally expressed, whereas the expression of the c-fos was undetectable in the peripheral leucocytes of 8 normal individuals; (2) the c-myc was obviously expressed in almost all leukemic cells irrespective of the cell types, while N-ras and c-fos were variable expressed; (3) the c-fos was expressed in all 4 cases of M4; (4) the c-myc transcript was detected but the N-ras and c-fos were not in 4 chronic leukemic cases; (5) the relationship between protooncogene expression and state of leukemia or after chemotherapy was also analysed.

The significance of proto-oncogene HGF/SF receptor c-Met mRNA expression in nasopharyngeal carcinoma

Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

THE EXPRESSION OF C－erbB－1 AND C－erbB－2ONCOGENES IN BASAL CELL CARCINOMA ANDSQUAMOUS CELL CARCINOMA OF SKIN

The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamous cell carcinoma (SCC). We found that the expression of c-erbB-1 oncogene in all BCC increased by different degrees and the expression of c-erbB-2 oncogene in BCC was significantly reduced or lost when compared to that in normal epidermal cells. Furthermore, apparent negative and positive rela-tionships were observed respectively between the tumor differentiation and the expression of cerbB-1 and c-erbB-2 oncogenes in SCC. It is suggested that the abnormal expression of c-erbB-1 and c-erbB-2 oncogenes in BCC and SCC may play a role in the development of skin tumors. The pattern of the c-erbB-1 and c-erbB-2 oncogenes expression in SCC may assist in distinguishing the biological behavior and prognosis of SCC.

Oncogenes, Oncogenesis, and Oxygen Radicals

The role that free radicals in general and oxygen radicals in particular play in carcinogenesis has attracted considerable attention in recent years. The oxygen radicals are undesirable but inevitable products of aerobic metabolism in the normal living cell. The cellular antioxidant defense system maintains an appropriate balance between necessary oxidative events and those that are excessive. When this critical balance cannot be maintained because of the overloading of the cellularredox system, oxygen radicals can induce cell damage. They can influence carcinogenesis by inducing DN A damage from direct oxidation or indirectly from DNA-binding products of lipid peroxidation. Oxygen radicals can induce conformational changes in the plasma membrane by lipid peroxidation and protein degradation, thus influencing membrane-associated cellular activities. They are capable of affecting membrane-bound protein kinases, growth factors and their receptors, and, therefore, signal transduction and oncogene activation. Thus, the oxygen radicals can have a major influence on oncogenes and oncogenesis. (C)1990 Academic Press.Inc.