Distinct gene expression profiles underlie morphological and etiological differences in pediatric cataracts

Purpose: Pediatric cataract is a major cause of preventable childhood blindness worldwide. Although genetic mutations or infections have been described in patients, the mechanistic basis of human cataract development remains poorly understood. Therefore, gene expression of structural, developmental, profibrotic, and transcription factors in phenotypically and etiologically distinct forms of pediatric cataracts were evaluated. Methods: This cross?sectional study included 89 pediatric cataract subjects subtyped into 1) prenatal infectious (cytomegalovirus, rubella, and combined cytomegalovirus with rubella infection), 2) prenatal non?infectious, 3) posterior capsular anomalies, 4) postnatal, 5) traumatic, and 6) secondary, and compared to clear, non?cataractous material of eyes with the subluxated lenses. Expression of lens structure?related genes (Aqp-0, HspA4/Hsp70, CrygC), transcription factors (Tdrd7, FoxE3, Maf, Pitx 3) and profibrotic genes (Tgf?, Bmp7, ?SmA, vimentin) in surgically extracted cataract lens material were studied and correlated clinically. Results: In cataract material, the lens?related gene expression profiles were uniquely associated with phenotype/etiology of different cataracts. Postnatal cataracts showed a significantly altered FoxE3 expression. Low levels of Tdrd7 expression correlated with posterior subcapsular opacity, whereas CrygC correlated significantly with anterior capsular ruptures. The expression of Aqp0 and Maf was elevated

Integrated aqueous humor ceRNA and miRNA–TF–mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

To conduct an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and the regulatory mechanism governing primary open?angle glaucoma (POAG) progression. Methods: Two datasets (GSE101727 and GSE105269) were downloaded from the Gene Expression Omnibus, and the messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) were identified between controls and POAG patients. Differentially expressed (DE) mRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein–protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA–miRNA–mRNA and miRNA–transcription factor (TF)–mRNA networks. Results: The GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 47 lncRNAs, six miRNAs, and 17 mRNAs. The proteins encoded by these 17 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA–TF–mRNA regulatory network containing two miRNAs (miR?135a?5p and miR?139?5p), five TFs (TGIF2, TCF3, FOS, and so on), and five mRNAs (SHISA7, ST6GAL2, TXNIP, and so on). Conclusion: The SHISA7, ST6GAL2, TXNIP, FOS, and DCBLD2 genes may be viable therapeutic targets for the prevention or treatment of POAG and are regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS)

Regulon: An overview of plant abiotic stress transcriptional regulatory system and role in transgenic plants / Regulon: Uma visão geral do sistema regulador da transcrição do estresse abiótico em plantas e papel nas plantas transgênica

Abstract Population growth is increasing rapidly around the world, in these consequences we need to produce more foods to full fill the demand of increased population. The world is facing global warming due to urbanizations and industrialization and in this concerns plants exposed continuously to abiotic stresses which is a major cause of crop hammering every year. Abiotic stresses consist of Drought, Salt, Heat, Cold, Oxidative and Metal toxicity which damage the crop yield continuously. Drought and salinity stress severally affected in similar manner to plant and the leading cause of reduction in crop yield. Plants respond to various stimuli under abiotic or biotic stress condition and express certain genes either structural or regulatory genes which maintain the plant integrity. The regulatory genes primarily the transcription factors that exert their activity by binding to certain cis DNA elements and consequently either up regulated or down regulate to target expression. These transcription factors are known as masters regulators because its single transcript regulate more than one gene, in this context the regulon word is fascinating more in compass of transcription factors. Progress has been made to better understand about effect of regulons (AREB/ABF, DREB, MYB, and NAC) under abiotic stresses and a number of regulons reported for stress responsive and used as a better transgenic tool of Arabidopsis and Rice.

Resumo O crescimento populacional está aumentando rapidamente em todo o mundo, e para combater suas consequências precisamos produzir mais alimentos para suprir a demanda do aumento populacional. O mundo está enfrentando o aquecimento global devido à urbanização e industrialização e, nesse caso, plantas expostas continuamente a estresses abióticos, que é uma das principais causas do martelamento das safras todos os anos. Estresses abióticos consistem em seca, sal, calor, frio, oxidação e toxicidade de metais que prejudicam o rendimento da colheita continuamente. A seca e o estresse salino são afetados de maneira diversa pela planta e são a principal causa de redução da produtividade das culturas. As plantas respondem a vários estímulos sob condições de estresse abiótico ou biótico e expressam certos genes estruturais ou regulatórios que mantêm a integridade da planta. Os genes reguladores são principalmente os fatores de transcrição que exercem sua atividade ligando-se a certos elementos cis do DNA e, consequentemente, são regulados para cima ou para baixo para a expressão alvo. Esses fatores de transcrição são conhecidos como reguladores mestres porque sua única transcrição regula mais de um gene; nesse contexto, a palavra regulon é mais fascinante no âmbito dos fatores de transcrição. Progresso foi feito para entender melhor sobre o efeito dos regulons (AREB / ABF, DREB, MYB e NAC) sob estresses abióticos e uma série de regulons relatados como responsivos ao estresse e usados ​​como uma melhor ferramenta transgênica de Arabidopsis e Rice.

Transcription factor EB attenuates neuronal damage following cerebral ischemia via regulating autophagy-lysosomal pathway / 国际脑血管病杂志

The disorder of autophagy lysosomal pathway (ALP) is an important pathogenesis of neuronal damage after cerebral ischemia, and the restoration of ALP may alleviate neuronal damage after cerebral ischemia. As the main transcription factor regulating ALP, transcription factor EB (TFEB) can directly regulate autophagosome generation, autophagosome-lysosome fusion, and autophagic flux by regulating the expression of autophagic genes and lysosomal genes. Therefore, regulating TFEB can alleviate ALP dysfunction and thereby reduce cerebral ischemic damage. This article reviews the structure, biological function of TFEB and its role in regulating ALP to alleviate neuronal damage after cerebral ischemia.

Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors / 生物工程学报

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

Regulon: An overview of plant abiotic stress transcriptional regulatory system and role in transgenic plants / Regulon: Uma visão geral do sistema regulador da transcrição do estresse abiótico em plantas e papel nas plantas transgênica

Population growth is increasing rapidly around the world, in these consequences we need to produce more foods to full fill the demand of increased population. The world is facing global warming due to urbanizations and industrialization and in this concerns plants exposed continuously to abiotic stresses which is a major cause of crop hammering every year. Abiotic stresses consist of Drought, Salt, Heat, Cold, Oxidative and Metal toxicity which damage the crop yield continuously. Drought and salinity stress severally affected in similar manner to plant and the leading cause of reduction in crop yield. Plants respond to various stimuli under abiotic or biotic stress condition and express certain genes either structural or regulatory genes which maintain the plant integrity. The regulatory genes primarily the transcription factors that exert their activity by binding to certain cis DNA elements and consequently either up regulated or down regulate to target expression. These transcription factors are known as masters regulators because its single transcript regulate more than one gene, in this context the regulon word is fascinating more in compass of transcription factors. Progress has been made to better understand about effect of regulons (AREB/ABF, DREB, MYB, and NAC) under abiotic stresses and a number of regulons reported for stress responsive and used as a better transgenic tool of Arabidopsis and Rice.

O crescimento populacional está aumentando rapidamente em todo o mundo, e para combater suas consequências precisamos produzir mais alimentos para suprir a demanda do aumento populacional. O mundo está enfrentando o aquecimento global devido à urbanização e industrialização e, nesse caso, plantas expostas continuamente a estresses abióticos, que é uma das principais causas do martelamento das safras todos os anos. Estresses abióticos consistem em seca, sal, calor, frio, oxidação e toxicidade de metais que prejudicam o rendimento da colheita continuamente. A seca e o estresse salino são afetados de maneira diversa pela planta e são a principal causa de redução da produtividade das culturas. As plantas respondem a vários estímulos sob condições de estresse abiótico ou biótico e expressam certos genes estruturais ou regulatórios que mantêm a integridade da planta. Os genes reguladores são principalmente os fatores de transcrição que exercem sua atividade ligando-se a certos elementos cis do DNA e, consequentemente, são regulados para cima ou para baixo para a expressão alvo. Esses fatores de transcrição são conhecidos como reguladores mestres porque sua única transcrição regula mais de um gene; nesse contexto, a palavra regulon é mais fascinante no âmbito dos fatores de transcrição. Progresso foi feito para entender melhor sobre o efeito dos regulons (AREB / ABF, DREB, MYB e NAC) sob estresses abióticos e uma série de regulons relatados como responsivos ao estresse e usados como uma melhor ferramenta transgênica de Arabidopsis e Rice.

Regulon: An overview of plant abiotic stress transcriptional regulatory system and role in transgenic plants

Abstract Population growth is increasing rapidly around the world, in these consequences we need to produce more foods to full fill the demand of increased population. The world is facing global warming due to urbanizations and industrialization and in this concerns plants exposed continuously to abiotic stresses which is a major cause of crop hammering every year. Abiotic stresses consist of Drought, Salt, Heat, Cold, Oxidative and Metal toxicity which damage the crop yield continuously. Drought and salinity stress severally affected in similar manner to plant and the leading cause of reduction in crop yield. Plants respond to various stimuli under abiotic or biotic stress condition and express certain genes either structural or regulatory genes which maintain the plant integrity. The regulatory genes primarily the transcription factors that exert their activity by binding to certain cis DNA elements and consequently either up regulated or down regulate to target expression. These transcription factors are known as masters regulators because its single transcript regulate more than one gene, in this context the regulon word is fascinating more in compass of transcription factors. Progress has been made to better understand about effect of regulons (AREB/ABF, DREB, MYB, and NAC) under abiotic stresses and a number of regulons reported for stress responsive and used as a better transgenic tool of Arabidopsis and Rice.

Resumo O crescimento populacional está aumentando rapidamente em todo o mundo, e para combater suas consequências precisamos produzir mais alimentos para suprir a demanda do aumento populacional. O mundo está enfrentando o aquecimento global devido à urbanização e industrialização e, nesse caso, plantas expostas continuamente a estresses abióticos, que é uma das principais causas do martelamento das safras todos os anos. Estresses abióticos consistem em seca, sal, calor, frio, oxidação e toxicidade de metais que prejudicam o rendimento da colheita continuamente. A seca e o estresse salino são afetados de maneira diversa pela planta e são a principal causa de redução da produtividade das culturas. As plantas respondem a vários estímulos sob condições de estresse abiótico ou biótico e expressam certos genes estruturais ou regulatórios que mantêm a integridade da planta. Os genes reguladores são principalmente os fatores de transcrição que exercem sua atividade ligando-se a certos elementos cis do DNA e, consequentemente, são regulados para cima ou para baixo para a expressão alvo. Esses fatores de transcrição são conhecidos como reguladores mestres porque sua única transcrição regula mais de um gene; nesse contexto, a palavra regulon é mais fascinante no âmbito dos fatores de transcrição. Progresso foi feito para entender melhor sobre o efeito dos regulons (AREB / ABF, DREB, MYB e NAC) sob estresses abióticos e uma série de regulons relatados como responsivos ao estresse e usados como uma melhor ferramenta transgênica de Arabidopsis e Rice.

Research progress on transcription factor ZNF24 in Tumors / 药学实践杂志

The transcription factor ZNF24 (also known as ZNF191 or KOX17) is a member of the Krüppel-like zinc finger transcription factor family, with a leucine-rich (Leu) SCAN domain (also known as LeR domain) at the N-terminus and four consecutive typical Kruppel-like zinc finger modities at the C-terminus. ZNF24 is a multifunctional transcription factor involved in the regulation of kinase transcriptional activity, vascular proliferation and development, especially in tumorigenesis and tumor progression. ZNF24 plays an important and complex dual-directional regulation role (promoting and inhibiting) in tumor development, invasion and metastasis by regulating the transcriptional expression of different target genes (such as VEGF, Wnt8B, Twist1, β-catenin and DGL1, etc.) and the competitive binding with protein factors (such as β-catenin). Therefore, elucidating the mechanism of ZNF24 in tumors would provide clues and ideas for the treatment of tumors. The researches status of ZNF24 in tumors were summarized in this paper.

Townes-Brocks syndrome caused by de novo mutation in spalt-like transcription factor 1 gene: a case report and literature review / 中华围产医学杂志

Objective:To summarize the clinical features and gene variations in children with Townes-Brocks syndrome (TBS).Methods:The clinical data of a female infant diagnosed with TBS caused by human spalt-like transcription factor 1 ( SALL1) gene mutation in Gansu Maternal and Child Health Hospital in May 2022 were analyzed retrospectively. Relevant articles up to July 2022 were retrieved from several databases including CNKI, VIP, Wanfang, Chinese Medical Journal Network and PubMed with the terms of " SALL1 gene" and "Townes-Brocks syndrome". Patients diagnosed with TBS caused by SALL1 gene mutation were retrieved and the clinical phenotype-genotype correlations in patients with TBS caused by frameshift mutation in SALL1 gene were analyzed and summarized. Descriptive statistical analysis was applied. Results:(1) Clinical data: The index patient was a 40-day-old girl exhibiting major clinical manifestations of polycystic kidney dysplasia, congenital external ear deformity, preaxial polydactyly and recto-perineal fistula. Whole exome sequencing and Sanger sequencing revealed a heterozygous variation of c.420delC (p.S141fs*42) in the SALL1 gene, while the same gene was found to be wild type in her parents and sister. The variant was predicted to be pathogenic (PVS1+PS2+PM2). (2) Literature review retrieved 161 cases of TBS, of which 71 were attributable to a frameshift mutation in SALL1 gene. Clinical phenotypes of the 71 cases and the index case were summarized. TBS was mainly characterized by external ear, hand and anal deformities, sometimes accompanied by hearing loss, abnormal kidney development and foot deformity. A small number of affected cases presented with rare clinical phenotypes such as abnormal eyes, hypothyroidism and abnormal development. At present, the human gene mutation database records 110 variations in the SALL1 gene, with a majority located in exon 2. The most common mutation type was frameshift variation, accounting for 52%, followed by missense variation and nonsense variation. Conclusion:TBS should be considered in children with ear, hand and anal malformations, accompanied by renal dysfunction and hearing loss, and genetic testing is recommended for timely diagnosis.

Targeting the JAK-STAT signaling pathway in the treatment of psoriasis / 中华皮肤科杂志

The Janus kinase (JAK) -signal transducer and activator of transcription (STAT) signaling pathway is closely related to the occurrence of psoriasis. Various cytokines, including interleukin (IL) -23, IL-22, interferon (IFN) -γ, etc., can promote some key pathologic processes (such as the proliferation and abnormal differentiation of keratinocytes, and infiltration of inflammatory cells) via the JAK-STAT pathway in psoriasis, which suggests that targeting JAK-STAT pathway is a new strategy for the treatment of psoriasis. In recent years, small-molecule JAK inhibitors have shown good efficacy and safety in the treatment of psoriasis, and drugs targeting STAT pathway have been under development, which provide more treatment options for psoriasis. This review summarizes progress in drugs targeting the JAK-STAT signaling pathway in the treatment of psoriasis.

Change in expression of tumor necrosis factor receptor-associated factor 6 in lung tissues of rats with pulmonary hypertension / 中华麻醉学杂志

Objective:To determine the change in the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in lung tissues of rats with pulmonary hypertension (PH).Methods:Sixteen SPF-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-220 g, were divided into 2 groups ( n=8 each) by the random number table method: control group (group C1) and PH group (group PH1). The model of PH was prepared by subcutaneous injection of monocrotaline. On day 28 after developing the model, the mean pulmonary arterial pressure (mPAP) was measured, and the Fulton index was calculated, and the percentage of media wall thickness of the small and medium pulmonary arteries and percentage of muscularized vessels were also calculated. The expression of TRAF6, transcription-3 (STAT3), phosphorylated STAT3 (p-STAT3) and Cyclin D1 in lung tissues was detected by Western blot, and p-STAT3/STAT3 ratio was calculated. The interaction between TRAF6 and STAT3 was determined by immunoprecipitation assay. Primarily cultured pulmonary artery smooth muscle cells of normal rats (group C2) and pulmonary artery smooth muscle cells of rats with PH (group PH2) were inoculated in 6-well plates ( n=3 each). The expression of TRAF6 mRNA was detected by quantitative polymerase chain reaction. The expression of TRAF6, STAT3, p-STAT3 and Cyclin D1 was detected by Western blot. Results:Compared with group C1, the mPAP, Fulton index, percentage of media wall thickness of the small and medium pulmonary arteries and percentage of muscularized vessels were significantly increased, the expression of TRAF6 and Cyclin D1 in lung tissues was up-regulated, the p-STAT3/STAT3 ratio was increased ( P<0.05 or 0.01), and the results of immunoprecipitation showed that TRAF6 interacted with STAT3 in group PH1. Compared with group C2, the expression of TRAF6 protein and mRNA and Cyclin D1 was significantly up-regulated, and the p-STAT3/STAT3 ratio was increased in group PH2 ( P<0.05 or 0.01). Conclusions:The expression of TRAF6 in the lung tissue is up-regulated in rats with PH, which may be related to pulmonary vascular remodeling by promoting the activation of STAT3.

Role of HSF1 in endogenous protective mechanism underlying mechanical ventilator-induced lung injury in mice: relationship with HMGB1 / 中华麻醉学杂志

Objective:To evaluate the role of heat shock transcription factor 1 (HSF1) in the endogenous protective mechanism underlying mechanical ventilator-induced lung injury (VILI) in mice and the relationship with high mobility group box 1 (HMGB1).Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) by the random number table method: control group (group C), VILI group (group VILI), negative control siRNA + VILI group (group NV) and HSF1 siRNA + VILI group (group siRNA). At 48 h before mechanical ventilation, negative control siRNA 5 nmol and HSF1 siRNA 5 nmol were intratracheally injected in NV and siRNA groups respectively, and the solution was diluted to 50 μl with the sterile phosphate buffer in both groups. Group C kept spontaneous breathing for 4 h, and the rest animals were mechanically ventilated (tidal volume 35 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%) for 4 h. Blood samples from the femoral artery were collected for arterial blood gas analysis immediately after endotracheal intubation and at 4 h of ventilation, and PaO 2 was recorded. Then the mice were sacrificed under deep anesthesia to collect lung tissues and bronchoalveolar lavage fluid (BALF). The concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and HMGB1 in BALF were determined by enzyme-linked immunosorbent assay. The pathological results were observed by hematoxylin-eosin staining, and lung injury was assessed and scored. The wet/dry (W/D) weight ratio of lung tissues was calculated. The expression of HMGB1 and HSF1 mRNA in lung tissues (by quantitative real-time polymerase chain reaction) and expression of HMGB1 and HSF1 protein in lung tissues (by Western blot) were determined. Results:Compared with group C, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated in group VILI, group NV and group siRNA ( P<0.05 or 0.01). Compared with group VILI and group NV, PaO 2 was significantly decreased at 4 h of ventilation, the concentrations of TNF-α, IL-1β and HMGB1 in BALF, W/D ratio and lung injury score were increased, and the expression of HMGB1 protein and mRNA in lung tissues was up-regulated, and the expression of HSF1 protein and mRNA was down-regulated in group siRNA ( P<0.05 or 0.01). There was no significant difference in the parameters mentioned above between group VILI and group NV ( P>0.05). Conclusions:HSF1 is involved in the endogenous protective mechanism underlying VILI in mice, which may be related to the down-regulation of HMGB1 expression and attenuation of inflammatory responses in lung tissues.

Different roles of helper T lymphocytes during dendritic cells vaccine in experimental breast cancer

Breast cancer is the most common women’s tumor. Treatments though effective, are often aggressive and leave the patients vulnerable to developing opportunistic infections. There is a need for less aggressive more effective new therapies. In this study, we have made an attempt to evaluate DCs immunotherapy by flow cytometry, analyzing the presence of infiltrating cells, cytokines and transcription factors in the spleens, lymph nodes and tumors of breast cancer mice undergoing immunotherapy. The 4T1 cell transfection was used to induce breast cancer in Balb/c mice aged 6 to 8 weeks. Mice were treated with 3 doses of DCs vaccine. After the treatment, animals were euthanized, the spleen, lymphnodes and tumors were removed and used to perform flow cytometry. Results have shown higher CD4+ T lymphocytes that produce IL-12 in the spleen of group treated with DCs vaccine (149,8-271,3) 172,4. Further, there was an increase in T-bet (976,1-1075) 1022 in the lymph nodes of tumor group treated with DCs and less FOXP3 (795,7 - 895) 832. Tumoral volume and the FOXP3 were decreased in the treated group. There was an increase in the transcription factor of Th1 profile, and of cytotoxic T lymphocytes, inferring a good immune response. With these observations, it can be concluded that the DC vaccine is effective in combating the development of tumors.

Biomarcadores da transição epitélio-mesenquimal em desordens potencialmente malignas e carcinoma de células escamosas de língua oral / Biomarkers of epithelial-mesenchymal transition in potentially malignant disorders and squamous cell carcinoma of the oral tongue

Durante a carcinogênese oral, as células malignas adquirem um fenótipo agressivo que resulta em aumento da motilidade individual e na capacidade para invadir tecidos circunvizinhos. Para tanto, as células epiteliais malignas desenvolvem um processo regulatório e programado denominado transição epitélio-mesenquimal (TEM), que é crucial para aquisição deste fenótipo maligno agressivo. O objetivo do presente estudo foi investigar o papel da expressão imunoistoquímica de proteínas sinalizadoras da TEM em displasias epiteliais orais e em carcinomas de células escamosas de língua oral (CCELO), avaliando suas respectivas associações com parâmetros clínico-patológicos e de prognóstico. Inicialmente, objetivando obter uma compreensão aprofundada sobre o tema proposto, foram desenvolvidas duas revisões sistemáticas de literatura avaliando o papel da TEM como possível marcador de prognóstico em casos diagnosticados como displasia epitelial oral e o papel dos fatores de transcrição nuclear associados ao processo de TEM na regulação da plasticidade celular e no compartamento biológico em linhagens celulares de carcinoma de células escamosas em região de cabeça e pescoço. Para o estudo imunoistoquímico, foram selecionados 47 casos de displasias epiteliais orais e 41 casos diagnosticados como CCELO, nos quais foram analisados a imunoexpressão das proteínas Twist1, Snail1, E-caderina e N-caderina. Foram investigadas possíveis associações entre o padrão de expressão destas proteínas com a gradação histopatológica das displasias epiteliais e com os aspectos clínico-patológicos, recidiva e sobrevida em CCELO. Foram observados diferentes padrões de marcação entre os grupos analisados, observando-se uma perda significativa da expressão da E-caderina membranar em casos de CCELO em comparação aos casos de displasias epiteliais orais (p = <0.0001). Foi observado uma pior sobrevida global em casos com baixa expressão da E-caderina membranar (HR = 0.27; p = 0.033) e alta expressão do Twist1 citoplasmático (HR = 3.19; p = 0.010). Ao analisar isoladamente o parâmetro intensidade de expressão, foi observada associação entre a alta intensidade da N-caderina citoplasmática com a sobrevida global (HR = 4.93; p = 0.006). Nossos achados sugerem que a perda da expressão da E-caderina e o aumento da expressão da N-caderina e dos fatores de transcrição nuclear Twist1 e Snail1 estão associados ao desenvolvimento e progressão da carcinogênese oral. Isoladamente, a perda da expressão membranar da E-caderina e o aumento da expressão citoplasmática do Twist1 e da N-caderina foram associados a uma pior sobrevida (AU).

During oral carcinogenesis, malignant cells acquire an aggressive phenotype that results in increased individual motility and the ability to invade surrounding tissues. Therefore, malignant epithelial cells develop a regulatory and programmed process called epithelial-mesenchymal transition (EMT), which is crucial for the acquisition of this aggressive malignant phenotype. The aim of the present study was to investigate the role of immunohistochemical expression of EMT signaling proteins in oral epithelial dysplasias and oral squamous cell carcinomas of the tongue (OTSCC), evaluating their respective associations with clinicopathological and prognostic parameters. Initially, aiming to obtain a deeper understanding of the proposed topic, two systematic literature reviews were developed evaluating the role of EMT as a possible prognostic marker in cases diagnosed as oral epithelial dysplasia and the role of nuclear transcription factors associated with the MET process in regulation of cellular plasticity and biological behavior in head and neck squamous cell carcinoma cell lines. For the immunohistochemical study, 47 cases of oral epithelial dysplasias and 41 cases diagnosed with OTSCC were selected, in which the immunoexpression of Twist1, Snail1, E-cadherin and Ncadherin proteins were analyzed. Possible associations between the expression pattern of these proteins and the histopathological grading of epithelial dysplasias and with the clinicopathological aspects, recurrence and survival in OTSCC were investigated. Different staining patterns were observed between the analyzed groups, with a significant loss of membrane E-cadherin expression in cases of OTSCC compared to cases of oral epithelial dysplasias (p = <0.0001). Worse overall survival was observed in cases with low membrane E-cadherin expression (HR = 0.27; p = 0.033) and high cytoplasmic Twist1 expression (HR = 3.19; p = 0.010). When analyzing the expression intensity parameter alone, an association was observed between high cytoplasmic N-cadherin intensity and overall survival (HR = 4.93; p = 0.006). Our findings suggest that loss of E-cadherin expression and increased expression of N-cadherin and nuclear transcription factors Twist1 and Snail1 are associated with the development and progression of oral carcinogenesis. Alone, loss of membrane expression of E-cadherin and increased cytoplasmic expression of Twist1 and N-cadherin were associated with worse survival (AU).

Resveratrol protects against interleukin-1β-induced chondrocyte injury by regulating the silent information regulator 1/frame transcription factor O1 pathway / 中华风湿病学杂志

Objective:To study the effect of resveratrol (RES) on interleukin-1β (IL-1β)-induced chondrocytes and its pathways of action.Methods:Wistar mammary rat chondrocytes were extracted and divided into 5 groups: control group, IL-1β group, RES+IL-1β group, RES+IL-1β+EX-527 [silent information regulator 1 (SIRT1) inhibitor] group and RES+IL-1β+AS [frame transcription factor O1 (FOXO1) inhibitor] group. Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect SIRT1, forkhead FOXO1 and matrix metalloproteinase 3 (MMP-3) mRNA expression. Protein expression of chondrocyte type Ⅱ collagen (Col-Ⅱ) detected by immunofluorescence, and the expression of chondrocyte SIRT1 and p-FOXO1/FOXO1 was measured by Western blot. The expression of chondrocyte inflammatory factors IL-6 and TNF-α was measured by enzyme-linked immunosorbent assay. One-way analysis of variance (ANOVA) was performed and two-way comparisons between groups were made using the least significant difference (LSD) method. P< 0.001 was statistically significant. Results:Compared to normal chondrocytes, the mRNA and protein expressions of Col-Ⅱ, SIRT1, FOXO1 and p-FOXO1/FOXO1 in chondrocytes induced by IL-1β was significantly decreased ( P<0.001). The secretion of tumor necrosis factor (TNF)-α [(24.70±2.84), t=19.24, P<0.001] and IL-6 [(3.35±0.28), t=12.97, P<0.001] was significantly increased, and the mRNA expression of MMP-3 [(2.46± 0.23), t=12.61, P<0.001] was significantly increased. The mRNA and protein expressions of Col-Ⅱ, SIRT1, FOXO1 and p-FOXO1/FOXO1 were significantly increased. The secretion of TNF-α [(12.60±1.05), t=10.14, P<0.001] and IL-6 [(2.00±0.15), t=9.89, P<0.001] was significantly reduced by RES treated IL-1β-induced chondrocytes. mRNA expression of MMP-3 [(1.30±0.14), t=10.460, P<0.001] was decreased. After adding SIRT1 inhibitor EX-527 or FOXO1 inhibitor AS, RES significantly reduced the mRNA and protein expression of Col-Ⅱ, SIRT1, FOXO1 and p-FOXO1/FOXO1 in IL-1β-induced chondrocytes ( P<0.001). The secretion of TNFα and IL-6 was significantly decreased ( P<0.001), and the mRNA expression of MMP-3 was significantly decreased ( P<0.001). Conclusion:RES significantly ameliorates IL-1β-induced cartilage extracellular matrix egradation and inflammatory responses via the SIRT1/FOXO1 pathway.

Research status and progress of acute myeloid leukemia stem cells / 中国基层医药

Acute myeloid leukemia is a clonal malignant proliferative disease of myeloid blasts of the hematopoietic system. The leukemia cell population is composed of cells of different stages. Acute myeloid leukemia stem cells are the cells that may cause diseases in immunodeficient animals and can regenerate themselves through continuous transplantation, which causes leukemia. Since more than 96% of leukemia stem cells are in the G0 stage, they may escape the effects of chemical drug stabbing, leading to drug resistance and recurrence of leukemia. Therefore, the key to the treatment of acute myeloid leukemia has always been how to remove leukemia stem cells without damaging hematopoietic stem cells. This review paper addresses the new developments in the immunophenotype of leukemia stem cells and leukemia stem cells-targeting therapy for acute myeloid leukemia.

Significance of expression of serum sHLA-G, ɑ-HBDH and STAT1 in acute myeloid leukemia and their relationship with prognosis / 中国基层医药

Objective:To investigate the significance of expression of serum soluble HLA-G (sHLA-G), alpha-hydroxybutyrate dehydrogenase (α-HBDH) and signal transducer and activator of transcription 1 (STAT1) in acute myeloid leukemia (AML) and their relationship with prognosis.Methods:A total of 107 patients with AML who received treatment in Xiaoshan Hospital, Wenzhou Medical University, from June 2016 to June 2019 were included in the AML group. An additional 100 healthy controls who concurrently received physical health examination in the same hospital were included in the control group. Serum samples were collected from both patients with AML and healthy controls. Serum concentration of sHLA-G concentration was determined using the double-antibody sandwich enzyme-linked immunosorbent assay. Serum α-HBDH concentration was determined using the rate method. Peripheral blood was collected from patients with AML and healthy controls. The relative expression of STAT1 was determined by quantitative real-time polymerase chain reaction.Results:sHLA-G and α-HBDH concentrations in the AML group were (13.26 ± 2.19) μg/L and (362.17 ± 38.47) U/L, respectively, which were significantly higher than those in the control group [(5.08 ± 0.43) μg/L, (108.94 ± 12.19) U/L, t = 36.69, 62.93, both P < 0.05]. The relative expression of STAT1 in the AML group was significantly higher than that in the control group [(3.17 ± 0.25) vs. (1.01 ± 0.01), t = 86.32, P < 0.05] Among patients with Hb ≤ 80 g/L, the number of patients with high sHLA-G expression was higher than that of patients with low sHLA-G expression ( χ2 = 7.15, P < 0.05). The number of patients with white blood cells > 10 × 10 9/L was significantly higher than that of patients with low sHLA-G expression ( χ2 = 17.31, P < 0.05). Among patients with Hb ≤ 80 g/L, the number of patients with high α-HBDH expression was significantly higher than that of patients with low α-HBDH expression ( χ2 = 10.76, P < 0.05). The number of patients with white blood cells > 10 × 10 9/L was significantly higher than that with low α-HBDH expression ( χ2 = 13.17, P < 0.05). Among patients with Hb ≤ 80 g/L, the number of patients with high STAT1 expression was significantly higher than that of patients with low STAT1 expression ( χ2 = 18.14, P < 0.05). The number of patients with white blood cells > 10 × 10 9/L was significantly higher than that of patients with low STAT1 expression ( χ2 = 18.51, P < 0.05). The overall survival time in patients with high sHLA-G, α-HBDH expression and STAT1 expression was (17.92 ± 1.72) months, (19.34 ± 1.57) months, and (16.36 ± 2.08) months, respectively, which were significantly lower than those in patients with low sHLA-G, α-HBDH and STAT1 expression [(28.93 ± 1.46) months, (27.53 ± 1.89) months, (30.48 ± 1.12) months, t = 35.08, 24.07, 38.32, all P < 0.05]. Conclusion:sHLA-G, α-HBDH and STAT1 are abnormally expressed in patients with AML. Higher sHLA-G, α-HBDH and STAT1 expression indicates poorer prognosis of AML. Therefore, sHLA-G, α-HBDH and STAT1 can be used as the potential targets for AML treatment and prognosis prediction. Findings from this study are highly innovative and scientific.

Construction of a prognostic model of transcription factors for colon cancer / 中华内分泌外科杂志

Objective:To investigate the relationship between transcription factors (TFs) and the prognosis of colon cancer, and to construct a prognosis model through TCGA and GEO dual databases, so as to quantify the risk of patients and guide clinical treatment decisions.Methods:The transcriptome and clinical data of colon cancer in TCGA and GEO databases were used in this study. The transcriptome data were annotated and the gene expression was calculated. The difference analysis of TFs in TCGA and GEO (log2FC > 1, P-value (Fdr) < 0.05) was performed. The difference TFs of double data intersection were used for correlation prognosis analysis ( P<0.01). The risk coefficient and risk value of prognosis-related TFs were calculated by COX multivariate analysis, and the prognosis model of TFs was constructed by COX model with "survival" and "glmnet" package. The survival curve ( P<0.001) and ROC curve (AUC>0.75) of the sequence set and verification set were drawn, and the distribution of risk value was visualized. After grouping according to risk value, GSEA enrichment analysis was calculated, gene set grid was constructed, target genes were predicted, and finally, pathway enrichment analysis of GO and KEGG was carried out. Results:387 TFs with different expressions in TCGA and GEO databases were used to draw heat map, volcanic map and TFs-related forest map, and the prognosis model of colon cancer was constructed according to COX multivariate analysis=0.310×HSF4+0.137×IRX3-0.127×ATOH1+0.290×OVOL3+0.137×HOXC6+0.155×SIX2+0.092×ZNF556-0.444×CXXC5+0.429×TIGD1+0.413×TCF7L1. Through enrichment analysis, our results showed that these prognostic factors may directly or indirectly act on cancer pathways, such as basic cell carcinoma and cancer signaling pathway, local tissue-cell adhesion, and extracellular matrix.Conclusions:The constructed TFs prognosis model of colon cancer can quantify the prognostic risk of colon cancer, and its high-risk group is an independent risk factor of colon cancer prognosis. This model is a new way to evaluate the prognosis of colon cancer.

Roles of the SoxC family in tumor development and its clinical significance / 国际肿瘤学杂志

SoxC transcription factors are a group of important protein molecules involved in gene transcription, translation and expression, which can regulate gene expression by specifically binding to corresponding target genes or proteins. The SoxC gene family has unique molecular structure features. Its members Sox4, Sox11 and Sox12 are abnormally expressed in a variety of tumors, and can be used as diagnostic and prognostic markers for different tumors. Investigating the pathogenic mechanisms of the SoxC transcription factor family and their clinical significance can increase the evidence for SoxC as a therapeutic target for tumors.

Effects of long non-coding RNA FAM224A on the proliferation and migration of ovarian cancer cells by regulating the expression of miRNA-590-3p / 肿瘤研究与临床

Objective:To explore the effects of long non-coding RNA (lncRNA) FAM224A on the proliferation and migration of ovarian cancer cells by regulating the expression of miRNA-590-3p (miR-590-3p).Methods:Human ovarian cancer cell lines OC3, SKOV-3, HO-8910, A2780 and human normal ovarian epithelial cell line IOSE80 were selected, and the relative expression of FAM224A in each cell line was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The cell line with the lowest relative expression level of FAM224A was screened for follow-up experiment. The cells were divided into FAM224A group (transfected with FAM224A mimic gene) and control group (transfected with control mimic gene). CCK-8 method and cell scratch test were used to detect the cell proliferation and migration ability of the two groups. The bioinformatics website LncBase v.2 predicted that the target gene that FAM224A might complementarily bind to was miR-590-3p. qRT-PCR was used to detect the relative expression levels of miR-590-3p and forkhead box protein A2 (FOXA2) mRNA, and the expressions of related proteins were detected by Western blot.Results:The relative expression levels of FAM224A in ovarian cancer cell lines OC3, SKOV-3, HO-8910, A2780 and normal ovarian epithelial cell line IOSE80 were 0.23±0.04, 0.65±0.05, 0.45±0.03, 0.63±0.08 and 1.02±0.11, respectively, and the difference was statistically significant ( F = 14.78, P < 0.01), and the cell line with the lowest relative expression level of FAM224A was OC3. The results of CCK-8 method showed that the proliferation ability of OC3 cells in the FAM224A group was lower than that in the control group on the 2nd, 3rd, 4th and 5th day of culture (all P < 0.05). The scratch healing rates of OC3 cells in the FAM224A group and the control group were (18.6±2.3)% and (71.7±7.2)%, respectively, and the difference was statistically significant ( t = 6.99, P < 0.01). The relative expression levels of FAM224A in OC3 cells in the FAM224A group and the control group was 12.36±1.45 and 1.14±0.24, respectively ( t = 13.08, P < 0.01); the relative expression levels of miR-590-3p were 0.19±0.06 and 1.04±0.20, respectively ( t = 4.01, P < 0.01); the relative expression levels of FOXA2 mRNA were 6.37±1.37 and 1.05±0.08, respectively ( t = 3.86, P < 0.01). Compared with the control group, the expression of FOXA2 protein in OC3 cells in the FAM224A group was increased, the expressions of cell proliferation protein cyclin-dependent kinase 2 (CDK2) and cyclin D3 were decreased, and the expression of cell migration protein Snail was decreased. Conclusions:FAM224A is low expressed in ovarian cancer cell lines. FAM224A reduces the proliferation and migration ability of ovarian cancer OC3 cells by inhibiting the expression of miR-590-3p.