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It has been evidenced that ROR2 influences the growth of many tumors, including non-small cell lung cancer, osteosarcoma, and breast cancer. This research examined the effect of the WNT1/ROR2 signaling pathway on the progression of triple-negative breast cancer (TNBC). Bioinformatics analysis results demonstrated that ROR2 had a higher messenger RNA (mRNA) expression level in TNBC tissues and was positively correlated with poor patient prognosis. Western blot analysis (WB) and quantitative reverse transcription polymerase chain reaction demonstrated that TNBC cells had relatively higher ROR2 mRNA and protein levels than normal cell lines. Transwell and Cell Counting Kit-8 (CCK-8) assay further proved that downregulating ROR2 expression dramatically slowed the MDA-MB-231 cell progression. WB detection of epithelial-mesenchymal transition (EMT)-related proteins suggested that knocking down ROR2 could alleviate the EMT tendency of cancer cells. The WNT1/ROR2 signaling pathway could be inhibited by the WNT inhibitor pyrvinium pamoate (PP). Experiments on in vitro cell functional recovery have demonstrated that PP could restore malignant phenotypes caused by ROR2 overexpression. Finally, the mouse model experiments further validated the anticancer effect of PP on TNBC. Generally speaking, the malignant progression of TNBC could be stimulated by the WNT1/ROR2 signaling pathway which can be inhibited by PP, suggesting the potential value of PP in controlling TNBC.
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Movimento Celular , Transição Epitelial-Mesenquimal , Invasividade Neoplásica , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Neoplasias de Mama Triplo Negativas , Proteína Wnt1 , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Humanos , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Feminino , Animais , Camundongos , Proteína Wnt1/metabolismo , Proteína Wnt1/genética , Linhagem Celular Tumoral , Via de Sinalização Wnt , Camundongos Nus , Camundongos Endogâmicos BALB C , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Pregnant women belong to the special population of drug therapy, and their physiological state, pharmacokinetics and pharmacodynamics are significantly different from the general population. Drug safety during pregnancy involves two generations, which is a hot issue widely concerned in the whole society. Global Trigger Tool (GTT) of the Institute for Healthcare Improvement (IHI) has been wildly used as a patient safety measurement strategy by several institutions and national programs, and the effectiveness had been demonstrated. But only one study reports the use of GTT in obstetric delivery until now. The aim of the study is to establish triggers detecting adverse drug events (ADEs) suitable for obstetric inpatients on the basis of the GTT, to examine the performance of the obstetric triggers in detecting ADEs experienced by obstetric units compared with the spontaneous reporting system and GTT, and to assess the utility and value of the obstetric trigger tool in identifying ADEs of obstetric inpatients. METHODS: Based on a literature review searched in PubMed and CNKI from January of 1997 to October of 2023, retrospective local obstetric ADEs investigations, relevant obstetric guidelines and the common adverse reactions of obstetric therapeutic drugs were involved to establish the initial obstetric triggers. According to the Delphi method, two rounds of expert questionnaire survey were conducted among 16 obstetric and neonatological physicians and pharmacists until an agreement was reached. A retrospective study was conducted to identity ADEs in 300 obstetric inpatient records at the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital from June 1 to September 30, 2018. Two trained junior pharmacists analyzed the first eligible records independently, and the included records reviewed by trained pharmacist and physician to identify ADEs. Sensitivity and specificity of the established obstetric triggers were assessed by the number of ADEs/100 patients and positive predictive value with the spontaneous reporting system (SRS) and GTT. Excel 2010 and SPSS22 were used for data analysis. RESULTS: Through two rounds of expert investigation, 39 preliminary triggers were established that comprised four modules (12 laboratory tests, 9 medications, 14 symptoms, and 4 outcomes). A total of 300 medical records were reviewed through the obstetric triggers, of which 48 cases of ADEs were detected, with an incidence of ADEs of 16%. Among the 39 obstetric triggers, 22 (56.41%) were positive and 11 of them detected ADEs. The positive predictive value (PPV) was 36.36%, and the number of ADEs/100 patients was 16.33 (95% CI, 4.19-17.81). The ADE detection rate, positive trigger rate, and PPV for the obstetric triggers were significantly augmented, confirming that the obstetric triggers were more specific and sensitive than SRS and GTT. CONCLUSION: The obstetric triggers were proven to be sensitive and specific in the active monitoring of ADE for obstetric inpatients, which might serve as a reference for ADE detection of obstetric inpatients at medical institutions.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pacientes Internados , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Segurança do Paciente , China/epidemiologiaRESUMO
Multidrug resistance is a primary factor in the poor response to chemotherapy and subsequent death in gastric cancer patients. However, the molecular mechanisms involved remain unclear. In this study, the high expression of special AT-rich sequence binding protein 1 (SATB1) in gastric cancer was found to be associated with reduced sensitivity to various chemotherapy drugs. Our results demonstrate that SATB1 can promote chemotherapy resistance in gastric cancer in vitro and in vivo. SATB1 exerts its effect by enhancing the activity of multiple ATP-binding cassette (ABC) transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) in gastric cancer cell lines. We also found that SATB1 affects ABC transporters by altering the subcellular localization of the ABC transporter rather than its expression. Subsequently, we confirmed that Ezrin binds to various ABC transporters and affects their subcellular localization. In addition, we found that SATB1 can also bind to the Ezrin promoter and regulate its expression. In the present study, we elucidate the mechanism of SATB1-mediated multidrug resistance in gastric cancer, providing a basis for SATB1 as a potential target for reversal of resistance.
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Proteínas de Ligação à Região de Interação com a Matriz , Neoplasias Gástricas , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/metabolismo , Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/farmacologiaRESUMO
The boron phosphide (BP) van der Waals (vdW) homostructure is designed to construct high-performance nano-optoelectronic devices due to its distinctive photoelectric properties. Using density functional theory, the electronic properties of twisted and untwisted BP bilayer structures are systematically calculated. We found that the 0° structure is a direct band gap semiconductor with a type II band alignment, the carrier mobility of which is increased to 104, and its photoelectric conversion efficiency is 17.3%. By analyzing the band structure and exciton binding energy calculated at 0° under an electric field, it is further found that 0° is a superior photoelectric material. As for the twist BP bilayer, the band gap changes with torsional structures under the applied electric field, which generates the Stark effect. The twist angles of bilayer BP, specifically 13.17°, 21.79°, 38.21°, and 46.83°, always maintain a direct band gap under the influence of an electric field. While 60° is an indirect band gap, the structure exhibits high resistance to the electric field. Our results reveal that bilayer BP is a potential application prospect in photovoltaic and optoelectronic fields and can provide more insights into optoelectronic devices.
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PURPOSE: To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer. METHODS: The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients. RESULTS: A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher "GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS", "GOBP_G2_DNA_DAMAGE_CHECKPOINT" and "GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT" GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072. CONCLUSIONS: Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.
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Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Próstata , Algoritmos , Linhagem Celular , Oxirredutases atuantes sobre Doadores de Grupo EnxofreRESUMO
The two-dimensional heterostructures with type-II band alignment and super-high carrier mobility offer an updated perspective for photovoltaic devices. Here, based on the first-principles calculation, a novel vertical NGyne/GaSe heterostructure with an intrinsic type-II band alignment, super-high carrier mobility (104cm2V-1s-1), and strong visible to ultraviolet light absorption (104-105cm-1) is constructed. We investigate the electronic structure and the interfacial properties of the NGyne/GaSe heterostructure under electric field and strain. The band offsets and band gap of the NGyne/GaSe heterostructure can be regulated under applied vertical electric field and strain efficiently. Further study reveals that the photoelectric conversion efficiency of the NGyne/GaSe heterostructure is vastly improved under a negative electric field and reaches up to 25.09%. Meanwhile, near-free electron states are induced under a large applied electric field, leading to the NGyne/GaSe heterostructure transform from semiconductors to metal. Our results indicate that the NGyne/GaSe heterostructure will have extremely potential in optoelectronic devices, especially solar cells.
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BACKGROUND: Among malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormancy of these prostate cancer disseminated tumor cells in the bone marrow is still unclear. Therefore, studying the dormancy mechanism of tumor cells in bone metastasis is of great significance for the treatment and the prevention of recurrence of prostate cancer. METHODS: We obtained single-cell RNA-seq data of tumors from mouse models of prostate cancer bone metastasis mouse model numbered (GSE147150) from the GEO database, and obtained RNA-seq expression data and clinical information from The Cancer Genome Atlas Program (TCGA) of prostate cancer patients from the USCS Xena database. Screening of differential genes and annotation of GO functions were performed separately. Subsequently, the screened differential genes were compared and analyzed with 50 classic Hallmark signaling pathways, and the prognosis analysis of prostate cancer patients in TCGA data was performed to discover the key genes of the dormant mechanism of tumor cells in bone metastasis, and obtain new biomarkers that can be used to predict the prognosis of patients. RESULTS: A total of 378 differentially expressed genes were screened, of which 293 were significantly up-regulated and 85 were significantly down-regulated. Among them, the up-regulated genes were mainly related to the immune response, and the down-regulated genes were mainly related to the cell cycle. Through GSVA (Gene set variation analysis), it is found that there are differences in a total of 3 signal pathways: COMPLEMENT, MYC_TARGETS_V1 and MYC_TARGETS_V2. By comparing and analyzing the significantly down-regulated genes in dormant tumor cells with MYC_TARGETS_V1, MYC_TARGETS_V2, three significantly down-regulated genes were obtained: Ccna2, Mad2L1 and Plk1. CONCLUSION: In summary, our findings indicate that the MYC targeting gene Mad2L1 is potentially related to the dormancy mechanism of prostate cancer. At the same time, Mad2L1, a gene associated with dormant prostate cancer cells, may be used as a biomarker for prognostic survival.
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Neoplasias Ósseas/secundário , Proteínas Mad2/genética , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Estudos RetrospectivosRESUMO
Intestinal epithelial cells are an essential barrier in human gastrointestinal tract, and healing of epithelial wound is a key process in many intestinal diseases. α-Lipoic acid (ALA) was shown to have antioxidative and anti-inflammatory effects, which could be helpful in intestinal epithelial injury repair. The effects of ALA in human colonic epithelial cells NCM460 and human colorectal adenocarcinoma cells Caco-2 were studied. ALA significantly promoted NCM460 and Caco-2 migration, increased mucosal tight junction factors ZO-1 and OCLN expression, and ALA accelerated cell injury repair of both cells in wound healing assay. Western blot analysis indicated that ALA inhibited a variety of mitogen-activated protein kinase (MAPK) signaling pathways in the epithelial cells. In conclusion, ALA was beneficial to repair of intestinal epithelial injury by regulating MAPK signaling pathways.
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Mucosa Intestinal , Sistema de Sinalização das MAP Quinases , Ácido Tióctico , Células CACO-2 , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Intestinos/patologia , Ácido Tióctico/farmacologiaRESUMO
Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.
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Nariz Eletrônico , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas/métodos , Análise Multivariada , Controle de Qualidade , Odorantes/análise , Compostos Orgânicos Voláteis/análiseRESUMO
OBJECTIVE: To explore the mechanism of Salidroside regulating the phenotypic transformation of cavernous smooth muscle cells (CCSMCs) in rats. METHODS: Primary CCSMCs were isolated from male SD rats, cultured in hypoxic environment for 24 hours, and treated with Salidroside at 30 µg/mL. Then the expressions of HIF-1α, platelet-derived growth factor receptor (PDGFR) and phenotypic transformation-related proteins α-SMA and Collagen I were detected by Western blot. The culture system of the CCSMCs was treated with exogenous PDGF-BB at 20 ng/mL for 24 hours, and the effects of Salidroside or PDGFR inhibitor Crenolanib (100 nmol/L) were observed. The expressions of PDGFR, phosphorylated PDGFR, phenotypic transformation-related proteins α-SMA and Collagen I, STAT3, phosphorylated STAT3, STAT5 and phosphorylated STAT5 were determined by Western blot. The intervention effects of Salidroside and/or the overexpression of STAT3 were observed after stimulation of the CCSMCs by exogenous PDGF-BB, followed by detection of the expressions of phenotypic transformation-related proteins α-SMA and Collagen I, STAT3 and phosphorylated STAT3 proteins. RESULTS: The expression of HIF-1α in the CCSMCs was significantly upregulated after cultured in hypoxic environment for 24 hours (P < 0.05), suggesting the successful construction of the hypoxia model of CCSMCs. Meanwhile, the expressions of PDGFRα, PDGFRß and Collagen I were remarkably increased (all P < 0.05), and that of α-SMA markedly decreased (P < 0.05) in the CCSMCs. However, the expressions of the all the proteins above were significantly inhibited by Salidroside intervention (all P < 0.05). After stimulated by exogenous PDGF-BB for 24 hours, the phosphorylation ratios of PDGFRα, PDGFRß and STAT3 and the expression of Collagen I were significantly elevated (all P < 0.05), that of α-SMA remarkably reduced (P < 0.05), and all were inhibited by intervention with crenolanib or Salidroside (all P < 0.05). No statistically significant difference was observed in the STAT5 phosphorylation ratio between different groups (P > 0.05). Overexpression of STAT3 in the CCSMCs treated with exogenous PDGF-BB and Salidroside significantly decreased the expression of α-SMA (P < 0.05) and increased that of Collagen I (P < 0.05). CONCLUSION: Salidroside could improve the phenotypic transformation of CCSMCs in male rats through the PDGFR/STAT3 signaling pathway, which needs further exploration and verification.
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Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Fator de Transcrição STAT5 , Ratos , Masculino , Animais , Becaplermina/metabolismo , Becaplermina/farmacologia , Ratos Sprague-Dawley , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/farmacologia , Células Cultivadas , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , ColágenoRESUMO
OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.
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BACKGROUND: The Global Trigger Tool (GTT),which is a method using "triggers" to review medical record retrospectively to identify possible adverse events. Several studies showed that the GTT was effective. However, there were only a few localized trigger tools that had been established to detect pediatric adverse drug events (ADEs) in China. This study aimed to establish a pediatric trigger tool based on GTT, to examine the performance by detecting pediatric inpatients ADEs in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of ADEs. METHODS: The triggers were established by three steps including literature search, triggers extraction and revision, and experts investigation. A retrospective cohort study was conducted to detect ADEs by using 200 pediatric inpatient records of Sichuan Provincial People's Hospital. RESULTS: Thirty-three preliminary triggers were established, and 2 rounds of experts investigation were conducted. Finally, 33 triggers were established. In the retrospective review, the positive trigger rate was 64.0%, while the positive predictive value (PPV) was 24.9%. The occurrence of inpatients with ADEs was 20.5%. ADEs/100 admissions were 49.0. ADEs/1000 patient days were 46.89. The most common ADE categories were leukocyte disorders, skin disorders and platelet disorders. The severity of 39 ADEs was grade 1, 55 ADEs was grade 2, 4 ADEs was grade 3. The highest frequency of ADE-related drugs was antineoplastic, followed by antibacterial. The length of stay and the leukemia in the diagnosed diseases were positively correlated with ADEs. CONCLUSIONS: The 33 pediatric triggers may detect ADEs effectively, but still need to be optimized. This study may provide some references for further research in order to improve the rationality and safety of medication.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Criança , China/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitalização , Hospitais , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND Thyroid carcinoma is a malignancy with high morbidity and mortality. Genetic alterations play pivot roles in the pathogenesis of thyroid carcinoma, where long noncoding RNA (lncRNA) have been identified to be crucial. This study sought to investigate the biological functions of lncRNA expression profiles in thyroid carcinoma. MATERIAL AND METHODS The lncRNAs expression profiles were acquired from The Cancer Genome Atlas (TCGA) database according to 510 thyroid cancer tissues and 58 normal thyroid tissues. By using R package edgeR, differentially expressed RNAs were obtained. Also, an overall survival model was established based on Cox regression and clinical data then testified by Kaplan-Meier plot, receiver operating characteristic (ROC)-curve and C-index analysis. We investigated the co-expressed genes with lncRNAs involved in the prognostic model, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted R package clusterProfile. RESULTS A total of 352 lncRNAs were identified as differentially expressed in thyroid carcinoma, and an overall survival model consisting of 8 signature lncRNAs was proposed (ROC=0.862, C-index=0.893, P<0.05), 3 of which (DOCK9-DT, FAM111A-DT, and LINC01736) represent co-expressed mRNAs. However, as an oncogene, only FAM111A-DT increased the prognostic risk in thyroid carcinoma. Furthermore, we found differential genes LINC01016, LHX1-DT, IGF2-AS, ND MIR1-1HG-AS1, significantly related to lymph node metastasis (P<0.05). CONCLUSIONS In this study, we clarified the differential lncRNA expression profiles which were related to the tumorigenesis and prognosis in thyroid carcinoma. Our results provide new rationale and understandings to the pathogenesis and regulatory mechanisms of thyroid carcinoma.
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RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Transcriptoma/genética , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Curva ROC , Receptores Virais/genética , Análise de SobrevidaRESUMO
We explored whether platelet-derived growth factor (PDGF)-BB regulates corpus cavernosum smooth muscle cell gap junctions and can ameliorate erectile dysfunction and how it modulates connexin43 (CX43) after bilateral cavernous neurectomy. Primary cultured rat corpus cavernosum smooth muscle cells were treated with PDGF-BB with or without a PDGFR inhibitor, Akt siRNA or the depletion or promotion of ß-catenin. PDGF-BB improved CCSMCs gap junction coupling and increased CX43 and PDGFRß expression; inhibition of PDGFR activity down-regulated CX43 and decreased Akt and nuclear ß-catenin. Knockdown or promotion of ß-catenin down-regulated and up-regulated CX43 expression respectively. Moreover, ß-catenin activation induced CX43 nuclear accumulation, which impeded CX43 down-regulation induced by PDGFR inhibition, suggesting that CX43 expression is positively correlated with nuclear ß-catenin expression. Furthermore, CX43 promoter luciferase and chromatin immunoprecipitation assays indicated that ß-catenin regulates CX43 transcription by directly interacting with its promoter. Male rats underwent bilateral cavernous neurectomy. After 12 weeks, they were injected with PDGF-BB, CX43 and PDGFRß expression was significantly lower than in the control group, which was reversed by PDGF-BB injection. These results suggested that PDGF-BB contributed to the improvement of gap junction intracellular communication among corpus cavernosum smooth muscle cells, increased CX43 through PDGFRß/Akt/nuclear ß-catenin signalling, and ameliorated cavernous nerve injury-induced erectile dysfunction.
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Becaplermina/farmacologia , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Pênis/irrigação sanguínea , Animais , Células Cultivadas , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Pênis/efeitos dos fármacos , Pênis/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Ratos , Transdução de Sinais/efeitos dos fármacos , beta Catenina/genética , beta Catenina/metabolismoRESUMO
A comprehensive investigation was carried out on graphyne/graphyne (Gyne/Gyne), graphyne-like BN/graphyne-like BN (BNyne/BNyne) and graphyne/graphyne-like BN (Gyne/BNyne) bilayer structures using van der Waals (vdW)-corrected density functional theory. These bilayers exhibited distinct stacking-dependent characteristics in their ground state electronic structure and also had different responses to external strain and a vertical electric field. For the Gyne/Gyne and Gyne/BNyne bilayers, the application of biaxial tensile strain led to an increase in the band gap, while the application of biaxial compressive strain in addition to uniaxial strain, either under tension or compression, induced a reduction in the band gap. However, in the case of the BNyne/BNyne bilayer, the application of biaxial tensile strain led to a decrease in the band gap, but an increase in the band gap occurred under biaxial compressive strain, which could be explained by a change in the ionic nature of the B-N bonds. Under a vertical electric field, the band gaps of the homo-bilayers (Gyne/Gyne and BNyne/BNyne) decreased and were symmetrical. However, the hetero-bilayer (Gyne/BNyne) exhibited a decreased band gap under a positive electric field, but an almost constant band gap under a negative electric field. The physical origin of the band gap variation under an electric field was unraveled using energy-band theory. Our findings pave the way for experimental research and provide valuable insight into two-dimensional vdW layered structures for use in next generation flexible nanoelectronics and optoelectronic devices.
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Due to its high electron mobility, good stability and potential for low-temperature synthesis ZnO has received considerable attention for use in solar cells, photodetectors and sensors. Whilst there have been reports involving the formation ZnO films with porous morphologies the majority of those have involved elaborate or time-consuming preparation methods. In this study we investigate a simple new method for preparing textured porous ZnO (tp-ZnO) films. We used colloidal instability triggered by the evaporation of a volatile stabilising ligand during spin-coating of a ZnO nanocrystal (NC) dispersion to deposit crack-free tp-ZnO films. The porosity of the tp-ZnO films was 56% and they could be prepared using amine-based ligands with boiling points less than or equal to 78 °C. To demonstrate the ability to use the tp-ZnO films as electron acceptors they were infiltrated with poly(3-hexylthiophene) (P3HT) and solar cells prepared. The power conversion efficiencies of the tp-ZnO/P3HT devices reached values that were three times higher than a control bilayer ZnO/P3HT device prepared using a sol-gel derived ZnO film. Because our method used a low temperature treatment and ZnO films are used in a wide variety of third-generation solar cells, the new tp-ZnO films introduced here may offer a low cost method for improving the efficiency of other solar cells.
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Oriented hierarchical fibrous-like ZnO nanowires with the diameter of about 3050 nm and the length of about 1530 um were successfully synthesized on the seed-coated Zn substrates by a simple two-step process. The morphology and structure of the obtained samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It is shown that fibrous-like ZnO nanowires with the aspect ratio of about 500Ë1000 present the dense reticular structure, which are grown on ZnO nanowire arrays. But beyond that, as-prepared samples are found to be good single crystalline with hexagonal wurtzite structure and preferential grow along the c-axis. A possible growth mechanism of oriented hierarchical fibrous-like ZnO nanowires is presented in detail, revealing that the synthesis of fibrous-like ZnO nanowires should be attributed to differences in the growth rate of the different crystallographic planes and the two growth ways. The photoluminescence (PL) spectra of oriented hierarchical fibrous-like ZnO nanowires grown at 240 min shows the 5 nm blue-shift and enhanced intensity property in the UV emission.
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A total of 121 medical cases concerning treating coronary heart disease (CHD) pa- tients with blood stasis syndrome (BSS) by Chinese Medicine were collected to establish a database for CHD patients with BSS. By using data mining authors tried to explore inherent laws of its symptoms and medication of Chinese Medicine, and to probe maximal frequent association patterns between its symp- toms and medication constitutions. Of the 121 medical cases, chest pain, chest stiffness, and headache were their common symptoms. Compatibilities of blood-activating drugs, stasis-resolving drugs, and qi- promoting drugs were most commonly used. The association between symptoms and compatibilities con- stituted a most often seen maximal frequent association pattern, which reflected an idea of treating both principal and subordinate symptoms.
Assuntos
Doença das Coronárias , Medicina Tradicional Chinesa , Circulação Coronária , Doença das Coronárias/diagnóstico , Doença das Coronárias/terapia , Mineração de Dados , Humanos , SíndromeRESUMO
Erectile dysfunction (ED) is a common male disease. Some related studies show that the prevalence of ED is nearly 52% in men aged 40 to 70 years and is increasing among younger males. Hypoxia is now considered to be an independent risk factor for ED and the mechanisms of hypoxia inducing ED are varied and complicated. Recently, an idea in penile rehabilitation has attracted much attention, which aims at improving erectile function by increasing oxygen supply to the cavernosum and reducing tissue fibrosis and apoptosis. The approaches to achieve non-sexual penile erection by increasing oxygen supply to the cavernosum, such as behavior therapy, medication, vacuum constriction device, and intracavernous injection, can simulate normal sexual erection and help patients with penile rehabilitation. This review focuses on the strategies for non-sexual penile erection in penile rehabilitation.
Assuntos
Disfunção Erétil/reabilitação , Oxigênio/administração & dosagem , Ereção Peniana , Adulto , Idoso , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Humanos , Hipóxia/complicações , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Pênis/irrigação sanguínea , Fatores de RiscoRESUMO
Penile erection is a primarily aneurovascular event,which depends on the relaxation of the corpus cavernosum smooth muscle cells and engorgement of the penis with blood. The compression of the subtunical venular plexus results in venular blockage.The intracavernosal pressure( ICP) is close to 5-7 mmHg in the flaccid state and rapidly increases to more than 100 mmHg in the tumescence phase. In the study of the animal model of erectile dysfunction,ICP measurement is the golden standard for evaluation of erectile function. In the recent years,telemetric technology has been successfully applied in monitoring the changes of rat ICP abroad,but no such report is seen domestically. This paper presents an overview on the development of the ICP measurement technology.