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The aim of this study is to assess the impact of intensive risk awareness management along with cardiac rehabilitation nursing in elderly patients with acute myocardial infarction and heart failure. We selected 101 elderly patients with acute myocardial infarction and heart aging treated from January 2022 to March 2023. They were divided into control and observation groups based on hospitalization numbers. The control group (nâ =â 50) received routine nursing, while the observation group (nâ =â 51) received intensive risk awareness management and cardiac rehabilitation nursing. We compared medication possession ratio (MPR), cardiac function, self-care ability scale scores, quality-of-life, incidents, and satisfaction between the 2 groups. Before intervention, there was no significant difference in MPR values between the 2 groups (Pâ >â .05). After intervention, MPR values increased in both groups, with a greater increase in the observation group (Pâ <â .05). Cardiac function showed no significant difference before intervention (Pâ >â .05), but after intervention, the observation group had lower left ventricular end-systolic and diastolic diameters and higher left ventricular ejection fraction compared to the control group (Pâ <â .05). Self-care skills, health knowledge, self-responsibility, and self-concept scores improved in both groups after intervention, with higher scores in the observation group (Pâ <â .05). The observation group had higher scores in various quality-of-life domains (Pâ <â .05). The total incidence of adverse events was lower in the observation group (5.88%) compared to the control group (20.00%) (Pâ <â .05). Patient satisfaction was significantly higher in the observation group (96.08%) than in the control group (84.00%) (Pâ <â .05). Intensive risk awareness management combined with cardiac rehabilitation nursing in elderly patients with acute myocardial infarction and heart aging can enhance medication compliance, improve quality-of-life, enhance self-care abilities, boost cardiac function, reduce incidents, and increase patient satisfaction.
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Reabilitação Cardíaca , Insuficiência Cardíaca , Infarto do Miocárdio , Qualidade de Vida , Humanos , Masculino , Feminino , Idoso , Insuficiência Cardíaca/reabilitação , Insuficiência Cardíaca/enfermagem , Infarto do Miocárdio/reabilitação , Infarto do Miocárdio/enfermagem , Reabilitação Cardíaca/métodos , Idoso de 80 Anos ou mais , Autocuidado/métodos , Satisfação do Paciente , Adesão à Medicação/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
This bioequivalence study is critically important for drug production. Recently, a local pharmaceutical company produced esomeprazole magnesium enteric-coated capsules, a major drug to help to eradicate Helicobacter pylori, but the bioequivalence is not well known. The present study aimed to evaluate the bioequivalence of the 2 esomeprazole magnesium enteric-coated capsules and their pharmacokinetics and safety in 3 biological equivalence trials: fasting, feeding, and mixing. The fasting and mixing trials used single-centered randomized, open-label, single-dose, 2-treatment, 2-period, and 2-sequence crossover design, while the fed trials used single-centered, randomized, open-label, single-dose, 2-treatment, 3-period, 3-sequence partial crossover design. For the fasting and mixing trials, each of the 32 subjects was fasted overnight prior to taking the test preparations or reference preparations. In the fed trial, 54 subjects were given a high-fat meal 1 hour before the drugs were administered. Blood specimens from all subjects were collected against the light within 14 hours, with the plasma drug concentration being detected by the validated ultra-performance liquid chromatography-tandem mass spectrometry analysis method. Geometric mean ratio of maximum concentration, the area under the concentration-time curve from time zero to the last measurable concentration, and area under the concentration-time curve from time zero to infinity with 90% confidence interval were calculated. The data from fasting, mixing, and fed trials met the bioequivalence criteria. No serious adverse reactions were found, suggesting that the test and reference preparations of esomeprazole magnesium enteric capsules have similar safety profile.
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População do Leste Asiático , Esomeprazol , Humanos , Disponibilidade Biológica , Cápsulas , Esomeprazol/efeitos adversos , Esomeprazol/farmacocinética , Esomeprazol/uso terapêutico , Voluntários Saudáveis , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Comprimidos com Revestimento Entérico , Equivalência Terapêutica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Doxorubicin, a first-line chemotherapeutic drug for breast cancer, kills cancer cells by inducing DNA-crosslinking damage. Dysregulated micro-RNA (miRNA) is associated with the drug resistance of tumors. However, little is known about the effect of miRNA-140-3p on DOX resistance of breast cancer. METHODS: The miRNA microarray was used to sequence the transcripts of DOX-chemoresistant breast cancer tissues and DOX-chemosensitive tissues. Then, the breast cancer tissue chip in the GEO database was also analyzed to screen the target gene. Flow cytometry, in situ hybridisation (ISH), immunohistochemistry (IHC), Western blot, cell proliferation assay, real-time PCR analyses (qRT-PCR), and pull-down assay were used to explore the effects of miRNA-140-3p and programmed death ligand-1 (PD-L1) on the chemoresistance of DOX-resistant breast cancer cells treated with DOX. In vivo, the DOX-resistant breast cancer cell lines treated with miRNA-140-3p overexpression were injected subcutaneously into mice to construct breast cancer subcutaneous xenograft tumor models. RESULTS: Based on miRNA microarray, GEO database, and bioinformatics analysis, it was found that miRNA-140-3p and PD-L1 are the core molecules in the DOX resistance regulatory network in breast cancer, and lower miRNA-140-3p and higher PD-L1 expression levels were observed in DOX-resistant breast cancer tissues and cells. IHC results showed that compared with breast cancer tissues with high miRNA-140-3p expression, PD-L1 protein expression levels in breast cancer tissues with low miRNA-140-3p were significantly higher (P<0.01). Moreover, compared with DOX-sensitive tissues, the levels of PD-L1 protein expression in DOX-resistant tissues were significantly higher (P<0.01). In in vitro and in vivo experiments, the introduction of miRNA-140-3p decreased PD-L1 expression. Mechanically, we found that the MCF-7/DOX and HS598T/DOX cells pretreated with miRNA-140-3p inhibitor or exosomes containing PD-L1 have higher stemness and lower apoptosis rate, which can be abrogated by co-treating cells with anti-PD-L1 antibody or miRNA-140-3p mimic. CONCLUSIONS: MiRNA-140-3p can suppress PD-L1 expression in breast cancer cell-derived exosomes, thereby attenuating the chemoresistance induced by DOX in breast cancer.
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Neoplasias da Mama , MicroRNAs , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Antígeno B7-H1/genética , Xenoenxertos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Doxorrubicina/farmacologia , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.
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Adaptação Fisiológica , Animais , Suínos , Filogenia , Especificidade da Espécie , Adaptação Fisiológica/genética , ÁfricaRESUMO
In this study, a positively charged near-infrared fluorescent probe (TPA-P+) was constructed by connecting a pyridine cation with triphenylamine and successfully used for the detection of heparin. The probe has the following characteristics: (1) TPA-P+ exhibited both AIE and TICT characteristics. (2) TPA-P+ could detect heparin by the introduction of a pyridine cation into TPA-P+, which increased the electrostatic interaction between the probe and heparin. (3) The probe has high sensitivity and good selectivity towards heparin and responds quickly. (4) Heparin detection using TPA-P+ was verified by protamine and was found to be reversible and effective. (5) The fluorescence intensity of TPA-P+ has good linearity with heparin concentration in the range of 0-16.0 µg mL-1 in human serum albumin.
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Corantes Fluorescentes , Heparina , Humanos , Protaminas , Piridinas , Eletricidade EstáticaRESUMO
BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Flavanonas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Farmacologia em Rede , Fosfatidilinositol 3-QuinasesRESUMO
In this work, a novel triphenylamine derivative probe TPA-1 was designed and synthesized with a mechanism of aggregation induced emission (AIE) and twisted intramolecular charge transfer (TICT) in a microenvironment. It can be used for the detection of keratin with AIE enhanced characterization in near infrared (NIR) emission. The sensitivity and selectivity for keratin detection were also studied. In the physiological pH range, the detection of TPA-1 to keratin was not interfered by other proteins and amino acids, and had excellent specificity and photostability. TPA-1 can also be used for viscosity detection.
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Corantes Fluorescentes , Queratinas , Aminas , Proteínas do Citoesqueleto , ViscosidadeRESUMO
AIMS: The aim of the study was to assess the effect of blocking TLR9 signaling on the proliferation of cervical cancer cells and its angiogenic property. BACKGROUND: Toll-Like Receptors (TLRs) have been implicated for their crucial role in not only cervical cancer but also in other malignancies. TLR9 is expressed on an array of cells such as macrophages, dendritic cells, melanocytes, and keratinocytes and is reported to modulate oncogenesis along with tumorigenesis by augmenting NF-κB mediated inflammation within the tumor environment. TLR9 has also been reported to positively regulate oncogenesis within the cervix and as a marker to evaluate malignant remodeling of cervical squamous cells. Therefore, this study was designed to explore the functional relevance of blocking the TLR9signaling pathway in cervical cancer cells. OBJECTIVE: The objective of the current study was to investigate the effect of human TLR9 antagonist, ODN INH-18, on apoptosis and cell cycle regulation, and angiogenic property of human cervical cancer Caski cells. METHODS: MTT assay was performed to measure cell viability and flow cytometry analysis was performed to assess cell cycle arrest. Quantitative Real-Time PCR (qRT-PCR) analysis was performed to measure fold change in the gene expression of various markers of apoptosis, cell cycle regulation, and angiogenesis. RESULTS: The qRT-PCR results showed a higher expression level of TLR9 mRNA in Caski cervical cancer cells as compared to normal cervical keratinocytes. The apoptotic, angiogenic, and cell cycle regulatory factors were also deregulated in Caski cells in comparison to normal keratinocytes. The MTT assay demonstrated that treatment of TLR9 antagonist, ODN INH18, significantly reduced the proliferation of Caski cells in a dose-dependent manner. Treatment of ODN INH18 led to substantial cell cycle arrest in Caski cells at G0/G1 phase. Moreover, the qRT-PCR results demonstrated that ODN INH18 treatment led to suppressed mRNA expression of Bcl-2 and enhanced expression of Bax, signifying the induction of apoptosis in Caski cells. Moreover, the expression of cyclin D1, Cdk4, and Cdc25A was found to be reduced whereas expression of p27 was increased in ODN INH18-treated Caski cells; indicating G0/G1 phase arrest. Interestingly, expression of VEGF and VCAM-1 was found to be significantly inhibited in ODN INH18-treated Caski cells, substantiating alleviation of angiogenic property of cervical cancer cells. CONCLUSION: The results of our study suggest that inhibiting TLR9 signaling might be an interesting therapeutic intervention for the treatment of cervical cancer.
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Transdução de Sinais , Neoplasias do Colo do Útero , Apoptose , Carcinogênese , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Feminino , Humanos , RNA Mensageiro , Transdução de Sinais/efeitos dos fármacos , Receptor Toll-Like 9/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genéticaRESUMO
[This corrects the article DOI: 10.3892/ol.2020.11686.].
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OBJECTIVE: To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). METHODS: From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5-38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4-24.4) and 17.7 months (95% CI 11.3-19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15-0.46); median OS was 26.0 months (95% CI 23.4-28.7) and 22.7 months (95% CI 21.2-24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11-0.37). CONCLUSIONS: CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.
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Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina , Compostos Organoplatínicos , Pós-Menopausa , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Resultado do TratamentoRESUMO
Cervical cancer (CC) is a common malignant tumor among women worldwide, remaining the fourth most frequent cause of cancer death in women. Currently, microRNA (miRNA) is a prevalent topic in tumor-related research. The present study focused on the mechanisms of miR-100 in CC progression. qRT-PCR analysis revealed that the miR-100 expression was notably decreased in CC tissues. In addition, miR-100 downregulation was confirmed to be significantly related to the malignant clinicopathologic features of CC patients. Furthermore, miR-100 overexpression was also verified to significantly repress CC cell proliferation, migration and invasion abilities through modulating the AKT/mTOR signaling pathway and epithelial-to-mesenchymal transition. Bioinformatics analysis and luciferase reporter assay identified that special AT-rich sequence-binding protein 1 was a functional target for miR-100 in CC cells. Moreover, miR-100 overexpression was found to markedly repress the CC tumor growth in vivo. In conclusion, the above results revealed that miR-100 functioned as a cancer suppressor in CC progression and may provide insights into the novel therapeutic target for CC treatment.
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Cis-regulatory elements play an important role in the development of traits and disease in organisms (Ma et al., 2020; Woolfe et al., 2005) and their annotation could facilitate genetic studies. The Encyclopedia of DNA Elements (ENCODE) (Davis et al., 2018) and Functional Annotation of Animal Genomes (FAANG) (FAANG Consortium et al., 2015) offer pioneering data on regulatory elements in several species. Currently, however, regulatory element annotation data remain limited for most organisms. In this study, we developed a tool (OrthReg) for annotating conserved orthologous cis-regulatory elements in targeted genomes using an annotated reference genome. Cross-species validation of this annotation tool using human and mouse ENCODE data confirmed the robustness of this strategy. To explore the efficiency of the tool, we annotated the pig genome and identified more than 28 million regulatory annotation records using the reference human ENCODE data. With this regulatory annotation, some putative regulatory non-coding variants were identified within domestication sweeps in European and East Asian pigs. Thus, this tool can utilize data produced by ENCODE, FAANG, and similar projects, and can be easily extended to customized experimental data. The extensive application of this tool will help to identify informative single nucleotide polymorphisms (SNPs) in post-genome-wide association studies and resequencing analysis of organisms with limited regulatory annotation data.
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Sequência de Bases , Sequência Conservada , Estudo de Associação Genômica Ampla/métodos , Genoma , Camundongos/genética , Sus scrofa/genética , Animais , Estudo de Associação Genômica Ampla/veterinária , HumanosRESUMO
The phylogeography of the European wild boar was mainly determined by postglacial recolonization patterns from Mediterranean refugia after the last ice age. Here we present the first analysis of SNP polymorphism within the complete mtDNA genome of West Russian (n = 8), European (n = 64), and North African (n = 5) wild boar. Our analyses provided evidence of unique lineages in the East-Caucasian (Dagestan) region and in Central Italy. A phylogenetic analysis revealed that these lineages are basal to the other European mtDNA sequences. We also show close connection between the Western Siberian and Eastern European populations. Also, the North African samples were clustered with the Iberian population. Phylogenetic trees and migration modeling revealed a high proximity of Dagestan sequences to those of Central Italy and suggested possible gene flow between Western Asia and Southern Europe which was not directly related to Northern and Central European lineages. Our results support the presence of old maternal lineages in two Southern glacial refugia (i.e., Caucasus and the Italian peninsula), as a legacy of an ancient wave of colonization of Southern Europe from an Eastern origin.
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Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1, CYP4F2, and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.
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Aclimatação/genética , Resistência à Doença/genética , Hipóxia/veterinária , Seleção Genética , Sus scrofa/fisiologia , Altitude , Animais , Genética Populacional , Genoma , Genômica , Hipóxia/genética , Mutação , Filogenia , TibetRESUMO
Sex-determining region Y-box 2 (SOX2) is an oncogene known to be amplified and overexpressed in various human malignancies, including lung squamous cell carcinoma (SCC). However, the role played by SOX2 in lung SCC development remains to be elucidated. We measured the levels of SOX2 and cyclin D1 mRNA and protein expression in lung SCC tissues and a lung SCC cell line, and found that both levels were dramatically upregulated in specimens of lung SCC tissue when compared with their expression levels in samples of adjacent nonneoplastic tissue. The lung SCC cell line also showed higher levels of SOX2 and cyclin D1 expression than a normal human bronchial epithelium cell line. After using RNA interference to knock down SOX2 expression in NCI-H520 lung SCC cells, their proliferation was reduced. Furthermore, overexpression of SOX2 promoted the proliferation of normal human bronchial epithelium cells. To further determine whether cyclin D1 was downstream target gene of SOX2, we measured the levels of cyclin D1 expression that occurred when SOX2 was knocked down or overexpressed. SOX2 knockdown significantly decreased the levels of cyclin D1 mRNA and protein expression, while SOX2 overexpression upregulated the levels of cyclin D1. We used bioinformatics data to identify potential cyclin D1 promoter binding sites for SOX2. Results of luciferase reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays confirmed that cyclin D1 was a direct target of transcription factor SOX2 in human lung SCC cells.
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Carcinoma de Células Escamosas/genética , Ciclina D1/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição SOXB1/metabolismo , Brônquios/citologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Células Epiteliais/citologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/fisiologiaRESUMO
Extrarenal Wilms' Tumors (ERWTs) are rare. There have been only 25 cases of ERWT arising from the female genital system reported in the literature. In this paper, we report a 60-year-old woman with a complaint of vaginal bleeding and a polypoid mass in the uterine cavity by sonography that was demonstrated as ERWT by pathology after resection. The pathological characteristics, histological origination, diagnosis, therapy and prognosis of ERWT in female reproductive system are discussed in this paper in the purpose of improving the diagnosis and therapy of this rare tumor.
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Neoplasias Renais , Neoplasias Uterinas , Tumor de Wilms , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/fisiopatologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/fisiopatologia , Neoplasias Uterinas/terapia , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/fisiopatologia , Tumor de Wilms/terapiaRESUMO
Lung cancer is one of the most common human malignancies worldwide, but its oncogenesis process remains unclear. Recent studies demonstrated that zinc (Zn) and Zn transporters were associated with the development and progression of human cancers. The role of Zn transporters including ZIPs and ZnTs in lung cancer, however, has never been evaluated. Thus, we aimed to investigate the expression levels of all human Zn transporters, including 14 ZIPs and 10 ZnTs, in eight different lung cancer cell lines and paired human tumor tissues. We observed great variations in ZIPs and ZnTs mRNA levels across cell lines and human lung cancer specimens. ZIPs showed a tendency to be upregulated, while ZnTs exhibited a downward expression trend. ZIP4 was overexpressed in six lung cancer cell lines and 59% (26/44) of tumor tissues, which was consistent with results from lung cancer datasets including TCGA database. Our results indicated that the dysregulation of Zn transporters may contribute to lung tumorigenesis.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Transporte/biossíntese , Neoplasias Pulmonares/metabolismo , Proteínas de Transporte/análise , Linhagem Celular Tumoral , HumanosRESUMO
Kruppel-like factors (KLFs) are a group of transcriptional regulators, being tumor-suppressive in various types of cancers, but not clear in human endometrial carcinoma (EC). We investigated the KLF-4 expression in both mRNA and protein levels in 29 EC specimens with RT-qPCR and Western blotting methods, and then to determine its promotion to Epithelial-to-mesenchymal transition (EMT) and proliferation of EC Ishikawa cells, via analyzing EMT-associated markers and via CCK-8 and colony forming assay. We found the downregulation of KLF-4 in the 29 EC specimens, correlating with the EC malignance. Moreover, we confirmed reduced levels of EMT and cell proliferation of Ishikawa cells post-KLF-4 overexpression. In conclusion, the significantly reduced KLF-4 correlated with the EC malignance. And the overexpressed KLF-4 promoted the EMT and proliferation of EC cells in vitro. The present study recognized the tumor suppressive role of KLF-4 in EC.
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Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/metabolismo , Transição Epitelial-Mesenquimal , Fatores de Transcrição Kruppel-Like/metabolismo , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Fator 4 Semelhante a KruppelRESUMO
RATIONALE: An unambiguous identification of compounds can be achieved by comparison of known fragmentation patterns. While the literature about fragmentation mechanisms of lignans, flavonoids and triterpenoids is few. So the present study analyses the fragmentation mechanisms of these compounds isolated from Streblus asper. METHODS: Electrospray ionization ion trap mass spectrometry (ESI-ITMS) and atmospheric pressure chemical ionization ion trap mass spectrometry (APCI-ITMS) were used to obtain the MS(n) spectra of the compounds. By analyzing the differences between the ions, the fragmentation mechanisms of these compounds were explored. RESULTS: Of the 29 compounds detected, 17, 7, and 5 were lignans, flavonoids and triterpenoids, respectively. The majority of lignans were found to give [M - H](-) ions of sufficient abundance for MS(n) analyses. The flavonoids were prone to the loss of CO and H2O. The triterpenoids always lost one formic acid molecule and two hydrogens, or one H2O from [M - H](-) to form the most abundant product ion in the MS(n) spectrum. CONCLUSIONS: ESI/APCI-ITMS were demonstrated to be fast, effective and practical tools to characterize the structures of flavonoids, triterpenoids and lignans. Results of the present study can help identify the analogous constituents by analyzing their MS(n) spectra.
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Flavonoides/química , Lignanas/química , Moraceae/química , Espectrometria de Massas em Tandem/métodos , Triterpenos/química , Flavonoides/análise , Lignanas/análise , Metanol , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Triterpenos/análiseRESUMO
BACKGROUND: The toll-like receptor (TLR)4-interleukin1ß (IL1ß) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1ß signaling pathway molecules expression. METHODS AND FINDINGS: The rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1ß were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1ß were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (ORâ=â1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted ORâ=â1.96). TLR4 mRNA and IL1ß were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively). CONCLUSIONS: The TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.