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1.
Cancer Innov ; 3(4): e122, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38948253

RESUMO

Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

2.
Cell Mol Biol Lett ; 29(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172714

RESUMO

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Linfoma Difuso de Grandes Células B , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Regiões Promotoras Genéticas , Linfoma Difuso de Grandes Células B/genética , Hematopoese , Linhagem Celular Tumoral , Proteínas Nucleares/metabolismo
3.
Biomed Environ Sci ; 36(8): 715-724, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37711083

RESUMO

Objective: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. Methods: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. Results: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. Conclusion: Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.


Assuntos
Neoplasias Pulmonares , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Cuidadores , Atividades Cotidianas , Estudos Transversais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Neoplasias Pulmonares/epidemiologia
4.
iScience ; 26(9): 107609, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664593

RESUMO

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-ß1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-ß1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

5.
Sci Rep ; 13(1): 9256, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286786

RESUMO

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2
6.
Breast Cancer Res Treat ; 196(1): 45-56, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36056297

RESUMO

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Linfócitos do Interstício Tumoral , Mutação , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Tirosina/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-35044904

RESUMO

A Gram-stain-positive, aerobic, non-sporulating, yellow-pigmented and rod or cocci-shaped bacterium, designated Arc0846-15T, was isolated from the kelp Laminaria japonica. Strain Arc0846-15T was found to grow at 16-35 °C (optimum, 28 °C), at pH 6.0-9.5 (optimum, 7.0) and in the presence of 0-6 % (w/v) NaCl (optimum, 2 %). Cells were positive for catalase and negative for oxidase activity. Phylogenetic analyses, based on 16S rRNA gene sequence comparisons, revealed that the nearest phylogenetic neighbour strains of strain Arc0846-15T were Ornithinimicrobium murale 01 Gi-040T (96.2 %), Ornithinimicrobium kibberense K22-20T (96.1 %) and Ornithinimicrobium humiphilum HKI 0124T (95.2 %). Based on phylogenomic analysis, the average nucleotide identity values between strain Arc0846-15T and the neighbour strains were 69.8, 69.7 and 69.8 %, respectively; the digital DNA-DNA hybridization values between strain Arc0846-15T and its three closest neighbour strains were 18.8, 19.1 and 19.3 %, respectively. The predominant menaquinone was MK-8 (H4). The dominant cellular fatty acids were C17 : 1 ω8c, iso-C15 : 0, iso-C16 : 0 and C17 : 0. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipid, one unidentified aminolipid and four unidentified lipids. The DNA G+C content of strain Arc0846-15T was 61.6 mol% based on the whole genome sequence. Based on the phylogenetic and phenotypic characteristics, strain Arc0846-15T is considered to represent a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium laminariae sp. nov. is proposed, with Arc0846-15T (=KCTC 49655T=MCCC 1K06093T) as the type strain.


Assuntos
Actinobacteria/classificação , Kelp , Laminaria , Filogenia , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Kelp/microbiologia , Laminaria/microbiologia , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
8.
Mol Pain ; 18: 17448069221075891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35083936

RESUMO

Tumor metastasis to bone is often accompanied by a severe pain syndrome (cancer-induced bone pain, CIBP) that is frequently unresponsive to analgesics, which markedly reduces patient quality of life and cancer treatment tolerance in patients. Prolonged pain can induce hypersensitivity via spinal plasticity, and several recent studies have implicated the involvement of vascular endothelial growth factor-A (VEGF-A) signaling in this process. Here, we speculated that CIBP is associated with VEGF-A/VEGFR2 signaling in the spinal cord. A mouse model of CIBP was established by intramedullary injection of Lewis lung carcinoma (LLC) cells in the mouse femur. Pain sensitization and potential amelioration via VEGF-A/VEGFR2 blockade were measured using paw withdrawal threshold to mechanical stimulation and paw withdrawal latency to thermal. Spinal VEGF-A/VEGFR2 signaling was blocked by intrathecal injection of the VEGF-A antibody or the specific VEGFR2 inhibitor ZM323881. Changes in the expression levels of VEGF-A, VEGFR2, and other pain-related signaling factors were measured using western blotting and immunofluorescence staining. Mice after LLC injection demonstrated mechanical allodynia and thermal hyperalgesia, both of which were suppressed via anti-VEGF-A antibody or ZM323881. Conversely, the intrathecal injection of exogenous VEGF-A was sufficient to cause pain hypersensitivity in naïve mice via the VEGFR2-mediated activation of protein kinase C. Moreover, the spinal blockade of VEGF-A or VEGFR2 also suppressed N-methyl-D-aspartate receptor (NMDAR) activation and downstream Ca2+-dependent signaling. Thus, spinal VEGF-A/VEGFR2/NMDAR signaling pathways may be critical mediators of CIBP.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Animais , Neoplasias Ósseas/metabolismo , Dor do Câncer/patologia , Carcinoma Pulmonar de Lewis , Camundongos , Neurônios/metabolismo , Dor/metabolismo , Qualidade de Vida , Fator A de Crescimento do Endotélio Vascular
10.
Arch Oral Biol ; 133: 105297, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34742001

RESUMO

OBJECTIVE: We aimed to identify the role of DOCK6 in oral squamous cell cancer (OSCC) in this study. DESIGN: DOCK6 expression in OSCC was analyzed using TCGA and GEO datasets and was verified by quantitative real-time PCR, Western blotting, and immunohistochemistry. Statistical analyses were performed to evaluate the relationships between DOCK6 expression and the clinicopathological characteristics of OSCC patients. Wound healing and Transwell assays were performed to assess OSCC cell migration and invasion, respectively. STRING and GO analyses and gene set enrichment analysis were used to identify DOCK6-interacting proteins, their functions and their potential pathways. RESULTS: DOCK6 was significantly upregulated at both the mRNA and protein levels in OSCC tissues (all P < 0.05). DOCK6 levels were positively correlated with age (P < 0.05), lymph node metastasis status (P < 0.001), clinical stage (P < 0.001), differentiation (P < 0.05), and poor clinical outcome (P < 0.05) in OSCC patients. Furthermore, univariate and multivariate analyses revealed that high DOCK6 expression (P < 0.01) and clinical stage III-IV (P < 0.05) might serve as independent prognostic factors for OSCC patients. Functionally, DOCK6 silencing significantly suppressed OSCC cell migration and invasion (all P < 0.05). Ten proteins that interact with DOCK6, more than ten functions related to cancer, and more than six pathways related to DOCK6 in OSCC were identified via bioinformatic methods. CONCLUSION: DOCK6 is upregulated in OSCC, is associated with a poor prognosis in OSCC patients and increases OSCC cells migration and invasion. These findings suggest that DOCK6 may be a potential therapeutic target with prognostic implication in patients with OSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Prognóstico
11.
J Cardiovasc Transl Res ; 15(4): 855-864, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34811697

RESUMO

Atherosclerosis (AS) is a chronic cardiovascular disease endangering human health and is one of the most common causes of myocardial infarction and stroke. Macrophage polarization plays a vital role in regulating plaque stability. As an important component of sunlight, ultraviolet B (UVB) has been proven to promote vitamin D and nitric oxide synthesis. This research used an AS model in ApoE-/- mice to study the effects of UVB on macrophage polarization and atherosclerotic plaque stability. In vitro, UVB irradiation increased arginase-I (Arg-I, M2 macrophage) and macrophage mannose receptor (CD206) expression, while the expression of inducible nitric oxide synthase (iNOS) (M1 macrophage) and CD86 was decreased. UVB promoted Akt phosphorylation in vitro. In vivo, UVB irradiation promoted the stabilization of atherosclerotic lesion plaques, while the phenotype of M2 macrophages increased. Our research provides new evidence for UVB in preventing and treating atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Humanos , Animais , Ativação de Macrófagos , Aterosclerose/metabolismo , Macrófagos/patologia , Placa Aterosclerótica/patologia , Fenótipo
12.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34904941

RESUMO

A Gram-stain-negative, motile, facultative anaerobic and rod-shaped bacterium, designated strain NR704-98T, was isolated from marine sediment of the northern South China Sea. Cells were positive for oxidase and catalase activity. Growth was observed at 4-30 °C (optimum 20-25 °C), at pH 6-9 (pH 7) and with 0.5-7 % NaCl (2 %). The 16S rRNA gene-based phylogenetic analysis revealed that the nearest phylogenetic neighbours of strain NR704-98T were Shewanella woodyi MS32T (97.9 %), Shewanella hanedai 281T (97.1 %), Shewanella sediminis HAW-EB3T (96.8 %) and Shewanella canadensis HAW-EB2T (96.7 %). Based on the results of phylogenomic analysis, the average nucleotide identity and the digital DNA-DNA hybridization values between strain NR704-98T and the previously mentioned type strains of species of the genus Shewanella were in the range of 74.9-93.1 % and 20.6-51.4 %, respectively. The respiratory quinones were Q-7 and Q-8. The predominant fatty acids (>10 %) of strain NR704-98T were C16 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and iso-C15 : 0. Phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminophospholipids and five unidentified lipids were detected in strain NR704-98T. Based on the phylogenetic and phenotypic characteristics, strain NR704-98T is considered to represent a novel species of the genus Shewanella, for which the name Shewanella nanhaiensis sp. nov. is proposed. The type strain is NR704-98T (=KCTC 82799T=MCCC 1K06091T).


Assuntos
Sedimentos Geológicos/microbiologia , Filogenia , Água do Mar/microbiologia , Shewanella , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Shewanella/classificação , Shewanella/isolamento & purificação , Vitamina K 2/química
13.
Ann Transl Med ; 9(18): 1458, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734010

RESUMO

BACKGROUND: The role of microRNAs (miRNAs) in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) remains to be fully elucidated. This study evaluated the expression profile of miRNAs in the lung tissue of patients with SSc-PAH. METHODS: Lung tissue samples were collected from 3 SSc-PAH patients and 4 healthy controls. A small RNA high throughput sequence approach was used for screening the differentially expressed miRNAs in the lung tissue samples. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 4 highly significant differentially expressed miRNAs. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for mRNAs were performed using the R package clusterProfiler software. RESULTS: A total of 82 upregulated miRNAs and 35 downregulated miRNAs were detected in the lung tissues of patients with SSc-PAH compared with healthy controls. GO enrichment analysis demonstrated that the upregulated target genes were closely involved in biological processes such as nervous system development, anatomical structure morphogenesis, system development, cellular macromolecule metabolic processes, and cellular processes. The downregulated target genes were involved in the plasma membrane bound cell projection morphogenesis and the regulation of macromolecule metabolic processes. The KEGG enrichment analysis showed that the upregulated genes were associated with important pathways involved in cancer biology, and the target genes of the downregulated miRNAs were involved in axon guidance. High throughput sequencing and qRT-PCR revealed that hsa-miR-205-5p and hsa-miR-539-3p were differentially expressed in SSc-PAH tissue. The target genes of hsa-miR-205-5p and hsa-miR-539-3p, IRF1and ADCYAP1, respectively, were verified using the high throughput dataset GSE48149. CONCLUSIONS: miRNAs may play an important role in the pathogenesis of SSc-PAH, and hsa-miR-205-5p and hsa-miR-539-3p may be potential therapeutic targets in patients with SSc-PAH.

14.
Biochim Biophys Acta Rev Cancer ; 1876(1): 188562, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964330

RESUMO

Reversible phosphorylation of proteins, controlled by kinases and phosphatases, is involved in various cellular processes. Dual-specificity phosphatases (DUSPs) can dephosphorylate phosphorylated serine, threonine and tyrosine residues. This family consists of 61 members, 44 of which have been identified in human, and these 44 members are classified into six subgroups, the phosphatase and tensin homolog (PTEN) protein phosphatases (PTENs), mitogen-activated protein kinase phosphatases (MKPs), atypical DUSPs, cell division cycle 14 (CDC14) phosphatases (CDC14s), slingshot protein phosphatases (SSHs), and phosphatases of the regenerating liver (PRLs). Growing evidence has revealed dysregulation of DUSPs as one of the common phenomenons and highlighted their key roles in human cancers. Furthermore, their differential expression may be a potential biomarker for tumor prognosis. Despite this, there are still many unstudied members of DUSPs need to further explore their precise roles and mechanism in cancers. Most importantly, the systematic review is very limited on the functional/mechanistic characteristics and clinical application of DUSPs at present. In this review, the structures, functions and underlying mechanisms of DUSPs are systematically reviewed, and the molecular and functional characteristics of DUSPs in different tumor types according to the current researches are summarized. In addition, the potential roles of the unstudied members and the possible different mechanisms of DUSPs in cancer are discussed and classified based on homology alignment and structural domain analyses. Moreover, the specific characteristics of their expression and prognosis are further determined in more than 30 types of human cancers by using the online databases. Finally, their potential application in precise diagnosis, prognosis and treatment of different types of cancers, and the main possible problems for the clinical application at present are prospected.


Assuntos
Biomarcadores Tumorais/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Neoplasias/enzimologia , Progressão da Doença , Fosfatases de Especificidade Dupla/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Neoplasias/genética , Neoplasias/patologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Tirosina Fosfatases/metabolismo , Transdução de Sinais
15.
Arch Microbiol ; 203(5): 2357-2364, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33656587

RESUMO

A Gram-stain-negative, aerobic, non-motile, yellow-pigmented rod-shaped and alginate-degrading bacterium, designated B1N29T, was isolated from the gut of the abalone Haliotis rubra obtained in Weihai, China. Strain B1N29T was found to grow at 4-35 ℃ (optimum, 25 ℃), at pH 6.5-9.0 (optimum, 7.0-7.5) and in the presence of 0.5-9% (w/v) NaCl (optimum, 2%). Cells were positive for oxidase and catalase activity. The 16S rRNA-based phylogenetic analysis revealed that the nearest phylogenetic neighbors of strain B1N29T were Tamlana carrageenivorans KCTC 62451T (98.2%) and Tamlana agarivorans KCTC 22176T (97.7%). Based on the phylogenomic analysis, the average nucleotide identity (ANI) values between strain B1N29T and the neighbor strains were 79.2 and 79.0%, respectively; the digital DNA-DNA hybridization (dDDH) values between strain B1N29T and its two closest neighbors were 22.8 and 23.0%, respectively. Menaquinone-6 (MK-6) was detected as the sole respiratory quinone. The dominant cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, anteiso-C15:0 and iso-C15:1 G. The polar lipids included phosphatidylethanolamine, one aminophospholipid, seven aminolipids and five unidentified lipids. Based on the phylogenetic and phenotypic characteristics, strain B1N29T is considered to represent a novel species of the genus Tamlana, for which the name Tamlana haliotis sp. nov. is proposed. The type strain is B1N29T (= KCTC 72683T = MCCC 1H00394T).


Assuntos
Flavobacteriaceae/classificação , Trato Gastrointestinal/microbiologia , Gastrópodes/microbiologia , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
16.
Biomed Environ Sci ; 34(3): 184-191, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33766214

RESUMO

OBJECTIVE: Evidence is lacking regarding the combined effects of smoking and obesity on mortality from coronary heart disease in male veterans. This study aimed to explore the combined effect of smoking and obesity on coronary heart disease mortality in male veterans in China. METHODS: A cohort of 1,268 male veterans from 22 veteran centers in Xi'an (Shaanxi Province, China) were followed up once every 2 years from February 1, 1987 to October 30, 2016. The endpoint was death from any cause. The hazard ratio ( HR) of each risk factor and the 95% confidence interval ( CI) were calculated using a multivariate Cox proportional hazard model. RESULTS: The total follow-up was 24394.21 person-years; each subject was followed up for a mean duration of 19.24 years. By the end of the study, of the 1,268 veterans, 889 had died, 363 were alive, and 16 were lost to follow-up. Cox regression analysis results revealed that current smoking ( HR: 1.552, 95% CI: 1.074-2.243), obesity ( HR: 1.625, 95% CI: 1.024-2.581), and the combined effect of the two factors ( HR: 2.828, 95% CI: 1.520-5.262) were associated with coronary heart disease mortality. CONCLUSION: Our results suggest that obese veterans who smoke might be an important target population for coronary heart disease mortality control.


Assuntos
Doença das Coronárias/mortalidade , Obesidade/complicações , Fumar , Veteranos/estatística & dados numéricos , Idoso , China/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
17.
Medicine (Baltimore) ; 100(10): e24033, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725817

RESUMO

INTRODUCTION: One of the purposes of echocardiography is to determine the nature of a space-occupying lesion. The conventional transthoracic echocardiogram (TTE) is the preferred method for the diagnosis of cardiac space-occupying lesions as it can reveal the baseline information. For patients with poor conditions, however, TTE cannot clearly display the boundary, it has a limited role in determining the nature of the lesions. PATIENT CONCERNS: A 47-year-old woman presented with intermittent fever for 7 days and chest distress/shortness of breath for 5 days. DIAGNOSIS: In our current case, we inferred the nature of space-occupying lesions in the left atrium more accurately using transesophageal echocardiography (TEE) than TTE, which may offer diagnostic evidence for surgical treatment. INTERVENTIONS: The patient underwent surgical resection of the left atrial tumor and reconstruction of the left atrial wall. However, the patient's posterior lobe of the mitral valve was infiltrated by tumor, which was difficult to completely remove. OUTCOMES: Echocardiography was performed 3 months after surgery and the tumor recurred in the posterior lobe of the mitral valve. Although almost all tumors have been removed by surgery, the average survival time is often less than 1 year, as it is difficult to completely remove and easy to relapse with poor prognosis. CONCLUSION: Transesophageal echocardiography (TEE) plays a relatively more important role in the determination and differential diagnosis of cardiac space-occupying lesions.


Assuntos
Ecocardiografia Transesofagiana , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Sarcoma/diagnóstico , Procedimentos Cirúrgicos Cardíacos , Diagnóstico Diferencial , Feminino , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Pessoa de Meia-Idade , Sarcoma/patologia , Sarcoma/cirurgia , Tomografia Computadorizada por Raios X
18.
Arthritis Care Res (Hoboken) ; 73(4): 603-611, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31961500

RESUMO

OBJECTIVE: Although several individual nutrients/foods are associated with uric acid status, the association of overall diet quality with hyperuricemia remains unclear. The current study was undertaken to examine the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and the odds of having hyperuricemia in a Chinese adult population. METHODS: Included were 71,893 Chinese participants in the Kailuan I study and the Kailuan II study (mean age 51.4 years) who were free of gout prior to or in 2014. Dietary intakes were assessed using a validated food frequency questionnaire, and the DASH diet score was calculated based on consumptions of vegetables, fruit, dairy, beans, whole grains, meat, fat, sodium, and sugar-sweetened beverages. Fasting blood samples were collected in 2014, and hyperuricemia was defined as serum uric acid concentrations of ≥7 mg/dl for men, and of ≥6 mg/dl for women. The association between DASH diet score and hyperuricemia was assessed using multiple logistic regression models, adjusting for age, sex, total energy, obesity, physical activity, education, smoking, alcohol drinking, blood pressure, fasting glucose, lipid profiles, renal function, and presence of cardiovascular disease. RESULTS: A High DASH diet score was associated with low odds of having hyperuricemia (adjusted odds ratio for quartile 4 versus quartile 1 0.70 [95% confidence interval 0.66, 0.75], P for trend < 0.001) after adjusting for potential confounders. The association between the DASH diet and hyperuricemia was more pronounced among older individuals (age ≥50 years), women, and physically inactive participants compared with their counterparts (P for interaction < 0.01 for all). CONCLUSION: The DASH diet was associated with a low likelihood of having hyperuricemia in Chinese adults.


Assuntos
Dieta Saudável , Abordagens Dietéticas para Conter a Hipertensão , Hiperuricemia/epidemiologia , Cooperação do Paciente , Comportamento de Redução do Risco , Ácido Úrico/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Hiperuricemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Comportamento Sedentário , Fatores Sexuais , Adulto Jovem
20.
Zhonghua Nan Ke Xue ; 26(1): 24-30, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33345473

RESUMO

OBJECTIVE: To investigate the role of the pannexin-1 (Panx1) protein in the invasion and migration of testicular cancer Tcam-2 cells and its possible action mechanism. METHODS: Tcam-2 cells were treated with carbenoxolone (CBX) at 100 µmol/L and probenecid (PBN) 200 µmol/L. Then the intercellular fluorescence transmission was assessed by real-time fluorescence assay, the extracellular ATP concentration measured by chemi-luminescence immunoassay, the invasive and migratory abilities of the Tcam-2 cells detected by Transwell assay, and the expressions of the proteins Panx1, p-ERK1/2, ERK1/2, vimentin, MMP-9 and E-cadherin in the TM3 Leydig cells and testicular cancer Tcam-2 cells determined by Western blot. RESULTS: Western blot showed that the expression of the Panx1 protein was significantly higher in the testicular cancer Tcam-2 cells than in the TM3 Leydig cells (2.79 ± 0.17 vs 1.00 ± 0.06, P<0.05). The rates of intercellular fluorescence transmission in the Tcam-2 cells treated with CBX and PBN were markedly decreased as compared with the blank control group (ï¼»61.54 ± 3.30ï¼½% and ï¼»68.06 ± 4.03ï¼½% vs ï¼»99.50 ± 3.12ï¼½%, P<0.01), and so were the extracellular ATP concentrations (ï¼»57.06 ± 5.80ï¼½% and ï¼»56.42 ± 7.70ï¼½% vs ï¼»110 ± 8.16ï¼½%, P<0.01). The numbers of migrated Tcam-2 cells in the CBX and PBN groups were significantly reduced in comparison with that in the control (11.5 ± 1.11 and 8.25 ± 1.23 vs 331.00 ± 30.80, P<0.05), and so were those of the invaded ones (11.75 ± 3.77 and 11.5 ± 3.5 vs 89.00 ± 13.09, P<0.01). CBX and PBN significantly down-regulated the expression of p-ERK1/2 as compared with that in the blank control group (0.538 ± 0.05 and 0.476 ± 0.02 vs 0.98 ± 0.03, P<0.05), as well as those of vimentin (0.541 ± 0.09 and 0.705 ± 0.07, P<0.01) and MMP-9 (0.439 ± 0.08 and 0.557 ± 0.065, P<0.01) but up-regulated that of E-cadherin (3.896 ± 0.06 and 3.551 ± 0.04, P<0.01). CONCLUSIONS: The Panx1 protein is highly expressed in testicular cancer Tcam-2 cells. CBX and PBN can inhibit the function of the panneixn1 channel and reduce the invasive and migratory abilities of the Tcam-2 cells, which is associated with the decreased expression of the p-ERK1/2 protein.


Assuntos
Movimento Celular , Conexinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Testiculares/patologia , Carbenoxolona/farmacologia , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Metaloproteinase 9 da Matriz , Probenecid/farmacologia
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