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1.
Diabetes ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974143

RESUMO

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is a transcription factor essential for fructose tolerance in mice. However, the functional significance of liver ChREBP in fructose metabolism remains unclear. Here, we show that liver ChREBP protects mice against fructose-induced hepatotoxicity by regulating liver glycogen metabolism and ATP homeostasis. Liver-specific ablation of ChREBP did not compromise fructose tolerance, but rather caused severe transaminitis and hepatomegaly with massive glycogen overload in mice fed high-fructose diet, while no obvious inflammation, cell death, or fibrosis was detected in the liver. In addition, liver ATP contents were significantly decreased by ChREBP deficiency in the fed state, and this was rendered more pronounced by fructose feeding. Mechanistically, liver contents of glucose-6-phosphate (G-6-P), an allosteric activator of glycogen synthase, were markedly increased in the absence of liver ChREBP, while fasting-induced glycogen breakdown was not compromised. Furthermore, hepatic overexpression of LPK, a ChREBP target gene in glycolysis, could effectively rescue glycogen overload and ATP reduction, as well as mitigate fructose-induced hepatotoxicity in ChREBP-deficient mice. Taken together, our findings establish a critical role of liver ChREBP in coping with hepatic fructose stress and protecting from hepatotoxicity by regulating LPK.

2.
Chemistry ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944445

RESUMO

Multiple-stimuli-responsive photoluminescence films based on a Zn(II)-organic framework, {[Zn2(Htpim)(3,4-pydc)2]·4DMF·4H2O}n (1, Htpim = 2,4,5-tri(4-pyridyl)-imidazole, 3,4-H2pydc = 3,4-pyridinedicarboxylic acid), were fabricated. This compound consisted of a 2D corrugated layer, {Zn(3,4-pydc)}n, which was further pillared using a Y-shaped pillar N-donor ligand (Htpim) to form a 3D pillared-layer framework with 1D open channels. The rectangular channels in the as-synthesized compound are fully occupied by guest DMF and H2O molecules. The framework exhibits instant and reversible thermochromic properties corresponding to the removal of different H2O and DMF guest molecules as temperature increases. The pale-yellow crystal undergoes significant red-shifting to a greenish emission centered at 530 nm. Compound 1 also showed remarkable solvatochromic effects in the presence of various organic solvents without affecting its structural integrity. In addition, polycrystalline MOF films were grown on an α-Al2O3 support for switchable and fast-response thermochromic and solvatochromic sensors.

3.
Endocrine ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31983029

RESUMO

PURPOSE: To effectively predict lateral neck lymph nodes (LLN) metastasis in papillary thyroid carcinoma (PTC) patients with central lymph nodes (CLN) invasion, and devise targeted treatment strategies. METHODS: Four hundred and thirty-four PTC patients with CLN metastasis from two medical centers were retrospectively analyzed. A new statistical model was established for predicting LLN involvement in these patients to guide lymph nodes management strategies. RESULTS: Patients with more than five positive CLN metastasis appeared to have extremely high risk (83.0%) of LLN involvement. For patients with five or less positive CLN invasion, multivariate logistic analyses were applied. Independent risk factors for LLN involvement were determined to be: age over 40, maximum tumor diameter of no less than 1.0 cm, existence of thyroid capsular invasion, and tumor with ipsilateral nodular goiter (iNG). These factors were used to construct a predictive nomogram. The accuracy and validity of our newly built model were verified by C-index 0.761 (95% CI, 0.707-0.815) in development cohort and 0.759 (95% CI, 0.745-0.773) in validation cohort and calibration curve. The patients were stratified into three groups based on their nomogram risk scores. Possible LLN involvement rates for low-risk, moderate-risk, and relatively high-risk subgroups were 8.9%, 22.8%, and 48.2%, respectively. CONCLUSIONS: Our newly established model can effectively predict possible LLN metastasis in PTC patients, and a new strategy selection flow chart was created for patients with positive CLN invasion. For patients in high-risk group, prophylactic LLN dissection is recommended, if not, adjuvant radioactive iodine or a closer follow-up scheme should at least be conducted. For those in low-risk group, surgical intervention is unnecessary and regular follow-up is recommended.

4.
Nucleic Acids Res ; 48(2): 879-894, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31777931

RESUMO

An important event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In both invertebrates and vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date the mechanisms that activate the Z-decay pathway in mammalian early embryos have not been investigated. Here, we identify murine maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic expression of terminal uridylyltransferases TUT4 and TUT7 and mRNA 3'-oligouridylation direct Z-decay. Components of the M-decay pathway, including BTG4 and the CCR4-NOT deadenylase, continue to function in Z-decay but require reinforcement from the zygotic factors for timely removal of maternal mRNAs. A long 3'-UTR and active translation confer resistance of Z-decay transcripts to M-decay during oocyte meiotic maturation. The Z-decay pathway is required for mouse embryo development beyond the four-cell stage and contributes to the developmental competence of preimplantation embryos.

5.
Pathol Res Pract ; 216(1): 152793, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31870593

RESUMO

The class II trans-activator (CIITA) is the master regulator of the major histocompatibility complex (MHC) gene expression. CIITA mutations have been previously associated with several kinds of tumors, while the role of CIITA polymorphisms (rs3087456) in laryngeal squamous cell carcinoma (LSCC) is little known. We evaluate the link between CIITA polymorphisms and the existence of LSCC in patients. This study was conducted with 200 Chinese Han patients (LSCC) and 200 healthy control subjects. The association of CIITA genetic polymorphism rs3087456 with the risk of LSCC was assessed through pyrosequencing. The CIITA expression in LSCC tumor tissue and adjacent normal tissue was detected by immunohistochemistry (IHC) staining. The relationship between the genotype of rs3087456 in controls and in clinical pathology features in LSCC were analyzed, and in-silico analysis was also used for the CIITA gene. The in-silico analysis results showed that the CIITA gene is closely related to genes such as RFX5 and RFXAP. The IHC results showed that CIITA was highly expressed in LSCC tumor tissues, compared with the corresponding adjacent normal tissues. The AG, AG + AA, and A genotypes of rs3087456 of CIITA gene notably increased the risk of LSCC compared to the controls. Our study suggests that CIITA polymorphism (rs3087456) is associated with a higher risk of developing LSCC in a Chinese cohort.

6.
Curr Med Sci ; 39(6): 1009-1018, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845235

RESUMO

Pancreatic fistula (PF) remains the most frequent complication after pancreaticoduodenectomy (PD). This study was undertaken to explore the risk factors of postoperative PF following PD and discuss the management of PF in our center. A single-center respective study, involving 241 patients who underwent PD between September 2015 and June 2018, was conducted. Differences in the demographic data, preoperative, intraoperative and postoperative variables between the group with PF [International Study Group on Pancreatic Surgery (ISGPS) grade B/C] and the group without PF (no PF and ISGPS grade BL) were evaluated. The diagnosis and grading of PF were in strict accordance with ISGPS. Risk factors were analyzed by univariate analysis and multivariate logistic regression analysis. The results showed that postoperative PF occurred in 50 (20.7%) of the patients; 25 (10.4%) patients had a PF type BL, 46 (19.1%) patients developed a PF type B and 4 (1.6%) had a PF type C. Univariate analysis showed that fasting blood glucose (P=0.02), pancreatic texture (P< 0.001) and pancreatic duct diameter (P=0.01) were correlated with PF. Multivariate logistic regression analysis identified one independent risk factor for postoperative PF: soft pancreatic texture (OR=3.251, P=0.002). Among the cases, there were three postoperative deaths, giving a 60-day hospital mortality rate of 1.2% (3/241), and the mortality related to PF was 4.0% (2/50). One of the patients died from multiple organ failure caused by postoperative abdominal hemorrhage. In conclusion, soft pancreatic texture is an independent risk factor for PF. Surgeons should be well aware of this risk factor when performing a PD.

8.
Cell Mol Life Sci ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676962

RESUMO

CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles. CFP1-dependent H3K4 trimethylation in oocytes was necessary to maintain the expression of key paracrine factors and to facilitate the communication between an oocyte and the surrounding granulosa cells. The distinct gene expression patterns in cumulus cells within preovulatory follicles were disrupted by the Cxxc1 deletion in oocytes. Both follicle growth and ovulation were compromised after CFP1 deletion, because Cxxc1 deletion in oocytes indirectly impaired essential signaling pathways in granulosa cells that mediate the functions of follicle-stimulating hormone and luteinizing hormone. Therefore, CFP1-regulated epigenetic modification of the oocyte genome influences the responses of ovarian follicles to gonadotropin in a cell-nonautonomous manner.

9.
Nucleic Acids Res ; 47(21): 11387-11402, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31598710

RESUMO

Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained decreased levels of many maternal mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell-cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3'-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.

10.
Eur J Surg Oncol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31537404

RESUMO

BACKGROUND: Surgery remains the most common therapeutic strategy for Chinese patients with hypopharyngeal squamous cell carcinoma (HSCC), yet the indications for postoperative adjuvant treatment (POAT) remain unclear. METHODS: We retrospectively analysed 385 patients with primary HSCC in our hospital between 2003 and 2014. Patients that received pharyngectomy without POAT were enrolled in this study for developing a nomogram that predicts their survival outcome. RESULTS: Multivariate analyses showed that the tumour size, oesophagal invasion, extracapsular spread or internal jugular vein adhesion, thyroid gland invasion, and the number of lymph node metastases (≤3 or >3) were significantly correlated to the overall survival (OS) of the patient and were included as risk factors in the nomogram. The C-index was 0.768 (95% CI, 0.719-0.817) in development cohort and 0.767 (95% CI, 0.753-0.781) in validation cohort. A calibration curve was also conducted and was found favourable. The patients were stratified into three groups based on their nomogram scores. In the high-risk group, patients that received POAT had a better OS than those that received only surgery. In the moderate-risk group, POAT did not show any significant association with the OS. However, patients in the low-risk group that received POAT showed a worse OS than those without. CONCLUSION: The newly-developed nomogram can effectively predict the survival outcome of patients with HSCC. According to the novel stratification criteria created, patients stratified as high-risk could benefit from POAT, while those in the low-risk group are advised not to receive POAT as this correlates with a worse OS.

12.
Ying Yong Sheng Tai Xue Bao ; 30(9): 3183-3194, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529894

RESUMO

Soil organic carbon is essential for maintaining terrestrial ecosystem function and mitigating soil degradation. Soil microorganisms participate in soil carbon cycling. They are affected by tillage methods and straw returning. A split-plot design was adopted in this experiment. The whole-plot treatment had two tillage methods, subsoil tillage (ST) and rotary tillage (RT). The split-plot treatment included full straw returning (F) and no straw returning (0). The microbial community structure and carbon sequestration genes were assessed by Illumina sequencing technique. Soil organic carbon contents were measured during 2012-2017. The results showed that 1) subsoil tillage and straw returning significantly increased pH, microbial biomass carbon, total nitrogen, silt content, and clay content, while significantly decreased sand content; 2) during the test period (2012-2017), soil organic carbon (SOC) content under all treatments showed an increasing trend, but the increment for average SOC content under straw returning and subsoiling treatments was significantly higher than that of no straw returning and rotary tillage by 33.2 % and 30.6%, respectively; 3) Proteobacteria was the most abundant type of bacteria in the soil, followed by Acidobacteria and Gemmatadanetes; 4) STF treatment maintained high microbial diversity; 5) Excepted for soil sand content, soil pH, microbial biomass carbon, total nitrogen, silt content and clay content all caused the variation of soil microbial community structure under the STF treatment in the direction of SOC accumulation; 6) in addition to the gene abundance in the di- and oligosaccharides metabolic pathway, the gene abundance in the metabolic pathways for CO2 fixation, central carbohydrate metabolism, fermentation, one-carbon metabolism, organic acids, sugar alcohols and glycoside hydrolases showed that subsoil tillage was significantly higher than rotary tillage, with posi-tively correlation with soil organic carbon content. Therefore, the combination of subsoil tillage and straw returning could improve basic soil properties, affect soil microbial community structure, and increase the capacity of soil carbon fixation, thus providing a realistic basis for solving soil degradation.


Assuntos
Agricultura , Microbiota , Microbiologia do Solo , Solo , Carbono/análise , Triticum
13.
Cell Mol Life Sci ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492966

RESUMO

Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of oocyte survival and meiotic cell cycle progression. DCAF13, a novel CRL4 adaptor, is essential for oocyte development. But the mechanisms by which CRL4-DCAF13 supports meiotic maturation remained unclear. In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 null oocytes are arrested at the prometaphase I. The DCAF13-dependent PTEN degradation mechanism fits in as a missing link between CRL4 ubiquitin E3 ligase and PI3K pathway, both of which are crucial for translational activation during oocyte GV-MII transition.

14.
Adv Sci (Weinh) ; 6(15): 1900295, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31406667

RESUMO

A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA-binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf  2bp2 (also commonly known as Imp2) in mouse embryos causes early embryonic developmental arrest in vitro at the 2-cell-stage. Transcriptomics and proteomics analyses of 2-cell-stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14, both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild-type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10-9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2-treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development-related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

15.
Medicine (Baltimore) ; 98(35): e16648, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464900

RESUMO

RATIONALE: Primary granulocytic sarcoma of the breast is a rare and poor-prognosis malignancy. Clinicians do not have sufficient knowledge of this disease and often misdirect it as other soft tissue sarcomas or inflammation. PATIENT CONCERNS: A 42-year-old female presented with a self-discovered asymptomatic growing and palpable right breast mass that had been present for 4 months. DIAGNOSES: The patient was diagnosed as primary myeloid sarcoma. INTERVENTIONS: The patient received modified radical mastectomy in the right breast and sentinel lymph node biopsy. Pathological diagnosis is primary granulocytic sarcoma. Then the patient accepted acute myeloid leukemia-induction chemotherapy. OUTCOMES: The follow-up of this patient has no evidence of disease progression or spread during 1 year. LESSONS: Granulocytic sarcoma in the breast tissue is rare. But it still should be considered in the differential diagnosis of any tumor in the breast. The present study discusses comprehensively the clinical and pathological characteristics to improve the understanding of myeloid sarcoma.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/terapia , Adulto , Citarabina/uso terapêutico , Diagnóstico Diferencial , Feminino , Mepesuccinato de Omacetaxina/uso terapêutico , Humanos , Quimioterapia de Indução , Mastectomia Radical Modificada , Biópsia de Linfonodo Sentinela , Resultado do Tratamento
16.
Chem Biol Drug Des ; 94(4): 1824-1834, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31293023

RESUMO

Due to the potencies in the treatments of cancer, infectious diseases, and autoimmune diseases, the developments of human TLR8 (hTLR8) agonists and antagonists have attracted widespread attentions. The hTLR8 agonists and antagonists have similar structures but with completely opposite biological effects. Up to date, the subtle differences in the structures between the hTLR8 agonists and antagonists are still unknown. In this work, emerging chemical pattern (ECP) was successfully used to extract the key chemical patterns of the hTLR8 agonists and antagonists. By using CAEP classifier, an optimal ECP model with only 3 descriptors was established with the overall prediction accuracy larger than 90%. Further hierarchical cluster analysis and molecular docking showed that the H-bond and hydrophobic properties are the key features distinguishing the hTLR8 agonists from antagonists. Comparing with the antagonists, the agonists show stronger specific H-bond properties, while antagonists have stronger non-specific hydrophobic properties. The significant differences in the structural properties may be closely related to the activation/inhibition mechanism of hTLR8.

17.
Front Oncol ; 9: 588, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312615

RESUMO

Background: NLRP3 inflammasome is an inflammatory mediator. The expression of NLRP3 inflammasome is associated with the development of various tumors and is closely related to the prognosis of tumors. However, the role of NLRP3 inflammasome in laryngeal squamous cell carcinoma (LSCC) remains unclear. This study aim to investigate the influence of NLPR3 inflammasome expression in LSCC, and especially the NLRP3 inflammasome expression level and the prognosis of LSCC after surgery in a Chinese population. Methods: We used quantitative real-time PCR and immunohistochemical (IHC) staining to calculate the mRNA (20 patients, fresh tissue) and protein expression (104 patients, paraffin tissue microarray) levels of the NLRP3 inflammasome (NLRP3/IL-18/IL-1ß/ASC/caspase-1), respectively. We also analyzed the relationship between NLRP3 inflammasome expression levels and LSCC cancer tissues compared with adjacent normal tissues and the clinical features of LSCC. Kaplan-Meier survival curves of overall survival (OS) and disease-free survival (DFS) in LSCC patients were compared and analyzed under different expression levels of the NLRP3 inflammasome. Results: Our results indicated that the mRNA expression of the NLRP3 inflammasome was higher in LSCC cancer tissues compared with adjacent normal tissues (p < 0.001). The IHC staining score also demonstrated that the expression of the NLRP3 inflammasome was higher than in the adjacent normal tissues (p < 0.001). The NLRP3 inflammasome expression also exhibited a close relationship with the clinicopathological characteristics (especially the stage of LSCC) of LSCC. Univariate Cox regression analysis and multivariate Cox regression analysis revealed that both NLRP3 and IL-1ß had an increased risk of LSCC progression (p < 0.05). The Kaplan-Meier log rank test (OS and DFS) demonstrated that high expression of NLRP3/IL-18/IL-1ß/ASC was statistically different than the low expression group (p < 0.05) of LSCC patients after surgery. Conclusion: The high expression group of the NLRP3 inflammasome (NLRP3/IL-18/IL-1ß/ASC) had a poorer prognosis (OS and DFS) than the low expression group of LSCC patients 5 years after surgery. The NLRP3 inflammasome (NLRP3/IL-18/IL-1ß/ASC) may be used as an auxiliary indicator to predict LSCC patient prognosis after surgery.

18.
J Surg Oncol ; 120(4): 698-706, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273803

RESUMO

BACKGROUND: This study aimed to create a nomogram for postoperative prediction of the risk of recurrence in laryngeal squamous cell carcinoma patients who received laryngectomy alone and to assess indications for postoperative adjuvant treatments (POAT). METHODS: A retrospective analysis of 1571 newly diagnosed laryngeal carcinoma patients was conducted. Those patients were divided into two groups-the development cohort (n = 1102) and the validation cohort (n = 469). Patients were classified into three subgroups according to their individual points calculated from the nomogram. The efficiency of POAT was examined among various subgroups. RESULTS: Five variables, including pT classification, pN classification, surgical margin, tumor differentiation, and primary location, were included in the nomogram. The C-index was 0.753 in development cohort and 0.744 in validation cohort. Patients were classified into three subgroups with incremental risks of recurrence. In the high-risk group, patients receiving POAT showed significantly better recurrence-free survival (RFS) than did those receiving surgery alone, while POAT was not significantly associated with RFS in either the low- or moderate-risk groups. CONCLUSIONS: The risk of tumor recurrence in patients with laryngeal carcinoma was quantified by our newly constructed nomogram. Patients categorized as high-risk were found to benefit from POAT in RFS.


Assuntos
Carcinoma de Células Escamosas/secundário , Tomada de Decisões , Neoplasias Laríngeas/patologia , Recidiva Local de Neoplasia/patologia , Nomogramas , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Período Pós-Operatório , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2379-2392, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31167124

RESUMO

BACKGROUND: Abnormalities of the L-arginine-nitric oxide pathway induce hypertension. 5-Lipoxygenase (5-LO) is the key enzyme involved in synthesis of leukotrienes (LTs). However, whether nitricoxide synthase dysfunction induces hypertensive vascular remodeling by regulating 5-LO activity and its downstream inflammatory metabolites remains unknown. METHODS AND RESULTS: Six-week L-NAME treatment significantly induced hypertension and vascular remodeling in both wild-type (WT) and 5-LO-knockout (5-LO-KO) mice, and blood pressure in caudal and carotid arteries was lower in 5-LO-KO than WT mice with L-NAME exposure. On histology, L-NAME induced less media thickness, media-to-lumen ratio, and collagen deposition and fewer Ki-67-positive vascular smooth muscle cells (VSMCs) but more elastin expression in thoracic and mesenteric aortas of 5-LO-KO than L-NAME-treated WT mice. L-NAME significantly increased LT content, including LTB4 and cysteinyl LT (CysLTs), in plasma and neutrophil culture supernatants from WT mice. On immunohistochemistry, L-NAME promoted the colocalization of 5-LO and 5-LO-activating protein on the nuclear envelope of cultured neutrophils, which was accompanied by elevated LT content in culture supernatants. In addition, LTs significantly promoted BrdU incorporation, migration and phenotypic modulation in VSMCs. CONCLUSION: L-NAME may activate the 5-LO/LT pathway in immune cells, such as neutrophils, and promote the products of 5-LO metabolites, including LTB4 and CysLTs, which aggravate vascular remodeling in hypertension. 5-LO deficiency may protect against hypertension and vascular remodeling by reducing levels of 5-LO downstream inflammatory metabolites.

20.
Gene ; 710: 193-201, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31176734

RESUMO

Accumulative researches have demonstrated the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BC). Our previous studies showed that lnc-DILC was an important tumor suppressor gene in both liver cancer and colorectal cancer. However, the role of lnc-DILC in BC remains to be elucidated. In the present study, we for first found that lnc-DILC was downregulated in human bladder cancer tissues. Lnc-DILC overexpression suppressed the proliferation, metastasis and expansion of bladder cancer stem cells (CSCs). Mechanically, lnc-DILC suppressed BC cells progression via STAT3 pathway. Special STAT3 inhibitor S3I-201 diminished the discrepancy of growth, metastasis and self-renewal ability between lnc-DILC-overexpression BC cells and their control cells, which further confirmed that STAT3 was acquired for lnc-DILC-disrupted BC cell growth, metastasis and self-renewal. Taken together, our results suggest that lnc-DILC is a novel bladder tumor suppressor and indicate that lnc-DILC inhibits BC progression via inactivating STAT3 signaling.


Assuntos
Regulação para Baixo , RNA Longo não Codificante/genética , Transdução de Sinais , Neoplasias da Bexiga Urinária/genética , Ácidos Aminossalicílicos/farmacologia , Benzenossulfonatos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Autorrenovação Celular/efeitos dos fármacos , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos
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