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1.
Org Lett ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35048703

RESUMO

A visible-light-mediated late-stage sulfonylation of anilines with sulfonamides under simple reaction conditions is presented. Various primary or secondary sulfonamides including several pharmaceuticals were incorporated successfully via N-S bond activation and C-H bond sulfonylation. The synthetic utility of this strategy is highlighted by the construction of complex anilines bearing diverse bioactive groups.

2.
Am J Cancer Res ; 11(10): 4807-4825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765294

RESUMO

Deubiquitinase (DUB) zinc finger RANBP2-type containing 1 (ZRANB1) has been reported to have a close relationship with cancers. However, its underlying role and molecular mechanisms in hepatocellular carcinoma (HCC) remain elusive. In this study, we demonstrated that ZRANB1 was highly expressed in HCC tissues. Additionally, ZRANB1 overexpression was correlated with poorer survival and ZRANB1 could be an independent predictor of poor prognosis for HCC patients. Through gain- and loss-of-function assays, we examined the oncogenic role of ZRANB1 in regulating HCC cell growth and metastasis in vitro and in vivo. To identify the downstream targets of ZRANB1 in regulating HCC tumorigenesis, we performed RNA-seq and demonstrated that Lysyl oxidase-like 2 (LOXL2) was the most significantly downregulated gene after ZRANB1 knockdown. Furthermore, the scatter plots indicated a significant positive correlation between ZRANB1 and LOXL2 expression in clinical HCC specimens. We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis in vitro and in vivo. The effects of ZRANB1 knockdown were reversed by LOXL2 overexpression. More importantly, ZRANB1 regulated LOXL2 through specificity protein 1 (SP1) and SP1 overexpression rescued the suppression of HCC growth and metastasis induced by ZRANB1 knockdown. Mechanistically, ZRANB1 bound with SP1 directly and stabilized the SP1 protein by deubiquitinating it. The expression patterns of ZRANB1, SP1 and LOXL2 were evaluated in HCC patients. In summary, our research highlights a novel role of ZRANB1 in the tumorigenesis of HCC and suggests a new candidate prognostic biomarker for HCC treatment.

3.
J Cell Mol Med ; 25(23): 10980-10989, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34773364

RESUMO

Deubiquitinating enzyme OTU domain-containing ubiquitin aldehyde-binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1-derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC.

4.
Huan Jing Ke Xue ; 42(11): 5500-5509, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708989

RESUMO

The spatial distribution, pollution degree, and ecological risk of heavy metals in the soil were studied by analyzing the contents of As, Hg, Cd, Cr, Pb, Zn, Ni, and Cu and pH values in surface soil samples of the eastern mountainous area of the Nanyang basin. The results showed that the contents of Cd, Cu, Cr, Ni, Pb, Zn, and As in the soil exceeded the screening value of soil pollution risk. The spatial distribution of soil heavy metals displayed regional-and island-shaped. The highest concentration of heavy metals was found in the south of the study area, where a mining area is located. Most of the samples had no pollution levels except some samples with high contents of Cd. For As, Cr, Pb, Zn, Ni, and Cu, the potential ecological risk of most samples were low, while Cd and Hg posed medium risk in most areas. The areas with high and relatively high ecological risk index accounted for 58.93% and 37.66%, respectively. Soil Hg, Cd, and Pb contents were related to anthropogenic activities such mineral mining. As derives from geological processes, while Zn, Ni, Cr, and Cu are both controlled by anthropogenic activities and geological processes. The mining of mineral resources is the main driving factor of soil heavy metal pollution and ecological risk in the study area.


Assuntos
Metais Pesados , Poluentes do Solo , Monitoramento Ambiental , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
5.
Folia Primatol (Basel) ; 92(4): 203-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555830

RESUMO

The rhesus macaque (Macaca mulatta) is the most widely distributed nonhuman primate species, and captive populations play an important role in biomedical research due to close phylogenetic and physiological similarity to human beings. However, to our best knowledge, the spondyloarthritis (SpA) in rhesus macaques has been exclusively reported in captive or semicaptive populations rather than wild counterparts. In the present study, we report 2 cases of SpA observed in Taihangshan macaques (Macaca mulatta tcheliensis) inhabiting the Taihangshan Macaque National Nature Reserve, Henan Province, China. Among these 2 cases, one can be diagnosed as ankylosing spondylitis (AS) following accepted medical criteria, and another case showed evident fusion at the pubic symphysis which could be specific to rhesus macaque AS. We discuss the potential causes leading directly or indirectly to the development of SpA.


Assuntos
Espondilartrite , Animais , China , Macaca mulatta , Filogenia
6.
Inorg Chem ; 60(19): 14872-14879, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34533941

RESUMO

A novel organodiphosphonate-based telluromolybdate cluster, (NH4)6Na3H13[TeMo10O37(CoMo2O6L)4]·11H2O [1; L = (O3P)2C(O)(CH2)3NH2], has been successfully synthesized by a simple one-pot aqueous reaction. Intriguingly, the [TeMo10O37]10- subunit with tetrahedral geometry of TeO4 is observed in the organophosphonate-functionalized polyoxometalates for the first time. Compound 1 was prepared in a buffer solution (pH = 5.5) with alendronic acid (Ale) and (NH4)6Mo7O24·4H2O as raw materials. The polyanion [TeMo10O37(CoMo2O6L)4]22- was constructed from four {Mo2O6L} subunits encapsulating an interesting Te-Mo heterometal subunit [TeMo10O37]10- through four CoO6 octahedra and has been fully characterized by routine techniques. In addition, compound 1, as a heterogeneous catalyst, shows good conversion (92%) and high selectivity (99%) for Knoevenagel condensation reaction.

7.
Chem Sci ; 12(27): 9556-9560, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34349930

RESUMO

A novel arylation of sulfonamides with boronic acids to afford numerous diaryl sulfones via a visible light-mediated N-S bond cleavage other than the typical transition-metal-catalyzed C(O)-N bond activation is described. This methodology, which represents the first catalyst-free protocol for the sulfonylation of boronic acids, is characterized by its simple reaction conditions, good functional group tolerance and high efficiency. Several successful examples for the late-stage functionalization of diverse sulfonamides indicate the high potential utility of this method in pharmaceutical science and organic synthesis.

8.
Aging (Albany NY) ; 13(15): 19317-19338, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380780

RESUMO

OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, has been shown to participate in progression of multiple malignancies. The accurate function of OTUD3 in hepatocellular carcinoma (HCC) progression remains elusive. We found that OTUD3 was significantly overexpressed in HCC, and higher OTUD3 expression was correlated with larger tumor size, more distant metastasis, and worse TNM stage. A series of gain- and loss-of-function assays were also performed to examine the oncogenic function of OTUD3 in promoting HCC cell growth and metastasis in vitro. Using a xenograft mouse model, we showed that OTUD3 accelerated HCC progression in vivo. Furthermore, alpha-actinin 4 (ACTN4) was identified as a downstream target of OTUD3 through mass spectrometry analysis, and the ACTN4 protein level was significantly related to OTUD3 expression. Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it. Finally, ACTN4 was found to be essential for OTUD3-mediated HCC proliferation and metastasis in vitro and in vivo. Collectively, our findings identify the oncogenic role of OTUD3 in HCC and suggest that OTUD3 can be considered as a pivotal prognostic biomarker and a potential therapeutic target.

9.
Mol Cell Endocrinol ; 537: 111440, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34428509

RESUMO

Ataxin-3 (ATXN3) is a ubiquitous deubiquitinating enzyme that plays an essential role in the carcinogenesis of numerous tumors and stabilizes the expression of substrates by deubiquitination. However, the functional role of ATXN3 in anaplastic thyroid carcinoma (ATC) remains unknown. In this research, we report that ATXN3 was overexpressed in ATC compared to that in paracancerous samples. Moreover, various gain/loss functional assays were performed to indicate that ATXN3 overexpression enhanced ATC cell proliferation and metastasis. We also found that ATXN3 and eukaryotic translation initiation factor 5A2 (EIF5A2) protein levels in ATC tissues are positively correlated, and ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. Mechanistically, ATXN3 promotes EIF5A2 expression by directly binding to EIF5A2 to reduce its ubiquitination and degradation. Therefore, for the first time, we clarified the role of ATXN3 in the carcinogenesis of ATC cells, which provides novel insights into potential therapeutic targets for ATC progression.

10.
Org Lett ; 23(15): 5988-5992, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34240873

RESUMO

This work describes a base-mediated borylsilylation of benzylic ammonium salts to synthesize geminal silylboronates bearing benzylic proton under mild reaction conditions. Deaminative silylation of aryl ammonium salts was also achieved in the presence of LiOtBu. This strategy which is featured with high efficiency, mild reaction conditions, and good functional group tolerance provides efficient routes for late-stage functionalization of amines.

11.
Food Funct ; 12(11): 4887-4896, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33977967

RESUMO

Compared with terrestrial organisms, the sterols in sea cucumber exhibit a sulfate group at the C-3 position. Our previous study demonstrated that dietary sterol sulfate was superior to phytosterol in alleviating metabolic syndrome by ameliorating inflammation and mediating cholesterol metabolism in high-fat-high-fructose diet mice, which indicated its potential anti-atherosclerosis bioactivity. In the present study, administration with sea cucumber-derived sterol sulfate (SCS) significantly decreased the cholesterol level in oleic acid/palmitic acid-treated HepG2 cells, while no significant changes were observed in the triacylglycerol level. RNA-seq analysis showed that the metabolic changes were mostly attributed to the steroid biosynthesis pathway. ApoE-/- mice were used as an atherosclerosis model to further investigate the regulation of SCS on cholesterol metabolism. The results showed that SCS supplementation dramatically reduced atherosclerotic lesions by 45% and serum low-density lipoprotein cholesterol levels by 59% compared with the model group. Dietary SCS inhibited hepatic cholesterol synthesis via downregulating SREBP-2 and HMGCR. Meanwhile, SCS administration increased cholesterol uptake via enhancing the expression of Vldlr and Ldlr. Noticeably, SCS supplementation altered bile acid profiles in the liver, serum, gallbladder and feces, which might cause the activation of FXR in the liver. These findings provided new evidence about the high bioactivity of sterols with the sulfate group on atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Fígado/metabolismo , Esteróis/farmacologia , Sulfatos/farmacologia , Animais , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Metabolismo dos Lipídeos , Lipogênese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Receptores de LDL , Triglicerídeos/metabolismo
12.
Food Funct ; 12(10): 4411-4423, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876786

RESUMO

Alzheimer's disease (AD) is an age-dependent, irreversible neurodegenerative disease, and one of the pathological features is amyloid-ß (Aß) deposition. Previous studies have shown that phosphatidylserine (PS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibited significant effects in preventing and alleviating the progress of AD. However, no studies have focused on the differences in the preventive effects on AD between EPA-PS and DHA-PS. Here, the effects of EPA-PS and DHA-PS on Aß production, Aß-induced neurotoxicity and Aß clearance have been studied. The results show that DHA-PS significantly reduced Aß production in CHO-APP/PS1 cells compared to EPA-PS. Moreover, both EPA-PS and DHA-PS significantly protected the primary hippocampal neurons against Aß-induced toxicity by inhibiting the mitochondrial-dependent apoptotic pathway and phosphorylation of JNK and p38. Compared to DHA-PS, EPA-PS administration significantly improved the Aß phagocytic capacity of BV2 cells. In addition, EPA-PS and DHA-PS significantly promoted the neurite outgrowth of primary hippocampal neurons. These findings might provide dietary guidance for the prevention of AD as well as a reference for the development of related functional foods.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Fosfatidilserinas/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Animais , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/uso terapêutico , Hipocampo/efeitos dos fármacos , Lipossomos , Neurônios/efeitos dos fármacos , Fosfatidilserinas/uso terapêutico
13.
World J Pediatr ; 17(2): 180-188, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33660136

RESUMO

BACKGROUND: This study was aimed to investigate the clinical and molecular epidemiology of Staphylococcus aureus (S. aureus) isolated from Chinese children and determine the possible relationship among the accessory gene regulator (agr) groups and genotypes, as well as among the virulence genes and disease types. METHODS: S. aureus strains were isolated from Beijing Children's Hospital between October 2017 and October 2019. The isolates and 19 virulence genes were characterized using multi-locus sequence typing, staphylococcal protein A (spa), staphylococcal cassette chromosome mec, and agr typing. RESULTS: A total of 191 non-repetitive S. aureus clinical isolates were divided into 33 sequence types (STs), 18 clonal complexes (CCs), and 59 spa types. ST59 (39.8%), t437 (37.7%), and agr I (84.8%) were the predominant types. CC59, CC25, CC22, CC951, CC8, and CC398 belonged to agr I. CC5 and CC15 were assigned to agr II, and CC30 was characterized as agr III. CC121 was classified under agr IV. The eta, etb, and bbp genes were more prevalent in agr IV (P < 0.001 for each), while tst was more prevalent in agr group III compared to the other groups (P < 0.001). Nearly all isolates that harbored lukS/F-PV belonged to agr I (P = 0.005). However, the correlation between disease types and agr groups was not significant (P > 0.05). CONCLUSIONS: An association among the agr groups and genotypes, as well as specific toxin genes, was observed among the S. aureus strains isolated from Chinese children. However, a statistical correlation was not found among the agr groups and disease types.


Assuntos
Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Virulência/genética , Fatores Etários , Criança , Pré-Escolar , China/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Estafilocócicas/epidemiologia
14.
Ying Yong Sheng Tai Xue Bao ; 32(2): 453-466, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650354

RESUMO

The Quaternary sediment in the Ningbo Coastal Plain was the deposit due to sea-land interaction, which recorded information of past climate changes. The region is therefore an ideal area to study paleoclimate changes and sedimentary characteristics. We determined the stratigraphic division and paleoenvironmental evolution based on 14C and paleomagnetic dating, along with detailed analyses of lithology, pollen assemblage, foraminifera and ostracodes assemblage, and grain size of sediment in core Z02 located in the southeastern Ningbo Coastal Plain. The results showed that the boundary between the Holocene and Upper Pleistocene in the core Z02 record was at 30.5 m, the boundary between the Upper and Middle Pleistocene was at 82.65 m, and the boundary between the Quaternary and Lower Cretaceous was at 90 m. The Middle Pleistocene section of the core contained few sediments, while the Lower Pleistocene section was completely missed. During the late Pleistocene, the hydrodynamic conditions experienced energy levels of medium to medium low to medium, and sedimentary facies changed from alluvial lake to overbank to river to lake to alluvial lake to lake to overbank. During the Holocene, the hydrodynamic changes experienced energy levels of medium low to low to medium, and the sedimentary facies changed from shoreland to shallow sea to shoreland lake. The Ningbo Coastal Plain had experienced tectonic uplift, weathering and erosion stage in the Early and Middle Pleistocene, from warm and humid to dry in the Late Pleistocene, and from warm and humid to dry and cool in the Holocene, as revealed by the core Z02 record. This study provided useful information in investigating past environmental changes in the subtropical coastal region of eastern China.


Assuntos
Lagos , Rios , China , Mudança Climática , Sedimentos Geológicos
15.
Ying Yong Sheng Tai Xue Bao ; 32(2): 486-494, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650357

RESUMO

Based on the high resolution record of fossil pollen data from a 190 cm sediment profile collected in a Betula microphylla-dominated wetland of Ebinur Lake in Xinjiang, we aimed to reveal the changes of vegetation and environment in this wetland over the past 3900 years. Results showed that, in the period between 3420 cal. aBP and 3940 cal. aBP, this area was a desert landscape dominated by plants from Chenopodiaceae and Artemisia. During the period of 2830-3420 cal. aBP, this area became a desert steppe dominated by Thelypteris palustris, surrounded by desert plants mainly composed of Chenopodiaceae and Artemisia. In the period between 2640 and 2830 cal. aBP, Typha pollen increased and occupied a dominant position. The area thus became a typical desert intrazonal wetland mainly composed of Typha. In the period between 1200 and 2640 cal. aBP, Phragmites australis began to grow vigorously and became the dominant species. In the period between 660 and 1200 cal. aBP, the population of Betula expanded rapidly, and P. australis plants continued to grow. During the period of 340-660 cal. aBP, the population of B. microphylla became the dominant species, and the abundance of P. australis decreased. However, there was still some P. australis wetlands in the area. Over the past 340 years, as the area of wetlands decreased and the surface water gradually declined, B. microphylla had grown on swampy meadow soils with suitable moisture conditions. In the past 200 years especially, the sharp increases of Chenopodiaceae pollen in palynological assemblage was closely related to the enhancement of human activities and climate change, resulting in the degradation of wetlands and endangerment of B. microphylla. Therefore, it is necessary to strengthen the protection of wetlands and endangered species in this area.


Assuntos
Lagos , Áreas Alagadas , Betula , China , Humanos , Solo
16.
PLoS One ; 16(3): e0247836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711033

RESUMO

Recently, the incidence of thyroid cancer (THCA) has been on the rise. RNA binding proteins (RBPs) and their abnormal expression are closely related to the emergence and pathogenesis of tumor diseases. In this study, we obtained gene expression data and corresponding clinical information from the TCGA database. A total of 162 aberrantly expressed RBPs were obtained, comprising 92 up-regulated and 70 down-regulated RBPs. Then, we performed a functional enrichment analysis and constructed a PPI network. Through univariate Cox regression analysis of key genes and found that NOLC1 (p = 0.036), RPS27L (p = 0.011), TDRD9 (p = 0.016), TDRD6 (p = 0.002), IFIT2 (p = 0.037), and IFIT3 (p = 0.02) were significantly related to the prognosis. Through the online website Kaplan-Meier plotter and multivariate Cox analysis, we identified 2 RBP-coding genes (RPS27L and IFIT3) to construct a predictive model in the entire TCGA dataset and then validate in two subsets. In-depth analysis revealed that the data gave by this model, the patient's high-risk score is very closely related to the overall survival rate difference (p = 0.038). Further, we investigated the correlation between the model and the clinic, and the results indicated that the high-risk was in the male group (p = 0.011) and the T3-4 group (p = 0.046) was associated with a poor prognosis. On the whole, the conclusions of our research this time can make it possible to find more insights into the research on the pathogenesis of THCA, this could be beneficial for individualized treatment and medical decision making.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas , Humanos , Prognóstico , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
18.
Endocrinology ; 162(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508120

RESUMO

COP9 signalosome subunit 5 (CSN5) plays a key role in carcinogenesis of multiple cancers and contributes to the stabilization of target proteins through deubiquitylation. However, the underlying role of CSN5 in thyroid carcinoma has not been reported. In this research, our data showed that CSN5 was overexpressed in thyroid carcinoma tissues compared with paracancerous tissues. Furthermore, a series of gain/loss functional assays were performed to demonstrate the role of CSN5 in facilitating thyroid carcinoma cell proliferation and metastasis. Additionally, we found there was a positive correlation between CSN5 and angiopoietin-like protein 2 (ANGPTL2) protein levels in thyroid carcinoma tissues and that CSN5 promoted thyroid carcinoma cell proliferation and metastasis through ANGPTL2. We also identified the underlying mechanism that CSN5 elevated ANGPTL2 protein level by directly binding it, decreasing its ubiquitination and degradation. Overall, our results highlight the significance of CSN5 in promoting thyroid carcinoma carcinogenesis and implicate CSN5 as a promising candidate for thyroid carcinoma treatment.


Assuntos
Proteínas Semelhantes a Angiopoietina/fisiologia , Complexo do Signalossomo COP9/fisiologia , Carcinogênese/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Peptídeo Hidrolases/fisiologia , Neoplasias da Glândula Tireoide/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Animais , Células Cultivadas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Processamento de Proteína Pós-Traducional/genética , Proteólise , Transdução de Sinais/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Ubiquitinação/genética
19.
Cell Biol Toxicol ; 37(4): 515-529, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33131013

RESUMO

Endothelial-mesenchymal transition (EndMT) is the transformation of endothelial cell morphology to mesenchymal cell morphology, accompanied by decline of endothelial function and enhancement of mesenchymal function, which promotes tumor progression and tumor cell invasion and metastasis. 27-Hydroxycholesterol (27-HC) is a cholesterol metabolite, which has a high content in human blood. 27-HC promotes breast cancer cell proliferation, invasion, and migration. We previously showed that 27-HC promotes EndMT; however, the underlying mechanism still needs to be further explored. We studied the role of the 14-3-3η/GSK-3ß/ß-catenin complex in EndMT. Our results show that 27-HC induces oxidative stress in HUVECs and activates the p38 signaling pathway, thereby inhibiting the binding of 14-3-3η/GSK-3ß/ß-catenin, promoting the increase of free ß-catenin and nuclear translocation, and finally inducing EndMT. Treatment with N-acetylcysteine (NAC) blocked 27-HC-induced ROS generation and p38 signaling pathway activation, prevented ß-catenin from release from binding, and inhibited EndMT. Blocking ROS production or p38 signaling or knocking down 14-3-3η inhibited 27-HC-induced EndMT and inhibited breast cancer cell metastasis. These findings indicate 14-3-3η is necessary for interactions between the p38 kinase and the GSK-3ß/ß-catenin complex and serves as an adaptor to transmit the upstream kinase signal to the downstream signal, thereby promoting EndMT and breast cancer cell migration.

20.
Technol Cancer Res Treat ; 19: 1533033820983812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371800

RESUMO

We do not know the clinical and prognostic factors that influence the survival of patients with gastric signet ring cell carcinoma (SRC). Therefore, a retrospective review was undertaken of 219 patients with SRC who had undergone gastrectomy between January 2009 and December 2012 in our hospital. Patient age, sex, TNM stage, vessel carcinoma embolus, perineural invasion, tumor site and operation type, postoperative chemotherapy, and five-year overall survival were recorded and evaluated. In our study, 93 cases (42.5%) were signet ring cell carcinoma only, and 126 cases (57.5%) were signet ring cell carcinoma coexisting with other components (such as adenocarcinoma or mucus adenocarcinoma). Eighty-three patients were female, 136 were male, 46 occurred at the gastroesophageal junction (21.0%), 63 at the fundus/body (28.8%), 80 were antrum/pylorus (36.5%), and 30 were whole stomach (13.7%). The prognosis of gastric antrum/ pylorus cancer was the best (P < 0.05). There were 133 patients (60.7%) with stage III, and the single factor analysis showed that the earlier the stage, the better the prognosis. The overall five-year survival rate was 30.1% in all patients. One-hundred and 41 patients (64.4%) received D2 radical surgery, 64 (29.2%) received D1 radical operation, and 14 (6.4%) received palliative resection, and the patients who received D2 had the best overall survival (P < 0.05). The survival time of the paclitaxel-based regimen in postoperative adjuvant chemotherapy tended to be prolonged. There was no statistical difference in overall survival between the percentage of signet-ring cells and sex. In summary, age, tumor stage, and surgical resection combined with D2 lymphadenectomy were independent prognostic factors for SRC. Adjuvant chemotherapy with a paclitaxel-based regimen may improve the survival of patients with SRC.


Assuntos
Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Adulto Jovem
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