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1.
World J Surg Oncol ; 19(1): 271, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503530

RESUMO

BACKGROUND: The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. METHODS: Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. RESULTS: A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. CONCLUSION: ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.


Assuntos
Laparoscopia , Neoplasias Gástricas , Gastrectomia , Humanos , Verde de Indocianina , Excisão de Linfonodo , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
2.
J Nutr Biochem ; : 108863, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517094

RESUMO

Autoimmune hepatitis (AIH) is an immune-mediated type of chronic liver inflammation accompanied by intestinal flora imbalance. Probiotics have been reported to ameliorate imbalances in the intestinal flora. This study aimed to investigate the effects of compound probiotic in the AIH mouse model. AIH mice were gavaged with compound probiotic and injected intraperitoneally with dexamethasone (dex) for 42 days. The results showed that these treatments suppressed hepatic inflammatory cell infiltration, serum transaminase, and Th1 and Th17 cells. However, Treg cells were increased only in the probiotics group, which indicates an immunomodulatory role of the compound probiotic. The compound probiotic maintained intestinal barrier integrity, blocked lipopolysaccharide (LPS) translocation, and inhibited the activation of the TLR4/NF-κB pathway and the production of inflammatory factors in the liver and ileum. Moreover, the compound probiotic treatment increased the abundance of beneficial bacteria and reduced the abundance of potentially harmful bacteria in gut. Compound probiotic may improve ileal barrier function while increasing the diversity of the intestinal flora, blocking the translocation of gut-derived LPS to the liver and therefore preventing activation of the TLR4/NF-κB pathway. The resulting inhibition of pro-inflammatory factor production facilitates AIH remission.

3.
Cell Death Dis ; 12(10): 890, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588421

RESUMO

Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34164891

RESUMO

Dimensionality is a fundamental parameter to modulate the properties of solid materials by tuning electronic structures. Covalent organic frameworks (COFs) are a prominent class of porous crystalline materials, but the study of dimensional dependence on their physicochemical properties is still lacking. Herein we illustrate photocatalytic performances of N,N-diaryl dihydrophenazine (PN)-based COFs are heavily dependent on the structural dimensionality. Six isostructural imine-bonded 2D-PN COFs and one 3D-PN COF were prepared. All can be heterogeneous photocatalysts to promote radical ring-opening polymerization of vinylcyclopropanes (VCPs), which typically produces polymers with a combination of linear (l) and cyclic (c) repeat units. The 2D-PN COFs have much higher catalytic activity than the 3D-PN COF, allowing the efficient synthesis of poly(VCPs) with controlled molecular weight, low dispersity and high l/c selectivity (up to 97 %). The improved performance can be ascribed to the 2D structure which has a larger internal surface area, more catalytically active sites, higher photosensitizing ability and photoinduced electron transfer efficiency.

5.
ASN Neuro ; 13: 17590914211016217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34053243

RESUMO

Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.

6.
Stem Cells ; 39(6): 787-802, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33544938

RESUMO

Metabolic state of hematopoietic stem cells (HSCs) is an important regulator of self-renewal and lineage-specific differentiation. Posttranslational modification of proteins via O-GlcNAcylation is an ideal metabolic sensor, but how it contributes to megakaryopoiesis and thrombopoiesis remains unknown. Here, we reveal for the first time that cellular O-GlcNAcylation levels decline along the course of megakaryocyte (MK) differentiation from human-derived hematopoietic stem and progenitor cells (HSPCs). Inhibition of O-GlcNAc transferase (OGT) that catalyzes O-GlcNAcylation prolongedly decreases O-GlcNAcylation and induces the acquisition of CD34+ CD41a+ MK-like progenitors and its progeny CD34- CD41a+ /CD42b+ megakaryoblasts (MBs)/MKs from HSPCs, consequently resulting in increased CD41a+ and CD42b+ platelets. Using correlation and co-immunoprecipitation analyses, we further identify c-Myc as a direct downstream target of O-GlcNAcylation in MBs/MKs and provide compelling evidence on the regulation of platelets by novel O-GlcNAc/c-Myc axis. Our data indicate that O-GlcNAcylation posttranslationally regulates c-Myc stability by interfering with its ubiquitin-mediated proteasomal degradation. Depletion of c-Myc upon inhibition of OGT promotes platelet formation in part through the perturbation of cell adhesion molecules, that is, integrin-α4 and integrin-ß7, as advised by gene ontology and enrichment analysis for RNA sequencing and validated herein. Together, our findings provide a novel basic knowledge on the regulatory role of O-GlcNAcylation in megakaryopoiesis and thrombopoiesis that could be important in understanding hematologic disorders whose etiology are related to impaired platelet production and may have clinical applications toward an ex vivo platelet production for transfusion.

7.
Int J Biol Sci ; 17(1): 298-306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390851

RESUMO

Postoperative adhesions (PA) are fibrotic tissues that are the most common driver of long-term morbidity after abdominal and pelvic surgery. The optimal drug or material to prevent adhesion formation has not yet been discovered. Comprehensive understanding of cellular and molecular mechanisms of adhesion process stimulates the design of future anti-adhesive strategies. Recently, disruption of peritoneal mesothelial cells were suggested as the 'motor' of PA formation, followed by a cascade of events (coagulation, inflammation, fibrinolysis) and influx of various immune cells, ultimately leading to a fibrous exudate. We showed that a variety of immune cells were recruited into adhesive peritoneal tissues in patients with small bowel obstruction caused by PA. The interactions among various types of immune cells contribute to PA development following peritoneal trauma. Our review focuses on the specific role of different immune cells in cellular and humoral mechanisms underpinning adhesion development.

8.
Gut Microbes ; 13(1): 1-12, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33382354

RESUMO

Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic APC mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of BRAF or KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.

9.
Nutr Cancer ; : 1-8, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026250

RESUMO

The incidence of short-term complications after laparoscopic surgery for gastric cancer is higher. Whether ω-3 fish oil fat emulsion can reduce short-term complications of gastric cancer after laparoscopic surgery is controversial. The purpose of this study was to explore the effect of ω-3 fish oil fat emulsion on postoperative recovery of patients with gastric cancer after laparoscopic surgery. A total of 111 patients were included in this study. These patients were given parenteral nutrition for 5 day or more after surgery. We used univariate analysis and multivariate analysis to determine whether ω-3 fish oil fat emulsion could affect the incidence of short-term complications after gastric cancer laparoscopic surgery. The incidence of postoperative short-term complications in patients with parenteral nutrition supplemented with ω-3 fish oil fat emulsion was significantly lower than that in patients without ω-3 fish oil fat emulsion (12/51 VS 26/60, P = 0.027). ω-3 fish oil fat emulsion is an independent risk factor for short-term postoperative complications in patients with gastric cancer (OR = 0.393, CI:0.155-0.996, P = 0.049). In conclusion, the addition of ω-3 fish oil fat emulsion to parenteral nutrition after operation can effectively reduce the incidence of short-term complications in patients with gastric cancer after laparoscopic surgery.

10.
J Am Chem Soc ; 142(38): 16346-16356, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32841013

RESUMO

The metal-organic framework (MOF) HKUST-1 with a tbo topology serves as an archetypal tunable and isoreticular framework platform for targeting desired applications, but the design and synthesis of tbo-covalent organic frameworks (COFs) remains a formidable challenge. Here we demonstrate the successful use of reticular chemistry as an appropriate strategy for the design and deliberate construction of COFs with a tbo topology. The judicious selection of the perquisite planar building blocks, 4-connected square tetramine of porphyrin and 3-connected trigonal trialdehydes of triphenylamine, allows the condensation of two tbo-COFs, the first examples of COFs with a tbo topology. The resulting COFs both crystallize in the cubic Pm3̅ space group and adopt a non-interpenetrated open framework, in which each tritopic linker connects to three square units forming a truncated Td-octahedron and occupies the alternating triangular faces of the truncated octahedron. Owing to the presence of two different types of photoredox-active moieties, the two COFs can be efficient heterogeneous photocatalysts for the oxidative hydroxylation of arylboronic acids and the reductive defluoroalkylation of trifluoromethyl aromatics with alkenes. The present finding will provide an impetus to examine the potential of tbo-COFs as a new platform for engineering multifunctional materials via expansion and functionalization of building blocks.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(7): 590-595, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32727642

RESUMO

Objective To observe the therapeutic effects of Prunella vulgaris on autoimmune hepatitis (AIH) in mice and explore its mechanism. Methods Forty C57BL/6 mice were randomly divided into normal group, AIH model group and 50, 100 and 200 mg/kg Prunella vulgaris-treated AIH groups with 8 mice each. AIH mice were established with mouse liver antigen S100 mixed with Freund's complete adjuvant (S100/FCA) by intraperitoneal injection. One week after modeling, the normal group and AIH model group were gavaged with 0.2 mL normal saline per day, and Prunella vulgaris-treated AIH groups with 50, 100 and 200 mg/kg of Prunella vulgaris instead per day. After 30 days of intervention, we detected the levels of serum aminotransferase (ALT) and aspartate aminotransferase (AST) by Rate method, hepatic histopathological changes by HE staining, the protein expression of IFN-γ, IL-17A and TGF-ß by immunohistochemistry, and the protein levels of BAX and caspase-3 by Western blot analysis. Results Compared with the AIH model group, the decrease of ALT and AST was found in the Prunella vulgaris-treated AIH groups. In addition, tissue necrosis and inflammatory cell infiltration in the Prunella vulgaris-treated AIH groups were less than those in the AIH model group. The lower expression of IFN-γ, IL-17A, BAX and caspase-3 were shown in the Prunella vulgaris-treated AIH groups in comparison with the AIH model group. However, anti-inflammatory factor TGF-ß increased in the Prunella vulgaris-treated AIH groups compared with the AIH model group. All results were dose-dependent. Conclusion Prunella vulgaris can remarkably lessen the symptoms of AIH mice through its anti-inflammatory and anti-apoptotic effects.


Assuntos
Hepatite Autoimune , Prunella , Animais , Aspartato Aminotransferases , Hepatite Autoimune/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
12.
Aging (Albany NY) ; 12(12): 11878-11892, 2020 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-32568098

RESUMO

BACKGROUND: Primary hepatocellular carcinoma (PHCC) has a poor prognosis and high short-term mortality rate, even after resection. Thus, early diagnosis in PHCC cases can help improve quality of life via personalized management strategies. RESULTS: The risk score system (RSS) were classified as low risk (<5 points), medium risk (5-10 points), or high risk (>10 points). The areas under the receiver operating characteristic curves were 0.80 in the training cohort and 0.69 in the validation cohort, which indicated satisfactory prognostic performance. The Hosmer-Lemeshow goodness of fit test (P>0.05) revealed consistent performance in both groups. The concordance index (C-index: 0.663, 95% CI: 0.618-0.708) revealed excellent discrimination and good calibration in the validation cohort. CONCLUSIONS: This simple RSS, which is based on clinical and laboratory data from patients undergoing resection of PHCC, might allow clinicians and medical staff to better manage PHCC. MATERIALS AND METHODS: A total of 672 PHCC cases were retrospectively obtained from the First Affiliated Hospital of Wenzhou Medical University between January 2007 and February 2015. Cox proportional hazard models were used to identify independent predictors of mortality. Kaplan-Meier curves and the log-rank test were used to examine the relationships between the prognostic factors and overall mortality.


Assuntos
Carcinoma Hepatocelular/mortalidade , Hepatectomia , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
13.
J Am Chem Soc ; 142(21): 9642-9652, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32363868

RESUMO

The design and development of robust and porous supported catalysts with high activity and selectivity is extremely significant but very challenging for eco-friendly synthesis of fine chemicals and pharmaceuticals. We report here the design and synthesis of highly stable chiral Zr(IV)-based MOFs with different topologies to support Ir complexes and demonstrate their network structures-dependent asymmetric catalytic performance. Guided by the modulated synthesis and isoreticular expansion strategy, five chiral Zr-MOFs with a flu or ith topology are constructed from enantiopure 1,1'-biphenol-derived tetracarboxylate linkers and Zr6, Zr9, or Zr12 clusters. The obtained MOFs all show high chemical stability in boiling water, strongly acidic, and weakly basic aqueous solutions. The two flu MOFs featuring the dihydroxyl groups of biphenol in open and large cages, after sequential postsynthetic modification with P(NMe2)3 and [Ir(COD)Cl]2, can be highly efficient and recyclable heterogeneous catalysts for hydrogenation of α-dehydroamino acid esters with up to 98% ee, whereas the three ith MOFs featuring the dihydroxyl groups in small cages cannot be installed with P(NMe2)3 to support the Ir complex. Incorporation of Ir-phosphorus catalysts into Zr-MOFs leads to great enhancement of their chemical stability, durability, and even stereoselectivity. This work therefore not only advances Zr-MOFs as stable supports for labile metal catalysts for heterogeneous asymmetric catalysis but also provides a new insight into how highly active chiral centers can result due to the framework topology.

15.
Cancer Lett ; 483: 66-74, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32142917

RESUMO

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5ß1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Integrina alfa5beta1/antagonistas & inibidores , Integrina beta1 , Integrinas/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Quinase 1 de Adesão Focal/metabolismo , Humanos , Integrina alfa5beta1/metabolismo , Integrina beta1/metabolismo , Integrinas/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , Transdução de Sinais , Tetraspanina 24/genética , Tetraspanina 24/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Am J Transl Res ; 11(6): 3438-3449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312356

RESUMO

Acute graft-versus-host disease (aGVHD) is one of the major complications after liver transplantation (LTx), which is induced by over-activation of T helper lymphocytes. Cenicriviroc (CVC) exerts its anti-inflammatory effect through inhibition of C-C chemokine receptor 5 (CCR5). However, whether CVC ameliorates aGVHD after liver transplantation remains unknown. In the present study, a rat aGVHD liver transplantation model (LTx-aGVHD) was constructed. CVC was intravenously injected from day 7 to day 14 after LTx. Liver and intestine samples were harvested to evaluate GVHD severity. Peripheral blood mononuclear cells (PBMCs) were collected and CCR5 antibodies were prepared to further explore the molecular mechanism in vitro. CVC significantly decreased the severity of GVHD associated skin and intestine injury. Quality of life of the LTx-GVHD rats was improved after CVC treatment. Flow cytometry further confirmed diminished peripheral donor-derived Th cells after CVC treatment. Molecularly, CVC treatment showed similar anti-inflammatory effects to CCR5 antibody injection. The level of CCR5, C-C motif chemokine ligand 5 (CCL5), and pro-inflammatory cytokines in the liver and intestines were inhibited after CVC treatment. Thus, CVC deactivated Th lymphocytes and decreased the severity of LTx-aGVHD through inhibition of CCR5.

18.
Artif Cells Nanomed Biotechnol ; 47(1): 1961-1970, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31116036

RESUMO

Alantolactone (Ala), a major sesquiterpene lactone extracted from Inula helenium, exerts potent anti-tumour activities in various cancers. However, the underlying mechanism of such activities is still ambiguous. This study focused on evaluating the anti-tumour effects and molecular mechanisms of Ala on HepG2 cells. Our results demonstrated that Ala might inhibit cellular proliferation, induce G2/M phase arrest and apoptosis in HepG2 cells. Specifically, this study confirmed that Ala induced G2/M phase arrest by upregulating p21, downregulating cyclin A1 and cyclin B1, and promoting cellular apoptosis by increasing the expression of cleaved caspase-3 and PARP. Furthermore, Ala caused an increase in reactive oxygen species (ROS) level and inhibition of ROS production significantly prevented Ala-induced apoptosis. Interestingly, the accumulation of ROS, in turn, suppressed the downstream AKT signalling. Finally, mitophagy of Ala-treated HepG2 cells was observed by Mito/Lyso staining. Mitophagy was significantly inhibited by downregulation of the expression of PINK1 and Parkin proteins. The inhibition of mitophagy by a mitophagy inhibitor was found to markedly enhance Ala-mediated apoptosis and growth inhibition in HepG2 cells. Consequently, Ala induced cellular apoptosis via ROS-mediated suppression of AKT signalling and inhibition of PINK1-mediated mitophagy. Thus, Ala has potential to be used for the treatment of liver cancer.


Assuntos
Apoptose/efeitos dos fármacos , Lactonas/farmacologia , Mitofagia/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Fosfoproteínas/metabolismo
19.
Cardiovasc J Afr ; 30(4): e1-e3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140542

RESUMO

Wellens' syndrome is a relatively common clinical entity; however, it is often missed, especially in young patients. Without prompt diagnosis and aggressive intervention, patients with Wellens' syndrome may rapidly go on to develop extensive anterior wall myocardial infarction and possibly sudden death. In this case report, we present a 33-year-old male patient with atypical chest pain, and discuss the significance of a prompt recognition of Wellens' syndrome.


Assuntos
Angina Pectoris/etiologia , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Eletrocardiografia , Adulto , Angina Pectoris/diagnóstico , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/terapia , Estenose Coronária/complicações , Estenose Coronária/terapia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Stents Farmacológicos , Diagnóstico Precoce , Humanos , Masculino , Intervenção Coronária Percutânea/instrumentação , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Cancer Lett ; 453: 1-9, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30928385

RESUMO

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer. Anesthetic regimens possibly influence cancer development. Exploration of novel, effective targets for liver cancer is the current hotspot in cancer treatment. A previous study conducted by us has demonstrated that enhanced expression of the µ-opioid receptor (MOR) promotes cell proliferation, adhesion, migration, and tumorigenesis. The current study investigates whether MOR regulates self-renewal of hepatocellular carcinoma stem cells (HCSCs). We utilize cell function assays, siRNA, shRNA, flow cytometry sorting, and other molecular biology techniques for this purpose. The results indicate that MOR expression is positively related to hepatocarcinoma progression. Silencing MOR greatly reduce HCC-related tumorigenesis both in vitro and in vivo and significantly extend the survival of tumor-bearing mice. Moreover, MOR silencing will greatly reduce colony formation by HCC cells, indicating down-regulation of cancer initiation. In conclusion, these results establish that MOR can be a novel and reliable HCSC marker and a potential therapeutic target against HCC via MOR-NFAT signaling.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Receptores Opioides mu/biossíntese , Animais , Carcinogênese , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Receptores Opioides mu/genética , Transcrição Genética
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