Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Biomaterials ; 311: 122703, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39002516

RESUMO

An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.


Assuntos
Hidrogéis , Imunoterapia , Lectinas Tipo C , Imunoterapia/métodos , Animais , Hidrogéis/química , Lectinas Tipo C/metabolismo , Humanos , Linhagem Celular Tumoral , Neoplasias/terapia , Neoplasias/imunologia , Camundongos Endogâmicos C57BL , Microambiente Tumoral/imunologia , Quitosana/química , Células Apresentadoras de Antígenos/imunologia , Vacinas Anticâncer/imunologia , Camundongos , Proteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Linfócitos T CD8-Positivos/imunologia
2.
Biochem Biophys Res Commun ; 708: 149780, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38518725

RESUMO

Diverse animal models have been used to study postpancreatitis diabetes mellitus (PPDM) development; however, no study has yet conducted a comparative analysis of the specific differences in glucose homeostasis and islet injury between these models. Therefore, we investigated the differences in pancreatic islet injury and glucose homeostasis among diverse strains in a cerulein-induced acute pancreatitis (AP) model to determine the appropriate animal model for PPDM. BALB/cJ, C57BL/6J, C57BL/6 N, and FVB/NJ mice were administered cerulein to induce AP. Serum amylase levels, pancreatic acinar injury, blood glucose homeostasis, islet function, and islet injury were measured and analyzed. All strains exhibited elevated amylase secretion post pancreatitis, and BALB/cJ, C57BL/6J, and C57BL/6 N mice exhibited sex-related differences. All strains exhibited pancreatic acinar injury post pancreatitis but mostly recovered within 15 days. Overall, glucose homeostasis remained balanced post pancreatitis in all strains compared to that in the control groups, except in FVB/NJ male and female mice, which exhibited an imbalance in glucose homeostasis on day 7 post pancreatitis. All the strains, except BALB/cJ mice, exhibited a decline in Homeostasis model assessment-ß(HOMA-ß) values post pancreatitis, with significant decrease in C57BL/6J females and FVB/NJ males. Islet size decreased post pancreatitis in all strains, except BALB/cJ mice. Pancreatic islet insulin secretion levels significantly decreased in male FVB/NJ mice post pancreatitis onset and did not recover within 15 days. Therefore, FVB/NJ male mice are a useful model for studying PPDM.


Assuntos
Pancreatite , Camundongos , Masculino , Feminino , Animais , Pancreatite/induzido quimicamente , Ceruletídeo/toxicidade , Doença Aguda , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Glicemia , Homeostase , Amilases
3.
Nat Commun ; 14(1): 4658, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537158

RESUMO

Material-based tactics have attracted extensive attention in driving the functional evolution of organisms. In aiming to design steerable bioartificial organisms to scavenge pathogenic waterborne viruses, we engineer Paramecium caudatum (Para), single-celled microorganisms, with a semiartificial and specific virus-scavenging organelle (VSO). Fe3O4 magnetic nanoparticles modified with a virus-capture antibody (MNPs@Ab) are integrated into the vacuoles of Para during feeding to produce VSOs, which persist inside Para without impairing their swimming ability. Compared with natural Para, which has no capture specificity and shows inefficient inactivation, the VSO-engineered Para (E-Para) specifically gathers waterborne viruses and confines them inside the VSOs, where the captured viruses are completely deactivated because the peroxidase-like nano-Fe3O4 produces virus-killing hydroxyl radicals (•OH) within acidic environment of VSO. After treatment, magnetized E-Para is readily recycled and reused, avoiding further contamination. Materials-based artificial organelles convert natural Para into a living virus scavenger, facilitating waterborne virus clearance without extra energy consumption.


Assuntos
Vírus , Radical Hidroxila , Peroxidase , Peroxidases , Anticorpos Antivirais
4.
Clin Lab ; 69(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37436373

RESUMO

BACKGROUND: The aim of the study was to provide a clinical treatment reference for acute pancreatitis (AP) with infection, we analyzed the clinical and genomic characteristic of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from AP with infection in China. METHODS: Our clinical database was retrospectively analyzed with focus on the carbapenem-resistant characteristics among AP with infection in our Intensive Care Unit (ICU). Whole-genome sequencing (WGS) was used to analyze the antibiotic resistance gene, and antimicrobial susceptibility testing (AST) was performed to study the relevant phenotype in vitro. The CRISPR-Cas9 system was used to verify the relevant phenotype. RESULTS: Based on 2,211 AST data of 627 AP patients with infection, CRKP had the highest proportion among carbapenem-resistant Enterobacteriaceae (CRE), at 37.8% for imipenem and 45.3% for meropenem. WGS revealed key ß-lactamase genes, specifically blaCTX-M-15, blaCTX-M-65, blaKPC-2, blaLAP-2, blaNDM-5, blaTEM-181, blaOXA-1, and blaSHV. A total of 31.3% of CRKP were NDM-5-KPC-2-producing strains, and NDM-5-producing CRKP was resistant to imipenem/meropenem combined with avibactam, with an MIC of 512 mg/L. In addition, after knocking out blaKPC-2 and blaNDM-5, NDM-5-producing and KPC-2-producing CRKP had the same resistance level to imipenem/ meropenem. CONCLUSIONS: We first provided key insights into the clinical and genomic characteristic of CRKP in AP with infection and then made it clear that NDM-5 and KPC-2 had the same resistance level to carbapenems.


Assuntos
Farmacorresistência Bacteriana , Infecções por Klebsiella , Klebsiella pneumoniae , Pancreatite , Humanos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , China , Farmacorresistência Bacteriana/genética , Genômica , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Pancreatite/tratamento farmacológico , Pancreatite/microbiologia , Estudos Retrospectivos
5.
Nat Biomed Eng ; 7(7): 928-942, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36959404

RESUMO

The threat of new viral outbreaks has heightened the need for ready-to-use vaccines that are safe and effective. Here we show that a subcutaneous vaccine consisting of live Zika virus electrostatically entrapped in a self-adjuvanting hydrogel recruited immune cells at the injection site and provided mice with effective protection against a lethal viral challenge. The hydrogel prevented the escape of the viral particles and upregulated pattern recognition receptors that activated innate antiviral immunity. The local inflammatory niche facilitated the engulfment of the virus by immune cells infiltrating the hydrogel, the processing and cross-presentation of antigens and the expansion of germinal centre B cells and induced robust antigen-specific adaptive responses and immune memory. Inflammatory immune niches entrapping live viruses may facilitate the rapid development of safe and efficacious vaccines.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Camundongos , Hidrogéis , Anticorpos Antivirais , Imunização , Vacinação , Infecção por Zika virus/prevenção & controle
6.
J Hazard Mater ; 446: 130643, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586333

RESUMO

Triphenyl phosphate (TPHP) is a widely used aryl organophosphate flame retardant (OPFR) that has attracted attention due to its frequent detection in the environment and living organisms. To date, the reproductive toxicity of TPHP has been investigated in organisms, but its molecular mechanisms are not fully understood. Caenorhabditis elegans (C. elegans) is the ideal animal for the study of reproductive toxicity following environmental pollutants, with short generation times, intact reproductive structures, and hermaphroditic fertilization. This study aimed to explore the reproductive dysfunction and molecular mechanisms induced by TPHP exposure in C. elegans. Specifically, exposure to TPHP resulted in a reduction in the number of eggs laid and developing embryos in utero, an increase in the number of apoptotic gonadal cells, and germ cell cycle arrest. The JNK signaling pathway is a potential pathway inducing reproductive toxicity following TPHP exposure based on transcriptome sequencing (RNA-seq). Moreover, TPHP exposure induced down-regulation of vhp-1 and kgb-2 gene transcription levels, and the knockout of vhp-1 and kgb-2 in the mutant strains exhibited more severe toxicity in apoptotic gonad cells, embryos, and eggs developing in utero, suggesting that vhp-1 and kgb-2 genes play a crucial role in TPHP-induced reproductive toxicity. Our data provide convergent evidence showing that TPHP exposure results in reproductive dysfunction through the JNK signaling pathway and improve our understanding of the ecotoxicity and toxicological mechanisms of aryl-OPFRs.


Assuntos
Caenorhabditis elegans , Retardadores de Chama , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Sistema de Sinalização das MAP Quinases , Organofosfatos/toxicidade , Retardadores de Chama/toxicidade , Retardadores de Chama/metabolismo
7.
ACS Appl Mater Interfaces ; 14(35): 39873-39884, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36018064

RESUMO

Despite the great potency of vaccines to combat infectious diseases, their global use is hindered by a lack of thermostability, which leads to a constant need for cold-chain storage. Here, aiming at long-term thermostability and eliminating cold-chain requirements of bioactive vaccines, we propose that efforts should focus on tailoring the conformational stability of vaccines. Accordingly, we design a nanocoating composed of histidine (His)-coordinated amorphous Zn and 2-methylimidazolate complex (His-aZn-mIM) on single nanoparticles of viral vaccines to introduce intramolecular coordinated linkage between viruses and the nanocoatings. The coordinated nanocoating enhances the rigidity of proteins and preserves the vaccine's activity. Importantly, integrating His into the original Zn-N coordinative environment symbiotically reinforces its tolerance to biological and hydrothermal solutions, resulting in the augmented thermostability following the Hofmeister effect. Thus, even after storage of His-aZn-mIM encapsulated Human adenovirus type 5 (Ad5@His-aZn-mIM) at 25 °C for 90 d, the potency loss of the coated Ad5 is less than 10%, while the native Ad5 becomes 100% ineffective within one month. Such a nanocoating gains thermostability by forming an ultrastable hydration shell, which prevents viral proteins from unfolding under the attack of hydration ions, providing a conformational stabilizer upon heat exposure. Our findings represent an easy-access biomimetic platform to address the long-term vaccine storage without the requirement of a cold chain.


Assuntos
Adenovírus Humanos , Vacinas Virais , Excipientes , Humanos , Conformação Molecular , Refrigeração
8.
Comput Intell Neurosci ; 2022: 9152605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619816

RESUMO

The introduction of digital technology in the healthcare industry is marked by ongoing difficulties with implementation and use. Slow progress has been made in unifying different healthcare systems, and much of the globe still lacks a fully integrated healthcare system. As a result, it is critical and advantageous for healthcare providers to comprehend the fundamental ideas of AI in order to design and deliver their own AI-powered technology. AI is commonly defined as the capacity of machines to mimic human cognitive functions. It can tackle jobs with equivalent or superior performance to humans by combining computer science, algorithms, machine learning, and data science. The healthcare system is a dynamic and evolving environment, and medical experts are constantly confronted with new issues, shifting duties, and frequent interruptions. Because of this variation, illness diagnosis frequently becomes a secondary concern for healthcare professionals. Furthermore, clinical interpretation of medical information is a cognitively demanding endeavor. This applies not just to seasoned experts, but also to individuals with varying or limited skills, such as young assistant doctors. In this paper, we proposed the comparative analysis of various state-of-the-art methods of deep learning for medical imaging diagnosis and evaluated various important characteristics. The methodology is to evaluate various important factors such as interpretability, visualization, semantic data, and quantification of logical relationships in medical data. Furthermore, the glaucoma diagnosis system is discussed in detail via qualitative and quantitative approaches. Finally, the applications and future prospects were also discussed.


Assuntos
Algoritmos , Aprendizado de Máquina , Humanos
9.
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.

10.
Biomaterials ; 276: 121062, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418816

RESUMO

Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.


Assuntos
Vacinas Virais , Adenoviridae/genética , Animais , Vetores Genéticos , Imunidade nas Mucosas , Camundongos , Fagocitose
11.
Front Microbiol ; 12: 669230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248878

RESUMO

Infected pancreatic necrosis (IPN) is a key risk factor in the progression of severe acute pancreatitis, and use of antibiotics is one of the main clinical actions. However, early prophylactic or unreasonable use of antibiotics promotes drug resistance in bacteria and also delays optimum treatment. To explore genomic evidence of rational antibiotic use in intensive care units, we isolated Klebsiella pneumoniae from IPN samples that showed the highest positive-culture rate in 758 patients. Based on whole-genome sequencing from eight strains, 42 antibiotic-resistant genes were identified in the chromatin and 27 in the plasmid, which included classic resistance-mechanism factors such as ß-lactamases [16.67% (7/42) in the chromatin and 25.93% (7/27) in the plasmid]. The K. pneumoniae isolates were identified to be resistant to multiple antibiotics used in clinics. In vivo and in vitro, ceftazidime-avibactam (CZA) plus aztreonam (ATM) (2.5:1) showed more significant antibacterial effectiveness than CZA alone. The isolated K. pneumoniae were of three different types according to the resistance phenotypes for CZA and ATM. Those co-harboring bla NDM-5, bla CTX-M-15, bla OXA-1, and bla SHV-187 showed higher resistance to CAZ than bla NDM-5. Those co-harboring bla CTX-M-65, bla SHV-182, and bla TEM-181 were significantly less resistant to ß-lactam than to other extended-spectrum ß-lactamases. However, ß-lactamases were inhibited by avibactam (AVI), except for NDM-5. ATM plus AVI showed a significant inhibitory effect on K. pneumoniae, and the minimum dosage of ATM was < 1 mg/L. In conclusion, we propose that ATM plus AVI could be a major therapy for complex infectious diseases caused by multidrug-resistant K. pneumoniae.

12.
Cell Commun Signal ; 18(1): 169, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109187

RESUMO

BACKGROUND: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. METHODS: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. RESULTS: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/ß-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/ß-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. CONCLUSIONS: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/ß-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC. Video abstract.


Assuntos
Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/patologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Via de Sinalização Wnt , Animais , Fator de Transcrição CDX2/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Progressão da Doença , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Lisina/metabolismo , Masculino , Metilação , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/genética , Análise de Sobrevida , Regulação para Cima/genética
13.
Trends Endocrinol Metab ; 30(10): 745-755, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405774

RESUMO

Metformin is the most widely prescribed oral hypoglycemic medication for type 2 diabetes worldwide. Metformin also retards aging in model organisms and reduces the incidence of aging-related diseases such as neurodegenerative disease and cancer in humans. In spite of its widespread use, the mechanisms by which metformin exerts favorable effects on aging remain largely unknown. Further, not all individuals prescribed metformin derive the same benefit and some develop side effects. Before metformin finds its way to mainstay therapy for anti-aging, a more granular understanding of the effects of the drug in humans is needed. This review provides an overview of recent findings from metformin studies in aging and longevity and discusses the use of metformin to combat aging and aging-related diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Medicina de Precisão/métodos
14.
Chemistry ; 24(45): 11518-11529, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-29377301

RESUMO

In nature, viruses can realize self-mineralization under metal-ion-abundant conditions. Interestingly, the mineralized state is a transition state of the virus when the host is not available. Mammalian viruses that share the similar chemical properties also stand a chance of transformation into a mineralized state. In this review, we focus on the possibility of mammalian viruses to undergo mineralization under a physiological environment and the development of biomineralized-based virus engineering. We will introduce the effect of biomineralization on the physiochemical or biological properties of viruses and we will discuss the relationship between mineral composition and biological potentials. The new biological prospects of mineralized-state viruses, including bypassing biological barriers, protection, and virus-host recognition, will provide new insight for the biosecurity and prevention of viral infection. With respect to vaccines, the mineralized state can modulate the immune recognition, change the immunization route, and elevate the vaccine efficacy. Together, these findings of the mineralized state of the virus may lead to a new understanding of virus biology, application, and prevention.


Assuntos
Minerais/química , Vacinas Virais/química , Vírus , Animais , Humanos , Vacinas , Vacinas Virais/imunologia
15.
Onco Targets Ther ; 10: 3685-3696, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769572

RESUMO

We sought to systematically evaluate the diagnostic and prognostic value of miR-203 in patients with colorectal cancer. To explore the diagnostic performance of miR-203, eligible studies were identified from biomedical databases. Based on these results, 11 studies were pooled and included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios of miR-203 were 0.83 (95% confidence interval, CI: 0.78-0.86), 0.80 (95% CI: 0.77-0.83), and 19.27 (95% CI: 7.23-51.36) for the diagnosis of colorectal cancer. The area under the curve for miR-203 for diagnosing colorectal cancer was 0.89. Patients with higher expression of tissue miR-203 had poor overall survival (pooled hazard ratio: 1.63; 95% CI: 1.03-2.57, P=0.04), but serum miR-203 was not predictive (pooled hazard ratio: 1.59; 95% CI: 0.31-8.12, P=0.58). The miR-203 values of tissue and serum merged together may perhaps predict superior overall survival (pooled hazard ratio: 1.62; 95% CI: 0.93-2.82), but the effect was not significant (P=0.09).

16.
Med Mol Morphol ; 50(2): 76-85, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27981410

RESUMO

Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.


Assuntos
Adenocarcinoma/genética , Proteína 7 Relacionada à Autofagia/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Animais , Apoptose/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Sequência de Bases , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Células HCT116 , Células HT29 , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Análise de Sobrevida
17.
Oncotarget ; 8(3): 5038-5047, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27926519

RESUMO

We sought to systematically evaluate the diagnostic and prognostic value miR106a in patients with colorectal cancer (CRC). An original study was conducted to explore correlations between tissue miR106a levels and outcomes for 138 patients diagnosed with CRC. To explore the diagnostic performance of miR106a, eligible studies were identified from medical databases from China and abroad. Based on these results, 15 studies (including our original study) were pooled and included in a meta-analyses. The pooled sensitivity, specificity, and diagnostic odds ratios of miR106a were 0.53 (95% confidence interval (CI): 0.49-0.57), 0.85 (95% CI: 0.82-0.88), and 7.22 (95% CI: 3.17-16.44) for diagnosis of CRC, and the area under the curve (AUC) for miR106a when diagnosing CRC was 0.72. Patients with higher expression of tissue miR106a had poor overall survival (pooled hazard ratio (HR): 1.50; 95% CI: 1.02-2.20), but not disease-free survival (pooled HR: 1.03; 95% CI: 0.40-2.65). Overexpression of miR106a may predict superior metastasis-free survival (pooled HR: 0.65; 95% CI: 0.33-1.27), but the effect was not significant in this study (p = 0.21).


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , MicroRNAs/genética , Área Sob a Curva , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Sensibilidade e Especificidade , Análise de Sobrevida
18.
Chemistry ; 22(49): 17857-17865, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27783445

RESUMO

The gelation behavior of cationic surfactants with different counterions, Br- , [FeCl3 Br]- , and [CeCl3 Br]- , in imidazolium ionic liquids (ILs) and protic ethylammonium nitrate was investigated. Small-angle X-ray scattering measurements and freeze-fracture transmission electron microscopy observations revealed the lamellar phases of metallosurfactant ionogels. The characteristics of imidazolium ILs, including the size and type, have effects on metallosurfactant ionogel properties, such as transformation temperatures, interlayer spacing, and mechanical strength. Cubic fluorite structured cerium oxide nanoparticles (CeO2 NPs) were produced by using metallosurfactant ionogels as precursors. Cubic fluorite CeO2 exhibited good catalase mimetic activity toward H2 O2 to generate O2 , providing more multiple mimetic enzyme activities of CeO2 NPs for H2 O2 .

19.
Cancer Res ; 76(16): 4897-907, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27312528

RESUMO

Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells. Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10-eEF1A1 or Ub-eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub-eEF1A1 levels and increased FAT10-eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. Cancer Res; 76(16); 4897-907. ©2016 AACR.


Assuntos
Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fator 1 de Elongação de Peptídeos/metabolismo , Ubiquitinas/metabolismo , Animais , Western Blotting , Proliferação de Células , Xenoenxertos , Humanos , Imunoprecipitação , Camundongos , Camundongos Nus , Microscopia Confocal , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Ubiquitina/metabolismo , Ubiquitinação
20.
Chem Asian J ; 11(5): 722-9, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26647361

RESUMO

Green and environmentally friendly ionogels formed by a sugar surfactant were prepared in two kinds of imidazolium-based ionic liquids. The phase transition from ribbon structures to lamellar structures induced by temperature and the transition mechanism were investigated in detail by means of freeze-fracture TEM and field-emission SEM observations, as well as small-angle X-ray scattering measurements. The rheological properties and tribological properties of two kinds of ionogels were systematically investigated. The difference in the lubricating properties and antiwear capability can be explained well by the mechanical and viscoelastic properties, as well as the different microstructures of samples destroyed by shear forces. This work provides a better understanding of the relationship between the structures, rheological properties, and tribological properties of ionogels.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA