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1.
Artigo em Inglês | MEDLINE | ID: mdl-31754437

RESUMO

Background: Lignocellulosic biomass has long been recognized as a potential sustainable source for industrial applications. The costs associated with conversion of plant biomass to fermentable sugar represent a significant barrier to the production of cost-competitive biochemicals. Consolidated bioprocessing (CBP) is considered a potential breakthrough for achieving cost-efficient production of biomass-based fuels and commodity chemicals. During the degradation of cellulose, cellobiose (major end-product of cellulase activity) is catabolized by hydrolytic and phosphorolytic pathways in cellulolytic organisms. However, the details of the two intracellular cellobiose metabolism pathways in cellulolytic fungi remain to be uncovered. Results: Using the engineered malic acid production fungal strain JG207, we demonstrated that the hydrolytic pathway by ß-glucosidase and the phosphorolytic pathway by phosphorylase are both used for intracellular cellobiose metabolism in Myceliophthora thermophila, and the yield of malic acid can benefit from the energy advantages of phosphorolytic cleavage. There were obvious differences in regulation of the two cellobiose catabolic pathways depending on whether M. thermophila JG207 was grown on cellobiose or Avicel. Disruption of Mtcpp in strain JG207 led to decreased production of malic acid under cellobiose conditions, while expression levels of all three intracellular ß-glucosidase genes were significantly up-regulated to rescue the impairment of the phosphorolytic pathway under Avicel conditions. When the flux of the hydrolytic pathway was reduced, we found that ß-glucosidase encoded by bgl1 was the dominant enzyme in the hydrolytic pathway and deletion of bgl1 resulted in significant enhancement of protein secretion but reduction of malate production. Combining comprehensive manipulation of both cellobiose utilization pathways and enhancement of cellobiose uptake by overexpression of a cellobiose transporter, the final strain JG412Δbgl2Δbgl3 produced up to 101.2 g/L and 77.4 g/L malic acid from cellobiose and Avicel, respectively, which corresponded to respective yields of 1.35 g/g and 1.03 g/g, representing significant improvement over the starting strain JG207. Conclusions: This is the first report of detailed investigation of intracellular cellobiose catabolism in cellulolytic fungus M. thermophila. These results provide insights that can be applied to industrial fungi for production of biofuels and biochemicals from cellobiose and cellulose.

2.
Oncol Rep ; 42(1): 213-223, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115559

RESUMO

Colorectal cancer (CRC) is one of the most common types of malignancy worldwide. Distant metastasis is a key cause of CRC­associated mortality. MEIS2 has been identified to be dysregulated in several types of human cancer. However, the mechanisms underlying the regulatory role of MEIS2 in CRC metastasis remain largely unknown. For the first time, the present study demonstrated that MEIS2 serves a role as a promoter of metastasis in CRC. In vivo and in vitro experiments revealed that knockdown of MEIS2 significantly suppressed CRC migration, invasion and the epithelial­mesenchymal transition. Furthermore, microarray and bioinformatics analyses were performed to investigate the underlying mechanisms of MEIS2 in the regulation of CRC metastasis. Additionally, it was identified that a high expression of MEIS2 was significantly associated with a shorter overall survival time for patients with CRC. The present study demonstrated that MEIS2 may serve as a novel biomarker for CRC.


Assuntos
Neoplasias Colorretais/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Análise de Sobrevida
3.
Biotechnol Biofuels ; 11: 323, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30534201

RESUMO

Background: Fumaric acid is widely used in food and pharmaceutical industries and is recognized as a versatile industrial chemical feedstock. Increasing concerns about energy and environmental problems have resulted in a focus on fumaric acid production by microbial fermentation via bioconversion of renewable feedstocks. Filamentous fungi are the predominant microorganisms used to produce organic acids, including fumaric acid, and most studies to date have focused on Rhizopus species. Thermophilic filamentous fungi have many advantages for the production of compounds by industrial fermentation. However, no previous studies have focused on fumaric acid production by thermophilic fungi. Results: We explored the feasibility of producing fumarate by metabolically engineering Myceliophthora thermophila using the CRISPR/Cas9 system. Screening of fumarases suggested that the fumarase from Candida krusei was the most suitable for efficient production of fumaric acid in M. thermophila. Introducing the C. krusei fumarase into M. thermophila increased the titer of fumaric acid by threefold. To further increase fumarate production, the intracellular fumarate digestion pathway was disrupted. After deletion of the two fumarate reductase and the mitochondrial fumarase genes of M. thermophila, the resulting strain exhibited a 2.33-fold increase in fumarate titer. Increasing the pool size of malate, the precursor of fumaric acid, significantly increased the final fumaric acid titer. Finally, disruption of the malate-aspartate shuttle increased the intracellular malate content by 2.16-fold and extracellular fumaric acid titer by 42%, compared with that of the parental strain. The strategic metabolic engineering of multiple genes resulted in a final strain that could produce up to 17 g/L fumaric acid from glucose in a fed-batch fermentation process. Conclusions: This is the first metabolic engineering study on the production of fumaric acid by the thermophilic filamentous fungus M. thermophila. This cellulolytic fungal platform provides a promising method for the sustainable and efficient-cost production of fumaric acid from lignocellulose-derived carbon sources in the future.

4.
Nutrients ; 10(7)2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30037014

RESUMO

Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber⁻DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-α, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-κB) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Etanol/efeitos adversos , Fígado Gorduroso Alcoólico/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Solanum , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colesterol/sangue , Citocinas/sangue , Fígado Gorduroso Alcoólico/sangue , Fígado Gorduroso Alcoólico/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue
5.
Int J Pharm ; 534(1-2): 308-315, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-28986321

RESUMO

The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency. Among them, TPLE-1 displayed higher PTX-loading, slower PTX-release and larger PTX-distribution in oil-phase, significantly reduced extraction by RES organs, increased tumor-uptake, showed stronger cytotoxicity against MCF-7 cells and more potent anticancer efficacy on MCF-7 tumor-bearing nude mice, and had greater plasma AUC0-∞ value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T1/2) in SD rats. It also exhibited the same in vivo efficacy as Taxol® and even produced less hemolysis and intravenous irritation. Moreover, its LD50 was 4.3-fold higher than that of Taxol®. All results demonstrate that TPLE-1 is a promising candidate drug due to its high tumor-accumulation and effectiveness, low toxicity, good safety and druggability in clinical application for the cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Emulsões/química , Lipídeos/química , Nanopartículas/química , Paclitaxel/administração & dosagem , Paclitaxel/química , Animais , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Tamanho da Partícula , Polietilenoglicóis/química , Coelhos , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
6.
Medicine (Baltimore) ; 96(17): e6607, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28445257

RESUMO

Systematic inflammatory response markers are considered as the most informative prognostic factors in many types of cancer. However, in synchronous colorectal cancer (synCRC), the prognostic value of inflammatory markers, including prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), had rarely been evaluated. Thus, this present study reviewed our consecutive patients with synCRC to investigate the prognostic value of those factors.The primary endpoint was overall survival (OS), and disease-free survival (DFS) was considered as the secondary endpoint. Receiver-operating characteristic curve analysis was conducted to determine optimal cutoff levels for the 5 markers. Kaplan-Meier survival curves and Cox proportional hazards models were applied to assess the relationship between OS, DFS, and inflammatory markers.In total, 114 patients with pathologically confirmed synCRC at initial diagnosis were identified among 5742 patients who underwent surgery for colorectal cancer from October 2009 to May 2013. In the multivariate analysis, elevated postoperative NLR (≥10.50) was confirmed as an independent prognostic factor for 3-year OS (P = .001; hazard ratio [HR] 4.123, 95% confidence interval [CI] 1.750-9.567) and DFS (P = .001; HR 3.342, 95% CI 1.619-6.898). In addition, for 3-year OS, both tumor grade and pN stage were confirmed as independent prognostic factors. And pN stage was confirmed as an independent prognostic factor for 3-year DFS.In conclusion, this study identified elevated postoperative NLR is associated with a poor prognosis in patients with synCRC underwent surgery resection, and the NLR provides improved accuracy for predicting clinical outcomes to stratify patients into different risk categories.


Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/cirurgia , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Primárias Múltiplas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Neoplasias Primárias Múltiplas/patologia , Neutrófilos/imunologia , Prognóstico , Curva ROC , Resultado do Tratamento , Adulto Jovem
7.
Surg Endosc ; 31(8): 3383-3390, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27864726

RESUMO

BACKGROUND: It can be difficult to locate the superior mesenteric vein and dissect around middle colic vessels during laparoscopic right hemicolectomy with complete mesocolon excision due to a high rate of vascular variations in the superior mesenteric vessels. Therefore, we report a modified technique for hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision and central vascular ligation, which addresses these two problems. METHODS: Thirty-one consecutive patients with right colon cancer underwent this procedure from March 2014 to August 2015. Extracorporeally, the transverse colon and distal ileum were excised with a transumbilical hand-port incision, and the distal part of the superior mesenteric vein was identified. Intracorporeally, with the assistance of the surgeon's left hand inserted through the incision, D3-lymphadenectomy with central vascular ligation was performed, and the colon with the tumor, which had no blood supply, was removed. Patients' demographic data and intraoperative, postoperative and pathological characteristics were examined. RESULTS: The median operative time was 130.0 (range 115-180) minutes. The median blood loss was 45.0 (range 20-300) milliliters. The median length of the hand-port incision was 7.3 (range 6.0-8.2) centimeters. The median numbers of lymph nodes and central lymph nodes was 34.0 (range 18-91) and 13.0 (range 3-28), respectively. Five (16.1%) of 31 patients had positive central lymph nodes. Specimen morphometric quantitation was as follows: the median distances from the tumor and nearest bowel wall to the high tie were 10.5 (range 5.0-15.0) and 8.0 (range 6.0-12.0) centimeters, respectively; the median resected area of the mesentery was 200.0 (range 96.0-300.0) square centimeters; the median width of the chain of lymph-adipose tissue at the central lymph nodes area was 2.0 (range 0.8-8.0) centimeters; and the median length of the central lymph-adipose chain was 19.0 (range 3.0-26.0) centimeters. CONCLUSIONS: Our procedure confers technical advantages and is feasible for treatment of right colon cancer.


Assuntos
Neoplasias do Colo/cirurgia , Laparoscopia Assistida com a Mão/métodos , Laparoscopia/métodos , Ligadura/métodos , Mesocolo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Colo Ascendente/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Medicine (Baltimore) ; 95(36): e4462, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27603340

RESUMO

To evaluate the impact of visceral obesity on laparoscopic total mesorectal excision (TME) and decide the best index to reflect completion of mesorectum and perioperative outcomes.Patients with rectal cancer who underwent laparoscopic TME were enrolled. The data including body mass index (BMI), visceral fat area (VFA), visceral fat area/body surface area (VFA/BSA), mesorectum fat ratio (MFR), pelvic fat area (PFA), pelvic fat ratio (PFR), completion of mesorectum, and other perioperative outcomes were collected. Data were analyzed.A total of 322 patients were enrolled between 2011 and 2014. There was no significantly difference between the BMI groups on completion of mesorectum and other outcomes (P ≥ 0.05). However, in VFA groups, completion of mesorectum (P = 0.002), operative time (P = 0.02), and incision length (P = 0.02) were significantly different. In VFA/BSA groups, completion of mesorectum (P = 0.002) and incision length (P = 0.009) were significantly different. When MFR was equal to 0.48, completion of mesorectum (P = 0.002), operative time (P = 0.001), incision length (P = 0.03), and blood loss (P = 0.04) were significantly different between the 2 groups. In PFA and PFR groups, there was no significantly difference (P ≥ 0.05). After the analysis of logistic regression, only VFA was the risk factor of incomplete mesorectum excision.BMI does not reflect the impact of obesity on laparoscopic rectal surgery. VFA is a better index in predicting the influence of visceral obesity on surgical quality and difficulty of laparoscopic rectal surgery than VFA/BSA and MFR.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Obesidade Abdominal/complicações , Neoplasias Retais/cirurgia , Adulto , Idoso , Distribuição da Gordura Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/complicações , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(1): 102-5, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-27062793

RESUMO

OBJECTIVE: To compare the two different methods to isolate the exosome from the ascites of colorectal cancer (CRC) patient and find the efficient one. METHODS: Exosome from the ascites of CRC patient were isolated by two different methods: density gradient exosome isolation (DG-Exo) and Exo-Quick isolation, and followed by identification with transmission electron microscopy observation and Western blot analysis. And then, Nanodrop was used for protein quantification. RESULTS: Exosome were isolated by both of the two methods. The protein concentration of the exosome isolated by the Exo-Quick isolation were higher than that of DG-Exo. CONCLUSION: Exo-Quick isolation can obtain higher purity and more complete exosome from the ascites.


Assuntos
Ascite , Neoplasias Colorretais/patologia , Exossomos/patologia , Western Blotting , Humanos , Microscopia Eletrônica de Transmissão , Proteínas/isolamento & purificação
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