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1.
J Med Virol ; 96(3): e29544, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511577

RESUMEN

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.


Asunto(s)
Anticuerpos Neutralizantes , Vacunación , Humanos , Inmunización Secundaria , ARN Mensajero/genética , Vacunas Combinadas , Anticuerpos Antivirales
2.
Antonie Van Leeuwenhoek ; 117(1): 18, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38190009

RESUMEN

A Gram-stain-positive, rod-shaped, non-spore-forming and non-motile bacterium, designated WY-20T, was isolated from a lakeside soil sample collected in Jiangxi Province, PR China. Growth was observed at 20-42 °C (optimum 30 °C), pH 5.0-8.0 (optimum pH 7.0) and salinity of 0-3.0% (w/v; optimum 0.5%). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain WY-20T belongs to the genus Nocardioides and showed the highest sequence similarity (98.1%) to N. phosphati WYH11-7T, followed by N. cavernaquae K1W22B-1T (97.8%), N. marmoriterrae JOS5-1T (97.2%) and N. jensenii NBRC 14755T (97.1%). The average nucleotide identity and digital DNA-DNA hybridization values between strains WY-20T and N. phosphati WYH11-7T were 83.5% and 26.2%, respectively. The predominant fatty acids (≥ 10% of the total fatty acids) were C18:1ω9c, C17:0, C16:0, summed feature 8 (C18:1ω7c and/or C18: 1ω6c) and C17:1ω9c. The major menaquinone was MK-8 (H4). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two unidentified phospholipids. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. Based on phenotypic, genotypic and phylogenetic pieces of evidence, strain WY-20T represents a novel species in the genus Nocardioides, for which the name Nocardioides jiangxiensis sp. nov. is proposed. The type strain is WY-20T (= GDMCC 4.317T = KACC 23379T).


Asunto(s)
Ácidos Grasos , Nocardioides , Filogenia , ARN Ribosómico 16S/genética , ADN
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 55-61, 2024 Feb.
Artículo en Zh | MEDLINE | ID: mdl-38433632

RESUMEN

Objective To build a whole-course nursing quality evaluation system for liver transplantation in children,so as to provide a basis for nursing quality evaluation and management. Methods With Donabedian's "structure-process-outcome" model as the theoretical framework,we employed literature analysis,Delphi method,and hierarchical analysis to determine the contents and weights of indexes in the whole-course nursing quality evaluation system for liver transplantation in children. Results The three rounds of survey based on questionnaires showed the questionnaire recovery rate of 100%,the expert authority coefficients of 0.95,0.96,and 0.98,and the Kendall's coefficients of concordance of 0.165,0.209,and 0.220,respectively(all P<0.001).The established nursing quality evaluation system included 3 first-level indexes,15 second-level indexes,and 67 third-level indexes. Conclusion The whole-course nursing quality evaluation system for liver transplantation in children that was built in this study can provide a basis for the evaluation of the nursing quality.


Asunto(s)
Trasplante de Hígado , Niño , Humanos
4.
Mol Cancer ; 22(1): 199, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062470

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most threatening tumors in the world, and chemotherapy remains dominant in the treatment of metastatic CRC (mCRC) patients. The purpose of this study was to develop a biomarker panel to predict the response of the first line chemotherapy in mCRC patients. METHODS: Totally 190 mCRC patients treated with FOLFOX or XEOLX chemotherapy in 3 different institutions were included. We extracted the plasma extracellular vesicle (EV) RNA, performed RNA sequencing, constructed a model and generated a signature through shrinking the number of variables by the random forest algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort (n = 80). We validated it in an internal validation cohort (n = 62) and a prospective external validation cohort (n = 48). RESULTS: We established a signature consisted of 22 EV RNAs which could identify responders, and the area under the receiver operating characteristic curve (AUC) values was 0.986, 0.821, and 0.816 in the training, internal validation, and external validation cohort respectively. The signature could also identify the progression-free survival (PFS) and overall survival (OS). Besides, we constructed a 7-gene signature which could predict tumor response to first-line oxaliplatin-containing chemotherapy and simultaneously resistance to second-line irinotecan-containing chemotherapy. CONCLUSIONS: The study was first to develop a signature of EV-derived RNAs to predict the response of the first line chemotherapy in mCRC with high accuracy using a non-invasive approach, indicating that the signature could help to select the optimal regimen for mCRC patients.


Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias del Colon , Neoplasias Colorrectales , Vesículas Extracelulares , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Bevacizumab/uso terapéutico , Estudios Prospectivos , Ácidos Nucleicos Libres de Células/genética , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , ARN , Biopsia Líquida , Vesículas Extracelulares/genética
5.
Antonie Van Leeuwenhoek ; 116(7): 687-695, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37156982

RESUMEN

A Gram-stain-negative, rod-shaped, polar flagellated or stalked and non-spore-forming bacterium, designated LB-2T, was isolated from activated sludge. Growth was observed at 20-30 °C (optimum 28 °C), pH 6.0-8.0 (optimum pH 7.0) and salinity of 0-0.5% (w/v; optimum 0.5%). Phylogenetic analysis based on the 16S rRNA gene indicated that strain LB-2T belongs to the genus Sphingomonas and showed the highest sequence similarity (96.7%) and less than 96.7% similarities to other type strains. The genome size of strain LB-2T was 4.10 Mb, with 66.8 mol% G + C content. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains LB-2T and S. canadensis FWC47T were 77.8% and 21%, respectively. The predominant cellular fatty acids were summed feature 8 (C18:1ω7c and/or C18 : 1ω6c) and C16:0. The major polar lipids were aminolipid, glycolipid, sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, four unidentified lipids, glycophospholipid, phosphatidylethanolamine and diphosphatidylglycerol. The predominant respiratory quinone was Q-10 and the major polyamine was sym-homospermidine. On the basis of phenotypic, genotypic and phylogenetic evidences, strain LB-2T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas caeni sp. nov. is proposed. The type strain is LB-2T (GDMCC 1.3630T = NBRC 115,102T).


Asunto(s)
Fosfolípidos , Sphingomonas , Fosfolípidos/química , Aguas del Alcantarillado , Filogenia , ARN Ribosómico 16S/genética , Ubiquinona/química , Ácidos Grasos/química , ADN , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética
6.
J Fish Dis ; 46(9): 917-927, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37205784

RESUMEN

Aeromonas hydrophila can pose a great threat to the survival of farmed fish. In current study, we investigated the pathological characteristics and immune response in gut-liver axis of white crucian carp (WCC) upon gut infection. WCC anally intubated with A. hydrophila exerted a tissue deformation in damaged midgut with elevated levels of goblet cells along with a significant decrease in tight junction proteins and villi length-to-width ratios. In addition, immune-related gene expressions and antioxidant properties increased dramatically in gut-liver axis of WCC following gut infection with A. hydrophila. These results highlighted the immune modulation and redox alteration in gut-liver axis of WCC in response to gut infection.


Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Animales , Aeromonas hydrophila/fisiología , Carpa Dorada/genética , Carpas/metabolismo , Inmunidad Innata/genética , Hígado/metabolismo , Infecciones por Bacterias Gramnegativas/veterinaria , Proteínas de Peces/genética
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(7): 828-832, 2023 Jul 10.
Artículo en Zh | MEDLINE | ID: mdl-37368384

RESUMEN

OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3;PM2_Supporting). CONCLUSION: Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.


Asunto(s)
Epilepsia , Síndrome de Williams , Niño , Humanos , Síndrome de Williams/genética , Síndrome de Williams/diagnóstico , Pruebas Genéticas , Facies , Epilepsia/genética , Cromosomas Humanos Par 7/genética , Deleción Cromosómica
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(2): 185-194, 2023 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-37283103

RESUMEN

OBJECTIVES: To investigate the effects and molecular mechanisms of asiatic acid on ß-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature ß cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α. RESULTS: Asiatic acid with the dose of 25 mg·kg-1·d-1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment ß index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic ß cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α. CONCLUSIONS: Asiatic acid improves ß cell insulin secretion function in T2DM mice by maintaining the ß cell maturity, which may be related to the TNF-α/Mfn2 pathway.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Islotes Pancreáticos , Ratones , Animales , Secreción de Insulina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Islotes Pancreáticos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Insulina/metabolismo , Insulina/farmacología , Insulina/uso terapéutico , Ratones Endogámicos ICR , Glucosa/metabolismo , Glucosa/farmacología , Glucosa/uso terapéutico , Interleucina-6/metabolismo , ARN Interferente Pequeño/farmacología , Adenosina Trifosfato , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/farmacología , GTP Fosfohidrolasas/uso terapéutico
9.
Nano Lett ; 21(12): 5409-5414, 2021 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-34124909

RESUMEN

Amides are essential in the chemistry of life. Detecting the chemical bond states within amides could unravel the nature of amide stabilization and planarity, which is critical to the structure and reactivity of such molecules. Yet, so far, no work has been reported to detect or measure the bond changes at the single-molecule level within amides. Here, we show that a transition between single and double bonds between N and C atoms in an amide can be monitored in real time in a nanogap between gold electrodes via the generation of distinctive conductance features. Density functional theory simulations show that the switching between amide isomers proceeds via a proton transfer process facilitated by a water molecule bridge, and the resulting molecular junctions display bimodal conductance states with a difference as much as nine times.


Asunto(s)
Amidas , Protones , Oro , Nanotecnología , Agua
10.
Nano Lett ; 21(24): 10333-10340, 2021 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-34874740

RESUMEN

Here, six phenanthrene (the smallest arm-chair graphene nanoribbon) derivatives with dithiomethyl substitutions at different positions as the anchoring groups were synthesized. Scanning tunneling microscopy break junction technique was used to measure their single molecule conductances between gold electrodes, which showed a difference as much as 20-fold in the range of ∼10-2.82 G0 to ∼10-4.09 G0 following the trend of G2,7 > G3,6 > G2,6 > G1,7 > G1,6 > G1,8. DFT calculations agree well with this measured trend and indicate that the single molecule conductances are a combination of energy alignment, electronic coupling, and quantum effects. This significant regio- and steric effect on the single molecule conductance of phenanthrene model molecules shows the complexity in the practice of graphene nanoribbons as building blocks for future carbon-based electronics in one hand but also provides good conductance tunability on the other hand.


Asunto(s)
Nanotubos de Carbono , Fenantrenos , Electrónica , Microscopía de Túnel de Rastreo , Nanotecnología
11.
Molecules ; 27(11)2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35684454

RESUMEN

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.


Asunto(s)
Trasplante de Riñón , Metabolómica , Biomarcadores , Cromatografía Líquida de Alta Presión , Humanos , Espectrometría de Masas/métodos , Metabolómica/métodos , Tacrolimus
12.
Small ; 17(36): e2101911, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34292668

RESUMEN

Creating single-molecule junctions with a long-lived lifetime at room temperature is an open challenge. Finding simple and efficient approaches to increase the durability of single-molecule junction is also of practical value in molecular electronics. Here it is shown that a flexible gold-coated nanopipette electrode can be utilized in scanning tunneling microscope (STM) break-junction measurements to efficiently enhance the stability of molecular junctions by comparing with the measurements using conventional solid gold probes. The stabilizing effect of the flexible electrode displays anchor group dependence, which increases with the binding energy between the anchor group and gold. An empirical model is proposed and shows that the flexible electrode could promote stable binding geometries at the gold-molecule interface and slow down the junction breakage caused by the external perturbations, thereby extending the junction lifetime. Finally, it is demonstrated for the first time that the internal conduit of the flexible STM tip can be utilized for the controlled molecule delivery and molecular junction formation.


Asunto(s)
Electrónica , Nanotecnología , Electrodos , Oro
13.
Cell Biol Toxicol ; 37(1): 35-49, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32399910

RESUMEN

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the ß-catenin expression level through the AKT1/GSK3ß signaling pathway. Meanwhile, the binding sites of ß-catenin were identified in the promoter region of SIX1 and it was also demonstrated that ß-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/ß-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.


Asunto(s)
Glucosa/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , beta Catenina/metabolismo , Animales , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Glucólisis , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de Señal , Análisis de Supervivencia
14.
Acta Biochim Biophys Sin (Shanghai) ; 53(5): 547-557, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33693450

RESUMEN

The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan-Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.


Asunto(s)
Antígeno B7-H1 , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-met , Neoplasias Gástricas , Regulación hacia Arriba , Anciano , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/genética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia
15.
Anal Chem ; 92(1): 1409-1415, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31829003

RESUMEN

Interrogating metabolite crosstalk in live cells is important to understand the interplay between metabolic and signal transduction pathways but is challenging due to the lack of efficient analytical techniques. Here we report a sequentially activated probe design strategy resulting in probe HF-6 being capable of imaging the crosstalk between H2O2 and formaldehyde in live cells. Fluorescence of HF-6 can only be triggered by first H2O2 activation followed by binding with formaldehyde. Facilitated by this sequentially activated mechanism, HF-6 imaging revealed H2O2-induced upregulation of formaldehyde in live SH-SY5Y cells, while little change of intracellular H2O2 level was observed when cells were stimulated with formaldehyde for limited time. These results establish a link for the crosstalk between H2O2 and formaldehyde in redox signaling and provide a starting point to study broader metabolite interactions.


Asunto(s)
Colorantes Fluorescentes/química , Formaldehído/análisis , Peróxido de Hidrógeno/análisis , Línea Celular Tumoral , Colorantes Fluorescentes/síntesis química , Formaldehído/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Estructura Molecular , Imagen Óptica
16.
IUBMB Life ; 72(11): 2432-2443, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32918845

RESUMEN

OBJECTIVE: DNA methyltransferases (DNMTs) take on a relevant role in epigenetic control of cancer proliferation and cell survival. However, the molecular mechanisms underlying the establishment and maintenance of DNA methylation in human cancer remain to be fully elucidated. This study was to investigate that how DNMT1 affected the biological characteristics of colorectal cancer (CRC) cells via modulating methylation of microRNA (miR)-152-3p and thymosin ß 10 (TMSB10) expression. METHODS: DNMT1, miR-152-3p, and TMSB10 expression, and the methylation of miR-152-3p in CRC tissues and cells were detected. SW-480 and HCT-116 CRC cells were transfected with DNMT1 or miR-152-3p-related sequences or plasmids to explore their characters in biological functions of CRC cells. The binding relationship between DNMT1 and miR-152-3p and the targeting relationship between miR-152-3p and TMSB10 were analyzed. The tumor growth was also detected in vivo. RESULTS: Upregulated DNMT1, TMSB10, reduced miR-152-3p, and methylated miR-152-3p were detected in CRC tissues and cells. Silenced DNMT1 or upregulated miR-152-3p reduced TMSB10 expression and suppressed CRC progression and tumor growth. Moreover, elevated DNMT1 could reverse the effect of miR-152-3p upregulation on CRC development and tumor growth. DNMT1 maintained methylation of miR-152-3p. TMSB10 was the direct target gene of miR-152-3p. CONCLUSION: The study highlights that silenced DNMT1 results in non-methylated miR-152-3p to depress TMSB10 expression, thereby inhibiting CRC development, which provides a new approach for CRC therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Timosina/metabolismo , Adulto , Anciano , Apoptosis , Biomarcadores de Tumor/genética , Ciclo Celular , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Tasa de Supervivencia , Timosina/genética , Células Tumorales Cultivadas
17.
Microb Cell Fact ; 19(1): 2, 2020 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-31906967

RESUMEN

BACKGROUND: L-ornithine is a valuable amino acid with a wide range of applications in the pharmaceutical and food industries. However, the production of L-ornithine by fermentation cannot compete with other methods, because of the low titers produced with this technique. Development of fermentation techniques that result in a high yield of L-ornithine and efficient strategies for improving L-ornithine production are essential. RESULTS: This study demonstrates that tween 40, a surfactant promoter of the production of glutamate and arginine, improves L-ornithine production titers in engineered C. glutamicum S9114. The intracellular metabolism under tween 40 triggered fermentation conditions was explored using a quantitative proteomic approach, identifying 48 up-regulated and 132 down-regulated proteins when compared with the control. Numerous proteins were identified as membrane proteins or functional proteins involved in the biosynthesis of the cell wall. Modulation of those genes revealed that the overexpression of CgS9114_09558 and the deletion of CgS9114_13845, CgS9114_02593, and CgS9114_02058 improved the production of L-ornithine in the engineered strain of C. glutamicum Orn8. The final strain with all the exploratory metabolic engineering manipulations produced 25.46 g/L of L-ornithine, and a yield of 0.303 g L-ornithine per g glucose, which was 30.6% higher than that produced by the original strain (19.5 g/L). CONCLUSION: These results clearly demonstrate the positive effect of tween 40 addition on L-ornithine accumulation. Proteome analysis was performed to examine the impact of tween 40 addition on the physiological changes in C. glutamicum Orn8 and the results showed several promising modulation targets for developing L-ornithine-producing strains.


Asunto(s)
Corynebacterium glutamicum/metabolismo , Ingeniería Metabólica/métodos , Microorganismos Modificados Genéticamente/metabolismo , Ornitina/biosíntesis , Polisorbatos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Corynebacterium glutamicum/genética , Genes Bacterianos , Genoma Bacteriano , Proteoma/metabolismo , Proteómica
18.
Ann Clin Microbiol Antimicrob ; 19(1): 34, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32758225

RESUMEN

BACKGROUND: Cytomegalovirus infection is one of the most common complications after solid organ transplantation. There have been several classes of antiviral drugs for the prevention of cytomegalovirus infection, such as acyclovir, valacyclovir, ganciclovir and valganciclovir. METHODS: We searched relevant prospective and multi-armed studies on PubMed from Jan. 1984 up to Mar. 2018. RESULTS: Seventeen prospective studies involving 2062 patients were included in the analysis. In the case of cytomegalovirus infection, the ganciclovir group (OR = 0.24, 95% CI 0.09-0.57) and the valacyclovir group (OR = 0.20, 95% CI 0.04-0.69) provided significantly better outcomes than the control group. The ganciclovir (OR = 0.37, 95% CI 0.13-0.86) and valacyclovir groups (OR = 0.31, 95% CI 0.07-0.98) showed moderate superiority compared to the acyclovir group. As for cytomegalovirus disease, the ganciclovir, valacyclovir and valganciclovir groups showed significant advantages compared with the control group (ganciclovir group: OR = 0.17, 95% CI 0.07-0.31, valacyclovir group: OR = 0.08, 95% CI 0.01-0.33, valganciclovir group: OR = 0.14, 95% CI 0.02-0.45). Similarly, the ganciclovir group (OR = 0.38, 95% CI 0.12-0.71) and the valacyclovir group (OR = 0.17, 95% CI 0.03-0.72) showed better results than the acyclovir group. CONCLUSION: Valacyclovir showed to be the most efficient antiviral for the prevention of cytomegalovirus infection and disease. Additional studies are required to evaluate putative side effects associated with valacyclovir administration.


Asunto(s)
Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Órganos/efectos adversos , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Teorema de Bayes , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Ganciclovir/uso terapéutico , Humanos , Masculino , Valaciclovir/uso terapéutico , Valganciclovir/uso terapéutico
19.
Appl Microbiol Biotechnol ; 104(12): 5505-5517, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32300856

RESUMEN

ClpX and ClpP are involved in many important functions, including stress responses and energy metabolism, in microorganisms. However, the ClpX and ClpP of microbes used in industrial scale have rarely been studied. Industrial bacterial fermentation experiences a variety of stresses, and energy metabolism is extremely important for industrial bacteria. Thus, the role played by the ClpX and ClpP of industrial bacteria in fermentation should be investigated. Most microorganisms have a single clpP gene, while Corynebacterium crenatum AS 1.542 possesses two clpPs. Herein, the clpX, clpP1, and clpP2 of C. crenatum were cloned, and its fusion protein was expressed and characterized. We also constructed clpX deletion mutant and complementation strain. Results indicate that ClpX serves an important function in thermal, pH, and ethanol stresses. It is also involved in NADPH synthesis and glucose consumption during fermentation.


Asunto(s)
Corynebacterium/enzimología , Endopeptidasa Clp/metabolismo , Metabolismo Energético , Fermentación , Estrés Fisiológico , Clonación Molecular , Corynebacterium/genética , Endopeptidasa Clp/genética , Regulación Bacteriana de la Expresión Génica , Glucosa/metabolismo , Microbiología Industrial , Eliminación de Secuencia
20.
Med Sci Monit ; 26: e930755, 2020 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-33378324

RESUMEN

It is now clear that the photomicrographs in Figure 2 are duplicates of the same image and that Figures 4 and 5 have been 'copied' from a publication "Lupeol triterpene exhibits potent antitumor effects in A427 human lung carcinoma cells via mitochondrial mediated apoptosis, ROS generation, loss of mitochondrial membrane potential and downregulation of m-TOR/PI3Ksol;AKT signalling pathway" by Wei He, Xiang Li, Shuyue Xia, PMID: 30003730. Because the manuscript contains non-credible results and has also breached copyright, this journal is retracting the above publication.

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