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1.
Bioorg Med Chem Lett ; 32: 127719, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33253878

RESUMEN

The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 â†’ 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.


Asunto(s)
Magnoliopsida/metabolismo , Polisacáridos/química , Sustancias Protectoras/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Hojas de la Planta/metabolismo , Tallos de la Planta/metabolismo , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología
2.
Endocr J ; 66(4): 309-317, 2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-30760653

RESUMEN

Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNF1A, INS, KCNJ11 and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.


Asunto(s)
Péptido C/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Adolescente , Adulto , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diagnóstico Diferencial , Femenino , Pruebas Genéticas , Factor Nuclear 1-alfa del Hepatocito/genética , Humanos , Masculino , Persona de Mediana Edad , Linaje , Adulto Joven
3.
Proc Natl Acad Sci U S A ; 112(11): E1257-62, 2015 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-25733869

RESUMEN

The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.


Asunto(s)
Anuros/genética , Evolución Molecular , Genoma/genética , Animales , Secuencia de Bases , Pollos/genética , Cromosomas/genética , Elementos Transponibles de ADN/genética , Femenino , Humanos , Familia de Multigenes , Sintenía/genética , Tibet
4.
Biomed Chromatogr ; 30(9): 1423-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26864353

RESUMEN

A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 µm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 ± 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Ácido Oleanólico/análogos & derivados , Saponinas/sangre , Espectrometría de Masas en Tándem/métodos , Animales , Disponibilidad Biológica , Ácido Oleanólico/sangre , Ácido Oleanólico/farmacocinética , Ratas , Saponinas/farmacocinética
5.
World J Surg Oncol ; 12: 31, 2014 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-24499532

RESUMEN

BACKGROUND: Electrocautery applications in surgical operations produce evasive odorous smoke in the cleanest operation rooms. Because of the incomplete combustion of electrical current in the tissues and blood vessels during electrocautery applications, electrocautery smoke (ES) containing significant unknown chemicals and biological forms is released. The potential hazards and cancer risk should be further investigated from the perspective of the occupational health of surgical staff. METHODS: The particle number concentration and the concentration of polycyclic aromatic hydrocarbons (PAHs) in ES were thoroughly investigated in 10 mastectomies to estimate the cancer risk for surgical staff. The particle number concentration and gaseous/particle PAHs at the surgeons' and anesthetic technologists' (AT) breathing heights were measured with a particle counter and filter/adsorbent samplers. PAHs were soxhlet-extracted, cleaned, and analyzed by gas chromatography/mass spectrometry. RESULTS: Abundant submicron particles and high PAH concentrations were found in ES during regular surgical mastectomies. Most particles in ES were in the size range of 0.3 to 0.5 µm, which may potentially penetrate through the medical masks into human respiration. The average particle/gaseous phase PAH concentrations at the surgeon's breathing height were 131 and 1,415 ng/m³, respectively, which is 20 to 30 times higher than those in regular outdoor environments. By using a toxicity equivalency factor, the cancer risk for the surgeons and anesthetic technologists was calculated to be 117 × 10(-6) and 270 × 10(-6), respectively; the higher cancer risk for anesthetic technologists arises due to the longer working hours in operation rooms. CONCLUSIONS: The carcinogenic effects of PAHs in ES on the occupational health of surgical staff should not be neglected. The use of an effective ES evacuator or smoke removal apparatus is strongly suggested to diminish the ES hazards to surgical staff.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Neoplasias de la Mama/cirugía , Electrocoagulación/efectos adversos , Mastectomía , Neoplasias/inducido químicamente , Exposición Profesional/efectos adversos , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Humo/efectos adversos , Femenino , Humanos , Exposición Profesional/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Pronóstico , Medición de Riesgo
6.
Proc Natl Acad Sci U S A ; 107(29): 12980-5, 2010 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-20615980

RESUMEN

Pigmentation patterning has long interested biologists, integrating topics in ecology, development, genetics, and physiology. Wild-type neonatal larvae of the silkworm, Bombyx mori, are completely black. By contrast, the epidermis and head of larvae of the homozygous recessive sex-linked chocolate (sch) mutant are reddish brown. When incubated at 30 degrees C, mutants with the sch allele fail to hatch; moreover, homozygous mutants carrying the allele sch lethal (sch(l)) do not hatch even at room temperature (25 degrees C). By positional cloning, we narrowed a region containing sch to 239,622 bp on chromosome 1 using 4,501 backcross (BC1) individuals. Based on expression analyses, the best sch candidate gene was shown to be tyrosine hydroxylase (BmTh). BmTh coding sequences were identical among sch, sch(l), and wild-type. However, in sch the approximately 70-kb sequence was replaced with approximately 4.6 kb of a Tc1-mariner type transposon located approximately 6 kb upstream of BmTh, and in sch(l), a large fragment of an L1Bm retrotransposon was inserted just in front of the transcription start site of BmTh. In both cases, we observed a drastic reduction of BmTh expression. Use of RNAi with BmTh prevented pigmentation and hatching, and feeding of a tyrosine hydroxylase inhibitor also suppressed larval pigmentation in the wild-type strain, pnd(+) and in a pS (black-striped) heterozygote. Feeding L-dopa to sch neonate larvae rescued the mutant phenotype from chocolate to black. Our results indicate the BmTh gene is responsible for the sch mutation, which plays an important role in melanin synthesis producing neonatal larval color.


Asunto(s)
Bombyx/enzimología , Bombyx/genética , Genes de Insecto/genética , Mutación/genética , Pigmentación/genética , Caracteres Sexuales , Tirosina 3-Monooxigenasa/metabolismo , Animales , Mapeo Cromosómico , Ligamiento Genético , Genoma/genética , Larva , Fenotipo , Reproducibilidad de los Resultados
7.
Molecules ; 18(10): 12192-207, 2013 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-24084022

RESUMEN

A rapid resolution liquid chromatography/time-of-flight tandem mass spectrometry (RRLC-TOF/MS) method was developed for qualitative and quantitative analysis of the major chemical constituents in Andrographis paniculata. Fifteen compounds, including flavonoids and diterpenoid lactones, were unambiguously or tentatively identified in 10 min by comparing their retention times and accurate masses with standards or literature data. The characteristic fragmentation patterns of flavonoids and diterpenoid lactones were summarized, and the structures of the unknown compounds were predicted. Andrographolide, dehydroandrographolide and neoandrographolide were further quantified as marker substances. It was found that the calibration curves for all analytes showed good linearity (R² > 0.9995) within the test ranges. The overall limits of detection (LODs) and limits of quantification (LOQs) were 0.02 µg/mL to 0.06 µg/mL and 0.06 µg/mL to 0.2 µg/mL, respectively. The relative standard deviations (RSDs) for intra- and inter-day precisions were below 3.3% and 4.2%, respectively. The mean recovery rates ranged from 96.7% to 104.5% with the relative standard deviations (RSDs) less than 2.72%. It is concluded that RRLC-TOF/MS is powerful and practical in qualitative and quantitative analysis of complex plant samples due to time savings, sensitivity, precision, accuracy and lowering solvent consumption.


Asunto(s)
Andrographis/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Calibración , Cromatografía Líquida de Alta Presión , Diterpenos/química , Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Etanol/química , Flavonas/química , Flavonas/aislamiento & purificación , Glucósidos/química , Glucósidos/aislamiento & purificación , Límite de Detección , Extracción en Fase Sólida , Solventes , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem , Tetrahidronaftalenos/química , Tetrahidronaftalenos/aislamiento & purificación
8.
Zhonghua Yi Xue Za Zhi ; 93(36): 2867-70, 2013 Sep 24.
Artículo en Zh | MEDLINE | ID: mdl-24373397

RESUMEN

OBJECTIVE: To explore the relationship between body fat distribution, insulin resistance, islet ß cell function and metabolic disorders in adult population. METHODS: From February to November 2012, a total of 174 subjects aged 20-68 years were recruited. Their anthropometric parameters, blood biochemical indices and the results of oral glucose tolerance test (OGTT) and insulin releasing test (IRT) were collected. Body fat distribution was measured with dual energy X-ray absorptiometry (DEXA). RESULTS: The values of trunk/total fat mass (T/B) and android/gynoid fat mass ratio (A/G) were positively correlated with blood pressure, blood lipid, plasma glucose, insulin resistance index (HOMA-IR) and high-sensitivity C-reactive protein. Compared with the group of normal metabolism, the group of metabolic disorders had higher T/B and A/G (P < 0.05). After multiple stepwise regression analysis, the main influencing factors of lnHOMA-IR and lnHOMA-ß were T/B and Grespectively.Logistic regression showed that A (OR = 3.01, 95%CI 1.86-8.17) was a risk factor for diabetes and A/G (OR = 2.71, 95%CI 1.75-6.56) a risk factor for dyslipidemia. CONCLUSIONS: Trunk and android fat deposition aggravates insulin resistance, metabolic disorders. And the main influencing factors of insulin resistance and islet ß cell function are trunk and gynoid fat respectively. Android fat mass is a major risk factor for glycolipid metabolism.


Asunto(s)
Distribución de la Grasa Corporal , Resistencia a la Insulina , Islotes Pancreáticos/metabolismo , Enfermedades Metabólicas/metabolismo , Adulto , Anciano , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Enfermedades Metabólicas/fisiopatología , Persona de Mediana Edad , Adulto Joven
9.
Molecules ; 17(7): 7903-13, 2012 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-22751226

RESUMEN

A simple and reliable ultra performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry method (UPLC-TOF-MS) was developed and validated for the simultaneous determination of the major bioactive constituents in Acanthopanax senticosus and its extract. The separation of five compounds was performed on a UPLC™ HSS T3 column (100 mm × 2.1 mm, 1.7 µm) with gradient elution using a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile containing 0.1% formic acid. All targeted compounds (syringin, chlorogenid acid, caffeic acid, eleutheroside E and isofraxidin) were baseline separated within 5.3 min in samples, which represented an approximate six-fold reduction in the analysis time in comparison to published HPLC method. Quantitation was carried out working in the V mode using the narrow widow extracted ion chromatograms (nwXICs) of each compound (extracted using a 20 mDa window). Furthermore, all calibration curves showed good linearity (r > 0.999) within the test ranges. The precision was evaluated by intra- and inter-day tests, which revealed relative standard deviation (RSD) values of less than 3.88%. The recoveries for the quantified compounds were between 96.3% and 103.7%, with RSD values below 2.89%. According to the literature, this study represents the first investigation of the simultaneous analysis of multiple components and the method can be applied to determine the amounts of the major compounds in Acanthopanax senticosus and its extract by UPLC-TOF-MS.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Eleutherococcus/química , Compuestos Orgánicos/análisis , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Calibración , Ácido Clorogénico/análisis , Ácido Clorogénico/química , Cumarinas/análisis , Cumarinas/química , Glucósidos/análisis , Glucósidos/química , Lignanos/análisis , Lignanos/química , Límite de Detección , Fenilpropionatos/análisis , Fenilpropionatos/química , Análisis de Componente Principal , Estándares de Referencia , Reproducibilidad de los Resultados
10.
Zhonghua Yi Xue Za Zhi ; 92(46): 3300-4, 2012 Dec 11.
Artículo en Zh | MEDLINE | ID: mdl-23328519

RESUMEN

OBJECTIVE: To investigate the potential role of adipocytes fatty acid binding protein (A-FABP)inhibitor to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from macrophage. METHODS: Co-culture system for RAW264.7 macrophage and MIN6 insulinoma cells was established through transwell combined with A-FABP inhibitor BMS309403 treatment for 48 h. Meanwhile, cultured RAW264.7 and MIN6 respectively were set up as controls. In the inhibitor group, BMS309403 preprocessing (5 µmol/L) was performed 2 h before co-culture. The expression of toll-like receptors(TLR)4 and A-FABP in RAW264.7 macrophages was detected by RT-PCR and Western blotting, interleukin (IL)-1ß and tumor necrosis factor(TNF)-α levels in the supernatant were detected by ELISA, Glucose-stimulated insulin level was detected by insulin radioimmuno-assay kits for the function of islets. RESULTS: (1) The mRNA and protein levels of both TLR4 and A-FABP in RAW264.7 macrophages as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly higher in co-culture group than in macrophages control group (P < 0.05). (2) Insulin secretion stimulated by high glucose was obviously decreased in co-culture group when compared with insulinoma cells control group [(16.0 ± 2.2) vs (41.1 ± 6.6) ng/ml, P < 0.05]. After the treatment with A-FABP inhibitor, the mRNA and protein levels of both TLR4 and A-FABP as well as the concentrations of IL-1ß and TNF-α in the supernatant were significantly lower than in co-culture control (P < 0.05). However, insulin secretion stimulated by high glucose was significantly enhanced when compared with insulinoma cells control group [(31.4 ± 3.3) vs (16.0 ± 2.2) ng/ml, P < 0.05]. CONCLUSIONS: This study demonstrated that co-culture of macrophage and islet cells can activate inflammation pathway, stimulate inflammatory cytokine release and decrease insulin secretion from islet cells. A-FABP inhibitor can protect islet cells from macrophage-mediated cytotoxicity and preserve its insulin secretory function.


Asunto(s)
Proteínas de Unión a Ácidos Grasos/antagonistas & inhibidores , Islotes Pancreáticos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Línea Celular , Técnicas de Cocultivo , Inflamación , Insulina/metabolismo , Secreción de Insulina , Interleucina-1beta/análisis , Islotes Pancreáticos/metabolismo , Ratones , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/análisis
11.
Food Chem ; 369: 130959, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34469836

RESUMEN

The huge economic loss of citrus fruit after harvest called for safe and efficient preservatives, as chemically synthesized agents threatened the environment and human health. Herein a biocontrol fungus Chaetomium globosum QY-1 near the orchard in riparian area was identified to have antimicrobial, antioxidant and tyrosinase inhibition activity, which meets the requirements of an ideal preservative. Metabolite profiling based on bioassay-guided fractionation was carried out, and eight polyketones were determined by MS and NMR. The most abundant CheA exhibited strong inhibition to Penicillium digitatum, the main pathogen caused citrus fruit rot. Among these metabolites, Epicoccone and Epicoccolide B showed higher antioxidant activity, while Epicoccone and CheA had higher tyrosinase inhibitory activity. All the activities were close to or even better than the positive control (Vc; glutathione; Vc and arbutin; Bellkute), implying that the metabolites of C. globosum had comprehensive effects as natural preservatives.


Asunto(s)
Antiinfecciosos , Chaetomium , Citrus , Humanos , Penicillium
12.
Food Chem ; 366: 130541, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34273855

RESUMEN

Penicillium oxalicum has been used as a biocontrol fungus in agriculture for many years, but the antimicrobial substances are still uncertain. Herein, we isolated a linear peptide named Sanxiapeptin in the culture broth of Penicillium oxalicum SG-4 collecting from the Three Gorges riparian zone. Sanxiapeptin exhibited potent inhibitory effect on citrus green mold Penicillium digitatum, the main fungi responsible for postharvest decay. Sanxiapeptin was elucidated as composing of five amino acids, which were ß-amino-α-methoxybutyric acid (Amoba), N-Me-l-Thr, d-Thr, N-Me-l-Val and l-Ser. By analyzing three chemically synthesized oligopeptides with similar structures, we found that the first amino acid of Amoba was crucial to the antifungal activity, as was the methylation of peptide bond. Sanxiapeptin may act as an antimicrobial agent by affecting the function of cell membranes or walls. The antimicrobial spectrum, safety and stability analysis supported that Sanxiapeptin was a promising antifungal agent for citrus preservation.


Asunto(s)
Citrus , Penicillium , Frutas , Enfermedades de las Plantas
13.
Biomolecules ; 12(12)2022 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-36551288

RESUMEN

BACKGROUND: The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. Compared with old-onset colorectal cancer (oCRC), yCRC has different clinical and molecular characteristics. However, the difference in the tumor microenvironment (TME) between yCRC and oCRC remains unclear. METHODS: Fourteen untreated CRC tumor samples were subjected to single-cell RNA sequencing analysis. RESULTS: B cells and naïve T cells are enriched in yCRC, while effector T cells and plasma cells are enriched in oCRC. Effector T cells of yCRC show decreased interferon-gamma response and proliferative activity; meanwhile, Treg cells in yCRC show stronger oxidative phosphorylation and TGF-ß signaling than that in oCRC. The down-regulated immune response of T cells in yCRC may be regulated by immune and malignant cells, as we observed a downregulation of antigen presentation and immune activations in B cells, dendritic cells, and macrophages. Finally, we identified malignant cells in yCRC and oCRC with high heterogeneity and revealed their interactions with immune cells in the TME. CONCLUSIONS: Our data reveal significant differences of TME between yCRC and oCRC, of which the TME of yCRC is more immunosuppressive than oCRC. Malignant cells play an essential role in the formation of the suppressive tumor immune microenvironment.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Microambiente Tumoral/genética , Linfocitos T Reguladores , Análisis de Secuencia de ARN
14.
Nat Commun ; 12(1): 4091, 2021 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-34215748

RESUMEN

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Heterogeneidad Genética , Evasión Inmune , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Células Neoplásicas Circulantes/inmunología , Anciano , Animales , Biomarcadores de Tumor/metabolismo , Ciclo Celular , Línea Celular Tumoral , Quimiocina CCL5/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/metabolismo , Pronóstico , RNA-Seq , Transcriptoma , Microambiente Tumoral
15.
Zhonghua Nei Ke Za Zhi ; 49(5): 405-9, 2010 May.
Artículo en Zh | MEDLINE | ID: mdl-20646415

RESUMEN

OBJECTIVES: To explore the effect of transient continuous subcutaneous insulin infusion (CSII) on ß cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetic patients and its potential mechanism. METHODS: Ten patients with newly diagnosed type 2 diabetes mellitus (T2DM) accepted CSII for two weeks. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII. Serum soluble E-selectin (sE-selectin) was used to evaluate the injury of vascular endothelial cell, while serum high sensitivity C reactive protein (hsCRP) and soluble CD14 (sCD14) were both used to assess inflammatory condition. RESULTS: (1) Compared with those before treatment, the blood glucose levels of IVGTT, the area under the curve of the blood glucose, glycosylated hemoglobin, TC and LDL-C in the patients were decreased after CSII (P < 0.05 or 0.01). (2) Compared with those before treatment, the insulin levels of IVGTT (except the fasting insulin), the area under the curve of insulin and acute insulin response were all increased after CSII (P < 0.05 or 0.01). (3) Compared with that before treatment, the glucose infusion ratio in the clamp test [(3.46 ± 1.66) mg x kg⁻¹ x min⁻¹ increased to (7.14 ± 2.37) mg x kg⁻¹ x min⁻¹] and HOMA-beta elevated, while HOMA-IR declined (P < 0.05 or 0.01 in all). (4) Compared with those before treatment, the levels of serum sE-selectin, sCD14 and hsCRP were decreased (P < 0.01, except for hsCRP). CONCLUSION: Transient intensive insulin therapy in patients with newly diagnosed T2DM is useful to restore beta cell function, attenuate insulin resistance, repair vascular endothelial injury and improve the disorder of blood sugar and lipid. The mechanism may be related with the inhibition of inflammation in patients.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Insulina/uso terapéutico , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones Subcutáneas , Insulina/administración & dosificación , Resistencia a la Insulina , Lípidos/sangre , Masculino , Persona de Mediana Edad
16.
Zhonghua Yi Xue Za Zhi ; 90(44): 3119-23, 2010 Nov 30.
Artículo en Zh | MEDLINE | ID: mdl-21211341

RESUMEN

OBJECTIVE: To investigate the activation of TLR4/NF-κB signaling pathway and the level of inflammation in volunteers with varying degrees of metabolic disorders and the effect of intervention by TLR4 monoclonal antibody. METHODS: THP-1 cell line was cultured with 10% serum of volunteers with various degrees of metabolic disorders (each 10 cases) for 24, 48 h. TLR4 and NF-κB p65 phosphorylation protein were measured by Western blot. TLR4 mRNA was measured by RT-PCR. The expression of IL-1ß and TNF-α were detected by ELISA. RESULTS: The TLR4 mRNA and protein, the level of NF-κB p65 phosphorylation protein in THP-1 cell line and IL-1ß and TNF-α expression in culture supernatant in normal, simple obesity, obesity with hyperglycemia, obesity with hyperlipidemia, obesity with three metabolic disorders groups had statistical significance (P < 0.05). The TLR4 mRNA and protein, the level of NF-κB p65 phosphorylation protein and the IL-1ß and TNF-α expression in obesity with three metabolic disorders group were higher than those in other group, and those were time-dependent (P < 0.05). TNF-α expression in normal, simple obesity, obesity with hyperglycemia, obesity with hyperlipidemia, obesity with three metabolic disorders group at 48 h were (222 ± 32), (246 ± 52), (322 ± 32), (322 ± 34) and(490 ± 83)ng/L, respectively, IL-1ß (ng/L) were (94 ± 19), (133 ± 19), (174 ± 22), (180 ± 30), (279 ± 38) (P < 0.05). CONCLUSIONS: The activation of TLR4/NF-κB signaling pathway on THP-1 cell line which is cultured by serum with various degrees of metabolic disorders is different, with the increasing of severity of metabolic disorders, TLR4/NF-κB signaling pathway activation levels also incr.


Asunto(s)
Síndrome Metabólico/metabolismo , Monocitos/metabolismo , Obesidad/sangre , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Factor de Transcripción ReIA/metabolismo , Adulto , Línea Celular , Femenino , Humanos , Inflamación , Interleucina-1beta/metabolismo , Masculino , Persona de Mediana Edad , Fosforilación , Suero , Factor de Necrosis Tumoral alfa/metabolismo
17.
Zhonghua Yi Xue Za Zhi ; 90(4): 231-5, 2010 Jan 26.
Artículo en Zh | MEDLINE | ID: mdl-20356535

RESUMEN

OBJECTIVE: To explore the relationship between plasma adipocyte fatty acid-binding protein (A-FABP), adiponectin (APN) levels and A-FABP/APN ratio with femoral intima-media thickness (FA-IMT) and endothelium-dependent vasodilation in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Plasma A-FABP and APN in 133 patients with newly diagnosed T2DM were measured by enzyme-linked immunosorbent assays. FA-IMT, endothelium-dependent and independent vasodilation of brachial artery was measured by high-resolution vascular ultrasound. Upper quartile of FA-IMT was regarded as a criterion of elevated FA-IMT, defined as early atherosclerosis (AS). The patients were subdivided into low FA-IMT group (FA-IMT < 0.60 mm, n = 34), middle FA-IMT group (0.60 mm /= 0.80 mm, n = 33). RESULTS: Plasma A-FABP/APN ratio was higher in early AS group than in low IMT control group [A-FABP/APN x 1000, 3.9(2.8 approximately 6.1) vs 2.9(1.8 approximately 5.7), P < 0.05]. FA-IMT correlated positively with plasma A-FABP/APN ratio (r = 0.216, P = 0.006) and negatively with APN (r = -0.179, P = 0.020). After adjusted for age, gender and BMI, FA-IMT still correlated positively with plasma A-FABP/APN ratio (r = 0.217, P = 0.007) and negatively with APN (r = -0.172, P = 0.026). Endothelium-dependent vasodilation correlated negatively with plasma A-FABP/APN ratio (r = -0.166, P = 0.028). After adjusted for age, gender and BMI, endothelium-dependent vasodilation still correlated negatively with plasma A-FABP/APN ratio (r = -0.153, P = 0.042). CONCLUSION: Plasma A-FABP/APN ratio is closely associated with FA-IMT and endothelium-dependent vasodilation. Plasma A-FABP/APN ratio may be a better clinical marker of AS and endothelial dysfunction than A-FABP or APN alone in patients with newly diagnosed T2DM.


Asunto(s)
Adiponectina/sangre , Diabetes Mellitus Tipo 2 , Endotelio Vascular/fisiopatología , Proteínas de Unión a Ácidos Grasos/sangre , Arteria Femoral/patología , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Factores Relajantes Endotelio-Dependientes/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 32(5): 509-12, 2010 Oct.
Artículo en Zh | MEDLINE | ID: mdl-21054956

RESUMEN

OBJECTIVE: To evaluate the value of ultrasonic monitoring in induced abortion during the first trimester. METHODS: Totally 110 healthy women with a singleton pregnancy between 9 and 11 gestational weeks were enrolled. All the procedures of induced abortion were performed routinely. Ultrasonography was performed when the procedure of induced abortion was completed. Patients with normal ultrasonographic results were assigned in the control group, while patients with abnormal ultrasonographic findings were enrolled in the study group,in which these patients underwent further operations until the ultrasonography showed clear endomembrane line. All the recurretaged tissue in the study group were sent for pathological examinations. RESULTS: Of these 110 patients, 28 (25.5%) entered study group and 82 (74.5%) entered control group. In the study group, trophoblastic cell or chorion was found in the recurretaged tissue in 11 patients (39.3%), in which 3 had trophoblastic cell embedded in smooth muscular tissue, 6 had pathologic deciduas, and 11 had pathologic secretory endometria. In this control group,1 patient (0.9%) had retained products of conception. The operation duration [(20.6∓2.1) min vs.(11.5∓3.5) min, P0.05]. CONCLUSIONS: Ultrasonic monitoring in induced abortion during the first trimester can decrease the incidence of retained products of conception and will not induce endometrial damage. It is especially useful for women whose fetuses were at older gestational ages.


Asunto(s)
Aborto Inducido/métodos , Monitoreo Intraoperatorio/métodos , Ultrasonografía , Adulto , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 22(2): 105-8, 2010 Feb.
Artículo en Zh | MEDLINE | ID: mdl-20170616

RESUMEN

OBJECTIVE: To study the effects and role of leptin pretreatment and ischemic preconditioning (IPC) on the reduction of myocardial ischemia/reperfusion injury (MIRI) in mouse. METHODS: Thirty-six male C57BL/6 mice were randomized into five groups: (1)sham operation group (n=12); (2) brief ischemia/reperfusion (I/R) treatment group (n=6), in which the mice were subjected to three cycles of a 3-minute regional ischemia followed by a 5-minute reperfusion (I/R cycle); (3) MIRI group (n=6), in which MIRI was established in the mice by blocking anterior descending branch of left coronary artery for 30 minutes, followed by 120 minutes reperfusion; (4) IPC group (n=6), in which three I/R cycles were performed on the mice followed by the MIRI protocol; (5) leptin pretreatment group (leptin group, n=6), in which 50 microg/kg of leptin was injected intraperitoneally to the mice 30 minutes before myocardial ischemia. From 6 mice of the sham operation group and from the mice of brief I/R group, serum samples were collected at different time points (0, 5, 30 and 120 minutes) after reperfusion to measure changes in serum leptin level. From the rest of the mice, blood and heart samples were harvested at 120 minutes after reperfusion to analyze the myocardial function and infarct size, leptin, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels. RESULTS: IPC procedure resulted in an increase in serum leptin level shortly after reperfusion. The leptin level increased significantly than that of sham operation group [(6.24+/-2.34) microg/L vs. (1.35+/-0.45) microg/L] at 5 minutes after I/R, and reached the peak value of (12.36+/-1.33) microg/L at 30 minutes after I/R. Then it gradually decreased to its original (0 minute after reperfusion) value [(1.96+/-1.33) microg/L] at 120 minutes after I/R. There was no difference compared with sham operation group [(1.16+/-0.25) microg/L, P>0.05]. Administration of leptin or IPC before MIRI significantly reduced infarct size [(11.50+/-2.26)%, (9.00+/-1.90)% vs. (37.00+/-2.53)%], the myocardial leptin levels [(8.36+/-3.42) microg/g, (6.71+/-2.03) microg/g vs. (15.51+/-3.92) microg/g], MPO [(17.10+/-3.95) microg/g, (13.33+/-2.88) microg/g vs. (30.83+/-4.06) microg/g], serum leptin levels [(15.03+/-1.87) microg/L, (11.85+/-0.72) microg/L vs. (29.55+/-2.31) microg/L], serum TNF-alpha [(35.10+/-10.12) ng/L, (27.04+/-5.18) ng/L vs. (81.34+/-14.20) ng/L], and IL-6 levels [(167.39+/-72.83) ng/L, (149.13+/-37.69) ng/L vs. (477.30+/-29.09) ng/L, all P<0.01]. CONCLUSION: Pretreatment using leptin results in preconditioning-like tolerance against infarction dysfunction. This cardiac protection effect is mediated, in part, via suppression of inflammation in preconditioned myocardium.


Asunto(s)
Precondicionamiento Isquémico Miocárdico , Leptina/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Animales , Modelos Animales de Enfermedad , Interleucina-6/sangre , Leptina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , Factor de Necrosis Tumoral alfa/sangre
20.
Zhonghua Nei Ke Za Zhi ; 48(2): 144-8, 2009 Feb.
Artículo en Zh | MEDLINE | ID: mdl-19549472

RESUMEN

OBJECTIVE: To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). METHODS: Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CB1R) in the proximal metaphysis of left tibia. RESULTS: At the end of the experiment, whole-body BMD in vivo in the control group [(0.156 +/- 0.008) g/cm(2)] was higher than that in the baseline group [(0.147 +/- 0.006) g/cm(2)], while the whole-body BMD in vivo [(0.147 +/- 0.006) g/cm(2)] and total BMD in vitro at femurs in the GC-treated group [(0.220 +/- 0.011) g/cm(2)] was lower than those in the control group [(0.240 +/- 0.024) g/cm(2)]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P < 0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0.05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0.05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P < 0.05). CONCLUSIONS: The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.


Asunto(s)
Glucocorticoides/efectos adversos , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Receptor Cannabinoide CB1/metabolismo , Animales , Densidad Ósea/efectos de los fármacos , Femenino , Osteoclastos/efectos de los fármacos , Osteoporosis/inducido químicamente , Ratas , Ratas Sprague-Dawley , Tibia/citología , Tibia/metabolismo
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