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1.
Sci Rep ; 10(1): 2473, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051517

RESUMO

Idiopathic portal hypertension (IPH) mimics liver cirrhosis in many aspects, and no efficient imaging method to differentiate the two diseases has been reported to date. In this study, the imaging and pathological characteristics were analysed for both IPH and cirrhosis. From January 2015 to March 2019, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) images and pathological results from 16 IPH and 16 liver cirrhosis patients, as well as imaging results of 16 normal patients as a control group, were retrospectively reviewed. The age of the patients was 39 ± 20 years. There was a significant difference in the mean lumen diameter, wall thickness and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the main and sagittal portal veins (P < 0.05), as well as in the lumen diameter and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the Segment 3 (S3) portal vein (P < 0.05). In IPH patients, the main imaging changes were portal vein wall thickening, stenosis or occlusion, a low enhancement area along the portal vein in the delay phase in contrast-enhanced imaging, and a non-homogeneous change in T1WI. The corresponding pathological changes included interlobular vein thickening, stenosis, occlusion, portal area fibrosis, and atrophy or apoptosis of hepatocytes. The main imaging characteristic of liver cirrhosis was a nodular change in T1WI, and the related pathological change was pseudolobule formation. The imaging characteristics of IPH include thickening of the portal vein vascular wall, stenosis of the portal vein lumen and the absence of diffuse cirrhosis-like nodules. These imaging features have a definite pathological basis and could help make differential diagnoses between IPH and cirrhosis.

2.
Nat Commun ; 11(1): 319, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949159

RESUMO

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.

3.
Insect Sci ; 27(1): 2-13, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29943911

RESUMO

The silkworm Bombyx mori is an important lepidopteran model insect in which many kinds of natural mutants have been identified. However, molecular mechanisms of most of these mutants remain to be explored. Here we report the identification of a gene Bm-app is responsible for the silkworm minute wing (mw) mutation which exhibits exceedingly small wings during pupal and adult stages. Compared with the wild type silkworm, relative messenger RNA expression of Bm-app is significantly decreased in the u11 mutant strain which shows mw phenotype. A 10 bp insertion in the putative promoter region of the Bm-app gene in mw mutant strain was identified and the dual luciferase assay revealed that this insertion decreased Bm-app promoter activity. Furthermore, clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases-mediated depletion of the Bm-app induced similar wing defects which appeared in the mw mutant, demonstrating that Bm-app controls wing development in B. mori. Bm-app encodes a palmitoyltransferase and is responsible for the palmitoylation of selected cytoplasmic proteins, indicating that it is required for cell mitosis and growth during wing development. We also discuss the possibility that Bm-app regulates wing development through the Hippo signaling pathway in B. mori.


Assuntos
Aciltransferases/genética , Bombyx/genética , Proteínas de Insetos/genética , Asas de Animais/crescimento & desenvolvimento , Aciltransferases/metabolismo , Animais , Bombyx/crescimento & desenvolvimento , Proteínas de Insetos/metabolismo , Pupa/genética , Pupa/crescimento & desenvolvimento
4.
Biomed Opt Express ; 10(11): 5687-5702, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31799040

RESUMO

In this study, a Q-switch pumped supercontinuum laser (QS-SCL) is used as a light source for in vivo imaging via ultrahigh-resolution optical coherence tomography and angiography (UHR-OCT/OCTA). For this purpose, an OCT system based on a spectral-domain detection scheme is constructed, and a spectrometer with a spectral range of 635 - 875 nm is designed. The effective full-width at half maximum of spectrum covers 150 nm, and the corresponding axial and transverse resolutions are 2 and 10 µm in air, respectively. The relative intensity noise of the QS-SCL and mode-locked SCL is quantitatively compared. Furthermore, a special processing algorithm is developed to eliminate the intrinsic noise of QS-SCL. This work demonstrates that QS-SCLs can effectively reduce the cost and size of UHR-OCT/OCTA instruments, making clinical applications feasible.

5.
Front Genet ; 10: 991, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681425

RESUMO

Cobitoidea is one of the two superfamilies in Cypriniformes; however, few genomes have been sequenced for Cobitoidea fishes. Here, we obtained a total of 252.90 Gb of short Illumina reads and 31.60 Gb of long PacBio Sequel reads, representing approximate genome coverage of 256× and 50×, respectively. The final assembled genome is about 583.47 Mb with contig N50 sizes of 2.87 Mb, which accounts for 91.44% of the estimated genome size of 638.07 Mb. Using Hi-C-based chromatin contact maps, 99.31% of the genome assembly was placed into 25 chromosomes, and the N50 is 22.3 Mb. The gene annotation completeness was evaluated by BUSCO, and 2,470 of the 2,586 conserved genes (95.5%) could be found in our assembly. Repetitive elements were calculated to reach 33.08% of the whole genome. Moreover, we identified 25,406 protein-coding genes, of which 92.59% have been functionally annotated. This genome assembly will be a valuable genomic resource to understand the biology of the Tibetan loaches and will also set a stage for comparative analysis of the classification, diversification, and adaptation of fishes in Cobitoidea.

6.
Zhongguo Zhen Jiu ; 39(11): 1169-72, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724351

RESUMO

OBJECTIVE: To observe the effect of grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) on neutrophil to lymphocyte ratio (NLR) and quality of life (QOL) in patients with advanced gastric cancer. METHODS: Sixty patients with advanced gastric cancer were randomly divided into an observation group and a control group, 30 cases in each one. In the control group, conventional chemotherapy regimen combined with symptomatic treatment,such as antiemetic, acid-suppressive, liver-protecting drugs. On the basis of the treatment in the control group, grain-moxibustion was applied at Zusanli (ST 36) and Weishu (BL 21) in the observation group, 9 cones for each acupoint, once a day for a total of 90 days. The levels of NLR were observed before and after treatment, and the clinical efficacy and quality of life were evaluated in the two groups. RESULTS: After treatment, the value of NLR in the observation group was significantly lower than before treatment (P<0.05), there was no significant difference before and after treatment in the control group (P>0.05), and the descend range of observation group was larger than the control group (P<0.05). The effective rates (RR) were 33.3% (10/30) in the observation group and 36.7% (11/30) in the control group, there was no significant difference between the two groups (P>0.05). After treatment, the QOL in the observation group was improved in diarrhea, loss of appetite, fatigue, nausea and vomiting, general health states (P<0.05), there was no significant difference in the control group before and after treatment in varions scores (P>0.05), and the observation group was superior to the control group in fatigue, sleep disorder, loss of appetite, diarrhea and general health states after treatment (P<0.05). CONCLUSION: Grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) can decrease NLR and improve QOL of patients with advanced gastric cancer.


Assuntos
Linfócitos/imunologia , Moxibustão , Neutrófilos/imunologia , Qualidade de Vida , Neoplasias Gástricas , Pontos de Acupuntura , Humanos , Moxibustão/métodos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Neoplasias Gástricas/terapia
7.
Cancer Cell ; 36(5): 559-573.e7, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31668946

RESUMO

Alterations in protein-protein interaction networks are at the core of malignant transformation but have yet to be translated into appropriate diagnostic tools. We make use of the kinetic selectivity properties of an imaging probe to visualize and measure the epichaperome, a pathologic protein-protein interaction network. We are able to assay and image epichaperome networks in cancer and their engagement by inhibitor in patients' tumors at single-lesion resolution in real time, and demonstrate that quantitative evaluation at the level of individual tumors can be used to optimize dose and schedule selection. We thus provide preclinical and clinical evidence in the use of this theranostic platform for precision medicine targeting of the aberrant properties of protein networks.

8.
Materials (Basel) ; 12(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489923

RESUMO

The surface of Q235 low carbon steel was modified by the metal inert-gas welding (MIG) method; a 304 stainless steel surfacing layer was fabricated to improve the properties of Q235 low carbon steel. For practical industry application, keyhole tungsten inter gas (K-TIG) welding was used to weld the surface-modified plates. The microstructure, elemental distribution, micro-hardness, and corrosion resistance of the surface-modified plates and the welded joints were analyzed. The corrosion tests of welded joints and surface-modified plates were carried out with the electrochemical method and hydrochloric acid immersion method, respectively, and surface morphology after corrosion was studied. The results show that the surface-modified plates and their welded joints were defect-free. The microstructure of the surfacing layer consisted of austenite, martensite, and ferrite; and the microstructure of the weld consisted mainly of martensite. The hardness and corrosion resistance of the surfacing layer was superior to that that of low carbon steel. The micro-hardness of the weld is higher than that of the stainless steel surfacing layer and the base material. The corrosion resistance of the surfacing layer is the best, and the corrosion resistance of the welding seam is better than that of the base material.

9.
J Chromatogr A ; 1606: 460386, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31400842

RESUMO

Dihydromyricetin, extracted from Ampelopsis grossedentata, has been widely used as one of Chinese health products in recent years. However, limited chiral separation method hinders the studies of pharmacological and pharmacokinetic activity differences of (+)-dihydromyricetin, (-)-dihydromyricetin, and (±)-dihydromyricetin. Herein, we developed a supercritical fluid chromatography approach for chiral separation of dihydromyricetin. Firstly, effects of chiral stationary phase, co-solvent, and flow rate of mobile phase have been investigated in detail. The resolution of 5.11 was achieved for dihydromyricetin enantiomers on amylose tris(3, 5-dimethylphenylcarbamate)-coated chiral stationary phase with the CO2-methanol mixture (60:40, v/v). With respect to the enantiomeric purity, production rate and solvent consumption of 15 stacked injections, sample loading for semi-preparative separation of dihydromyricetin was optimized in three given equivalents set by volume overloading. Along with increase of sample loading per injection from 40 mg to 120 mg, the productivity of dihydromyricetin increased from 0.07 g (racemate)/g (chiral stationary phase) /24 h to 0.27 g (racemate) /g (chiral stationary phase)/24 h, and the consumption of methanol significantly reduced from 5.86 L/g (racemate) to 1.76 L/g (racemate). Moreover, (-)-dihydromyricetin exhibited better anti-inflammatory activity in TLR 2-related Raw 264.7 cells than (+)-dihydromyricetin and (±)-dihydromyricetin.


Assuntos
Anti-Inflamatórios/farmacologia , Cromatografia com Fluido Supercrítico/métodos , Flavonóis/análise , Flavonóis/química , Animais , Flavonóis/farmacologia , Concentração Inibidora 50 , Camundongos , Células RAW 264.7 , Reologia , Solventes , Estereoisomerismo
10.
Plant Cell Environ ; 42(12): 3340-3354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31380565

RESUMO

Pollen adhesion and hydration are the earliest events of the pollen-stigma interactions, which allow compatible pollen to fertilize egg cells, but the underlying mechanisms are still poorly understood. Rice pollen are wind dispersed, and its pollen coat contains less abundant lipids than that of insect-pollinated plants. Here, we characterized the role of OsGL1-4, a rice member of the Glossy family, in pollen adhesion and hydration. OsGL1-4 is preferentially expressed in pollen and tapetal cells and is required for the synthesis of very long chain alkanes. osgl1-4 mutant generated apparently normal pollen but displayed excessively fast dehydration at anthesis and defective adhesion and hydration under normal condition, but the defective adhesion and hydration were rescued by high humidity. Gas chromatography-mass spectrometry analysis suggested that the humidity-sensitive male sterility of osgl1-4 was probably due to a significant reduction in C25 and C27 alkanes. These results indicate that very long chain alkanes are components of rice pollen coat and control male fertility via affecting pollen adhesion and hydration in response to environmental humidity. Moreover, we proposed that a critical point of water content in mature pollen is required for the initiation of pollen adhesion.

11.
BMC Genomics ; 20(1): 419, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133070

RESUMO

BACKGROUND: The golden birdwing butterfly (Troides aeacus formosanus) is a rarely observed species in Taiwan. Recently, a typical symptom of nuclear polyhedrosis was found in reared T. aeacus larvae. From the previous Kimura-2 parameter (K-2-P) analysis based on the nucleotide sequence of three genes in this isolate, polh, lef-8 and lef-9, the underlying virus did not belong to any known nucleopolyhedrovirus (NPV) species. Therefore, this NPV was provisionally named "TraeNPV". To understand this NPV, the nucleotide sequence of the whole TraeNPV genome was determined using next-generation sequencing (NGS) technology. RESULTS: The genome of TraeNPV is 125,477 bp in length with 144 putative open reading frames (ORFs) and its GC content is 40.45%. A phylogenetic analysis based on the 37 baculoviral core genes suggested that TraeNPV is a Group I NPV that is closely related to Autographa californica nucleopolyhedrovirus (AcMNPV). A genome-wide analysis showed that TraeNPV has some different features in its genome compared with other NPVs. Two novel ORFs (Ta75 and Ta139), three truncated ORFs (pcna, he65 and bro) and one duplicated ORF (38.7 K) were found in the TraeNPV genome; moreover, there are fewer homologous regions (hrs) than there are in AcMNPV, which shares eight hrs within the TraeNPV genome. TraeNPV shares similar genomic features with AcMNPV, including the gene content, gene arrangement and gene/genome identity, but TraeNPV lacks 15 homologous ORFs from AcMNPV in its genome, such as ctx, host cell-specific factor 1 (hcf-1), PNK/PNL, vp15, and apsup, which are involved in the auxiliary functions of alphabaculoviruses. CONCLUSIONS: Based on these data, TraeNPV would be clarified as a new NPV species with defective AcMNPV genomic features. The precise relationship between TraeNPV and other closely related NPV species were further investigated. This report could provide comprehensive information on TraeNPV for evolutionary insights into butterfly-infected NPV.


Assuntos
Baculoviridae/genética , Borboletas/virologia , Genoma Viral , Animais , Baculoviridae/classificação , Baculoviridae/isolamento & purificação , Borboletas/crescimento & desenvolvimento , Replicação do DNA , DNA Viral/química , Genes Duplicados , Genes Virais , Genômica , Especificidade de Hospedeiro/genética , Larva/virologia , Fases de Leitura Aberta , Filogenia , Homologia de Sequência do Ácido Nucleico , Transcrição Genética , Proteínas Estruturais Virais/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-30936118

RESUMO

Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochaperones, and other cofactors. Changes in the expression levels of components of the chaperome, in the interaction strength among chaperome components, alterations in chaperome constituency, and in the cellular location of chaperome members, are all hallmarks of cancer. Here we aim to provide an overview on how chemical biology has played a role in deciphering such complexity in the biology of the chaperome in cancer and in other diseases. The focus here is narrow and on pathologic changes in the chaperome executed by enhancing the interaction strength between components of distinct chaperome pathways, specifically between those of HSP90 and HSP70 pathways. We will review chemical tools and chemical probe-based assays, with a focus on HSP90. We will discuss how kinetic binding, not classical equilibrium binding, is most appropriate in the development of drugs and probes for the chaperome in disease. We will then present our view on how chaperome inhibitors may become potential drugs and diagnostics in cancer.

13.
Rev Sci Instrum ; 90(2): 021715, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30831741

RESUMO

To ensure the high performance of beamlines in Taiwan Photon Source, the metrology of the beamline optical components is essential to realize the theoretical optical simulation. The design and performance of a long-trace profiler (LTP) with moving optical head is described. A LTP is used as a metrological tool for the assembly and correction of optical components at the beamline. For a water-cooled mirror, a LTP serves to optimize the surface profile to a slope error of 0.1 µrad (rms) and adequate thermal conductance. To correct a bendable cooling mirror in a twisted condition, the sagittal slope is decreased by a screw adjustment through the LTP measurement. For the double-crystal monochromator (DCM) with flow-induced vibrations, we proposed an approach to stiffen the bellows hose partially inside the vacuum chamber. From an investigation of the vibrational spectra of the DCM before and after the treatment with the aid of the autocollimator, the current approach is confirmed to be an effective solution for suppression of vibration.

14.
PLoS One ; 14(2): e0208287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30726209

RESUMO

The molecular chaperone Hsp90 is an essential and highly abundant central node in the interactome of eukaryotic cells. Many of its large number of client proteins are relevant to cancer. A hallmark of Hsp90-dependent proteins is that their accumulation is compromised by Hsp90 inhibitors. Combined with the anecdotal observation that cancer cells may be more sensitive to Hsp90 inhibitors, this has led to clinical trials aiming to develop Hsp90 inhibitors as anti-cancer agents. However, the sensitivity to Hsp90 inhibitors has not been studied in rigorously matched normal versus cancer cells, and despite the discovery of important regulators of Hsp90 activity and inhibitor sensitivity, it has remained unclear, why cancer cells might be more sensitive. To revisit this issue more systematically, we have generated an isogenic pair of normal and oncogenically transformed NIH-3T3 cell lines. Our proteomic analysis of the impact of three chemically different Hsp90 inhibitors shows that these affect a substantial portion of the oncogenic program and that indeed, transformed cells are hypersensitive. Targeting the oncogenic signaling pathway reverses the hypersensitivity, and so do inhibitors of DNA replication, cell growth, translation and energy metabolism. Conversely, stimulating normal cells with growth factors or challenging their proteostasis by overexpressing an aggregation-prone sensitizes them to Hsp90 inhibitors. Thus, the differential sensitivity to Hsp90 inhibitors may not stem from any particular intrinsic difference between normal and cancer cells, but rather from a shift in the balance between cellular quiescence and activity.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Humanos , Camundongos , Chaperonas Moleculares/genética , Células NIH 3T3 , Proto-Oncogenes/genética , Transdução de Sinais/efeitos dos fármacos
15.
Phytopathology ; 109(6): 972-982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30714883

RESUMO

Plant survival in the terrestrial ecosystem is influenced by both beneficial and harmful microbes. Trichoderma spp. are a group of filamentous fungi that promote plant growth and resistance to harmful microbes. Previously, we showed that the genus Trichoderma could effectively suppress Fusarium wilt in cucumber. However, the mechanisms that underlie the effects of the genus Trichoderma on plant defense have not been fully substantiated. Two essential metabolic pathways, such as the ascorbate (AsA)-glutathione (GSH) cycle and the oxidative pentose phosphate pathway (OPPP), have been shown to participate in plant tolerance to biotic stressors; nevertheless, the involvement of these pathways in Trichoderma-induced enhanced defense remains elusive. Here, we show that Trichoderma harzianum could alleviate oxidative and nitrostative stress by minimizing reactive oxygen species (ROS; hydrogen peroxide and superoxide) and reactive nitrogen species (nitric oxide [NO]) accumulation, respectively, under Fusarium oxysporum infection in cucumber roots. The genus Trichoderma enhanced antioxidant potential to counterbalance the overproduced ROS and attenuated the transcript and activity of NO synthase and nitrate reductase. The genus Trichoderma also stimulated S-nitrosylated glutathione reductase activity and reduced S-nitrosothiol and S-nitrosylated glutathione content. Furthermore, the genus Trichoderma enhanced AsA and GSH concentrations and activated their biosynthetic enzymes, γ-GCS and l-galactono-1,4-lactone dehydrogenase. Interestingly, the genus Trichoderma alleviated Fusarium-inhibited activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, enzymes involved in the OPPP. Such positive regulation of the key enzymes indicates the adequate maintenance of the AsA-GSH pathway and the OPPP, which potentially contributed to improve redox balance, energy flow, and defense response. Our study advances the current knowledge of Trichoderma-induced enhanced defense against F. oxysporum in cucumber.


Assuntos
Cucumis sativus , Fusarium , Doenças das Plantas/microbiologia , Trichoderma , Raízes de Plantas , Espécies Reativas de Oxigênio
16.
J Formos Med Assoc ; 118(1 Pt 2): 311-323, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29857951

RESUMO

BACKGROUND/PURPOSE: To explore the association of patient injury patterns and entrapped locations inside damaged buildings in the 2016 Taiwan earthquake. METHODS: A retrospective analysis was conducted using the Tainan incident registry system. Residents inside nine conjunctive, 16-story (49.3 m in height) reinforced concrete buildings were categorized as non-injured, injured, and dead. Residents were classified into different groups according to their entrapped locations in height and the severity of building damage. The field triage acuity and trauma severity among groups were compared. Statistical significance was set at the level of 0.05. RESULTS: There were 309 enrollees with 76 (24.6%) non-injured, 118 (38.2%) injured, and 115 (37.2%) dead. Residents either in the high floors (odds ratio [OR] = 2.9, 95% CI: 1.5-5.8, p = 0.003) or in the collapsed buildings (OR = 18.2, 95% CI: 7.6-43.6, p < 0.001) were more likely to be dead. Injured patients who were located in the high floors were more likely to have severe field triage acuities (adjusted OR = 14.7, 95% CI: 1.8-118.0, p = 0.012); intracranial hemorrhage (12.5%), intrathoracic injury (18.8%), or intra-abdominal damage (12.5%) (All p < 0.05); the need for emergency surgical intervention (31.3%, p = 0.035); and major trauma (18.8%, p = 0.001). Residents in the collapsed buildings were more likely to have a crush injury (80.0%, p < 0.001) or crush syndrome (80.0%, p < 0.001). CONCLUSION: People entrapped at different heights of floors or in differently damaged buildings could have a distinct pattern of injury. Our findings may facilitate strategic approaches of patients entrapped in damaged buildings and may contribute to future training for field searches and rescues after earthquakes.


Assuntos
Desastres , Terremotos , Ferimentos e Lesões/classificação , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Criança , Medicina de Desastres , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taiwan/epidemiologia , Triagem/estatística & dados numéricos , Ferimentos e Lesões/mortalidade , Adulto Jovem
17.
Ann Hum Genet ; 83(3): 124-133, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30506894

RESUMO

OBJECTIVE: To investigate the correlation of tumor necrosis factor α (TNF-α) polymorphisms with upper gastrointestinal bleeding (UGIB) induced by enteric-coated aspirin in coronary heart disease (CHD) patients. METHODS: In total, 154 CHD patients taking enteric-coated aspirin were enrolled in this study. Patients were divided into the UGIB group (n = 57) and non-UGIB group (n = 97) based on the presence or absence of signs of UGIB, respectively. TNF-α polymorphism (-857C > T, -863C > A, and -1031T > C) genotyping was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP). RESULTS: Patients who had the CC genotype and C allele of -1031T > C exhibited a significantly increase risk of UGIB after receiving enteric-coated aspirin (CC vs. TT: odds (OR) (95% confidence interval (CI)): 7.568 (1.527-37.49), P = 0.005; C vs. T: OR (95% CI): 1.852 (1.036-3.312), P = 0.036). Patients who had CA and CA + AA genotypes and the A allele of -863C > A also exhibited an increased risk of aspirin-induced UGIB (CA vs. CC: OR (95% CI): 2.415 (1.143-5.101), P = 0.019: CA + AA vs. CC: OR (95% CI): 2.218 (1.123-4.381), P = 0.021; A vs. C: OR (95% CI): 1.788 (1.039-3.078), P = 0.035). However, the TNF-α -857 C > T polymorphism was unrelated to the induction of UGIB by enteric-coated aspirin in CHD patients (P > 0.05). In addition, the haplotypes of CCC (-1031T > C, -863C > A, and -857C > T) markedly reduced the risk of aspirin-induced UGIB in CHD patients. CONCLUSION: TNF-α -863A and -1031C increased the risk of UGIB induction by enteric-coated aspirin in CHD patients, whereas TNF-α -857C > T was not correlated with the UGIB risk.


Assuntos
Aspirina/efeitos adversos , Doença das Coronárias/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Fator de Necrose Tumoral alfa/genética , Idoso , Alelos , Aspirina/uso terapêutico , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Biol Chem ; 294(6): 2162-2179, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409908

RESUMO

The chaperome is the collection of proteins in the cell that carry out molecular chaperoning functions. Changes in the interaction strength between chaperome proteins lead to an assembly that is functionally and structurally distinct from each constituent member. In this review, we discuss the epichaperome, the cellular network that forms when the chaperome components of distinct chaperome machineries come together as stable, functionally integrated, multimeric complexes. In tumors, maintenance of the epichaperome network is vital for tumor survival, rendering them vulnerable to therapeutic interventions that target critical epichaperome network components. We discuss how the epichaperome empowers an approach for precision medicine cancer trials where a new target, biomarker, and relevant drug candidates can be correlated and integrated. We introduce chemical biology methods to investigate the heterogeneity of the chaperome in a given cellular context. Lastly, we discuss how ligand-protein binding kinetics are more appropriate than equilibrium binding parameters to characterize and unravel chaperome targeting in cancer and to gauge the selectivity of ligands for specific tumor-associated chaperome pools.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos/métodos , Chaperonas Moleculares , Proteínas de Neoplasias , Neoplasias , Mapas de Interação de Proteínas/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Humanos , Chaperonas Moleculares/antagonistas & inibidores , Chaperonas Moleculares/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
19.
J Mol Recognit ; 32(5): e2772, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30520537

RESUMO

In this paper, a miRNA-based quartz crystal microbalance (QCM) biosensor was fabricated and used to the rapid and effective sensing of miRNA. The specific hybridization between probe miRNA and different selected miRNAs (miR-27a, miR-27b, and Let-7a) cause a different interaction mode, thus display different frequency change and response patterns in the QCM sensor, which were used to detect miR-27a and miR-27b. The selective sensing of miR-27a in mixed miRNA solution was also achieved. This miRNA-based QCM biosensor has the advantages of real-time, label-free, and short cycle detection.

20.
Chem Sci ; 9(2): 457-462, 2018 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30310560

RESUMO

The core-shell structure of endohedral fullerenes results in good protection of the encapsulated spin carriers from the environment. In this research, the quantum coherence behavior of the endohedral fullerene Sc3C2@C80 in CS2 solution is characterized from 5 K to room temperature. Below the critical temperature of around 140 K, the inner group is hindered, and the EPR spectrum consists of a single broad line. The spin carriers display a maximum phase memory time of 17.2(7) µs at 10 K. In the high temperature region, the inner group is mobile, and the EPR spectrum consists of 22 homogeneously broadened lines due to isotropic hyperfine coupling. The maximum phase memory time for each transition is around 139(1) ns at 200 K which allows arbitrary superposition state manipulations to be performed. This research demonstrates that Sc3C2@C80 displays temperature-crossover behaviour due to weak interaction between the Sc3C2 core and the C80 shell.

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