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1.
Biosens Bioelectron ; 152: 112037, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056731

RESUMO

Immunochromatography assays are simple and low-cost point-of-care diagnostics. However, the dependence on paper-based capillary forces limits improvements in speed of the assay. An electro-driven immunochromatography assay (EICA) is described that uses electroosmotic flow (EOF) to increase the driving force, as well as upconversion nanoparticles for high-sensitivity detection. EOF increased the signal intensity by 64.0% and reduced the assay time from 15 min to 5 min, and the EICA exhibited good specificity and sensitivity (1.2 × 103 CFU/mL) for pure cultures of Yersinia pestis EV76. It also had a strong tolerance to acid-base conditions (pH 2-12), salt solutions (NaCl ≤ 0.5 mol/L), viscous materials (polyethylene glycol 20,000 ≤ 25 mg/mL), and proteins (bovine serum albumin ≤200 mg/mL). For real soil samples, the EICA exhibited a low limit of detection (LOD) of 1.2 × 104 CFU/mL with good repeatability and reliability. Thus, EICA is applicable for detection of Y. pestis in soil, and should provide a rapid and sensitive tool for point-of-care diagnosis and detection.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32036743

RESUMO

Characterizing bacterial communities is of great significance for targeted control of bacteria-induced clogging during geothermal water recharge. Based on a series of laboratory-scale percolation experiments, the variations in bacterial community diversity, composition, and structure were investigated during simulated geothermal water recharge using high-throughput sequencing technology. The Chao, Shannon, and Evenness indexes were used to quantify the richness, diversity, and evenness of the bacterial community, respectively. The results show that the richness of the bacterial community initially increased and then decreased in the sand columns during the experiments of geothermal water recharge, while the changes in bacterial diversity and evenness were not apparent. A variety of bacterial phyla were found, among which Proteobacteria was predominant (88.31%), followed by Actinobacteria, Bacteroidetes, and Firmicutes (4.23%, 3.44%, and 2.49%). For the non-Proteobacterial phyla, Actinobacteria gradually disappeared while Bacteroidetes and Firmicutes were detected during the percolation experiments. This study implies that, despite the variations in the bacterial community, a core group of bacteria persists during geothermal water recharge, and thus a targeted control of bacteria-induced clogging during geothermal water recharge should be feasible.

3.
Anal Biochem ; 593: 113594, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978458

RESUMO

A novel, simple and efficient chemiluminescence system has been developed for the determination of monoamine neurotransmitters and metabolites. By using the Ag (III)-luminol chemiluminescence system as a detector, a high performance liquid chromatography chemiluminescence method (HPLC-CL) was established and used to detect seven monoamine neurotransmitters. Under the optimized conditions, the detection limits (3S/N) of epinephrine (E), levodopa (l-DOPA), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxypentylacetic acid (5-HIAA) were 20.0 µg dm-3,15.0 µg dm-3, 15.0 µg dm-3, 8.0 µg dm-3, 2.0 µg dm-3, 2.0 µg dm-3 and 3.0 µg dm-3, respectively. Moreover, they were well within the linear range of 50-1000 µg dm-3, 50-1000 µg dm-3, 50-1000 µg dm-3, 25-1000 µg dm-3, 5-25 µg dm-3, 5-25 µg dm-3 and 10-30 µg dm-3, respectively. The average recovery varied between 84.82% and 110.4%. The method has the attributes of simplicity, high sensitivity, and high efficiency. The sensitization and inhibition mechanisms for luminol-[Ag(HIO6)2]5-- analytes CL system were proposed by CL spectra and free-radical capture experiment.

4.
Mol Cell Probes ; : 101513, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31968218

RESUMO

AIM: This study aims to explore the role and mechanism of exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs-Exo) in regulating proliferation and apoptosis of acute myeloid leukemia (AML) cell line THP-1. METHODS: hBM-MSCs-Exo was isolated by ultra-centrifugation and administered into THP-1 cells to elucidate the effects of exosomes in THP-1 cells. Cell proliferation and apoptosis were examined by CCK-8 assay and flow cytometry, respectively. The expression of miR-222-3p, IRF2, and INPP4B were measured by qRT-PCR and western blot. The interaction between miR-222-3p and IRF2 was analyzed by luciferase reporter assay. RESULTS: Lower cell viability rate, higher apoptosis ratio, higher miR-222-3p expression, and lower IRF1/INPP4B expression were observed in THP-1 cells exposed to BM-MSCs-Exo. The proliferation-inhibitory and pro-apoptotic effects of BM-MSCs-Exo on THP-1 cells were markedly compromised when miR-222-3p expression in BM-MSCs-Exo was inhibited. Furthermore, miR-222-3p directly targeted IRF2 and negatively regulated IRF2/INPP4B signaling in THP-1 cells. Moreover, overexpression of either IRF2 or INPP4B counteracted the proliferation-inhibitory and pro-apoptotic effects mediated by BM-MSCs-Exo. CONCLUSION: BM-MSCs delivered miR-222-3p via exosomes to inhibit cell proliferation and promote cell apoptosis by targeting IRF2 and negatively regulating IRF2/INPP4B signaling in THP-1 cells.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 35-41, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950787

RESUMO

Objective: We analyzed the brain structure of schizophrenia patients from multiple perspectives to explore the relationship between the duration of untreated psychosis (DUP) and clinical outcomes. Methods: For 85 patients and 86 controls, clinical symptoms and cognitive function were evaluated, magnetic resonance imaging (MRI) and free surfer analysis were used to extract the cortical indicator, such as brain cortex thickness, surface area, volume, and so on. The patients were divided into four subgroups according to the boundary of March, June and two year due to the distribution and median of DUP. Finally multi-group comparison and correlation analysis for above indicators were analysed. Results: DUP was associated with the surface area of the left insula, parsorbitalis, right hippocampus, superior frontal gyrus, frontal pole, and temporal pole; DUP mainly influenced the cortical thickness of left posterior cingulate gyrus, postcentral gyrus, right lateral occipital cortex, parsopercularis, medial orbitofrontal cortex, and the bilateral precentral gyrus. For cortical volume, DUP significantly affected left postcentral gyrus, right precuneus, lateral occipital cortex, parsopercularis, lingual gyrus, superior temporal gyrus, bilateral cuneus, pericalcarine cortex, precentral gyrus,superior parietal lobule, and insula.The first three months after onset is a critical period for the deterioration of cortical morphology and clinical function. Conclusion: DUP in first-episode schizophrenia is associated with cortical morphological changes of temporal lobe, precentral, orbitofrontal cortex and the majority of medial regions of occipital lobe, it is very important to conduct early intervention for patients.


Assuntos
Córtex Cerebral , Imagem por Ressonância Magnética , Transtornos Psicóticos , Esquizofrenia , Córtex Cerebral/diagnóstico por imagem , Humanos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/terapia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Lobo Temporal/diagnóstico por imagem , Fatores de Tempo
6.
Sci Total Environ ; 713: 136665, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31955111

RESUMO

Arsenic (As) and cadmium (Cd) typically exhibit divergent fates in soil, which complicates efforts to decrease As and Cd accumulation in the edible parts of crops. Here, we performed pot experiments to examine the effect of sulfate application on As and Cd accumulation in the grain of wheat grown in contaminated soil. Compared to the control (no sodium sulfate addition), application of 120 mg kg-1 sodium sulfate decreased the rhizosphere soil pH from 7.27 to 7.10 and increased the soil extractable Cd concentration; however, it did not significantly influence the soil extractable As concentration. However, sodium sulfate addition decreased As and Cd concentrations in wheat grain, in association with decreased As and Cd translocation from root and straw to grain, rather than from soil to root. Furthermore, sodium sulfate addition significantly decreased membrane lipid peroxidation and enhanced photosynthesis, while increasing the uptake of nitrogen, phosphorus, and sulfur. These effects increased the growth and grain weight of plants grown in As and Cd co-contaminated soil. Our findings provide insight into the mechanisms by which sulfate modulates As and Cd uptake and translocation in wheat; moreover, our findings will enable formulation of strategies to decrease As and Cd concentrations in the grain of wheat grown in As and Cd co-contaminated soil.

7.
Int J Legal Med ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31637457

RESUMO

Forensic diatom test has been considered as a significant tool for diagnosis of drowning. Most of the studies in this field discussed the methodology of extracting, enriching and detecting diatoms from different tissues and drowning media. There are few studies on the basic principle of diatom test which was based on the theory developed by forensic scientists many years ago. This study was designed to analyze the length and width of diatoms in different organs and drowning medium samples of drowning cases. This study is designed to find evidence of diatoms penetrating the alveoli-capillary barrier. Samples from 100 drowning cases were analyzed using the methodology we developed: the Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy method (MD-VF-Auto SEM method). The results showed that the length and width of diatoms in the liver and kidney tissues are smaller than that of the lung tissues and water samples. Our studies also found that the pennate diatoms are easier to penetrate through the alveoli-capillary barrier, travel in the blood stream and finally deposit in the distant tissues including liver and kidney. These findings provided evidences to support the process of diatoms penetrating the alveoli-capillary barrier.

8.
J Agric Food Chem ; 67(42): 11796-11804, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31589426

RESUMO

High molecular weight glutenin subunits (HMW-GSs) are important components of wheat (Triticum aestivum L.) gluten proteins that affect the processing quality of wheat dough. However, the contributions of individual HMW-GS to sponge cake quality still remain unclear. To investigate the effects of 1Bx7 and 1By9 at Glu-B1 on wheat gluten properties and sponge cake quality, we screened an ethylmethanesulfonate (EMS)-mutagenized wheat population and obtained two independent mutants that lack 1Bx7 and another two mutants that lack 1By9. The absence of 1Bx7 or 1By9 significantly affects the accumulation levels of gluten proteins and the formation of a gluten network. Quality testing indicated that the lack of 1Bx7 or 1By9 leads to weaker dough strength and inferior sponge cake performance. These results demonstrate that 1Bx7 and 1By9 make important contributions to gluten functionality and sponge cake quality.


Assuntos
Pão/análise , Glutens/química , Triticum/química , Culinária , Glutens/genética , Peso Molecular , Subunidades Proteicas/química , Subunidades Proteicas/genética , Triticum/genética
9.
Onco Targets Ther ; 12: 5793-5803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410024

RESUMO

Background: ASAP3 was first identified as a protein that promotes cell proliferation in hepatocellular carcinoma and later reported to be an Arf6-specific Arf GTPase-activating protein that regulates cell migration associated with cancer cell invasion. Materials and methods: Patients and tissue samples were from Hubei Cancer Hospital, human lung adenocarcinoma cell lines were obtained from the cell bank of the Chinese Academy of Science, nude mice (BALB/c nu/nu) were obtained from Shanghai SLAC Laboratory Animal Co. Ltd. Our methods contained immunohistochemistry, Western blotting, reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, stable transfection of lung adenocarcinoma cells, chromatin immunoprecipitation (CHIP) and luciferase assay, wound healing and cell migration assay. Results: In this study, we show that ASAP3 overexpression promotes migration and invasiveness in human lung adenocarcinoma cells and accelerates tumor progression in a xenograft mouse model. In patient tumor samples, ASAP3 overexpression was significantly associated with lymph node metastasis and reduced overall survival. We also show that ASAP3 expression is induced under hypoxic conditions through hypoxia-inducible factor 1α (HIF-1α), which binds directly to HER1 or/and HER2 (hypoxia response element) in the ASAP3 promoter. ASAP3 overexpression counteracts the inhibition of lung adenocarcinoma progression caused by HIF-1α knockdown both in vitro and in vivo. Conclusion: Our results identify ASAP3 as a downstream target of HIF-1α that is critical for metastatic progression in lung adenocarcinoma.

10.
Sci Total Environ ; 691: 848-857, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31326808

RESUMO

Microplastics (MPs) have become a global environmental concern because of their ubiquitous presence. While extensive microplastic researches have focused on the marine environment, pervasive MPs contamination in soil and their detrimental impacts have been largely overlooked. Excessive concentrations of MPs and additives have been found in soil derived from the use of plastic mulches and the application of sewage sludge to fields. They may pose directly or indirectly as adverse effects on flora and fauna. The objectives of this review are (1) to summarize the abundance, sources, and properties of MPs in soil; (2) to analyze combined effects of MPs and various other environmental pollutants on soil system; and (3) to discuss the possible risks posed by MPs to soil biodiversity, food safety and human health. This review will highlight key future research areas for scientists and policymakers, and increase overall understanding of soil MPs pollution and its potential environmental impacts.

11.
EMBO J ; 38(14): e100978, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304625

RESUMO

Viral infection triggers the formation of mitochondrial antiviral signaling protein (MAVS) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS-mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF34 regulates immunity and mitophagy by targeting MAVS. RNF34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG-I-like receptor (RLR)-mediated antiviral immunity. Moreover, RNF34 catalyzes the K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP52-dependent autophagic degradation. Specifically, RNF34 initiates the K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG-I stimulation. Notably, RNF34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF34-mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Mitocôndrias/metabolismo , Viroses/imunologia , Proteína DEAD-box 58/metabolismo , Células HEK293 , Células HeLa , Humanos , Imunidade Inata , Lisina/metabolismo , Proteólise , Transdução de Sinais , Células THP-1 , Ubiquitinação , Viroses/metabolismo
12.
J Gastroenterol Hepatol ; 34(12): 2152-2157, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31318990

RESUMO

BACKGROUND AND AIM: An endoscopic clip device was newly designed to accomplish the closure of large gastrointestinal defects. The aim of this study was to determine the feasibility and efficacy of this device in an ex vivo experimental setting. METHODS: This prospective study was conducted in porcine colons (n = 5). A large (3-4 cm) linear full-thickness incision was created using a scalpel externally. The device was used for endoscopic closure. The procedure time, number of clips, and success rate of closure were determined. RESULTS: Ten defects were created in five porcine colons (two incisions in each specimen). Successful closure was achieved in all defects. The mean procedure time was 24.30 ± 4.42 min, the mean leak pressure is 28.30 ± 9.49 mmHg, and the mean number of additional conventional hemostatic clips used was 5.10 ± 0.99. CONCLUSIONS: The results indicated that this clip achieved the convenient and reliable closure of large defects in the colon wall in an ex vivo porcine model and seems to be a promising option for closing large gastrointestinal perforations.

13.
PeerJ ; 7: e7104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31245178

RESUMO

Background: Wheat is one of the most important staple crops worldwide. Fusarium head blight (FHB) severely affects wheat yield and quality. A novel bread wheat mutant, ZK001, characterized as cleistogamic was isolated from a non-cleistogamous variety Yumai 18 (YM18) through static magnetic field mutagenesis. Cleistogamy is a promising strategy for controlling FHB. However, little is known about the mechanism of cleistogamy in wheat. Methods: We performed a FHB resistance test to identify the FHB infection rate of ZK001. We also measured the agronomic traits of ZK001 and the starch and total soluble sugar contents of lodicules in YM18 and ZK001. Finally, we performed comparative studies at the proteome level between YM18 and ZK001 based on the proteomic technique of isobaric tags for relative and absolute quantification. Results: The infection rate of ZK001 was lower than that of its wild-type and Aikang 58. The abnormal lodicules of ZK001 lost the ability to push the lemma and palea apart during the flowering stage. Proteome analysis showed that the main differentially abundant proteins (DAPs) were related to carbohydrate metabolism, protein transport, and calcium ion binding. These DAPs may work together to regulate cellular homeostasis, osmotic pressure and the development of lodicules. This hypothesis is supported by the analysis of starch, soluble sugar content in the lodicules as well as the results of Quantitative reverse transcription polymerase chain reaction. Conclusions: Proteomic analysis has provided comprehensive information that should be useful for further research on the lodicule development mechanism in wheat. The ZK001 mutant is optimal for studying flower development in wheat and could be very important for FHB resistant projects via conventional crossing.

14.
Psychiatry Res Neuroimaging ; 288: 12-20, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31059954

RESUMO

Progressive brain volume atrophy has been reported in patients with schizophrenia. However, whether this progress differs between patients with primary negative symptoms (deficit schizophrenia; DS) and those without such symptoms (nondeficit schizophrenia; NDS) is unknown. Here, we examined grey matter volume (GMV) and white matter volume (WMV) changes over 12 months in 34 first-episode treatment-naive patients with schizophrenia (14 DS and 20 NDS) and 32 healthy controls (HCs) using structural magnetic resonance imaging and voxel-based morphometry. At baseline, compared to HCs, patients with DS but not NDS had less WMV in bilateral posterior limb of the internal capsule (PLIC) and cerebellar tonsil (P < 0.05, FDR corrected) and smaller GMV in the cerebellar culmen (P < 0.05, FWE corrected). At follow-up, NDS group showed WMV reduction in bilateral PLIC (P < 0.05, FDR corrected), while DS group showed no progressive WMV changes. While both patient groups exhibited GMV reduction in the hippocampus and insular cortex, patients with NDS showed additional GMV loss in the frontal and cingulate cortex and a selective increase in GMV in the left thalamus (P < 0.05 FWE corrected). Our study revealed double dissociations in developmental brain volume changes in the first year after clinical contact for psychosis in DS versus NDS patients.

16.
Biol Res ; 52(1): 11, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876449

RESUMO

BACKGROUND: The present study aimed to investigate the underlying role of interferon-regulatory factor 2 (IRF2)-inositol polyphosphate-4-phosphatase, type-II (INPP4B) axis in the regulation of autophagy in acute myeloid leukemia (AML) cells. METHODS: Quantitative real time PCR (QRT-PCR) and western blot were performed to determine the expression levels of IRF2, INPP4B and autophagy-related markers in AML cell lines. Autophagy was assessed by elevated Beclin-1 expression, the conversion of light chain 3 (LC3)-I to LC3-II, downregulated p62 expression and green fluorescent protein (GFP)-LC3 puncta formation. The colony formation and apoptosis assays were performed to determine the effects of IRF2 and INPP4B on the growth of AML cells. RESULTS: IRF2 and INPP4B were highly expressed in AML cell lines, and were positively correlated with autophagy-related proteins. Overexpression of IRF2 or INPP4B stimulated autophagy of AML cells, whereas inhibition of IRF2 or INPP4B resulted in the attenuation of autophagy. More importantly, IRF2 or INPP4B overexpression reversed autophagy inhibitor, 3-methyladenine (3-MA)-induced proliferation-inhibitory and pro-apoptotic effects, while IRF2 or INPP4B silencing overturned the proliferation-promoting and anti-apoptotic effects of autophagy activator rapamycin. CONCLUSION: IRF2-INPP4B signaling axis attenuated apoptosis through induction of autophagy in AML cells.


Assuntos
Apoptose , Autofagia , Fator Regulador 2 de Interferon/metabolismo , Leucemia Mieloide Aguda/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Imunofluorescência , Humanos , Leucemia Mieloide Aguda/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
17.
BMC Infect Dis ; 19(1): 158, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764764

RESUMO

BACKGROUND: Clinical characteristics (taxonomy, virulence genes and antimicrobial resistance ) of Aeromonas in isolated from extra-intestinal and intestinal infections were investigated to describe epidemiology, associated virulence factors and optimal therapy options. METHODS: Clinical samples (n = 115) of Aeromonas were collected from a general hospital in Beijing between the period 2015 and 2017. Taxonomy was investigate by Multilocus phylogenetic analysis (MLPA), 10 putative virulence factors by use of polymerase chain reaction (PCR) and antimicrobial resistance to 15 antibiotics by use of the microbroth dilution method. RESULTS: The most common species of Aeromonas detected in samples of intestinal tract included; A. caviae (43.9%), A. veronii (35.7%), and A. dhakensis (12.2%). Prevalent species of Aeromonas collected from extra-intestinal infections included; A. hydrophila (29.4%), A. caviae (29.4%), and A. dhakensis (23.5%). A. hydrophila were detected in 1% of stool samples and 29.4% (5/17) of extra-intestinal infections. A. hydrophila strains in extra-intestinal infections were related to malignancy. The most common medical conditions among patients with Aeromonas infections included malignancy and liver-transplant related cholecystitis. Multiple drug resistance (MDR) was prevalent in extra-intestinal isolates (82.3%, 14/17) and was greater than the prevalence in intestinal isolates (30.6%, 30/98) (P < 0.05). Resistant rates of extra-intestinal isolates were 70.6, 35.3, 23.5 and 5.9% for ceftriaxone, ciprofloxacin, gentamicin and imipenem, respectively, and were higher than found in previous studies. Despite differences in the number and type of virulence genes among samples of Aeromonas, no significant correlation was found between invasion and virulent genes in intestinal or extra-intestinal infections. CONCLUSIONS: Overall results of this study support a role for Aeromonas spp. as a potential causative infectious agent of gastroenteritis, and malignancy, liver cirrhosis, post liver transplantation in immunocompromised patients. A. hydrophila was more prevalent in samples of extra-intestinal infections when compared to samples of intestinal infections, and was especially prominent in samples of patients presenting with malignancy. Aeromonas isolates from extra-intestinal samples had high rates of drug resistance but 3rd generation cephalosporins, fluoroquinolones and aminoglycosides remain as options to treat severe diarrhea. However, increasing MDR of extra-intestinal infection samples warrants monitoring.


Assuntos
Aeromonas/classificação , Aeromonas/isolamento & purificação , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/microbiologia , Enteropatias/microbiologia , Infecções Intra-Abdominais/microbiologia , Fatores de Virulência/genética , Adolescente , Adulto , Aeromonas/efeitos dos fármacos , Aeromonas/genética , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , China/epidemiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Feminino , Gastroenterite/tratamento farmacológico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Enteropatias/tratamento farmacológico , Enteropatias/epidemiologia , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Filogenia , Prevalência , Virulência/genética , Adulto Jovem
18.
J Enzyme Inhib Med Chem ; 34(1): 651-656, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30746966

RESUMO

Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Cumarínicos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/síntese química , Antioxidantes/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Ratos Wistar , Relação Estrutura-Atividade , Peixe-Zebra
19.
Technol Cancer Res Treat ; 18: 1533033818824314, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30803373

RESUMO

The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Apoptose , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Ciclo Celular , Proliferação de Células , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Prognóstico , Taxa de Sobrevida
20.
Hepatology ; 70(3): 851-870, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30723919

RESUMO

The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor-promoting inflammation by up-regulating UPR target genes and proinflammatory cytokines. However, the molecular basis of this endoplasmic reticulum (ER) stress transmission remains largely unclear. Here, we identified the secreted form of Golgi protein 73 (GP73), a Golgi-associated protein functional critical for hepatocellular carcinoma (HCC) growth and metastasis, is indispensable for ER stress transmission. Notably, ER stressors increased the cellular secretion of GP73. Through GRP78, the secreted GP73 stimulated ER stress activation in neighboring macrophages, which then released cytokines and chemokines involved in the tumor-associated macrophage (TAM) phenotype. Analysis of HCC patients revealed a positive correlation of GP73 with glucose-regulated protein 78 (GRP78) expression and TAM density. High GP73 and CD206 expression was associated with poor prognosis. Blockade of GP73 decreased the density of TAMs, inhibited tumor growth, and prolonged survival in two mouse HCC models. Conclusion: Our findings provide insight into the molecular mechanisms of extracellular GP73 in the amplification and transmission of ER stress signals.

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