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1.
Biomed Pharmacother ; 121: 109552, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715370

RESUMO

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.

2.
ACS Appl Mater Interfaces ; 11(38): 34725-34735, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31479233

RESUMO

Huntington's disease (HD) is an incurable disease with progressive loss of neural function, which is influenced by epigenetic, oxidative stress, metabolic, and nutritional factors. Targeting inhibition of huntingtin protein aggregation is a strategy for HD therapy, but the efficacy is unsatisfactory. Studies found that selenium (Se) levels in the brain are insufficient for HD disease individuals, while improvement in Se homeostasis in the brain may attenuate neuronal loss and dysfunction. In this study, we applied selenium nanoparticles (NPs) (Nano-Se) for the HD disease therapy by regulating HD-related neurodegeneration and cognitive decline based on transgenic HD models of Caenorhabditis elegans (C. elegans). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected C. elegans from damages in stress conditions. The molecular mechanism further revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and downregulated the expression of histone deacetylase family members at mRNA levels. The results suggested that Nano-Se has great potential for Huntington's disease therapy. In conclusion, the mechanism about how Nano-Se NPs protect from damages in stress conditions and how they repair neural functions will benefit HD disease therapy. This study will also guide rational design of Nano-Se NPs or other selenium compounds to improve HD therapy in the future.

3.
Emerg Infect Dis ; 25(10): 1932-1945, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31538920

RESUMO

Market surveillance showed continuing circulation of avian influenza A(H5N6) virus in live poultry markets in Guangdong Province in 2017, despite compulsory vaccination for avian influenza A(H5Nx) and A(H7N9). We analyzed H5N6 viruses from 2014-2018 from Guangdong Province, revealing antigenic drift and decreased antibody response against the vaccine strain in vaccinated chickens.

4.
Mol Carcinog ; 58(12): 2254-2265, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31513316

RESUMO

Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR-19a-3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor-kappaB (NF-κB) binds to the promoter of miR-19a-3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR-19a-3p inhibits the expression of insulin-like growth factor binding protein-3 (IGFBP-3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR-19a-3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP-3 expression, and which can be inhibited by NF-κB, suggesting an NF-κB/miR-19a-3p/IGFBP-3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.

5.
Viruses ; 11(6)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234565

RESUMO

Picobirnaviruses (PBVs) are mostly found in animal alimentary samples. In this study, among 576 respiratory specimens from 476 mammals and 100 chickens, genogroup I PBVs were detected in three cattle and three monkeys, and a genogroup II PBV-positive sample was collected from one cattle specimen. More than one PBV sequence type was observed in two and one genogroup I PBV-positive samples from cattle and monkeys, respectively. Twenty-four complete/near-complete segments 2 (nine from respiratory and 15 from alimentary samples) from the cattle and monkey genogroup I PBVs and one complete segment 2 from the cattle genogroup II PBV were sequenced. Similar to other studies, the cattle PBVs also showed a high diversity. In contrast, the monkey PBVs observed in this study were clustered into three distinct clades. Within each clade, all the sequences showed >99% amino acid identities. This unique phenomenon is probably due to the fact that monkeys in our locality reside in separated troops with minimal inter-troop contact.

6.
Nat Nanotechnol ; 14(7): 719-727, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31235893

RESUMO

Anthropogenic carbon nanotubes, with a fibrous structure and physical properties similar to asbestos, have recently been found within human lung tissues. However, the reported carbon-nanotube-elicited pulmonary pathologies have been mostly confined to inflammatory or neoplastic lesions in the lungs or adjacent tissues. In the present study, we demonstrate that a single pulmonary exposure to multi-walled carbon nanotubes dramatically enhances angiogenesis and the invasiveness of orthotopically implanted mammary carcinoma, leading to metastasis and rapid colonization of the lungs and other organs. Exposure to multi-walled carbon nanotubes stimulates local and systemic inflammation, contributing to the formation of pre-metastatic and metastatic niches. Our study suggests that nanoscale-material-elicited pulmonary lesions may exert complex and extended influences on tumour progression. Given the increasing presence of carbon nanotubes in the environment, this report emphasizes the urgent need to escalate efforts assessing the long-term risks of airborne nanomaterial exposure in non-lung cancer progression.

7.
Int Immunopharmacol ; 72: 204-210, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30999210

RESUMO

Acute pancreatitis (AP) is a common acute abdominal disease with local or systemic inflammatory response, caused by abnormal activation of digestive enzymes. Baicalein has been shown to exert anti-inflammatory effects and to attenuate the pathological changes of AP. The aim of the research was to investigate the effects of baicalein on caerulein induced pancreatitis, and to elucidate the putative underlying mechanism. In this study, the therapeutic potential of baicalein and its mechanism were investigated in a caerulein-induced AP in vivo and in vitro model. The results indicate that baicalein treatment alleviates the caerulein-induced pathological damage in the pancreas. Baicalein decreased the expression level of pro-inflammatory cytokines and chemokines of the pancreas in caerulein treated mice and of isolated pancreatic acinar cells. Moreover, baicalein inhibited the expression of NF-κB p65 and the phosphorylation of p38 MAPK, ERK (extracellular signal-regulated kinase) as well as STAT 3, which indicates that baicalein exerts its anti-inflammatory effects via dampening the NF-κB, MAPK and STAT 3 signaling pathways. Together, this study provides experimental evidence for the clinical application of Scutellaria baicalensis Georgi or baicalein and indicates that baicalein may be a promising candidate for treatment of AP patients in the future.

8.
Planta ; 249(6): 1889-1902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30864013

RESUMO

MAIN CONCLUSION: MYB15 promoter of Vitis quinquangularis has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms. China is a center of origin for Vitis and is home to diverse wild Vitis genotypes, some of which show superior pathogen resistance, although the underlying molecular basis for this has not yet been elucidated. In the current study, we identified a transcription factor, MYB15, from the Chinese wild grape, Vitis quinquangularis, whose promoter region (pVqMYB15) was shown to be induced by basal immunity (also called PAMP-triggered immunity, PTI) triggered by flg22, following heterologous expression in Nicotiana benthamiana and homologous expression in grapevine. By analyzing the promoter structure and activity, we identified a unique 283 bp sequence that plays a key role in the activation of basal immunity. In addition, we showed that activation of the MYB15 promoter correlates with differences in the expression of MYB15 and RESVERATROL SYNTHASE (RS) induced by the flg22 elicitor. We further tested whether the MYB15 induction triggered by flg22 was consistent with MYB15 and RS expression following inoculation with Plasmopara viticola in grape (V. quinquangularis and Vitis vinifera) leaves. Mapping upstream signals, we found that calcium influx, an RboH-dependent oxidative burst, an MAPK cascade, and jasmonate and salicylic acid co-contributed to flg22-triggered pVqMYB15 activation. Our data suggest that the MYB15 promoter has potential as a target for disease resistance breeding, and its involvement in PTI is associated with a range of defense mechanisms.


Assuntos
Resistência à Doença/genética , Oomicetos/fisiologia , Doenças das Plantas/imunologia , Reguladores de Crescimento de Planta/metabolismo , Fatores de Transcrição/metabolismo , Vitis/genética , China , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Ácido Salicílico/metabolismo , Fatores de Transcrição/genética , Vitis/imunologia , Vitis/fisiologia
9.
Molecules ; 24(6)2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30917586

RESUMO

The purpose of this research was to extract and separate the compounds from frankincense, and then evaluate their anti-inflammatory effects. The isolated compound was a representative tetracyclic triterpenes of glycine structure according to ¹H-NMR and 13C-NMR spectra, which is ß-elemonic acid (ß-EA). We determined the content of six different localities of frankincense; the average content of ß-EA was 41.96 mg/g. The toxic effects of ß-EA administration (400, 200, 100 mg/kg) for four weeks in Kunming (KM) mice were observed. Compared with the control group, the body weight of mice, the visceral coefficients and serum indicators in the ß-EA groups showed no systematic variations. The anti-inflammatory effects of ß-EA were evaluated in LPS-induced RAW264.7 cells, xylene-induced induced ear inflammation in mice, carrageenin-induced paw edema in mice, and cotton pellet induced granuloma formation in rats. ß-EA inhibited overproduction of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), soluble TNF receptor 1 (sTNF R1), Eotaxin-2, Interleukin 10 (IL-10) and granulocyte colony-stimulating factor (GCSF) in the RAW264.7 cells. Intragastric administration with ß-EA (300, 200, and 100 mg/kg in mice, and 210, 140, and 70 mg/kg in rats) all produced distinct anti-inflammatory effects in vivo in a dose-dependent manner. Following treatment with ß-EA (300 mg/kg, i.g.), the NO level in mice ears and PGE2 in mice paws both decreased (p < 0.01). In conclusion, our study indicates that ß-EA could be a potential anti-inflammatory agent for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dinoprostona/metabolismo , Franquincenso/química , Inflamação/tratamento farmacológico , Triterpenos/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Carragenina/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas In Vitro , Inflamação/induzido quimicamente , Lipopolissacarídeos/efeitos adversos , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Ratos , Triterpenos/química , Triterpenos/farmacologia , Xilenos/efeitos adversos
10.
Chemosphere ; 223: 263-274, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784734

RESUMO

Particulate matter (PM) exposure poses many adverse effects on human health. However, it is challenging to clearly differentiate between the contributions of individual pollutants on toxicity from complex mixtures of ambient air pollutants. The aim of this study is to generate aerosols constituted by silica nanoparticles (NPs) and bisulfate to serve as simulators of particle-associated high-sulfur air pollution. Then, the health impacts of sulfur dioxide were evaluated at the cellular level using an air-liquid interface (ALI) exposure chamber. BEAS-2B cells were exposed to either nano-silica or bisulfite aerosol individually or bisulfate-coated silica (SiO2-NH2@HSO3) for 3 h using the ALI. The cellular toxicities were carefully compared based on the exposure dosages. The ALI exposure of SiO2 NPs alone did not produce any apparent cytotoxicity in cells, but the aerosol exposure of SiO2-NH2@HSO3 significantly decreased the cell viability and enhanced the production of cellular reactive oxygen species in a dose-dependent manner. Consequently, the excessive oxidative stress resulted in mitochondrial damage as well as cellular apoptosis. ALI exposure can possibly reflect the realistic physiological exposure condition of the human respiratory system. As a derivative of the sulfur dioxide component of air pollution, sulfate exacerbates the toxic effects of inhalable PMs. This result may be due to the large surface area of the nanoparticles, with the possibility of carrying more sulfite to the target cells during aerosol exposure. The sulfate levels offer a meaningful complement to the present PM2.5 index of air pollution for achieving better human health protection.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/análise , Modelos Biológicos , Material Particulado/efeitos adversos , Aerossóis , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Medição de Risco , Dióxido de Silício/efeitos adversos , Sulfatos/efeitos adversos
11.
Mol Med Rep ; 19(3): 2057-2064, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664158

RESUMO

The present study aimed to investigate the anti­arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6, IL­10, IL­12 and IL­17A. Furthermore, indices of the thymus and spleen were determined. The anti­proliferative effects of curculigoside were detected with Cell Counting kit­8 assays in rheumatoid arthritis­derived fibroblast­like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)­κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen­induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF­α, IL­1ß, IL­6, IL­10, IL­12 and IL­17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration­dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)­κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti­arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF­κB signaling pathway.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Benzoatos/administração & dosagem , Glucosídeos/administração & dosagem , Janus Quinase 1/genética , Janus Quinase 3/genética , Fator de Transcrição STAT3/genética , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo II/toxicidade , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/genética , Interleucinas/genética , Ratos , Transdução de Sinais , Sinoviócitos/efeitos dos fármacos , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/genética
12.
Part Fibre Toxicol ; 16(1): 6, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683122

RESUMO

BACKGROUND: Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain. The exact relationship between increased airborne toxicant exposure and neurological deterioration in the human central nervous system, is still unclear. However, the nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred. METHOD: Computational fluid-particle dynamics modeling of inhaled nanoparticles (1 to 100 nm) under low to moderate breathing conditions (5 to 14 L/min - human; and 0.14 to 0.40 L/min - rat) were performed in physiologically realistic human and rat nasal airways. The simulation emphasized olfactory deposition, and variations in airflow and particle flux caused by the inter-species airway geometry differences. Empirical equations were developed to predict regional deposition rates of inhaled nanoparticles on human and rat olfactory mucosa in sedentary breathing. Considering, breathing and geometric differences, quantified correlations between human and the rat olfactory deposition dose against a variety of metrics were proposed. RESULTS: Regional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition (< 3.5 and 8.1%) occurring for high diffusivity particles of 1.5 nm and 5 nm, respectively. Due to significant filtering of extremely small particles (< 2 nm) by abrupt sharp turns at front of the rat nose, only small fractions of the inhaled nanoparticles (in this range) reached rat olfactory than that in human (1.25 to 45%); however, for larger sizes (> 3 nm), significantly higher percentage of the inhaled nanoparticles reached rat nasal olfactory than that in human (2 to 32 folds). Taking into account the physical and geometric features between human and rat, the total deposition rate (#/min) and deposition rate per unit surface area (#/min/mm2) were comparable for particles> 3 nm. However, when body mass was considered, the normalized deposition rate (#/min/kg) in the rat olfactory region exceeded that in the human. Nanoparticles < 1.5 nm were filtered out by rat anterior nasal cavity, and therefore deposition in human olfactory region exceeded that in the rat model. CONCLUSION: Regional deposition dose of inhaled nanoparticles in a human and rat olfactory region was governed by particle size and the breathing rate. Interspecies correlation was determined by combining the effect of deposition dosage, physical\geometric features, and genetic differences. Developed empirical equations provided a tool to quantify inhaled nanoparticle dose in human and rat nasal olfactory regions, which lay the ground work for comprehensive interspecies correlation between the two species. Furthermore, this study contributes to the fields in toxicology, i.e., neurotoxicity evaluation and risk assessment of UFPs, in long-term and low-dose inhalation exposure scenarios.


Assuntos
Exposição por Inalação/análise , Modelos Biológicos , Nanopartículas/metabolismo , Bulbo Olfatório/metabolismo , Mucosa Olfatória/metabolismo , Animais , Biologia Computacional , Relação Dose-Resposta a Droga , Humanos , Tamanho da Partícula , Ratos , Especificidade da Espécie , Distribuição Tecidual
13.
ACS Appl Mater Interfaces ; 11(6): 5701-5713, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30644711

RESUMO

The development of an intelligent biomaterial system that can efficiently accumulate at the tumor site and release a drug in a controlled way is very important for cancer chemotherapy. PEG is widely selected as a hydrophilic shell to acquire prolonged circulation time and enhanced accumulation at the tumor site, but it also restrains the cellular transport and uptake and leads to insufficient therapeutic efficacy. In this work, a PEG-detachable pH-responsive polymer that forms micelles from copolymer cholesterol grafted poly(ethylene glycol) methyl ether- Dlabile-poly(ß-amino ester)- Dlabile-poly(ethylene glycol) methyl ether (MPEG- Dlabile-PAE- g-Chol) is developed to overcome the aforementioned challenges based on pH value changes among normal physiological, extracellular (pHe), and intracellular (pHi) environments. PEGylated doxorubicin (DOX)-loaded polymeric micelles (DOX-PMs) can accumulate at the tumor site via an enhanced permeability and retention effect, and the PEG shell is detachable induced by cleavage of the pHe-labile linker between the PEG segment and the main chain. Meanwhile, the pHi-sensitive poly(ß-amino ester) segment is protonated and has a high positive charge. The detachment of PEG and protonation of PAE facilitate cellular uptake of DOX-PMs by negatively charged tumor cells, along with the escape from endo-/lysosome due to the "proton-sponge" effect. The DOX molecules are controlled release from the carriers at specific pH values. The results demonstrate that DOX-PMs have the capability of showing high therapeutic efficacy and negligible cytotoxicity compared with free DOX in vitro and in vivo. Overall, we anticipate that this PEG-detachable and tumor-acidity-responsive polymeric micelle can mediate effective and biocompatible drug delivery "on demand" with clinical application potential.


Assuntos
Portadores de Fármacos/química , Micelas , Polietilenoglicóis/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Preparações de Ação Retardada , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Distribuição Tecidual
14.
Biomed Res Int ; 2018: 1460835, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30539002

RESUMO

Lynch syndrome is a genetically and clinically heterogeneous disorder; it is caused by a germline mutation in DNA mismatch repair (MMR) genes. Individuals with a heterozygous mutation in MLH1 have an increased risk for developing colorectal cancer. Here we described a 5-generation Chinese Lynch syndrome family with different severity and onset age. A novel heterozygous germline mutation (c.3G>T, p.Met1Ile) in MLH1 gene was discovered by next generation sequencing. Our study also revealed by qPCR that the MLH1 mRNA expression in peripheral blood of patients in this family was remarkably lower than that of the unaffected carriers and non-carriers. The research results indicated that the mRNA expression level may provide predictive suggestions of treatment and management for carriers with the initiation codon mutation of MLH1 in this family. Further studies are undertaken in this family as well as other families with Lynch syndrome to interrogate the exact reasons affecting the MLH1 mRNA expression level and whether mRNA expression in peripheral blood could be a significant factor for early diagnosis and surveillance of Lynch syndrome.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Códon de Iniciação/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Proteína 1 Homóloga a MutL/genética , Mutação/genética , Adulto , Idade de Início , Sequência de Bases , Neoplasias Colorretais Hereditárias sem Polipose/genética , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/metabolismo , Linhagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
J Cell Physiol ; 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30387131

RESUMO

Dysfunction of the intestinal barrier function occurs in hepatic injury, but the specific mechanisms responsible are largely unknown. Recently, NOD-like receptor 3 (NLRP3) inflammasome functions in impairing endothelial barrier function. In this study, we test the hypothesis that TXNIP-NLRP3 axis repression prevents against intestinal barrier function disruption in nonalcoholic steatohepatitis (NASH). First, lipopolysaccharide (LPS)-induced alterations in expression of ZO-1 and occludin, myeloperoxidase (MPO) activity, reactive oxygen species (ROS) level, and transepithelial electric resistance (TEER) in intestinal epithelial cells (IECs) isolated from C57BL/6 wild-type (WT) and TXNIP-/- mice were evaluated. The underlying regulatory mechanisms of TXNIP knockout in vivo were investigated with the detection of expressions of TXNIP, NLRP3 and ZO-1, and occludin, the interaction of TXNIP-NLRP3, MPO activity, ROS level, permeability of intestinal mucosa, levels of inflammatory factors in serum, and LPS concentration. We identified that TXNIP knockout promoted ZO-1 and occludin expression, yet reduced MPO activity, ROS level, and cell permeability in IECs, indicating restored the intestinal barrier function. However, LPS upregulated TXNIP and NLRP3 expression, as well as contributed to the interaction between TXNIP and NLRP3 in vitro. Furthermore, TXNIP was significantly upregulated in the intestinal mucosa of NASH mice and its knockout repaired the intestinal barrier disrupt, inhibited expression of inflammatory factors, and reduced LPS concentration as well as hepatic injury in vivo. Taken together, our findings demonstrated that inhibited the activation of the TXNIP-NLRP3 axis reduced MPO activity and oxidative stress and thus restoring the intestinal barrier function in NASH. TXNIP-NLRP3 axis may be a promising therapeutic strategy for the NASH treatment.

16.
Plant Cell Rep ; 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30302553

RESUMO

KEY MESSAGE: The structural differences of MYB14 promoter in two grapevine genotypes affect the expression of MYB14 and stilbene synthesis in response to Al3+ and UV-C radiation. Grapevines provide an important fruit crop worldwide, but production is often limited by pathogen infection. Stilbenes, a class of secondary metabolite, represent phytoalexins that contribute to defence against pathogens in many plants, including grapevine. It is known that the transcription factors MYB14 and MYB15 are required for the activation of the promoters of resveratrol synthase to regulate stilbene biosynthesis. In the current study, we observed that stilbene levels were more highly induced by Al3+ and UV-C radiation treatments in the cultivar Vitis labrusca 'Concord' than in the cultivar V. vinifera 'Cabernet Sauvignon'. We investigated whether genetic/structural variations in the MYB14 and MYB15 promoters between these two representative genotypes are responsible for the differences in stilbene accumulation. Significant differences in the structure and activity of the promoter of MYB14, but not MYB15 were identified between the two genotypes, following heterologous expression in Nicotiana benthamiana system and treatments with Al3+ and UV-C. Hydrogen peroxide (H2O2) was detected in Concord soon after the stress treatments, but after diphenyleneiodonium chloride pre-treatment, the expressing level of VlMYB14, the promoter activity of VlMYB14 and the accumulation of stilbenes was significantly reduced. A model is presented where the induction of MYB14 contributes to stilbene accumulation in Concord following Al3+ and UV-C treatments involving reactive oxygen species (ROS) production as an early signal.

17.
Emerg Infect Dis ; 24(10): 1795-1805, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30226157

RESUMO

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.

18.
J Dig Dis ; 19(5): 301-313, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29696816

RESUMO

OBJECTIVE: To explore the effects of mothers against decapentaplegic homolog family member 4 (Smad4) deletion on inflammation and fibrogenesis in nonalcoholic steatohepatitis (NASH). METHODS: Biopsied liver samples from NASH patients and normal liver tissue samples from patients who had received liver resection for trauma were collected. Smad4Co/Co and wild-type (WT) mice were used to construct the NASH model using a high-fat diet (HFD) or methionine- and choline-deficient diet (MCD). HE staining and TUNEL assay were used to observe the pathological changes and cell apoptosis, respectively. Quantitative real-time polymerase chain reaction was used to detect the expression of inflammatory, fibrogenesis and apoptosis-related genes, and immunohistochemistry to determine the protein expression of SMAD4, MCP-1 and α-SMA. RESULTS: SMAD4 protein expression significantly increased in NASH patients than in the control group. Compared with WT mice, HFD- and MCD-fed Smad4Co/Co mice showed decreased hepatic steatosis, inflammation, liver cell apoptosis and nonalcoholic fatty liver activity score, reduced plasma glucose, triglyceride, free fatty acids, alanine aminotransferase and aspartate aminotransferase levels but increased adiponectin. Moreover, Smad4Co/Co decreased the expression of inflammatory markers (TNF-α, MCP-1, IFN-γ), fibrogenetic markers (COL1A1, α-SMA and TGF-ß1), lipogenic (Srebp1c, Fas and Acc) and proapoptotic genes (Bax and caspase-3), but increased the expression of ß-oxidation (Ppar-α, Cpt1 and Aco) and antiapoptotic genes (Bcl-2). CONCLUSION: Smad4 deletion may inhibit lipogenesis, stimulate ß-oxidation, improve lipid metabolism and liver function, alleviate inflammation and fibrosis, and reduce cell apoptosis in NASH.


Assuntos
Hepatite/etiologia , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Proteína Smad4/metabolismo , Proteína Smad4/fisiologia , Adolescente , Adulto , Animais , Apoptose , Feminino , Humanos , Metabolismo dos Lipídeos , Fígado/patologia , Modelos Logísticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína Smad4/genética , Adulto Jovem
19.
J Biomed Nanotechnol ; 14(3): 564-574, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29663928

RESUMO

Silver-containing dressings are widely used for wound care owing to their broad-spectrum microbicidal activity. However, the potential adverse effects on human health emerging from exposure to their active ingredients (silver ions or nanoparticles) have resulted in widespread concerns about their use. The release profiles of various chemical forms of silver (Ag) from silver-containing dressing are closely related to their bioavailability and potential adverse effects on the body. In this research, we demonstrated a tiered experimental approach for systematic characterization and assessment of silver-containing wound dressing, which provides information for risk assessments. The combination of scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray, X-ray photoelectron spectroscopy, and X-ray diffraction allowed for systematic characterization of silver-containing dressings including their morphology, size, composition, valence state, and crystal forms, which have a close relationship with their silver release profile, antimicrobial activity, and potential toxicity. We developed an Ag release experiment using a reciprocating holder method and an ultrafiltration membrane column to separate the silver nanoparticles (AgNPs) and silver ions released from the dressing. Furthermore, by adjusting the Ag-ion concentration in the release media (simulated body fluid) we could effectively eliminate the interference from AgCl particles, which have a similar size to the AgNPs. We used our method to analyze the release profiles and the chemical form of the Ag present in three commercial silver-containing dressings. A large variation in the total Ag content, amount of released Ag-ions, and amount of released AgNPs was observed in the three dressings that were tested. The silver release profiles were highly dependent on the crystal structures, surface coating process, and binding modes. The cytotoxicity assays were consistent with the characterization data. This tiered approach provides valuable information of optimized AgNPs usage and proper manufacturing process for further safe applications. This study establishes a systematic characterization methodology for better understanding of risk assessment of nano-embeded consumer products.

20.
Anal Bioanal Chem ; 410(24): 6051-6066, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29550875

RESUMO

Nanomaterials (NMs) are widely used in various areas because of their unique and useful physicochemical properties. However, they may pose toxicity risks to human health after exposure. Applicable and reliable approaches are needed for risk assessment of NMs. Herein, an intelligent analytical strategy for safety assessment of NMs is proposed that focuses on toxicity assessment using an in vitro cell model. The toxicity assessment by testing on the adverse outcome pathway in a cell culture system was defined by application of a tiered testing approach. To provide an overview of the applicable approach for risk assessment of NMs, we discuss the most commonly used techniques and analytical methods, including computational toxicology methods in dosimetry assessment, high-throughput screening for toxicity testing with high efficiency, and omics-based toxicology assessment methods. The final section focuses on the route map for an integrated approach to a testing and assessment strategy on how to extrapolate the in vitro NM toxicity testing data to in vivo risk assessment of NMs. The intelligent analytical strategy, having evolved step-by-step, could contribute to better applications for safety evaluation and risk assessment of NMs in reality.


Assuntos
Nanoestruturas/toxicidade , Testes de Toxicidade/métodos , Animais , Transformação Celular Neoplásica/induzido quimicamente , Biologia Computacional/métodos , Humanos , Nanoestruturas/química , Medição de Risco , Transdução de Sinais/efeitos dos fármacos
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