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1.
Acta Pharmacol Sin ; 45(4): 831-843, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38052867

RESUMO

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a refractory inflammatory disease with epithelial-mesenchymal transition (EMT) as one of the key features. Since ubiquitin modification has been shown to regulate the EMT process in other diseases, targeting ubiquitin ligases may be a potential strategy for the treatment of CRSwNP. In this study we investigated whether certain E3 ubiquitin ligases could regulate the EMT process in CRSwNP, and whether these regulations could be the potential drug targets as well as the underlying mechanisms. After screening the potential drug target by bioinformatic analyses, the expression levels of three potential E3 ubiquitin ligases were compared among the control, eosinophilic nasal polyp (ENP) and non-eosinophilic nasal polyp (NENP) group in clinical samples, and the significant decrement of the expression level of NEDD4L was found. Then, IP-MS, bioinformatics and immunohistochemistry studies suggested that low NEDD4L expression may be associated with the EMT process. In human nasal epithelial cells (hNECs) and human nasal epithelial cell line RPMI 2650, knockdown of NEDD4L promoted EMT, while upregulating NEDD4L reversed this effect, suggesting that NEDD4L inhibited EMT in nasal epithelial cells. IP-MS and Co-IP studies revealed that NEDD4L mediated the degradation of DDR1. We demonstrated that NEDD4L inhibited the ß-catenin/HIF-1α positive feedback loop either directly (degrading ß-catenin and HIF-1α) or indirectly (mediating DDR1 degradation). These results were confirmed in a murine NP model in vivo. This study for the first time reveals the regulatory role of ubiquitin in the EMT process of nasal epithelial cells, and identifies a novel drug target NEDD4L, which has promising efficacy against both ENP and NENP by suppressing ß-catenin/HIF-1α positive feedback loop.


Assuntos
Transição Epitelial-Mesenquimal , Terapia de Alvo Molecular , Pólipos Nasais , Ubiquitina-Proteína Ligases Nedd4 , Rinossinusite , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Doença Crônica , Retroalimentação , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/enzimologia , Rinossinusite/tratamento farmacológico , Rinossinusite/enzimologia , Ubiquitinas/metabolismo , Ubiquitina-Proteína Ligases Nedd4/antagonistas & inibidores , Ubiquitina-Proteína Ligases Nedd4/metabolismo
2.
J Asian Nat Prod Res ; 26(8): 900-909, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38753580

RESUMO

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.


Assuntos
Autofagia , Diterpenos , Euphorbia , Euphorbia/química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Autofagia/efeitos dos fármacos , Estrutura Molecular , Humanos
3.
Artigo em Inglês | MEDLINE | ID: mdl-36790415

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have been recognized as a potential health risk and are widespread in nature due to their intrinsic chemical stability and high recalcitrance to degradation. A taxonomic study was carried out on strain P9T, which was isolated from a PAH-degrading consortium, enriched from the mangrove sediment from Zhangzhou, PR China. The isolate was chemoheterotrophic, aerobic, Gram-stain-negative, short-rod shaped, and motile by one polar flagellum. Growth was observed at salinities from 0.5-6.0 % (optimum, 3 %), at pH 4-9 (optimum, pH 7) and at 10-41 °C (optimum, 25-30 °C). It did not synthesize bacteriochlorophyll a. Catalase and oxidase activities were positive. Acid was produced from starch, amygdalin, arbutin, cellobiose, d-fructose, maltose, d-mannitol, melezitose, melibiose, raffinose, d-ribose, sucrose, trehalose, d-xylose, aesculin ferric citrate, gentiobiose, glycogen, l-arabinose, l-rhamnose, methyl α-d-glucopyranoside, methyl ß-d-xylopyranoside, N-acetylglucosamine and salicin, and weakly positive for d-arabitol, d-galactose, lactose, turanose and glycerol. Phylogenetic analysis revealed that strain P9T fell within the clade comprising the type strains of Salipiger species and formed an independent cluster with Salipiger profundus, which was distinct from other members of the family Rhodobacteraceae. The 16S rRNA gene sequence comparisons showed that strain P9T was most closely related to Salipiger bermudensis HTCC 260T (96.7 %), and other species of the genus Salipiger (95.7-94.2 %). Strain P9T had the highest digital DNA-DNA hybridization value with S. profundus CGMCC 1.12377T (25.0 %) and the highest average nucleotide identity (ANIb and ANIm) values with S. profundus CGMCC 1.12377T(80.3 and 85.8 %, respectively). The sole respiratory quinone was quinone 10. The dominant fatty acids were C18 : 1 ω7c (61.4 %), C16 : 0 (17.5 %) and C19 : 0 ω8c cyclo (7.6 %). The G+C content of the chromosomal DNA was 65.8 mol%. In the polar lipid profile, phospholipid, phosphatidylglycerol, aminolipid, glycolipid and phosphatidylethanolamine were the major compounds. Based on the phenotypic and phylogenetic data, strain P9T represents a novel species of the genus Salipiger, for which the name Salipiger pentaromativorans sp. nov. is proposed. The type strain is P9T (=CCTCC AB 209290T=LMG 25701T=MCCC 1F01055T).


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Rhodobacteraceae , Ácidos Graxos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Composição de Bases , Análise de Sequência de DNA , Fosfolipídeos/química , Quinonas
4.
Environ Sci Technol ; 57(44): 16940-16952, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37886817

RESUMO

Harnessing the potential of specific antibiotic-degrading microalgal strains to optimize microalgal-bacterial granular sludge (MBGS) technology for sustainable antibiotic wastewater treatment and antibiotic resistance genes (ARGs) mitigation is currently limited. This article examined the performance of bacterial granular sludge (BGS) and MBGS (of Haematococcus pluvialis, an antibiotic-degrading microalga) systems in terms of stability, nutrient and antibiotic removal, and fate of ARGs and mobile genetic elements (MGEs) under multiclass antibiotic loads. The systems exhibited excellent performance under none and 50 µg/L mixed antibiotics and a decrease in performance at a higher concentration. The MBGS showed superior potential, higher nutrient removal, 53.9 mg/L/day higher chemical oxygen demand (COD) removal, and 5.2-8.2% improved antibiotic removal, notably for refractory antibiotics, and the system removal capacity was predicted. Metagenomic analysis revealed lower levels of ARGs and MGEs in effluent and biomass of MBGS compared to the BGS bioreactor. Particle association niche and projection pursuit regression models indicated that microalgae in MBGS may limit gene transfers among biomass and effluent, impeding ARG dissemination. Moreover, a discrepancy was found in the bacterial antibiotic-degrading biomarkers of BGS and MBGS systems due to the microalgal effect on the microcommunity. Altogether, these findings deepened our understanding of the microalgae's value in the MBGS system for antibiotic remediation and ARG propagation control.


Assuntos
Antibacterianos , Microalgas , Antibacterianos/farmacologia , Águas Residuárias , Esgotos/microbiologia , Genes Bacterianos , Bactérias/genética , Resistência Microbiana a Medicamentos/genética
5.
Ecotoxicol Environ Saf ; 267: 115616, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37871386

RESUMO

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.


Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Gravidez , Feminino , Humanos , Teorema de Bayes , Estudos Transversais , Líquido Folicular , Interleucina-6 , Fertilização in vitro
6.
Eur Arch Otorhinolaryngol ; 280(8): 3707-3720, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36939907

RESUMO

OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/diagnóstico , Rinite/metabolismo , Proteína Catiônica de Eosinófilo/metabolismo , Peroxidase , Doença Crônica , Sinusite/diagnóstico , Sinusite/metabolismo , Biomarcadores , Pólipos Nasais/diagnóstico , Pólipos Nasais/metabolismo
7.
Molecules ; 28(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36985591

RESUMO

Continuously growing demand for natural products with pharmacological activities has promoted the development of microbial transformation techniques, thereby facilitating the efficient production of natural products and the mining of new active compounds. Furthermore, due to the shortcomings and defects of microbial transformation, it is an important scientific issue of social and economic value to improve and optimize microbial transformation technology in increasing the yield and activity of transformed products. In this review, the aspects regarding the optimization of fermentation and the cross-disciplinary strategy, leading to the microbial transformation of increased levels of the high-efficiency process from natural products of a plant or microbial origin, were discussed. Additionally, due to the increasing craving for targeted and efficient methods for detecting transformed metabolites, analytical methods based on multiomics were also discussed. Such strategies can be well exploited and applied to the production of more efficient and more natural products from microbial resources.


Assuntos
Produtos Biológicos , Produtos Biológicos/metabolismo , Fermentação , Biotransformação , Tecnologia
9.
J Asian Nat Prod Res ; 24(7): 685-690, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34308707

RESUMO

A new aurone glycoside named licoagroaurone 6-O-α-ʟ-arabinopyranoside (1), together with six known compounds (2-7), was isolated from EtOAc-soluble extract of the aerial parts of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their inhibitory activities against α-glucosidase in vitro. Among them, compounds 1 and 6 showed significant inhibitory activities on α-glucosidase with the IC50 values of 47.1 and 57.7 µM, respectively.


Assuntos
Saussurea , Inibidores de Glicosídeo Hidrolases/farmacologia , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Saussurea/química , alfa-Glucosidases
10.
Hemoglobin ; 46(4): 245-248, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36210651

RESUMO

ß-Thalassemia (ß-thal), a highly prevalent disease in tropical and subtropical regions of Southern China, is caused mainly by point mutations in the ß-globin gene cluster. However, large deletions have also been found to contribute to some types of ß-thal. We identified a novel 5 kb deletion in the ß-globin cluster in a Chinese patient using multiplex ligation-dependent probe amplification (MLPA), and characterized it with single molecule real-time (SMRT) sequencing, gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. The deletion was located between positions 5226189 and 5231091 on chromosome 11 (GRCh38), extending from 4 kb upstream of the 5' untranslated region (5'UTR) to the second intron of the ß-globin gene. The patient with this deletion presented with microcytosis and hypochromic red cells, as well as relatively high Hb F and Hb A2 levels. Our research indicated that SMRT sequencing is a useful tool for accurate detection of large deletions. Our study broadens the spectrum of deletional ß-thalassemias and provides a perspective for further study of the function of the ß-globin cluster.


Assuntos
Globinas beta , Talassemia beta , Humanos , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Deleção de Genes , Família Multigênica , Reação em Cadeia da Polimerase Multiplex , Deleção de Sequência
11.
Molecules ; 27(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36500382

RESUMO

Baijiu is a unique and traditional distilled liquor in China. Flavor plays a crucial rule in baijiu. Up to now, the research on the flavor of baijiu has progressed from the identification of volatile compounds to the research on key aroma compounds, but the release mechanism of these characteristic compounds is still unclear. Meanwhile, volatile compounds account for only a tiny fraction, whereas ethanol and water account for more than 98% of the content in baijiu. By summarizing the ethanol-water hydrogen bond structure in different alcoholic beverages, it was found that flavor compounds can affect the association strength of the ethanol-water hydrogen bond, and ethanol-water can also affect the interface distribution of flavor compounds. Therefore, the research on ethanol-water microstructure in baijiu is helpful to realize the simple visualization of adulteration detection, aging determination and flavor release mechanism analysis of baijiu, and further uncover the mystery of baijiu.


Assuntos
Etanol , Odorantes , Etanol/análise , Odorantes/análise , Água/análise , Bebidas Alcoólicas/análise , China
12.
Inorg Chem ; 60(9): 6576-6584, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33890781

RESUMO

The two acentric aluminoborates (ABOs) [M(dap)3]2{Al[B5O7(OH)3][B5O8(OH)2][B6O9(OH)2]} (M and dap represent Co(1)/Ni(2) and 1,2-diaminopropane, respectively) templated by chiral metal complexes (CMCs) have been solvothermally synthesized. The isostructural 1 and 2 crystallize in the chiral space group P21. Both feature unprecedented 2D wavelike layers built by three kinds of oxoboron (B-O) clusters ([B5O7(OH)3]2-, [B5O8(OH)2]3-, and [B6O9(OH)2]2-) and AlO4 tetrahedra. In the frameworks of 1 and 2, AlO4 and [B6O9(OH)2]2- units are strictly alternating into 1D chains. Further, [B5O8(OH)2]3- clusters link adjacent chains to form 2D wavelike layers. In addition, the [B5O7(OH)3]2- units as the hanging clusters are supported on two sides of the wavelike layers through AlO4 groups, resulting in the first example of a wavelike layer ABO composed of three kinds of B-O clusters and four types of channels. 1 and 2 display second-harmonic generation (SHG) signals about ∼1.3 and ∼0.93 times that of KH2PO4 (KDP) and belong to the class of wide-band-gap semiconductors.

13.
Inorg Chem ; 60(23): 18283-18290, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34797632

RESUMO

Four inorganic-organic hybrid borates, K[B6O9(OH)(en)]·H2O (1, en = ethylenediamine), K[B6O9(OH)(1,3-dap)]·H2O (2, 1,3-dap = 1,3-diaminopropane), K[B6O9(OH)(1,6-dah)0.5]·H2O (3, 1,6-dah = 1,6-diaminlhexane) and [(1,3-dap)Cd@B5O8(OH)]·0.5H2O (4), were made under solvothermal conditions. 1 and 2 are isostructural and feature a 2D layer built by B6O9(OH) clusters and modified by en and 1,3-dap via B-N-C linkages. By replacing en and 1,3-dap with longer and more flexible 1,6-dah, a new type of oxoboron cluster organic framework 3 was obtained, which was composed of the same B6O9(OH) cluster layers as in 1 and 2 and 1,6-dah linkers. By replacing alkali metal K with transition metal Cd under similar synthetic conditions, another type of oxoboron cluster organic framework 4 was made in which the Cd-centered wheel cluster layers and 1,3-dap linkers were connected via Cd-N-C linkages.

14.
Nanotechnology ; 32(24)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33706293

RESUMO

Recently, the experimentally synthesized Nb2SiTe4was found to be a stable layered narrow-gap semiconductor, and the fabricated field-effect transistors (FETs) based on few-layers Nb2SiTe4are good candidates for ambipolar devices and mid-infrared detection (Zhaoet al2019ACS Nano1310705-10). Here, we use first-principles combined with Boltzmann transport theory and non-equilibrium Green's function method to investigate the thermoelectric transport coefficients of monolayer Nb2XTe4(X = Si, Ge) and the gate voltage effect on the thermoelectric performance of the FET based on monolayer Nb2SiTe4. It is found that both monolayers have largep-type Seebeck coefficients due to the 'pudding-mold-type' valence band structure, and they both exhibit anisotropic thermoelectric behavior with optimal thermoelectric figure of merit of 1.4 (2.2) at 300 K and 2.8 (2.5) at 500 K for Nb2SiTe4(Nb2GeTe4). The gate voltage can effectively increase the thermoelectric performance for the Nb2SiTe4-based FET. The high thermoelectric figure of merit can be maintained in a wide temperature range under a negative gate voltage. Furthermore, the FET exhibits a good gate-tunable Seebeck diode effect. The present work suggests that Nb2XTe4monolayers are promising candidates for 2D thermoelectric materials and thermoelectric devices.

15.
Planta Med ; 87(3): 225-235, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33348408

RESUMO

Four new ß-resorcylic acid lactones, including penochrochlactone A (2: ), 4-O-desmethyl-aigialomycin B (4: ), and penochrochlactones C and D (5: and 6: ), two compounds isolated from a natural source for the first time, 5α, 6ß-acetonide-aigialomycin B (1: ) and penochrochlactone B (3: ), together with six known compounds, aigialomycin F (7: ), aigialomycins A, B, and D (8: -10: ), zeaenol (11: ), and oxozeaenol (12: ), were isolated from a mycelial solid culture of the endophytic fungus Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia by sequential purification over silica gel, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and chemical conversions. In addition, all the new compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Penochrochlactone C (5: ) displayed moderate cytotoxicity against the HeLa tumor cell line with an IC50 value of 9.70 µM. In the antibacterial assays, compounds 4:  - 6: exhibited moderate activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa with MIC values between 9.7 and 32.0 µg/mL.


Assuntos
Kadsura , Penicillium , Antibacterianos/farmacologia , Lactonas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular
16.
J Craniofac Surg ; 32(1): 313-316, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33156166

RESUMO

INTRODUCTION: Central retinal artery occlusion (CRAO), an ocular stroke, causes severe and permanent visual impairment. Thrombolytic therapy is currently the main treatment option for CRAO. Intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) has been extensively applied in the treatment of CRAO with the proven advantages of effectiveness and safety. This meta-analysis aimed to assess the efficacy of intravenous rt-PA thrombolysis for the management of CRAO by evaluating the pooled evidence. METHODS: A comprehensive literature search of electronic databases including PubMed, OVID, and Cochrane Library was conducted up to and including March 2019. All studies reporting visual outcomes after CRAO with thrombolytic therapy were collected. Data on visual acuity and adverse events were recorded and assessed in this analysis. Data were inputted into the statistical software of STATA. The studies were weighed by the inverse of the variance and merged in a random-effects model. RESULTS: The systematic review process yielded 7 eligible studies including 121 patients with CRAO who received the intravenous rt-PA treatment. Sixty-two patients showed improvement in visual acuity (52.0%; 95% CI, 34.0%-70.0%) following rt-PA intravenous thrombolytic therapy. The observed improvement rate in the intravenous rt-PA treatment group was significantly higher than the conservative treatment group (40.4% vs. 13.0%; OR = 5.16; 95% CI, 1.90-14.05). The incidence rate of complications was relatively low (11 out of the 121 patients). Hemorrhage (9/11) was the major reported complication. Mortality was zero. DISCUSSION: This meta-analysis indicated that intravenous rt-PA thrombolysis could be an effective and safe strategy for the management of CRAO. However, a more detailed large-scale clinical trial is warranted to strengthen the evidence-based therapeutic guidance.


Assuntos
Oclusão da Artéria Retiniana , Acidente Vascular Cerebral , Fibrinolíticos/uso terapêutico , Humanos , Oclusão da Artéria Retiniana/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico
17.
J Cell Mol Med ; 24(24): 14171-14183, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33124187

RESUMO

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic ß-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in ß-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in ß-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in ß-cells via enhancing cbl-b expression.


Assuntos
Estresse do Retículo Endoplasmático , Células Secretoras de Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica , Peróxido de Hidrogênio/metabolismo , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica , Ubiquitinação
18.
Int J Syst Evol Microbiol ; 70(3): 1822-1829, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048985

RESUMO

Two Gram-stain-negative, aerobic, motile and rod-shaped bacteria, one designated as strain AXBT, capable of degrading estrogens, and another, YL23T, capable of degrading estrogen and bisphenol A, were isolated from activated sludge in Xiamen City, PR China. The optimum temperature and pH of both strains were 25-35 °C and pH 7.0-8.0. While strain AXBT could tolerate 3 % (w/v) NaCl, YL23T could only grow between 0-1 % (w/v) NaCl. They contained ubiquinone-10 as the major quinone, spermidine as the major polyamine, summed feature 8 (comprising C18:1ω6c and/or C18:1ω7c) as the major fatty acids and diphosphatidylglycerol, phosphatidylcholine, phosphatidyldimethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid as the major polar lipids. The DNA G+C contents of strains AXBT and YL23T were 63.6 and 63.7 mol%, respectively. Based on the results of 16S rRNA gene sequence analysis, strains AXBT and YL23T belonged to the genus Sphingobium. Strain AXBT was most closely related to Sphingobium chlorophenolicum NBRC 16172T (97.5 %) and Sphingobium chungbukense DJ77T (97.2 %), and strain YL23T was most closely related to S. chlorophenolicum NBRC 16172T (97.4 %) and S. quisquiliarum P25T (97.1 %). Average nucleotide identity values between these two strains and S. chlorophenolicum NBRC 16172T, S. chungbukense DJ77T, Sphingobium chinhatense IP26T, Sphingobium quisquiliarum P25T and Sphingobium japonicum UT26ST were from 80.7 to 85.8 %. In conclusion, strains AXBT and YL23T represent novel species of the genus Sphingobium, for which the names Sphingobium estronivorans sp. nov. and Sphingobium bisphenolivorans sp. nov. are proposed, respectively. The type strains of S. estronivorans and S. bisphenolivorans are AXBT (=MCCC 1K01232T=DSM 102173T) and YL23T (=MCCC 1K02300T=DSM 102172T), respectively.


Assuntos
Filogenia , Esgotos/microbiologia , Sphingomonadaceae/classificação , Águas Residuárias/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espermidina/química , Sphingomonadaceae/isolamento & purificação , Ubiquinona/análogos & derivados , Ubiquinona/química
19.
Support Care Cancer ; 28(8): 3533-3542, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32090284

RESUMO

PURPOSE: Sarcopenia is increasingly recognized as an independent risk factor for poor outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT), and it is a potentially modifiable factor. The purpose of the present systematic review and meta-analysis is to summarize and integrate current evidence in this field. METHODS: We searched EMBASE, MEDLINE, and Cochrane DSR through Ovid and PubMed websites to identify relevant studies. Studies evaluated sarcopenia before HSCT and reported associations between sarcopenia and post-transplant outcomes were included. Two authors independently applied eligibility criteria, assessed quality, and extracted data. Odds ratio (OR) and their 95% confidence intervals (CIs) were pooled to examine the association between sarcopenia and post-transplant outcomes by using the review manager 5.3 software. RESULTS: Seven retrospective cohort studies met our inclusion criteria. The overall quality of studies was low to moderate. Sarcopenia was associated with higher non-relapse mortality [odds ratio (OR) 1.97; 95% CI 1.45, 2.68; P < 0.0001; I2 = 0%] and shorter overall survival [odds ratio (OR) 0.44; 95% CI 0.26, 0.75; P = 0.002; I2 = 65%] in patients undergoing HSCT. CONCLUSIONS: Clinicians could use sarcopenia to balance the risks and benefits of transplantation as early as possible; in addition, interventions can be used to prevent sarcopenia and improve physical function and quality of life. Well-designed, prospective, and large-scale clinical studies are needed to consolidate the evidence.


Assuntos
Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Sarcopenia/patologia , Sobreviventes de Câncer , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Clin Lab ; 66(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33073959

RESUMO

BACKGROUND: Lung cancer is the most prevalent and deadliest cancer worldwide. The present study aims to determine the prognosis value of low expression long non-coding RNAs (lncRNAs) in LUAD. METHODS: RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) data-base. Dysregulated genes between LUAD and paracancerous tissue were screened by GeneSpringGX. Prognostic lncRNAs which were low expressed in LUAD were filtrated by Ualcan, then further verified through the TCGA database. The association between clinicopathological features and the expression level of these lncRNAs was tested by chi-square test. Cox regression analysis was performed to test independent prognosis risk factors. Diagnostic efficiency was predicted by receiver operating characteristic (ROC) analysis. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore potential functions of these prognostic signatures. RESULTS: Nine prognostic lncRNAs (LINC00092, LINC00908, WWC2-AS2, RPL13AP17, CHIAP2, SFTA1P, SIGLEC17P, CYP2B7P1, CYP4Z2P) were screened out through Ualcan and further verified by TCGA. Among them, six lncRNAs (RPL13AP17, CHIAP2, SFTA1P, SIGLEC17P, CYP2B7P1, CYP4Z2P) were pseudogene transcripts. Multivariate Cox regression analysis showed that three lnRNAs (LINC00908, WWC2-AS2 CYP2B7P) were independent prognostic risk factors for OS and two lncRNAs (WWC2-AS2, SIGLEC17P) were independent prognostic risk factors for RFS in LUAD patients. Meanwhile, they showed powerful diagnostic value by ROC curve analysis. GO analysis revealed correlation genes of prognostic signatures were mainly enriched in plasma membrane, plasma membrane part, purine nucleotide binding, cytoskeleton and ribonucleotide binding and KEGG pathway analysis showed mainly enriched in cell adhesion molecules. CONCLUSIONS: The results illuminated that four lncRNAs (LINC00908, WWC2-AS2, CYP2B7P, SIGLEC17P) may be a powerful diagnostic and prognostic assessment tool for human LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , RNA Longo não Codificante , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Prognóstico , RNA Longo não Codificante/genética
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