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1.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35012978

RESUMO

Preventing pathogenic viral and bacterial transmission in the human environment is critical, especially in potential outbreaks that may be caused by the release of ancient bacteria currently trapped in the permafrost. Existing commercial disinfectants present issues such as a high carbon footprint. This study proposes a sustainable alternative, a bioliquid derived from biomass prepared by hydrothermal liquefaction. Results indicate a high inactivation rate of pathogenic virus and bacteria by the as-prepared bioliquid, such as up to 99.99% for H1N1, H5N1, H7N9 influenza A virus, and Bacillus subtilis var. niger spores and 99.49% for Bacillus anthracis Inactivation of Escherichia coli and Staphylococcus epidermidis confirmed that low-molecular-weight and low-polarity compounds in bioliquid are potential antibacterial components. High temperatures promoted the production of antibacterial substances via depolymerization and dehydration reactions. Moreover, bioliquid was innoxious as confirmed by the rabbit skin test, and the cost per kilogram of the bioliquid was $0.04427, which is notably lower than that of commercial disinfectants. This study demonstrates the potential of biomass to support our biosafety with greater environmental sustainability.


Assuntos
Biomassa , Contenção de Riscos Biológicos , Meio Ambiente , Energia Renovável , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Humanos , Testes de Sensibilidade Microbiana , Peso Molecular , Pandemias , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/ultraestrutura
2.
Lett Appl Microbiol ; 76(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36977573

RESUMO

In this research, we evaluated the effect of exogenous lactic acid bacteria and Amomum villosum essential oil (AVEO) on the chemical composition, microbial community composition, microbial functional diversity, and fermentation quality of Broussonetia papyrifera (BP) and Pennisetum sinese (PS) mixed silages. The BP:PS mixing ratios were 100:0, 70:30, 50:50, 30:70, and 0:100. After 3 and 30 days of ensiling at 22°C-25°C, microbial diversity and function, and fermentation quality, were assessed. Increasing PS content resulted in decreased ammoniacal nitrogen and pH, increased water-soluble carbohydrate content, increased relative abundance of Lactococcus and Acinetobacter, and reduced relative abundance of Caproiciproducens and Pseudomonas. A 50:50 BP:PS ratio effectively improved the fermentation quality compared to anaerobic fermentation with BP or PS alone, while AVEO treatment further improved fermentation quality by increasing Lactococcus relative abundance. Moreover, as fermentation proceeded, ensiling enhanced the 'Human diseases', 'Environmental information processing', and 'Cellular processes' functions at the first level, as well as the 'Two-component system' and 'ABC transporters' functions at the third level. Different additives affected the fermentation of BP and PS mixed silage by regulating microbial community succession and metabolic pathways during ensiling.


Assuntos
Broussonetia , Lactobacillales , Pennisetum , Zingiberaceae , Humanos , Fermentação , Pennisetum/microbiologia , Silagem/microbiologia
3.
Pharmacol Res ; 178: 106188, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35338002

RESUMO

Hyperbilirubinemia is a serious hazard to human health due to its neurotoxicity and lethality. So far, successful therapy for hyperbilirubinemia with fewer side effects is still lacking. In this study, we aimed to clarify the effects of oridonin (Ori), an active diterpenoid extracted from Rabdosia rubescens, on hyperbilirubinemia and revealed the underlying molecular mechanism in vivo and in vitro. Here, we showed that liver X receptor alpha (LXRα) deletion eliminated the protective effect of Ori on phenylhydrazine hydrochloride-induced hyperbilirubinemia mice, indicating that LXRα acted as a key target for Ori treatment of hyperbilirubinemia. Ori significantly increased the expression of LXRα and UDP-glucuronosyltransferase 1A1 (UGT1A1) in the liver of wild-type (WT) mice, which were lost in LXRα-/- mice. Ori or LXR agonist GW3965 also reduced lipopolysaccharide/D-galactosamine-induced hyperbilirubinemia via activating LXRα/UGT1A1 in WT mice. Liver UGT1A1 enzyme activity was elevated by Ori or GW3965 in WT mice. Further, Ori up-regulated LXRα gene expression, increased its nuclear translocation and stimulated UGT1A1 promoter activity in HepG2 cells. After silencing LXRα by siRNA, Ori-induced UGT1A1 expression was markedly reduced in HepG2 cells and primary mouse hepatocytes. Taken together, Ori stimulated the transcriptional activity of LXRα, resulting in the up-regulation of UGT1A1. Therefore, Ori or its analogs might have the potential to treat hyperbilirubinemia-related diseases through modulating LXRα-UGT1A1 signaling.


Assuntos
Bilirrubina , Hiperbilirrubinemia , Animais , Diterpenos do Tipo Caurano , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/tratamento farmacológico , Hiperbilirrubinemia/genética , Receptores X do Fígado , Camundongos
4.
BJOG ; 129 Suppl 2: 32-39, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36485070

RESUMO

OBJECTIVE: To investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer. DESIGN: A treatment-free survival (TFS) analysis. SETTING: Five-centre trial. POPULATION: An extended follow-up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut-off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB). METHODS: Overall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality-adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality-adjusted OS = ut  × T + TFS + urel  × REL. MAIN OUTCOME MEASURES: The area under each Kaplan-Meier curve was estimated using the 96-month restricted mean time, with threshold utility analyses used to illustrate quality-adjusted OS comparisons. RESULTS: In the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively (p = 0.005), with a significant quality-adjusted OS gain (13.2-16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS (p = 0.268) or quality-adjusted OS (range: 1.4-6.3 months). CONCLUSIONS: Both TFS and quality-adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Infusões Intravenosas , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Análise de Sobrevida
5.
Drug Dev Res ; 82(4): 575-580, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33377532

RESUMO

Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti-inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d-GalN (400 mg/kg) and LPS (40 µg/kg). The levels of inflammatory factors were measured by RT-PCR, Western blot, and enzyme-linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d-GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase-1, IL-18, and IL-1ß. This study showed that oridonin has a protective effect on d-GalN/LPS-induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Galactosamina , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Chem Res Toxicol ; 33(7): 1798-1808, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32538071

RESUMO

Emodin is the main toxic component in Chinese medicinal herbs such as rhubarb. Our previous studies demonstrated that genetic polymorphisms of UDP-glucuronosyltransferase 2B7 (UGT2B7) had an effect on the glucuronidation and detoxification of emodin. This study aimed to reveal the transcriptional regulation mechanism of UGT2B7 on emodin glucuronidation and its effect on toxicity. Emodin glucuronic activity and genome and transcriptome data were obtained from 36 clinical human kidney tissues. The genome-wide association studies (GWAS) identified that four single nucleotide polymorphisms (SNPs) (rs6093966, rs2868094, rs2071197, and rs6073433), which were located on the hepatocyte nuclear factor 4α (HNF4A) gene, were significantly associated with the emodin glucuronidation (p < 0.05). Notably, rs2071197 was significantly associated with the gene expression of HNF4A and UGT2B7 and the glucuronidation of emodin. The gene expression of HNF4A showed a high correlation with UGT2B7 (R2 = 0.721, p = 5.83 × 10-11). The luciferase activity was increased 7.68-fold in 293T cells and 2.03-fold in HepG2 cells, confirming a significant transcriptional activation of UGT2B7 promoter by HNF4A. The knockdown of HNF4A in HepG2 cells (36.6%) led to a significant decrease of UGT2B7 (19.8%) and higher cytotoxicity (p < 0.05). The overexpression of HNF4A in HepG2 cells (31.2%) led to a significant increase of UGT2B7 (24.4%) and improved cell viability (p < 0.05). Besides, HNF4A and UGT2B7 were both decreased in HepG2 cells and rats after treatment with emodin. In conclusion, emodin used long term or in high doses could inhibit the expression of HNF4A, thereby reducing the expression of UGT2B7 and causing hepatotoxicity.


Assuntos
Emodina/farmacocinética , Glucuronídeos/metabolismo , Glucuronosiltransferase/genética , Fator 4 Nuclear de Hepatócito/genética , Animais , Linhagem Celular , Emodina/farmacologia , Estudo de Associação Genômica Ampla , Glucuronosiltransferase/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Rim/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único , Ratos Sprague-Dawley
7.
BMC Infect Dis ; 20(1): 629, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842982

RESUMO

BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.


Assuntos
Biodiversidade , Progressão da Doença , Microbiota/genética , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Vagina/microbiologia , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactobacillus/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologia
8.
Appl Microbiol Biotechnol ; 104(10): 4593-4603, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32306050

RESUMO

River-bay system is a transitional zone connecting land and ocean and an important natural source for methane emission. Methanogens play important roles in the global greenhouse gas budget and carbon cycle since they produce methane. The abundance and community assemblage of methanogens in such a dynamic system are not well understood. Here, we used quantitative PCR and high-throughput sequencing of the mcrA gene to investigate the abundance and community composition of methanogens in the Shenzhen River-Bay system, a typical subtropical river-bay system in Southern of China, during the wet and dry seasons. Results showed that mcrA gene abundance was significantly higher in the sediments of river than those of estuary, and was higher in wet season than dry season. Sequences of mcrA gene were mostly assigned to three orders, including Methanosarcinales, Methanomicrobiales, and Methanobacteriales. Specifically, Methanosarcina, Methanosaeta, and Methanobacterium were the most abundant and ubiquitous genera. Methanogenic communities generally clustered according to habitat (river vs. estuary), and salinity was the major factor driving the methanogenic community assemblage. Furthermore, the indicator groups for two habitats were identified. For example, Methanococcoides, Methanoculleus, and Methanogenium preferentially existed in estuarine sediments, whereas Methanomethylovorans, Methanolinea, Methanoregula, and Methanomassiliicoccales were more abundant in riverine sediments, indicating distinct ecological niches. Overall, these findings reveal the distribution patterns of methanogens and expand our understanding of methanogenic community assemblage in the river-bay system. Key Points • Abundance of methanogens was relatively higher in riverine sediments. • Methanogenic community in estuarine habitat separated from that in riverine habitat. • Salinity played a vital role in regulating methanogenic community assemblage.


Assuntos
Bactérias/classificação , Baías/microbiologia , Metano/biossíntese , Microbiota/genética , Rios/microbiologia , Salinidade , Estações do Ano , Bactérias/metabolismo , China , Enzimas de Restrição do DNA/genética , Ecossistema , Sedimentos Geológicos/microbiologia , Microbiota/fisiologia , Filogenia , RNA Ribossômico 16S/genética , Análise Espacial
9.
Microb Ecol ; 77(2): 417-428, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612184

RESUMO

Bathyarchaeota is a diverse, abundant, and widespread archaeal phylum that may play an important role in global carbon cycling. The vertical distribution of Bathyarchaeota and environmental impact on bathyarchaeotal community in deep-sea and lake sediments are known; however, little information is available on Bathyarchaeota in eutrophic and brackish environments, such as mangrove wetlands. In the current study, we investigated the bathyarchaeotal community in the mangrove ecosystem of Futian Nature Reserve, Shenzhen. By slicing the profile into 2-cm layers from the surface to bottom, 110 sediment samples were obtained from three mangrove and three mud flat profiles. High-throughput sequencing of archaeal 16S rRNA genes, quantification of bathyarchaeotal 16S rRNA genes with optimized quantitative primers, and the ensuing statistical analyses revealed the vertical distribution of Bathyarchaeota in the mangrove ecosystem, indicating that Bathyarchaeota was the dominant archaeal phylum therein, with Bathyarchaeota subgroups 6, 8, 15, and 17 as the most abundant subgroups. The abundance of Bathyarchaeota was higher in the mangrove than in the mud flat and other oligotrophic or freshwater habitats. Total organic carbon (TOC) and nitric oxide were significantly correlated with the abundance of Bathyarchaeota, and pH was the major factor shaping the community composition. Further, the data suggested that Bathyarchaeota subgroup 6 preferentially dwelled in slightly acidic, high TOC, and subsurface environments, indicating a potentially distinct role in the global geochemical cycle. These findings expand the knowledge of the distribution and niche preference of Bathyarchaeota, emphasizing the need for continuous characterization of bathyarchaeotal subgroups.


Assuntos
Archaea/isolamento & purificação , Biodiversidade , Archaea/classificação , Archaea/genética , Ciclo do Carbono , DNA Arqueal/genética , Sedimentos Geológicos/análise , Sedimentos Geológicos/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Lagos/análise , Lagos/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/análise , Água do Mar/microbiologia , Áreas Alagadas
10.
BMC Infect Dis ; 19(1): 677, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370796

RESUMO

BACKGROUND: In this study, the association between high-risk human papillomavirus (hrHPV) infection and the vaginal microbiome in pregnant women was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of four groups, 38 hrHPV-infected pregnant women (PHR, n = 38), pregnant women without HPV infection (PN, n = 48), nonpregnant women with hrHPV infection (NPHR, n = 19) and nonpregnant women without HPV infection (NPN, n = 30), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: The results revealed that both pregnancy and HPV infection can increase vaginal bacterial microbial richness and diversity, with the bacterial composition being most influenced by pregnancy. Lactobacillus was the most dominant genus among all samples. NPN samples were dominated by CST (community state type) III, mainly composed of Lactobacillus iners. Both pregnancy and hrHPV infection were accompanied by an increased proportion of CST I (dominated by Lactobacillus crispatus), as opposed to CST III. Bifidobacterium, Bacillus, Megasphaera, Sneathia, Prevotella, Gardnerella, Fastidiosipila and Dialister were found to be biomarkers for hrHPV-infected women, though different genera (Bifidobacterium, Megasphaera, Bacillus, Acidovorax, Oceanobacillus and Lactococcus) were associated with hrHPV-infected pregnant women. CONCLUSIONS: This work uncovered a probable synergistic effect of hrHPV infection and pregnancy on the vaginal microbial composition. HPV infection in pregnant women was associated with a more complex and diverse microbial environment.


Assuntos
Microbiota , Infecções por Papillomavirus/microbiologia , Vagina/microbiologia , Vagina/virologia , Adulto , Povo Asiático , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microbiota/genética , Infecções por Papillomavirus/virologia , Gravidez , RNA Ribossômico 16S/genética
11.
J Virol ; 91(15)2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28490592

RESUMO

Rta, an Epstein-Barr virus (EBV) immediate-early protein, reactivates viral lytic replication that is closely associated with tumorigenesis. In previous studies, we demonstrated that in epithelial cells Rta efficiently induced cellular senescence, which is an irreversible G1 arrest likely to provide a favorable environment for productive replications of EBV and Kaposi's sarcoma-associated herpesvirus (KSHV). To restrict progression of the cell cycle, Rta simultaneously upregulates CDK inhibitors and downregulates MYC, CCND1, and JUN, among others. Rta has long been known as a potent transcriptional activator, thus its role in gene repression is unexpected. In silico analysis revealed that the promoter regions of MYC, CCND1, and JUN are common in (i) the presence of CpG islands, (ii) strong chromatin immunoprecipitation (ChIP) signals of CCCTC-binding factor (CTCF), and (iii) having at least one Rta binding site. By combining ChIP assays and DNA methylation analysis, here we provide evidence showing that Rta binding accumulated CpG methylation and decreased CTCF occupancy in the regulatory regions of MYC, CCND1, and JUN, which were associated with downregulated gene expression. Stable residence of CTCF in the viral latency and reactivation control regions is a hallmark of viral latency. Here, we observed that Rta-mediated decreased binding of CTCF in the viral genome is concurrent with virus reactivation. Via interfering with CTCF binding, in the host genome Rta can function as a transcriptional repressor for gene silencing, while in the viral genome Rta acts as an activator for lytic gene loci by removing a topological constraint established by CTCF.IMPORTANCE CTCF is a multifunctional protein that variously participates in gene expression and higher-order chromatin structure of the cellular and viral genomes. In certain loci of the genome, CTCF occupancy and DNA methylation are mutually exclusive. Here, we demonstrate that the Epstein-Barr virus (EBV) immediate-early protein, Rta, known to be a transcriptional activator, can also function as a transcriptional repressor. Via enriching CpG methylation and decreasing CTCF reloading, Rta binding efficiently shut down the expression of MYC, CCND1, and JUN, thus impeding cell cycle progression. Rta-mediated disruption of CTCF binding was also detected in the latency/reactivation control regions of the EBV genome, and this in turn led to viral lytic cycle progression. As emerging evidence indicates that a methylated EBV genome is a preferable substrate for EBV Zta, the other immediate-early protein, our results suggest a mechanistic link in understanding the molecular processes of viral latent-lytic switch.


Assuntos
Metilação de DNA , Regulação da Expressão Gênica , Herpesvirus Humano 4/fisiologia , Proteínas Imediatamente Precoces/metabolismo , Proteínas Repressoras/metabolismo , Transativadores/metabolismo , Ativação Viral , Fator de Ligação a CCCTC , Regulação para Baixo , Interações Hospedeiro-Patógeno , Transcrição Gênica
12.
Toxicol Appl Pharmacol ; 359: 91-101, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30248416

RESUMO

Aggravating effect of probenecid (a traditional anti-gout agent) on emodin-induced hepatotoxicity was evaluated in this study. 33.3% rats died in combination group, while no death was observed in rats treated with emodin alone or probenecid alone, indicating that emodin-induced (150 mg/kg) hepatotoxicity was exacerbated by probenecid (100 mg/kg). In toxicokinetics-toxicodynamics (TK-TD) study, aspartate aminotransferase (AST) and systemic exposure (area under the serum concentration-time curve, AUC) of emodin and its glucuronide were significantly increased in rats after co-administrated with emodin and probenecid for 28 consecutive days. Results showed that the increased AUC (increased by 85.9%) of emodin was mainly caused by the decreased enzyme activity of UDP-glucuronosyltransferases (UGTs, decreased by 11.8%-58.1%). In addition, AUC of emodin glucuronide was increased 5-fold, which was attributed to the decrease of multidrug-resistant-protein 2 (MRP2) protein levels (decreased by 54.4%). Similarly, in vitro experiments proved that probenecid reduced the cell viability of emodin-treated HepG2 cells through inhibiting UGT1A9, UGT2B7 and MRP2. Our findings demonstrated that emodin-induced hepatoxicity was exacerbated by probenecid through inhibition of UGTs and MRP2 in vivo and in vitro, indicating that gout patients should avoid taking emodin-containing preparations in combination with probenecid for a long time.


Assuntos
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Catárticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Emodina/toxicidade , Glucuronosiltransferase/antagonistas & inibidores , Probenecid/toxicidade , Fármacos Renais/toxicidade , Animais , Catárticos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Sinergismo Farmacológico , Emodina/farmacocinética , Células Hep G2 , Humanos , Cinética , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Probenecid/farmacocinética , Ratos , Ratos Sprague-Dawley , Fármacos Renais/farmacocinética
13.
Mol Pharm ; 15(9): 3931-3945, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30011215

RESUMO

Emodin is a main anthraquinone compound which exists in Chinese traditional medicines including Polygonum multiflorum and Rhubarb. It is documented to have obvious liver and kidney toxicity. This study aims to (a) estimate gender differences of the hepatotoxicity and toxicokinetics in rats after oral administration of emodin (60 and 150 mg/kg/d) for a consecutive 28 days and (b) clarify relative mechanisms caused by glucuronidation and disposition. Hepatotoxicity was significantly higher in female rats than that in male rats, as evidenced by histopathological and biochemical tests. Similarly, the toxicokinetic profiles of emodin have time and gender differences, which could cause time and gender differences in hepatotoxicity. The metabolic and transcriptomics data of 55 human liver and 36 human kidney samples demonstrated that UDP-glucuronosyltransferase 2B7 (UGT2B7) was the predominant enzyme for emodin glucuronidation. A genome-wide association study (GWAS) identified that rs11726899 located within ∼50 kb of the transcript of UGT2B could significantly affect emodin metabolism. Knockdown of UGT2B7 in HepG2 cells significantly decreased emodin glucuronidation and increased cytotoxicity of emodin. The gene expression and protein levels of UGT2B7 were decreased, but those of the multidrug-resistant-protein 2 (MRP2) were increased in HepG2 cells after being treated with 50 µM emodin for 48 h. Long-term use of emodin could decrease the intrinsic clearance (CLint, decreased by 18.5%-35.4%) values of zidovidue (UGT2B7 substrate) glucuronide in both male and female liver microsomes from rats administrated with emodin for 28 days, thus causing the accumulation of emodin. However, higher self-induced MRP2 expression and lower hepatotoxicity were observed in emodin-treated male rats compared to that in female rats. Therefore, gender differences in the hepatotoxicity and toxicokinetics of emodin are potentially mediated by the coupling of UGT2B7 and MRP2 in vivo.


Assuntos
Emodina/metabolismo , Animais , Western Blotting , Emodina/farmacocinética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Técnicas In Vitro , Rim/metabolismo , Fígado/metabolismo , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Controle de Qualidade , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais , Toxicocinética
16.
J Food Sci Technol ; 55(4): 1244-1255, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29606739

RESUMO

The effects of solid-state fermentation with Cordyceps militaris (L.) Fr. on the nutritional, physicochemical, and functional properties as well as angiotensin I converting enzyme (ACE) inhibitory activity of red bean (Phaseolus angularis [Willd.] W.F. Wight.) flour were determined. Fermentation increased the amount of small peptides but significantly decreased large peptides. Fermentation also increased proteins and essential amino acids (by 9.31 and 13.89%, respectively) and improved the in vitro protein digestibility (6.54%) of red beans. Moreover, fermentation increased the water holding capacity (from 2.36 to 2.59 mL/g), fat absorption capacity (from 84.65 to 114.55%), emulsion activity (from 10.96 to 52.77%), emulsion stability (from 5.43 to 53.82%), and foaming stability (from 11.95 to 20.68%). Fermented red bean flour achieved a lower least gelation concentration of 14% than that of the control (18%). In contrast to the non-fermented red bean, the fermented red bean showed ACE inhibitory activity, with IC50 value of 0.63 mg protein/mL. Overall, fermentation improved the nutritional, physicochemical, and functional properties as well as the biological activity of red bean flour. Thus, fermented red bean flour may serve as a novel nutritional and functional ingredient for applications in food design.

17.
J Sci Food Agric ; 97(4): 1158-1163, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27293203

RESUMO

BACKGROUND: Understanding the metabolic and transcription basis of pumpkin seed oil (PSO) intervention on metabolic disease (MD) is essential to daily nutrition and health. RESULTS: This study analyzed the liver metabolic variations of Wistar rats fed normal diet (CON), high-fat diet (HFD) and high-fat plus PSO diet (PSO) to establish the relationship between the liver metabolite composition/transcript profile and the effects of PSO on MD. By using proton nuclear magnetic resonance spectroscopy together with multivariate data analysis, it was found that, compared with CON rats, HFD rats showed clear dysfunctions of choline metabolism, glucose metabolism and nucleotide and amino acid metabolism. Using quantitative real-time polymerase chain reaction (qPCR), it was found that, compared with HFD rats, PSO rats showed alleviated endoplasmic reticulum stress accompanied by lowered unfolded protein response. CONCLUSION: These findings provide useful information to understand the metabolic alterations triggered by MD and to evaluate the effects of PSO intervention. © 2016 Society of Chemical Industry.


Assuntos
Cucurbita/química , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado/efeitos dos fármacos , Doenças Metabólicas/metabolismo , Metaboloma , Óleos de Plantas/farmacologia , Aminoácidos/metabolismo , Animais , Colina/metabolismo , Gorduras na Dieta , Glucose/metabolismo , Fígado/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Metabolômica , Nucleotídeos/metabolismo , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Sementes/química , Transcrição Gênica , Resposta a Proteínas não Dobradas/efeitos dos fármacos
19.
Asian-Australas J Anim Sci ; 29(6): 855-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26954114

RESUMO

The objective of this study was to compare the physicochemical and nutritional properties of breast and thigh meat from commercial Chinese crossbred chickens (817 Crossbred chicken, 817C), imported commercial broilers (Arbor Acres broiler, AAB), and commercial spent hens (Hyline Brown, HLB). The crossbred chickens, commercial broilers and spent hens were slaughtered at their typical market ages of 45 d, 40 d, and 560 d, respectively. The results revealed that several different characteristic features for the three breeds. The meat of the 817C was darker than that of the other two genotypes. The 817C were also characterized by higher protein, lower intramuscular fat, and better texture attributes (cooking loss, pressing loss and Warner-Bratzler shear force [WBSF]) compared with AAB and HLB. The meat of the spent hens (i.e. HLB) was higher in WBSF and total collagen content than meat of the crossbred chickens and imported broilers. Furthermore, correlation analysis and principal component analysis revealed that there was a clear relationship among physicochemical properties of chicken meats. With regard to nutritional properties, it was found that 817C and HLB exhibited higher contents of essential amino acids and essential/non-essential amino acid ratios. In addition, 817C were noted to have highest content of microelements whereas AAB have highest content of potassium. Besides, 817C birds had particularly higher proportions of desirable fatty acids, essential fatty acids, polyunsaturated/saturated and (18:0+18:1)/16:0 ratios. The present study also revealed that there were significant differences on breast meat and thigh meat for the physicochemical and nutritional properties, regardless of chicken breeds. In conclusion, meat of crossbred chickens has some unique features and exhibited more advantages over commercial broilers and spent hens. Therefore, the current investigation would provide valuable information for the chicken meat product processing, and influence the consumption of different chicken meat.

20.
J Transl Med ; 12: 24, 2014 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-24460842

RESUMO

BACKGROUND: T regulatory cell (Treg) plays a critical role in respiratory allergy and allergen-specific immunotherapy (SIT), and γδ T cells might participate in mediating Treg quantity and/or function in some immunological diseases. To further characterize whether γδ T cells could influence Treg in allergic rhinitis (AR) and SIT, we investigated the expression pattern of Treg's Foxp3 gene and γδ T cell receptor (TCR) Vγ subfamily genes in peripheral blood mononuclear cells (PBMCs) of AR patients before and after SIT. METHODS: Eighteen AR patients undergoing effective SIT with house dust mite extract for one year were recruited. Visual Analogue Scale (VAS) was applied to evaluate the severity. Immunofluorescence quantification analysis was performed to determine the serum specific IgE (sIgE) content. Real-time PCR was used to detect the expression levels of Foxp3 and TCR Vγ subfamilies. Ten healthy volunteers were recruited as the controls. RESULTS: Nasal uni-VAS score after SIT was significantly lower than that before SIT, while serum sIgE content was similar before and after SIT. Expression levels of Foxp3 and TCR Vγ subfamilies in AR patients before treatment were significantly lower than those in healthy subjects. Expression levels of VγI and II were similar before and after SIT, while expression levels of Foxp3 and VγIII after SIT were significantly higher than those before. Before SIT, the significant positive correlation was observed between expression levels of Foxp3 and VγI, II, III, while negative correlation was observed between Foxp3, VγIII and VAS. After SIT, the significant positive correlation between expression levels of Foxp3 and VγIII and negative correlation between Foxp3, VγIII and VAS were observed. CONCLUSIONS: Treg and Vγ subfamily T cells were in a dynamic equilibrium in AR patients before and after effective immunotherapy for one year. The early improvement of symptoms following immunotherapy might be independent of the serum sIgE content in AR patients, but associated with the reconstitution of T cell immunity.


Assuntos
Dessensibilização Imunológica , Perfilação da Expressão Gênica , Receptores de Antígenos de Linfócitos T gama-delta/genética , Rinite Alérgica Perene/genética , Rinite Alérgica Perene/terapia , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunoglobulina E/sangue , Masculino , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Rinite Alérgica , Rinite Alérgica Perene/sangue , Rinite Alérgica Perene/imunologia , Escala Visual Analógica , Adulto Jovem
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