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1.
BMC Plant Biol ; 20(1): 59, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019505

RESUMO

BACKGROUND: Basal leaf removal is widely practiced to increase grape cluster sunlight exposure that controls berry rot and improves quality. Studies on its influence on volatile compounds in grape berries have been performed mostly in Mediterranean or marine climate regions. It is uncertain whether similar efficiency can be achieved when grape berries are grown under continental climate. This study aimed to dissect the variation in volatile compound production and transcriptome in sunlight-exposed grape berries in a dry-hot climate region and to propose the key genes related to the variation. RESULTS: Four cluster sunlight exposure strategies, including basal leaf removal at pepper-corn size stage, leaf removal at véraison (LR-V), leaf moving at véraison (LM-V), and half-leaf removal at véraison, were implemented at the north foot of the Mt. Tianshan region of northwestern China. Various cluster exposure treatments resulted in a decline in the concentrations of norisoprenoids and monoterpenes in ripening grape berries. Both ß-carotene and lutein, the substrates of norisoprenoid biosynthesis, were reduced by cluster sunlight exposure. K-means cluster analysis showed that some genes involved in biosynthesis such as VviTPS55, VviTPS60, VviTPS66, VviCCD4a and VviCCD4b exhibited lower expression levels in exposed berries at least at one of the tested stages. Two C6-derived esters with fruity attributes, ethyl hexanoate and hexyl acetate, were reduced markedly. In contrast, main C6 alcohol compound levels were elevated in the LR-V- and LM-V-treated grape berries, which corresponded to the up-regulated expression of VviLOXA, VviLOXO and VviADH1 in the oxylipin pathway. Most of the differentially expressed genes in the exposed and control berries were enriched to the "stress response" processes, and this transcriptome difference was accumulated as the berries matured. Besides, LR-V treatment stimulated a significant up-regulation in photosynthesis-related genes in the grape berries, which did not happen with LM-V treatment. CONCLUSIONS: Cluster sunlight exposure in dry-hot climate viticulture resulted in different volatile-targeted transcriptomic and metabolic responses from those obtained in the temperate Mediterranean or marine climate region. Therefore, a modified canopy management should be adopted to improve the aroma of grape berries.

2.
Nat Immunol ; 21(4): 477-478, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32099101

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
J Neuroinflammation ; 17(1): 34, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980031

RESUMO

BACKGROUND: Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear. METHODS: We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund's adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model. RESULTS: CFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4-6 dorsal root ganglions (DRGs) in rats. Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, CFA treatment promoted binding of C/EBPα to the NGF gene promoter region and C/EBPα siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats. CONCLUSION: Collectively, the results indicated that CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of C/EBPα with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.

4.
J Cell Biochem ; 121(2): 1463-1474, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31599078

RESUMO

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.

5.
Neurol Sci ; 41(3): 661-667, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31754876

RESUMO

As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson's Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson's disease. Increased SN echogenicity is correlated with VH in Parkinson's disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

6.
Biomed Pharmacother ; 121: 109642, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731191

RESUMO

BACKGROUND: Recently, a growing number of reports indicated that long non-coding RNAs (lncRNAs) were involved in the development of various cancers. However, the performance of LINC00511 is still limited in hepatocellular carcinoma (HCC). Thus, we attempted to assess the effect of LINC00511 and underlying mechanism in HCC progression. METHODS: TCGA and GEO database acted as supporters to provide us clinical samples data. Overall survival (OS) analyses were plotted using Kaplan-Meier method. Five cell lines were utilized to detect LINC00511 expression level and Cell Counting Kit-8 (CCK-8), colony formation and transwell assays were conducted to examine the effects on cell behaviors. The correlations between LINC00511 and miR-195 or eyes absent homolog 1 (EYA1) were confirmed by luciferase reporter assay. Quantitative real-time PCR and western blotting were fulfilled to ascertain the mRNA and protein expression levels. RESULTS: In this study, we found that LINC00511 was high-regulated in HCC tissue samples and cell lines, which might be linked with unfavorable prognosis of HCC patients and clinical parameters. Loss-of-function experiments determined that LINC00511 deficiency inhibited cell proliferation, colony formation and invasive activity in HepG2 cells, while gain-of-function experiments showed the counter impacts in Huh7 cells. Bioinformatics tools and luciferase reporter assays revealed that LINC00511 may act as a competing endogenous RNA (ceRNA) for miR-195 and positively correlate with EYA1, which was reinforced by rescue experiments. CONCLUSION: Taken together, these findings indicated that LINC00511 interacted with EYA1 promoted HCC development via mediating miR-195, proposing a promising therapeutic biomarker for HCC diagnosis and prognosis.

7.
Nat Immunol ; 20(12): 1621-1630, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31740800

RESUMO

Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the microRNA miR-1 promoted IFN-γ-mediated clearance of Listeria monocytogenes in macrophages by indirectly stabilizing the Stat1 messenger RNA through the degradation of the cytoplasmic long noncoding RNA Sros1. Inducible degradation or genetic loss of Sros1 led to enhanced IFN-γ-dependent activation of the innate immune response. Mechanistically, Sros1 blocked the binding of Stat1 mRNA to the RBP CAPRIN1, which stabilized the Stat1 mRNA and, consequently, promoted IFN-γ-STAT1-mediated innate immunity. These observations shed light on the complex RNA-RNA regulatory networks involved in cytokine-initiated innate responses in host-pathogen interactions.


Assuntos
Citoplasma/metabolismo , Listeria monocytogenes/fisiologia , Listeriose/imunologia , Macrófagos/imunologia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Fator de Transcrição STAT1/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Imunidade Inata , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Ligação Proteica , Células RAW 264.7 , Estabilidade de RNA , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT1/genética
8.
J Hum Hypertens ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595025

RESUMO

Sustained and inadequately controlled hypertension can promote the development of age-related macular degeneration (AMD) through multiple biologic pathways. Epidemiologic studies of high blood pressure, antihypertensive therapies, and the risk of AMD thus far have been inconclusive. However, few studies evaluated risks according to the use of different classes of antihypertensive drugs or took combinations of use into account. We performed a prospective cohort study by linking the California Teachers Study (CTS) cohort (N = 88 481) to statewide hospital discharge records up to December 31, 2012. History of high blood pressure, regular use of antihypertensive medications, and comprehensive risk factor information was collected via self-administered questionnaires at baseline in 1995-1996, and information on specific classes of antihypertensive drugs was provided by a subsample of CTS participants who completed a follow-up questionnaire in 2000. We identified 1762 female teachers with AMD during 14.8 years of follow-up on average. Applying Cox proportional hazard regression, we estimated increased risks of AMD among women treated for hypertension at baseline (HR = 1.15, 95% CI: 1.03, 1.30); the magnitude of the association increased with longer duration of antihypertensive treatment. In the subsample with more specific information on type of medication use, we estimated a 45% increased risk of AMD among women receiving diuretics as monotherapy compared to women with medications more potent than diuretics (HR = 1.45, 95% CI 1.10, 1.90). In women treated with a combination of antihypertensive drugs, we observed no increased risk of AMD for any individual class of drugs.

9.
Food Chem Toxicol ; 134: 110806, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521635

RESUMO

Insulin resistance causes several adverse effects such as hypertension, diabetes and different aspects of cardiovascular diseases. Patrinia scabiosaefolia Fisch. ex Trev. is a traditional Chinese edible herbal, whose n-BuOH extract significantly increased glucose transportin 3T3-L1 adipocytes at the concentration of 12.5 µM. To determine its active constituent, its chemical components and bioactivities were investigated. Two compounds (1-2) could significantly improve insulin resistance in 3T3-L1 adipocytes at concentrations around 25.0 µM (P < 0.001). Compound 2 was more effective to lower the content of glucose content at 12.5 µM (P < 0.001). Compound 1 was a new compound identified by spectroscopic methods. Western-blot experiment demonstrated an upregulation of p-IRS-1, p-Akt, and GLUT4 induced by compounds 1 and 2. Hence, we speculated that compounds 1 and 2 could activate PI3K and Akt signaling by up-regulating of p-IRS-1 which resulted in the activation of PI3K before phosphorylating Akt, ultimately led to translocation of GLUT4. These events finally improve glucose transport. Our results may provide the scientific basis for the development and effective use of P. scabiosaefolia against type 2 diabetes.


Assuntos
Resistência à Insulina , Glicosídeos Iridoides/farmacologia , Patrinia/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Relação Dose-Resposta a Droga , Glucose/metabolismo , Glucosídeos/farmacologia , Insulina/metabolismo , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray
10.
Toxicology ; 425: 152246, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369815

RESUMO

T-2 toxin is a secondary metabolite produced by Fusarium species and commonly contaminates food and animal feed. T-2 toxin can induce hepatotoxicity through apoptosis and oxidative stress; however, the underlying mechanism is not clear. Recent studies indicated that RASSF4, a member of the RASSF family, participates in cell apoptosis and some cancers due to its inactivation via DNA hypermethylation. However, its role in T-2 toxin-induced liver toxicity is poorly understood. Therefore, in this study, female Wistar rats were given a single dose of T-2 toxin at 2 mg/kg b.w. and were sacrificed at 1, 3 and 7 days post-exposure. A normal rat liver cell line (BRL) was exposed to different concentrations of T-2 toxin (10, 20, 40 nM) for 4, 8, 12 h, respectively. Histopathological analysis revealed with apoptosis in some liver cells and clear proliferation under T-2 toxin exposure. Expression analysis by immunohistochemical assays, quantitative real-time PCR (qPCR) and western blot demonstrated that T-2 toxin activated PI3K-Akt/Caspase/NF-κB signaling pathways. Additionally, DNA methylation assays revealed that the expression of RASSF4 was silenced by promoter hypermethylation after exposure to T-2 toxin for 1 and 3 days as compared to the control group. Moreover, joint treatment of 5-Aza-2'-deoxycytidine (DAC) (5 µM) and T-2 toxin (40 nM) increased expression of RASSF4 and PI3K-Akt/caspase/NF-κB signaling pathways-related genes, inducing cell apoptosis. These findings for the first time demonstrated that DNA methylation regulated the RASSF4 expression under T-2 toxin, along with the activation of its downstream pathways, resulting in apoptosis.

11.
World Neurosurg ; 132: e529-e534, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449993

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a common type of injury, and about half of patients affected by SCI will suffer from neuropathic pain within a year after injury. However, the treatment effect of neuropathic pain is far from satisfactory. Our study attempted to reveal whether salvianolic acid B (SalB) could relieve the neuropathic pain caused by SCI in mice by inhibiting the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) pathway. METHODS: The mice were randomly divided into a sham group, model group, high-dose treatment group, and low-dose treatment group. The high- and low-dose groups received varying doses of SalB after modeling. RESULTS: The increase of pain sensitivity was evaluated by detecting paw withdrawal mechanical threshold and withdrawal thermal latency. Messenger RNA and protein expression levels of TLR4 and myD88 were detected by using quantitative reverse-transcription polymerase chain reaction and western blot, respectively. Compared with the model group, there was a significant reduction in paw withdrawal mechanical threshold and withdrawal thermal latency after SalB treatment. CONCLUSIONS: SalB reduced the release of tumor necrosis factor-α and substance P by inhibiting the TLR4/MyD88 pathway in the SCI mouse model. This not only resulted in lower pain, but also contributed to long-term relief of mechanical hyperalgesia.


Assuntos
Benzofuranos/farmacologia , Fator 88 de Diferenciação Mieloide/efeitos dos fármacos , Neuralgia/metabolismo , Limiar da Dor/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Hiperalgesia/etiologia , Hiperalgesia/imunologia , Hiperalgesia/metabolismo , Masculino , Camundongos , Neuralgia/etiologia , Neuralgia/imunologia , Distribuição Aleatória , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/imunologia
12.
Biomed Res Int ; 2019: 3176483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355254

RESUMO

Three lignans, phillyrin, forsythia ester A, and rosin-ß-D-furan glucose, were isolated from Forsythia suspensa which is a famous Traditional Chinese Medicine used for clearing heat and detoxifying, reducing swelling and dispersing knot, and dispersing wind heat. In this study, the effects of phillyrin, forsythia ester A, and rosin-ß-D-furan glucose on insulin resistance of 3T3-L1 adipocytes were investigated by the method of glucose oxidase-peroxidase (GOD-POD) and the mechanism was assayed by the method of western blot. The results indicated that phillyrin, forsythia ester A, and rosin-ß-D-furan glucose could improve the glucose uptake in 3T3-L1 adipocytes under insulin resistance (IR). Among them, phillyrin showed significant activity in increasing glucose consumption at the concentrations of 100 µM and 200 µM (P < 0.001). The mechanism of improving insulin resistance may be that phillyrin could raise the protein phosphorylation of IRS-1 and Akt and the expression levels of GLUT4 protein.


Assuntos
Adipócitos/metabolismo , Forsythia/química , Glucosídeos , Resistência à Insulina , Folhas de Planta/química , Células 3T3-L1 , Adipócitos/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/biossíntese , Glucosídeos/química , Glucosídeos/farmacologia , Proteínas Substratos do Receptor de Insulina/biossíntese , Camundongos , Proteínas Proto-Oncogênicas c-akt/biossíntese
13.
Biotechnol Lett ; 41(6-7): 719-732, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31114947

RESUMO

OBJECTIVES: To identify genes that affected protein expression in Chinese hamster ovary (CHO) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein. RESULTS: Here two sub-clones from a methotrexate-treated parental recombinant CHO cell line were selected. The two sub-clones, with different expression levels (qp were 42.8 pg/cell/day and 14.0 pg/cell/day), were analyzed through RNA-seq. More than 600 genes were identified as differently expressed, and we found that the differentially expressed genes were involved in processes such as RNA processing, transcription, protein catabolism, and protein transport. Among these, we cloned genes encoding proteins that were involved in transcription and protein transport to investigate their effect on protein production. CONCLUSIONS: We found that some genes involved in transcription and protein transport would improve recombinant protein production in CHO cells.


Assuntos
Biotecnologia/métodos , Células CHO/metabolismo , Regulação da Expressão Gênica , Transporte Proteico , Proteínas Recombinantes/metabolismo , Transcrição Genética , Animais , Cricetulus , Feminino , Perfilação da Expressão Gênica , Proteínas Recombinantes/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-31069175

RESUMO

Yersinia pestis is the etiological agent of the notorious plague that has claimed millions of deaths in history. Of the four known Y. pestis biovars (Antiqua, Medievalis, Orientalis, and Microtus), Microtus strains are unique for being highly virulent in mice but avirulent in humans. Here, human peripheral lymphocytes were infected with the fully virulent 141 strain or the Microtus strain 201, and their transcriptomes were determined and compared. The most notable finding was that robust responses in the pathways for cytokine-cytokine receptor interaction, chemokine signaling pathway, Toll-like receptor signaling and Jak-STAT signaling were induced at 2 h post infection (hpi) in the 201- but not the 141-infected lymphocytes, suggesting that human lymphocytes might be able to constrain infections caused by strain 201 but not 141. Consistent with the transcriptome results, much higher IFN-γ and IL-1ß were present in the supernatants from the 201-infected lymphocytes, while inflammatory inhibitory IL-10 levels were higher in the 141-infected lymphocytes. The expressions of CSTD and SLC11A1, both of which are functional components of the lysosome, increased in the 201-infected human macrophage-like U937 cells. Further assessment of the survival rate of the 201 bacilli in the U937 cells and murine macrophage RAW 264.7 cells revealed no viable bacteria in the U937 cells at 32 hpi.; however, about 5-10% of the bacteria were still alive in the RAW264.7 cells. Our results indicate that human macrophages can clear the intracellular Y. pestis 201 bacilli more efficiently than murine macrophages, probably by interfering with critical host immune responses, and this could partially account for the host-specific pathogenicity of Y. pestis Microtus strains.


Assuntos
Linfócitos/imunologia , Linfócitos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Yersinia pestis/crescimento & desenvolvimento , Yersinia pestis/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Viabilidade Microbiana
15.
Biosci Rep ; 39(5)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30923228

RESUMO

Background: MicroRNA can regulate gene expression, and participate in multiple vital activities, such as inflammation, oxidative stress epigenetic modification, cell proliferation, and apoptosis. It plays an important role in the genesis and development of cardiovascular disease.Objective: To assess the role of microRNA-208a in ketamine-induced cardiotoxicity.Methods: All rats were randomly selected into two groups: sham and model groups. After fixed, all rats in the model group was intraperitoneally (IP) injected with 100 mg/kg of ketamine. Heart samples were stained with HE assay. Total RNAs from serum were used to hybridize with the SurePrint G3 Rat Whole Genome GE 8×60 K Microarray G4858A platform.Results: In the rat model with ketamine-induced cardiotoxicity, microRNA-208a expression was increased. Then, over-expression of microRNA-208a increased inflammation and oxidative stress in vitro model. However, down-regulation of microRNA-208a decreased inflammation and oxidative stress in vitro model. Over-expression of microRNA-208a suppressed CHD9 and Notch1, and induced p65 protein expression in vitro model. Overexpression of CHD9 reduced the effects of microRNA-208a on inflammation and oxidative stress in heart cell through Notch/p65 signal pathways. Notch1 activation reduced the effects of microRNA-208a on inflammation and oxidative stress in heart cell through p65 signal pathways.Conclusion: MicroRNA-208a may be a potential biomarker for ketamine-induced cardiotoxicity through inflammation and oxidative stress by Notch/NF-κB signal pathways by CHD9.

16.
3 Biotech ; 9(2): 54, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30729078

RESUMO

Arabinoxylan (AX) is abundant in cereal grains used as feed for ducks. However, the duck intestinal microbes responsible for the degradation of AX are not fully understood. In this study, oat AX was degraded and utilized by different duck intestinal microbiota in vitro. Changes in short-chain fatty acids (SCFAs), branch-chain fatty acids, and the pH resulted from a 72-h AX fermentation in intestinal samples were measured. The addition of AX increased the concentration of isobutyric acid and decreased the concentrations of SCFAs. The pH values decreased significantly in the intestinal samples. Gut microbiota were assessed using high-throughput sequencing of the 16S ribosomal RNA gene, and the results indicated that AX stimulated the growth of Megamonas and Bifidobacterium species, with Megamonas exhibiting the greatest stimulation. Overall, the results suggest that oat AX is utilized by specific bacteria in duck intestines, providing the theoretical basis for the impacts of AX on animal health.

17.
Front Microbiol ; 10: 175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30800111

RESUMO

Polycystic ovary syndrome (PCOS) is a frequent endocrine and metabolic syndrome in reproductive-age women. Recently, emerging evidence has shown that gut microbiota is closely related to metabolic diseases such as type 2 diabetes, obesity and PCOS. In the present study, we established dihydrotestosterone (DHT)-induced PCOS rats and used Illumina MiSeq sequencing (PE300) to examine the composition, diversity, and abundance of the gut microbiota in PCOS. We compared the effects of three PCOS treatments: Diane-35 (estrogen and progesterone), probiotics and berberine. The DHT-induced rats showed constant estrous cycles, the loss of mature ovarian follicles, insulin resistance and obesity. The reproductive and metabolic functions in the PCOS rats were improved by treatment with Diane-35 and probiotics. Diane-35 and probiotics could restore the diversity of the gut microbiota, and the recovery of gut microbiota disorders improved the reproductive function in PCOS-like rats. However, berberine drastically reduced the species diversity and amount of gut microbiota and showed no improvement in PCOS. The findings of this study will help us to better understand the influence of the gut microbiota in the metabolic and reproductive alterations in PCOS as well as suggest opportunities for future personal dietary guidance for PCOS.

18.
Arch Virol ; 164(4): 1173-1180, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30810804

RESUMO

Global outbreaks of norovirus (NOV) gastroenteritis are associated with the most prevalent genotype, GII.4. Mutations in the protruding domain 2 (P2 domain) of the norovirus major capsid protein (VP1) result in the emergence of various NOV variants, however, it is unclear whether the minor capsid protein (VP2) also affects the generation of VP1 variants. In this study, using a human 293T expression system, we investigated the interactions of VP1 and VP2 of three GII.4 strains, focusing on the changes in expression and cellular localization. We found that co-transfection with VP1 and VP2 leads to a significant increase in expression of both proteins compared to that in cells transfected with VP1 or VP2 alone. In contrast to VP1 expressed in the absence of VP2, which was dispersed throughout the cytosol, VP2 expressed in the absence of VP1 was found to be located in the nucleus. This could be attributed to a predicted specific nuclear localization signal found in this gene. When both proteins were expressed, VP1 was found together with VP2 in the nucleus. These results thus suggest that the VP2 of GII.4 NOVs affects the function and cellular location of VP1 and that, with the cooperation of VP2, VP1 could play a critical role in affecting cell functions by impairing the downstream transcriptional signaling and chromatin remodeling in the cell nuclei.


Assuntos
Infecções por Caliciviridae/virologia , Proteínas do Capsídeo/metabolismo , Núcleo Celular/virologia , Norovirus/metabolismo , Capsídeo/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Humanos , Norovirus/química , Norovirus/genética , Sinais de Localização Nuclear , Transporte Proteico
19.
Breast Cancer Res Treat ; 174(3): 785-794, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30659431

RESUMO

PURPOSE: Venous thromboembolism (VTE) is the second most common cause of death in hospitalized patients with cancer, and cancer treatments may exacerbate VTE risk. Patients with hormone-receptor-positive breast cancer usually receive adjuvant endocrine therapy for 5 years or longer. The aim of this study is to examine VTE risk following long-term use of aromatase inhibitor (AI) compared with tamoxifen use among breast cancer survivors. METHODS: A prospective cohort of 12,904 postmenopausal women who were diagnosed with a first primary hormone-receptor-positive breast cancer and free from previous cardiovascular disease or VTE from 1991 to 2010 were followed through December 2011. Data elements were captured from the comprehensive electronic health records of a large California health plan, Kaiser Permanente. Women who developed deep vein thrombosis (DVT) or pulmonary embolism (PE) were identified as having VTE. We calculated person-year rates of VTE by endocrine therapy groups. Multivariable Cox proportional hazards models were applied to assess the association between time-dependent endocrine therapy and VTE risk. RESULTS: We identified 623 VTE events during a median follow-up of 5.4 years. The crude rates were 4.6 and 2.8 per 1000 person-years for DVT and PE, respectively. Compared with tamoxifen use, AI use was associated with at least 41% lower VTE risk (adjusted HR 0.59, 95% CI 0.43, 0.81). Greater risk reductions in AI users were seen in women who also underwent adjuvant chemotherapy. CONCLUSIONS: These findings supplement existing evidence to inform treatment decisions that balance cancer control and cardiovascular toxic outcomes.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/administração & dosagem , Tromboembolia Venosa/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/complicações , Sobreviventes de Câncer , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Tamoxifeno/efeitos adversos , Resultado do Tratamento , Tromboembolia Venosa/induzido quimicamente
20.
AAPS PharmSciTech ; 20(1): 37, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30604142

RESUMO

The purpose of this study was to research a novel combination of Plasdone-S630 and HPMCAS-HF as hot-melt carrier used in ziprasidone hydrochloride for enhanced oral bioavailability and dismissed food effect. Ziprasidone hydrochloride solid dispersion (ZH-SD) was prepared by hot-melt extrusion technique, and its optimized formulation was selected by the central composite design (CCD), which was characterized for powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), in vitro dissolution study, and stability study. Finally, the in vivo study in fasted/fed state was carried out in beagle dogs. Based on PXRD analysis, HME technique successfully dispersed ziprasidone with a low crystallinity hydrochloride form in the polymers. According to the analysis of FTIR, hydrogen bonds were formed between drug and polymers during the process of HME. Without any noticeable bulk, crystalline could be found from the micrograph of ZH-SD when analyzed the result of scanning electron microscope (SEM). Pharmacokinetics studies indicated that the bioavailability of ZH-SD formulation had no significant difference in fasted and fed state, and the Cmax and AUC of ZH-SD were two fold higher than Zeldox® in fasted state. This result indicated that ziprasidone has achieved a desired oral bioavailability in fasted state and no food effect.


Assuntos
Jejum , Metilcelulose/análogos & derivados , Piperazinas/síntese química , Povidona/síntese química , Tiazóis/síntese química , Administração Oral , Animais , Disponibilidade Biológica , Cães , Combinação de Medicamentos , Jejum/metabolismo , Metilcelulose/administração & dosagem , Metilcelulose/síntese química , Metilcelulose/metabolismo , Excipientes Farmacêuticos/administração & dosagem , Excipientes Farmacêuticos/metabolismo , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Povidona/administração & dosagem , Povidona/metabolismo , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tiazóis/administração & dosagem , Tiazóis/farmacocinética , Difração de Raios X/métodos
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