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1.
ISA Trans ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31320139

RESUMO

In this paper, the modeling of front wheels Steer-by-Wire (SBW) system is further developed into 4-wheel SBW (4WSBW) system for electric vehicles with Ackerman Geometry taken into consideration. Moreover, a novel adaptive integral terminal sliding mode control (AITSMC) scheme is presented to control the wheel steering angles in both single-wheel situation and four-wheel situation. Based on Lyapunov criterion, stability proof guarantees that the tracking error in closed-loop converges to zero in finite time. In comparison with Proportional-Integral-Derivative (PID) based control, terminal sliding mode control (TSMC) and adaptive TSMC (ATSMC), the proposed control scheme only requiring information of the inertia of the wheels and the motors possesses two major advantages. First, robustness and finite-time convergence are ensured without obtaining information of disturbances caused by road conditions and parameters of viscous friction. Second, tracking error is further suppressed with noise impact in feedback loop caused by sensors while maintaining fast convergence rate. The synthesized performance of the 4WSBW vehicles is significantly improved and numerical simulations are conducted on the dynamic model of the system to corroborate the merits of the proposed control scheme.

2.
J Mol Med (Berl) ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321478

RESUMO

S100A4, a member of the S100 calcium-binding protein family, has been identified in a subpopulation of liver macrophages and promotes liver fibrosis via hepatic stellate cell activation. However, the specific role of S100A4 in alcoholic liver disease (ALD) has not been well investigated. Here, S100A4 knockout (S100A4-/-) mice were used in a chronic-binge ethanol model for studying the role of S100A4 and its related molecular mechanism in ALD. S100A4 expression was increased in ethanol-induced liver tissues of wild-type (WT) mice. Macrophage-derived S100A4 promoted liver inflammation but suppressed lipid accumulation under the ethanol feeding condition. S100A4 deficiency promoted ethanol-induced liver injury and hepatic fat accumulation. Further mechanistic studies found that S100A4 inhibited liver fat accumulation mainly by activating the STAT3 pathway and downregulating lipogenic gene expression, especially that of SREBP-1c. In AML-12 cells, a STAT3 inhibitor abolished STAT3 levels and decreased the expression of SREBP1c. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly promoted ethanol-induced liver injury and fatty accumulation. Thus, S100A4 may represent a potential candidate target for the prevention and treatment of ethanol-induced fatty liver. In this study, we discovered the special role of S100A4 in alcoholic liver disease. S100A4 deficiency attenuated ethanol-induced hepatitis and promoted hepatic fat accumulation in ethanol-induced liver tissues. Further mechanistic studies have found that S100A4 promotes early alcoholic hepatitis mainly by activating the STAT3 pathway and its downstream proinflammatory gene expression. Interestingly, activation of the STAT3 pathway downregulates lipogenic gene expression, especially SREBP-1c. KEY MESSAGES: In this study, we discovered the special role of S100A4 in alcoholic liver disease. S100A4 deficiency attenuated ethanol-induced hepatitis and promoted hepatic fat accumulation in ethanol-induced liver tissues. Further mechanistic studies have found that S100A4 promotes early alcoholic hepatitis mainly by activating the STAT3 pathway and its downstream proinflammatory gene expression. Interestingly, activation of the STAT3 pathway downregulates lipogenic gene expression, especially SREBP-1c.

3.
J Cell Physiol ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332789

RESUMO

Transforming growth factor ß (TGF-ß) is part of the transforming growth factor ß superfamily which is involved in many physiological processes and closely related to the carcinogenesis. Here, we discuss the TGF-ß structure, function, and its canonical Smads signaling pathway. Importantly, TGF-ß has been proved that it plays both tumor suppressor as well as an activator role in tumor progression. In an early stage, TGF-ß inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGF-ß signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial-mesenchymal transition, and immune escape. Furthermore, we are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF-ß synthesis and block its signaling pathways such as antibodies, antisense molecules, and small-molecule tyrosine kinase inhibitors. Thus, it is highlighting the crucial role of TGF-ß in tumor therapy and may provide opportunities for the new antitumor strategies in patients with cancer.

4.
Artif Cells Nanomed Biotechnol ; 47(1): 2810-2820, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31284775

RESUMO

Cellular quiescence (G0) is a sleep-like cellular state that allows cells to maintain the ability to re-enter and exit the proliferative cycle. Quiescent cancer cells are considered a therapeutic challenge since they are often resistant to conventional chemoradiotherapy resulting in disease progression and relapse. To date, the majority of published studies have focused on identifying molecules that target proliferating tumor cells while limited information is available on methods to target quiescent cancer cells. This review provides a summary of the relevant molecular mechanisms underlying quiescence maintenance and pharmacological interventions aimed at either eliminating this cancer cell subpopulation or indefinitely maintaining the quiescence state. Furthermore, the irradiation responses of quiescent cancer cells, in particular, the influence of manipulating intratumor hypoxia and radiation properties on radiosensitivity, are discussed. The main aim of this article is to provide a theoretical basis for the effective targeted killing of dormant tumor cells.

5.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2102-2109, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355568

RESUMO

The main chemical constituents of naphthopyrone reference extract( NRE) with definite content and relatively fixed chemical composition were analyzed and determined. Ultra-high performance liquid chromatography-LTQ-Orbitrap XL mass spectrometry and high performance liquid chromatography were used to systematically study NRE from the aspects of main chemical components and determination. The results showed that the chemical composition of naphthopyrone reference extract of Cassiae Semen was relatively fixed,and seven naphthalopyranones were identified. Cassiaside B_2,cassiaside C_2,rubrofusarin-6-O-ß-D-gentiobioside and cassiaside C were the main chemical constituents of NRE,of which the determination and uncertainty results were( 11. 40+ 0. 26) %,( 11. 68+0. 24) %,( 16. 60+0. 22) %,( 28. 8+0. 48) %,respectively. This study contributed to the accurate evaluation of NRE and the foundation for the application of NRE in the quality control of Cassiae Semen,and provided a new idea for the replacement of single chemical reference substance by the reference extract of traditional Chinese medicine.


Assuntos
Cassia/química , Medicamentos de Ervas Chinesas/normas , Extratos Vegetais/normas , Sementes/química , Certificação , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Controle de Qualidade
6.
Liver Transpl ; 25(8): 1251-1264, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152624

RESUMO

Liver transplantation (LT) is currently considered an important method in treating hepatocellular carcinoma (HCC) and an alternative treatment for other liver malignancies. Here, we demonstrated that the graft-versus-tumor (GVT) effect exists in allogeneic liver transplantation (allo LT). Recipient-derived T cells played a critical role in the GVT process of allo LT, as demonstrated by extensive infiltration and significant activation of recipient T cells in the tumor after surgery. Moreover, this process was related to donor-derived T/B cells by improving the immune microenvironment in the tumor, as demonstrated by elevated levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-6, IL-16, chemokine (C-X-C motif) ligand 10 (CXCL10), and CXCL11 and decreased levels of IL-10 and IL-4 at tumor sites. Additionally, tacrolimus (FK506) treatment inhibited the GVT effect on allo LT. Donor liver-derived T/B cells infiltrate extrahepatic tumors to trigger a strong T-cell-mediated immune response and thus improve the tumor immune microenvironment.

7.
J Clin Hypertens (Greenwich) ; 21(8): 1082-1090, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31241860

RESUMO

There is no study to compare different class of antihypertensive drugs on new-onset diabetes mellitus (NOD) in elderly. We aimed to investigate the risk of antihypertensive drugs on NOD in elderly patients. The databases were retrieved in an orderly manner from the dates of their establishment to October, 2018, including Medline, Embase, Clinical Trials, and the Cochrane Database, to collect randomized controlled trials (RCTs) of different antihypertensive drugs in elderly patients (age > 60 years). Then, a network meta-analysis was conducted using R and Stata 12.0 softwares. A total of 14 RCTs involving 74 042 patients were included. The relative risk of NOD mellitus associated with six classes of antihypertensive drugs was analyzed, including placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics, and ß blockers. Patients with ACEIs or ARBs appeared to have significantly reduced risk of NOD compare with placebo: ACEIs (OR = 0.49, 95% CrI 0.28-0.85), ARBs (OR = 0.37, 95% CrI 0.26-0.52), while CCBs, diuretics, and ß blockers appeared to have not significantly reduced risk of NOD mellitus compare with placebo: CCBs (OR = 1.10, 95% CrI 0.85-1.60), diuretics (OR = 1.40, 95% CrI 0.92-2.50), ß blockers (OR = 1.40, 95% CrI 0.93-2.10). The SUCRA of placebo, ACEIs, ARBs, CCBs, diuretics, and ß blockers was, respectively, 65.3%, 69.3%, 92.3%, 44.1%, 12.1%, and 16.5%. According to the evidence, ARBs have an advantage over the other treatments in reducing the risk of NOD in elderly patients.

8.
Mol Med Rep ; 19(4): 3168-3178, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816496

RESUMO

Loss of peritubular capillaries is a notable feature of progressive renal interstitial fibrosis. Astaxanthin (ASX) is a natural carotenoid with various biological activities. The present study aimed to evaluate the effect of ASX on unilateral ureteral obstruction (UUO)­induced renal fibrosis in mice. For that purpose, mice were randomly divided into five treatment groups: Sham, ASX 100 mg/kg, UUO, UUO + ASX 50 mg/kg and UUO + ASX 100 mg/kg. ASX was administered to the mice for 7 or 14 days following UUO. The results demonstrated that UUO­induced histopathological changes in the kidney tissue were prevented by ASX. Renal function was improved by ASX treatment, as evidenced by decreased blood urea nitrogen and serum creatinine levels. Furthermore, the extent of renal fibrosis and collagen deposition induced by UUO was suppressed by ASX. The levels of collagen I, fibronectin and α­smooth muscle actin were increased by UUO in mice or by transforming growth factor (TGF)­ß1 treatment in NRK­52E cells, and were reduced by ASX administration. In addition, ASX inhibited the UUO­induced decrease in peritubular capillary density by upregulating vascular endothelial growth factor and downregulating thrombospondin 1 levels. Inactivation of the TGF­ß1/Smad signaling pathway was involved in the anti­fibrotic mechanism of ASX in UUO mice and TGF­ß1­treated NRK­52E cells. In conclusion, ASX attenuated renal interstitial fibrosis and peritubular capillary rarefaction via inactivation of the TGF­ß1/Smad signaling pathway.


Assuntos
Fibrinolíticos/farmacologia , Nefropatias/etiologia , Nefropatias/patologia , Rarefação Microvascular/etiologia , Rarefação Microvascular/patologia , Obstrução Ureteral/complicações , Animais , Biomarcadores , Biópsia , Linhagem Celular , Modelos Animais de Doenças , Fibrose , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Masculino , Camundongos , Rarefação Microvascular/tratamento farmacológico , Rarefação Microvascular/metabolismo , Ratos , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Xantofilas/farmacologia
9.
Transgenic Res ; 28(2): 257-266, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30830582

RESUMO

Phytophthora root and stem rot (PRR) caused by an oomycete pathogen Phytophthora sojae is one of the most devastating and widespread diseases throughout soybean-producing regions worldwide. The diversity and variability of P. sojae races make effective control of the pathogen challenging. Here, we introduced an elicitor of plant defense response, the harpinXooc-encoding hrf2 gene from the rice bacterial pathogen Xanthomonas oryzae pv. oryzicola into soybean and evaluated resistance to P. sojae infection. Molecular analysis confirmed the integration and expression of hrf2 in the transgenic soybean. After inoculation with P. sojae, non-transformed control (NC) plants exhibited typical PRR symptoms, including necrotic and wilting leaves, and plant death, whereas most of the transgenic plants showed slightly chlorotic leaves and developed normally. Through T3 to T5 generations, the transgenic events displayed milder disease symptoms and had higher survival rates compared to NC plants, indicating enhanced and stable resistance to P. sojae infection, whereas without P. sojae inoculation, no significant differences in agronomic traits were observed between the transgenic and non-transformed plants. Moreover, after inoculation with P. sojae, significant upregulation of a set of plant defense-related genes, including salicylic acid- and jasmonic acid-dependent and hypersensitive response-related genes was observed in the transgenic plants. Our results indicate that hrf2 expression in transgenic soybean significantly enhanced resistance to P. sojae by eliciting multiple defense responses mediated by different signaling pathways. The potential functional role of the hrf2 gene in plant defense against P. sojae and other pathogens makes it a promising tool for broadening disease resistance in soybean.


Assuntos
Resistência à Doença , Interações Hospedeiro-Parasita/genética , Phytophthora/patogenicidade , Doenças das Plantas/parasitologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/parasitologia , Soja/parasitologia , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Transdução de Sinais , Soja/genética , Soja/crescimento & desenvolvimento
10.
Environ Int ; 127: 35-51, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30901640

RESUMO

Given the ongoing studies on the adverse effects of organophosphate ester (OPE) flame retardants and plasticizers on human health, there is an increasing scientific interest in the risk of exposure to OPEs via dietary intake. Using peer-reviewed literature published up to 2018, this review surveyed and compiled the available and reported data on the concentrations and distributions of 30 OPEs based on their occurrence in various food samples from around the world. Regardless of sampling locations or food categories, 22 OPEs were detectable in at least one of analyzed sample, and there were clear variations in OPE levels among samples from different locations or food categories. For instance, cereals and fats/oils were the most contaminated by OPEs in China and Belgium, whereas fats/oils and desserts were the main polluted products in Sweden. In contrast, vegetables, fruits, fluid dairy products, and cereals were reported as the primary categories of food polluted by OPEs in Australia. Animal-based food categories such as eggs, fish and meat were the least contaminated, whereas the highest median OPE concentrations were found in meat and fish from the United State. The levels and distribution patterns of OPEs in foodstuffs demonstrated a tremendous difference even when collected from the same country and the same food item. Rice from China had the highest tris(2­chloroethyl) phosphate (TCEP, mean: 29.8 ng/g dw) levels, whereas 2­ethylhexyl­diphenyl phosphate (EHDPP, mean: 4.17 ng/g ww), triphenyl phosphate (TPHP, mean: 26.14 ng/g ww), tris(2-chloroisopropyl) phosphate (TCIPP, mean: 0.87 ng/g ww) and tributyl phosphate (TNBP, median: 0.55 ng/g ww) concentrations were the highest in the same food category from Sweden, Belgium, Australia, and the United States, respectively. These discrepancies may be due to a variety of reasons such as differences in OPE physico-chemical properties, extent of usage, uptake, metabolic pathways, industrial food manufacturing processes, OPE level differences as a function of habitat, and accumulation and degradability of OPEs in different species. It is worth noting that, due to its worldwide usage in food packaging materials, EHDPP was more prominently found in processed food compared to non-processed food. Based on reported OPE levels in various foods, this review conducted a preliminary assessment of human exposure to OPEs through dietary intake, which suggested that the OPE estimated daily intake (EDI) for humans was around 880 ng/kg bw/day (95th percentile). This value was well below the corresponding OPE health reference dose given by the U.S. EPA (≥15,000 ng/kg bw/day). Even so, dietary exposure to OPEs via food intake may be not negligible based on some important factors such as dilution effects, cooking processes, and the contribution of as yet unknown means of OPE exposure. Overall, this review highlights several gaps in our understanding of OPEs in foodstuffs: 1) the investigation of contamination levels of OPEs in foodstuffs should be extended to other regions, especially North America and European countries, where OPEs are widely used and frequently detected in environmental samples, and 2) newly identified OPE derivatives/by-products, e.g., OP diesters and hydroxylated metabolites, which have been reported as end-products of OPE enzymatic metabolism or degradation through aqueous hydrolysis, and which may co-exist with parent OPEs, could also be screened with precursor OPEs in foodstuffs in future studies.

11.
Int J Mol Sci ; 20(3)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754640

RESUMO

The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression. In addition, mTOR also negatively regulates autophagy via different ways. We discuss mTOR signaling and its key upstream and downstream factors, the specific genetic changes in the mTOR pathway and the inhibitors of mTOR applied as therapeutic strategies in eight solid tumors. Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.


Assuntos
Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Ensaios Clínicos como Assunto , Humanos , Neoplasias/patologia , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do Tratamento
12.
Int J Biol Macromol ; 130: 68-78, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797009

RESUMO

We isolated and characterized a Mussel polysaccharide, α-D-glucan (MP-A), from Mytilus coruscus earlier. In this work, the pharmacological activity and mechanisms of MP-A as an oral supplement for non-alcoholic fatty liver disease (NAFLD) were explored. High fat diet (HFD) was utilized to induce NAFLD in Sprague Dawley male rats and MP-A (0.6 g/kg) was supplemented for 4 weeks. The results showed that MP-A supplementation reduced blood lipid levels, intrahepatic lipid accumulation and NAFLD activity score in HFD-fed rats. Additionally, the analysis of 16S rDNA sequencing on gut microbiota samples revealed that HFD could induce microbial dysbiosis. However, MP-A supplementation could remodel gut microbiota structure, inhibit LPS-TLR4-NF-κB pathway activation, and restrain subsequent inflammation factors secretion. Furthermore, MP-A regulated the lipid metabolism by promoting the production of short chain fatty acids and suppressing PPAR γ and SREBP-1c expression. Our results support that MP-A can prevent against NAFLD and act as an oral supplementation for hepatoprotection via modulating gut microbiota and related gut-liver axis signaling pathways.


Assuntos
Bivalves/química , Microbioma Gastrointestinal/efeitos dos fármacos , Glucanos/farmacologia , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Triglicerídeos/metabolismo
13.
J Reprod Immunol ; 131: 30-35, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30634133

RESUMO

OBJECTIVE: To investigate whether epigenetic modification of CD4+CD25- T-cells in vitro can make up for the inadequacy of CD4+CD25+Foxp3+ Treg in animal model of spontaneous abortion and prevent immune response-mediated spontaneous abortion. METHODS: Trichostatin A (TSA) was applied to inhibit histone deacetylases (HDACs) and thereby to epigenetically modify the special location of Foxp3 gene in CD4+CD25- T-cells of CBA/J mice. The expressions of CD25, Foxp3, CTLA-4 and PD-1 of CD4+ T cells isolated from spleen of mice were characterized by flow cytometric analysis. Concentrations of transforming growth factor- ß (TGF-ß) and IL-10 in the supernatants of cultured Treg were measured using ELISA. The purified CD4+ T cells treated with different reagents were injected into pregnant CBA/J mice mated with DBA/2J males on Day 1 and 4 of pregnancy, respectively. The embryo resorption rate was assessed on Day 14 of pregnancy. RESULTS: TSA treatment significantly increased the population of CD4+CD25+Foxp3+ iTreg. Those TSA induced Treg expressed high levels of PD-1 and CTLA-4, and secreted high levels of TGF-ß and IL-10. Adoptive transfer of those iTreg at both early stage and implantation of stage of pregnancy significantly increased population of CD4+CD25+Foxp3+ Treg in spleens of recipient miscarriage prone mice and significantly reduced resorption in those mice. CONCLUSION: Epigenetic regulation of Foxp3 can generate functional regulatory T-cells. Adoptive transfer of TSA- induced CD4+CD25+Foxp3+ Treg at an early stage of pregnancy can induce maternal-fetal immune tolerance and reduce embryo resorption in miscarriage prone mice.

14.
Int J Syst Evol Microbiol ; 69(3): 816-820, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30694172

RESUMO

A Gram-stain-negative, rod-shaped (0.2-0.4 µm×1.2-1.7 µm), endophytic bacterium, designated HBUM179779T, was isolated from the stem of a medicinal plant,Gynura bicolor, collected from Pixian county in Sichuan province, China. The strain did not produce endospores and its cells could secrete mucus. The predominant menaquinone was MK-7. The polar lipids were phosphatidylethanolamine, phosphatidylinositolmannosides, two unknown aminolipids, two unknown glycolipids and an unknown phospholipid. Branched fatty acids (iso-) and hydroxy fatty acids were the main fatty acids, which mainly included iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HBUM179779T fell within the family Chitinophagaceae, and its closest neighbour was Pseudoflavitalea rhizosphaerae T16R-265T (94.46 %). However, strain HBUM179779T did not make a coherent clade with members of the recognized organisms. The average nucleotide identity value between strain HBUM179779T and Pseudoflavitalea rhizosphaerae T16R-265T was 67.1 %. On the basis of the phylogenetic and phenotypic characteristics of this bacterium, a novel genus and species, Gynurincola endophyticus gen. nov., sp. nov., is proposed. The type strain is HBUM179779T (=CGMCC 1.15525T=NBRC 112424T).


Assuntos
Asteraceae/microbiologia , Bacteroidetes/classificação , Filogenia , Caules de Planta/microbiologia , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Plantas Medicinais/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
J Antibiot (Tokyo) ; 72(4): 210-217, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30635615

RESUMO

To find novel amphotericin B (AmB) derivatives with high therapeutic potential, low toxicity, and water solubility, a series of nine N-substituted AmB derivatives were evaluated for their antifungal activity using the broth dilution method and for their hemolytic toxicity with sterile defibrinated sheep blood. Qualitative screening of the effect of the derivatives on two reference Candida albicans strains and of their solubility was performed based on the value of n (n is a positive integer), resulting in the identification of an optimal compound, NH2-(AEEA)5-AmB (DMR005; AEEA is 8-amino-3,6- dioxaoctanoic acid). Preliminary safety assessments of DMR005 were carried out via the MTT cell viability assay in vitro and acute toxicity assay in vivo. In general, DMR005 not only has higher water solubility and less toxicity than the parent polyene but also retains antifungal potency.


Assuntos
Anfotericina B/síntese química , Anfotericina B/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Anfotericina B/análogos & derivados , Anfotericina B/toxicidade , Animais , Antifúngicos/toxicidade , Sobrevivência Celular , Técnicas Citológicas , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Envenenamento/patologia , Ovinos , Solubilidade
16.
Anaerobe ; 55: 136-141, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30529715

RESUMO

Though the problem of neonatal piglet diarrhea is well known, the differences in the bacterial diversity and community composition between healthy and diarrheal piglets are still unknown. We investigated these differences in neonatal piglets from Jiangxi Province, China. Healthy (H, n = 20) and diarrheal (D, n = 20) piglets were selected from six regions. The fecal microbial communities were analyzed by sequencing the V3V4 region of 16S rRNA gene. We found the ratio of major phyla (Fusobacteria, Bacteroidetes, Firmicutes and Proteobacteria) was >99% of 7 phyla. The overall alpha diversity indices, such as chao, sobs, coverage and Shannon, were not significantly different. Moreover, the relative abundance of the predicted functions was highly similar in the two groups. Our results indicated that Clostridium was divided into two major groups: Clostridium sensu stricto_1 and stricto_2. Sensu stricto_2 was highly abundant in the D group and low abundance in the H group, whereas the results of sensu stricto_1 were opposite. Comparative analyses within the H or D groups showed that Escherichia-Shigella and Streptococcus at the genus level and unclassified Lactobacillus at the species level were significant difference. Comparative analyses of the two groups showed that unclassified Prevotellaceae at the genus level and Fusobacterium mortifierum were significantly different and had high linear discriminant analysis (LDA) scores. The significantly different microbes composition results also existed in the same litter, based on excluding regions influence. These results suggested that piglet diarrhea was closely associated with these microbes. This study provides insights into gut microbial interactions and prevention of piglet diarrhea.


Assuntos
Bactérias/classificação , Diarreia/veterinária , Microbioma Gastrointestinal , Doenças dos Suínos/microbiologia , Animais , Animais Recém-Nascidos , Bactérias/genética , China , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Diarreia/microbiologia , Variação Genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suínos
17.
Biotechnol Appl Biochem ; 66(2): 192-201, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30578642

RESUMO

Limonin, a compound of highly oxidized triterpenoids, has potential functions in preventing or slowing the occurrences of many diseases. In this study, five different bacterial strains were isolated and identified from Citrus maxima (Burm.) Merr. cv. Shatian Yu. Morphological characteristics and 16S rRNA gene sequencing identified them as Bacillus spp, in which two limonin-producing endophytes named P and P9 were discovered by high-performance liquid chromatography and mass spectrometry using an inorganic salt medium and two natural media; also the production was greater in natural medium 1 (4.377 and 0.299 mg/L, respectively) than in natural medium 2 (0.159 and 0.025 mg/L, respectively). The growth and fermentation characteristics of strain P were studied, and during the liquid cultivation of Bacillus sp. P, limonin began to accumulate at the eighth hour in the inorganic salt medium, peaked at the 16th hour, and then decreased sharply. Single-factor experiments revealed that the optimum fermentation conditions for limonin production included 14-H-old cells, 15% inoculum, and 3 g/L glucose.


Assuntos
Bacillus/crescimento & desenvolvimento , Bacillus/isolamento & purificação , Citrus/microbiologia , Limoninas/biossíntese
18.
Cell Res ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514900

RESUMO

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

19.
J Biochem Mol Toxicol ; : e22241, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30431689

RESUMO

Ring1 and YY1 binding protein (RYBP), a new member of the polycomb group protein family, has been reported to play an important role in various biological processes. Recently, more and more studies have demonstrated an implication of RYBP in cancer development. However, the specific role of RYBP in anaplastic thyroid cancer (ATC) remains unknown. In this study, we investigated for the first time the expression pattern and biological functions of RYBP in ATC. We showed that RYBP was lowly expressed in ATC tissues and cell lines. We also found that overexpression of RYBP inhibited ATC cell proliferation, invasion, and cisplatin resistance. Furthermore, we observed that upregulation of RYBP decreased the phosphorylation of EGFR and ERK1/2 in ATC cells. Taken together, our data indicated that RYBP might be considered as a promising therapeutic target for the treatment of ATC.

20.
Front Hum Neurosci ; 12: 381, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30455636

RESUMO

Research about decoding neurophysiological signals mainly aims to elucidate the details of human motion control from the perspective of neural activity. We performed brain connectivity analysis with EEG to propose a brain functional network (BFN) and used a feature extraction algorithm for decoding the voluntary hand movement of a subject. By analyzing the characteristic parameters obtained from the BFN, we extracted the most important electrode nodes and frequencies for identifying the direction of movement of a hand. The results demonstrated that the most sensitive EEG components were for frequencies delta, theta, and gamma1 from electrodes F4, F8, C3, Cz, C4, CP4, T3, and T4. Finally, we proposed a model for decoding voluntary movement of the right hand by using a hierarchical linear model (HLM). Through a voluntary hand movement experiment in a spiral trajectory, the Poisson coefficient between the measurement trajectory and the decoding trajectory was used as a test standard to compare the HLM with the traditional multiple linear regression model. It was found that the decoding model based on the HLM obtained superior results. This paper contributes a feature extraction method based on brain connectivity analysis that can mine more comprehensive feature information related to a specific mental state of a subject. The decoding model based on the HLM possesses a strong structure for data manipulation that facilitates precise decoding.

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