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1.
Bioinformatics ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904845

RESUMO

MOTIVATION: Predicting the association between microRNAs (miRNAs) and diseases plays an import role in identifying human disease-related miRNAs. As identification of miRNA-disease associations via biological experiments is time-consuming and expensive, computational methods are currently used as effective complements to determine the potential associations between disease and miRNA. RESULTS: We present a novel method of neural inductive matrix completion with graph convolutional network (NIMCGCN) for predicting miRNA-disease association. NIMCGCN first uses graph convolutional networks (GCNs) to learn miRNA and disease latent feature representations from the miRNA and disease similarity networks. Then, learned features were input into a novel neural inductive matrix completion (NIMC) model to generate an association matrix completion. The parameters of NIMCGCN were learned based on the known miRNA-disease association data in a supervised end-to-end way. We compared the proposed method with other state-of-the-art methods. The AUC results showed that our method is significantly superior to existing methods. Furthermore, 50, 47, and 48 of the top 50 predicted miRNAs for three high-risk human diseases, namely, colon cancer, lymphoma, and kidney cancer, were verified using experimental literature. Finally, 100% prediction accuracy was achieved when breast cancer was used as a case study to evaluate the ability of NIMCGCN for predicting a new disease without any known related miRNAs. AVAILABILITY AND IMPLEMENTATION: https://github.com/ljatynu/NIMCGCN/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2.
Mol Phylogenet Evol ; 145: 106729, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926307

RESUMO

The Cleisostoma-Gastrochilus clades are among the most speciose and diverse groups of Asian orchids and are a taxonomically problematic group. Phylogenetic relationships among the genera of these clades have remained unresolved with traditional sequences from one or a few markers. We present large-scale phylogenomic data sets, incorporating complete chloroplast genome sequences from 53 species (including 41 species sequenced in this study), to compare plastome structure and to resolve the phylogenetic relationships of these clades. The plastomes of Cleisostoma-Gastrochilus clades possessed the quadripartite structure and plastome genes of typical angiosperms with sizes ranging from 142 to 149 kb and encoding a set of 118-120 genes. Unusual structural features were detected in the plastome of Uncifera acuminata, including the presence of a large 17-kb inversion (19 genes) in the Large Single-Copy region and the loss of the rpl32 gene in Cleisostoma fuerstenbergianum. The pseudogenization of ndh genes was widespread in these clades. Phylogenomic analyses, including 68 plastid protein-coding genes, showed that these clades can be subdivided into three major groupings and six subgroupings: Vandopsis undulata, the Gastrochilus clade (including the Trichoglottis and Gastrochilus subclades) and the Cleisostoma clade (including the Vandopsis, Diploprora, Cleisostoma and Schoenorchis subclades). Two genera, Vandopsis and Cleisostoma, were not monophyletic. A new genus, Cymbilabia, was proposed to avoid non-monophyly of Vandopsis. Our results demonstrate the power of plastid phylogenomics to improve the phylogenetic relationships of intricate groups and provide new insight into plastome evolution in Orchidaceae.

4.
Acta Pharmacol Sin ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949292

RESUMO

Metrnl is a newly identified secreted protein highly expressed in the intestinal epithelium. This study aimed to explore the role and mechanism of intestinal epithelial Metrnl in ulcerative colitis. Metrnl-/- (intestinal epithelial cell-specific Metrnl knockout) mice did not display any phenotypes of colitis under basal conditions. However, under administration of 3% dextran sodium sulfate (DSS) drinking water, colitis was more severe in Metrnl-/- mice than in WT mice, as indicated by comparisons of body weight loss, the presence of occult or gross blood per rectum, stool consistency, shrinkage in the colon, intestinal damage, and serum levels of inflammatory factors. DSS-induced colitis activated autophagy in the colon. This activation was partially inhibited by intestinal epithelial Metrnl deficiency, as indicated by a decrease in Beclin-1 and LC3-II/I and an increase in p62 in DSS-treated Metrnl-/- mice compared with WT mice. These phenomena were further confirmed by observation of autophagosomes and immunofluorescence staining for LC3 in epithelial cells. The autophagy-related AMPK-mTOR-p70S6K pathway was also activated in DSS-induced colitis, and this pathway was partially blocked by intestinal epithelial Metrnl deficiency, as indicated by a decrease in AMPK phosphorylation and an increase in mTOR and p70S6K phosphorylation in DSS-treated Metrnl-/- mice compared with WT mice. Therefore, Metrnl deficiency deteriorated ulcerative colitis at least partially through inhibition of autophagy via the AMPK-mTOR-p70S6K pathway, suggesting that Metrnl is a therapeutic target for ulcerative colitis.

5.
Chem Commun (Camb) ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956887

RESUMO

A novel strategy through a temperature-responsive dissolution and recrystallization process has successfully achieved 100% atomic utilization and easy recyclability of heterogeneous metal organic framework dimethylammonium zinc formate (DMZnF) catalysts for highly efficient dehydrogenation of DMF-H2O for hydrogen generation. DMZnF dissolves as a homogeneous catalyst at high reaction temperatures and then is recrystallized and recycled as a heterogeneous catalyst at low temperatures.

6.
Mikrochim Acta ; 187(1): 77, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894422

RESUMO

Amino-functionalized polyhedral oligomeric silsesquioxanes (POSS-8NH2) were covalently bound to the surface of polydopamine-coated magnetized graphene oxide. It was then reacted with 4-formylphenylboronic acid to prepare a "cubic boronic acid"-bonded magnetic graphene oxide adsorbent. The new adsorbent exhibits better selectivity and much higher adsorption capacity for ortho-phenols over adsorbents where small boronic ligands are directly bound to the surface of the material. It is shown to enable selective and faster enrichment of the catecholamines epinephrine (EP), dopamine (DA) and isoprenaline (IP) with high selectivity over many potential interferents that can occur in urine. The analytes were then quantified by HPLC with fluorometric detection. Under optimal conditions, response is linear (R2 ≥ 0.9907), limits of detection are low (0.54-2.3 ng·mL-1), and reproducibility is acceptable (inter- and intra-day assay RSDs of≤10.9%). The method was successfully applied to the determination of endogenous EP and DA and exogenous IP in urine samples. Graphical abstractSchematic of boronic acid (BA)-modified polyhedral oligomeric silsesquioxanes (POSS) on polydopamine-coated magnetized graphene oxide (magGO). The material (magGO@POSS-BA) has good selectivity and higher adsorption capacity to ortho-phenols and can be applied to enrich the catecholamines in urine.

7.
Bioorg Med Chem Lett ; 30(2): 126791, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740251

RESUMO

Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22 µM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.

8.
Biol Trace Elem Res ; 193(1): 1-6, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30820755

RESUMO

To observe and compare the effects of healthy instruction and Zhiqi granules on lead, calcium, iron, and zinc levels in serum of children with moderately elevated blood lead levels (BLLs). At the same time, the possible mechanisms were discussed. A total of 60 eligible boys aged 4-6 years were selected and divided into two groups (the healthy instruction group and the Zhiqi group) randomly. The boys in the healthy instruction group only received the healthy instruction. Besides the healthy instruction, the boys in the Zhiqi group received 2 g Zhiqi granules orally one time daily. The study lasted for 4 weeks. BLL and serum iron, zinc, and calcium levels of the subjects in the two groups before and after interventions were measured and compared. After the interventions, the BLL in the Zhiqi group lowered significantly, but the decrease of the BLL in the healthy instruction group is not significant, and there was a significant difference in the BLL between the two groups. When the trial was completed, the serum iron level in the Zhiqi group increased significantly, but that in the healthy instruction group changed slightly, and a significant difference was seen between the two groups. There were no significant differences in both serum Ca and Zn levels in these two groups before and after the interventions. Meanwhile, there were no significant differences in serum Ca and Zn levels between the two groups after the interventions. The results suggested that daily intake of Zhiqi granules for 4 weeks together with healthy instruction resulted in a decrease of the BLL and an elevation of the serum iron level.

9.
Bioelectrochemistry ; 131: 107349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31476657

RESUMO

Several textile industry processes produce complex organics, azo dyes and sulfide streams that pose a severe challenge to environmental protection. In this work, single-chamber air cathode microbial fuel cells were used to investigate the interaction mechanisms among Congo red decolorization, sulfide oxidation and bioelectricity generation. The results showed that effective removal of sulfide (>98%) and azo dyes (>88%) was achieved at an initial sulfide/dye ratio of 0.9 under neutral conditions, accompanied by a maximum power output of approximately 23.50 mW m-2. In this study, biogenic sulfide played a major role in azo dye decolorization and power generation compared with the chemical sulfide. The results indicated that bulk reduction of sulfide and cell lysis products during biogenic sulfide production by sulfate-reduction bacteria could accelerate the chemical reduction of azo dyes. Moreover, S0, SO42- and S2O32- were identified as degradation products, and the intermediates primarily included 3,4-diaminonaphthalene-1-sulfonic acid, sodium 4-aminonaphthalene-1-sulfonate and 4, 4'-diamine biphenyl. Microbial community analysis showed that Proteobacteria (80.7%), Gammaproteobacteria (48.1%), and Dokdonella (29.5%) dominated at the phylum, class, and genus levels, respectively, of the anodic biofilm. This study offers a feasible option for the treatment of recalcitrant organics, azo dyes and sulfide pollutants using single-chamber air cathode MFCs.


Assuntos
Compostos Azo/metabolismo , Fontes de Energia Bioelétrica , Eletrodos , Microbiota , Sulfetos/metabolismo , Compostos Azo/isolamento & purificação , Cor , Vermelho Congo/metabolismo , Gammaproteobacteria/metabolismo , Filogenia , Proteobactérias/metabolismo
10.
Exp Cell Res ; 387(2): 111783, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31857113

RESUMO

The rare gestational trophoblastic neoplasia placental site trophoblastic tumor (PSTT) frequently demonstrates a high degree of vascularization, which may facilitate the tumor metastasis. However, the underlying mechanisms remain largely unknown. In the present study, we found that early growth response 1 (EGR1) was highly expressed in the carcinoma-associated fibroblasts (CAFs) of PSTT tissues. Further data showed that miR-363 down-regulated EGR1 expression whereas long non-coding RNA NONHSAT003875 (lnc003875) up-regulated EGR1 expression in PSTT derived CAFs. lnc003875 exerted no effect on miR-363 expression, but it recovered the decrease of EGR1 caused by miR-363 mimic. The conditioned media from PSTT CAFs treated with miR-363 mimic abrogated the tube formation capacity of human umbilical vein endothelial cells (HUVECs), which can be partially restored by lnc003875 over-expression. Moreover, over-expression of EGR1 promoted the secretion of Angiopoietin-1 (Ang-1) in PSTT derived CAFs and improved the tube formation of HUVECs, which could be effectively abrogated by Ang-1 siRNAs. In vivo vasculogenesis assay demonstrated that lnc003875/EGR1 in PSTT derived CAFs promoted the vasculogenesis of HUVECs in C57BL/6 mice. Collectively, these findings indicated that lnc003875/miR-363/EGR1/Ang-1 in CAFs may be crucial for the angiogenesis of PSTT.

11.
Stem Cells Dev ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31830866

RESUMO

The secretome of mesenchymal stem cell offers a series of immuno-regulatory properties and is regarded as an effective method of mitigating secondary neuroinflammation induced by traumatic brain injury (TBI). The secretome of adipose-derived MSCs (ASC-ST) was collected under hypoxia conditions. Proteomics data were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and concentrations of major components were tested. Following the TBI caused by an electric cortical contusion impactor, rats were injected ASC-ST via caudal veins for 7 days. The neurological functional prognosis of TBI rats was significantly improved, and the vasogenic edema of brain tissues that was measured 14 days after TBI was relieved by ASC-ST, corresponding to brain water content levels. ASC-ST ameliorated TBI-induced neuroinflammatory environments that caused the edema, the apoptosis of the neural cells, and the nerve fiber damage by increasing the number of M2 phenotypes present while reducing the number of M1 phenotype microglia present. Furthermore, IL-6 and TNF-α levels were reduced while TGF-ß and TSG-6 levels were increased after secretome treatment. Altogether, ASC-ST is capable of improving neural functioning by modulating TBI-induced neuroinflammation and its related secondary insults. ASC-ST may be one of the most promising candidates for regulating the secondary inflammatory reactions of central nervous systems for clinical use.

12.
Aging (Albany NY) ; 11(24): 12278-12294, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848325

RESUMO

Spinal cord injury (SCI) remains the most common cause of paralysis, and there are no effective therapies for SCI patients. Neural stem cell (NSC)-derived exosomes can attenuate apoptosis and neuroinflammation after traumatic spinal cord injury, but the mechanisms underlying these effects remain unclear. Here, we examined the efficacy of miRNAs isolated from exosomes as treatments for SCI and characterized their mechanisms of action. Furthermore, we evaluated the effects of exosomes formed in the presence of insulin growth factor-1 (IFG-1, IGF-Exo), which promotes neural proliferation and regeneration, as well as normal exosomes (Nor-Exo) and compared control and H2O2-treated groups both in vitro and in vivo. Using microRNA sequencing and qRT-PCR, we identified miR-219a-2-3p, levels of which were higher in the IGF-Exo than Nor-Exo group and played crucial anti-inflammatory and anti-apoptosis roles. Additional experiments revealed that IGF-Exo inhibits YY1 expression through up-regulation of miR-219a-2-3p. This in turn inhibits the NF-κB pathway, partly inhibiting neuroinflammation and promoting the neuroprotective effects after SCI.

13.
J Mater Sci Mater Med ; 30(11): 123, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31686219

RESUMO

Prognosis and treatment evaluation of spinal cord injury (SCI) are still in the long-term research stage. Prognostic factors for SCI treatment need effective biomarker to assess therapeutic effect. Quantitative diffusion tensor imaging (DTI) may become a potential indicators for assessing SCI repair. However, its correlation with the results of locomotor function recovery and tissue repair has not been carefully studied. The aim of this study was to use quantitative DTI to predict neurological repair of SCI with transplanting collagen/chitosan scaffold binding basic fibroblast growth factor (bFGF). To achieve our research goals, T10 complete transection SCI model was established. Then collagen/chitosan mixture adsorbed with bFGF (CCS/bFGF) were implanted into rats with SCI. At 8 weeks after modeling, implanting CCS/bFGF demonstrated more significant improvements in locomotor function according to Basso-Beattie-Bresnahan (BBB) score, inclined-grid climbing test, and electrophysiological examinations. DTI was carried out to evaluate the repair of axons by diffusion tensor tractgraphy (DTT), fractional anisotropy (FA) and apparent diffusion coefficient (ADC), a numerical measure of relative white matter from the rostral to the caudal. Parallel to locomotor function recovery, the CCS/bFGF group could significantly promote the regeneration of nerve fibers tracts according to DTT, magnetic resonance imaging (MRI), Bielschowsky's silver staining and immunofluorescence staining. Positive correlations between imaging and locomotor function or histology were found at all locations from the rostral to the caudal (P < 0.0001). These results demonstrated that DTI might be used as an effective predictor for evaluating neurological repair after SCI in experimental trails and clinical cases.

14.
Nano Lett ; 19(11): 8270-8277, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31661288

RESUMO

Nanomaterials with intrinsic enzyme-like characteristics exhibit their great potentials as alternatives to natural enzymes. Among various enzymes, the finding of substitutes of DNA photolyases, a family of photoenzymes for repairing the ultraviolet (UV)-induced DNA damage by forming cyclobutane pyrimidine dimers (CPDs) between two adjacent thymines in a DNA strand, is still unsuccessful. CPDs raise significant health concerns in various skin diseases. Essentially, DNA photolyases selectively split dimers into monomers by photoelectrons under visible-light irradiation, and this is a photocatalytic process. However, the majority of semiconductors are unprosperous due to the accompanied photogenerated reactive oxygen species (ROS), which decompose CPDs into fragments and thereby lead to a nonselective photocatalysis. Fortunately, CeO2 as a semiconductor might deliver the selectively photocatalytic repair of UV-induced DNA damages, where the photoelectrons are used for the CPD cleavage, and the photogenerated ROS are locally suppressed for its antioxidant nature. Herein, we reported the defective porous CeO2 delivered the photolyase-like activity by enhancing visible-light absorption, enabling the effective interaction between CPDs and catalysts, and subsequently triggering the selective photocleavage of CPDs into monomers. Further, in vitro cellular and in vivo animal evaluations illustrated its high potentials as alternatives to DNA photolyases.

15.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3116-3122, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602861

RESUMO

The quality marker( Q-maker) of traditional Chinese medicine( TCM) has been the core concept of TCM quality evaluation and control in recent years. Based on the knowledge and long-term practice of the researches on TCM quality,we put forward that " Taking the effectiveness as the core,the measurability and peculiarity as necessary conditions,and considering compatibility for TCM formulae,TCM Q-makers are selected and confirmed,and then the transmission and traceability should be investigated as its functional attributes". Selecting the commonly used representative TCM as the research object,based on the score of TCM effectiveness,measurability and peculiarity,a layered three-dimensional integrated technology was adopted for the quantitative evaluation and grading identification of the Q-markers for TCM. And after Q-markers for TCM are selected and confirmed,the transmission variation of the Q-markers is studied in the whole process from the formation of TCM to its function representation. Based on TCM chemical and biological characteristics as well as effectiveness,and integrating multidisciplinary techniques and methods,researches on innovative methods for system identification and confirmation of the TCM Q-makers are developed emphatically to form representative and exemplary extensive application,which will provide significant theoretical and methodological support for effectively improving the quality control level of TCM.


Assuntos
Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Chinesa/normas , Biomarcadores , Controle de Qualidade
16.
Zhongguo Zhen Jiu ; 39(10): 1075-80, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31621260

RESUMO

OBJECTIVE: To observe the effect of bloodletting acupuncture at twelve jing-well points of hand on microcirculatory disturbance in mice with traumatic brain injury (TBI), and to explore the protective effect of bloodletting therapy on TBI. METHODS: Sixty clean adult male C57BL/6J mice were randomly divided into a sham-operation group, a model group and a treatment group, 20 mice in each group. The TBI model was established by using electronic controlled cerebral cortex impact instrument in the model group and the treatment group. The mice in the treatment group were treated with bloodletting acupuncture at bilateral "Shaoshang" (LU 11), "Shangyang" (LI 1), "Zhongchong" (PC 9), "Guanchong" (TE 1), "Shaochong" (HT 9) and "Shaoze" (SI 1) immediately after trauma. The mice in the sham-operation group only opened the bone window but did not receive the strike. The regional cerebral blood flow (rCBF) was monitored by laser speckle contrast analysis (LASCA) using a PeriCam PSI System before trauma, immediately after trauma and 1, 2, 12, 24, 48, 72 h after trauma. The brain water content was measured by wet-dry weight method 24 h after trauma. The severity of functional impairment at 2, 12, 24, 48 and 72 h after trauma was evaluated by modified neurological scale scores (mNSS). RESULTS: ① 2 h after trauma, the mNSS in the model group and treatment group were >7 points, suggesting the successful establishment of model; compared with the sham-operation group, the mNSS was increased significantly from 12 to 72 h after trauma in the model group ( all P<0.01), but the mNSS in the treatment group was significantly lower than that in the model group from 2 to 24 h after trauma (P<0.01, P<0.05). ② Compared with the sham-operation group, rCBF in the model group was decreased significantly immediately after trauma (P<0.01), and the rCBF in the model group was lower than that in the sham-operation group from 1 to 72 h after trauma ( all P<0.01); rCBF in the treatment group began to rise and was significantly higher than that in the model group 1-2 h after trauma (P<0.01); 12-48 h after trauma, the increasing of rCBF in the two groups tended to be gentle until 72 h after injury, and rCBF in the model group was decreased while that in the treatment group continued to rise and was higher than that in the model group (P<0.01). ③ 24 h after trauma, the brain water content in the model group was significantly higher than that in the sham-operation group (P<0.01), and brain water content in the treatment group was significantly lower than that in the model group (P<0.01). CONCLUSION: The bloodletting acupuncture at twelve jing-well points of hand could improve microcirculation disturbance, increase microcirculation perfusion, alleviate secondary brain edema and promote the recovery of nerve function in mice with TBI.


Assuntos
Terapia por Acupuntura , Sangria , Lesões Encefálicas Traumáticas , Pontos de Acupuntura , Animais , Lesões Encefálicas Traumáticas/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação , Distribuição Aleatória
17.
Eur J Med Chem ; 183: 111731, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577977

RESUMO

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC50 = 1.02 µM), HGC-27 cells (IC50 = 1.61 µM), SGC-7901 (IC50 = 2.30 µM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.


Assuntos
Antineoplásicos , Benzimidazóis/química , Neoplasias Gástricas/tratamento farmacológico , Sulfonamidas , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Drogas , Humanos , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia
18.
J Immunol ; 203(8): 2150-2162, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31554695

RESUMO

Hepatic immune system is uniquely challenged to mount a controlled effector response to pathogens while maintaining tolerance to diet and microbial Ags. We have identified a novel population of innate-like, unconventional CD8αα+TCRαß+ T cells in naive mice and in human peripheral blood, called CD8αα Tunc, capable of controlling effector T cell responses. They are NK1.1+ (CD161+ in human), express NK-inhibitory receptors, and express the promyelocytic leukemia zinc finger (PLZF) transcription factor that distinguishes them from conventional CD8+ T cells. These cells display a cytotoxic phenotype and use a perforin-dependent mechanism to control Ag-induced or T cell-mediated autoimmune diseases. CD8αα Tunc are dependent upon IL-15/IL-2Rß signaling and PLZF for their development and/or survival. They are Foxp3-negative and their regulatory activity is associated with a functionally distinct Qa-1b-dependent population coexpressing CD11c and CD244. A polyclonal TCR repertoire, an activated/memory phenotype, and the presence of CD8αα Tunc in NKT- and in MAIT-deficient as well as in germ-free mice indicates that these cells recognize diverse self-protein Ags. Our studies reveal a distinct population of unconventional CD8+ T cells within the natural immune repertoire capable of controlling autoimmunity and also providing a new target for therapeutic intervention.

19.
J Agric Food Chem ; 67(41): 11464-11473, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532211

RESUMO

The intestinal epithelium is derived from intestinal stem cells (ISCs) and has direct contact with nutrients and toxins. However, whether methionine (Met) or a methionine hydroxyl analogue (2-hydroxy-4-(methylthio)butanoic acid (HMB)) can alleviate deoxynivalenol (DON)-induced intestinal injury remains unknown. Mice were treated orally with Met or HMB on days 1-11 and with DON on days 4-8. On day 12, the mice were sacrificed, and the jejunum was collected for crypt isolation and culture. Mouse enteroids were treated with DON and Met or HMB ex vivo. The results showed that Met and HMB increased the average daily feed intake and average daily gain of the mice. Met and HMB also improved the jejunal structure and barrier integrity and promoted ISC expansion, as indicated by the increased enteroid formation efficiency and area, under DON-induced injury conditions. In addition, DON-induced decreases in ISC activity were rescued Wnt/ß-catenin signaling reactivation by Met or HMB in vivo and ex vivo. Collectively, our findings reveal that Met and HMB alleviated DON-induced intestinal injury by improving ISC expansion and reactivating Wnt/ß-catenin signaling. Our study thus provides a nutritional intervention for intestinal diseases involving Wnt/ß-catenin signaling.


Assuntos
Enteropatias/tratamento farmacológico , Metionina/análogos & derivados , Metionina/administração & dosagem , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Tricotecenos/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Enteropatias/genética , Enteropatias/metabolismo , Enteropatias/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Células-Tronco/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
20.
Sci Total Environ ; 694: 133697, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401514

RESUMO

A promising strategy for radionuclides immobilization on the functionalized carbon-based materials is a pursuing issue. Here, we developed phosphorylated hydrothermal carbon spheres (HCSs@PO4) through chemical-grafted method using phytic acid as a phosphorus source. When served as U(VI) scavenger from simulated environmental wastewater, the resulting HCSs@PO4 showed excellent adsorption capacity toward U(VI) (552.49 mg·g-1 at pH 5.0 and T = 298 K), outperforming that of HCSs (32.06 mg·g-1) and state-of the-art materials. A weak ionic strength-dependence of U(VI) enrichment with HCSs@PO4 was investigated by a series of pH experiments, indicating an inner-sphere surface complexation. Through thermodynamic study, high temperature promoted the adsorptive ability of HCSs@PO4 toward U(VI), revealing the endothermic and spontaneous nature. Additional selective adsorption applications were conducted to evaluate the ability of HCSs@PO4 to capture uranium fission byproducts and other radioactive ions. Analyses of characteristic means (FT-IR and XPS) revealed enhanced uptake performance of HCSs@PO4 originated from grafting abundant phosphate groups, which exhibited the stronger surface complexation toward U(VI) than sluggish hydroxyl and carboxyl groups. The findings herein highlighted a facile and powerful technique for the manufacture of phosphorylated carbon-based materials of radioactive wastewater remediation.

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