Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 604
Filtrar
1.
Environ Pollut ; 260: 113984, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32041019

RESUMO

1-nitropyrene (1-NP) is a key component of diesel exhaust-sourced fine particulate matter (PM2.5). Our recent study demonstrated that gestational 1-NP exposure caused placental proliferation inhibition and fetal intrauterine growth restriction (IUGR). This study aimed to investigate the role of genotoxic stress on 1-NP-induced placental proliferation inhibition and fetal IUGR. Human trophoblasts were exposed to 1-NP (10 µM). Growth index was reduced and PCNA was downregulated in 1-NP-exposed placental trophoblasts. More than 90% of 1-NP-exposed trophoblasts were arrested in either G0/G1 or G2/M phases. CDK1 and cyclin B, two G2/M cycle-related proteins, and CDK2, a G0/G1 cycle-related protein, were reduced in 1-NP-exposed trophoblasts. Phosphorylated Rb, a downstream molecule of CDK2, was inhibited in 1-NP-exposed trophoblasts. Moreover, DNA double-strand break was observed and γ-H2AX, another indicator of DNA double-strand break, was upregulated in 1-NP-exposed trophoblasts. Phosphorylated ATM, a key molecule of genotoxic stress, and its downstream molecule Chk2 were elevated. By contrast, Cdc25A, a downstream target of Chk2, was reduced in 1-NP-exposed trophoblasts. Phenyl-N-t-butylnitrone (PBN), a free radical scavenger, inhibited 1-NP-induced genotoxic stress and trophoblast cycle arrest. Animal experiment showed that N-acetylcysteine (NAC), an antioxidant, rescued 1-NP-induced placental proliferation inhibition and fetal IUGR in mice. These results provide evidence that reactive oxygen species (ROS)-mediated cellular genotoxic stress partially contributes to 1-NP-induced placental proliferation inhibition and fetal IUGR.

2.
Cancer Gene Ther ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31959909

RESUMO

Multiple myeloma (MM) is a plasma cell malignancy. The minichromosome maintenance (MCM) family involve in DNA replication and is vital in limiting replication in cell cycle. The prognostic role of MCMs in MM is still unclear. We took four independent GEO datasets to analyze the relationship between the expression of MCMs and myeloma progression and survival. The expression of MCMs showed an upward trend with myeloma progression in 205 patients. High MCM2/3/4/6/8 expression was associated with both poor EFS and OS (all p < 0.050). Multivariate analysis demonstrated that high MCM2 expression, B2M, and LDH were independent risk factors. Moreover, the combination of MCM2/B2M and MCM2/LDH was a better tool in prognostication. In conclusion, high MCM2 expression is an independent adverse prognostic factor and could be used as a prognostic biomarker in MM.

3.
Adv Exp Med Biol ; 1217: 79-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898223

RESUMO

Stem cells can remain quiescent, self-renewal, and differentiate into many types of cells and even cancer stem cells. The coordination of these complex processes maintains the homeostasis of the organism. Ubiquitination is an important posttranslational modification process that regulates protein stability and activity. The ubiquitination levels of stem cell-associated proteins are closely related with stem cell characteristics. Cullin-RING Ligases (CRLs) are the largest family of E3 ubiquitin ligases, accounting for approximately 20% of proteins degraded by proteasome. In this review, we discuss the role of CRLs in stem cell homeostasis, self-renewal, and differentiation and expound their ubiquitination substrates. In addition, we also discuss the effect of CRLs on the formation of cancer stem cells that may provide promising therapy strategies for cancer.

4.
Pharmacogenomics J ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31902948

RESUMO

The prognosis role of CCT3 in MM and the possible pathways it involved were studied in our research. By analyzing ten independent datasets (including 48 healthy donors, 2220 MM, 73 MGUS, and 6 PCL), CCT3 was found to express higher in MM than healthy donors, and the expression level was gradually increased from MGUS, SMM, MM to PCL (all P < 0.01). By analyzing three independent datasets (GSE24080, GSE2658, and GSE4204), we found that CCT3 was a significant indicator of poor prognosis (all P < 0.01). KEGG and GSEA analysis showed that CCT3 expression was associated with JAK-STAT3 pathway, Hippo signaling pathway, and WNT signaling pathway. In addition, different expressed genes analysis revealed MYC, which was one of the downstream genes regulated by JAK-STAT3 pathway, was upregulated in MM. This confirms that JAK-STAT3 signaling pathway may promote the progress of disease which was regulated by CCT3 expression. Our study revealed that CCT3 may play a supporting role at the diagnosis of myeloid, and high expression of CCT3 suggested poor prognosis in MM. CCT3 expression may promote the progression of MM mainly by regulating MYC through JAK-STAT3 signaling pathway.

5.
J Autoimmun ; : 102404, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31952907

RESUMO

The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4+ T cells, CD19+ B cell, and CD14+ monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4+ T cell differentiation, proliferation and apoptosis. We further examined TGFß-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4+ T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4+ T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4+ T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4+ T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4+ T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4+ T cells. Defective EZH2 in CD4+ T cells might contribute to Treg deficiency in RA.

6.
Phys Chem Chem Phys ; 22(3): 976-980, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31895363

RESUMO

We introduced the host-guest chemistry of newly-designed fullerene receptors consisting of buckybowl and alkyne subunits. DFT computations indicated that the huge π-π overlap results in significant binding energy that is larger than those of other known fullerene hosts. The flexibility of the carbon skeleton ensures that corannulenes can be easily twisted to capture different guests and thus are expected as universal hosts for fullerene encapsulation.

7.
Pharmacogenomics J ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31988488

RESUMO

Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem or progenitor cells characterized by abnormal proliferation of primary and immature myeloid cells in bone marrow and peripheral blood. Gene mutation and expression profiles can be used as prognosis predictors for different prognostic subgroups. Secretory carrier-associated membrane proteins (SCAMPs) are a multigenic family with five members and act as cell surface vectors in the post-Golgi recycling pathways in mammals. Nevertheless, the prognostic and clinical influence of SCAMP family has hardly ever been illustrated in AML. In our study, expression patterns of SCAMP family (SCAMP1-5) were analyzed in 155 AML patients which were extracted from the Cancer Genome Atlas database. In chemotherapy, only subgroup, higher SCAMP1 level was significantly associated with longer EFS and OS (all P = 0.002), and SCAMP1 was confirmed to be an independent favorable factor in un-transplanted patients by Multivariate analysis (all P < 0.05). Nevertheless, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment subgroup, none of the SCAMP genes had any effect on the clinical survival. Our study found that high expression level of SCAMP1 is a favorable prognostic factor in AML, but allo-HSCT may neutralize its prognostic effect.

8.
J Cell Mol Med ; 24(1): 1067-1075, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31755224

RESUMO

The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event-free survival (EFS) than the low expressers among the chemotherapy-only group (all P < .001); EFS and OS were similar in the high and low DDIT4 expressers of the allogeneic haematopoietic stem cell transplantation (allo-HSCT) group. Furthermore, in the DDIT4high group, patients treated with allo-HSCT had longer EFS and OS than those who received chemotherapy alone (all P < .01). In the DDIT4low group, OS and EFS were similar in different treatment groups. Secondly, we analysed two other cytogenetically normal AML (CN-AML) cohorts derived from the Gene Expression Omnibus database, which confirmed that high DDIT4 expression was associated with poorer survival. Gene Ontology (GO) enrichment analysis showed that the genes related to DDIT4 expression were mainly concentrated in the acute and chronic myeloid leukaemia signalling pathways. Collectively, our study indicates that high DDIT4 expression may serve as a poor prognostic factor for AML, but its prognostic effects could be outweighed by allo-HSCT.

9.
Ecotoxicol Environ Saf ; 189: 109977, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759747

RESUMO

1-Nitropyrene (1-NP), a key component of fine particulate matter (PM2.5), is a representative of nitrated polycyclic aromatic hydrocarbons (NPAHs). The aim of this research is to investigate proinflammatory effects of acute 1-NP exposure in mouse lungs and human A549 cells. All mice except controls were intratracheally instilled with 1-NP (20 µg/mouse). A549 cell, a human lung cancer cell line, was cultured with or without 1-NP (5 µM). Acute 1-NP exposure elevated lung weight and caused infiltration of inflammatory cells, especially neutrophils in mouse lungs. Although it had little effect on serum TNF-α and KC, acute 1-NP exposure elevated the levels of TNF-α and KC in BALF. Correspondingly, acute 1-NP exposure upregulated pulmonary Il-1ß, Il-6, Tnf-α and Kc. Mechanistically, acute 1-NP exposure activated nuclear factor kappa B (NF-κB) in mouse lungs and human A549 cells. Additionally, acute 1-NP exposure induced Akt phosphorylation in mouse lungs and human A549 cells. Moreover, acute 1-NP exposure induced phosphorylation of pulmonary JNK and ERK1/2, molecules of the mitogen-activated protein kinase (MAPK) pathway. This study provides evidence that acute 1-NP exposure induces inflammatory responses through activating various inflammatory signaling pathways in mouse lungs and human A549 cells.

10.
Blood ; 135(2): 108-120, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31697816

RESUMO

NF-κB and Notch signaling can be simultaneously activated in a variety of B-cell lymphomas. Patients with B-cell lymphoma occasionally develop clonally related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B-cell transformation and whether the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-κB and Notch signaling in committed B cells is sufficient to induce B-cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeit at low frequency, into myeloid leukemia. Mechanistically, coactivation of NF-κB and Notch signaling endows committed B cells with the ability to self renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPα and/or downregulation of B-cell transcription factors, is an early event in both B-cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of green fluorescent protein, which had been lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-κB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.

11.
Mol Phylogenet Evol ; 143: 106673, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707137

RESUMO

The early-branching Cladrastis clade of papilionoid legumes (Leguminosae, Papilionoideae) has an intriguing amphi-Pacific disjunct distribution in eastern Asia and temperate-tropical Americas. Here we used nuclear and three plastid regions to reconstruct the phylogenetic relationships and divergence times in the Cladrastis clade, as well as the evolution of morphological characters that might have been key in its biogeographic history. The ancestral character state estimation revealed that the most recent common ancestor of the Cladrastis clade was deciduous trees possessing compressed, winged fruits. The Cladrastis clade was inferred to have originated in the mid-latitude thermophilic forests of North America in the early Eocene, followed by the split between ancestors of wing-fruited Platyosprion and the non-wing-fruited group, and later the divergence of Cladrastis s.s. from the non-wing-fruited group in middle Eocene. Platyosprion and Cladrastis s.s. display an "out-of-North-America" biogeographic pattern and might have migrated to Asia via the Bering land bridge (BLB) or the North Atlantic land bridges (NALB) during middle to late Eocene. Our results, coupled with the relatively well documented fossil record for the clade, suggest that Platyosprion experienced an extinction event in North America caused by climatic cooling around the Eocene-Oligocene transition, which drove a major vegetation shift in western North America, in turn serving as a barrier for the vicariance of Pickeringia and Styphnolobium. The evolution of shrubby habit and sclerophyllous leaves in the former might be adaption to the chaparral vegetation in southwestern North America; the latter gained the trait of moniliform, succulent fruit. Styphnolobium further dispersed southward to tropical North America in the Oligocene, and eastward to Asia through BLB during middle Miocene. Subsequent sundering of BLB facilitated the vicariance of St. affine and St. japonicum.

12.
Cancer Sci ; 111(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729097

RESUMO

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.


Assuntos
Calcitriol/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Fator de Transcrição STAT3/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo
13.
Angew Chem Int Ed Engl ; 59(1): 203-208, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31663271

RESUMO

Two-dimensional (2D) hybrid perovskites have shown many attractive properties associated with their soft lattices and multiple quantum well structure. Herein, we report the synthesis and characterization of two new multifunctional 2D hybrid perovskites, (PED)CuCl4 and (BED)2 CuCl6 , which show reversible thermochromic behavior, dramatic temperature-dependent conductivity change, and strong ferromagnetism. Upon temperature change, the (PED)CuCl4 and (BED)2 CuCl6 crystals exhibit a reversible color change between yellow and red-brown. The associated structural changes were monitored by in situ temperature-dependent powder X-ray diffraction (PXRD). The (BED)2 CuCl6 exhibits superior thermal stability, with a thermochromic working temperature up to 443 K. The conductivity of (BED)2 CuCl6 changes over six orders of magnitude upon temperature change. The 2D perovskites exhibit ferromagnetic properties with Curie temperatures around 13 K.

14.
J Exp Bot ; 71(2): 507-519, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31270541

RESUMO

Climate change will negatively affect crop production by exacerbating the incidence of disease and decreasing the efficacy of conventional approaches to disease control. Nanotechnology is a promising new strategy for plant disease management that has many advantages over conventional products and approaches, such as better efficacy, reduced input requirements, and lower eco-toxicity. Studies on crop plants using various nanomaterials (NMs) as protective agents have produced promising results. This review focuses on the use of NMs in disease management through three different mechanisms: (i) as antimicrobial agents; (ii) as biostimulants that induce plant innate immunity; and (iii) as carriers for active ingredients such as pesticides, micronutrients, and elicitors. The potential benefits of nanotechnology are considered, together with the role that NMs might play in future disease management and crop adaptation measures.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31820097

RESUMO

It has been brought to our attention that in our article, explanations about cable bacteria are not rigorous. We apologize for these and note the specific reporting issues and errors below, with their corrections.

16.
Ecol Evol ; 9(22): 12639-12648, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31788203

RESUMO

Wind speed is one of the most important factors for seed wind dispersal. A wind speed reduction region, which could be influenced by vegetation arrangement, will form in the lee of vegetation and therefore affects the seed dispersal. Here, by taking shrub as an example, quantitative differences in seed dispersals of low vegetation between single element and windbreak-like clumps are numerically investigated. The local variation of stream-wise wind speed is focused. Empirically parameterized functions of leeward wind distributions are employed. It reveals that the accumulative probability of dispersed seeds from a point source with considering leeward wind reduction could be well fitted by a logistic function. For a fixed release height or vegetation porosity, accumulative probabilities for single element and those for windbreak-like clumps would intersect at a leeward location. This intersection location decreases linearly with release height but exponentially with porosity. The fitting parameter r 0 (the center of logistic function) for single element increases as the same manner for windbreak-like clumps, with regard to the increase of release height, porosity, and height. But, the increasing rates for single element are higher than those for windbreak-like clumps. The fitting parameter p (the power index of logistic function) for single element is generally larger than that for windbreak-like clumps. With the increase of release height, p decreases at first but increases then for single element, while it shows opposite trend for windbreak-like clumps. p decreases with porosity for both single element and windbreak-like clumps. But, the decreasing rate for single element is lower than that for windbreak-like clumps. p increases exponentially with height for windbreak-like clumps, while it almost keeps constant for single element. These results suggest the potential importance of vegetation arrangement on seed dispersal and therefore possibly provide additional reason for the disagreement among observed dispersal kernels.

17.
ACS Nano ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31834779

RESUMO

Rechargeable lithium-sulfur batteries have attracted tremendous scientific attention owing to their high energy density. However, their practical application is greatly hindered by the notorious shuttling of soluble lithium polysulfide (LPS) intermediates with sluggish redox reactions and uncontrolled precipitation behavior. Herein, we report a semiliquid cathode composed of an active LPS solution/carbon nanofiber (CNF) composite layer, capped with a carbon nanotube (CNT) thin film decorated with metallic Mo nanoclusters that regulate the electrochemical redox reactions of LPS. The trace amount (0.05 mg cm-2) of metallic Mo on the CNT film provides sufficient capturing centers for the chemical immobilization of LPS. Together with physical blocking of LPS by the compact CNT film, free diffusion of LPS is significantly restrained and the self-discharge behavior of the Li-S cell is thus effectively suppressed. Importantly, the metallic Mo nanoclusters enable fast catalytic conversion of LPS and regular deposition of lithium sulfide. As a result, the engineered cathode exhibits a high active sulfur utilization (1401 mAh g-1 at 0.1 C), stable cycling (500 cycles at 1 C with 0.06% decay per cycle), high rate performance (694 mAh g-1 at 5 C), and low self-discharge rate (3% after 72 h of rest). Moreover, a high reversible areal capacity of 4.75 mAh cm-2 is maintained after 100 cycles at 0.2 C for a cathode with a high sulfur loading of 7.64 mg cm-2. This work provides significant insight into the structural and materials design of an advanced sulfur-based cathode that effectively regulates the electrochemical reactions of sulfur species in high-energy Li-S batteries.

18.
Biomed Res Int ; 2019: 8397521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828134

RESUMO

Retinal ganglion cell (RGC) death is the central and irreversible endpoint of optic neuropathies. Current management of optic neuropathies and glaucoma focuses on intraocular pressure-lowering treatment which is insufficient. As such, patients are effectively condemned to irreversible visual impairment. This review summarizes experimental treatments targeting RGCs over the last decade. In particular, we examine the various treatment modalities and determine their viability and limitations in translation to clinical practice. Experimental RGC treatment can be divided into (1) cell replacement therapy, (2) neuroprotection, and (3) gene therapy. For cell replacement therapy, difficulties remain in successfully integrating transplanted RGCs from various sources into the complex neural network of the human retina. However, there is significant potential for achieving full visual restoration with this technique. Neuroprotective strategies, in the form of pharmacological agents, nutritional supplementation, and neurotrophic factors, are viable strategies with encouraging results from preliminary noncomparative interventional case series. It is important to note, however, that most published studies are focused on glaucoma, with few treating optic neuropathies of other etiologies. Gene therapy, through the use of viral vectors, has shown promising results in clinical trials, particularly for diseases with specific genetic mutations like Leber's hereditary optic neuropathy. This treatment technique can be further extended to nonhereditary diseases, through transfer of genes promoting cell survival and neuroprotection. Crucially though, for gene therapy, teratogenicity remains a significant issue in translation to clinical practice.

19.
Front Med ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31884527

RESUMO

Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including cell division, immune responses, and apoptosis. Ubiquitin-mediated control over these processes can be reversed by deubiquitinases (DUBs), which remove ubiquitin from target proteins and depolymerize polyubiquitin chains. Recently, much progress has been made in the DUBs. In humans, the ovarian tumor protease (OTU) subfamily of DUBs includes 16 members, most of which mediate cell signaling cascades. These OTUs show great variation in structure and function, which display a series of mechanistic features. In this review, we provide a comprehensive analysis of current progress in character, structure and function of OTUs, such as the substrate specificity and catalytic activity regulation. Then we discuss the relationship between some diseases and OTUs. Finally, we summarize the structure of viral OTUs and their function in immune escape and viral survival. Despite the challenges, OTUs might provide new therapeutic targets, due to their involvement in key regulatory processes.

20.
J Chromatogr A ; : 460712, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759641

RESUMO

A simple magnetization method was developed for the preparation of magnetic materials from conventional solid phase packing though coprecipitation and solvothermal approaches. And the prepared magnetic materials were used for magnetic solid phase extraction (MSPE) of biogenic amines (BAs) from beers. Furthermore, to improve the analytical throughput, a solid phase "on-situ" quadraplex isotope dimethyl labeling method was developed for the quantification of BAs by liquid chromatography-high resolution mass spectrometry (LCHRMS). Compared to conventional in-solution labeling, the "on-situ" labeling could simplify the sample preparation procedure and efficiently remove the residuals such as inorganic salts and excessive labeling reagents. The quadraplex labeling, which enabled three real samples and one internal standard sample to be analyzed simultaneously in a single LCHRMS run. For the tested 8 BAs (cadaverine, phenethylamine, spermine, spermidine, tyramine, histamine, putrescine and tryptamine), LODs of 0.02-0.05 µg/L and LOQs of 0.05-0.1 µg/L were achieved at good reproducibility (RSD of 0.5-4.6% and 2.2-7.0% for intra- and inter-day reproducibility, respectively). With this method, six beer samples were analyzed, and these 8 BAs were all detected in the range of low µg/L to 2.9 mg/L, which were lower than maximal residual level (MRL) required in the regulations of China and EU.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA