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1.
Phytother Res ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000538

RESUMO

Plant-derived bioactive compounds, often called phytochemicals, are active substances extracted from different plants. These bioactive compounds can release therapeutic potential abilities via reducing antitumor drugs side effects or directly killing cancer cells, and others also can adjust cancer initiation and progression via regulating microRNAs (miRNAs) expression, and miRNA can regulate protein-coding expression by restraining translation or degrading target mRNA. A mass of research showed that plant-derived bioactive compounds including tanshinones, astragaloside IV, berberine, ginsenosides and matrine can inhibit tumor growth and metastasis by rescuing aberrant miRNAs expression, which has influence on tumor progression, microenvironment and drug resistance in multifarious cancers. This review aims to provide a novel understanding of plant-derived bioactive compounds targeting miRNAs and shed light on their future clinical applications.

2.
BMC Pregnancy Childbirth ; 20(1): 578, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004015

RESUMO

BACKGROUND: Magnesium sulfate (MgSO4) is the standard drug for eclampsia prophylaxis and treatment. In China, the effective therapeutic serum magnesium level is 1.8-3.0 mmol/L. There is little information on how to achieve and maintain effective therapeutic concentrations. This study aimed to investigate risk factors for sub-therapeutic serum concentrations of MgSO4 in patients with severe preeclampsia. METHODS: Patients with severe preeclampsia who received MgSO4 intravenous infusion were retrospectively reviewed. The maternal demographic characteristics, regimens for the administration of MgSO4, and lab test results of patients were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were conducted for the risk factors influencing the serum magnesium concentration. RESULTS: A total of 93 patients with severe preeclampsia were included in the study. 52 (55.91%) patients did not attain therapeutic serum magnesium levels. A multivariate logistic regression analysis identified creatinine clearance (Ccr), whether the loading dose was given, and measurement time of serum magnesium concentration (referring to the time from start of MgSO4 infusion to blood draw for serum sampling) as independent risk factors for sub-therapeutic serum magnesium concentration (P < 0.05). ROC curve analysis indicated that the continuous variable Ccr had a significant predictive value for the serum magnesium concentration, which resulted in a cutoff point of 133 mL/min; while measurement time had limited predictive value, with cutoff point of 2.375 h. CONCLUSIONS: Ccr, whether the loading dose was given, and measurement time were independent risk factors for sub-therapeutic serum magnesium concentration. A loading dose of MgSO4 everytime before the maintenance dose, as well as the duration of MgSO4 maintenance dose of more than 2.375 h are recommended for all the patients with severe PE. Routine evaluation of serum magnesium levels is a recommended practice for women with severe PE and whose Ccr is ≥133 mL/min.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33017219

RESUMO

OBJECTIVE: To explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy. METHODS: In this study, oral and intestinal microbial composition was surveyed using 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features using Quantitative Real-Time PCR (QPCR) approach of 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes. RESULTS: The 16S rRNA results showed that the relative abundances of Gammaproteobacteria of pregnant women in the hypothyroidism group were higher than those in the control group, while the levels of Firmicutes in the control group were higher than those in the hypothyroidism group. The serum CRP level, the weight gain during pregnancy and the incidence of fetal distress in the hypothyroidism group were higher than control group. The QPCR results also showed the same changes of the intestinal in the two groups. CONCLUSION: There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.

4.
Infect Genet Evol ; : 104585, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035644

RESUMO

Innate immunity is the first line against the invasion of pathogenic microorganisms. Over the past several years, the antiviral activity and mechanisms of the IFIT5 gene have been confirmed in mammals. However, more information is needed on the functions and molecular mechanisms of IFIT5 in response to viral infection in chickens. In this study, we examined the expression profile of chicken IFIT5 in the different tissues and explored how chicken IFIT5 transduces upstream signaling to the downstream adaptor. Relative expression of IFIT5 was highest in spleen, indicating tissue- and species-specificity. Expression of IFIT5 was significantly up-regulated following Newcastle disease virus (NDV)-, polyinosinic:polycytidylic acid [poly (I:C)]-, and poly(deoxyadenylic-thymidylic)[poly (dA:dT)]-triggered antiviral immune response. Chicken MDA5, MAVS, and IRF7 genes positively regulated the expression of IFIT5, and overexpression with IFIT5 could promote IRF7- and nuclear factor kappa B (NF-κB)-mediated gene expression following transfection with NDV and poly (I:C). These results suggested that chicken IFIT5 is an important enhancer of the innate immunity response.

5.
J Struct Biol ; : 107637, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059036

RESUMO

Medial calcification has been associated with diabetes, chronic kidney disease, and genetic disorders like pseudoxanthoma elasticum. Recently, we showed that genetic reduction of arterial elastin content reduces the severity of medial calcification in matrix Gla protein (MGP)-deficient and Eln haploinsufficient Mgp-/-;Eln+/- mice. This study suggests that there might be a direct effect of elastin amount on medial calcification. We studied this in vitro, using novel in vitro systems, which are based on elastin or elastin-like polypeptides. We first examined the mineral deposition properties of a transfected pigmented epithelial cell line that expresses elastin and other elastic lamina proteins. When grown in inorganic phosphate-supplemented medium, these cells deposited calcium phosphate minerals, which could be prevented by an N'-terminal peptide of MGP (m3pS) carrying phosphorylated serine residues. We next confirmed these findings using a cell-free elastin-like polypeptide (ELP3) scaffold, where the peptide prevented mineral maturation. Overall, this work describes a novel cell culture model for elastocalcinosis and examines the inhibition of mineral deposition by the m3pS peptide in this and a cell-free elastin-based scaffold. Our study provides strong evidence suggesting the critical functional roles of MGP's phosphorylated serine residues and proposes a possible mechanism of their action.

6.
Aging (Albany NY) ; 122020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051402

RESUMO

More than 10 GWASs have reported numerous genetic loci associated with tuberculosis (TB). However, the functional effects of genetic variants on TB remains largely unknown. In the present study, by combining a reported GWAS summary dataset (N = 452,264) with 3 independent eQTL datasets (N = 2,242) and other omics datasets downloaded from public databases, we conducted an integrative genomics analysis to highlight SNPs and genes implicated in TB risk. Based on independent biological and technical validations, we prioritized 26 candidate genes with eSNPs significantly associated with gene expression and TB susceptibility simultaneously; such as, CDC16 (rs7987202, rs9590408, and rs948182) and RCN3 (rs2946863, rs2878342, and rs3810194). Based on the network-based enrichment analysis, we found these 26 highlighted genes were jointly connected to exert effects on TB susceptibility. The co-expression patterns among these 26 genes were remarkably changed according to Mycobacterium tuberculosis (MTB) infection status. Based on 4 independent gene expression datasets, 21 of 26 genes (80.77%) showed significantly differential expressions between TB group and control group in mesenchymal stem cells, mice blood and lung tissues, as well as human alveolar macrophages. Together, we provide robust evidence to support 26 highlighted genes as important candidates for TB.

7.
Biol Trace Elem Res ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078306

RESUMO

Cadmium pollution is serious heavy metal pollution in environmental pollution and impacts on livestock productivity. However, the effect and mechanisms of cadmium toxicity on the broiler remain unclear. This study aimed to explore the liver oxidative damage and reveal the related long non-coding RNA (lncRNA) expression patterns in the broiler liver with cadmium exposure. The broilers were fed with diets containing CdCl2 and detected the oxidative stress indexes in the liver tissues. Transcriptome sequencing of broiler liver was performed to identify cadmium exposure-related differentially expressed lncRNAs (DElncRNAs). The functions and pathways of DElncRNAs were analyzed by GO and KEGG. The sequencing results were verified by the quantitative real-time polymerase chain reaction. Cadmium exposure induced tissue structure disorder, focal hemorrhage, and irregular hepatocytes in the broiler liver, and significantly decreased GSH level and enzyme activities, and increased MDA expression in the liver. A total of 74 DElncRNAs were obtained in cadmium group compared with the control group, which were enriched in the GO terms, including intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, branched-chain amino acid biosynthetic process. The enriched KEGG pathways, including lysine biosynthesis, valine, leucine and isoleucine biosynthesis, and pantothenate and CoA biosynthesis, were related to oxidative stress. PCR analysis indicated that the changes in ENSGALG00000053559, ENSGALG00000053926, and ENSGALG00000054404 expression were consistent with sequencing. Our results provide novel lncRNAs involved in oxidative stress in the broiler liver with cadmium exposure.

8.
Chemosphere ; 264(Pt 1): 128395, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33007567

RESUMO

Superhydrophilic membranes with simultaneous underwater superoleophobicity are highly desirable and worth exploring for separation of emulsified oil from water. In this work, combining the strong negative charges of phytic acid (PA) and the high cationic charge density of polyethyleneimine (PEI), an eco-friendly PA@PEI polyelectrolyte complex was synthetized in aqueous solution. And then the polyelectrolyte complex was deposited onto hydrophobic PVDF membranes through a one-step assembly approach with high convenience, endowing the membranes with superhydrophilic and underwater superoleophobic property. The as-prepared PA@PEI/PVDF membrane shows outstanding static and dynamic water stability, and was successfully used to separate multiple oil-in-water emulsions, with an average rejection rate exceeding 98.5% and a water flux up to 12203.6 L m-2∙h-1∙bar-1. Furthermore, the water flux can be recovered to a high level after four separation-washing cycles, showing excellent antifouling performance and recovery capability. Together with its natural raw materials and environmentally friendly preparation strategy, the PA@PEI/PVDF membrane shows great potential in practical treatment of emulsified oily wastewater.

9.
Cancer Res ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907840

RESUMO

Our understanding of noncoding mutations in cancer genomes has been derived primarily from mutational recurrence analysis by aggregating clinical samples on a large scale. These cohort-based approaches cannot directly identify individual pathogenic noncoding mutations from personal cancer genomes. Therefore, although most somatic mutations are localized in the noncoding cancer genome, their effects on driving tumorigenesis and progression have not been systematically explored and noncoding somatic alleles have not been leveraged in current clinical practice to guide personalized screening, diagnosis, and treatment. Here we present a deep learning framework to capture pathogenic noncoding mutations in personal cancer genomes, which perturb gene regulation by altering chromatin architecture. We deployed the system specifically for localized prostate cancer by integrating large-scale prostate cancer genomes and the prostate-specific epigenome. We exhaustively evaluated somatic mutations in each patient's genome and agnostically identified thousands of somatic alleles altering the prostate epigenome. Functional genomic analyses subsequently demonstrated that affected genes displayed differential expression in prostate tumor samples, were vulnerable to expression alterations, and were convergent onto androgen-receptor-mediated signaling pathways. Accumulation of pathogenic regulatory mutations in these affected genes was predictive of clinical observations, suggesting potential clinical utility of this approach. Overall, the deep learning framework has significantly expanded our view of somatic mutations in the vast noncoding genome, uncovered novel genes in localized prostate cancer, and will foster the development of personalized screening and therapeutic strategies for prostate cancer.

10.
Materials (Basel) ; 13(17)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887219

RESUMO

A periodic-layered structure was observed in solid-(Cr, Fe)2B/liquid-Al diffusion couple at 750 °C. The interface morphology, the reaction products, and the potential formation mechanism of this periodic-layered structure were investigated using an electron probe microanalyzer (EPMA), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), and energy-dispersive spectroscopy (EDS). The results indicate that the reaction between (Cr, Fe)2B and liquid Al is a diffusion-controlled process. The formation of intermetallics involves both the superficial dissolution of Fe and Cr atoms and the inward diffusion of Al at the interface. The layered structure, as characterized by various experimental techniques, is alternated by a single FeAl3 layer and a (FeAl3 + Cr3AlB4) dual-phase layer. A potential mechanism describing the formation process of this periodic-layered structure was proposed based on the diffusion kinetics based on the experimental results.

11.
J Clin Lab Anal ; : e23561, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32881061

RESUMO

BACKGROUND: Although the effect of hemolysis has been extensively evaluated on clinical biochemical tests, a practical guidance for laboratory staff to rapidly determine whether a hemolyzed blood sample is acceptable and how to interpret the results is lacking. Here, we introduce a chart as a convenient reference for dealing with such samples. METHODS: Serum samples with 0.1%, 0.3%, 1%, 3%, and 10% hemolysis were prepared from sonicated endogenous red blood cells and received 35 wet and 22 dry clinical biochemical tests, respectively. The contributing part in the biochemical test result at each hemolysis condition was derived by subtracting the original test result of this sample with no hemolysis. The net results were used for analyses and preparation of the reference chart. RESULTS: The reference chart displayed the analytically calculated hemolysis interference and related statistical analyses. The chart also provided the color appearance of serum samples at each hemolysis condition for clinical staffs to determine whether a hemolyzed sample could be accepted. CONCLUSION: In clinical laboratories, preparation of such a reference chart is extremely useful in dealing with hemolyzed blood samples for clinical biochemical tests.

12.
Nat Commun ; 11(1): 4655, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938918

RESUMO

Purely organic room-temperature phosphorescence has attracted attention for bioimaging but can be quenched in aqueous systems. Here we report a water-soluble ultralong organic room-temperature phosphorescent supramolecular polymer by combining cucurbit[n]uril (CB[7], CB[8]) and hyaluronic acid (HA) as a tumor-targeting ligand conjugated to a 4-(4-bromophenyl)pyridin-1-ium bromide (BrBP) phosphor. The result shows that CB[7] mediated pseudorotaxane polymer CB[7]/HA-BrBP changes from small spherical aggregates to a linear array, whereas complexation with CB[8] results in biaxial pseudorotaxane polymer CB[8]/HA-BrBP which transforms to relatively large aggregates. Owing to the more stable 1:2 inclusion complex between CB[8] and BrBP and the multiple hydrogen bonds, this supramolecular polymer has ultralong purely organic RTP lifetime in water up to 4.33 ms with a quantum yield of 7.58%. Benefiting from the targeting property of HA, this supramolecular polymer is successfully applied for cancer cell targeted phosphorescence imaging of mitochondria.


Assuntos
Mitocôndrias/efeitos dos fármacos , Polímeros/química , Células A549 , Células HEK293 , Humanos , Ácido Hialurônico/química , Ligação de Hidrogênio , Medições Luminescentes , Microscopia Confocal , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Polímeros/metabolismo , Taxoides/química , Temperatura
13.
Cell Mol Immunol ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917979

RESUMO

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+ subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32918318

RESUMO

This work demonstrates photoredox vicinal dichlorination of alkenes, based on the homolysis of CuCl 2 in response to irradiation with visible light. This catalysis proceeds via a ligand to metal charge transfer process and provides an exciting opportunity for the synthesis of 1,2-dichloride compounds using an inexpensive, low molecular weight chlorine source. This new process exhibits a wide substrate scope, excellent functional group tolerance, extraordinarily mild conditions and does not require external ligands. Mechanistic studies show that the ready formation of chlorine atom radicals is responsible for the facile formation of C-Cl bonds in this synthetic process.

15.
PLoS One ; 15(9): e0239153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941510

RESUMO

BACKGROUND: Cell released microvesicles specifically, exosomes, play an important role in mediating immunologic escape, treatment resistance, and disease persistence of Hepatitis C virus (HCV) infection. Reports on the molecular compositions of exosomes released by cells under diverse conditions, especially during viral infections, suggest that their cargo contents are not randomly loaded. However, the precise molecular mechanisms directing the selective cargo sorting and loading inside infectious viral exosomes remains elusive. AIM: To decipher the role of Reticulon 3 (RTN3) in the selective molecular cargo sorting and loading inside infectious viral exosomes during HCV infection. METHODS: We used Huh7 cells-JFH1 HCV infection and HCV Full-Length (FL) replicon systems. Additionally, we analyzed human liver and serum exosome samples from healthy and treatment naïve HCV infected individuals. Our experiments made use of molecular biology and immunology techniques. RESULTS: HCV infection (JFH1-Huh7 or HCV-FL replicon cells) was associated with increased RTN3L&S isoforms expression in cells and cell released exosomes. Accordingly, increased expression of RTN3L&S was observed in liver and serum exosome samples of HCV infected individuals compared to healthy controls. RNA-ChIP analysis revealed that RTN3L&S interacted with dsHCV RNA. Lentiviral CRISPR/Cas9 mediated knockdown (KD) of RTN3 and plasmid overexpression (OE) of wild type, C- and N-terminal deletion mutants of RTN3L&S in HCV- infected Huh7 cells differentially impacted the cellular release of infectious viral exosomes. RTN3L&S KD significantly decreased, while RTN3S OE significantly increased the number of Huh7 cell-released infectious exosomes. The C-terminal domain of RTN3 interacted with and modulated the loading of dsHCV RNA inside infectious exosomes. Antiviral treatment of HCV infected Huh7 cells reduced virus-induced RTN3L&S expression and attenuated the release of infectious exosomes. CONCLUSION: RTN3 constitutes a novel regulator and a potential therapeutic target that mediates the specific loading of infectious viral exosomes.

17.
Mar Environ Res ; 162: 105151, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32956972

RESUMO

This study investigated the physicochemical surface changes of various plastics caused by indigenous communities. The first invading microbes on plastics in 4 different aquatic communities including seawater, freshwater, marine sediments and lake sediments were developed in microcosm incubation experiments. A mixture of weathered plastics (PE, PS, PET) was incubated with different indigenous communities under their respective habitat simulations. All microbial communities were able to form populations on all plastic surfaces with time-dependent development. Biofilm also affected floatation of plastics and the communities on PE foam (PF) were dominated by genera affiliated with plastic and hydrocarbon degraders. The results showed that indigenous populations were able to degrade plastic pieces and utilize them as carbon sources where the weight of PF was reduced more effectively than PS and PET. Besides, carbonyl groups that were seen with FTIR on initial PF disappeared after microbial treatment along with signs of bioerosion on the plastic surface.

18.
Arch Pharm (Weinheim) ; : e2000131, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32785974

RESUMO

Malaria, caused by the genus Plasmodium, remains a global public health concern. It is estimated by the World Health Organization that over 40% of the world's population lives in areas at risk for malarial transmission, and around half a million people succumb to this infectious disease annually, which is related to the rapid spread of drug-resistant parasite strains. Indole derivatives, which possess broad-spectrum pharmacological properties, play a crucial role in the discovery of new drugs. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug-sensitive and drug-resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents. This review outlines the advances in indole alkaloids and hybrids with antimalarial potential in the recent decade.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32820450

RESUMO

To accelerate the transformation and application of basic research results, the Chinese government has repeatedly mentioned in a government work report that it is necessary to support research and innovation collaborations between knowledge research institutions and enterprises. However, few studies have focused on the evolution of collaborations between these organizations and the impact of collaborations on innovation performance (IP) in the field of renewable energy under the background of government-funded support (GFS). Based on scientific publications, we construct a GFS collaboration network in the wind power field to investigate the evolution of network structure characteristics, attribute proximity variables, and applied research collaboration (ARC), and we study the impact of network evolution on the IP of actors. The results show that the focal actor of the collaboration network prefers to engage in ARC with partners who are familiar and have the same knowledge base in different provinces. This collaboration tendency will reduce geographical proximity and increase the direct ties, indirect ties, technological proximity, and ARC of the ego network. Among them, direct ties have an inverted U-shaped effect on IP, geographical proximity has a significantly negative impact on IP, and the remaining variables have positive impacts on IP. Taken together, when the direct ties is within a certain range, these collaboration tendencies in a GFS collaboration network positively affect the IP of research institutions and enterprises.

20.
Int J Clin Pract ; : e13654, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770797

RESUMO

PURPOSE: Severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high mortality. However, the evolution of computed tomography (CT) manifestations of severe COVID-19 pneumonia remains unclear, more evidence regarding its evolution process is urgent needed. METHOD: The clinical, laboratory and imaging data of eleven patients with severe COVID-19 pneumonia were collected to investigate the evolution process of severe COVID-19 cases. RESULTS: The main initial CT manifestations of severe COVID-19 pneumonia were multiple ground-glass opacities and/or consolidation. Evolution of CT manifestations showed that acute exudative lesions of severe COVID-19 pneumonia could be gradually resolved after active intervention. CONCLUSIONS: Most of patients with severe COVID-19 pneumonia showed marked improvement of acute exudative lesions on chest imagings, and satisfactory prognosis of severe COVID-19 pneumonia could be achieved after active treatment.

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