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1.
BMC Microbiol ; 20(1): 40, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111158

RESUMO

BACKGROUND: Acinetobacter baylyi ADP1 is an ideal bacterial strain for high-throughput genetic analysis as the bacterium is naturally transformable. Thus, ADP1 can be used to investigate DNA mismatch repair, a mechanism for repairing mismatched bases. We used the mutS deletion mutant (XH439) and mutL deletion mutant (XH440), and constructed a mutS mutL double deletion mutant (XH441) to investigate the role of the mismatch repair system in A. baylyi. RESULTS: We determined the survival rates after UV irradiation and measured the mutation frequencies, rates and spectra of wild-type ADP1 and mutSL mutant via rifampin resistance assay (RifR assay) and experimental evolution. In addition, transformation efficiencies of genomic DNA in ADP1 and its three mutants were determined. Lastly, the relative growth rates of the wild type strain, three constructed deletion mutants, as well as the rifampin resistant mutants obtained from RifR assays, were measured. All three mutants had higher survival rates after UV irradiation than wild type, especially the double deletion mutant. Three mutants showed higher mutation frequencies than ADP1 and favored transition mutations in RifR assay. All three mutants showed increased mutation rates in the experimental evolution. However, only XH439 and XH441 had higher mutation rates than the wild type strain in RifR assay. XH441 showed higher transformation efficiency than XH438 when donor DNA harbored transition mutations. All three mutants showed higher growth rates than wild-type, and these four strains displayed higher growth rates than almost all their rpoB mutants. The growth rate results showed different amino acid mutations in rpoB resulted in different extents of reduction in the fitness of rifampin resistant mutants. However, the fitness cost brought by the same mutation did not vary with strain background. CONCLUSIONS: We demonstrated that inactivation of both mutS and mutL increased the mutation rates and frequencies in A. baylyi, which would contribute to the evolution and acquirement of rifampicin resistance. The mutS deletion is also implicated in increased mutation rates and frequencies, suggesting that MutL may be activated even in the absence of mutS. The correlation between fitness cost and rifampin resistance mutations in A. baylyi is firstly established.

2.
J Asian Nat Prod Res ; : 1-8, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162545

RESUMO

Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.

3.
Angiogenesis ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157473

RESUMO

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled "VEGF + VEGFR-2 shRNA" has a metadata label of S4d-plexinB1 shRNA2". In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled "VEGF shRNA" in the published figure, but the metadata label is "S4DshRNA-HN121-20X". In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as "IgG" in the paper, but the metadata show a label of "Restore (V+S).tif". The third published image has a label of "anti-VEGF IgG", and the metadata show a label of "con sh.tif". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

4.
Nano Lett ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32212665

RESUMO

Identifying highly selective catalysts and accurately measuring NH3 yield without false-positives from contaminations remain two challenges in electrochemical nitrogen reduction reaction (NRR). Here, we report N-defective carbon nitride grown on carbon paper (CN/C) as a highly selective electrocatalyst. The NH3 yield was determined reliably by the slope of mNH3-time plot rather than averaging the accumulated amount over time. Results showed the as-synthesized CN/C600 (synthesized at 600 °C) with a higher density of C=N-C N2C vacancies achieved an NH3 production of 2.9 µg mgcat.-1 h-1 at -0.3 V (versus RHE), ∼5.7-fold higher than CN/C500. The Faradaic efficiency for CN/C600 is among the highest of 62.1%, 33.9%, and 16.8% at -0.1 V, -0.2 V, and -0.3 V, respectively. The NH3 production was verified by isotope 15N2 experiments. Further increase of N-defects on CN/C600 using plasma etching led to higher NH3 yield than comparably larger current, pointing to N-defects sites for promoting NRR.

5.
Biol Trace Elem Res ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32219642

RESUMO

Several studies have indicated an association between dietary copper and zinc intake and hypertension, but mainly limited to adult studies. Few studies have examined the associations between copper and zinc and high blood pressure (BP) in children. This study aims to evaluate the associations of zinc and copper with the risk of high BP in children and adolescents aged 8-17 years using the 2007-2016 National Health and Nutritional Examination Surveys (NHANES). A total of 7749 participants (3912 males and 3837 females) were included in the analyses. High BP was defined as (1) the participant (age ≥ 16 years) or the participant's parent/guardian (age < 16 years) reported that the participant had a diagnosis of hypertension irrespective of the BP value; or (2) the participant (age ≥ 16 years) or the participant's parent/guardian (age < 16 years) reported that the participant was currently taking an antihypertensive medication irrespective of the BP value; or (3) a participant classified as having elevated BP /hypertension according to the American Academy of Pediatrics (AAP) new guidelines. Zinc and copper intakes from diet and supplements were assessed with 24-h dietary recall. Positive correlation was found between copper intake and high BP for females, and the ORs (95% CI) across quartiles 2 to 4 compared with quartile 1 were 1.28 (0.81-2.03), 2.06 (1.26-3.36), and 2.69 (1.45-4.98) after adjusting age, gender, race/ethnicity, body mass index (BMI), serum cotinine levels, annual family income, total daily energy intake, and intakes of calcium, sodium, and potassium. Negative correlation was found for males, and the multivariate-adjusted ORs (95% CI) across quartiles 2 to 4 compared with quartile 1 were 0.81 (0.57-1.14), 0.63 (0.42-0.92), and 0.60 (0.37-1.00), respectively. A statistically significantly OR (95% CI) [1.70 (1.08-2.67)] between zinc intake and high BP was observed for participants with normal weight comparing quartiles 3 to quartile 1 of dietary zinc intake. This study suggests that dietary copper and zinc intake may affect BP in children and adolescents. Further longitudinal studies should be warranted to confirm these findings.

6.
Ren Fail ; 42(1): 282-288, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32216514

RESUMO

Introduction: Sclerostin has been reported to be a novel biomarker associated with the bone-vascular axis. In this study, we determined the relationships between serum sclerostin and all-cause mortality, the prevalence of cardiovascular events (CVEs), and coronary artery calcifications (CACs) in dialysis patients.Methods: A total of 165 dialysis patients (84 hemodialysis [HD] and 81 peritoneal dialysis [PD]) were enrolled in this study. We performed multivariable linear regression analysis to test the relationships between serum sclerostin levels and demographics and clinical parameters. We also performed Cox proportional hazard regression analysis to determine independent predictors of overall survival and CVEs.Results: The median serum sclerostin level was 250.9 pg/mL in dialysis patients. Kaplan-Meier analysis showed that both overall and CVE-free survival rates were significantly lower in the high serum sclerostin group (serum sclerostin level >250.9 pg/mL) compared to the low serum sclerostin group (serum sclerostin level ≤250.9 pg/mL) in patients with PD (p < 0.05). In patients with HD, only CVE-free survival rates notably declined in the high serum sclerostin group compared to the low serum sclerostin group (p = 0.029). However, serum sclerostin level was only an independent predictor of all-cause mortality and CVEs in patients with PD after adjusting for confounding factors (p < 0.05), and therefore was not an independent predictor for patients with HD (p > 0.05).Conclusions: A low serum sclerostin was associated with better overall survival and lower prevalence of CVEs in patients with PD, but had no relationships in patients with HD. We found that serum sclerostin level was not correlated with CACs in either patients with HD or PD.

7.
Phytochemistry ; 174: 112329, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32203742

RESUMO

Ten undescribed xanthone derivatives, garoliganthins A-I and oliganthaxanthone C, along with eight known compounds, were isolated from the twigs of Garcinia oligantha Merr. Their structures and absolute configurations were determined by extensive spectroscopic methods, single-crystal X-ray diffraction analysis, electronic circular dichroism analysis, and chiral HPLC/HPLC-CD analysis combined with density functional theory calculations. Garoliganthin A is an unprecedented tetrahydro-xanthone derivative possessing a bicycle [3.2.2] nonane skeleton, and garoliganthins B-E are the first examples of a new class of rearranged xanthone derivatives with six-membered lactone core scaffold. The cytotoxic effects of the isolates on four human cancer cell lines (HeLa, PC-3, A549, and K562) were measured using an MTT assay. Seven compounds showed good inhibitory activities against four cancer cell lines with IC50 values ranging from 2.1 to 16.8 µM.

8.
J Pharm Biomed Anal ; 185: 113226, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163851

RESUMO

Aconitum carmichaelii Debeaux is a widely used herbal medicine, which has anti-inflammatory and analgesic activities. However, due to its high toxicity, poisoning incidents often occur all over the world. To systematically understand the pharmacokinetics (PK) and tissue distribution of A. carmichaelii, 18 representative alkaloids, including 8 amine- (ADA), 4 monoester- (MDA) and 6 diester-type (DDA) diterpenoid alkaloids, were simultaneously quantified by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QQQ-MS) with dynamic multiple reaction monitoring (MRM) mode. PK results suggested that benzoylmesaconine, mesaconitine, 10-OH-aconitine and aconitine had lower bioavailability, which might relate to the substitution at C-3. In tissue distribution, alkaloids present higher concentrations in the liver, kidney, and only songorine, neoline and benzoyldeoxyaconine were detected in the brain. Moreover, the concentrations of extremely toxic DDAs in high-dose group were much higher than that of low-dose group, indicating that these DDAs might be the main reason for the toxicity of Aconitum. The results also suggested that benzoyldeoxyaconine and deoxyaconitine should be determined for the quality control of A. carmichaelii due to their high concentrations in both herbal extract and tissues. The systematic investigation into these 18 representative alkaloids could basically illuminate the PK and distribution of A. carmichaelii in rats, and provide some information for clinical studies.

9.
Clin Transl Sci ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32112504

RESUMO

High salt (HS) intake is closely associated with the ignition and progression of hypertension. The mechanisms might be involved in endothelial dysfunction, nitric oxide deficiency, oxidative stress, and proinflammatory cytokines. Propolis is widely used as a natural antioxidant and is a well-known functional food for its biological activities, which includes anti-inflammation, antimicrobial, and liver detoxification. In this study, we successfully replicated a high-salt diet-induced hypertensive rat model. We found that in the long-term high-salt diet group, the myocardial function of the rats was altered and led to a significant decrease (around 49%) in heart function. However, doses of Chinese water-soluble propolis (WSP) were found directly proportional (11%, 60%, 91%, respectively) to the myocardial function improvement in hypertensive rats. The results from the blood circulation test and HE stains showed that propolis had protective effects on myocardial functions and blood vessels in hypertensive rats. Also, based on the results of WB and PCR, WSP effectively regulated Nox2 and Nox4 levels and was responsible for a decrease in ROS synthesis. Our findings demonstrate that Chinese WSP has a significant effect on the blood pressure of hypertensive rats and their cardiovascular functions that improved significantly. The improvement in the cardiovascular functions might be related to the process of anti-oxidation, anti-inflammation, and the improvements of the endothelial function in hypertensive rats.

10.
J Clin Lab Anal ; : e23230, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32112599

RESUMO

BACKGROUND: To explore the clinical value of the serum superoxide dismutase-to-standard deviation of erythrocyte distribution width ratio (SRSR) in systemic lupus erythematosus (SLE). METHODS: A total of 222 SLE patients from the Rheumatology and Immunology Department in the Second Affiliated Hospital of Chongqing Medical University from January 2017 to April 2019 were collected as the experimental group, and a total of 202 healthy physical examiners were extracted as the control group. Neutrophil-to-lymphocyte ratio (NLR), superoxide dismutase-to-standard deviation of erythrocyte distribution width ratio (SRSR), and platelet-to-lymphocyte ratio (PLR) were calculated from the collected data and then compared the level of the above three indexes between the two groups. In addition, we analyzed the association between SRSR and clinically relevant indicators. RESULTS: We found that the SRSR of SLE patients was significantly lower than healthy control group, by analyzing the receiver operating characteristic (ROC) curve; it revealed that the SRSR had higher specificity and sensitivity than either superoxide dismutase (SOD) or standard deviation of erythrocyte distribution width (RDW-SD) alone. The area under the curve (AUC) for SRSR was significantly larger than either SOD or RDW-SD alone, and the AUC for SRSR was also larger than NLR and PLR. And it was found that SRSR was independently correlated with SLE disease activity through multiple linear regression analysis. CONCLUSION: SRSR is a useful biomarker for the diagnosis of SLE, and it is of great significance in the clinical application.

11.
Phytomedicine ; 68: 153136, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062477

RESUMO

BACKGROUND: The high discontinuation rate in RA patients who use LEF might be attributed to their intolerance rather than irresponsibility. The concomitant administration of Leflunomide (LEF) with Chinese herbal medicine (CHM) provides a potential solution to preventing the adverse drug reactions (ADRs) induced by LEF during the treatment of rheumatoid arthritis (RA). PURPOSE: To investigate whether co-administration of LEF with CHM could bring in both increased therapeutic outcomes and reduced ADRs due to the framework of treatment at the level of entire body. STUDY DESIGN: The mechanism of LEF in RA treatment and the ADRs it induced was introduced based on recent papers. Reported clinical examples of CHM concurrent use with LEF was revealed to provide more evidence. The management of the ADRs caused by LEF was suggested by current researches on the concomitant therapy of CHM with LEF. RESULTS: The active ingredients, compounds and medicinal herbs all demonstrated properties in relieving toxicities and reducing ADRs when used with LEF and reported in several clinical cases. The wide application of concurrent use of CHM with LEF is however hindered by the complex pathogenesis of RA which requires further scientific grounds for diagnosis and treatment. CONCLUSION: This review introduced that the adoption of CHM is emerging as a novel strategy for the management of ADRs caused by LEF.

12.
Cell ; 180(4): 729-748.e26, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32059776

RESUMO

We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/ß-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.

13.
J Matern Fetal Neonatal Med ; : 1-7, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098533

RESUMO

Introduction: Changzhou has been confronted with great challenges in birth defects (BDs) prevention, as the prevalence rates of BDs in Changzhou increased rapidly. The aims of this study were to describe the epidemiology of BDs in perinatal infants (PIs, including dead fetus, stillbirth, or live birth between 28 weeks of gestation and 7 days after birth) in Changzhou during the period from 2014 to 2018.Methods: The BD surveillance data of PIs were collected from 56 hospitals of Changzhou. The prevalence rate of BDs with 95% confidence interval (CI) were calculated by Poisson distribution. Univariate and multivariate Poisson regression was performed to identify the changing trends of prevalence rates of BDs by year and the association of regarding BD characteristics including year, infant gender, maternal age, and season with BDs successively.Results: From 2014 to 2018, there were a total of 238,712 PIs of which 1707 had BDs, with the average prevalence of 71.509 per 10,000 PIs, showing a remarkable uptrend (aPRR = 1.133, 95%CI: 1.094-1.173). The ten leading BDs were polydactyly, congenital heart defects (CHD), syndactyly, microtia, cleft lip and palate (CLP), hypospadias, cleft palate, other malformation of external ear (OMEE), congenital atresia of rectum and anus, and congenital talipes equinovarus (CTE). During the study period, the prevalence rates of polydactyly, CHD and syndactyly increased significantly (PRR = 1.195, 95%CI: 1.109-1.288, PRR = 1.194, 95%CI: 1.105-1.291, and PRR = 1.143, 95%CI: 1.007-1.297, respectively); the prevalence rates of congenital esophageal atresia decreased significantly (PRR = 0.571, 95%CI: 0.395-0.826). The risk of BDs was higher in male PIs versus female PIs (aPRR = 1.235, 95%CI: 1.123-1.358).Conclusions: A significant increase in the prevalence of BDs was detected from 2014 to 2018 in Changzhou. CHD, polydactyly, and syndactyly increased much and congenital esophageal atresia declined much. Male PIs was risk factor for occurrence of BDs. Collecting information on factors associated with BDs, setting the report time of BDs system at smaller gestational age so as to get an exact prevalence and make better prevention strategy, strengthening the publicity and education, improving the ability of monitoring, and wider use of new diagnosis technology are important to reduce the prevalence of BDs in PIs.

14.
Angiogenesis ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100176

RESUMO

Figure 3c of this article originally contained standard deviation values which had not been calculated correctly. A single standard deviation value was used for all 5 time points for each condition.

15.
Angiogenesis ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103388

RESUMO

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figure 1C, the graph showing PDGF-B does not match the original data for the 24-hour time point. The graph shows the value to be over 1000 pg/ml, but the original data have a value of 106.626. In Figure 1F, the data were entered manually to create the standard deviation bars. The data manually entered do not match the original data. When the standard deviations for the original data were calculated, the p values were no longer significant using a paired student t test. In Figure 2C, the original data do not match the published data. In Figure 4B, the images in the first lane and the fifth lane are from the same micrograph (i.e., the same set of conditions). However, the published figure claims that they are different conditions. The metadata in this figure also shows different cell lines than those noted in the article. The first and last images are labelled as "Du145 shAR3 anti AR3.jpg". The second image is labelled as "Du145 shAR8 anti AR8.jpg". The third image is labelled as "Cos1 mARs3 mS3-2 antibody-2.jpg." The fourth image is labelled as "R1 3634 bleed.jpg". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

16.
Exp Cell Res ; 389(1): 111893, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035133

RESUMO

Compared with noninvasive tumor cells, glioma cells overexpress chemokine receptor type 4 (CXCR4), which exhibits significantly greater expression in invasive tumor cells than in noninvasive tumor cells. C-X-C motif chemokine ligand 12 (CXCL12, also known as stromal derived factor-1, SDF-1) and its cell surface receptor CXCR4 activate a signaling axis that induces the expression of membrane type-2 matrix metalloproteinase (MT2-MMP), which plays a pivotal role in the invasion and migration of various cancer cells; however, the specific mechanism involved in this is unclear. Recently, studies have shown that invadopodia can recruit and secrete related enzymes, such as matrix metalloproteinases (MMPs), to degrade the surrounding extracellular matrix (ECM), promoting the invasion and migration of tumor cells. Phosphorylated cortactin (pY421-cortactin) is required for the formation and maturation of invadopodia, but the upstream regulatory factors and kinases involved in phosphorylation have not been elucidated. In this study, we found that CXCL12/CXCR4 was capable of inducing glioma cell invadopodia formation, probably by regulating cortactin phosphorylation. The interaction of cortactin and Arg (also known as Abl-related nonreceptor tyrosine kinase, ABL2) in glioma cells was demonstrated. The silencing of Arg inhibited glioma cell invadopodia formation and invasion by blocking cortactin phosphorylation. Moreover, CXCL12 could not induce glioma cell invasion in Arg-knockdown glioma cells. Based on these results, it can be concluded that Arg mediates CXCL12/CXCR4-induced glioma cell invasion, and CXCL12/CXCR4 regulates invadopodia maturation through the Arg-cortactin pathway, which indicates that Arg could be a candidate therapeutic target to inhibit glioma cell invasion.

17.
J Ethnopharmacol ; 253: 112645, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32045684

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Coreopsis tinctoria Nutt. flower (CTF) has been used traditionally in China for treating hypertension and diabetes as well as reducing body weight and blood fat. However, the vascular protection effect of the CTF has not been studied to date. AIM OF THE STUDY: This study aimed to screen and identify bioactive fractions from the CTF with a diabetic endothelial protection effect and to clarify the underlying mechanism. MATERIALS AND METHODS: The vascular protection effect of Fraction A was studied in high-fat diet and streptozocin-induced diabetic models. The endothelial protection effect of Fraction A-2 was further studied in an in vitro vascular endothelial dysfunction model induced by high glucose. In a high glucose-induced human umbilical vein endothelial cell (HUVEC) model, Fractions A-2-2 and A-2-3 were screened, and their detailed mechanisms of endothelial protection were studied. Liquid chromatography mass spectrometry (LC-MS) was used to identify the main components in Fractions A-2-2 and A-2-3. RESULTS: Fraction A treatment significantly improved the endothelium-dependent vasodilation of the mesenteric artery induced by acetylcholine in diabetic rats. The maximum relaxation was 79.82 ± 2.45% in the control group, 64.36 ± 9.81% in the model group, and 91.87 ± 7.38% in the Fraction A treatment group (P < 0.01). Fraction A treatment also decreased rat tail pressure compared with the model group at the 12th week. The systolic blood pressure was 152.7 5 ± 16.99 mmHg in the control group, 188.50 ± 5.94 mmHg in the model group, and 172.60 ± 14.31 mmHg in the Fraction A treatment group (P < 0.05). The mean blood pressure was 128.50 ± 13.79 mmHg in the control group, 157.00 ± 6.06 mmHg in the model group, and 144.80 ± 11.97 mmHg in the Fraction A treatment group (P < 0.05). In an in vitro vascular endothelium-dependent vasodilation dysfunction model induced by high glucose, Fraction A-2 improved the vasodilation of the mesenteric artery. The maximum relaxation was 82.15 ± 16.24% in the control group, 73.29 ± 14.25% in the model group, and 79.62 ± 13.89% in the Fraction A-2 treatment group (P < 0.05). In a high glucose-induced HUVEC model, Fraction A-2-2 and Fraction A-2-3 upregulated the expression of IRS-1, Akt, and eNOS and increased the levels of p-IRS-1Ser307, p-Akt Ser473, and p-eNOSSer1177 and also decreased the expression of NOX4, TNF-α, IL-6, sVCAM, sICAM, and NF-κB (P < 0.01). With the intervention of AG490 and LY294002, the above effects of Fraction A-2-2 and Fraction A-2-3 were inhibited (P < 0.01). LC-MS data showed that in Fraction A-2-2 and Fraction A-2-3, there were 10 main components: flavanocorepsin; polyphenolic; flavanomarein; isochlorogenic acid A; dicaffeoylquinic acid; coreopsin; marein; coreopsin; luteolin-7-O-glucoside; and 3',5,5',7-tetrahydroxyflavanone-O-hexoside. CONCLUSION: The protective effect of the CTF on diabetic endothelial dysfunction may be due to its effect on the JAK2/IRS-1/PI3K/Akt/eNOS pathway and the related oxidative stress and inflammation. The results strongly suggested that Fraction A-2-2 and Fraction A-2-3 were the active fractions from the CTF, and the CTF might be a potential option for the prevention of vascular complications in diabetes.

18.
JCI Insight ; 5(6)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32078587

RESUMO

We report that transgenic mice expressing measles virus nucleocapsid protein (MVNP) in osteoclasts (OCLs) (MVNP mice) are Paget's disease (PD) models and that OCLs from patients with PD and MVNP mice express high levels of OCL-derived IGF1 (OCL-IGF1). To determine OCL-IGF1's role in PD and normal bone remodeling, we generated WT and MVNP mice with targeted deletion of Igf1 in OCLs (Igf1-cKO) and MVNP/Igf1-cKO mice, and we assessed OCL-IGF1's effects on bone mass, bone formation rate, EphB2/EphB4 expression on OCLs and osteoblasts (OBs), and pagetic bone lesions (PDLs). A total of 40% of MVNP mice, but no MVNP/Igf1-cKO mice, had PDLs. Bone volume/tissue volume (BV/TV) was decreased by 60% in lumbar vertebrae and femurs of MVNP/Igf1-cKO versus MVNP mice with PDLs and by 45% versus all MVNP mice tested. Bone formation rates were decreased 50% in Igf1-cKO and MVNP/Igf1-cKO mice versus WT and MVNP mice. MVNP mice had increased EphB2 and EphB4 levels in OCLs/OBs versus WT and MVNP/Igf1-cKO, with none detectable in OCLs/OBs of Igf1-cKO mice. Mechanistically, IL-6 induced the increased OCL-IGF1 in MVNP mice. These results suggest that high OCL-IGF1 levels increase bone formation and PDLs in PD by enhancing EphB2/EphB4 expression in vivo and suggest OCL-IGF1 may contribute to normal bone remodeling.

19.
Environ Sci Technol ; 54(6): 3306-3315, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32109355

RESUMO

Aeromonas species are indigenous in diverse aquatic environments and play important roles in environmental remediation. However, the pollutant transformation mechanisms of these bacteria remain elusive, and their potential in pollution control is largely unexploited so far. In this work, we report an efficient and simple genome regulation tool to edit Aeromonas hydrophila and identify its biomolecular pathways for pollutant transformation. The genome regulation system, which is based on the type II clustered regularly interspaced short palindromic repeat interference (CRISPRi) system from Streptococcus pyogenes, can serve as a reversible and multiplexible platform for gene knockdown in A. hydrophila. A single-plasmid CRISPRi system harboring both dCas9 and the sgRNA was constructed in A. hydrophila and used to silence diverse genes with varied sizes and expression levels. With this system, up to 467-fold repression of gfp expression was achieved, and the function of the essential gene-ftsZ was identified quickly and accurately. Furthermore, simultaneous transcriptional repression of multiple targeted genes was realized. We discovered that the ars operon played an essential role in arsenic detoxification, and the extracellular electron transfer (EET) pathway was involved in methyl orange reduction, but not in vanadium reduction by A. hydrophila. Our method allows better insights and effective genetic manipulation of the pollutant transformation processes in Aeromonas, which might facilitate more efficient utilization of the Aeromonas species and other microbial species for environmental remediation applications.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Poluentes Ambientais , Aeromonas hydrophila , Proteínas de Bactérias , Expressão Gênica , Técnicas de Silenciamento de Genes
20.
Rev Sci Instrum ; 91(1): 013908, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012592

RESUMO

Revealing interfacial structure and dynamics has been one of the essential thematic topics in material science and condensed matter physics. Synchrotron-based x-ray scattering techniques can deliver unique and insightful probing of interfacial structures and dynamics, in particular, in reflection geometries with higher surface and interfacial sensitivity than transmission geometries. We demonstrate the design and implementation of an in situ shearing x-ray measurement system, equipped with both inline parallel-plate and cone-and-plate shearing setups and operated at the advanced photon source at Argonne National Laboratory, to investigate the structures and dynamics of end-tethered polymers at the solid-liquid interface. With a precise lifting motor, a micrometer-scale gap can be produced by aligning two surfaces of a rotating upper shaft and a lower sample substrate. A torsional shear flow forms in the gap and applies tangential shear forces on the sample surface. The technical combination with nanoscale rheology and the utilization of in situ x-ray scattering allow us to gain fundamental insights into the complex dynamics in soft interfaces under shearing. In this work, we demonstrate the technical scope and experimental capability of the in situ shearing x-ray system through the measurements of charged polymers at both flat and curved interfaces upon shearing. Through the in situ shearing x-ray scattering experiments integrated with theoretical simulations, we aim to develop a detailed understanding of the short-range molecular structure and mesoscale ionic aggregate morphology, as well as ion transport and dynamics in soft interfaces, thereby providing fundamental insight into a long-standing challenge in ionic polymer brushes with a significant technological impact.

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