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1.
Arch Oral Biol ; 109: 104584, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630006

RESUMO

OBJECTIVES: To investigate whether rutin could protect human periodontal ligament stem cells (hPDLSCs) from TNF-α induced damage to osteogenic differentiation in inflammatory environment and detect the underlying mechanism. MATERIALS AND METHODS: hPDLSCs were identified by flow cytometery. TNF-α was used to stimulate hPDLSCs to establish an inflammation model in vitro. Alkaline phosphatase (ALP) staining, ALP activity test, and Alizarin Red staining were used to detect the changes of osteogenic differentiation ability. The mRNA and protein levels of osteogenic genes were evaluated by RT-PCR and Western Blot. The expression of mTOR was also detected by Western Blot. RESULTS: hPDLSCs were positive to MSCs specific surface markers. The inflammatory environment in vitro could be established by stimulating hPDLSCs with TNF-α (20 ng/mL). TNF-α (20 ng/mL) could decrease the ALP activity and mineralization ability of hPDLSCs and down-regulate the expression of osteogenic genes in inflammatory environment. Moreover, rutin could affect TNF-α (20 ng/mL) induced damage to osteogenic differentiation of hPDLSCs in a dose-dependent manner, 10 µmol/L rutin could significantly reverse the damage caused by TNF-α. In addition, rutin inhibited TNF-α-activated mTOR signal transduction by inhibiting the phosphorylation of mTOR, similar to the effects of rapamycin(a specific mTOR inhibitor). CONCLUSIONS: Rutin could protect hPDLSCs from TNF-α induced damage to osteogenic differentiation in inflammatory environment, and rutin is expected to become a new candidate drug for the treatment of bone defect of periodontitis.

2.
Sci Total Environ ; 698: 134320, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518779

RESUMO

Soil acidification is a major environmental issue associated with intensive agricultural land use. Rapid urbanization has inevitably caused great changes in agricultural land use around urban areas. However, the effects of agricultural land-use change and soil parent material on the pH dynamics of the whole soil profile remain poorly understood. Based on a paired soil resampling campaign in the 1980s and 2010s, this study evaluated the effects of agricultural land-use change and parent materials on the pH dynamics of the soil profile across the Chengdu Plain of China. The results showed that soil pH significantly decreased by 1.20, 0.72, 0.66 and 0.68 units at the 0-20, 20-40, 40-60 and 60-100 cm soil depths, respectively. Conversions of traditional rice-wheat/rapeseed rotations to rice-vegetable rotations and afforested land significantly increased the magnitude of pH decline at the 0-60 cm soil depth. Soils formed from Q4 grey-brown alluvium and Q4 grey alluvium, which had a lower soil bulk density (BD) and higher sand content, showed a much higher magnitude of pH decline than soils formed from Q3 (Quaternary Pleistocene) old alluvium, and significant acidification of deep soils only occurred in soils formed from Q4 (Quaternary Holocene) grey-brown alluvium and Q4 grey alluvium. These results suggested that agricultural land-use change aggravated acidification in the soil profile and the soil acidification degrees were parent material-dependent; in particular, significant acidification of deep soils was more inclined to occur in soils with lower soil BD and higher sand content due to their effects on the downward movement of acids and the penetration resistance of plant roots. More attention should be given to minimizing or preventing acidification of both topsoil and deep soils aggravated by agricultural land-use change across urban agricultural areas.

3.
BMJ Open Diabetes Res Care ; 7(1): e000735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798896

RESUMO

Objective: To derive, and externally validate, a risk score for cardiovascular death among patients with type 2 diabetes and newly diagnosed diabetic nephropathy (DN). Research design and methods: Two independent prospective cohorts with type 2 diabetes were used to develop and externally validate the risk score. The derivation cohort comprised 2282 patients with an incident, clinical diagnosis of DN. The validation cohort includes 950 patients with incident, biopsy-proven diagnosis of DN. The outcome was cardiovascular death within 2 years of the diagnosis of DN. Logistic regression was applied to derive the risk score for cardiovascular death from the derivation cohort, which was externally validated in the validation cohort. The score was also estimated by applying the United Kingdom Prospective Diabetes Study (UKPDS) risk score in the external validation cohort. Results: The 2-year cardiovascular mortality was 12.05% and 11.79% in the derivation cohort and validation cohort, respectively. Traditional predictors including age, gender, body mass index, blood pressures, glucose, lipid profiles alongside novel laboratory test items covering five test panels (liver function, serum electrolytes, thyroid function, blood coagulation and blood count) were included in the final model.C-statistics was 0.736 (95% CI 0.731 to 0.740) and 0.747 (95% CI 0.737 to 0.756) in the derivation cohort and validation cohort, respectively. The calibration slope was 0.993 (95% CI 0.974 to 1.013) and 1.000 (95% CI 0.981 to 1.020) in the derivation cohort and validation cohort, respectively.The UKPDS risk score substantially underestimated cardiovascular mortality. Conclusions: A new risk score based on routine clinical measurements that quantified individual risk of cardiovascular death was developed and externally validated. Compared with the UKPDS risk score, which underestimated the cardiovascular disease risk, the new score is a more specific tool for patients with type 2 diabetes and DN. The score could work as a tool to identify individuals at the highest risk of cardiovascular death among those with DN.

4.
Sci Total Environ ; : 135524, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31784154

RESUMO

Polyhalogenated carbazoles (PHCZs) are emerging environmental contaminants that have caused wide concerns due to their dioxin-like toxicity and environmental persistence. It would be desirable to determine all of these chemicals using a simple analytical method. Within this study, a simple and sensitive method combining accelerated solvent extraction (ASE) with gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) was established to simultaneously analyze eleven frequently detected PHCZs in soil, including CCZ-3, CCZ-36, CCZ-1368, CCZ-2367, BCZ-3, BCZ-27, BCZ-36, BCZ-136, BCZ-1368, 1-B-36-CCZ, 18-B-36-CCZ. The calibration curves of the target analytes showed good linearity (R2 > 0.99, level = 6), and method detection limits (MDLs) ranging from 1.5 to 14.6 pg g-1. The average recoveries of the analytes in soil samples ranged from 64% to 126% with the RSD ranging from 2.0% to 10%. The developed method was successfully used for determination of these eleven PHCZs in soil samples from a tie-dye area in southwest China. Total concentrations of these eleven PHCZs ranging up to 46.3 ng g-1 dw. CCZ-36, BCZ-3, CCZ-3, 1-B-36-CCZ, 18-B-36-CCZ, and BCZ-1368 were the most abundant compounds in soil.

5.
Shanghai Kou Qiang Yi Xue ; 28(4): 356-361, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792473

RESUMO

PURPOSE: To explore the effect of rutin on osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment. METHODS: Periodontal ligament stem cells (PDLSCs) were obtained by limited dilution method in vitro. PDLSCs were identified by flow cytometery. Lipopolysaccharide(LPS) was used to stimulate human periodontal ligament stem cells to establish an inflammation model in vitro. The experiment was divided into 4 groups: in group 1, only α-MEM was used to culture PDLSCs; in group 2, α-MEM medium containing LPS was used to culture PDLSCs, in group 3, rutin was added to α-MEM medium containing LPS to PDLSCs; and in group 4, α-MEM medium containing rutin was used to culture PDLSCs. Cell counting kit-8 was used to detect cell proliferation activity. Alkaline phosphatase(ALP) staining, ALP activity test, alizarin red staining, RT-PCR, and Western blot were used to detect the changes of osteogenic differentiation ability. The data were analyzed by SPSS 17.0 software package. RESULTS: The results of CCK-8 and ALP activity analysis showed that rutin at 10 µmol/L could significantly promote the proliferation and differentiation of periodontal stem cells under inflammatory state. ALP staining and alizarin red staining proved that (10 µmol/L) rutin could improve osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment. RT-PCR and Western blot results showed that rutin could enhance the expression of osteogenic genes and proteins such as COL1, ALP, and RUNX2 under inflammatory state. CONCLUSIONS: Rutin can promote osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment.

6.
Curr Alzheimer Res ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755388

RESUMO

OBJECTIVE: To characterize the specific metabolomics profiles in the outer membrane vesicles (OMVs) of patients with Alzheimer's disease (AD) and to explore potential metabolic biomarkers and their diagnostic roles. METHODS: Nine AD patients and age- and sex-matched healthy controls were enrolled, and feces were collected. OMVs were extracted, purified, and then analyzed using liquid chromatography-tandem mass chromatography (LC-MS/MS) method coupled with a series of multivariate statistical analyses. RESULTS: Remarkable differences were found between the OMVs from AD patients and those from healthy controls. A list of differential metabolites and several top-altered metabolic pathways were identified. The levels of aspartate, L-aspartate, imidazole-4-acetate and L-glutamate were confirmed to be highly upregulated in AD-OMVs. Other differential metabolites, such as arachidic acid, prostaglandin G2, and leukotriene B4, were also identified. Furthermore, the differential metabolites possessed higher areas under the ROC curve (AUCs). CONCLUSION: Metabolic activity is significantly altered in the OMVs from AD patients. This data might be helpful for identifying novel biomarkers and their diagnostic roles in AD. Furthermore, OMVs metabolomics analysis combined with GWAS could enrich our understanding of the genetic spectrum of AD and lead to early predictions and diagnosis and clinical applications of better AD treatments.

7.
Appl Microbiol Biotechnol ; 103(21-22): 9169-9180, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673743

RESUMO

Pseudomonas stutzeri strain XL-2 exhibited significant performance on biofilm formation. Extracellular polymeric substances (EPS) secreted by strain XL-2 were characterized by colorimetry and Fourier transform infrared (FT-IR) spectroscopy. The biofilm growth showed a strong positive correlation (rP=0.96, P<0.01) to extracellular protein content, but no correlation to exopolysaccharide content. Hydrolyzing the biofilm with proteinase K caused a significant decrease in biofilm growth (t=3.7, P<0.05), whereas the changes in biofilm growth were not significant when the biofilm was hydrolyzed by α-amylase and ß-amylase, implying that proteins rather than polysaccharides played the dominant role in biofilm formation. More specifically, confocal laser scanning microscopy (CLSM) revealed that the extracellular proteins were tightly bound to the cells, resulting in the cells with EPS presenting more biofilm promotion protein secondary structures, such as three-turn helices, ß-sheet, and α-helices, than cells without EPS. Both bio-assays and quantitative analysis demonstrated that strain XL-2 produced signal molecules of N-acylhomoserine lactones (AHLs) during biofilm formation process. The concentrations of C6-HLS and C6-oxo-HLS were both significantly positively correlated with protein contents (P<0.05). Dosing exogenous C6-HLS and C6-oxo-HLS also resulted in the increase in protein content. Therefore, it was speculated that C6-HLS and C6-oxo-HLS released by strain XL-2 could up-regulate the secretion of proteins in EPS, and thus promote the formation of biofilm.

8.
J Immunol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676674

RESUMO

C-C chemokine receptor 2 (CCR2) is a key driver of monocyte/macrophage trafficking to sites of inflammation and has long been considered a target for intervention in autoimmune disease. However, systemic administration of CCR2 antagonists is associated with marked increases in CCL2, a CCR2 ligand, in the blood. This heretofore unexplained phenomenon complicates interpretation of in vivo responses to CCR2 antagonism. We report that CCL2 elevation after pharmacological CCR2 blockade is due to interruption in a balance between CCL2 secretion by a variety of cells and its uptake by constitutive internalization and recycling of CCR2. We observed this phenomenon in response to structurally diverse CCR2 antagonists in wild-type mice, and also found substantially higher CCL2 plasma levels in mice lacking the CCR2 gene. Our findings suggest that CCL2 is cleared from blood in a CCR2-dependent but G protein (Gαi, Gαs or Gαq/11)-independent manner. This constitutive internalization is rapid: on a given monocyte, the entire cell surface CCR2 population is turned over in <30 minutes. We also found that constitutive receptor internalization/recycling and ligand uptake are not universal across monocyte-expressed chemokine receptors. For example, CXCR4 does not internalize constitutively. In summary, we describe a mechanism that explains the numerous preclinical and clinical reports of increased CCL2 plasma levels following in vivo administration of CCR2 antagonists. These findings suggest that constitutive CCL2 secretion by monocytes and other cell types is counteracted by constant uptake and internalization by CCR2-expressing cells. The effectiveness of CCR2 antagonists in disease settings may be dependent upon this critical equilibrium.

9.
Int J Med Robot ; : e2042, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702110

RESUMO

BACKGROUND: Haptic devices with active translation and orientation outputs are highly preferred in surgical teleoperation. However, commercial products are expensive, while state-of-the-art research prototypes are difficult to reproduce outside the original laboratories. METHODS: This paper presents the design and experimental characterizations of two styluses for the CombX, a haptic device with both force and torque outputs constructed from two TouchX haptic devices, which have only force outputs at their styluses. The arrangement was optimized to improve the specifications. Additional functions for surgical teleoperation were also integrated. RESULTS: The CombX has a translation workspace larger than 160 × 160 × 160 mm3 . After calibration, it can provide force outputs of up to 16.32 N and torque outputs of up to 316 mNm. The CombX has also been successfully used to teleoperate a continuum surgical manipulator for two surgical tasks. CONCLUSION: The results show that the CombX is a viable option for surgical teleoperation.

10.
Environ Int ; 134: 105193, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31775093

RESUMO

Dioxin exposure is reported to affect nervous system development and increase the risk of neurodegenerative diseases. Generally, dioxin exerts its neurotoxicity via aryl hydrocarbon receptor (AhR). Neurofilament (NF) light (NFL) protein is a biomarker for both neuronal differentiation and neurodegeneration and its expression is controlled by the mitogen-activated protein kinase (MAPK) pathway. However, the effects of dioxin on NFL expression and involved mechanisms are incompletely understood. We aimed to investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on NFL expression and elucidate the underlining signaling pathways and their potential crosstalk, specifically between MAPK and AhR pathway. We employed primary cultured rat cortical neurons to evaluate the effect of TCDD exposure on NFL expression. We also used nerve growth factor (NGF)-treated PC12 cells with specific inhibitors to investigate the involvement of and potential crosstalk between the MAPK pathway and the AhR pathway in mediating the effects of TCDD on NFL expression. After TCDD exposure, NFL mRNA and protein levels were upregulated in cultured neurons. NFL protein was preferentially found in the cell body compared with neurites of the cultured neurons. In PC12 cells, TCDD enhanced both NGF-induced NFL expression and phosphorylation of ERK1/2 and p38. The addition of MAPK-pathway inhibitors (PD98059 and SB230580) partially blocked the TCDD-induced NFL upregulation. CH223191, an AhR antagonist, reversed the upregulation of NFL and phosphorylation of ERK1/2 and p38 induced by TCDD. This study demonstrated TCDD-induced upregulation of NFL in cultured neurons, with protein retained in the cell body. TCDD action was dependent on activation of AhR and MAPK, while crosstalk was found between these two signaling pathways.

11.
Mol Ther Nucleic Acids ; 18: 681-695, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31707205

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD mechanism and also be the potential targets. MicroRNA-146a-5p (miR-146a) is well known in the regulation of the inflammatory response, and the functional SNP of miR-146a was associated with AD risk. In this study, using a noninvasive nasal administration, we discovered that a miR-146a agomir (M146AG) rescued cognitive impairment in the APP/PS1 transgenic mouse and alleviated the overall pathological process in the AD mouse model, including neuroinflammation, glia activation, Aß deposit, and tau phosphorylation in hippocampi. Furthermore, the transcriptional analysis revealed that besides the effect of neuroinflammation, M146AG may serve as a multi-potency target for intervention in AD. In addition, Srsf6 was identified as a target of miR-146a, which may play a role in AD progression. In conclusion, our study supports that the nasal-to-brain pathway is efficient and operable for the brain administration of microRNAs (miRNAs), and that miR-146a may be a new potential target for AD treatment.

12.
Int J Mol Med ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31746374

RESUMO

Following the publication of this article, the authors noticed that the published versions of Figs. 2, 7 and 8 contained incorrect western bands. In examining their raw data, the authors realized that they had used the fibroblasts of keloids [high expression of alpha­smooth muscle actin (α­SMA)] instead of adult dermal fibroblasts (low expression of α­SMA) in certain experiments. Note that no significant differences in morphology exist between myofibroblasts (from keloids) and fibroblasts (from normal dermal tissue). These errors were brought to light since the authors identified that the expression of α­SMA in Fig. 8 was higher compared with that in Fig. 4. After careful scrutiny, they established that the first author, Bin Zhao, who performed the experiments and analyzed the data shown in Figs. 2, 7 and 8, had mislabelled the myofibroblasts as fibroblasts. However, for all the other experiments in the above­mentioned article, the cells had been used correctly. The authors regret that these errors were featured in the above­mentioned article, which may possibly have caused confusion for the readers, and the corrected versions of Figs. 2, 7 and 8 are shown opposite and on the next page. These changes did not affect either the results or the conclusions reported in this paper. The authors apologize to the Editor of International Journal of Molecular Medicine and to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 39: 153­159, 2017; DOI: 10.3892/ijmm.2016.2816].

14.
Org Lett ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746206

RESUMO

Oxalic acid monothioester (OAM), an easily accessible and storable reagent, was reported herein as a thioester synthetic equivalent for palladium-catalyzed decarboxylative thiocarbonylation of organohalides and hydrothiocarbonylation of unsaturated carbon-carbon bonds at room temperature with high chemo- and regioselectivity. The reaction is applicable to the synthesis of cysteine-derived thioesters, thus allowing chemical modification of cysteine-containing peptides. Decarboxylation of OAM proceeds through oxidative addition of Pd(0) to the acyl-S bond, which accounts for the very mild reaction conditions.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31746308

RESUMO

BACKGROUND AND PURPOSE: Although limited by side effects and development of resistance, doxorubicin still represent the most common chemotherapy for breast cancer. Thus, the identification of critical molecules to alleviate doxorubicin resistance is crucial. Here, we provide a molecular rationale for the breast cancer patients potentially benefitting from doxorubicin based on the expression levels of SIRT1, a identified member of longevity genes. METHODS: SIRT1-overexpressed and SIRT1-knockdown breast cancer cells were established to investigate the functions of SIRT1 in regulating doxorubicin resistance both in vitro and in vivo. Cell proliferation was analyzed via CCK8 assay, cell apoptosis was studied by TUNEL anslysis. Molecule interaction was analyzed through co-immunoprecipitation and immunofluorescence techniques. Sensibility to doxorubicin was assessed in vivo through nude mice tumorigenicity experiment. RESULTS: First, SIRT1 was found higher-expressed in breast cancer doxorubicin-resistant cells MCF-7/ADR than that in doxorubicin- sensitive cells MCF-7. Moreover, SIRT1-knockdown MCF-7/ADR cells showed higher susceptible to doxorubicin both in vitro and in vivo models, whereas overexpressing of SIRT1 obviously inhibited this phenotype. Accordingly, SIRT1 was found interacted with Akt, consequently promoted the activity of Akt in MCF-7/ADR cells in vitro and positively correlated with the expression of P-Akt in vivo. Reversion the activity of Akt partially downturned the doxorubicin-resistant effects mediated by SIRT1. CONCLUSION: This investigation suggested the value of SIRT1 as biomarker of response to doxorubicin, leading to the development of new tools for the management of breast cancer patients.

16.
Medicine (Baltimore) ; 98(46): e17995, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725665

RESUMO

Insulin resistance is usually a key factor in the development of type 2 diabetes. The triglyceride glucose (TyG) index is a marker of insulin resistance which is also implicated in the risk of nephropathy among people with type 2 diabetes. This study aimed to examine associations and potential thresholds between TyG index and the risk of newly diagnosed biopsy-proven diabetic nephropathy in people with type 2 diabetes. A nested case-control study incorporating 950 incident biopsy-proven diabetic nephropathy cases and age, gender matched 4750 patients with treated type 2 diabetes as controls selected by risk-set sampling method was implemented. The dose-response association between TyG index with subsequent risk of newly diagnosed biopsy-proven diabetic nephropathy after adjustment for age, gender, blood pressure, and other major cardiovascular risk factors were examined by conditional logistic regression model. A non-linear relationship was identified between TyG index and the risk of newly diagnosed biopsy-proven diabetic nephropathy with a potential threshold of TyG at 9.05-9.09. Similar relationships with the same threshold were also found in the analyses by fasting glucose and triglyceride levels. TyG index might be a prognostic factor in predicting newly development of biopsy-proven diabetic nephropathy among patients with treated type 2 diabetes. In people with type 2 diabetes, TyG index above 9.05-9.09 could be a prognostic threshold to identify individuals at high risk of diabetic nephropathy. Further replication studies are warranted.

17.
Cancer Med ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749325

RESUMO

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.

18.
J Hazard Mater ; : 121510, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31704120

RESUMO

Graphene oxide (GO)-anisotropic noble metal hybrid systems were developed as highly sensitive and reproducible surface enhanced Raman scattering (SERS) platform, in which ultrathin GO was embedded between two metallic layers of flower-like Ag nanoparticles (AgNFs) and gold nanostars (AuNSts). Due to multi-dimensional plasmonic coupling effect, the well-designed AgNFs-GO-AuNSts sandwich structures possessed ultrahigh sensitivity with the detection limit of R6G as low as 1.0 × 10-13 M and high enhancement factor of 2.59 × 107. Additionally, the GO interlayer could function as protective shell to suppress the oxidation of bottom silver layer and efficiently position the target analytes within hot spots. These features endow the substrate with high stability and excellent reproducibility (Signal variations < 7%). Particularly, the GO sandwiched substrate can be explored for the direct capture and sensitive detection of polychlorinated biphenyls (PCBs) without any organic modifier as molecule harvester. This minimum detected concentration was estimated as low as 3.4 × 10-6 M. The detection method based on GO mediated sandwich substrate avoids complicated surface modification manipulations and improves the substrate cleanness. Moreover, the resultant sandwich substrates can be used to recognize fingerprint peaks of different PCBs in their complex mixture, revealing great potential applications in SERS-based simultaneous detection of multiple pollutants with low affinity.

19.
DNA Cell Biol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721599

RESUMO

There is increasing evidence suggesting that dysregulation of miR-155 and its target angiotensin receptor type 1 (AT1R) are linked to the incidence of ischemic stroke (IS), but the underlying mechanisms remain to be clarified. In this study, we therefore sought to investigate how miR-155 and AT1R polymorphisms affect IS risk. We included 579 IS patients and 509 age-matched controls in the present analysis, genotyping individuals for the rs767649 polymorphism in miR-155, as well as for the rs1492099 and rs275653 polymorphisms in AT1R via iMLDR-TM genotyping technology. The allele and genotype frequencies for the assessed polymorphisms were comparable in IS patients and controls, without any detectable association between AT1R haplotype and IS risk. We conducted additional trial of ORG 10172 in acute stroke treatment-mediated stratification, which indicated that the AT1R rs1492099 T allele was linked to a decreased risk of large-artery atherosclerosis (LAA) stroke. We further found that those with the AT1R rs275653 AA genotype had a decreased risk of small-artery occlusion (SAO) strokes. We further confirmed elevated miR-155 expression in IS patients, but observed no link between the rs767649 polymorphism and expression of this microRNA. Similarly, rs1492099 and rs275653 polymorphisms did not impact AT1R expression levels. The miR-155 rs767649 polymorphism does not seem to be a key determinant of IS risk, whereas the AT1R rs1492099 polymorphism is linked to reduced LAA-stroke risk, and the rs275653 AA genotype is potentially protective against SAO strokes.

20.
J Med Chem ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724864

RESUMO

The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy towards the inhibition of MYC via the disruption of the protein-protein-interaction between MYC and its chromatin cofactor WDR5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small molecule inhibitors of this interaction with potent in vitro binding affinity, and report structurally related negative controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors, and anticipate that the molecules disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.

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