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1.
Biomed Pharmacother ; 127: 110154, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32325347

RESUMO

LASP2 was recently demonstrated to serve as multifaceted roles in several types of cancers. However, its underlying mechanism in the progression of human liver cancer has not been explored. The aims of the current study were to detect LASP2 expression in a liver tissue microarray, and to determine whether LASP2 contributes to malignant phenotypes of HepG2 human hepatoblastoma cells. Our results revealed that LASP2 expression was downregulated in liver cancer tissues relative to normal non-cancerous tissues, and its downregulated expression was closely correlated with malignant process of liver cancer. In vitro, upregulation of LASP2 expression by transfection with LASP2 vector significantly suppressed HepG2 cells viability, colony formation and migration activities. Conversely, the viability, colony formation and migration abilities of HepG2 cells were increased when downregulating LASP2 expression by transfection with small interfering RNA targeting LASP2. Interaction study showed that silencing of LASP2 in HepG2 cells triggered high expression of Cyclin D1, ERK and p-ERK, and low expression of Bax, respectively. In addition, LASP2 silencing-induced malignant phenotypes were further attenuated after HepG2 cells treatment with ERK1/2 blocker PD98059. Collectively, our data suggest a link between LASP2 and MAPK/ERK axis in the development of hepatoblastoma and LASP2 may be a potential marker for assessment of liver cancer prognosis and staging.

2.
Hypertens Pregnancy ; 39(2): 126-138, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32200685

RESUMO

Objectives: The protective effects of interleukin(IL)-35 against injury to human umbilical vein endothelial cells (HUVECs) induced by the serum of pre-eclampsia patients were analyzed.Methods: This cross-sectional study included 24 patients with pre-eclampsia (PE) and 24 normotensive pregnant women.Results: Compared to normotensive pregnant women, patients with pre-eclampsia had lower IL-35 levels (P < 0.05). In addition, our in vitro experiments, IL-35 inhibited the PE serum-induced apoptosis of HUVECs and the levels of reactive oxygen species in HUVECs.Conclusion: Decreases in the serum IL-35 level may play an important role in the pathogenesis of endothelial dysfunction in patients with pre-eclampsia.

3.
J Am Heart Assoc ; 9(5): e013542, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32114888

RESUMO

Background Trends in acute myocardial infarction (AMI) incidence rates for diverse races/ethnicities are largely unknown, presenting barriers to understanding the role of race/ethnicity in AMI occurrence. Methods and Results We identified AMI hospitalizations for Kaiser Permanente Southern California members, aged ≥35 years, during 2000 to 2014 using discharge diagnostic codes. We excluded hospitalizations with missing race/ethnicity information. We calculated annual incidence rates (age and sex standardized to the 2010 US census population) for AMI, ST-segment-elevation myocardial infarction, and non-ST-segment-elevation myocardial infarction by race/ethnicity (Hispanic and non-Hispanic racial groups: Asian or Pacific Islander, black, and white). Using Poisson regression, we estimated annual percentage change in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction incidence by race/ethnicity and AMI incidence rate ratios between race/ethnicity pairs, adjusting for age and sex. We included 18 630 776 person-years of observation and identified 44 142 AMI hospitalizations. During 2000 to 2014, declines in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction were 48.7%, 34.2%, and 69.8%, respectively. Age- and sex-standardized AMI hospitalization rates/100 000 person-years declined for Hispanics (from 307 to 162), Asians or Pacific Islanders (from 271 to 158), blacks (from 347 to 199), and whites (from 376 to 189). Annual percentage changes ranged from -2.99% to -4.75%, except for blacks, whose annual percentage change was -5.32% during 2000 to 2009 and -1.03% during 2010 to 2014. Conclusions During 2000 to 2014, AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction hospitalization incidence rates declined substantially for each race/ethnic group. Despite narrowing rates among races/ethnicities, differences persist. Understanding these differences can help identify unmet needs in AMI prevention and management to guide targeted interventions.

4.
J Pharm Sci ; 109(5): 1772-1779, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32070699

RESUMO

Hypodermic needles and syringes are currently the main route of the transdermal administration. Many complaints associated with needle-stick injuries, needle phobia, and needle abuse have motivated the development of alternative drug delivery strategies. Pneumatic needle-free injections stand out from various alternative strategies because of the convenience in adjusting the driving pressure and the injection volume. This study proposed a novel control method of the pneumatic needle-free injection for delivering larger volume drugs to the target sites at desired rates and time by controlling the driving pressure. The dynamic characteristics of this injection mode were evaluated in the impact experiments and the results confirmed the reliability of this controllable system in controlling the outlet pressure and jet velocity. The injection performances of it were compared with that of other injection modes through in vivo and in vitro experiments. This controllable system was able to control the injection depth and it was more conducive to the lateral diffusion of the liquid jets in gelatin. Moreover, it could not only enlarge the diffusion of diclofenac solution in rats, but also accelerate the metabolism of diclofenac solution in rats. All experimental results confirmed the reliability of this controllable injection system.

5.
Circulation ; 141(7): 509-519, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32065770

RESUMO

BACKGROUND: In recent decades, the rates of incident acute myocardial infarction (AMI) have declined in the United States, yet disparities by sex remain. In an integrated healthcare delivery system, we examined temporal trends in incident AMI among women and men. METHODS: We identified hospitalized AMI among members ≥35 years of age in Kaiser Permanente Southern California. The first hospitalization for AMI overall, and for ST-segment-elevation MI and non-ST-segment-elevation MI was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge diagnosis codes in each calendar year from 2000 through 2014. Age- and sex-standardized incidence rates per 100 000 person-years were calculated by using direct adjustment to the 2010 US Census population. Average annual percent changes (AAPCs) and period percent changes were calculated, and trend tests were conducted using Poisson regression. RESULTS: We identified 45 331 AMI hospitalizations between 2000 and 2014. Age- and sex-standardized incidence rates of AMI declined from 322.4 (95% CI, 311.0-333.9) in 2000 to 174.6 (95% CI, 168.2-181.0) in 2014, representing an AAPC of -4.4% (95% CI, -4.2 to -4.6) and a period percent change of -46.6%. The AAPC for AMI in women was -4.6% (95% CI, -4.1 to -5.2) between 2000 and 2009 and declined to -2.3% (95% CI, -1.2 to -3.4) between 2010 and 2014. The AAPC for AMI in men was stable over the study period (-4.7% [95% CI, -4.4 to -4.9]). The AAPC for ST-segment-elevation MI hospitalization overall was -8.3% (95% CI, -8.0% to -8.6%).The AAPC in ST-segment-elevation MI changed among women in 2009 (2000-2009: -10.2% [95% CI, -9.3 to -11.1] and in 2010-2014: -5.2% [95% CI, -3.1 to -7.3]) while remaining stable among men (-8.0% [95% CI, -7.6 to -8.4]). The AAPC for non-ST-segment-elevation MI hospitalization was smaller than for ST-segment-elevation MI among both women and men (-1.9% [95% CI, -1.5 to -2.3] and -2.8% [95% CI, -2.5 to -3.2], respectively). CONCLUSIONS: These results suggest that the incidence of hospitalized AMI declined between 2000 and 2014; however, declines in AMI have slowed among women in comparison with men in recent years. Determining unmet care needs among women may reduce these sex-based AMI disparities.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32088824

RESUMO

A theoretical approach was followed to optimize the design of a cylindrical photobioreactor for wastewater treatment based on algal culture. In particular, the problem of uneven light distribution that impairs algal growth was minimized by optimizing the area of uniform illumination distribution for a bioreactor design that can be enlarged without affecting its performance. The theoretical analysis was based on modeled simulations to determine the best configuration and illumination mode. The Monte Carlo method was used to simulate the illumination distribution inside the bioreactor, and the relationships between the width of the area with uniform illumination and related parameters were explored. Based on these theoretical considerations and predictions, an actual experimental photobioreactor was built containing a working area (where culture of Chlorella pyrenoidosa was enabled) and a catchment area for effluent. The performance of this bioreactor was tested with synthetic wastewater as a substrate. The light distribution was found to be relatively uniform inside the bioreactor, supporting excellent algal growth and resulting in maximum removal rates of 84.41% for total nitrogen, 99.73% for total phosphorus, 85.03% for NH4+-N, and 75.94% for chemical oxygen demand (COD) over a period of 32 days of operation. The presented approach provides new insights for improving the efficiency and scalability of photobioreactors and promotes their development for wastewater treatment and resource utilization.

7.
Chem Commun (Camb) ; 56(17): 2614-2617, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32016279

RESUMO

A ruthenium-catalyzed allylic C(sp3)-H activation strategy has been employed to develop an intermolecular coupling of alkenyl sulfonamides with alkynes. This protocol features the diastereoselective construction of [3.3.0] and [4.3.0] bicyclic sultams in one step.

8.
J Integr Med ; 18(3): 196-202, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32067923

RESUMO

Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

9.
J Colloid Interface Sci ; 564: 28-36, 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-31896425

RESUMO

As for electrocatalysis, single-atom metal catalysts have been proved to lower the cost and utilize precious metals more efficiently. Herein, single-atom Pt catalyst supported on holey ultrathin g-C3N4 nanosheets (Pt-CNHS) was synthesized via a facile liquid-phase reaction of g-C3N4 and H2PtCl6. The single-atom Pt can achieve high dispersibility and stability, which can promote the utilization efficiency as well as enhance the electrochemical activity. When employed as Li-O2 batteries' cathode catalyst, Pt-CNHS exhibits excellent electrocatalytic activity. Li-O2 batteries utilizing Pt-CNHS show much higher discharge specific capacities than those with pure CNHS. Li-O2 batteries with Pt-CNHS cathode can be cycled stably for 100 times under the discharge capacity of 600 mAh g-1. Based on experimental results and density functional theory calculations, the superior electrocatalytic activity of Pt-CNHS can be ascribed to the large surface area, the enhanced electrical conductivity and the efficient interfacial mass transfer through Pt atoms and porous structure of CNHS.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31957251

RESUMO

PURPOSE: Nonsmall cell lung cancer (NSCLC) patients with brain metastases (BM) have a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with whole-brain irradiation (WBI) with or without chemotherapy for NSCLC patients with BM. MATERIALS AND METHODS: A Markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]) from the Chinese healthcare perspective. RESULTS: When considering progression as intracranial progression and overall progression, respectively, the incremental cost-effectiveness ratio was $14 882.64/QALY and $13 484.21/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (ACER) and net benefit showed advantage of icotinib (ACER: $34 521.42/QALY for intracranial progression and $36 562.63/QALY for overall progression; net benefit: -$8407.36 for intracranial progression and -$9836.41 for overall progression). One-way sensitivity analyses demonstrated that no thresholds were encountered. The probabilistic sensitivity analyses showed even at a WTP under $18 000/QALY, icotinib could be cost-effective. CONCLUSION: Icotinib was cost-effective compared with WBI with or without chemotherapy.

11.
Pharmacoepidemiol Drug Saf ; 29(2): 182-188, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31797475

RESUMO

PURPOSE: The objective was to develop a natural language processing (NLP) algorithm to identify vaccine-related anaphylaxis from plain-text clinical notes, and to implement the algorithm at five health care systems in the Vaccine Safety Datalink. METHODS: The NLP algorithm was developed using an internal NLP tool and training dataset of 311 potential anaphylaxis cases from Kaiser Permanente Southern California (KPSC). We applied the algorithm to the notes of another 731 potential cases (423 from KPSC; 308 from other sites) with relevant codes (ICD-9-CM diagnosis codes for anaphylaxis, vaccine adverse reactions, and allergic reactions; Healthcare Common Procedure Coding System codes for epinephrine administration). NLP results were compared against a reference standard of chart reviewed and adjudicated cases. The algorithm was then separately applied to the notes of 6 427 359 KPSC vaccination visits (9 402 194 vaccine doses) without relevant codes. RESULTS: At KPSC, NLP identified 12 of 16 true vaccine-related cases and achieved a sensitivity of 75.0%, specificity of 98.5%, positive predictive value (PPV) of 66.7%, and negative predictive value of 99.0% when applied to notes of patients with relevant diagnosis codes. NLP did not identify the five true cases at other sites. When NLP was applied to the notes of KPSC patients without relevant codes, it captured eight additional true cases confirmed by chart review and adjudication. CONCLUSIONS: The current study demonstrated the potential to apply rule-based NLP algorithms to clinical notes to identify anaphylaxis cases. Increasing the size of training data, including clinical notes from all participating study sites in the training data, and preprocessing the clinical notes to handle special characters could improve the performance of the NLP algorithms. We recommend adding an NLP process followed by manual chart review in future vaccine safety studies to improve sensitivity and efficiency.

12.
Am J Hematol ; 95(3): 238-244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31804739

RESUMO

The genetic and molecular abnormalities underlying histological transformation (HT) of nodal marginal zone lymphoma (NMZL) to diffuse large B-cell lymphoma (DLBCL) are not well known. While del(20q12) is commonly deleted in myelodysplastic syndrome it has not previously been associated with DLBCL. We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin. Here we report eight matched cases of transformed MZL(tMZL): six from nodal MZL (tNMZL) and two from splenic MZL (tSMZL). We found >20% del(20q12) in 4/6 tNMZL, but not in tSMZL, nor in unmatched DLBCL, MZL with increased large cells (MZL-ILC), or MZL cases. To examine whether transformation is associated with a specific gene signature, the matched cases were analyzed for multiplexed gene expression using the Nanostring PanCancer Pathways panel. The differential gene expression signature revealed enrichment of inflammatory markers, as previously observed in MZL. Also, tMZL and de novo DLBCL were enriched for extracellular matrix proteins such as collagen and fibronectin, vascular development protein PDGFRß, DNA repair protein RAD51, and oncogenic secrete protein Wnt11. A subset of genes is expressed differentially in del(20q12) tMZL cases vs non-del(20q12) tMZL cases. These results suggest a specific pathway is involved in the histological transformation of NMZL, which could serve as an indicator of aggressive clinical course in this otherwise indolent neoplasm.

13.
Vasc Med ; 25(1): 3-12, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31512991

RESUMO

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% (n = 3442) with CLI and 68.9% (n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% (n = 4481) who were not on a statin in the year before diagnosis, 13.5% (n = 607) newly initiated therapy within 1 month (CLI: 10.1% (n = 150); without CLI: 15.3% (n = 457)). Following diagnosis, 12.5% (n = 660) discontinued statin therapy within 1 year (CLI: 15.5% (n = 202); without CLI: 11.5% (n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.

14.
Cardiovasc Res ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790138

RESUMO

AIMS: Sustained activation of ß-adrenergic signaling induces cardiac fibrosis, which marks progression to heart failure. GHSR (growth hormone secretagogue receptor) is the receptor for ghrelin, which is an orexigenic gastric hormone with newly defined cardiovascular effects. The present study determined the effects of GHSR deficiency in a mouse model of isoproterenol (ISO)-induced cardiac fibrosis and examined the underlying mechanism. METHODS AND RESULTS: Histochemical studies showed that GHSR deficiency exacerbated cardiac fibrosis. Quantitative RT-PCR, western blotting and immunofluorescence staining demonstrated that cardiac fibroblasts isolated from GHSR-/- mice exhibited increased expression of marker genes for myofibroblast trans-differentiation (α-SMA, SM22, and calponin) upon Transforming growth factor-ß (TGF-ß) treatment compared to wild-type mice. RNA-Sequencing of heart transcriptomes revealed that differentially expressed genes in GHSR-/- hearts were enriched in such biological processes as extracellular matrix (ECM) organization, inflammatory response, lipid metabolism, cell cycle, migration and adhesion. Particularly, GHSR deficiency increased Wnt/ß-catenin pathway activation in ISO-induced myocardial fibrosis. In addition, loss of GHSR in macrophages instigated inflammasome activation with increased cleavage and release of IL-18. CONCLUSIONS: These results for the first time demonstrated that GHSR deficiency aggravated ISO-induced cardiac fibrosis, suggesting that GHSR was a potential target for the intervention of cardiac fibrosis. TRANSLATIONAL PERSPECTIVE: We revealed a cardiac protective role of GHSR, a receptor for gastric hormone ghrelin. Our study provided a novel therapeutic strategy against cardiac fibrosis.

15.
J Neurosci ; 39(40): 7976-7991, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31363064

RESUMO

Alzheimer's disease (AD) is associated with the cleavage of the amyloid precursor protein (APP) to produce the toxic amyloid-ß (Aß) peptide. Accumulation of Aß, together with the concomitant inflammatory response, ultimately leads to neuronal death and cognitive decline. Despite AD progression being underpinned by both neuronal and immunological components, therapeutic strategies based on dual targeting of these systems remains unexplored. Here, we report that inactivation of the p110δ isoform of phosphoinositide 3-kinase (PI3K) reduces anterograde axonal trafficking of APP in hippocampal neurons and dampens secretion of the inflammatory cytokine tumor necrosis factor-alpha by microglial cells in the familial AD APPswe/PS1ΔE9 (APP/PS1) mouse model. Moreover, APP/PS1 mice with kinase-inactive PI3Kδ (δD910A) had reduced Aß peptides levels and plaques in the brain and an abrogated inflammatory response compared with APP/PS1 littermates. Mechanistic investigations reveal that PI3Kδ inhibition decreases the axonal transport of APP by eliciting the formation of highly elongated tubular-shaped APP-containing carriers, reducing the levels of secreted Aß peptide. Importantly, APP/PS1/δD910A mice exhibited no spatial learning or memory deficits. Our data highlight inhibition of PI3Kδ as a new approach to protect against AD pathology due to its dual action of dampening microglial-dependent neuroinflammation and reducing plaque burden by inhibition of neuronal APP trafficking and processing.SIGNIFICANCE STATEMENT During Alzheimer's disease (AD), the accumulation of the toxic amyloid-ß (Aß) peptide in plaques is associated with a chronic excessive inflammatory response. Uncovering new drug targets that simultaneously reduce both Aß plaque load and neuroinflammation holds therapeutic promise. Using a combination of genetic and pharmacological approaches, we found that the p110δ isoform of phosphoinositide 3-kinase (PI3K) is involved in anterograde trafficking of the amyloid precursor protein in neurons and in the secretion of tumor necrosis factor-alpha from microglial cells. Genetic inactivation of PI3Kδ reduces Aß plaque deposition and abrogates the inflammatory response, resulting in a complete rescue of the life span and spatial memory performance. We conclude that inhibiting PI3Kδ represents a novel therapeutic approach to ameliorate AD pathology by dampening plaque accumulation and microglial-dependent neuroinflammation.

16.
Clin Infect Dis ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31437269

RESUMO

BACKGROUND: Urinary tract infections (UTIs) occur commonly, but recent data on UTI rates are scarce. It is unknown how the growth of virtual health care delivery affects outpatient UTI management and trends in the United States. PATIENTS AND METHODS: From January 1, 2008 to December 31, 2017, UTIs from outpatient settings (office, emergency, and virtual visits) were identified from electronic health records at Kaiser Permanente Southern California using multiple UTI definitions. Annual rates estimated by Poisson regression were stratified by sex, care setting, age, and race/ethnicity. Annual trends were estimated by linear or piecewise Poisson regression. RESULTS: UTIs occurred in 1,065,955 individuals. Rates per 1000 person-years were 53.7 (95% CI: 50.6 to 57.0) by diagnosis code with antibiotic and 25.8 (95% CI: 24.7 to 26.9) by positive culture. Compared to office and emergency visits, UTIs were increasingly diagnosed in virtual visits, where rates by diagnosis code with antibiotic increased annually by 21.2% (95% CI: 16.5% to 26.2%) in females and 29.3% (95% CI: 23.7% to 35.3%) in males. Only 32% of virtual care diagnoses had a culture order. Overall, UTI rates were highest and increased the most in older adults. Rates were also higher in Hispanic and White females and Black and White males. CONCLUSION: Outpatient UTI rates increased from 2008 to 2017, especially in virtual care and among older adults. Virtual care is important for expanding access to health services, but strategies are needed in all outpatient care settings to ensure accurate UTI diagnosis and reduce inappropriate antibiotic treatment.

17.
Front Immunol ; 10: 1895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440258

RESUMO

Procyanidins, a subclass of flavonoids found in commonly consumed foods, possess potential anti-inflammatory activity. Manipulation of M1/M2 macrophage homeostasis is an effective strategy for the treatment of metabolic inflammatory diseases. The objective of this study was to determine the effect of procyanidins on macrophage polarization. Procyanidin B2 (PCB2), the most widely distributed natural procyanidins, enhanced the expressions of M2 macrophage markers (Arg1, Ym1, and Fizz1). PCB2 activated peroxisome proliferator-activated receptor γ (PPARγ) activity and increased the expressions of PPARγ target genes (CD36 and ABCG1) in macrophages. Inhibition of PPARγ using siRNA or antagonist GW9662 attenuated the PCB2-induced expressions of M2 macrophage markers. In addition, we identified cognate PPAR-responsive elements (PPREs) within the 5'-flanking regions of the mouse Arg1, Ym1, and Fizz1 genes. Furthermore, macrophages isolated from db/db diabetic mice showed lower expressions of M2 markers. PCB2 effectively restored the Arg1, Ym1, and Fizz1 expressions in a PPARγ-dependent manner. These findings support the notion that PCB2 regulated macrophage M2 polarization via the activation of PPARγ. Our results provide a new mechanism by which procyanidins exert their beneficial anti-inflammatory effects.

18.
Nat Commun ; 10(1): 2409, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160579

RESUMO

An ideal anti-counterfeiting technique has to be inexpensive, mass-producible, nondestructive, unclonable and convenient for authentication. Although many anti-counterfeiting technologies have been developed, very few of them fulfill all the above requirements. Here we report a non-destructive, inkjet-printable, artificial intelligence (AI)-decodable and unclonable security label. The stochastic pinning points at the three-phase contact line of the ink droplets is crucial for the successful inkjet printing of the unclonable security labels. Upon the solvent evaporation, the three-phase contact lines are pinned around the pinning points, where the quantum dots in the ink droplets deposited on, forming physically unclonable flower-like patterns. By utilizing the RGB emission quantum dots, full-color fluorescence security labels can be produced. A convenient and reliable AI-based authentication strategy is developed, allowing for the fast authentication of the covert, unclonable flower-like dot patterns with different sharpness, brightness, rotations, amplifications and the mixture of these parameters.

19.
Adv Mater ; 31(32): e1902479, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31231886

RESUMO

Great challenges remain concerning the cost-effective manufacture of high-performance metal meshes for transparent glass heaters (TGHs). Here, a high-performance silver mesh fabrication technique is proposed for TGHs using electric-field-driven microscale 3D printing and a UV-assisted microtransfer process. The results show a more optimal trade-off in sheet resistance (Rs = 0.21 Ω sq-1 ) and transmittance (T = 93.9%) than for indium tin oxide (ITO) and ITO substitutes. The fabricated representative TGH also exhibits homogeneous and stable heating performance, remarkable environmental adaptability (constant Rs for 90 days), superior mechanical robustness (Rs increase of only 0.04 in harsh conditions-sonication at 100 °C), and strong adhesion force with a negligible increase in Rs (2-12%) after 100 peeling tests. The practical viability of this TGH is successfully demonstrated with a deicing test (ice cube: 21 cm3 , melting time: 78 s, voltage and glass thickness: 4 V, 5 mm). All of these advantages of the TGHs are attributed to the successful fabrication of silver meshes with high resolution and high aspect ratio on the glass substrate using the thick film silver paste. The proposed technique is a promising new tool for the inexpensive fabrication of high-performance TGHs.

20.
Vaccine ; 37(26): 3478-3484, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31088744

RESUMO

INTRODUCTION: Pain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California. METHODS: ZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0-10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients. RESULTS: We interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR = 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR = 0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70 years versus those ≥70 years and was similar or lower in females versus males. CONCLUSION: We used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN.

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