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1.
Biomed Chromatogr ; : e4805, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012315

RESUMO

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating nonalcoholic fatty liver disease (NAFLD) in China, composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF are still indistinct to date. Thus, a high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF) method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed into rats, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first time to explore the constituents of QHF and its metabolism in vivo and in vitro, which realize the first step to clarify the chemical basis of QHF qualitatively, and lay the foundation for further research on the anti-NAFLD mechanism of QHF.

2.
Reprod Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046427

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common gynaecological endocrine disorders, and more than 60% of PCOS patients have varying degrees of insulin resistance (IR). The regulatory role of microRNAs (miRNAs) at post-transcriptional levels in human cumulus cells relating to IR in PCOS remains unclear. In this case-control study, 26 PCOS patients with IR (PCOS-IR) and 24 patients without IR (PCOS-control) were enrolled. We determined the differentially expressed miRNA and mRNA using next-generation sequencing technology, and these miRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (PCR). These miRNA regulating pathways (e.g., MAPK pathway) were analysed by bioinformatics analysis, and the Rap1b was demonstrated to be targeted by miR-612 based on quantitative real-time PCR, western blot and luciferase activity assay. A total of 59 known miRNAs and 617 differentially expressed genes were identified that differentially expressed between PCOS-IR and PCOS-control cumulus cells. Moreover, the potential regulating roles of miRNAs and their targeting genes in pathophysiology of IR and PCOS were analysed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and several key processes were enriched, such as MAPK activity. Furthermore, Rap1b, a regulator of the MAPK pathway, was demonstrated to be suppressed directly by miR-612 in PCOS-IR cumulus cells based on negative expression correlation validation, dual luciferase activity assay and reduction of Rap1b expression after miR-612 mimics transfection. Our results suggested that miRNAs and their targeted pathways in ovarian cumulus cells may play important roles in the aetiology and pathophysiology of PCOS with IR.

3.
Sci China Life Sci ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32048164

RESUMO

Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria. Here, we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by the mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components involved in mitochondrial protein and RNA importation, such as TOM40 and PNPASE, interact with mecciRNAs and regulate protein entry. The expression of mecciRNAs is regulated, and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.

4.
Am J Clin Nutr ; 111(2): 448-458, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891374

RESUMO

BACKGROUND: In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration. OBJECTIVES: We aimed to overcome limitations of previously conducted coffee trials in a randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity. METHODS: We conducted a 24-wk randomized placebo-controlled trial in 126 overweight, non-insulin sensitive (HOMA-IR ≥1.30), Chinese, Malay, and Asian-Indian males and females aged 35-69 y. Participants were randomly assigned to receive 4 cups of instant regular coffee (n = 62) or 4 cups of a coffee-like placebo beverage (n = 64) per day. The primary outcome was the amount of glucose metabolized per kilogram of body weight per minute (Mbw) assessed during steady-state conditions with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism. RESULTS: Coffee consumption did not significantly change insulin sensitivity compared with placebo (percentage mean difference in Mbw = 4.0%; 95% CI: -8.3, 18.0%; P = 0.53). Furthermore, no significant differences in fasting plasma glucose (2.9%; 95% CI: -0.4, 6.3%; P = 0.09) or biological mediators of insulin resistance, such as plasma adiponectin (2.3%; 95% CI: -1.4, 6.2%; P = 0.22), were observed between coffee and placebo groups over 24 wk of intervention. Participants in the coffee arm experienced a loss of fat mass (FM) (-3.7%; 95% CI: -6.3, -1.1%; P = 0.006) and reduction in urinary creatinine concentrations (-21.2%; 95% CI: -31.4, -9.5%; P = 0.001) compared with participants in the placebo arm over 24 wk of intervention. CONCLUSIONS: Consuming 4 cups/d of caffeinated coffee for 24 wk had no significant effect on insulin sensitivity or biological mediators of insulin resistance but was associated with a modest loss of FM and reduction in urinary creatinine concentrations.This trial was registered at clinicaltrials.gov as NCT01738399. Registered on November 28, 2012. Trial sponsor: Nestlé Research, Lausanne, Switzerland. Trial site: National University of Singapore.

5.
Funct Plant Biol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31930956

RESUMO

The chemical composition, crystal morphology and expression levels of associated genes involved in the cuticular wax of three pear cultivars 'Housui', 'Cuiguan' and 'Yuluxiang' after treatment with palmitic acid (PA), hexacosanoic acid (HA), ethephon and methyl jasmonate (Meja) were determined. A total of 59 cuticular wax compounds were detected across all samples. The wax coverage of 'Housui' fruits increased by 71.74, 93.48 and 89.13% after treatment with PA, ethephon and Meja, respectively, and treatment with PA, HA and Meja also increased the wax coverage in 'Cuiguan' (65.33, 20.00 and 21.33% respectively) and in 'Yuluxiang' (38.60, 63.16 and 42.11% respectively) fruits. Heatmap clustering analysis and partial least-squares-discriminate analysis (PLS-DA) also revealed that the different treatments exerted various influences on cuticular wax among the different cultivars. In addition, the wax component coverage and wax crystal structures showed variations among the different cultivars as well as different treatments. Gene expression analysis revealed 11 genes likely to be involved in pear fruit wax synthesis, transport and regulation. Taken together, the results of this study demonstrate that the differences in the cuticular waxes of the fruits of different cultivars after treatment with PA, HA, ethephon or Meja might lead to a better understanding of the regulatory effect of a substrate or elicitor on the composition and deposition of cuticular waxes.

6.
BMC Plant Biol ; 20(1): 14, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914928

RESUMO

BACKGROUND: The BAHD acyltransferase superfamily exhibits various biological roles in plants, including regulating fruit quality, catalytic synthesizing of terpene, phenolics and esters, and improving stress resistance. However, the copy numbers, expression characteristics and associations with fruit aroma formation of the BAHD genes remain unclear. RESULTS: In total, 717 BAHD genes were obtained from the genomes of seven Rosaceae, (Pyrus bretschneideri, Malus domestica, Prunus avium, Prunus persica, Fragaria vesca, Pyrus communis and Rubus occidentalis). Based on the detailed phylogenetic analysis and classifications in model plants, we divided the BAHD family genes into seven groups, I-a, I-b, II-a, II-b, III-a, IV and V. An inter-species synteny analysis revealed the ancient origin of BAHD superfamily with 78 syntenic gene pairs were detected among the seven Rosaceae species. Different types of gene duplication events jointly drive the expansion of BAHD superfamily, and purifying selection dominates the evolution of BAHD genes supported by the small Ka/Ks ratios. Based on the correlation analysis between the ester content and expression levels of BAHD genes at different developmental stages, four candidate genes were selected for verification as assessed by qRT-PCR. The result implied that Pbr020016.1, Pbr019034.1, Pbr014028.1 and Pbr029551.1 are important candidate genes involved in aroma formation during pear fruit development. CONCLUSION: We have thoroughly identified the BAHD superfamily genes and performed a comprehensive comparative analysis of their phylogenetic relationships, expansion patterns, and expression characteristics in seven Rosaceae species, and we also obtained four candidate genes involved in aroma synthesis in pear fruit. These results provide a theoretical basis for future studies of the specific biological functions of BAHD superfamily members and the improvement of pear fruit quality.

7.
Crit Rev Anal Chem ; : 1-12, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914794

RESUMO

1-Deoxynojirimycin (1-DNJ), a polyhydroxylated alkaloid, is a highly selective and potent glycosidase inhibitor that has garnered great interest as a tool to study cellular recognition and as a potential therapeutic agent. The development of analytical methods for the quantification polyhydroxylated alkaloids in natural products requires a multifaceted approach. Many publications over the past five decades have described analytical methods for this compound. However, recently more advanced techniques have come to prominence for sample extraction, purification, detection, and identification. This review provides an updated, extensive overview of the available methods for the extraction, purification, identification or detection of 1-DNJ. The review highlights different strategies for the design of 1-DNJ detection methods, which we analyzed in light of recent detection data. Finally, we conclude with perspectives on possible strategies for increasing the efficiency of identification and quantification of 1-DNJ in the future.

8.
Nat Biomed Eng ; 4(1): 125-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31740768

RESUMO

In contrast to traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here we show in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (FAH)-positive hepatocytes in the liver, and rescued weight loss in mice. We also generated FAH+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of a chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABEs. Our findings suggest that adenine base editing can be used for the correction of genetic diseases in adult animals.

9.
Prep Biochem Biotechnol ; 50(1): 37-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31453755

RESUMO

Casein was the major protein in the milk of mammals and it was massively lost in the discharged wastewater during dairy product manufacture. This work was aimed at recovering casein from the dairy wastewater by using foam fractionation. In order to improve the foam stability, xanthan gum was used as the foam stabilizer based on the association between protein and polysaccharide. The results of the scanning electron microscope (SEM) and fluorescence emission spectrum suggested that casein could be associated with xanthan gum primarily through electrostatic attraction, which was significantly affected by pH. Moreover, the introduction of xanthan gum had a marked impact on the surface tension, foam ability, foam stability, turbidity, zeta potential and average particle size of casein dispersion. Foam fractionation was performed under the suitable operation condition of pH 6.0, loading liquid volume 400 mL, amount ratio of casein and xanthan gum 1:2, volumetric airflow rate 100 mL/min and pore diameter of gas distributor 0.180 mm. The enrichment ratio and the recovery percentage of casein reached as high as 16.81 and 86.51%, respectively. This work is expected to provide a cost-effective method to recover the trace desired material through improving foam stability based on intermolecular forces.Research highlightsFoam fractionation has been proposed to recover casein from dairy wastewater.Xanthan gum has been used to improve the foam stability of casein.The main interaction between casein and xanthan gum was an electrostatic attraction.Xanthan gum contributed to weakening the flowability of interstitial liquid.

10.
Hepatology ; 71(1): 275-290, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31188495

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with few effective treatments, and the underlying mechanisms that drive HCC pathogenesis remain poorly characterized. Identifying genes and pathways essential for HCC cell growth will aid the development of new targeted therapies for HCC. Using a kinome CRISPR screen in three human HCC cell lines, we identified transformation/transcription domain-associated protein (TRRAP) as an essential gene for HCC cell proliferation. TRRAP has been implicated in oncogenic transformation, but how it functions in cancer cell proliferation is not established. Here, we show that depletion of TRRAP or its co-factor, histone acetyltransferase KAT5, inhibits HCC cell growth through induction of p53-independent and p21-independent senescence. Integrated cancer genomics analyses using patient data and RNA sequencing identified mitotic genes as key TRRAP/KAT5 targets in HCC, and subsequent cell cycle analyses revealed that TRRAP-depleted and KAT5-depleted cells are arrested at the G2/M phase. Depletion of topoisomerase II alpha (TOP2A), a mitotic gene and TRRAP/KAT5 target, was sufficient to recapitulate the senescent phenotype of TRRAP/KAT5 knockdown. Conclusion: Our results uncover a role for TRRAP/KAT5 in promoting HCC cell proliferation by activating mitotic genes. Targeting the TRRAP/KAT5 complex is a potential therapeutic strategy for HCC.

11.
Food Chem ; 306: 125615, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622833

RESUMO

Phycocyanin (PC), a plant-based protein with interesting biological activity, is rarely directly applied in the food industry because it has structural and functional limitations. This study combined ultra-high-pressure (UHP) treatment with glycation to improve PC functionality and explored resulting structural changes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, scanning electron microscopy, Fourier-transform infrared spectroscopy, circular dichroism, and UV-visible spectroscopy. The UHP treatment obviously improved the speed and degree of glycation and the composite-modified PC (CM-PC) showed high solubility and good emulsifying and foaming performance. Scanning electron microscopy images showed the CM-PC surface was loose and fluffy. Gel electrophoresis, Fourier-transform infrared spectroscopy, and circular dichroism results demonstrated that the content of α-helix decreased from 78.1% in PC to 26.6% in CM-PC, and hydroxyl groups were introduced. UV-visible spectroscopy showed that the mechanism of composite modification involved stretching of the PC and promotion of binding with sugars.


Assuntos
Ficocianina/química , Spirulina/química , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Emulsões/metabolismo , Glicosilação , Pressão , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
12.
J Exp Med ; 217(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31658987

RESUMO

Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to first-cousin parents, displaying idiopathic asthenozoospermia but no ciliary-related symptoms. Whole-exome sequencing identified a missense variant (c.G5408A, p.C1803Y) in DNAH17, a functionally uncharacterized gene, recessively cosegregating with asthenozoospermia in the family. DNAH17, specifically expressed in testes, was localized to sperm flagella, and the mutation did not alter its localization. However, spermatozoa of all three patients showed higher frequencies of microtubule doublet(s) 4-7 missing at principal piece and end piece than in controls. Mice carrying a homozygous mutation (Dnah17M/M) equivalent to that in patients recapitulated the defects in patients' sperm tails. Further examinations revealed that the doublets 4-7 were destabilized largely due to the storage of sperm in epididymis. Altogether, we first report that a homozygous DNAH17 missense variant specifically induces doublets 4-7 destabilization and consequently causes asthenozoospermia, providing a novel marker for genetic counseling and diagnosis of male infertility.

13.
J Nanosci Nanotechnol ; 20(6): 3356-3360, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748027

RESUMO

We report the formation of gold nanoparticles on indium tin oxide conducting glass (ITO) surface via electrodeposition method at room temperature. The prepared nano-Au electrodes has been fabricated for sensitive detection of Pb2+, and showed highly selective response toward Pb2+. The electrochemical detection of Pb2+ were determined by differential pulse stripping voltammetric (DPSV). The nano-Au electrochemical sensor could detect Pb2+ from 0.5 to 10 µM with detection limits of 0.06 µM (S/N= 3) and sensitivity of 0.27996 mA µM-1. The proposed sensor is simple, reliable, sensitive, selective, and low-cost, thus holds potential for practical application in Pb2+ detection.

14.
Appl Opt ; 58(32): 8894-8899, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31873667

RESUMO

Nanorod and nanosphere ${{\rm Gd}_2}{{\rm O}_3}\!:\!{{\rm Tb}^{3 + }}$Gd2O3:Tb3+ particles were synthesized from chloride precursors ${{\rm GdCl}_3}$GdCl3 and ${{\rm TbCl}_3}$TbCl3 by NaOH addition in a diethylene glycol medium. The nanospheres and the nanorods of ${{\rm Gd}_2}{{\rm O}_3}\!:\!{{\rm Tb}^{3 + }}$Gd2O3:Tb3+ were tunably obtained by adjusting the addition speed of NaOH. The structure, morphologies, and the luminescence properties of nanorod and nanosphere ${{\rm Gd}_2}{{\rm O}_3}\!:\!{{\rm Tb}^{3 + }}$Gd2O3:Tb3+ were characterized by x-ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy, and fluorescence spectrometry, respectively. The results confirmed that the structure of nanorod and nanosphere ${{\rm Gd}_2}{{\rm O}_3}\!:\!{{\rm Tb}^{3 + }}$Gd2O3:Tb3+ is cubic ${{\rm Gd}_2}{{\rm O}_3}$Gd2O3, and the luminescence of nanospheres is more intense than that of nanorods. The low cytotoxicity measured by the MTT method indicated the good biocompatibility of the samples.

15.
Opt Express ; 27(23): 32949-32957, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878370

RESUMO

We demonstrate an 806 nm laser diode end-pumped continuous-wave (CW) and actively Q-switched (AQS) orthogonally-polarized dual-wavelength Nd:YLF laser operating at 1314 and 1321 nm. Benefitting from the small difference of the stimulated emission cross sections at 1314 and 1321 nm in Nd:YLF crystal, the power equalized emissions at both wavelengths were achieved by simply titling the output coupler. A maximum CW output power of 9.2 W was obtained with the incident pump power of 32.5 W, giving an optical-to-optical conversion efficiency of approximately 28% and a slope efficiency of approximately 33%. Furthermore, active Q-switching was realized by inserting a Brewster-cut acousto optic modulator. For an incident pump power of 30 W, this oscillator delivered an average power of 6.5 W at a pulse repetition frequency (PRF) of 20 kHz, and a pulse energy of 2.6 mJ with a peak power of approximately 72 kW at a PRF of 1 kHz.

16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(6): 964-968, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31875370

RESUMO

Transrectal contrast-enhanced ultrasound (CEUS) is an important examination for rectal tumors. The inhomogeneity of the CEUS images has important clinical significance. However, there is no objective method to evaluate this index. In this study, a method based on gray-level co-occurrence matrix (GLCM) is proposed to extract texture features of images and grade these images according the inhomogeneity. Specific processes include compressing the gray level of the image, calculating the texture statistics of gray level co-occurrence matrix, combining feature selection and principal component analysis (PCA) for dimensionality reduction, and training and validating quadratic discriminant analysis (QDA). After ten cross-validation, the overall accuracy rate of machine classification was 87.01%, and the accuracy of each level was as follows: Grade Ⅰ 52.94%, Grade Ⅱ 96.48% and Grade Ⅲ 92.35% respectively. The proposed method has high accuracy in judging grade Ⅱ and Ⅲ images, which can help to identify the grade of inhomogeneity of contrast-enhanced ultrasound images of rectal tumors, and may be used to assist clinical doctors in judging the grade of inhomogeneity of contrast-enhanced ultrasound of rectal tumors.


Assuntos
Neoplasias Retais , Análise Discriminante , Humanos , Ultrassonografia
17.
BMC Biol ; 17(1): 93, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771567

RESUMO

BACKGROUND: Cathepsin L and some other cathepsins have been implicated in the development of obesity in humans and mice. The functional inactivation of the proteases reduces fat accumulation during mammalian adipocyte differentiation. However, beyond degrading extracellular matrix protein fibronectin, the molecular mechanisms by which cathepsins control fat accumulation remain unclear. We now provide evidence from Caenorhabditis elegans and mouse models to suggest a conserved regulatory circuit in which peripheral cathepsin L inhibition lowers fat accumulation through promoting central serotonin synthesis. RESULTS: We established a C. elegans model of fat accumulation using dietary supplementation with glucose and palmitic acid. We found that nutrient supplementation elevated fat storage in C. elegans, and along with worm fat accumulation, an increase in the expression of cpl-1 was detected using real-time PCR and western blot. The functional inactivation of cpl-1 reduced fat storage in C. elegans through activating serotonin signaling. Further, knockdown of cpl-1 in the intestine and hypodermis promoted serotonin synthesis in worm ADF neurons and induced body fat loss in C. elegans via central serotonin signaling. We found a similar regulatory circuit in high-fat diet-fed mice. Cathepsin L knockout promoted fat loss and central serotonin synthesis. Intraperitoneal injection of the cathepsin L inhibitor CLIK195 similarly reduced body weight gain and white adipose tissue (WAT) adipogenesis, while elevating brain serotonin level and WAT lipolysis and fatty acid ß-oxidation. These effects of inhibiting cathepsin L were abolished by intracranial injection of p-chlorophenylalanine, inhibitor of a rate-limiting enzyme for serotonin synthesis. CONCLUSION: This study reveals a previously undescribed molecular mechanism by which peripheral CPL-1/cathepsin L inhibition induces fat loss in C. elegans and mice through promoting central serotonin signaling.

18.
Front Neurol ; 10: 1102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695669

RESUMO

Background: Behcet's disease (BD) is multi-systemic vasculitis, which generally is repeated oral and genital ulcerations as well as ocular and skin lesions. Today, the pathogenesis of BD remains mostly unknown. It is also suggested that the disease is probably related to autoinflammatory and autoimmune disorders, and innate immunity damages were perceived as key in its pathologic process. Only 5% of BD patients have neurological involvement, and it usually occurs in 4-6 years after the initial symptoms. Early onset of neurological impairment makes it difficult to diagnose and treat definitely. Case Presentation: A 38-year-old man was admitted to our hospital with numbness and weakness of the left extremities. Diffusion magnetic resonance imaging (MRI) revealed focal infarction in the posterior limb of the internal capsule. Skin pathology suggested small vessel vasculitis, and high-resolution MRI revealed intracranial arteritis. The patient had a negative skin pathery test and then developed a scar at the venous puncture site at the early stage of disease. Laboratory examination showed that interleukin 8 (IL-8) increased. The patient was treated with an immunosuppressive agent including mycophenolate mofetil, hydroxychloroquine, and colchicine. All symptoms were alleviated after half a year's treatment. There was neither stroke nor recurrence of oral ulcer thereafter. Conclusion: This case demonstrates that neurological involvement might be an early symptom of BD. IL-8 could act as a novel target for the treatment of BD theoretically and probably play a key role in disease recovery.

19.
ACS Appl Mater Interfaces ; 11(49): 46054-46061, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718129

RESUMO

Carbon dots (CDs) that exhibit emission over the whole visible spectrum are desired for use in light-emitting diodes (LEDs). Here, CDs displaying tunable fluorescence over the whole visible region are synthesized. Different concentrations of CDs are uniformly dispersed in epoxy resin and coated on 405 nm LED chips to obtain monochrome blue, cyan, green, yellow, red, and deep red LEDs that yield a color gamut covering 99.4% of the National Television Standards Committee (NTSC) standard. These monochrome LEDs display similar high stability. Furthermore, warm and neutral white LEDs are produced by coating cyan- and red-emitting CD layers on 405 nm LED chips, achieving color-rendering indexes (CRIs) of 96.4 and 96.6, respectively. Two fluorescent conversion layers derived from one material at different concentrations simplify the preparation of high-CRI white LEDs. The uniform weak changes of the cyan and red photoluminescence peaks during operation ensure the high stability of these CD-based white LEDs. This research provides a new avenue to develop low-cost, easy-to-prepare CDs with tunable emission colors as alternative phosphors for LED-based high-performance displays and lighting.

20.
Int J Mol Sci ; 20(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614690

RESUMO

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate existing clinical evidence of PPAR modulators, highlighting their clinical prospects and challenges. Findings from clinical trials revealed that different agonists of the same PPAR subtype could present different safety profiles and clinical outcomes in a disease-dependent manner. Pemafibrate, due to its high selectivity, is likely to replace other PPARα agonists for dyslipidemia and cardiovascular diseases. PPARγ agonist pioglitazone showed tremendous promises in many non-metabolic disorders like chronic kidney disease, depression, inflammation, and autoimmune diseases. The clinical niche of PPARß/δ agonists is less well-explored. Interestingly, dual- or pan-PPAR agonists, namely chiglitazar, saroglitazar, elafibranor, and lanifibranor, are gaining momentum with their optimistic outcomes in many diseases including type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and primary biliary cholangitis. Notably, the preclinical and clinical development for PPAR antagonists remains unacceptably deficient. We anticipate the future design of better PPAR modulators with minimal off-target effects, high selectivity, superior bioavailability, and pharmacokinetics. This will open new possibilities for PPAR ligands in medicine.

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