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1.
Food Chem ; 325: 126919, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32387992

RESUMO

HPLC-ESI-MS/MS, molecular docking simulation and in situ single-pass intestinal perfusion (SPIP) study were used to identify, select, and confirm the binding affinities between peptides identified from desalted duck egg white peptides (DPs) and calcium sensing receptor (CaSR), respectively. F3 fraction from DPs possessed superior calcium binding activity (P < 0.05), and 16 peptides enriched aromatic amino acids and other 33 peptides were identified. FAE, FNE, INSW, FDPE and NFE presented well binding affinities with CaSR in molecular docking. Additionally, SPIP results showed that NFE and INSW significantly reduced the increased PTH levels by 45.8% and 48.8%, respectively (P < 0.05), and increased calcium percent absorption, calcium absorption rate constant (Ka) and calcium effective permeability (Peff) (P < 0.05), as well as up-regulated mRNA levels of CaSR (P < 0.05). Moreover, NFE and INSW could interact with the VFT domain of CaSR, which exhibited the potential activities in regulation of CaSR.

2.
Neurochem Res ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388695

RESUMO

Glioma is the most common primary brain tumor and the most malignant type of glioma is glioblastoma with the character of high mortality, high recurrence rate and poor prognosis. MicroRNAs act as an important component in glioma development and thus may be a potential target for the treatment of glioma. There were some researches indicated that miR-210-3p played a role in glioma development, but if it can inhibit glioma growth, as well as the underlying mechanism, is still uncertain. In the present study, we investigated the effects of miR-210-3p and its potential target gene Iscu on glioma (C6) cells proliferation and migration in vitro as well as the influence of miR-210-3p on glioma growth in vivo. The results showed that miR-210-3p inhibited the proliferation and migration of C6 cells by regulating the expression of its target gene Iscu in vitro. We also demonstrated that glioma growth was suppressed in immunodeficient mice when they were implanted with C6 cells overexpressing miR-210-3p. Our data indicated that miR-210-3p played an important role in the prevention of glioma growth by targeting Iscu and so miR-210-3p/Iscu axis might be a potential target for the treatment of glioma.

3.
Pharmacol Res ; : 104864, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32416217

RESUMO

Acute myeloid leukemia (AML) is a malignant disease originating from hematopoietic stem cells (HSC). Chemotherapy and/or HSC transplantation is unsatisfactory due to serious side effects, multidrug resistance, and high relapse rate. Thus, alternative strategies are urgently needed to develop more effective therapies. Liriope muscari baily saponins C (DT-13) is a novel compound isolated from Liriope muscari (Decne.) Baily, and exhibited a potent cytotoxicity against several solid tumors. However, the anti-AML activity of DT-13 and the potential mechanisms are still unknown. This study is the first to demonstrate that DT-13 had preferential cytotoxicity against AML cells, and remarkably inhibited proliferation and colony forming ability. Moreover, DT-13 induced the death receptor pathway-dependent apoptosis of HL-60 and Kasumi-1 cells by up-regulating Fas, FasL, DR5 and TRAIL as well as promoted the cleavage of caspase 8, caspase 3 and PARP. Meanwhile, DT-13 induced the differentiation with morphological change related to myeloid differentiation, elevated NBT and α-NAE positive cell rates, differentiation markers CD11b and CD14 as well as level of transcription factors C/EBPα and C/EBPß. RNA-sequencing analysis revealed that KLF2 may be one of the potential targets regulated by DT-13. Further studies indicated that KLF2 played a critical role in DT-13-induced apoptosis and differentiation. Moreover, activation of AMPK-FOXO was proved to be the upstream of KLF2 pathway that contributed to the induction of apoptosis and differentiation by DT-13. Additionally, restoration of KLF2 by DT-13 was highly correlated with the AMPK-related histone acetylation mechanisms. Finally, DT-13 exhibited an obvious anti-AML effect in NOD/SCID mice with the engraftment of HL-60 cells. Our study suggests that DT-13 may serve as a novel agent for AML by AMPL-KLF2-mediated apoptosis and differentiation.

4.
Cell Death Dis ; 11(5): 331, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382038

RESUMO

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

5.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120314350, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32349534

RESUMO

OBJECTIVE: Recent studies suggest that the P2Y12 receptor of vascular smooth muscle cells in atherosclerotic plaques aggravates atherosclerosis, and P2Y12 receptor inhibitors such as CDL (clopidogrel) may effectively treat atherosclerosis. It is imperative to identify an effective biomarker for reflecting the P2Y12 receptor expression on vascular smooth muscle cells in plaques. Approach and Results: We found that there was a positive correlation between the level of circulating sLRP1 (soluble low-density lipoprotein receptor-related protein 1) and the number of LRP1+ α-SMA+ (α-smooth muscle actin), P2Y12+, or P2Y12+ LRP1+ cells in plaques from apoE-/- mice fed a high-fat diet. Furthermore, activation of the P2Y12 receptor increased the expression and shedding of LRP1 in vascular smooth muscle cells by inhibiting cAMP/PKA/SREBP-2. Conversely, genetic knockdown or pharmacological inhibition of the P2Y12 receptor had the opposite effects. Additionally, CDL decreased the number of lesional LRP1+ α-SMA+ cells and the levels of circulating sLRP1 by activating cAMP/PKA/SREBP-2 in apoE-/- mice fed a high-fat diet. CONCLUSIONS: Our study suggests that sLRP1 may be a biomarker that reflects the P2Y12 receptor level in plaques and has the potential to be an indicator for administering P2Y12 receptor inhibitors for patients with atherosclerosis.

6.
J Mater Chem B ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323684

RESUMO

Near-infrared (NIR) light-responsive nanoparticles of organic small-molecule dyes hold great promise as phototherapeutic dyes (PDs) for clinical translation due to their intrinsic merits, including well-defined structure, high purity, and good reproducibility. However, they have been explored with limited success in the development of photostable NIR PDs with extraordinary photoconversion for highly effective phototherapy. Herein, we have described amphiphilic BODIPY dye aggregates within the polymeric micelles (Micelles) as potent bifunctional PDs for dually cooperative phototherapy under NIR irradiation. Micelles possessed an intensive NIR absorption, high photostability, and favorable non-radiative transition, thereby exhibiting both remarkable singlet oxygen generation and photothermal effect under NIR light irradiation. Besides, Micelles had preferable cellular uptake, effective cytoplasmic drug translocation as well as enhanced tumor accumulation. Owing to the combined virtues, Micelles showed clinical potential as bifunctional PDs for photo-induced cancer therapy. This work thus provides a facile strategy to exploit advanced PDs for practical phototherapeutic applications.

7.
Mol Carcinog ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32319143

RESUMO

Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.

8.
Invest Ophthalmol Vis Sci ; 61(3): 54, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32232349

RESUMO

Purpose: To investigate the effects and mechanisms of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate on the formation of ocular surface squamous metaplasia induced by topical benzalkonium chloride (BAC) in a mouse model. Methods: Ocular surface squamous metaplasia was induced in 16 days by topical BAC application in mice. During the period of induction, mice were divided into four groups: no additional treatment (BAC+UT), topical vehicle (BAC+Vehicle), topical fenofibrate (BAC+Feno), or topical fenofibrate plus intraperitoneal injection of MK886 (BAC+Feno+MK886). The parameters of tear film were evaluated on day 16, and eye specimens were collected. Histologic investigation; PAS assays; immunostaining for cytokeratin 10 (K10), Ki67, and F4/80; and PCR assays for TNF-α and IL-6 were performed. Cell Counting Kit 8 (CCK-8) assays were performed to evaluate the inhibitory effects of fenofibrate on RAW264.7 cells. Results: Fenofibrate suppressed the formation of BAC-induced instable tear film. In the BAC+Feno group, the expression of K10 and Ki67 was lower than in the other three groups. The number of goblet cells was reduced in eyes of the BAC+UT and BAC+Vehicle groups but was maintained in eyes of the BAC+Feno group. The number of F4/80-positive cells and the levels of TNF-α and IL-6 mRNA were significantly reduced in the cornea of the BAC+Feno group. These effects of fenofibrate could be attenuated by MK886. The cell viability of RAW264.7 cells could be significantly inhibited by fenofibrate in a dose-dependent pattern. Conclusions: Topical application of fenofibrate suppressed the formation of ocular surface squamous metaplasia, which might be mediated through the PPAR-α signaling pathway.

9.
Xenobiotica ; : 1-8, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32238050

RESUMO

Osthol, a pharmacologically active ingredient in various traditional Chinese medicines, is predominantly metabolized by CYP2C9. It may be co-administered with other drugs which are metabolized by CYP2C9 in clinical medicine. However, CYP2C9*1/*2/*3 genotype on the pharmacokinetics of osthole and its metabolic diversity between rat and human are unclear.In this study, we investigated the effects of osthole on enzyme activity of CYP2C11/CYP2C9 in rat liver microsomes (RLMs) and human liver microsomes (HLMs), to distinguish metabolic manner of osthole in different species. Interestingly, we found that osthole inhibits the activity of CYP2C11 in a non-competitive manner in RLMs, while inhibits CYP2C9 activity in a competitive manner in pooled HLMs. Then, the effects of CYP2C9*1/*2/*3 allele on the pharmacokinetics of osthole were identified. In human CYP2C9 isoform, the Ki value of 21.93 µM (CYP2C9*1), 18.10 µM (CYP2C9*2), 13.12 µM (CYP2C9*3) indicate that there are individual differences in the inhibition of osthole on CYP2C9 activity.We investigated how the indomethacin pharmacokinetics was affected by osthole in SD rat. To estimate the area under the curve (AUC), maximum plasma concentration (Cmax) and apparent clearance (CL/F), indomethacin (10 mg/kg) was given orally combined with osthole (20 mg/kg) in adult SD rat. We found the value of PK on indomethacin, such as the AUC0-∞, was from 176.40 ± 17.29 to 173.74 ± 27.69 µg/ml h-1, Cmax from 9.02 ± 1.24 to 9.89 ± 0.82 µg/ml and CL/F from 0.11 ± 0.01 to 0.12 ± 0.04 mg/kg/h which were unsignificantly changed compared with the control groups. However, the Tmax was prolonged from 2.00 ± 0.00 h to 7.33 ± 1.15 h, and T1/2 increased from 8.38 ± 2.30 h to 11.37 ± 2.11 h. These results indicate that osthole could potentially affect the metabolism of indomethacin in vivo.

10.
Plant Biol (Stuttg) ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32270571

RESUMO

Flowers, the reproductive organs of angiosperms, show a high degree of diversity in morphological structure and flowering habits to ensure pollination and fertilization of plants. Effect of flower movement on pollination and fertilization was investigated in Ipomoea purpurea (Convolvulaceae) in this study. Fluorescence microscope was used to observe the germination of pollen grains at different temperatures. From 4:00 am to 6:00 am, the stigma was taller than the filaments so that self-pollination had no chance to be completed and cross-pollination was carried out by insects. Pollen grains germinated rapidly after falling on the stigma, the pollen tube reached the ovule to complete the fertilization after 2-3 h. From 7:00 am to 9:00 am, filaments of two stamens grew rapidly and reached the same height as the stigma to allow self-crossing. But at this time, the natural temperature was already high and not conducive to the germination of pollen grains. The corolla formed a closed inverted bell-shaped corolla, where the inner microenvironment ensured the completion of pollen germination and fertilization. Preferential cross-pollination and delayed self-crossing of I. purpurea provided a doubly guaranteed mechanism for pollination and fertilization, allowing its adaptation to high temperature climate.

11.
Molecules ; 25(8)2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32325911

RESUMO

Plutonium mononitride is one of the main fuels for Generation IV reactors and can be prepared from nitrogenation of plutonium hydride. We investigated the adsorption and dissociation of nitrogen on PuH2 (111) surface to elaborate the initial stage of nitrogenation. The adsorption energies varied greatly with respect to the adsorption sites and orientations of the adsorbed molecule. The nitrogen exhibited preferential adsorption above the ccp site, where the molecular nitrogen was nearly parallel to the PuH2 surface and pointed to the nearest Pu atom. The orbital hybridization and the electrostatic attraction between the Pu and N weakened the N-N bond in the adsorbed molecule. The mechanism of the dissociation process was investigated within transition state theory, and the analysis of the activation barrier indicated that dissociation of nitrogen is not the rate-determining step of nitrogenation. These findings can contribute to a better understanding of the nuclear fuel cycle.

12.
Food Res Int ; 131: 108974, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32247485

RESUMO

Two novel calcium delivery systems with high calcium-binding ability were prepared with desalted duck egg white peptides (DPs) and chitosan oligosaccharide (COS) by Amadori-type linkage and transglutaminase (TGase) induced reaction. Fourier transform infrared spectroscopy (FTIR), Zeta potential and particle size analyses were used to characterize the copolymers. These two copolymers reversed the inhibition of phytic acid (PA) in calcium transport in Caco-2 cell monolayers. PA-induced calcium deficiency mice model indicated that copolymers could reverse the side effect of PA, promote calcium bioavailability, and improve gut health. Overall, these results confirmed the potentialities of DPs-COS copolymers as nutraceuticals/functional food for oral calcium delivery to promote calcium absorption and improve gut health.

13.
Food Funct ; 11(4): 3563-3573, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32270801

RESUMO

Selenium-biofortified crops are a quality functional food resource because of their anti-tumor and anti-cancer properties. In the present study, the conjugates of selenium-biofortified soybean protein and polyphenols were prepared and evaluated by alkali-induced synthesis and in vitro antioxidant tests. Moreover, the antioxidant mechanisms of protecting mice skin damaged by UV-B were studied. The results showed that the antioxidant activity of the conjugate between 7S globulin from selenium-enriched soybean (Se-7S) and EGCG (Se-7S-EGCG) was significantly higher (P < 0.05) than that of Se-7S-GA. Structural characterizations implied that the polymerization of polyphenols with amino acid residues occurred. Se-7S-EGCG inhibited the apoptosis of epidermal cells induced by UV-B. The overexpression of phosphorylated proteins in the MAPK signaling pathway, the activation of related inflammatory factors, and the boost in the MMPs were reversed by Se-7S-EGCG. Overall, this research provides a theoretical and experimental basis for the application of protein and polyphenol conjugates in food and medicine fields.

14.
Crit Care ; 24(1): 73, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131872

RESUMO

INTRODUCTION: Patient safety and critical care quality remain a challenging issue in the ICU. However, the effects of the national quality improvement (QI) program remain unknown in China. METHODS: A national ICU QI program was implemented in a controlled cohort of 586 hospitals from 2016 to 2018. The effects of the QI program on critical care quality were comprehensively investigated. MAIN RESULTS: A total of 81,461,554 patients were enrolled in 586 hospitals, and 1,587,724 patients were admitted to the ICU over 3 years. In 2018, there was a significantly higher number of ICU beds (2016 vs. 2018: 10668 vs. 13,661, P = 0.0132) but a lower doctor-to-bed ratio (2016 vs. 2018: 0.64 (0.50, 0.83) vs. 0.60 (0.45, 0.75), P = 0.0016) and nurse-to-bed ratio (2016 vs. 2018: 2.00 (1.64, 2.50) vs. 2.00 (1.50, 2.40), P = 0.031) than in 2016. Continuous and significant improvements in the ventilator-associated pneumonia (VAP) incidence rate, microbiology detection rate before antibiotic use and deep vein thrombosis (DVT) prophylaxis rate were associated with the implementation of the QI program (VAP incidence rate (per 1000 ventilator-days), 2016 vs. 2017 vs. 2018: 11.06 (4.23, 22.70) vs. 10.20 (4.25, 23.94) vs. 8.05 (3.13, 17.37), P = 0.0002; microbiology detection rate before antibiotic use (%), 2016 vs. 2017 vs. 2018: 83.91 (49.75, 97.87) vs. 84.14 (60.46, 97.24) vs. 90.00 (69.62, 100), P < 0.0001; DVT prophylaxis rate, 2016 vs. 2017 vs. 2018: 74.19 (33.47, 96.16) vs. 71.70 (38.05, 96.28) vs. 83.27 (47.36, 97.77), P = 0.0093). Moreover, the 6-h SSC bundle compliance rates in 2018 were significantly higher than those in 2016 (6-h SSC bundle compliance rate, 2016 vs. 2018: 64.93 (33.55, 93.06) vs. 76.19 (46.88, 96.67)). A significant change trend was not found in the ICU mortality rate from 2016 to 2018 (ICU mortality rate (%), 2016 vs. 2017 vs. 2018: 8.49 (4.42, 14.82) vs. 8.95 (4.89, 15.70) vs. 9.05 (5.12, 15.80), P = 0.1075). CONCLUSIONS: The relationship between medical human resources and ICU overexpansion was mismatched during the past 3 years. The implementation of a national QI program improved ICU performance but did not reduce ICU mortality.

15.
Autophagy ; : 1-21, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32160082

RESUMO

Vascular smooth muscle cells (VSMCs) are an important source of foam cells in atherosclerosis. The mechanism for VSMC-derived foam cell formation is, however, poorly understood. Here, we demonstrate that the P2RY12/P2Y12 receptor is important in regulating macroautophagy/autophagy and VSMC-derived foam cell formation in advanced atherosclerosis. Inhibition of the P2RY12 receptor ameliorated lipid accumulation and VSMC-derived foam cell formation in high-fat diet-fed apoe-/- mice (atherosclerosis model) independent of LDL-c levels. Activation of the P2RY12 receptor blocked cholesterol efflux via PI3K-AKT, while genetic knockdown or pharmacological inhibition of the P2RY12 receptor inhibited this effect in VSMCs. Phosphoproteomic analysis showed that the P2RY12 receptor regulated the autophagy pathway in VSMCs. Additionally, activation of the P2RY12 receptor inhibited MAP1LC3/LC3 maturation, SQSTM1 degradation, and autophagosome formation in VSMCs. Genetic knockdown of the essential autophagy gene Atg5 significantly attenuated P2RY12 receptor inhibitor-induced cholesterol efflux in VSMCs. Furthermore, activation of the P2RY12 receptor led to the activation of MTOR through PI3K-AKT in VSMCs, whereas blocking MTOR activity (rapamycin) or reducing MTOR expression reversed the inhibition of cholesterol efflux mediated by the P2RY12 receptor in VSMCs. In vivo, inhibition of the P2RY12 receptor promoted autophagy of VSMCs through PI3K-AKT-MTOR in advanced atherosclerosis in apoe-/- mice, which could be impeded by an autophagy inhibitor (chloroquine). Therefore, we conclude that activation of the P2RY12 receptor decreases cholesterol efflux and promotes VSMC-derived foam cell formation by blocking autophagy in advanced atherosclerosis. Our study thus suggests that the P2RY12 receptor is a therapeutic target for treating atherosclerosis.Abbreviations: 2-MeSAMP: 2-methylthioadenosine 5'-monophosphate; 8-CPT-cAMP: 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic-monophosphate; ABCA1: ATP binding cassette subfamily A member 1; ABCG1: ATP binding cassette subfamily G member 1; ACTB: actin beta; ADPßs: adenosine 5'-(alpha, beta-methylene) diphosphate; ALs: autolysosomes; AMPK: AMP-activated protein kinase; APOA1: apolipoprotein A1; APs: autophagosomes; ATG5: autophagy related 5; ATV: atorvastatin; AVs: autophagic vacuoles; CD: chow diet; CDL: clopidogrel; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; dbcAMP: dibutyryl-cAMP; DIL-oxLDL: dioctadecyl-3,3,3,3-tetramethylin docarbocyanine-oxLDL; EIF4EBP1/4E-BP1: eukaryotic translation initiation factor 4E binding protein 1; EVG: elastic van gieson; HE: hematoxylin-eosin; HDL: high-density lipoprotein; HFD: high-fat diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDL-c: low-density lipoprotein cholesterol; LDs: lipid droplets; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; Masson: masson trichrome; MCPT: maximal carotid plaque thickness; MK2206: MK-2206 2HCL; NBD-cholesterol: 22-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-23,24-bisnor-5-cholen-3ß-ol; OLR1/LOX-1: oxidized low density lipoprotein receptor 1; ORO: oil Red O; ox-LDL: oxidized low-density lipoprotein; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TIC: ticagrelor; ULK1: unc-51 like autophagy activating kinase 1; VSMCs: vascular smooth muscle cells.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32205038

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. METHODS: A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. RESULTS: A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. CONCLUSIONS: Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.

17.
PLoS One ; 15(3): e0229471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126092

RESUMO

With the development of e-commerce, online shopping has become one of the most important consumer channels. However, the lack of government supervision, insufficient review of e-commerce platforms, illegal sales of online sellers and invalid consumer complaints have led to frequent green product quality problems during online shopping. Therefore, this paper considers that the online seller may be driven by interests, colluding with the e-commerce platform and selling low quality green product. At the same time, we introduce consumer feedback, and take the government supervision department, the online seller and the e-commerce platform as actors of the evolutionary game. In this paper, the evolutionary strategy choices of each actor were analyzed, and the influence of different factors on the evolutionary stability results was explored. Research indicates: firstly, consumer complaints play an indirect regulatory role for the online seller; secondly, the enhancement of the loss-sharing relationship between the online seller and the e-commerce platform can promote the legal operation of the two and prevent collusion; thirdly, the impact of consumer complaints on the choice of the e-commerce platform depends on the government supervision department's penalty for the e-commerce platform; finally, the e-commerce platform establishes a reasonable reward system, which can make up for the defects of the online seller using advanced technology to avoid punishment. Our paper uses Matlab 2017 for simulation analysis and provides effective advices on how to urge the government supervision department to effectively supervise, promote the e-commerce platform to enhance review, urge the online seller to legal sale, and encourage consumers to legally defend their rights.

18.
Zhen Ci Yan Jiu ; 45(2): 164-8, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144929

RESUMO

Non-invasive transcutaneous auricular vagus nerve stimulation (ta-VNS) is established on the basis of auricular acupuncture and the principle of vagus nerve stimulation (VNS). The results of the comparative study of 4 indications of VNS show that ta-VNS achieves almost the equivalent effect as VNS. Moreover, the ta-VNS is advantageous at safety, economy and portability. Regarding the clinical prevention and treatment of polycystic ovary syndrome (PCOS), it is still controversial for the effect of acupuncture and moxibustion therapy including auricular acupuncture. Moreover, it is the difficulty for the principle of acupoint selection and the treatment mechanism of this therapy to be in line with modern medicine. As neuroendocrine disease, PCOS and the ovary, its target organ are all associated with the vagus nerve. It is a new idea to introduce the ta-VNS in treatment of PCOS by regulating the reproductive and endocrinal disturbance of PCOS in terms of vagus nerve and improving the acupuncture and moxibustion therapy, such as the auricular acupuncture. In the paper, the potential mechanism of the ta-VNS in treatment of PCOS is presented: 1)the ta-VNS treats PCOS by improving insulin resistance; 2)the ta-VNS relieves PCOS-induced psychological disorders through the treatment of depression; 3)the ta-VNS is applicable in treatment of PCOS complications, such as hypertension and diabetes.


Assuntos
Síndrome do Ovário Policístico , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Pontos de Acupuntura , Feminino , Humanos , Nervo Vago
19.
Schizophr Bull ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32144421

RESUMO

Our understanding of cerebellar involvement in brain disorders has evolved from motor processing to high-level cognitive and affective processing. Recent neuroscience progress has highlighted hierarchy as a fundamental principle for the brain organization. Despite substantial research on cerebellar dysfunction in schizophrenia, there is a need to establish a neurobiological framework to better understand the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellum in schizophrenia. To help to establish such a framework, we investigated the abnormalities in the distribution of sensorimotor-supramodal hierarchical processing topography in the cerebellum and cerebellar-cerebral circuits in schizophrenia using a novel gradient-based resting-state functional connectivity (FC) analysis (96 patients with schizophrenia vs 120 healthy controls). We found schizophrenia patients showed a compression of the principal motor-to-supramodal gradient. Specifically, there were increased gradient values in sensorimotor regions and decreased gradient values in supramodal regions, resulting in a shorter distance (compression) between the sensorimotor and supramodal poles of this gradient. This pattern was observed in intra-cerebellar, cerebellar-cerebral, and cerebral-cerebellar FC. Further investigation revealed hyper-connectivity between sensorimotor and cognition areas within cerebellum, between cerebellar sensorimotor and cerebral cognition areas, and between cerebellar cognition and cerebral sensorimotor areas, possibly contributing to the observed compressed pattern. These findings present a novel mechanism that may underlie the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellar and cerebro-cerebellar circuits in schizophrenia. Within this framework of abnormal motor-to-supramodal organization, a cascade of impairments stemming from disrupted low-level sensorimotor system may in part account for high-level cognitive cerebellar dysfunction in schizophrenia.

20.
Life Sci ; 252: 117571, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201278

RESUMO

AIMS: Nanoparticles (NPs) exposure is associated with increased risk of cardiovascular diseases, but the underlying mechanism is still obscure. In this study, we investigated the role of NADPH oxidase 4 (NOX4) in copper oxide nanoparticles (CuONPs)-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Morphology changes were examined under the microscope. Cell viability was determined by MTS assay and Calcein AM assay. Apoptosis and the levels of superoxide anion (O2-) and hydrogen peroxide (H2O2) were measured by fluorescence activated cell sorting (FACS). Oxidative stress was detected by assaying the levels of glutathione/glutathione disulfide (GSH/GSSG) and malondialdehyde (MDA). Protein expression levels were determined by western blotting. KEY FINDINGS: We revealed that O2- rather than H2O2 was the major component of reactive oxygen species (ROS) in CuONPs-treated HUVECs. Meanwhile, CuONPs downregulated expression of O2--eliminating enzyme NOX4 both at mRNA and protein levels, but did not affect the expression of SOD2 and catalase. NOX4 knockdown caused more accumulation of O2-, and a further decrease of H2O2 in CuONPs-treated HUVECs, suggesting that NOX4 regulates the conversion of O2- to H2O2 in CuONPs-treated HUVECs. Furthermore, we revealed that NOX4 knockdown aggravated CuONPs-induced oxidative stress, characterized by a decrease of GSH/GSSG ratio, an increase of MDA level, and upregulation of HSPA5 and γH2AX. Finally, we showed that NOX4 knockdown exacerbated CuONPs-induced apoptotic cell death in HUVECs, indicating that NOX4 could protect ECs from CuONPs-induced cell death. SIGNIFICANCE: Our study provides the evidence that NOX4 protects vascular endothelial cells from CuONPs-induced oxidative stress and cell death.

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