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1.
Pharmacol Res ; 161: 105233, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031908

RESUMO

Hepatocellular carcinoma (HCC), with its high recurrence and metastasis rates, is a leading cause of cancer-related mortality, and available treatments include surgical resection and liver transplantation. TOGA is a novel conjugate combining 18ß-glycyrrhetinic acid (GA), an active component of licorice, and tetramethylpyrazine, an effective component of Chuanxiong, with a small-molecule amino acid. This study examined the anti-hepatoma effects of TOGA and its specific mechanisms of action. We found that TOGA significantly prevented tumor growth in both nude mice carrying liver cancer xenograftsand mice carrying orthotopic tumors with little toxicity. NanoString analysis screening illustrated that TOGA may exert its anti-tumor effects by targeting interleukin (IL)-1R receptor 1 (IL-1R1). Further, TOGA significantly prevented the invasion and migration of HepG2 cells induced by tumor-associated macrophages (TAMs) or IL-1ß, as confirmed by the reduced expression of the epithelial-mesenchymal transition (EMT)-related proteins Snail and Vimentin. Furthermore, IL-1ß-induced activation of the IL-1R1/IκB/IKK/NF-κB signaling pathway in HepG2 cells was proved to be inhibited by TOGA. Taken together, TOGA effectively prevents the support of TAMs from fueling tumorigenesis through a mechanism related to the NF-κB pathway, and it may be a promising GA-modified drug for the treatment of HCC.

2.
Clin Infect Dis ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048116

RESUMO

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.

3.
J Phys Chem Lett ; : 9110-9116, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049137

RESUMO

State coupling certainly determines the topologic features of the molecular potential energy surface (PES) and potentially diversifies chemical reaction pathways. Here we report the new PESs of BrCN- in the low-lying electronic states that are distinctly different from the previous predictions in the short Br-CN bond region but validated by the high-resolution ion velocity imaging measurements of low-energy dissociative electron attachment (DEA) to BrCN. Besides the vibrating CN- ions produced in the fast Br-CN bond stretching motions, we confirm that the ro-vibrating CN- ions with a nearly isotropic angular distribution are produced by receiving a torque in the combinational motion of Br-CN bond bending and stretching. The latter process is closely related to the potential well of BrCN- at the first excited state A2Π3/2 that arises from the Π-Σ state couplings. Our findings not only suggest that the PESs of other anionic cyanogen halides are in dire need of reexamination but also show that ion velocity imaging of the DEA process is a powerful experimental method for evaluating the theoretical PESs of molecular anions.

4.
Pharmacol Ther ; : 107702, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022300

RESUMO

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life, and health and causes huge economic losses. Increasing evidence has shown that peroxisome proliferator-activated receptors (PPARs) can regulate the progression of cardiac fibrosis. For the first time, this review systematically summarizes the literature on cardiac fibrosis from the perspective of PPARs from 2010 to 2020. Moreover, the role of each PPARs in cardiac fibrosis was clarified in this scientific revision from the perspectives of pharmacologically active substances, known agonists, natural extract compounds, and nucleic-acid-based drugs in different CVD models. Furthermore, the combination of multiple PPARs on the treatment of cardiac fibrosis is discussed. This scientific review provides new ideas for targeting PPARs in the treatment of cardiac fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against cardiac fibrosis based on PPAR activity.

5.
Mutagenesis ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043986

RESUMO

Glutamine (Gln) is a non-essential amino acid central for generating building blocks and cellular energy in tumours and rapidly proliferating non-transformed cells. However, the influence of Gln on regulating chromosomal stability of transformed and non-transformed cells remain poorly understand. We hypothesised that Gln is required for maintaining a homeostatic level of chromosomal stability. To this end, transformed cells HeLa and A375 and non-transformed cells NCM460 and HUVEC cells were intervened with varying concentrations of Gln (10, 1, 0.1 and 0.01 mM), with or without cisplatin (0.1 µg/ml), for 24 h. The cytokinesis-block micronucleus (MN) assay was used to determine chromosomal instability (CIN), the extent of which is reflected by the frequency of MN, nucleoplasmic bridge (NPB) and nuclear bud (NB). We demonstrated an unexpected decrease in the spontaneous rate of MN, but not NPB and NB, after Gln restriction in HeLa and A375 cells. Gln restriction reduced cisplatin-induced MN, but not NPB and NB, in HeLa and A375 cells. We further revealed that Gln restriction suppressed the proliferation of HeLa cells with high CIN induced by nocodazole, partially explaining why Gln restriction decreased the frequency of spontaneous and cisplatin-induced MN in transformed cells. In contrast, Gln restriction increased MN and NB, but not NPB, in NCM460 cells. In HUVEC cells, Gln restriction increased MN, NPB and NB. Meanwhile, Gln restriction sensitised NCM460 cells to cisplatin-induced genotoxicity. A similar but more pronounced pattern was observed in HUVEC cells. Collectively, these results suggest that the in vitro influences of Gln metabolism on CIN depend on cellular contexts: Transformed cells require high Gln to fine tune their CIN in an optimal rate to maximise genomic heterogeneity and fitness, whereas non-transformed cells need high Gln to prevent CIN.

6.
Sci Rep ; 10(1): 16500, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020532

RESUMO

Taiwanofungus camphoratus is a highly valued medicinal mushroom that is endemic to Taiwan, China. In the present study, the mitogenome of T. camphoratus was assembled and compared with other published Polyporales mitogenomes. The T. camphoratus mitogenome was composed of circular DNA molecules, with a total size of 114,922 bp. Genome collinearity analysis revealed large-scale gene rearrangements between the mitogenomes of Polyporales, and T. camphoratus contained a unique gene order. The number and classes of introns were highly variable in 12 Polyporales species we examined, which proved that numerous intron loss or gain events occurred in the evolution of Polyporales. The Ka/Ks values for most core protein coding genes in Polyporales species were less than 1, indicating that these genes were subject to purifying selection. However, the rps3 gene was found under positive or relaxed selection between some Polyporales species. Phylogenetic analysis based on the combined mitochondrial gene set obtained a well-supported topology, and T. camphoratus was identified as a sister species to Laetiporus sulphureus. This study served as the first report on the mitogenome in the Taiwanofungus genus, which will provide a basis for understanding the phylogeny and evolution of this important fungus.

7.
Medicine (Baltimore) ; 99(41): e22107, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031258

RESUMO

BACKGROUND: Insomnia is a common sleep disorder, which seriously affects people's quality of life and work ability. In China, auricular therapy and moxibustion therapy have a long history in treating insomnia. Clinical studies have shown that auricular point and moxibustion can effectively improve insomnia symptoms. At present, auricular point combined with moxibustion in the treatment of insomnia has been widely used in China, but its overall effectiveness and safety are still unclear. There is a lack of systematic evaluation of auricular point combined with moxibustion in the treatment of insomnia. This paper aims to evaluate the efficacy and safety of auricular point combined with moxibustion in the treatment of insomnia. METHODS: Retrieve randomized controlled trials of auricular point combined with moxibustion from PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from their establishment to August 2020. Search Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry for unpublished gray literature. Two researchers independently applied RevMan 5.3 software for data extraction and risk assessment of bias. RESULTS: This study evaluated the efficacy and safety of auricular point combined with moxibustion in the treatment of insomnia from Pittsburgh sleep quality index, Rhone planck sleepiness scale, Traditional Chinese medicine syndrome scores, Hamilton anxiety scale (HAMA), Hamilton Depression, 5-hydroxytryptamine, incidence of adverse reactions, and other aspects. CONCLUSION: This study will provide theoretical support for the clinical application of auricular point combined with moxibustion in the treatment of insomnia. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/8VZRJ.

8.
Medicine (Baltimore) ; 99(41): e22663, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031330

RESUMO

RATIONALE: GNE myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase(GNE) gene and is clinically characterized by progressive weakness and atrophy of the lower-limb muscles with quadriceps sparing. Nearly all GNE mutations that have been reported thus far in various ethnic populations around the world have been missense or nonsense mutations. PATIENT CONCERNS: We describe the case of a 32-year-old woman with GNE myopathy. The patient presented with progressive weakness of the lower-limb muscles that had spread to her legs. Her serum creatine kinase level was higher than the normal range. Mild myogenic changes were detected in the tibialis anterior muscles on electromyography, and moderate fatty infiltration was observed in various lower-limb muscles on magnetic resonance imaging. Histopathological examination of a skeletal muscle biopsy specimen revealed variation in muscle fiber size, rimmed vacuoles, and disorganized intermyofibrillar networks. DNA sequencing testing revealed a compound heterozygous mutation consisting of a known mutation (c.620A > T in exon 3) and a novel (exon 1 deletion) mutation. DIAGNOSES: Taken together, the clinical features, laboratory testing and DNA findings eventually made the diagnosis of GNE myopathy. INTERVENTIONS AND OUTCOMES: Based on the diagnosis of the GNE myopathy, the patient was administered sialic acid 6 g a day for 1 year, and up to now, her symptoms did not progress further. LESSONS: We have reported the case of a GNE myopathy patient with compound heterozygous GNE gene mutations. This case expands the genotypic spectrum of GNE myopathy.

9.
Neurosurg Rev ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009643

RESUMO

Most studies reported that cystic vestibular schwannoma (CVS) surgery has a less favourable prognosis than solid vestibular schwannoma (SVS) surgery. However, some studies report that it is unclear whether surgical outcomes for these conditions exhibit significant differences. The aim of this meta-analysis was to pool the current literature and describe and analyse any differences in the clinical symptoms and surgical outcomes among CVS and SVS. PubMed, Embase, and Cochrane databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines through April 22, 2020. Outcomes were analysed using a meta-analysis of the proportions. The results of the search yielded 17 studies that met the criteria for inclusion and analysis, involving 3074 participants (including 821 patients with CVSs and 2253 patients with SVSs). No significant differences in the extent of tumour resection (gross-total resection versus non-gross-total resection; RR, 0.93; 95% CI, 0.86-1.01; p = 0.096) and most other outcomes were noted between CVS and SVS cohorts. However, facial nerve function (House-Brackmann Grade I or II versus III or more) of CVS patients was worse (RR, 0.86; 95% CI, 0.78-0.93; p < 0.001) compared with SVS patients with more than 1 year of follow-up after surgery. The criteria of cystic acoustic neuroma needs to be further unified, and prospective cohort studies with larger sample sizes should be performed for further verification of these results in the future.

10.
Blood ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025009

RESUMO

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from the Toll-like receptors and interleukin receptors to downstream NF-kB. MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation occurred frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. Here we show that an E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked non-proteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin 1 receptor-associated kinases and elevated NF-kB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P was unable to constitutively activate NF-kB. A20, a negative regulator of NF-kB signaling, mediated K48-linked polyubiquitination of RNF138 for proteasomal degradation. Depletion of A20 further augmented MYD88L265P-mediated NF-kB activation and lymphoma growth. Furthermore, A20 expression was negatively correlated with RNF138 expression and NF-kB activation in lymphomas with MYD88L265P and in those without. Strikingly, RNF138 expression was positively correlated with NF-kB activation in lymphomas with MYD88L265P, but not in those without MYD88L265P. Collectively, our study reveals a novel mutation-specific biochemical reaction that drive B-cell oncogenesis, providing a therapeutic opportunity for targeting oncogenic MYD88L265P, while sparing MYD88WT that is critical to innate immunity.

11.
Inflammation ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025329

RESUMO

Gefitinib (Iressa), is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), used in the targeted treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Skin toxicity is the major adverse effect observed in patients treated with EGFR-targeted TKIs such as gefitinib and erlotinib. To date, a corresponding skin animal model has not been established to address the mechanisms of these effects. Therefore, we analyzed the skin rash phenotype and its pathological features in Brown Norway (BN) rats treated with gefitinib 2.5 mg, 5.0 mg, or 10 mg/100 g/day for 4 weeks. We found that treatment with gefitinib led to weight loss, rash, itching, and hair loss in a dose-dependent manner. We also investigated the skin pathology and found that the animal model showed thickening of the epidermis, loss of moisture, and apoptosis of keratinocytes. Immunohistochemistry, flow cytometry, and analysis of monocytes and leukocytes in the blood revealed increased macrophage infiltration was associated with the cutaneous toxicities induced by gefitinib in the BN rats. Finally, we found that gefitinib-induced cutaneous toxicity is significantly associated with three inflammatory cytokines known to be secreted by activated macrophages, TREM-1, CINC-2, and CINC-3.

12.
J Tradit Chin Med ; 40(5): 812-819, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33000582

RESUMO

OBJECTIVE: To investigate effect of electroacupuncture (EA) with Bushen Jiannao on learning and memory ability in senescence-accelerated mouse prone 8 (SAMP8) mice and the related mechanisms. METHODS: 8-month-old senescence-accelerated-resistant (SAMR1) and SAMP8 mice were treated with EA at Baihui (GV 20), Shenshu (BL 23), and Taixi (KI 3) acupoint once a week for 8 weeks. The Morris water maze, enzyme linked immunosorbent assay, immunohistochemistry, and Western blot were used to assess Alzheimer's disease (AD)-associated cognitive and neuroinflammatory phenotypes. RESULTS: Our data showed that EA treatment decreased activation of microglia and astrocytes, decreased levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-17, and improved spatial memory deficits in SAMP8 mice. EA therapy with Bushen Jiannao exhibited anti-inflammatory properties and improved cognitive function. CONCLUSION: The present study indicates that EA treatment based on the interaction between kidney and brain can improve learning and memory ability by inhibiting activation of astrocytes and microglia and decreasing expression of pro-inflammatory cytokines, TNF-α and IL-17. EA treatment based on the interaction between kidney and brain may be an effective treatment for AD.

13.
Curr Pharm Des ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001005

RESUMO

Depression is a widespread and persistent psychiatric disease. Due to various side effects and no curative treatments of conventional antidepressant drugs, botanical medicines have attracted considerable attention as a complementary and alternative approach. The pathogenesis of depression is quite complicated and unclear. Metabolomics is a promising new technique for the discovery of novel biomarkers for exploring the potential mechanisms of diverse diseases and assessing the therapeutic effects of drugs. In this article, we systematically reviewed the study of botanical medicine for the treatment of depression using metabolomics over a period from 2010 to 2019. Additionally, we summarized the potential biomarkers and metabolic pathways associated with herbal medicine treatment for depression. Through comprehensive evaluation of herbal medicine as novel antidepressants and understanding of their pharmacomechanisms, a new perspective on expanding the application of botanical medicines for the treatment of depression is provided.

14.
Aging (Albany NY) ; 122020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052136

RESUMO

Matrix metalloproteinase-8 (MMP-8) is a gene associated with inflammation and prognosis in colorectal cancer (CRC). Here, we studied the link between the rs11225395 polymorphism of MMP-8 gene and CRC risk. We recruited 551 CRC cases and 623 controls from among a subpopulation of Han Chinese patients. Data found that this variant was connected to an increased risk of CRC (TT versus CC: OR, 1.76; 95%CI, 1.09-2.84; P = 0.021; T versus C: OR, 1.29; 95%CI, 1.07-1.56; P = 0.007). Stratified analyses indicated a positive association among smokers (TT versus CC: OR, 2.31; 95%CI, 1.12-4.79; P = 0.024), males, and patients ≥ 60 years old. Crossover analysis showed that the potential interaction between smoking or drinking and the MMP-8 rs11225395 polymorphism was related to elevated risk for CRC. The rs11225395 polymorphism was also connected with lymph node metastasis and TNM stage. Moreover, the CRC cases carrying a TT genotype of MMP-8 rs11225395 presented had poorer overall survival than the CC genotype carriers. These findings show that MMP-8 rs11225395 correlates with an elevated risk of CRC and poor patient prognosis in a subpopulation of the Han Chinese subpopulation. Thus, the MMP-8 rs11225395 polymorphism could potentially function as a biomarker predictive of CRC susceptibility.

15.
J Cell Mol Med ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32969198

RESUMO

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.

16.
BMC Public Health ; 20(1): 1418, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943035

RESUMO

BACKGROUND: Many studies have shown an association of childhood respiratory diseases with short-term temperature variability such as diurnal temperature range (DTR) and temperature change between two neighboring days (TCN). However, the impact of temperature variability on allergic rhinitis (AR) has not been investigated so far. This study sought to evaluate the short-term effect of temperature variability (i.e., TCN and DTR) on AR, as well as to identify vulnerable subpopulations. METHOD: We collected daily data on emergency room visits and outpatients for AR and weather variables in Hefei, China during 2014-2016. A distributed lag non-linear model that controlled for long-term trend and seasonality, mean temperature, relative humidity, day of week was used to fit the associations of AR with DTR and TCN. Stratified analyses by age, sex and occupation were also performed. RESULTS: During the study period, there were a total of 53,538 cases and the average values of DTR and TCN were 8.4 °C (range: 1.0 °C to 21.2 °C) and 0 °C (range: - 12.2 °C to 5.9 °C), respectively. While we did not observe an adverse effect of DTR on AR, TCN was significantly associated with increased risk of AR. Specifically, a large temperature drop between two adjacent days (3.8 °C, 5th percentile of TCN) has a delayed and short-lasting effect on AR, with the estimated relative risk of 1.02 (95% confidence interval: 1.01 to 1.04) at lag 12. Moreover, boys and children older than 15 years seemed to be more vulnerable to the effect of TCN. CONCLUSIONS: This study provided evidence of an adverse effect of large temperature drops between two adjacent days on childhood AR. Attention paid to boys and older children may help prevent AR attacks.

17.
J Am Chem Soc ; 142(39): 16748-16756, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32869633

RESUMO

During the past few decades, fabrication of functional rotaxane-branched dendrimers has become one of the most attractive yet challenging topics within supramolecular chemistry and materials science. Herein, we present the successful fabrication of a family of new rotaxane-branched dendrimers containing up to 21 platinum atoms and 42 photosensitizer moieties through an efficient and controllable divergent approach. Notably, the photosensitization efficiencies of these rotaxane-branched dendrimers gradually increased with the increase of dendrimer generation. For example, third-generation rotaxane-branched dendrimer PG3 revealed 13.3-fold higher 1O2 generation efficiency than its corresponding monomer AN. The enhanced 1O2 generation efficiency was attributed to the enhancement of intersystem crossing (ISC) through the simple and efficient incorporation of multiple heavy atoms and photosensitizer moieties on the axles and wheels of the rotaxane units, respectively, which has been validated by UV-visible and fluorescence techniques, time-dependent density functional theory calculations, photolysis model reactions, and apparent activation energy calculations. Therefore, we develop a new promising platform of rotaxane-branched dendrimers for the preparation of effective photosensitizers.

18.
J Food Sci ; 85(10): 3273-3281, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32918279

RESUMO

Huangjiu is a traditional wine in China with special taste and flavor. However, changes of aroma compounds during storage of Huangjiu remain unclear. In this study, aroma compounds in Jinse Nianhua Huangjiu of three different storage ages were qualitatively and quantitatively analyzed via headspace solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS). Based on odor activity value (OAV), the most important aroma compounds were found to be esters, aldehydes, alcohols, acids, ketones, phenols, and lactones. Even though the types of the aroma compounds were similar in different-aged Huangjiu, the concentrations of some compounds varied. Some aroma compounds' thresholds and OAV in Huangjiu were obtained by AC'Scent Intl. Olfactometer. It showed the key aroma compounds in Huangjiu had a positive correlation with their OAV instead of concentration. Quantitative structure-activity relationship (QSAR) models were developed to predict the flavor thresholds for alcohols, acids, and esters in Huangjiu, with higher accuracy for alcohols (R2 = 0.978) and acids (R2 = 0.987). This study will provide valuable information to unveil the regulation of Huangjiu flavor from molecular basis. PRACTICAL APPLICATION: The built mathematical model enables to predict changes of aroma compounds in Huangjiu during storage, based on the relationship between the quantum structure parameters of those aroma compounds and the odor activity value of flavor chemicals. This research will contribute to simplifying the wine flavor analysis for wine industry and also help to identify the age of the Huangjiu for customers.

19.
Nat Commun ; 11(1): 4765, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958780

RESUMO

Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.


Assuntos
Antígenos CD36/metabolismo , Endocitose/fisiologia , Ácidos Graxos/metabolismo , Lipoilação , Células 3T3-L1 , Aciltransferases/metabolismo , Adipócitos/metabolismo , Animais , Antígenos CD36/deficiência , Antígenos CD36/genética , Cavéolas/metabolismo , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Humanos , Gotículas Lipídicas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Obesidade/tratamento farmacológico , Fosforilação , Transdução de Sinais , Quinase Syk/antagonistas & inibidores , Quinase Syk/metabolismo , Ganho de Peso/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
20.
Clin J Am Soc Nephrol ; 15(10): 1394-1402, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32963018

RESUMO

BACKGROUND AND OBJECTIVES: Since December 2019, coronavirus disease 2019 (COVID-19) outbreak occurred and has rapidly spread worldwide. However, little information is available about the AKI in COVID-19. We aimed to evaluate the incidence, risk factors, and prognosis of AKI in adult patients with COVID-19. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort study of 1392 patients with COVID-19 admitted to a tertiary teaching hospital. Clinical characteristics and laboratory data were extracted from electronic hospitalization and laboratory databases. AKI was defined and staged according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Risk factors for AKI and the association of AKI with in-hospital mortality were assessed. RESULTS: A total of 7% (99 of 1392) of patients developed AKI during hospitalization, 40% (40 of 99) of which occurred within 1 week of admission. Factors associated with a higher risk of AKI include severe disease (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.37 to 3.67), higher baseline serum creatinine (OR, 2.19; 95% CI, 1.17 to 4.11), lymphopenia (OR, 1.99; 95% CI, 1.12 to 3.53), and elevated D-dimer level (OR, 2.68; 95% CI, 1.07 to 6.70). The in-hospital mortality in patients with AKI stage 1, stage 2, and stage 3 was 62%, 77%, and 80%, respectively. AKI was associated with in-hospital mortality even after adjustment for confounders (OR, 5.12; 95% CI, 2.70 to 9.72). CONCLUSIONS: AKI is uncommon but carries high in-hospital mortality in patients with COVID-19.

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