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1.
Bioact Mater ; 31: 136-150, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37637078

RESUMO

Atypical teratoid/rhabdoid tumor (ATRT) is a rare childhood malignancy that originates in the central nervous system. Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1. ATRT has no standard treatment, and a major limiting factor in therapeutic development is the lack of reliable ATRT models. We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells (Epi-iPSCs), followed by brief neural induction, to generate an ATRT-like model. The dual knockout Epi-iPSCs retained their stemness with the capacity to differentiate into three germ layers. High expression of OCT4 and NANOG in neurally induced knockout spheroids was comparable to that in two ATRT cell lines. Beta-catenin protein expression was higher in SMARCB1-deficient cells and spheroids than in normal Epi-iPSC-derived spheroids. Nucleophosmin, Osteopontin, and Ki-67 proteins were also expressed by the SMARCB1-deficient spheroids. In summary, the tumor model resembled embryonal features of ATRT and expressed ATRT biomarkers at mRNA and protein levels. Ribociclib, PTC-209, and the combination of clofilium tosylate and pazopanib decreased the viability of the ATRT-like cells. This disease modeling scheme may enable the establishment of individualized tumor models with patient-specific mutations and facilitate high-throughput drug testing.

2.
J Ethnopharmacol ; 318(Pt A): 116885, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37422099

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Metastasis is the leading cause of death in lung cancer worldwide, and immune escape plays a vital role in the process of metastasis. Clinical studies have proven that Jinfukang (JFK) can effectively treat lung cancer metastasis by regulating T lymphocytes. However, it is still unknown whether JFK plays a role in treating lung cancer metastasis by regulating T-cell receptors (TCRs). AIM OF THE STUDY: To explore the effect of JFK in inhibiting lung cancer metastasis by regulating TCR. MATERIALS AND METHODS: A lung metastasis model was established in C57BL/6J and BALB/c-nude mice by tail vein injection of Lewis lung cancer cells. JFK was given by continuous intragastric administration. Anatomical observation combined with hematoxylin-eosin staining was used to evaluate lung metastasis. T cells, MDSCs, and macrophages in the peripheral blood were detected by flow cytometry, and the proliferation and immune cell infiltration of lung metastases were observed by immunohistochemistry and immunofluorescence. The diversity and gene expression of TCR in peripheral blood and lung tissues were detected by immune repertoire sequencing, and bioinformatics analysis was carried out. RESULTS: Compared with the control group, the number of pulmonary metastatic nodules in JFK-treated mice showed a decreasing trend, and it significantly reduced the burden of lung tumor metastasis in mice. We found that the expression level of Ki-67 protein in lung metastatic tumor tissues of mice treated with JFK was significantly reduced, while the infiltration level of CD8+ T lymphocytes and NK cells was significantly increased. In addition, we also found that JFK could significantly increase the proportion of CD4+ T, CD8+ T and NKT cells in the peripheral blood of mice. Moreover, JFK reduced the ratio of M-MDSCs and increased the ratio of PMN-MDSCs in the peripheral blood of mice. JFK increased the ratio of M1 macrophages in the peripheral blood of Lewis tumor-bearing mice. The sequencing of TCR in the peripheral blood and lung tissue of mice indicated that there was no notable difference in TCR diversity as the tumor progressed and JFK treatment was administered. However, the downregulation of TRBV16, TRBV17, TRBV1 and the upregulation of the TRBV12-2 gene in the TCR caused by tumor progression can be reversed by JFK. CONCLUSION: These results suggest that JFK may upregulate the proportion of CD4+ T, CD8+ T and NKT cells in peripheral blood, reverse the TCR changes caused by tumor metastasis, and promote the infiltration of CD8+ T and NK cells in tumor tissues, thereby inhibiting the growth of tumors and ultimately reducing the burden of lung cancer metastasis. This will provide new strategies for developing Chinese herbal medicine to treat metastasis by regulating TCR.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Animais , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos Nus , Camundongos Endogâmicos C57BL , Neoplasias Pulmonares/patologia , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfócitos T CD8-Positivos
3.
J Ethnopharmacol ; 318(Pt A): 116888, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37437793

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is one of non-specific inflammatory bowel disease that mainly affects the colon. Recently, UC has become a significant social and economic problem worldwide. Baitouweng decoction (BD), a traditional Chinese medicine described in the "Treatise on Febrile Diseases", has been used for centuries to treat intestinal diseases. However, its underlying mechanism remains largely unexplored. AIM OF STUDY: In this study, we aimed to investigate the effect of BD on autophagy for repairing the colonic barrier in DSS-induced colitis mice and explored its role in regulating the autophagic signaling pathway AMPK/mTOR. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 7 days. The effectiveness of BD in treating DSS-induced colitis was evaluated through body weight, disease activity index (DAI), colon length, pathological changes, organ index, and proportion of blood cells. Moreover, intestinal epithelial permeability was analyzed by examining FITC-dextran leakage, the bacterial load of mesenteric lymph nodes (MLNs), and bacterial infiltration of colon tissues. Barrier function was evaluated by assessing the number and proportion of colonic goblet cells and the expression of tight junction proteins, including ZO-1, claudin-1, and occludin. Furthermore, the levels of autophagy were assessed by examining the number of autophagosomes and the expression of the autophagy-related proteins LC3, Beclin1, and P62. Additionally, network pharmacology research was conducted to analyze the potential mechanisms underlying the medicinal effects, as indicated by the role of AMPK/mTOR in regulating the autophagic signaling pathway. RESULTS: BD improved colitis symptoms in mice by restoring body weight and colon length and reducing inflammatory cell infiltration. Additionally, BD decreased the diffusion of FITC-dextran and bacterial translocation in MLNs, as well as bacterial infiltration of the colonic mucosa. The number and proportion of colonic goblet cells, the expression of ZO-1, Claudin-1, and Occludin, and the levels of autophagy were also increased by BD. Network pharmacology analysis suggested that BD might affect intestinal autophagy through the AMPK signaling pathway, which was confirmed by the activation of AMPK phosphorylation and the downregulation of mTOR expression following BD treatment. CONCLUSION: Our study demonstrated that BD repaired the intestinal epithelial barrier in DSS-induced colitis mice by activating AMPK phosphorylation and inhibiting mTOR expression to promote autophagy.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Ocludina/metabolismo , Claudina-1/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Serina-Treonina Quinases TOR/metabolismo , Mucosa Intestinal , Autofagia , Peso Corporal , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
4.
Environ Sci Ecotechnol ; 18: 100311, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37712051

RESUMO

The distribution and fractionation of persistent organic pollutants (POPs) in different matrices refer to how these pollutants are dispersed and separated within various environmental compartments. This is a significant study area as it helps us understand the transport efficiencies and long-range transport potentials of POPs to enter remote areas, particularly polar regions. This study provides a comprehensive review of the progress in understanding the distribution and fractionation of POPs. We focus on the contributions of four intermedia processes (dry and wet depositions for gaseous and particulate POPs) and determine their transfer between air and soil. These processes are controlled by their partitioning between gaseous and particulate phases in the atmosphere. The distribution patterns and fractionations can be categorized into primary and secondary types. Equations are developed to quantificationally study the primary and secondary distributions and fractionations of POPs. The analysis results suggest that the transfer of low molecular weight (LMW) POPs from air to soil is mainly through gas diffusion and particle deposition, whereas high molecular weight (HMW) POPs are mainly via particle deposition. HMW-POPs tend to be trapped near the source, whereas LMW-POPs are more prone to undergo long-range atmospheric transport. This crucial distinction elucidates the primary reason behind their temperature-independent primary fractionation. However, the secondary distribution and fractionation can only be observed along a temperature gradient, such as latitudinal or altitudinal transects. An animation is produced by a one-dimensional transport model to simulate conceptively the transport of CB-28 and CB-180, revealing the similarities and differences between the primary and secondary distributions and fractionations. We suggest that the decreasing temperature trend along latitudes is not the major reason for POPs to be fractionated into the polar ecosystems, but drives the longer-term accumulation of POPs in cold climates or polar cold trapping.

5.
Environ Sci Ecotechnol ; 17: 100308, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37701858

RESUMO

Sulfamethoxazole (SMX) is a significant environmental concern due to its adverse effects and ecological risks. SMX elimination in aquatic environments via photocatalysis presents a viable solution, given its high oxidation potential. However, such a solution remains controversial, primarily due to a lack of selectivity. Here we introduce a molecularly imprinted TiO2@Fe2O3@g-C3N4 (MFTC) photocatalyst designed for the selective degradation of SMX. To assess MFTC's selectivity, we applied it to degrade synthetic wastewater containing SMX alongside interfering species sulfadiazine (SDZ), ibuprofen (IBU), and bisphenol A (BPA). The results demonstrated a selective degradation efficiency rate of 96.8%, nearly twice that of competing pollutants. The molecularly imprinted sites within the catalyst played a crucial role by selectively capturing SMX and enhancing its adsorption, thereby improving catalytic efficiency. The degradation process involved •OH and •O2- free radicals, with a newly proposed double Z-scheme mechanism and potential pathway for SMX degradation by the MFTC photocatalytic system. This study enriches the application of photocatalysis using molecularly imprinted nanocomposite materials for treating complex pollutant mixtures in water.

6.
Food Chem ; 432: 137187, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37625297

RESUMO

Natural preservatives are causing a rethinking of current preservation means. As a sweetener resource, exploitation of Stevia rebaudiana leaves (SRLs) is still restricted due to human conventional cognition. Herein, Lactobacillus plantarum fermented SRLs containing diverse free secondary metabolites derived from microbial deglycosylation and bioenzymatic decomposition were investigated. The apparent resistance to typical foodborne bacteria (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomoas aeruginosa, Bacillus amyloliquefaciens) by fermented SRLs and their extracts were validated. The metabolite diversity and in-depth organic solvent extraction gave the possibilities for better antimicrobial actions, anti-HepG2/SGC-7901 cells in vitro in contrast with aqueous extract of unfermented SRLs. Crucially, compound identification and attribution revealed that fermentation products may be maximally contributing to antimicrobial and antitumor mechanisms rather than intrinsic plant and/or microbial components. Additionally, pork sausage models with 15 g/kg ethyl acetate extract as a preservative candidate presented preferred storage characteristics (21 days and 37 °C) compared to those without ethyl acetate extract, e.g. the minimal total plate count (3.86 ± 0.27 log CFU/g), peroxsignide value (8.02 ± 0.92 meq/kg), and acid value (2.01 ± 0.04 (KOH)/(mg/g)).


Assuntos
Lactobacillus plantarum , Neoplasias , Stevia , Humanos , Conservantes Farmacêuticos , Linhagem Celular , Escherichia coli
7.
Food Chem ; 432: 137213, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37633145

RESUMO

Antibiotic residues cause extensive damage to food security, thus arousing serious concerns. Hence, rapid and sensitive detection of antibiotic residues is crucial to food safety. This study aimed to propose a portable, visual, intelligent and rapid method for tetracycline detection. We developed a ratiometric fluorescent sensor based on the Eu3+-functionalized regular octahedral UiO-66-NH2 material. The developed sensor could quantify tetracycline in the concentration range of 0.5-200 µM with a detection limit as low as 0.2 µM under the optimum conditions. Furthermore, the analytical results obtained using the designed sensor in the actual samples were basically consistent with those obtained using high-performance liquid chromatography. Based on these achievements, a smartphone application-integrated fluorescent testing paper was designed for facile, intelligent, and visual detection of tetracycline. The integrated portable sensor not only saved cost and time for testing but also provided a forward-looking approach to fast, sensitive detection of antibiotic residues.


Assuntos
Európio , Compostos Heterocíclicos , Smartphone , Tetraciclina , Antibacterianos , Corantes
8.
Food Chem ; 432: 137199, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37633141

RESUMO

This study aims to the effect of arabinoxylan (AX) on gluten quality. Ultrasonic treatment is utilized to degrade water unextractable arabinoxylans (WUAX) from wheat bran, which obtains three molecular weights of AX. The results indicate that the shear viscosity and particle size of AX were decreased and the ζ-potential was increased after ultrasonic treatment. Analysis of the gluten shows that the free SH of gluten with 6% WUAX, SAX10, and SAX30 (ultrasound duration for 10 min and 30 min) was increased by 51.9%, 48.1%, and 17.0%, respectively, whereas the free SH of 2% SAX30-gluten was increased by 19.8%. Furthermore, WUAX impaired the viscoelasticity properties of gluten, while SAX30 improved the viscoelasticity of gluten. WUAX induced the open, fragile, and discontinuous structure of gluten. On the contrary, SAX30 promoted the formation of the compact and regular gluten structure. Overall, ultrasonic as a non-chemical treatment could be used to improve the quality of whole-wheat foods.


Assuntos
Farinha , Triticum , Peso Molecular , Glutens , Água
9.
J Ethnopharmacol ; 318(Pt B): 116994, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37541400

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a kind of chronic intestinal inflammation accompanied with abdominal pain, diarrhea and hematochezia. Huanglian Ganjiang decoction (HGD) derived from "Beiji Qianjin Yao Fang" was used for UC patients clinically. However, the specific mechanism of HGD in treating UC remain unclear. AIM OF STUDY: Our study devoted to demonstrating the therapeutic effect of HGD for colitis and clarifying the underlying mechanism. MATERIALS AND METHODS: UPLC-MS was carried out to identify the ingredients of HGD. UC mice were induced by giving 3% dextran sulfate sodium (DSS) solution for one week and treated by HGD for another week. Body weight fluctuation, disease activity index (DAI), colon length and pathological change of colon tissues were observed to evaluate therapeutical effect of HGD. ELISA and qPCR were carried out to estimate the inflammatory state. Western blot, qPCR and immunofluorescence were used to access the expression of tight junction proteins. Tandem mass tag (TMT)-Based proteomics and network pharmacology was launched to screen and predict the potential targets and pathway regulated by HGD. RESULTS: Based on the UPLC-MS/MS analysis, 100 components were identified in HGD. After 7-day treatment, HGD significantly alleviated colitis-associated symptoms including body weight loss, shorted colon, increase of DAI score, histopathologic lesions. HGD also reduced inflammatory cytokines IL-6 and IL-1ß levels, increased the number of goblet cells and restored tight junction proteins Occludin, Claudin-1 in colon. Network pharmacology study predicted that tight junction and MAPK pathway might be affected by HGD in colitis mice. APOC1 was screened out as key target in HGD-treated mice using TMT-based proteomics study. Further Western blot results showed that HGD reduced expressions of APOC1, p-P38 and p-JNK. CONCLUSION: HGD improves general symptoms of colitis mice at medium and high doses, which may be associated with restoring tight junction and intestinal barrier integrity and function through suppression of APOC1-JNK/P38 MAPK signal pathway.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Cromatografia Líquida , Proteômica , Espectrometria de Massas em Tandem , Colite/tratamento farmacológico , Colo , Inflamação/patologia , Transdução de Sinais , Proteínas de Junções Íntimas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
10.
J Ethnopharmacol ; 318(Pt B): 116988, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37541401

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Si Miao Formula (SMF), a traditional Chinese medicine, originated from the "Cheng Fang Bian Du" during the Qing Dynasty and is commonly employed for the treatment of gout and hyperuricemia. We have demonstrated the anti-NAFLD effect of SMF by regulating hepatic lipid metabolism in high fat and high sucrose (HFHS) feeding mice in our previous report. However, the material basis of SMF for its anti-NAFLD effect remains unknown. AIM OF THE STUDY: To compare the effeciacy of different components of SMF and identify the material basis for its anti-NAFLD effect. MATERIALS AND METHODS: In the present study, a "Leave-one out" strategy was adopted by removing one herb from SMF each time, and the anti-NAFLD effects of four decomposed recipes containing three herbs were evaluated in C57BL/6J mice fed with an HFHS diet for 16 weeks. The chemical components of SMF and the absorbed entities in serum were assayed using UHPLC-Q-Exactive-Orbitrap HRMS. Finally, a new chemical combination with four compounds (berberine, betaine, caffeic acid, p-coumaric acid, 2:2:1:1) were generated (SMF component composition, SMF_CC), and its anti-NAFLD effect was evaluated by comparing with the original SMF in the mouse model. RESULTS: Varified effects on NAFLD mice were observed among the decomposed recipes of SMF, while the original SMF showed advantages over its decomposed recipes. A total of 111 chemicals were identified from SMF, and 21 of them were detected in serum after oral administration of SMF. Comparing to SMF, SMF_CC showed comparable anti-NAFLD effect in HFHS-diet-fed mice, which was associated with the inhibition of hepatic fatty acid synthesis and transport, as well as inflammation. CONCLUSION: Our current results suggested that the original SMF was better than its decomposed recipes in NAFLD management, and the derived SMF_CC was also effective in inhibiting NAFLD formation, highlighting its potential of being a novel natural agent for NAFLD therapy.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Fígado , Metabolismo dos Lipídeos
11.
Talanta ; 266(Pt 2): 125022, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37619472

RESUMO

Aging and neurodegenerative disease are accompanied by lipid perturbations in the brain. Understanding the changes in the contents and functional activity of lipids remains a challenge not only because of the many areas in which lipids perform bioactivities but also because of the technical limitations in identifying lipids and their metabolites. In the present study, we aimed to evaluate how brain lipids are altered in Alzheimer's disease (AD)-like pathology by using mass spectrometry imaging (MSI). The spatial distributions and relative abundances of lipids in the brains were compared between APP/PS1 mice and their age-matched wild-type (WT) mice by matrix-assisted laser desorption ionization (MALDI) MSI assays. The comparisons were correlated with the analysis using a spectrophotometric method to determine the relative contents of sulfatides in different brain regions. Significant changes of brain lipids between APP/PS1 and WT mice were identified: eight sulfoglycosphingolipid species, namely, sulfatides/sulfated hexosyl ceramides (ShexCer) and two glycerophosphoinositol (GroPIn) species, PI 36:4 and PI 38:4. The declines in the spatial distributions of these ShexCer and GroPIn species in the APP/PS1 mice brains were associated with learning- and memory-related brain regions. Compared with young WT mice, aged WT mice showed significant decreases in the levels of these ShexCer and GroPIn species. Our results provide technical clues for assessing the impact of brain lipid metabolism on the senescent and neurodegenerative brain. The decline in sulfatides and GroPIns may be crucial markers during brain senescence and AD pathology. Appropriate lipid complementation might be important potentials as a therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Camundongos , Sulfoglicoesfingolipídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Cognição , Modelos Animais de Doenças , Ceramidas , Sulfatos
12.
Talanta ; 266(Pt 2): 125099, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651911

RESUMO

Considering the significant potential of microRNA (miRNA) as an efficient biomarker and great challenge of accurate analysis of lowly abundant miRNA, herein, we proposed a target-induced multipath-to-one-substrate strategy to monitor miRNA in vivo and in vitro accurately with high-efficient performances. In presence of target miRNA, it could directly generate the catalytic hairpin assembly (CHA) amplification cycle based on hybridizing with hairpin 1 (H1) and H2 respectively to structure the H1-H2 duplex, then the H1-H2 duplex could activate the cleavage ability of CRISPR/Cas12a to cleavage H1 which represent miRNA indirectly consume H1, which achieve co-consumption of the same substrate H1 by multiple pathways. And thus, the quenched fluorescent signal on H1 could be recovered due to the enlarger distance between fluorescent probe and quencher by the formation of H1-H2 duplex or cleavage of H1, all of which were related directly with target miRNA or indirectly with H1-H2 duplex activated cleavage ability of CRISPR/Cas12a, generating ultrahigh sensitive analytical ability and high-efficient analytical performances, such as more simple, fast, efficient and so on, especially a linear correlation from 100 pM to 100 nM with a detection limit of 78 pM, opening a new door to monitor expression level of biomolecules for early diagnosis and prognosis evaluation of various diseases.


Assuntos
Corantes Fluorescentes , MicroRNAs , Catálise , MicroRNAs/genética
13.
Talanta ; 266(Pt 2): 125092, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633040

RESUMO

This review summarizes recent advances of deep eutectic solvents (DESs) in sample preparation and determination methods of pesticides in food, environmental, and biological matrices since 2019. Emphasis is placed on new DES categories and emerging microextraction techniques. The former incorporate hydrophobic deep eutectic solvents, magnetic deep eutectic solvents, and responsive switchable deep eutectic solvents, while the latter mainly include dispersive liquid-liquid microextraction, liquid-liquid microextraction based on in-situ formation/decomposition of DESs, single drop microextraction, hollow fiber-liquid phase microextraction, and solid-phase microextraction. The principles, applications, advantages, and limitations of these microextraction techniques are presented. Besides, the use of DESs in chromatographic separation, electrochemical biosensors, fluorescent sensors, and surface-enhanced Raman spectroscopy are discussed. This review is expected to provide a valuable reference for extracting and detecting pesticides or other hazardous contaminants in the future.

14.
Front Physiol ; 14: 1191058, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731540

RESUMO

Hypobaric hypoxia (HH) characteristics induce impaired cognitive function, reduced concentration, and memory. In recent years, an increasing number of people have migrated to high-altitude areas for work and study. Headache, sleep disturbance, and cognitive impairment from HH, severely challenges the physical and mental health and affects their quality of life and work efficiency. This review summarizes the manifestations, mechanisms, and preventive and therapeutic methods of HH environment affecting cognitive function and provides theoretical references for exploring and treating high altitude-induced cognitive impairment.

15.
Nat Commun ; 14(1): 5451, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37673856

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , PPAR alfa/genética , Ácidos e Sais Biliares , Citoplasma , Camundongos Knockout , Ácidos Graxos
16.
Genome Biol ; 24(1): 202, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37674236

RESUMO

BACKGROUND: Quantitative proteomics is an indispensable tool in life science research. However, there is a lack of reference materials for evaluating the reproducibility of label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based measurements among different instruments and laboratories. RESULTS: Here, we develop the Quartet standard as a proteome reference material with built-in truths, and distribute the same aliquots to 15 laboratories with nine conventional LC-MS/MS platforms across six cities in China. Relative abundance of over 12,000 proteins on 816 mass spectrometry files are obtained and compared for reproducibility among the instruments and laboratories to ultimately generate proteomics benchmark datasets. There is a wide dynamic range of proteomes spanning about 7 orders of magnitude, and the injection order has marked effects on quantitative instead of qualitative characteristics. CONCLUSION: Overall, the Quartet offers valuable standard materials and data resources for improving the quality control of proteomic analyses as well as the reproducibility and reliability of research findings.


Assuntos
Proteômica , Espectrometria de Massas em Tandem , Cromatografia Líquida , Reprodutibilidade dos Testes , Proteoma
17.
Front Plant Sci ; 14: 1269286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719216

RESUMO

Introduction: Choline participates in plant stress tolerance through glycine betaine (GB) and phospholipid metabolism. As a salt-sensitive turfgrass species, Kentucky bluegrass (Poa pratensis) is the main turfgrass species in cool-season areas. Methods: To improve salinity tolerance and investigate the effects of choline on the physiological and lipidomic responses of turfgrass plants under salinity stress conditions, exogenous choline chloride was applied to Kentucky bluegrass exposed to salt stress. Results: From physiological indicators, exogenous choline chloride could alleviate salt stress injury in Kentucky bluegrass. Lipid analysis showed that exogenous choline chloride under salt-stress conditions remodeled the content of phospholipids, glycolipids, and lysophospholipids. Monogalactosyl diacylglycerol, digalactosyl diacylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylcholine content were increased and phosphatidic acid content were decreased in plants after exogenous choline chloride under salt treatment. Plant leaf choline content increased, but GB was not detected in exogenous choline chloride treatment plants under nonstress or salt-stress conditions. Discussion: GB synthesis pathway related genes showed no clear change to choline chloride treatment, whereas cytidyldiphosphate-choline (CDP-choline) pathway genes were upregulated by choline chloride treatment. These results reveal that lipid remodeling through choline metabolism plays an important role in the salt tolerance mechanism of Kentucky bluegrass. Furthermore, the lipids selected in this study could serve as biomarkers for further improvement of salt-sensitive grass species.

18.
Ther Adv Endocrinol Metab ; 14: 20420188231198620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719790

RESUMO

Background: As a part of metabolic syndrome, hyperuricemia has a higher incidence in patients with diabetes than in the general population owing to various underlying factors. Objectives: The objective of the present study was to investigate the prevalence of hyperuricemia among patients with diabetes and identify associated factors. Design: A cross-sectional study. Methods: Herein, we included patients with diabetes managed at nine healthcare centers in Chenghua District, Chengdu, from February 2021 to November 2021. Clinical data, lifestyle habits, and laboratory data were collected to determine the prevalence and factors associated with hyperuricemia. Results: In total, we included 1577 patients with diabetes (males, 50.35%; females, 49.65%). The median serum uric acid level was 337.9 µmol/L, and the prevalence of hyperuricemia in patients with diabetes was 21.24%. The prevalence of hyperuricemia in male patients was significantly higher than in females (29.35% in males versus 13.03% in females, p < 0.001). Male patients with obesity (p = 0.006) or triglyceride (TG) ⩾ 1.7 mmol/L (p < 0.001) had a high risk of developing hyperuricemia, and hyperuricemia was negatively associated with estimated glomerular filtration rate (eGFR) ⩾ 60 mL/min/1.73 m2 (p < 0.001), glycosylated hemoglobin (HbA1c) ⩾ 7% (p < 0.001), fenofibrate (p = 0.010), and sodium-glucose cotransporter 2 (SGLT-2) inhibitors (p = 0.035). Considering females, overweight (p = 0.004), alanine transaminase (ALT) > 40 U/L (p < 0.001), and TG ⩾ 1.7 mmol/L (p = 0.015) showed a significant positive correlation with hyperuricemia, while eGFR ⩾ 60 mL/min/1.73 m2 (p < 0.001) was negatively associated with the risk of hyperuricemia. Conclusion: Hyperuricemia is highly prevalent in patients with diabetes, especially in males. In addition to traditionally associated factors, fenofibrate and SGLT-2 inhibitors were also associated with the risk of hyperuricemia. Registration: The study protocol was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registration number was ChiCTR 2100042742.

19.
Front Nutr ; 10: 1175961, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720374

RESUMO

Background: The correlation between dietary vitamin B1 intake and cardiovascular diseases, as well as the all-cause and cardiovascular-associated mortality, is not well known. A large-scale data pool was used to examine the aforementioned correlations of Vitamin B1. Methods: This paper analyzed the dietary data from the survey conducted by National Health and Nutrition Examination (NHANES; 1999-2018). The correlation of vitamin B1 intake in each quartile with cardiovascular diseases such as hypertension, coronary heart disease, myocardial infarction and heart failure was analyzed using multivariate logistic regression models. The hazard ratios for dietary vitamin B1 intake in each quartile, along with all-cause and cardiovascular-associated mortality, were performed using multivariate cox regression analysis, setting the lowest quartile (Q1) as a reference. The restricted cubic spline (RCS) method was used to study the nonlinear relationship. Subgroup stratification and sensitivity analyses were used to further investigate the association between them. Results: The study enrolled 27,958 subjects (with a mean follow-up time of 9.11 years). After multivariate adjustment, dietary vitamin B1 intake was significantly associated with hypertension, heart failure and cardiovascular mortality, with the most significant association in quartile 4 (Q4) of vitamin B1 intake. The results of the restricted cubic spline showed that vitamin B1 intake was nonlinearly associated with hypertension, whereas it was linearly associated with heart failure and cardiovascular mortality. Meanwhile, a dose-response correlation was observed, indicating that increased vitamin B1 intake leads to reduced risk of both cardiovascular prevalence and mortality. The stratified analysis showed that the correlation between age ≥ 50 years, overweight, smoking history, drinking history and dyslipidemia were more significant in male patients. The associations remained similar in the sensitivity analyses. Conclusion: The large NHANES-based studies indicate a gradual trend toward decreasing the risk of hypertension and heart failure prevalence and cardiovascular mortality with increasing dietary vitamin B1 intake. This association is especially significant in elderly-aged men, overweight individuals, smokers, drinkers, and dyslipidemia patients.

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