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1.
Int J Nanomedicine ; 17: 2019-2039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558339

RESUMO

Background: Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability. Materials and Methods: In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide. Results: In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus. Conclusion: These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy.

2.
Environ Pollut ; : 119463, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569622

RESUMO

The occurrence of excessive ammonium in groundwater threatens human and aquatic ecosystem health across many places worldwide. As the fate of ammonium in groundwater systems is often affected by a complex mixture of transport and biogeochemical transformation processes, identifying the sources of groundwater ammonium is an important prerequisite for planning effective mitigation strategies. Elevated ammonium was found in both a shallow and an underlying deep groundwater system in an alluvial aquifer system beneath an agricultural area in the central Yangtze River Basin, China. In this study we develop and apply a novel, indirect approach, which couples the random forest classification (RFC) of machine learning method and fluorescence excitation-emission matrices with parallel factor analysis (EEM-PARAFAC), to distinguish multiple sources of ammonium in a multi-layer aquifer. EEM-PARAFAC was applied to provide insights into potential ammonium sources as well as the carbon and nitrogen cycling processes affecting ammonium fate. Specifically, RFC was used to unravel the different key factors controlling the high levels of ammonium prevailing in the shallow and deep aquifer sections, respectively. Our results reveal that high concentrations of ammonium in the shallow groundwater system primarily originate from anthropogenic sources, before being modulated by intensive microbially mediated nitrogen transformation processes such as nitrification, denitrification and dissimilatory nitrate reduction to ammonium (DNRA). By contrast, the linkage between high concentrations of ammonium and decomposition of soil organic matter, which ubiquitously contained nitrogen, suggested that mineralization of soil organic nitrogen compounds is the primary mechanism for the enrichment of ammonium in deeper groundwaters.

3.
BMC Cancer ; 22(1): 500, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524212

RESUMO

BACKGROUND: Ewing sarcoma (ES) is sensitive to systemic therapy, including chemotherapy and anti-angiogenesis Tyrosine Kinase Inhibitors(aaTKIs). However, the prognosis of patients with metastatic disease remains poor. Recurrence or distant metastasis after a complete response (CR) or near-CR due to systemic therapy is not rare. METHODS: We reviewed data from 187 ES patients between 2014-2019 treated at a single institute in China. Patients with extensive lung/pleural metastases (L/Pmeta) who had a CR or near-CR after first- or second-line chemotherapy with or without aaTKIs were retrospectively enrolled. Event-free survival (EFS) and overall survival (OS) were determined using the Kaplan-Meier method. For patients who had L/P recurrence, images were reviewed to define the exact location of each recurrent lesion, compared with the primary L/P lesion before chemotherapy and summarized as the relapse pattern. RESULTS: Seventeen patients and 21 cases of CR/nCR (5 by VDC/IE, 3 by VIT, and 13 by AVI) were finally analyzed. Median follow-up for surviving patients was 39.6 (range, 14.5-60.9) months. Median EFS and OS were 9.3 (95% confidence interval [CI], 2.0-16.6) months and 37.5 (95% CI, 21.8-53.1) months, respectively. The 2-year EFS was 19% and the 2-year OS was 70.6%, respectively. Most patients (82.4%) received whole lung irradiation (WLI). Lung/pleural relapse occurred in 71.4% (15/21) of CR/nCR cases. Most notably, all recurrent lesions exactly coincided with the original metastatic lesions before chemotherapy (exactly in situ) in 9 of the 15 recurrent cases, which was thus the major relapse pattern, whereas 42.9% had distant metastases other than L/Pmeta. CONCLUSIONS: Survival of ES patients with extensive L/Pmeta remains poor, even if they have a CR after systemic therapy. Recurrence exactly in situ is the major relapse pattern. WLI is not sufficient to prevent local recurrence in lung or pleura. More aggressive local treatment for metastatic lesions is warranted.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Sarcoma de Ewing , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/patologia , Terapia Combinada , Humanos , Pulmão/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Pleura/patologia , Estudos Retrospectivos , Sarcoma de Ewing/patologia
5.
Ying Yong Sheng Tai Xue Bao ; 33(4): 972-980, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543049

RESUMO

Soil acidification is an important factor leading to poor growth and root rot disease of Panax notoginseng in the understorey of forests. In this study, different amounts of quicklime (0, 500, 1000, 1500 and 2000 kg·hm-2) were amended into acid soil under forest. We evaluated the effect of quikelime addition on soil chemical properties, phenols, rhizosphere microorganisms and growth of P. notoginseng. The results showed that an appro-priate amount of quicklime addition (500-1000 kg·hm-2) could significantly increase soil pH, decrease the content of phenols (p-hydroxybenzoic acid, vanillin, syringic acid, ferulic acid and vanillic acid), promote P. notoginseng growth, and reduce the incidence of root rot disease. An appropriate amount of quicklime (500-1000 kg·hm-2) could significantly reduce the fungi:bacteria ratio, increase bacteria diversity, and increase the relative abundance of Ascomycota and Proteobacteria as well as Massilia and Sphingomonas. However, excessive quicklime addition (1500-2000 kg·hm-2) could reduce the content of available nitrogen and organic matter, and inhibit P. notoginseng growth. Therefore, 500-1000 kg·hm-2 of quicklime amendment could improve the chemical properties and microbial community of acid soil under forest, thereby promoting P. notoginseng growth, and reducing the incidence of root rot disease.


Assuntos
Ascomicetos , Panax notoginseng , Compostos de Cálcio , Florestas , Óxidos , Fenóis , Raízes de Plantas/microbiologia , Solo/química , Microbiologia do Solo
6.
Cell Mol Neurobiol ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35556192

RESUMO

At present, the diagnosis of ischemic stroke mainly depends on neuroimaging technology, but it still has many limitations. Therefore, it is very important to find new biomarkers of ischemic stroke. Recently, ß-actin has attracted extensive attention as a biomarker of a variety of cancers. Although several recent studies have been investigating its role in ischemic stroke and other cerebrovascular diseases, the understanding of this emerging biomarker in neurology is still limited. We examined human and preclinical studies to gain a comprehensive understanding of the literature on the subject. Most relevant literatures focus on preclinical research, and pay more attention to the role of ß-actin in the process of cerebral ischemia, but some recent literatures reported that in human studies, serum ß-actin increased significantly in the early stage of acute cerebral ischemia. This review will investigate the basic biology of ß-actin, pay attention to the potential role of serum ß-actin as an early diagnostic blood biomarker of ischemic stroke, and explore its potential mechanism in ischemic stroke and new strategies for stroke treatment in the future.

7.
Small ; : e2200954, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35557492

RESUMO

Activated porous carbons (APCs) are traditionally produced by heat treatment and KOH activation, where the production time can be as long as 2 h, and the produced activated porous carbons suffer from relatively low specific surface area and porosity. In this study, the fast high-temperature shock (HTS) carbonization and HTS-KOH activation method to synthesize activated porous carbons with high specific surface area of ≈843 m2 g-1 , is proposed. During the HTS process, the instant Joule heating (at a heating speed of ≈1100 K s-1 ) with high temperature and rapid quenching can effectively produce abundant pores with homogeneous size-distribution due to the instant melt of KOH into small droplets, which facilitates the interaction between carbon and KOH to form controllable, dense, and small pores. The as-prepared HTS-APC-based supercapacitors deliver a high energy density of 25 Wh kg-1 at a power density of 582 W kg-1 in the EMIMBF4 ionic liquid. It is believed that the proposed HTS technique has created a new pathway for manufacturing activated porous carbons with largely enhanced energy density of supercapacitors, which can inspire the development of energy storage materials.

8.
Cerebrovasc Dis ; : 1-9, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512630

RESUMO

BACKGROUND AND OBJECTIVES: The Canadian TIA Score has been verified as a good predictive tool for subsequent stroke risk in Caucasian patients; however, it had insufficient external verification of other races. We aimed to validate the Canadian TIA Score in Chinese patients and compared it with ABCD2 for subsequent stroke risk after transient ischemic attack (TIA). METHODS: The Third China National Stroke Registry (CNSR-III) was a nationwide, multicenter prospective registry recruiting consecutive patients with acute ischemic stroke or TIA within 7 days of the onset from August 2015 to March 2018. The Canadian TIA Score was verified in patients diagnosed with TIA from the CNSR-III (N = 1,184). The outcomes were subsequent stroke at 7 days, 14 days/discharge, 3 months, and 1 year. Outcomes were recorded by face-to-face assessment or telephone interview. The prognostic performance of the scoring system was assessed by the area under the receiver operator characteristic curve (AUC). RESULTS: Of 1,184 TIA patients (mean [IQR] age, 61.00 [53.00-69.00] years; 413 women [34.88%]), there were 40 patients (3.38%) having subsequent stroke within 7 days, 45 (3·80%) within 14 days/hospitalization, 66 (5·57%) within 3 months, and 100 (8·45%) within 1 year. The Canadian TIA Score (AUC 0 63-0·68) seemed to be a better prognostic score of stroke risk than the ABCD2 score (AUC 0·61-0·62), although no significant differences were noted. In the subgroup of atypical TIA, the Canadian TIA Score showed significantly stronger predictivity than the ABCD2 score within 7 days (0.80 [0.62-0.98] vs. 0.52 [0.30-0.73]; difference in AUC, 0.28 [0.03-0.53]; p, 0.026), and marginal significantly stronger predictivity within 1 year (0.71 [0.61-0.80] vs. 0.58 [0.48-0.68]; difference in AUC, 0.12 [-0.01 to 0.25]; p, 0.06). CONCLUSION: The Canadian TIA Score might be a better prognostic score than the ABCD2 score for post-TIA stroke risk, especially in patients with atypical TIA.

9.
Small ; : e2200525, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35491512

RESUMO

Metal aerogels represent an emerging type of functional porous materials with promising applications in diverse fields, but the fabrication of metal aerogels with specific structure and property still remains a challenge. Here, the authors report a new approach to fabricate metal aerogels by using ultrasmall metal nanoclusters (NCs) as functional building blocks. By taking D-penicillamine-stabilized gold NCs (AuNCs) with a diameter of 1.4 nm as an example, Au aerogels with ultrafine ligament size (3.5 nm) and good enzyme-mimic properties are synthesized. Detailed characterization shows that the obtained Au aerogels possess typical 3D self-supported porous network structure with high gold purity and surface area. Time-lapse spectroscopic and microscopic monitoring of the gelation process reveal that these ultrasmall AuNCs first grow into large nanoparticles before fusion into nanowire networks, during which both pH and the precursor concentration are identified to be the determining factor. Owing to their highly porous structure and abundant metal nodes, these self-supported Au aerogels display excellent peroxidase-like properties. This work provides a strategy for fabricating advanced metal aerogels by taking ultrasmall-sized metal NCs as building blocks, which also opens new avenues for engineering the structure and properties of metal aerogels for further advancing their applications.

10.
JAMA Netw Open ; 5(5): e229960, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35503220

RESUMO

Importance: The lack of experienced ophthalmologists limits the early diagnosis of retinal diseases. Artificial intelligence can be an efficient real-time way for screening retinal diseases. Objective: To develop and prospectively validate a deep learning (DL) algorithm that, based on ocular fundus images, recognizes numerous retinal diseases simultaneously in clinical practice. Design, Setting, and Participants: This multicenter, diagnostic study at 65 public medical screening centers and hospitals in 19 Chinese provinces included individuals attending annual routine medical examinations and participants of population-based and community-based studies. Exposures: Based on 120 002 ocular fundus photographs, the Retinal Artificial Intelligence Diagnosis System (RAIDS) was developed to identify 10 retinal diseases. RAIDS was validated in a prospective collected data set, and the performance between RAIDS and ophthalmologists was compared in the data sets of the population-based Beijing Eye Study and the community-based Kailuan Eye Study. Main Outcomes and Measures: The performance of each classifier included sensitivity, specificity, accuracy, F1 score, and Cohen κ score. Results: In the prospective validation data set of 208 758 images collected from 110 784 individuals (median [range] age, 42 [8-87] years; 115 443 [55.3%] female), RAIDS achieved a sensitivity of 89.8% (95% CI, 89.5%-90.1%) to detect any of 10 retinal diseases. RAIDS differentiated 10 retinal diseases with accuracies ranging from 95.3% to 99.9%, without marked differences between medical screening centers and geographical regions in China. Compared with retinal specialists, RAIDS achieved a higher sensitivity for detection of any retinal abnormality (RAIDS, 91.7% [95% CI, 90.6%-92.8%]; certified ophthalmologists, 83.7% [95% CI, 82.1%-85.1%]; junior retinal specialists, 86.4% [95% CI, 84.9%-87.7%]; and senior retinal specialists, 88.5% [95% CI, 87.1%-89.8%]). RAIDS reached a superior or similar diagnostic sensitivity compared with senior retinal specialists in the detection of 7 of 10 retinal diseases (ie, referral diabetic retinopathy, referral possible glaucoma, macular hole, epiretinal macular membrane, hypertensive retinopathy, myelinated fibers, and retinitis pigmentosa). It achieved a performance comparable with the performance by certified ophthalmologists in 2 diseases (ie, age-related macular degeneration and retinal vein occlusion). Compared with ophthalmologists, RAIDS needed 96% to 97% less time for the image assessment. Conclusions and Relevance: In this diagnostic study, the DL system was associated with accurately distinguishing 10 retinal diseases in real time. This technology may help overcome the lack of experienced ophthalmologists in underdeveloped areas.


Assuntos
Retinopatia Diabética , Doenças do Nervo Óptico , Doenças Retinianas , Adulto , Inteligência Artificial , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Masculino , Retina/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem
11.
Cell Mol Life Sci ; 79(5): 268, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499593

RESUMO

FBXW2 is a poorly characterized F-box protein, as a tumor suppressor that inhibits growth and metastasis of lung cancer by promoting ubiquitylation and degradation of oncogenic proteins, including SKP2 and ß-catenin. However, what the biological functions of FBXW2 in prostate cancer cells and whether FBXW2 targets other substrates to involve in progression of prostate cancer is still unclear. Here, we reported that overexpression of FBXW2 attenuated proliferation and metastasis of PCa models both in vitro and in vivo, while FBXW2 depletion exhibited the opposite effects. Intriguingly, FBXW2 was an E3 ligase for EGFR in prostate cancer. EGFR protein level and its half-life were extended by FBXW2 depletion, while EGFR protein level was decreased, and its half-life was shortened upon overexpression of FBXW2, but not its dominant-negative mutant. Importantly, FBXW2 bond to EGFR via its consensus degron motif (TSNNST), and ubiquitylated and degraded EGFR, resulting in repression of EGF function. Thus, our data uncover a novel that FBXW2 as a tumor suppressor of prostate cancer, inhibits EGFR downstream by promoting EGFR ubiquitination and degradation, resulting in repression of cell proliferation and metastasis.


Assuntos
Proteínas F-Box , Neoplasias da Próstata , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Humanos , Masculino , Neoplasias da Próstata/patologia , Ubiquitinação
12.
Appl Ergon ; 103: 103775, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500523

RESUMO

The aim of this study is to identify the best practices and future research directions for driver lane-change intention (DLCI) prediction using eye-tracking technologies based on a systematic literature review. We searched five academic literature databases and then conducted an in-depth review, structured coding, and analysis of 40 relevant articles. The literature on DLCI prediction is summarized in terms of input features, feature extraction and prediction time windows, labeling methods, and machine learning algorithms. The results show that eye tracking data features along with other data sources can be useful inputs for the prediction of DLCI. Major challenges in this line of research include determining the optimal time window for feature extraction and developing and evaluating the appropriate machine learning algorithm. Suggestions for future research and practice for DLCI prediction in intelligent vehicles are discussed.

13.
Food Chem ; 390: 133194, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35576807

RESUMO

Histamine is the prime culprit of toxicity resulting from seafood consumption, whereas conventional detection methods are not convenient to meet the needs of rapid histamine analysis nowadays. Based on upconversion nanoparticles (UCNPs) and inner filter effects (IFE), a novel ratiometric fluorescence nanosystem was developed for the efficient detection of histamine. Through pre-treatment with solid-phase extraction (SPE) and colorific azo coupling reaction of histamine, the fluorescence of UCNPs at 548 nm was quenched, while fluorescence at 664 nm was unchanged. Thus, ratiometric fluorescence I548/I664 was inversely proportional to histamine concentration at a wide range of 10-200 mg/L. The detection limit was 7.34 mg/L, one order of magnitude lower than that of the traditional colorimetric method (25 mg/L). In addition, such a convenient and environment-friendly detection system was further employed to quantify the histamine in fish, shrimp, and shellfish samples, showing excellent application potential in seafood safety.

14.
Reprod Biol Endocrinol ; 20(1): 80, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597951

RESUMO

SCOPE: Male fertility and sperm quality are negatively affected by psychological stress. Chronic restraint stress (CRS) is a common psychological stress that has a negative effect on sperm. Betaine (BET), an active ingredient isolated from Lycium barbarum, has anti-oxidant, anti-inflammatory and other pharmacological activities. This study aims to explore whether betaine has a therapeutic effect on sperm deformity and vitality under CRS and its mechanism. METHODS AND RESULTS: Chronic restraint stress was induced in 8-week-old male C57BL/6 J mice by fixation for 6 h a day for 35 days. Mice were intraperitoneally injected with betaine (BET) or normal saline (NS) for 14 days. Thirty-five days later, the animals were sacrificed. The results showed that the detrimental effects of CRS on testes as evident by disrupted histoarchitecture, increased oxidative stress, inflammation and apoptosis that compromised male fertility. BET injections can reverse these symptoms. CONCLUSIONS: BET can improve spermatogenesis dysfunction caused by CRS, which may provide potential dietary guidance.


Assuntos
Betaína , Testículo , Animais , Betaína/metabolismo , Betaína/farmacologia , Betaína/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Espermatogênese , Testículo/metabolismo
15.
Int J Mol Sci ; 23(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35563360

RESUMO

Maize (Zea mays) is an important multi-functional crop. The growth and yield of maize are severely affected by drought stress. Previous studies have shown that microRNAs (miRNAs) in maize play important roles in response to abiotic stress; however, their roles in response to drought stress in maize roots is unclear. In our study, we found 375 miRNAs in the roots of 16 inbred lines. Of the 16 lines, zma-MIR168, zma-MIR156, and zma-MIR166 were highly expressed, whereas zma-MIR399, zma-MIR2218, and zma-MIR2275 exhibited low expression levels. The expression patterns of miRNA in parental lines and their derived RILs are different. Over 50% of miRNAs exhibited a lower expression in recombinant inbred lines than in parents. The expression of 50 miRNAs was significantly altered under water stress (WS) in at least three inbred lines, and the expression of miRNAs in drought-tolerant lines changed markedly. To better understand the reasons for miRNA response to drought, the degree of histone modifications for miRNA genes was estimated. The methylation level of H3K4 and H3K9 in miRNA precursor regions changed more noticeably after WS, but no such phenomenon was seen for DNA methylation and m6A modification. After the prediction of miRNA targets using psRNATarget and psRobot, we used correlation analysis and qRT-PCR to further investigate the relationship between miRNAs and target genes. We found that 87 miRNA-target pairs were significantly negatively correlated. In addition, a weighted gene co-expression network analysis using miRNAs, as well as their predicted targets, was conducted to reveal that miR159, miR394, and miR319 may be related to maize root growth. The results demonstrated that miRNAs might play essential roles in the response to drought stress.

16.
Cells ; 11(9)2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35563879

RESUMO

We demonstrated previously that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) play a critical role in angiogenesis. Here, we examine whether this pro-angiogenic efficacy is enhanced in EVs derived from MSCs overexpressing GATA-4 (MSCGATA-4). Methods and Results. EVs were isolated from MSCGATA-4 (EVGATA-4) and control MSCs transduced with an empty vector (EVnull). EVs from both cell types were of the same size and displayed similar molecular markers. Compared with EVnull, EVGATA-4 increased both a tube-like structure formation and spheroid-based sprouting of human umbilical vein endothelial cells (HUVECs). The EVGATA-4 increased the numbers of CD31-positive cells and hemoglobin content inside Matrigel plugs subcutaneously transplanted into mice for 2 weeks. Moreover, EVGATA-4 encapsulated higher levels of let-7 family miRs compared to EVnull. The transfer of exosomal let-7 miRs into HUVECs was recorded with an accompanied down-regulation of thrombospondin-1 (THBS1) expression, a major endogenous angiogenesis inhibitor. The loss-and-gain of function studies of let-7 miRs showed that let-7f knockdown significantly decreased EVGATA-4-mediated vascularization inside Matrigel plugs. In contrast, let-7f overexpression promoted HUVEC migration and tube formation. Conclusion. Our results indicate that EVs derived from genetically modified MSCs with GATA-4 overexpression had increased pro-angiogenic capacity due to the delivery of let-7 miRs that targeted THBS1 in endothelial cells.

17.
Front Mol Biosci ; 9: 874186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601831

RESUMO

Background: Several members of the SLC26A family of transporters, including SLC26A3 (DRA), SLC26A5 (prestin), SLC26A6 (PAT-1; CFEX) and SLC26A9, form multi-protein complexes with a number of molecules (e.g., cytoskeletal proteins, anchoring or adaptor proteins, cystic fibrosis transmembrane conductance regulator, and protein kinases). These interactions provide regulatory signals for these molecules. However, the identity of proteins that interact with the Cl-/HCO3 - exchanger, SLC26A4 (pendrin), have yet to be determined. The purpose of this study is to identify the protein(s) that interact with pendrin. Methods: A yeast two hybrid (Y2H) system was employed to screen a mouse kidney cDNA library using the C-terminal fragment of SLC26A4 as bait. Immunofluorescence microscopic examination of kidney sections, as well as co-immunoprecipitation assays, were performed using affinity purified antibodies and kidney protein extracts to confirm the co-localization and interaction of pendrin and the identified binding partners. Co-expression studies were carried out in cultured cells to examine the effect of binding partners on pendrin trafficking and activity. Results: The Y2H studies identified IQ motif-containing GTPase-activating protein 1 (IQGAP1) as a protein that binds to SLC26A4's C-terminus. Co-immunoprecipitation experiments using affinity purified anti-IQGAP1 antibodies followed by western blot analysis of kidney protein eluates using pendrin-specific antibodies confirmed the interaction of pendrin and IQGAP1. Immunofluorescence microscopy studies demonstrated that IQGAP1 co-localizes with pendrin on the apical membrane of B-intercalated cells, whereas it shows basolateral expression in A-intercalated cells in the cortical collecting duct (CCD). Functional and confocal studies in HEK-293 cells, as well as confocal studies in MDCK cells, demonstrated that the co-transfection of pendrin and IQGAP1 shows strong co-localization of the two molecules on the plasma membrane along with enhanced Cl-/HCO3 - exchanger activity. Conclusion: IQGAP1 was identified as a protein that binds to the C-terminus of pendrin in B-intercalated cells. IQGAP1 co-localized with pendrin on the apical membrane of B-intercalated cells. Co-expression of IQGAP1 with pendrin resulted in strong co-localization of the two molecules and increased the activity of pendrin in the plasma membrane in cultured cells. We propose that pendrin's interaction with IQGAP1 may play a critical role in the regulation of CCD function and physiology, and that disruption of this interaction could contribute to altered pendrin trafficking and/or activity in pathophysiologic states.

18.
Front Med (Lausanne) ; 9: 905007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602473

RESUMO

More than 200 cases of lipoprotein glomerulopathy (LPG) have been reported since it was first discovered 30 years ago. Although relatively rare, LPG is clinically an important cause of nephrotic syndrome and end-stage renal disease. Mutations in the APOE gene are the leading cause of LPG. APOE mutations are an important determinant of lipid profiles and cardiovascular health in the population and can precipitate dysbetalipoproteinemia and glomerulopathy. Apolipoprotein E-related glomerular disorders include APOE2 homozygote glomerulopathy and LPG with heterozygous APOE mutations. In recent years, there has been a rapid increase in the number of LPG case reports and some progress in research into the mechanism and animal models of LPG. We consequently need to update recent epidemiological studies and the molecular mechanisms of LPG. This endeavor may help us not only to diagnose and treat LPG in a more personized manner but also to better understand the potential relationship between lipids and the kidney.

19.
Angew Chem Int Ed Engl ; : e202205491, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506663

RESUMO

The eco-friendly properties enable two-dimensional (2D) Cu-based perovskites as ideal candidates for next-generation optoelectronics, but practical application is limited by low photoelectric conversion efficiency because of poor carrier transport abilities. Here, we report enhanced structural stability of 2D CuBr4 perovskites under compression up to 30 GPa, without obvious volume collapse or structural amorphization, by inserting organic C6 H5 CH2 NH3 (PMA) groups between layers. The band gap value of (PMA)2 CuBr4 can be effectively tuned from 1.8 to 1.47 eV by employing external pressures, leading to a broadened absorption range of 400-800 nm. Notably, we successfully detected photoconductivity of the photoresponse at pressures from 10 to 40 GPa; the maximum value of 5×10-3  S cm-1 is observed at 28 GPa, indicating potential applications for high performance photovoltaic candidates under extreme conditions.

20.
J Ethnopharmacol ; 293: 115252, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405255

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.

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