Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
1.
J Synchrotron Radiat ; 31(Pt 3): 635-645, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656774

RESUMO

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

2.
Inorg Chem ; 63(1): 462-473, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38141022

RESUMO

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N,N,N',N'-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N,N'-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

3.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34642248

RESUMO

Microbial communities regulate ecosystem responses to climate change. However, predicting these responses is challenging because of complex interactions among processes at multiple levels of organization. Organismal traits that determine individual performance and ecological interactions are essential for scaling up environmental responses from individuals to ecosystems. We combine protist microcosm experiments and mathematical models to show that key traits-cell size, shape, and contents-each explain different aspects of species' demographic responses to changes in temperature. These differences in species' temperature responses have complex cascading effects across levels of organization-causing nonlinear shifts in total community respiration rates across temperatures via coordinated changes in community composition, equilibrium densities, and community-mean species mass in experimental protist communities that tightly match theoretical predictions. Our results suggest that traits explain variation in population growth, and together, these two factors scale up to influence community- and ecosystem-level processes across temperatures. Connecting the multilevel microbial processes that ultimately influence climate in this way will help refine predictions about complex ecosystem-climate feedbacks and the pace of climate change itself.


Assuntos
Microbiota , Temperatura , Mudança Climática , Ecossistema , Especificidade da Espécie
4.
Chem Biodivers ; 21(4): e202400002, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38411310

RESUMO

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.


Assuntos
Chaetomium , Policetídeos , Vaccinium myrtillus , Chaetomium/química , Policetídeos/química , Lipopolissacarídeos/farmacologia , Estrutura Molecular
5.
Proc Biol Sci ; 290(1992): 20222263, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36722083

RESUMO

Anthropogenic increases in temperature and nutrient loads will likely impact food web structure and stability. Although their independent effects have been reasonably well studied, their joint effects-particularly on coupled ecological and phenotypic dynamics-remain poorly understood. Here we experimentally manipulated temperature and nutrient levels in microbial food webs and used time-series analysis to quantify the strength of reciprocal effects between ecological and phenotypic dynamics across trophic levels. We found that (1) joint-often interactive-effects of temperature and nutrients on ecological dynamics are more common at higher trophic levels, (2) temperature and nutrients interact to shift the relative strength of top-down versus bottom-up control, and (3) rapid phenotypic change mediates observed ecological responses to changes in temperature and nutrients. Our results uncover how feedback between ecological and phenotypic dynamics mediate food web responses to environmental change. This suggests important but previously unknown ways that temperature and nutrients might jointly control the rapid eco-phenotypic feedback that determine food web dynamics in a changing world.


Assuntos
Cadeia Alimentar , Nutrientes , Temperatura , Estado Nutricional
6.
BMC Psychiatry ; 23(1): 822, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946206

RESUMO

Schizophrenia (SCZ) is a chronic, highly relapsing, severe mental disorder with an unclear etiology. Cytokine-mediated neuroimmune abnormalities have been repeatedly revealed. IL-1ß was reported to play a vital role in expanding the inflammatory response. However, the underlying molecular mechanism is poorly understood. In this study, we found that miR-3653-3p with the NLRP3 binding site in Targetscan was differentially expressed in miRNA high-throughput sequencing in schizophrenia (SCZ), and indeed, its downregulation in SCZ peripheral blood was also verified by RT-qPCR (P-value = 0.015). Furthermore, we found that the mRNAs of caspase 1 and IL-1ß are elevated in people who suffer from SCZ (P = 0.044 and P = 0.001, respectively). Moreover, the interaction of NLRP3, Caspase1, and IL-1ß was found in the peripheral blood of patients with SCZ. The expression level of miR-3653-3p was negatively correlated with NLRP3 and IL-1ß mRNA contents (r = 0.487, P = 0.04 and r = 0.508, P = 0.037, respectively). NLRP3 mRNA was positively correlated with caspase1 mRNA. Meanwhile, the expression of miR-3653-3p was also negatively correlated with negative symptom subscores of PANSS (r = 0.450, P = 0.046). IL-1ß mRNA is positively correlated with the total scores of PANSS (r = 0.690, P = 0.002) and the sub-scores of general psychopathology of PANSS (r = 0.583, P = 0.014). Additionally, a significant positive relationship exists between IL-1ß and the total duration (r = 0.638, P = 0.006). We found that the combination of miR-3653-3p, caspase 1, and IL-1ß have better diagnostic values. The results indicate that miR-3653-3p, caspase 1, and IL-1ß can potentially be biomarkers of SCZ, identifying negative symptoms or a chronic course. A further understanding of the involvement of IL-1ß in SCZ may be a crucial molecular effector for the chronic course to intervene.


Assuntos
MicroRNAs , Esquizofrenia , Humanos , Caspase 1/genética , Caspase 1/metabolismo , Interleucina-1beta/genética , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Mensageiro , Esquizofrenia/diagnóstico , Esquizofrenia/genética
7.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985661

RESUMO

Mitochondria have a crucial role in regulating energy metabolism and their dysfunction has been linked to tumorigenesis. Cancer diagnosis and intervention have a great interest in the development of new agents that target biomolecules within mitochondria. However, monitoring and modulating mitochondria RNA (mtRNA), an essential component in mitochondria, in cells is challenging due to limited functional research and the absence of targeting agents. In this study, we designed and synthesized a fluorescent quinolinium derivative, QUCO-1, which actively lit up with mtRNA in both normal and cancer cells in vitro. Additionally, we evaluated the function of QUCO-1 as an mtRNA ligand and found that it effectively induced severe mitochondrial dysfunction and OXPHOS inhibition in RKO colorectal cancer cells. Treatment with QUCO-1 resulted in apoptosis, cell cycle blockage at the G2/M phase, and the effective inhibition of cell proliferation. Our findings suggest that QUCO-1 has great potential as a promising probe and therapeutic agent for mtRNA, with the potential for treating colorectal cancer.


Assuntos
Neoplasias Colorretais , Mitocôndrias , Humanos , RNA Mitocondrial/metabolismo , Mitocôndrias/metabolismo , Proliferação de Células , Apoptose , Corantes Fluorescentes/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral
8.
Breast Cancer Res ; 24(1): 68, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36258226

RESUMO

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers. METHODS: Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS mRNA levels were also determined by fluorescence in situ hybridization in patient tumor microarrays (TMAs) with concurrent normal, DCIS, and invasive breast cancer, and association of NRAS mRNA levels with DCIS and invasive breast cancer was assessed by paired Wilcoxon signed-rank test. Pearson's correlation was calculated between NRAS mRNA levels and basal biomarkers in the TMAs, as well as in patient datasets. RNA-seq data were generated in cell lines, and unsupervised hierarchical clustering was performed after combining with RNA-seq data from a previously published patient cohort. RESULTS: Invasive breast cancers showed higher NRAS mRNA levels compared to DCIS samples. These NRAShigh lesions were also enriched with basal-like features, such as basal gene expression signatures, lower ER, and higher p53 protein and Ki67 levels. We have shown previously that NRAS drives aggressive features in DCIS-like and basal-like SUM102PT cells. Here, we found that NRAS-silencing induced a shift to a luminal gene expression pattern. Conversely, NRAS overexpression in the luminal DCIS SUM225 cells induced a basal-like gene expression pattern, as well as an epithelial-to-mesenchymal transition signature. Furthermore, these cells formed disorganized mammospheres containing cell masses with an apparent reduction in adhesion. CONCLUSIONS: These data suggest that elevated NRAS levels in DCIS are not only a marker but can also control the emergence of basal-like features leading to more aggressive tumor activity, thus supporting the therapeutic hypothesis that targeting NRAS and/or downstream pathways may block disease progression for a subset of DCIS patients with high NRAS.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Carcinoma Ductal de Mama/patologia , Proteína Supressora de Tumor p53/genética , Neoplasias da Mama/patologia , Hibridização in Situ Fluorescente , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Mensageiro , Progressão da Doença , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo
9.
J Chem Inf Model ; 62(6): 1368-1375, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35290042

RESUMO

Fluorescent molecules are important tools in biological detection, and numerous efforts have been made to develop compounds to meet the desired photophysical properties. For example, tuning the wavelength allows an appropriate penetration depth with minimal interference from the autofluorescence/scattering for a better signal-to-noise contrast. However, there are limited guidelines to rationally design or computationally predict the optical properties from first principles, and factors like the solvent effects will make it more complicated. Herein, we established a database (SMFluo1) of 1181 solvated small-molecule fluorophores covering the ultraviolet-visible-near-infrared absorption window and developed new machine learning models based on deep neural networks for accurately predicting photophysical parameters. The optimal system was applied to 120 out-of-sample compounds, and it exhibited remarkable accuracy with a mean relative error of 1.52%. In this new paradigm, a deep learning algorithm is promising to complement conventional theoretical and experimental studies of fluorophores and to greatly accelerate the discovery of new dyes. Due to its simplicity and efficiency, data from newly developed fluorophores can be easily supplemented to this system to further improve the accuracy across various dye families.


Assuntos
Corantes Fluorescentes , Redes Neurais de Computação , Humanos , Aprendizado de Máquina , Solventes
10.
J Helminthol ; 96: e65, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065626

RESUMO

In this study, we report the first complete mitochondrial genome of the tapeworm Nippotaenia mogurndae in the order Nippotaeniidea Yamaguti, 1939. This mitogenome, which is 14,307 base pairs (bp) long with an A + T content of 72.2%, consists of 12 protein-coding genes, 22 transfer RNA (tRNA) genes, two rRNA genes, and two non-coding regions. Most tRNAs have a conventional cloverleaf structure, but trnS1 and trnR lack dihydrouridine arms of tRNA. The two largest non-coding regions, NCR1 (220 bp) and NCR2 (817 bp), are located between trnY and trnS2 and between nad5 and trnG, respectively. Phylogenetic analyses of mitogenomic data indicate that N. mogurndae is closely related to tapeworms in the order Cyclophyllidea.


Assuntos
Cestoides , Infecções por Cestoides , Genoma Mitocondrial , Animais , Cestoides/genética , Infecções por Cestoides/veterinária , Filogenia , RNA de Transferência/genética
11.
Anal Chem ; 93(49): 16297-16301, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34843219

RESUMO

Because of the lack of facile and accurate methods to track stress granule (SG) dynamics in live cells and in vivo, in-depth studies of the biological roles of this attractive membraneless organelle have been limited. Herein, we report the first small-molecule probe, TASG, for the selective, convenient and real-time monitoring of SGs. This novel molecule can simultaneously bind to SG RNAs, the core SG protein G3BP1, and their complexes, triggering a significant enhancement in fluorescence intensity, making TASG broadly applicable to SG imaging under various stress conditions in fixed and live cells, ex vivo and in vivo. Using TASG, the complicated endogenous SG dynamics were revealed in both live cells and C. elegans. Collectively, our work provides an ideal probe that has thus far been absent in the field of SG investigations. We anticipate that this powerful tool may create exciting opportunities to investigate the underlying roles of SGs in different organisms.


Assuntos
Condensados Biomoleculares , Caenorhabditis elegans , Animais , DNA Helicases , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(3): 350-354, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32543141

RESUMO

OBJECTIVE: To study the alterations of endoplasmic reticulum (ER) stress and mitochondrial damage after acute myocardial infarction (AMI). METHODS: A total of 40 SD rats were used in this study and 32 of them were subjected to AMI by ligation of left anterior descending artery. The rats were sacrificed and the heart tissues were collected after 1 h, 2 h, 4 h and 6 h of AMI ( n=8 per group). The mRNA levels of activating transcription factor 6 alpha ( ATF6) and immunoglobulin heavy chain binding potein ( BiP), as well as the expression of mitochondrial DNA (mtDNA) in cytoplasm were detected by RT-PCR. The ATP levels in the cardiomyocytes were detected by a commercial ATP assay kit. RESULTS: The mRNA levels of ATF6 and BiP were significantly increased after 1 h of AMI, which were maintained at high level from 2 h of AMI to the end of the experiment ( P<0.05). The ATP concentrations in the cardiomyocytes were significantly elevated after 1 h of AMI but remarkably decreased after 4 h and 6 h of AMI ( P<0.05). The release of mtDNA in cytoplasm was significantly increased after 2 h of AMI, followed by further elevations at 4 h and 6 h after AMI ( P<0.05). CONCLUSION: Mitochondrial damage is secondary to ER stress in AMI.


Assuntos
Estresse do Retículo Endoplasmático , Infarto do Miocárdio , Miócitos Cardíacos , Animais , Apoptose , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley
13.
J Clin Lab Anal ; 32(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28220979

RESUMO

OBJECTIVE: Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. DESIGN: A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. RESULTS: TB-IGRA results were in positive proportion to the lymphocytes, CD4+ T cells and CD4+ CD28+ T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T Tcells were both increased and the CD4+ IFN-γ+ T had positive correlation with the value of TB-IGRA. CONCLUSIONS: IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators.


Assuntos
Testes de Liberação de Interferon-gama/estatística & dados numéricos , Tuberculose/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Interferon gama/análise , Interferon gama/imunologia , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose/epidemiologia
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(4): 971-4, 2015 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-26197585

RESUMO

A cavity ring-down spectrometer (CRDS) was built based on telecom distributed feedback (DFB) diode lasers. The ring down cavity was formed by mirrors of 99. 997% reflectivity with a separation of 130 cm, with an empty ring down time of about 150 µs. A minimum detectable absorption coefficient of 5 x 10(-12) cm(-1) was obtained by averaging about 1,000 recorded spectra. The ring down cavity is thermo-isolated, and used as an interferometer to calibrate the recorded spectrum. A feedback control scheme was applied to step scan the laser frequency, successively matching each of the longitudinal modes of the cavity. By measuring the CO contents in a standard gas sample, the quantitative capability of the CRDS instrument was demonstrated, and a CO detection limit of 4 ppb was achieved. The instrument was applied to monitor the CO concentration in ambient air.

15.
Appl Opt ; 53(32): 7716-23, 2014 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-25402995

RESUMO

A cavity ring-down spectrometer is built for trace gas detection using telecom distributed feedback (DFB) diode lasers. The longitudinal modes of the ring-down cavity are used as frequency markers without active-locking either the laser or the high-finesse cavity. A control scheme is applied to scan the DFB laser frequency, matching the cavity modes one by one in sequence and resulting in a correct index at each recorded spectral data point, which allows us to calibrate the spectrum with a relative frequency precision of 0.06 MHz. Besides the frequency precision of the spectrometer, a sensitivity (noise-equivalent absorption) of 4×10-11 cm-1 Hz-1/2 has also been demonstrated. A minimum detectable absorption coefficient of 5×10-12 cm-1 has been obtained by averaging about 100 spectra recorded in 2  h. The quantitative accuracy is tested by measuring the CO2 concentrations in N2 samples prepared by the gravimetric method, and the relative deviation is less than 0.3%. The trace detection capability is demonstrated by detecting CO2 of ppbv-level concentrations in a high-purity nitrogen gas sample. Simple structure, high sensitivity, and good accuracy make the instrument very suitable for quantitative trace gas analysis.


Assuntos
Gases/análise , Microquímica/instrumentação , Análise Espectral/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Calibragem , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Artigo em Inglês | MEDLINE | ID: mdl-38736427

RESUMO

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

17.
Sci Rep ; 14(1): 6262, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491084

RESUMO

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Linfócitos T Reguladores , Medula Espinal/patologia , Células Apresentadoras de Antígenos , Camundongos Endogâmicos C57BL
18.
Stem Cell Res Ther ; 15(1): 95, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566259

RESUMO

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Humanos , Ratos , Animais , Cromatografia Líquida , Proteômica , Lipopolissacarídeos/farmacologia , Espectrometria de Massas em Tandem , Lesão Pulmonar Aguda/terapia , Síndrome do Desconforto Respiratório/terapia , Obesidade , Controle de Qualidade , Vesículas Extracelulares/fisiologia , Células-Tronco Mesenquimais/fisiologia
19.
J Asthma ; 50(2): 209-14, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23294145

RESUMO

BACKGROUND: The presence of transient receptor potential vanilloid 2 (TRPV2) in human peripheral blood cells may suggest a role under pathological conditions. The aim of this study was to explore the relationship between the expression profile of TRPV2 gene and childhood asthma in the north of China. The effects of allergens exposure on the expression of TRPV2 gene were also investigated. METHODS: Sixty asthmatics children confirmed by physician diagnosis and 60 healthy children as a control group were recruited. Serum total IgE and specific IgE were measured. Using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), TRPV2 was detected in total RNA extracted from peripheral blood lymphocytes. Student's t-test and chi-square test were used to analyze the relationship between TRPV2 transcript and different parameter variables on susceptibility of childhood asthma. Multiple logistic regression was used to analyze the associations between TRPV2 gene and allergens. RESULTS: The expression level of TRPV2 gene was increased 2.6 times in asthmatic children compared with controls (p < .01). The up-regulation of TRPV2 gene and sensitization to one of three the allergens-spring pollen, dust mite, and dog and cat hair-were correlated with childhood asthma. In addition, the hypersensitivity to spring pollen, cockroach, and dust mite and up-regulation of TRPV2 gene expression may be the risk factors for the childhood asthma in Beijing. CONCLUSIONS: The increased expression of TRPV2 gene in peripheral lymphocytes is closely correlated with childhood asthma in the north of China. This study provides a potential new biomarker of childhood asthma and lays the basis for further clarification of the pathogenesis underlying asthma.


Assuntos
Asma/metabolismo , Canais de Cátion TRPV/metabolismo , Alérgenos/imunologia , Asma/sangue , Asma/genética , Asma/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/sangue , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Modelos Logísticos , Masculino , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/sangue , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/imunologia , População Urbana
20.
Ecol Evol ; 13(1): e9685, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36644704

RESUMO

Biomass dynamics capture information on population dynamics and ecosystem-level processes (e.g., changes in production over time). Understanding how rising temperatures associated with global climate change influence biomass dynamics is thus a pressing issue in ecology. The total biomass of a species depends on its density and its average mass. Consequently, disentangling how biomass dynamics responds to increasingly warm and variable temperatures ultimately depends on understanding how temperature influences both density and mass dynamics. Here, we address this issue by keeping track of experimental microbial populations growing to carrying capacity for 15 days at two different temperatures, and in the presence and absence of temperature variability. We develop a simple mathematical expression to partition the contribution of changes in density and mass to changes in biomass and assess how temperature responses in either one influence biomass shifts. Moreover, we use time-series analysis (Convergent Cross Mapping) to address how temperature and temperature variability influence reciprocal effects of density on mass and vice versa. We show that temperature influences biomass through its effects on density and mass dynamics, which have opposite effects on biomass and can offset each other. We also show that temperature variability influences biomass, but that effect is independent of any effects on density or mass dynamics. Last, we show that reciprocal effects of density and mass shift significantly across temperature regimes, suggesting that rapid and environment-dependent eco-phenotypic dynamics underlie biomass responses. Overall, our results connect temperature effects on population and phenotypic dynamics to explain how biomass responds to temperature regimes, thus shedding light on processes at play in cosmopolitan and abundant microbes as the world experiences increasingly warm and variable temperatures.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa