Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 310
Filtrar
1.
Mol Cell ; 75(4): 791-806.e8, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31303470

RESUMO

YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2/ERα target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ERα cofactors in regulating cancer growth, highlighting the potential of YAP/TEAD as possible actionable drug targets for ERα+ breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Elementos Facilitadores Genéticos , Estrogênios/farmacologia , Proteínas Musculares/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Células MCF-7 , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Nus , Proteínas Musculares/genética , Proteínas de Neoplasias/genética , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
2.
EMBO Rep ; 24(5): e55903, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36975049

RESUMO

In the arthropod gut, commensal microbiota maintain the immune deficiency (Imd)/Relish pathway for expression of antimicrobial peptides, whereas pathogenic bacteria induce dual oxidase 2 (Duox2) for production of extracellular microbicidal reactive oxygen species (ROS). The Imd/Relish pathway and the Duox2/ROS system are regarded as independent systems. Here, we report that these two systems are bridged by the tumor necrosis factor (TNF) ortholog PcEiger in the red swamp crayfish Procambarus clarkii. PcEiger expression is induced by commensal bacteria or the Imd/Relish pathway. PcEiger knockdown alters bacterial abundance and community composition due to variations in the oxidative status of the intestine. PcEiger induces Duox2 expression and ROS production by regulating the activity of the transcription factor Atf2. Moreover, PcEiger mediates regulation of the Duox2/ROS system by commensal bacteria and the Imd/Relish pathway. Our findings suggest that the Imd/Relish pathway regulates the Duox2/ROS system via PcEiger in P. clarkii, and they provide insights into the crosstalk between these two important mechanisms for arthropod intestinal immunity.


Assuntos
Astacoidea , Fatores de Transcrição , Animais , Astacoidea/metabolismo , Astacoidea/microbiologia , Espécies Reativas de Oxigênio , Oxidases Duais/genética , Fatores de Transcrição/metabolismo , Intestinos , Imunidade Inata
3.
BMC Genomics ; 25(1): 354, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594645

RESUMO

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.


Assuntos
Actinidia , Proteínas de Homeodomínio , Proteínas de Homeodomínio/genética , Genoma de Planta , Filogenia , Actinidia/genética , Zíper de Leucina/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Perfilação da Expressão Gênica
4.
Anal Chem ; 96(19): 7550-7557, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38706132

RESUMO

Developing precise tumor cell-specific mitochondrial ferroptosis-related inhibition miRNA imaging methods holds enormous potential for anticancer drug screening and cancer treatment. Nevertheless, traditional amplification methods still tolerated the limited tumor specificity because of the "off-tumor" signal leakage resulting from their "always-active" sensing mode. To overcome this limitation, we herein developed a dual (exogenous 808 nm NIR light and endogenous APE1) activated nanoladder for precise imaging of mitochondrial ferroptosis-related miRNA with tumor cell specificity and improved imaging resolution. Exogenous NIR light-activation can regulate the ferroptosis-related inhibition miRNA imaging signals within mitochondria, and endogenous enzyme-activation can confine signals to tumor cells. Based on this dual activation design, off-tumor signals were greatly reduced and tumor-to-background contrast was enhanced with an improved tumor/normal discrimination ratio, realizing tumor cell-specific precise imaging of mitochondrial ferroptosis-related inhibition miRNA.


Assuntos
Ferroptose , MicroRNAs , Mitocôndrias , Ferroptose/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , MicroRNAs/análise , Mitocôndrias/metabolismo , Animais , Camundongos , Imagem Óptica , Linhagem Celular Tumoral , Raios Infravermelhos , Nanopartículas/química
5.
Anal Chem ; 96(23): 9379-9389, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38805056

RESUMO

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Animais , Fatores de Tempo , Análise de Dados
6.
BMC Plant Biol ; 24(1): 473, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38811869

RESUMO

BACKGROUND: Carbon nano sol (CNS) can markedly affect the plant growth and development. However, few systematic analyses have been conducted on the underlying regulatory mechanisms in plants, including tobacco (Nicotiana tabacum L.). RESULTS: Integrated analyses of phenome, ionome, transcriptome, and metabolome were performed in this study to elucidate the physiological and molecular mechanisms underlying the CNS-promoting growth of tobacco plants. We found that 0.3% CNS, facilitating the shoot and root growth of tobacco plants, significantly increased shoot potassium concentrations. Antioxidant, metabolite, and phytohormone profiles showed that 0.3% CNS obviously reduced reactive oxygen species production and increased antioxidant enzyme activity and auxin accumulation. Comparative transcriptomics revealed that the GO and KEGG terms involving responses to oxidative stress, DNA binding, and photosynthesis were highly enriched in response to exogenous CNS application. Differential expression profiling showed that NtNPF7.3/NtNRT1.5, potentially involved in potassium/auxin transport, was significantly upregulated under the 0.3% CNS treatment. High-resolution metabolic fingerprints showed that 141 and 163 metabolites, some of which were proposed as growth regulators, were differentially accumulated in the roots and shoots under the 0.3% CNS treatment, respectively. CONCLUSIONS: Taken together, this study revealed the physiological and molecular mechanism underlying CNS-mediated growth promotion in tobacco plants, and these findings provide potential support for improving plant growth through the use of CNS.


Assuntos
Carbono , Metabolômica , Nicotiana , Reguladores de Crescimento de Plantas , Transcriptoma , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crescimento & desenvolvimento , Carbono/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , Metaboloma , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/genética
7.
PLoS Pathog ; 18(11): e1010967, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36417479

RESUMO

Small antibacterial effectors, including lysozymes, lectins, and antimicrobial peptides, are key regulators of intestinal immunity. However, whether there is coordination among them during regulation is an interesting, but largely unknown, issue. In the present study, we revealed that small effectors synergistically regulate peptidoglycan-derived intestinal immunity in the kuruma shrimp, Marsupenaeus japonicus. A C-type lysozyme (LysC) was screened as a responsive factor for the intestine-bacteria interaction. LysC functions to restrict intestinal bacteria, mainly by cleaving Photobacterium damselae peptidoglycan to generate muropeptides which are powerful stimulators that induce anti-lipopolysaccharides factor B1 (AlfB1), an effective bactericidal peptide. The muropeptides also induce a C-type lectin (Ctl24), which recognizes peptidoglycan and coats bacteria. By counteracting LysC-mediated muropeptide release and AlfB1's bactericidal activity, Ctl24 prevents the continuous elimination of intestinal bacteria. Therefore, this study demonstrates a mechanism by which small immune effectors coordinate to achieve intestinal homeostasis, and provides new insights into peptidoglycan-derived intestinal immunity in invertebrates.


Assuntos
Penaeidae , Peptidoglicano , Animais , Parede Celular , Intestinos , Lectinas Tipo C
8.
J Med Virol ; 96(2): e29402, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38380744

RESUMO

Few real-world analyses of the ability of vaccines to protect against severe COVID-19 have been published. In this real-world study, we compared the prevalence of severe or critical COVID-19 between patients at our hospital who were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or who had been vaccinated partial, full, or booster course with the CoronaVac, containing inactivated virus propagated in Vero cells. Data from electronic health records were retrospectively analyzed for 4090 inpatients with COVID-19 who were treated at West China Hospital, Chengdu between December 6, 2022 and February 14, 2023. Clinicodemographic characteristics and COVID-19 severity were compared among patients who had been vaccinated 0, 1, 2 or more times with inactivated vaccine CoronaVac. To evaluate vaccine effectiveness over time, we plotted Kaplan-Meier curves with the percentage of patients with the outcome of severe or critical COVID-19 from the time of their last vaccine dose according to vaccination status. Ordinal logistic regression was used to assess associations between vaccination status and COVID-19 severity. Cox regression was used to identify risk factors for severe or critical COVID-19. Among the 4090 patients, 171 had been vaccinated partial and 423 twice with the full CoronaVac regimens, while 905 had been vaccinated three times (boosted). The prevalence of severe or critical COVID-19 among patients was 11 percentage points lower among those vaccinated (40%) at least twice than among those unvaccinated (51%) (p<0.001), while it was 10% points lower among those who had received a booster (41%) than among those unvaccinated (51%) (p<0.001). Protection against severe or critical COVID-19 due to vaccination was significantly weakened by being older than 65 years, being male, or having diabetes, chronic heart disease, autoimmune disease, or chronic lung disease. Completing a full course of immunization with inactivated vaccine CoronaVac against SARS-CoV-2 can reduce the risk of severe or critical COVID-19 due to the Omicron BA.5 subvariant.


Assuntos
COVID-19 , Chlorocebus aethiops , Animais , Humanos , Masculino , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos Retrospectivos , Células Vero , China/epidemiologia , Vacinas de Produtos Inativados
9.
BMC Cancer ; 24(1): 95, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233827

RESUMO

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Sarcopenia/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Eritrócitos/patologia , Curva ROC , Prognóstico
10.
Clin Exp Rheumatol ; 42(3): 736-745, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37877411

RESUMO

OBJECTIVES: The deletion of chondrocyte autophagy seems to play a key role in the pathogenesis of osteoarthritis (OA). Patients with OA often have vitamin D (VD) deficiency, and VD supplementation can improve pain and alleviate the progression of joint structures in patients. In this study, we aimed to investigate whether VD could enhance autophagy by activating the adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signalling pathway and protect against OA. METHODS: In this study, the levels of target proteins and genes were examined by western blot and qRT-PCR. Apoptotic cells were detected using TUNEL staining. Characteristics of autophagy were observed by LysoTracker red staining, mRFP-GFP-LC3 adenovirus transfection, and transmission electron microscopy. siRNA-mediated AMPK and mTOR knockdown were used to investigate the role of the AMPK/ mTOR signalling pathway in VD-induced autophagy. Haematoxylin and eosin and safranin-O/fast green staining were used detect cartilage alterations. RESULTS: We suggested that VD significantly reduced chondrocyte death and alleviated extracellular matrix degradation. Further studies showed that VD promoted the expression of the autophagy-related protein LC3II through the AMPK/mTOR signalling pathway in chondrocytes, activated lysosome activity, promoted the formation of autophagy-associated lysosomes, which played a crucial role in the degradation of intracellular organelles and maintained homeostasis. The anti-apoptotic effect of VD on chondrocytes was associated with the activation of autophagy. The group of AMPK-normal and mTOR-knockdown in the presence of VD inhibited chondrocyte apoptosis by promoting autophagy. CONCLUSIONS: This study highlights that VD can activate chondrocyte autophagy through the AMPK/mTOR signalling pathway.


Assuntos
Condrócitos , Osteoartrite , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Vitamina D/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia , Autofagia , Osteoartrite/metabolismo , Apoptose
11.
Phys Chem Chem Phys ; 26(11): 9074, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38439689

RESUMO

Correction for 'Ionic migration induced loss analysis of perovskite solar cells: a poling study' by Xue Zheng et al., Phys. Chem. Chem. Phys., 2022, 24, 7805-7814, https://doi.org/10.1039/D1CP05450C.

12.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34725149

RESUMO

The Toba volcanic system in Indonesia has produced two of the largest eruptions (>2,000 km3 dense-rock equivalent [DRE] each) on Earth since the Quaternary. U-Pb crystallization ages of zircon span a period of ∼600 ky before each eruptive event, and in the run-up to each eruption, the mean and variance of the zircons' U content decrease. To quantify the process of accumulation of eruptible magma underneath the Toba caldera, we integrated these observations with thermal and geochemical modeling. We show that caldera-forming eruptions at Toba are the result of progressive thermal maturation of the upper crustal magma reservoir, which grows and chemically homogenizes, by sustained magma influx at average volumetric rates between 0.008 and 0.01 km3/y over the past 2.2 My. Protracted thermal pulses related to magma-recharge events prime the system for eruption without necessarily requiring an increased magma-recharge rate before the two supereruptions. If the rate of magma input was maintained since the last supereruption of Toba at 75 ka, eruptible magma is currently accumulating at a minimum rate of ∼4.2 km3 per millennium, and the current estimate of the total volume of potentially eruptible magma available today is a minimum of ∼315 km3 Our approach to evaluate magma flux and the rate of eruptible magma accumulation is applicable to other volcanic systems capable of producing supereruptions and thereby could help in assessing the potential of active volcanic systems to feed supereruptions.

13.
Ecotoxicol Environ Saf ; 279: 116491, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805832

RESUMO

Transplant treatment with chlorantraniliprole (CAP) is a proactive approach to protect transplanted plants from pests during early establishment and has been comprehensively applied in tobacco fields in Guangdong Province, China. However, it is not known whether the high dose of CAP in transplant treatments has lethal or sublethal effects on the generalist predator Rhynocoris fuscipes Fabricius (Hemiptera: Reduviidae). To address this concern, the mortalities of R. fuscipes were assessed when 2nd instar larvae of R. fuscipes were in direct contact with or consuming CAP and when their eggs were exposed to CAP. Furthermore, 2nd instar nymphs R. fuscipes were long-term exposed to CAP until they reached adulthood, and their life table parameters were determined. After exposure to CAP, the activity of detoxification enzymes (P450, CaeE and GST) and the functional respond of R. fuscipes to their preys Agrotis ipsilon larvae were determined. In this study, CAP at all concentrations did not significantly increase the mortality of 2nd instar of R. fuscipes nymphs in comparison with the control. The detoxification enzyme (P450, CarE and GST) activities and the number of A. ipsilon larvae consumed by R. fuscipes in the transplant treatment were not affected by CAP after 3-d or long-term exposure. These results indicated that CAP was harmless to R. fuscipes according to IOBC protocols. However, during the treatment of 2nd instar nymphs with a label rate of 15 g AI/ha and a 5× label rate of 75 g AI/ha, CAP significantly prolonged the pre-adult and pre-oviposition periods, and treated adults had lower oviposition. Attention should be given to the time interval between transplant treatment and the release of this biocontrol agent into the field to minimize the impact of CAP on the predator R. fuscipes.


Assuntos
Fertilidade , Inseticidas , Larva , Ninfa , Comportamento Predatório , ortoaminobenzoatos , Animais , ortoaminobenzoatos/toxicidade , Larva/efeitos dos fármacos , Inseticidas/toxicidade , Ninfa/efeitos dos fármacos , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Fertilidade/efeitos dos fármacos , Comportamento Predatório/efeitos dos fármacos , Hemípteros/efeitos dos fármacos , Hemípteros/fisiologia , China , Feminino , Heterópteros/efeitos dos fármacos , Heterópteros/fisiologia , Cadeia Alimentar
14.
Int J Food Sci Nutr ; 75(1): 81-91, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37933616

RESUMO

This study aimed to prospectively explore the relationship between fruit and vegetable intake (FVI) and type 2 diabetes (T2D) risk amongst 13,175 Chinese adults. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of T2D events in relation to FVI. Results showed that the highest quintile of FVI was inversely associated with T2D risk in men (HR = 0.72, 95% CI: 0.50, 0.98) and women (HR = 0.74, 95% CI: 0.55, 0.97), whereas no such associations were observed between total vegetable intake and T2D in either men (HR = 0.92, 95% CI: 0.65, 1.26) or women (HR = 1.02, 95% CI: 0.77, 1.38). In addition, greater fruit intake was inversely associated with T2D risk in men (HR = 0.42, 95% CI: 0.28, 0.63) and women (HR = 0.64, 95% CI: 0.45, 0.90). Overall, FVI and total fruit intake were inversely associated with T2D risk amongst Chinese adults.


Assuntos
Diabetes Mellitus Tipo 2 , Masculino , Adulto , Humanos , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Verduras , Fatores de Risco , Frutas , Inquéritos Nutricionais , China/epidemiologia
15.
J Environ Manage ; 354: 120267, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38408392

RESUMO

Waste threatens human health and the environment. How can we persuade people to participate in waste separation? In order to address this challenge, the present experimental study (N = 280) investigated the effects of perceived importance (high, medium, low) and language intensity (assertive, non-assertive) on people's intention to separate waste based on the social influence theory and the value-identity-personal norm model. The results showed that high perceived importance and assertive language were positively and significantly associated with waste separation intention. Furthermore, the mediating analysis revealed that environmental self-identity and personal norm were serial mediators in the relationship between perceived importance and waste separation intention. Therefore, strengthening perceived importance and enhancing internalization processes (environmental self-identity and personal norm) contribute to promoting waste separation intention. The findings of this study provide both theoretical and practical contributions to promote waste separation.


Assuntos
Intenção , Idioma , Humanos , Inquéritos e Questionários
16.
Immunology ; 168(4): 580-596, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36221236

RESUMO

Hypoxia-induced pulmonary hypertension (HPH) is a progressive and lethal disease characterized by the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) and obstructive vascular remodelling. Previous research demonstrated that Breg cells were involved in the pathogenesis of pulmonary hypertension. This work aimed to evaluate the regulatory function of Breg cells in HPH. HPH mice model were established and induced by exposing to chronic hypoxia for 21 days. Mice with HPH were treated with anti-CD22 or adoptive transferred of Breg cells. The coculture systems of Breg cells with CD4+ T cells and Breg cells with PASMCs in vitro were constructed. Lung pathology was evaluated by HE staining and immunofluorescence staining. The frequencies of Breg cells, Tfh cells and Tfr cells were analysed by flow cytometry. Serum IL-21 and IL-10 levels were determined by ELISA. Protein levels of Blimp-1, Bcl-6 and CTLA-4 were determined by western blot and RT-PCR. Proliferation rate of PASMCs was measured by EdU. Compared to the control group, mean PAP, RV/(LV + S) ratio, WA% and WT% were significantly increased in the model group. Anti-CD22 exacerbated abnormal hemodynamics, pulmonary vascular remodelling and right ventricle hypertrophy in HPH, which ameliorated by adoptive transfer of Breg cells into HPH mice. The proportion of Breg cells on day 7 induced by chronic hypoxia was significantly higher than control group, which significantly decreased on day 14 and day 21. The percentage of Tfh cells was significantly increased, while percentage of Tfr cells was significantly decreased in HPH than those of control group. Anti-CD22 treatment increased the percentage of Tfh cells and decreased the percentage of Tfr cells in HPH mice. However, Breg cells restrained the Tfh cells differentiation and expanded Tfr cells differentiation in vivo and in vitro. Additionally, Breg cells inhibited the proliferation of PASMCs under hypoxic condition in vitro. Collectively, these findings suggested that Breg cells may be a new therapeutic target for modulating the Tfh/Tfr immune balance in HPH.


Assuntos
Linfócitos B Reguladores , Hipertensão Pulmonar , Ratos , Camundongos , Animais , Hipertensão Pulmonar/etiologia , Linfócitos B Reguladores/metabolismo , Ratos Sprague-Dawley , Células T Auxiliares Foliculares/metabolismo , Remodelação Vascular/fisiologia , Pulmão/patologia , Hipóxia/complicações , Hipóxia/metabolismo , Proliferação de Células
17.
Cancer Sci ; 114(3): 837-854, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36382580

RESUMO

N6-methyladenosine (m6A) is a highly abundant RNA modification in eukaryotic cells. Methyltransferase-like 3 (METTL3), a major protein in the m6A methyltransferase complex, plays important roles in many malignancies, but its role in cervical cancer metastasis remains uncertain. Here, we found that METTL3 was significantly upregulated in cervical cancer tissue, and its upregulation was associated with a poor prognosis in cervical cancer patients. Knockdown of METTL3 significantly reduced cervical cancer cell migration and invasion. Conversely, METTL3 overexpression markedly promoted cervical cancer cell metastasis in vitro and in vivo. Furthermore, METTL3 mediated the m6A modification of cathepsin L (CTSL) mRNA at the 5'-UTR, and the m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) bound to the m6A sites and enhanced CTSL mRNA stability. Our results indicated that METTL3 enhanced CTSL mRNA stability through an m6A-IGF2BP2-dependent mechanism, thereby promoting cervical cancer cell metastasis. These findings provide insights into a novel m6A modification pattern involved in cervical cancer development.


Assuntos
Metiltransferases , Neoplasias do Colo do Útero , Feminino , Humanos , Metiltransferases/genética , Catepsina L/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo
18.
Funct Integr Genomics ; 23(3): 272, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37568053

RESUMO

Plants release a mixture of volatile compounds when subjects to environmental stress, allowing them to transmit information to neighboring plants. Here, we find that Nicotiana benthamiana plants infected with tobacco mosaic virus (TMV) induces defense responses in neighboring congeners. Analytical screening of volatiles from N. benthamiana at 7 days post inoculation (dpi) using an optimized SPME-GC-MS method showed that TMV triggers the release of several volatiles, such as (E)-2-octenal, 6-methyl-5-hepten-2-one, and geranylacetone. Exposure to (E)-2-octenal enhances the resistance of N. benthamiana plants to TMV and triggers the immune system with upregulation of pathogenesis-related genes, such as NbPR1a, NbPR1b, NbPR2, and NbNPR1, which are related to TMV resistance. Furthermore, (E)-2-octenal upregulates jasmonic acid (JA) that levels up to 400-fold in recipient N. benthamiana plants and significantly affects the expression pattern of key genes in the JA/ET signaling pathway, such as NbMYC2, NbERF1, and NbPDF1.2, while the salicylic acid (SA) level is not significantly affected. Our results show for the first time that the volatile (E)-2-octenal primes the JA/ET pathway and then activates immune responses, ultimately leading to enhanced TMV resistance in adjacent N. benthamiana plants. These findings provide new insights into the role of airborne compounds in virus-induced interplant interactions.


Assuntos
Nicotiana , Vírus do Mosaico do Tabaco , Humanos , Nicotiana/genética , Nicotiana/metabolismo , Vírus do Mosaico do Tabaco/metabolismo , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Doenças das Plantas/genética
19.
Anal Chem ; 95(2): 638-649, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36599407

RESUMO

Data-dependent acquisition (DDA) mode in ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) can provide massive amounts of MS1 and MS/MS information of compounds in untargeted metabolomics and can thus facilitate compound identification greatly. In this work, we developed a new platform called AntDAS-DDA for the automatic processing of UHPLC-HRMS data sets acquired under the DDA mode. Several algorithms, including extracted ion chromatogram extraction, feature extraction, MS/MS spectrum construction, fragment ion identification, and MS1 spectrum construction, were developed within the platform. The performance of AntDAS-DDA was investigated comprehensively with a mixture of standard and complex plant data sets. Results suggested that features in complex sample matrices can be extracted effectively, and the constructed MS1 and MS/MS spectra can benefit in compound identification greatly. The efficiency of compound identification can be improved by about 20%. AntDAS-DDA can take full advantage of MS/MS information in multiple sample analyses and provide more MS/MS spectra than single sample analysis. A comparison with advanced data analysis tools indicated that AntDAS-DDA may be used as an alternative for routine UHPLC-HRMS-based untargeted metabolomics. AntDAS-DDA is freely available at http://www.pmdb.org.cn/antdasdda.


Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Íons , Análise de Dados
20.
BMC Plant Biol ; 23(1): 646, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097981

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to play important roles in the response of plants to various abiotic stresses, including drought, heat and salt stress. However, the identification and characterization of genome-wide salt-responsive lncRNAs in tobacco (Nicotiana tabacum L.) have been limited. Therefore, this study aimed to identify tobacco lncRNAs in roots and leaves in response to different durations of salt stress treatment. RESULTS: A total of 5,831 lncRNAs were discovered, with 2,428 classified as differentially expressed lncRNAs (DElncRNAs) in response to salt stress. Among these, only 214 DElncRNAs were shared between the 2,147 DElncRNAs in roots and the 495 DElncRNAs in leaves. KEGG pathway enrichment analysis revealed that these DElncRNAs were primarily associated with pathways involved in starch and sucrose metabolism in roots and cysteine and methionine metabolism pathway in leaves. Furthermore, weighted gene co-expression network analysis (WGCNA) identified 15 co-expression modules, with four modules strongly linked to salt stress across different treatment durations (MEsalmon, MElightgreen, MEgreenyellow and MEdarkred). Additionally, an lncRNA-miRNA-mRNA network was constructed, incorporating several known salt-associated miRNAs such as miR156, miR169 and miR396. CONCLUSIONS: This study enhances our understanding of the role of lncRNAs in the response of tobacco to salt stress. It provides valuable information on co-expression networks of lncRNA and mRNAs, as well as networks of lncRNAs-miRNAs-mRNAs. These findings identify important candidate lncRNAs that warrant further investigation in the study of plant-environment interactions.


Assuntos
MicroRNAs , RNA Longo não Codificante , Nicotiana/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Estresse Salino , RNA Mensageiro/genética , Redes Reguladoras de Genes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA