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1.
J Exp Bot ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457346

RESUMO

The legume-rhizobium symbiosis represents as a unique model within the realm of plant-microbe interactions. Unlike typical cases of pathogenic invasion, the infection of rhizobia and their residence within symbiotic cells do not elicit a noticeable immune response in plants. Nevertheless, there is still much to uncover regarding the mechanisms through which plant immunity influences rhizobia symbiosis. In this study, we identify an important player in this intricate interplay: the Lotus japonicus PRP1, which serves as a positive regulator of plant immunity but also exhibits the capacity to decrease rhizobial colonization and nitrogen fixation within nodules. The PRP1 gene encodes an uncharacterized protein and is named as Pathogenesis-Related Protein1, owing to its ortholog in Arabidopsis thaliana, a pathogenesis-related family protein (At1g78780). The PRP1 gene displays high expression levels in nodules compared to other tissues. We observed an increase in rhizobium infection in the L. japonicus prp1 mutants, while PRP1-overexpressing plants exhibited a reduction in rhizobium infection compared to control plants. Intriguingly, L. japonicus prp1 mutants produced nodules with a pinker color compared to wild-type controls, accompanied by elevated levels of leghemoglobin and an increased proportion of infected cells within the prp1 nodules. The Nodule Inception (NIN) could directly bind to the PRP1 promoter, activating PRP1 gene expression. Furthermore, we found that PRP1 is a positive mediator of innate immunity in plants. In summary, our study provides clear evidence of the intricate relationship between plant immunity and symbiosis. PRP1, acting as a positive regulator of plant immunity, simultaneously exerts suppressive effects on rhizobial infection and colonization within nodules.

2.
Adv Clin Exp Med ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353506

RESUMO

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

4.
Sci Rep ; 13(1): 18489, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37898705

RESUMO

This study aimed to screen for small nuclear RNAs (snRNAs) associated with the prognosis of acute myeloid leukemia (AML) by using The Cancer Genome Atlas (TCGA) whole-transcriptome sequencing dataset. A total of 130 AML patients from TCGA cohort with complete prognostic information and transcriptome data were enrolled in the current study. Comprehensive survival and functional enrichment analyses were performed to explore the prognostic value and potential biological functions of prognostic snRNAs in AML patients. In the current study, we screened 72 snRNAs that were notably associated with the clinical outcome of AML and developed an expression signature consist of ten snRNAs, that can be accurately applied to assess the overall survival of AML patients. Functional mechanism analysis revealed that this expression signature may be strongly linked to some classical tumor-associated pathways, such as Notch and Wnt pathways, as well as being closely related to B and T cell receptor pathways. Furthermore, we screened six compounds (chicago sky blue 6 B, 5230742, clorsulon, nefopam, nicardipine, and streptomycin) that may serve as targeted therapeutic drugs for AML using connectivity maps. Tumor immunoassays indicated significant differences in the immune microenvironment of the bone marrow tissue between high-risk and low-risk AML patients. Immune infiltration analysis also revealed significant differences in the abundance of multiple immune cells in the bone marrow of the two groups of AML patients groups. In conclusion, our results revealed a novel prognostic expression signature of AML consisting of ten snRNAs, and we conducted a preliminary exploration of its potential biological functions and tumor immunity.


Assuntos
Leucemia Mieloide Aguda , Humanos , Prognóstico , Biomarcadores , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Osso e Ossos , Chicago , Microambiente Tumoral
6.
Heliyon ; 9(8): e18760, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560639

RESUMO

The gas-liquid membrane contactor (GLMC) is a new and promising kind of gas separation technique, but still exhibits limitations, especially in membrane performance. In order to solve the above problems, we fabricated and characterized novel OH/SiO2/PES composite membranes using gas phase hydrolysis and graft coating methods, respectively. In the preparation process, whether to use alkali to pretreat the membrane was used as an evaluation index. The CO2/CH4 separation performance was tested using the modified OH/SiO2/PES hollow fiber membrane as the membrane contactor in GLMC. In the experiment, we conducted a single factor experiment with diethanolamine (DEA) as the adsorbent to analyze the effect of the flow rate and concentration of DEA on the separation of CO2/CH4. The collected gas had a CH4 content of 99.92% and a CO2 flux of 10.1059 × 10-3 mol m-2 s-1 while DEA at a concentration of 1 mol/L was flowing at a rate of 16 L/h. The highest separation factor occurred at this moment, which was 833.67. Overall, the CO2/CH4 separation performance in GLMC was enhanced with the use of the fluorinated OH/SiO2/PES composite membrane.

7.
Med Sci Monit ; 29: e938715, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37276190

RESUMO

BACKGROUND Despite an increasing number of published articles on intravoxel incoherent motion (IVIM) in the past decade, almost all have focused on the technique and clinical applications of IVIM, with little attention to the collective knowledge and scientific analysis of this field. The aim of the present study was to construct a knowledge framework and to explore hotspots and emerging trends concerning use of IVIM in humans. MATERIAL AND METHODS The articles concerning IVIM MRI published from 1988 to 2021 were retrieved from the Science Citation Index Expended of the Web of Science Core Collection on 17, August 2021. The downloaded data were imported into Excel 2016 and CiteSpace V for scientometric analysis. RESULTS A total of 921 articles were included in this study and most of them were published since 2012. China (n=392) was the most productive country and the Philips Healthcare (n=46) was the most productive institution. Christian Federau had the largest number of publications (n=18). An article by Andreou A et al (2013) was the most important reference with the most co-citations (n=100) and centrality (0.06). The 5 hotspots in IVIM were perfusion, diffusion-weighted imaging, intravoxel incoherent motion, apparent diffusion coefficient, and magnetic resonance imaging. The 2 frontier topics were "brain perfusion" and "accuracy". According to the clustering of co-citation analysis, "liver", "diffusion weighting", "pancreas", and "brain" were the main research directions. CONCLUSIONS Scientometric analysis of IVIM literature with CiteSpace software can provide researchers with valuable information about knowledge framework, hotspots, and emerging trends concerning IVIM in humans.


Assuntos
Abdome , Imagem de Difusão por Ressonância Magnética , Humanos , Movimento (Física) , Imagem de Difusão por Ressonância Magnética/métodos , Pâncreas , Perfusão
8.
Nat Commun ; 14(1): 1884, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019890

RESUMO

Boron neutron capture therapy (BNCT) was clinically approved in 2020 and exhibits remarkable tumour rejection in preclinical and clinical studies. It is binary radiotherapy that may selectively deposit two deadly high-energy particles (4He and 7Li) within a cancer cell. As a radiotherapy induced by localized nuclear reaction, few studies have reported its abscopal anti-tumour effect, which has limited its further clinical applications. Here, we engineer a neutron-activated boron capsule that synergizes BNCT and controlled immune adjuvants release to provoke a potent anti-tumour immune response. This study demonstrates that boron neutron capture nuclear reaction forms considerable defects in boron capsule that augments the drug release. The following single-cell sequencing unveils the fact and mechanism that BNCT heats anti-tumour immunity. In female mice tumour models, BNCT and the controlled drug release triggered by localized nuclear reaction causes nearly complete regression of both primary and distant tumour grafts.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias , Masculino , Feminino , Animais , Camundongos , Boro/uso terapêutico , Neoplasias/tratamento farmacológico , Imunoterapia , Nêutrons , Compostos de Boro/uso terapêutico
9.
Cancer ; 129(13): 2013-2022, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36951498

RESUMO

BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Masculino , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Neoplasia Residual/diagnóstico , Síndromes Mielodisplásicas/terapia , Fatores de Risco
10.
Behav Sci (Basel) ; 13(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36829324

RESUMO

The current problems of the low digital upgrading of rural e-commerce, single marketing method and high homogeneous competition will seriously hinder the development of rural e-commerce and rural revitalization. Therefore, finding how to guide the digital upgrading of rural e-commerce will be a key step in achieving rural revitalization and common prosperity. Based on 1387 Zhejiang rural e-commerce digital upgrading questionnaires, this paper analyzes willingness regarding rural e-commerce digital upgrading and its influencing factors using planned behavior theory and structural equation modeling. The findings show that (1) behavioral attitudes are the main influencing factors of upgrading willingness, and subjective norms are secondary influencing factors; (2) in terms of the behavioral attitudes of rural e-merchants, the greater the proportion of their online sales or the higher the proportion of online income, the better behavioral attitudes formed on this basis can promote the willingness to digitally upgrade rural e-merchants; (3) in terms of subjective norms, when rural e-merchant subjects perceive that the increased local participation in e-merchant association is too large or online income tends to saturate the total income, the more subjective norms can influence their willingness to digitally upgrade.

12.
Mol Plant Microbe Interact ; 36(5): 273-282, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36572969

RESUMO

Powdery mildew severely affects several important crops and cash plants. Disruption of mildew resistance locus O (MLO) genes elevates resistance against powdery mildew in several plants. However, whether rubber tree (Heveae brasiliensis) MLO proteins are linked to susceptibility remains unknown, owing to technical limitations in the genetic manipulation of this woody plant. A previous study showed that the H. brasiliensis MLO-like protein HbMLO12 demonstrates high amino acid sequence similarity with the known Arabidopsis MLO protein AtMLO12. In this study, we investigated whether HbMLO12 regulates susceptibility to powdery mildew. H. brasiliensis leaves take up exogenously synthesized double-stranded RNAs (dsRNAs), and foliar application of dsRNA homologous to HbMLO12 gene specifically induces HbMLO12 silencing in H. brasiliensis leaf tissues. Notably, HbMLO12 silencing inhibited fungal infection and elevated the immune response during interaction with the rubber tree powdery mildew fungus. Furthermore, the heterologous expression of HbMLO12 suppressed bacterial flg22- and fungal chitin-induced immune responses and enhanced bacterial infection in Arabidopsis. Our study provides evidence that HbMLO12 contributes to susceptibility to powdery mildew. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ascomicetos , Hevea , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hevea/genética , Hevea/metabolismo , Ascomicetos/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Doenças das Plantas/microbiologia , Resistência à Doença/genética
13.
Front Endocrinol (Lausanne) ; 14: 1324993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38303976

RESUMO

Reproductive system diseases pose prominent threats to human physical and mental well-being. Besides being influenced by genetic material regulation and changes in lifestyle, the occurrence of these diseases is closely connected to exposure to harmful substances in the environment. Endocrine disrupting chemicals (EDCs), characterized by hormone-like effects, have a wide range of influences on the reproductive system. EDCs are ubiquitous in the natural environment and are present in a wide range of industrial and everyday products. Currently, thousands of chemicals have been reported to exhibit endocrine effects, and this number is likely to increase as the testing for potential EDCs has not been consistently required, and obtaining data has been limited, partly due to the long latency of many diseases. The ability to avoid exposure to EDCs, especially those of artificially synthesized origin, is increasingly challenging. While EDCs can be divided into persistent and non-persistent depending on their degree of degradation, due to the recent uptick in research studies in this area, we have chosen to focus on the research pertaining to the detrimental effects on reproductive health of exposure to several EDCs that are widely encountered in daily life over the past six years, specifically bisphenol A (BPA), phthalates (PAEs), polychlorinated biphenyls (PCBs), parabens, pesticides, heavy metals, and so on. By focusing on the impact of EDCs on the hypothalamic-pituitary-gonadal (HPG) axis, which leads to the occurrence and development of reproductive system diseases, this review aims to provide new insights into the molecular mechanisms of EDCs' damage to human health and to encourage further in-depth research to clarify the potentially harmful effects of EDC exposure through various other mechanisms. Ultimately, it offers a scientific basis to enhance EDCs risk management, an endeavor of significant scientific and societal importance for safeguarding reproductive health.


Assuntos
Disruptores Endócrinos , Praguicidas , Bifenilos Policlorados , Humanos , Disruptores Endócrinos/toxicidade , Bifenilos Policlorados/toxicidade , Genitália
14.
Medicine (Baltimore) ; 101(46): e31700, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401382

RESUMO

BACKGROUND: Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein. OBJECTIVES: To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs). METHODS: On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed. RESULTS: Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]). CONCLUSION: Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Osteoartrite do Joelho , Humanos , Idoso , Osteoartrite do Joelho/tratamento farmacológico , Antraquinonas/efeitos adversos , Progressão da Doença , Diarreia/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Sci Rep ; 12(1): 17432, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261598

RESUMO

An inhibited neural response to reward is typical of clinical depression and can predict an individual's overall depressive symptoms. However, the mechanism underlying this are unclear. Previous studies have found that anhedonia and inattention may mediate the relationship between reward sensitivity and depressive symptoms. Therefore, this study aimed to verify the relationship between reward sensitivity and overall depressive symptoms in a depressive tendency sample as well as to explore the mechanism underlying the ability of neural responses to reward to predict overall depressive symptoms via a mediation model. Sixty-four participants (33 with depressive tendencies and 31 without; dichotomized by BDI-II) finished simple gambling tasks while their event-related potential components (ERPs) were recorded and compared. Linear regression was conducted to verify the predictive effect of ERPs on overall depressive symptoms. A multiple mediator model was used, with anhedonia and distractibility as mediators reward sensitivity and overall depressive symptoms. The amplitude of reward positivity (ΔRewP) was greater in healthy controls compared to those with depressive tendencies (p = 0.006). Both the gain-locked ERP component (b = - 1.183, p = 0.007) and the ΔRewP (b = - 0.991, p = 0.024) could significantly negatively predict overall depressive symptoms even after controlling for all anxiety symptoms. The indirect effects of anhedonia and distractibility were significant (both confidence intervals did not contain 0) while the direct effect of reward sensitivity on depressive symptom was not significant (lower confidence interval = - 0.320, upper confidence interval = 0.065). Individuals with depressive tendencies display impaired neural responses to reward compared to healthy controls and reduced individual neural responses to reward may reflect the different biotypes of depression such as anhedonia and inattention.


Assuntos
Transtorno Depressivo Maior , Jogo de Azar , Humanos , Anedonia/fisiologia , Recompensa , Potenciais Evocados
16.
Sci Rep ; 12(1): 15316, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097275

RESUMO

The purpose was to predict the risk of acute kidney injury (AKI) within 100 days after hematopoietic stem cell transplantation (HSCT) in patients with hematologic disease by using a new predictive nomogram. Collect clinical data of patients with hematologic disease undergoing HSCT in our hospital from August 2012 to March 2018. Parameters with non-zero coefficients were selected by the Least Absolute Selection Operator (LASSO). Then these parameters were selected to build a new predictive nomogram model. Receiver operating characteristic (ROC) curve, calibration curve, C-index, and decision curve analysis (DCA) were used for the validation of the evaluation model. Finally, the nomogram was further evaluated by internal verification. According to 2012 Kidney Disease Improving Global Guidelines (KDIGO) diagnostic criteria, among 144 patients, the occurrence of AKI within 100 days after HSCT The rate was 29.2% (42/144). The C-index of the nomogram was 0.842. The C-value calculated by the internal verification was 0.809. The AUC was 0.842, and The DCA range of the predicted nomogram was from 0.01 to 0.71. This article established a high-precision nomogram for the first time for predicting the risk of AKI within 100 days after HSCT in patients with hematologic diseases. The nomogram had good clinical validity and reliability. For clinicians, it was very important to prevent AKI after HSCT.


Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Hematopoéticas , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Nomogramas , Reprodutibilidade dos Testes , Fatores de Risco
17.
Food Res Int ; 156: 111321, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35651075

RESUMO

Doushen is a traditional Chinese fermented soybean product prepared with sterilizated soybeans under open conditions. However, little is known on the bacterial community and their influence on the flavor of Doushen. In the present study, Doushen samples with and without chili pepper were collected to reveal the bacterial community and assess a correlation between bacterial community and VFCs in the two kinds of Doushen samples. We identified four phyla and 97 bacterial genera in the two kinds of Doushen samples. In addition, a total of 17 significantly different OTUs were detected by LEfSe (Line Discriminant Analysis (LDA) Effect Size). Results of Principal coordinates analysis (PCoA), unweighted pair-group method (UPGMA) and functional and phenotypes prediction showed that bacterial communities in the two kinds of Doushen were significantly different. Spearman correlation analysis showed that all the dominant genera, except Clostridium Sensu stricto 1, were significantly correlated with the characteristic VFCs. This study provides a theoretical basis for improving the flavour quality of traditional homemade Doushen.


Assuntos
Capsicum , Bactérias/genética , Capsicum/microbiologia , Clostridium
18.
Respir Res ; 23(1): 100, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459189

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous and fatal lung disease. In addition to dense fibrous tissue, abnormal angiogenesis is also an important feature of IPF. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-fibrous factor. The purpose of this experiment is to observe the effect of PEDF on bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: In vivo, pathological examination and detection of related factors were performed on pulmonary fibrosis induced by BLM in rats, and the temporal and spatial distribution of PEDF was investigated. Furthermore, lung gene delivery (PEDF-adeno-associated virus) was performed to investigate the effect of PEDF on pulmonary fibrosis. In vitro, lentiviral vectors were used to construct PEDF over-expression or knock out primary rat lung (PRL) fibroblasts. The effect of PEDF on fibroblast activation under TGF-ß1 stimulation was evaluated, and the activation of TGF-ß1/smad pathway and PPAR-γ expression (in the presence or absence of PPAR-γ inhibitors) were analyzed. RESULTS: In vivo results showed that PEDF expression decreased during the inflammatory phase and increased during the fibrotic phase. PEDF could inhibit the progression of pulmonary fibrosis in rats. In vitro results showed that PEDF could effectively inhibit TGF-ß1-stimulated fibroblast activation and reduce the production of α-SMA and collagen-I. PEDF could inhibit the TGF-ß1/smad pathway by up-regulating the activity of PPAR-γ. CONCLUSIONS: PEDF can act as an anti-fibrotic factor, inhibit fibroblast activation by upregulating PPAR-γ activity and reduce BLM-induced pulmonary fibrosis in rats.


Assuntos
Bleomicina , Fibrose Pulmonar Idiopática , Animais , Bleomicina/toxicidade , Proteínas do Olho , Fibroblastos/metabolismo , Fibrose , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural , Receptores Ativados por Proliferador de Peroxissomo/efeitos adversos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos , Serpinas , Fator de Crescimento Transformador beta1/farmacologia
19.
Bone Marrow Transplant ; 57(7): 1108-1115, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35488073

RESUMO

Our main purpose was to evaluate health-related quality of life (HRQOL) in ß-thalassemia major patients who underwent transplantation from September 2012 to November 2019. The PedsQL 4.0 scale proxy version was administered to 221 transplant patients aged 5-18 years. Their HRQOL results in the proxy-report were compared with those in the proxy-report of 429 matched healthy peers and 198 matched nontransplant patients. Compared with their healthy peers, the transplant patients exhibited worse HRQOL in the physical health domain (P < 0.001), school domain (P < 0.001) and overall scores (P = 0.006). Patients within 4 years after transplantation exhibited physical functioning (P < 0.001), school functioning (P < 0.001) and overall HRQOL damage (P = 0.001); the scores across all domains for patients more than 4 years after transplantation were not significantly different from those for the healthy controls. The transplant patients rated their HRQOL for all domains better than the nontransplant patients (P < 0.001). The HRQOL of patients after human leukocyte antigen (HLA)-matched related and HLA-matched unrelated donor transplantation were not significantly different. Chronic graft-versus-host disease and two or more comorbidities were independently negatively associated with overall HRQOL outcomes (P = 0.032 and P < 0.001, respectively). In conclusion, patients more than 4 years after transplantation achieve an HRQOL equal to that of their healthy peers.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Criança , Antígenos HLA , Humanos , Qualidade de Vida , Talassemia beta/terapia
20.
Acta Pharmacol Sin ; 43(6): 1395-1407, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34522006

RESUMO

Myocardial infarction (MI) causes disturbances in myocardial energy metabolism, ultimately leading to a poor prognosis. Cytosolic glycogen autophagy (glycophagy) and mitochondrial autophagy (mitophagy) are upregulated in MI to optimize energy metabolism but to a limited extent. Asiatic acid (AA), a pentacyclic triterpene derived from the traditional Chinese herb Centella asiatica, displays anti-inflammatory, antioxidant, and antiapoptotic activities. AA has been found to alleviate focal cerebral and liver ischemic injury by reversing mitochondrial dysfunction. In this study, we investigated whether AA exerted cardioprotective effects against MI by activating glycophagy and mitophagy to improve the energy balance. In vitro cardioprotective effects were examined in neonatal mouse cardiomyocytes subjected to oxygen-glucose deprivation for 12 h. Treatment with AA (2-50 µM) significantly increased cell viability and improved the energy metabolism evidenced by increased ATP level and phosphocreatine/ATP ratio. In vivo cardioprotective effects were studied in a mouse model of MI. Administration of AA (5-125 mg·kg-1·d-1, ig) significantly reduced infarct size and ischemic myocardial injury, and improved cardiac function. AA treatment also promoted mitophagy and relieved mitochondrial edema evidenced by increased number of mitophagosomes in ischemic myocardium in vivo and increased mitochondria-light chain 3 (LC3)-II colocalization in ODG-treated cardiomyocytes in vitro. Mitophagy activation was accompanied by activation of the AMPK signaling pathway. Knockdown of AMPK abolished AA-activated mitophagy. Furthermore, we showed that glycophagy was upregulated in OGD cardiomyocytes evidenced by increased starch binding domain protein 1 (STBD1)-GABA type A receptor-associated protein-like 1(GABARAPL1) interaction and extracellular acidification rate, whereas AA treatment further promoted glycophagy accompanied by PI3K/Akt activation. PI3K inhibitor LY294002 or Akt inhibitor GSK690693 blocked the effects of AA on glycophagy and glycolysis. Finally, simultaneous inhibition of glycophagy and mitophagy abolished the cardioprotective effects and energy regulation of AA. These results demonstrate that AA protects ischemic cardiomyocytes by modulating glycophagy- and mitophagy-based energy metabolism through the PI3K/Akt and AMPK pathways.


Assuntos
Traumatismos Cardíacos , Infarto do Miocárdio , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Metabolismo Energético , Camundongos , Mitofagia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
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