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1.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338732

RESUMO

PIN-formed (PIN) proteins-specific transcription factors that are widely distributed in plants-play a pivotal role in regulating polar auxin transport, thus influencing plant growth, development, and abiotic stress responses. Although the identification and functional validation of PIN genes have been extensively explored in various plant species, their understanding in woody plants-particularly the endangered species Phoebe bournei (Hemsl.) Yang-remains limited. P. bournei is an economically significant tree species that is endemic to southern China. For this study, we employed bioinformatics approaches to screen and identify 13 members of the PIN gene family in P. bournei. Through a phylogenetic analysis, we classified these genes into five sub-families: A, B, C, D, and E. Furthermore, we conducted a comprehensive analysis of the physicochemical properties, three-dimensional structures, conserved motifs, and gene structures of the PbPIN proteins. Our results demonstrate that all PbPIN genes consist of exons and introns, albeit with variations in their number and length, highlighting the conservation and evolutionary changes in PbPIN genes. The results of our collinearity analysis indicate that the expansion of the PbPIN gene family primarily occurred through segmental duplication. Additionally, by predicting cis-acting elements in their promoters, we inferred the potential involvement of PbPIN genes in plant hormone and abiotic stress responses. To investigate their expression patterns, we conducted a comprehensive expression profiling of PbPIN genes in different tissues. Notably, we observed differential expression levels of PbPINs across the various tissues. Moreover, we examined the expression profiles of five representative PbPIN genes under abiotic stress conditions, including heat, cold, salt, and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. In summary, this study systematically analyzes the expression patterns of PIN genes and their response to abiotic stresses in P. bournei using whole-genome data. Our findings provide novel insights and valuable information for stress tolerance regulation in P. bournei. Moreover, the study offers significant contributions towards unraveling the functional characteristics of the PIN gene family.


Assuntos
Proteínas de Plantas , Estresse Fisiológico , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas , Íntrons/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Perfilação da Expressão Gênica/métodos , Genoma de Planta
2.
Mediators Inflamm ; 2023: 5007488, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484603

RESUMO

Interstitial inflammation is an important mechanism of pathological damage in renal injury caused by hyperuricemia. Protease-activated receptor-2 (PAR2) is a class of targets that act upstream of the PI3K/AKT/NF-κB pathway and is involved in various inflammatory diseases. We induced a hyperuricemia model in rats by adenine and ethambutol gavage in an in vivo experiment. We demonstrated that PAR2 and PI3K/AKT/NF-κB pathway expression were significantly upregulated in renal tissues, with massive inflammatory cell infiltration in the renal interstitium and renal tissue injury. Treating hyperuricemic rats with AZ3451, a selective metabotropic antagonist of PAR2, we demonstrated that PAR2 antagonism inhibited the PI3K/AKT/NF-κB pathway and attenuated tubular dilation and tubulointerstitial inflammatory cell infiltration. The phospholipid metabolism profiles provided a perfect separation between the normal and hyperuricemic rats. In addition, we also found that AZ3451 can affect phospholipid metabolism. Our work suggests that PAR2 may mediate hyperuricemia-mediated renal injury by activating the PI3K/AKT/NF-κB pathway. The PAR2 antagonist AZ3451 may be a promising therapeutic strategy for hyperuricemia-induced inflammatory responses.


Assuntos
Hiperuricemia , Ratos , Animais , Hiperuricemia/tratamento farmacológico , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor PAR-2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Rim/metabolismo , Fosfolipídeos/metabolismo , Fosfolipídeos/uso terapêutico
3.
Mikrochim Acta ; 190(10): 393, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37712989

RESUMO

The great selectivity and trans-cleavage activity of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a had been coupled with high amplification efficiency of hybridization chain reaction (HCR) and magnetic-assisted enrichment, high sensitivity of electrochemiluminescence (ECL) detection to develop an ultra-sensitive biosensor for microRNA-21 (miRNA-21). The CRISPR/Cas13a was used to recognize target RNA with high specificity and performed the trans-cleavage activity. An initiation strand was generated to bind to the probe on the surface of nanomagnetic beads and then trigged HCR to produce long double-strand DNAs (dsDNAs) to realize signal amplification. Ru(phen)32+ can be inserted in the groove of the dsDNAs and acts as the ECL indicator, which can be separated through magnetic enrichment and allowed the platform to reduce the signal background. Under the optimized conditions, there is a good linear correlation between the ECL intensity and the logarithm of miRNA-21 concentration in the range 1 fM-10 nM; the limit of detection (LOD) was 0.53 fM. The proposed system was applied to detect miRNA-21 from the urine of acute kidney injury (AKI) patients with good results.


Assuntos
Líquidos Corporais , MicroRNAs , Humanos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Hibridização de Ácido Nucleico , Fenômenos Magnéticos
4.
J Anesth ; 29(3): 442-445, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25315455

RESUMO

Iatrogenic diversion of the inferior vena cava (IVC) into the left atrium (LA) is usually reported as a rare complication following large posteroinferior atrial septal defect (ASD) surgery. It may cause acute or chronic hypoxemia, and other potentially life-threatening complications such as stroke. We present a case in which the ASD patch straddled the IVC entrance diagnosed immediately by transesophageal echocardiography (TEE) during the period of patient separated from cardiopulmonary bypass, avoiding the related complications. Our report further underlines the important role of TEE to monitor and guide ASD surgical management, especially secundum ASD with inferior extension or inferior sinus venosus defects, for the early diagnosis of iatrogenic surgical errors.


Assuntos
Ecocardiografia Transesofagiana/métodos , Comunicação Interatrial/cirurgia , Erros Médicos , Veia Cava Inferior/patologia , Adulto , Ponte Cardiopulmonar/métodos , Feminino , Átrios do Coração/cirurgia , Comunicação Interatrial/diagnóstico , Humanos , Doença Iatrogênica
5.
Physiol Plant ; 150(3): 339-54, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24102457

RESUMO

Green 'Anjou' pear and its bud mutation, red 'Anjou' were compared to understand their differences in phenolic metabolism and its effect on primary metabolism. In the flesh of the two cultivars, no difference was detected in the concentration of any phenolic compound, the transcript level of MYB10 or the transcript levels or activities of key enzymes involved in anthocyanin synthesis. Compared with green 'Anjou', the shaded peel of red 'Anjou' had higher anthocyanin concentrations, higher transcript levels of MYB10 and higher activity of UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT), suggesting that MYB10 regulates UFGT to control anthocyanin synthesis in red 'Anjou' peel. In the sun-exposed peel, activities of phenylalanine ammonia lyase, dihydroflavonol reductase, flavonol synthase and anthocyanidin synthase as well as UFGT were higher in red 'Anjou' than in green 'Anjou'. The peel of red 'Anjou' had higher activities of sorbitol dehydrogenase, raffinose synthase and sucrose synthase and higher levels of raffinose, myo-inositol and starch, indicating that sorbitol metabolism, raffinose synthesis and starch synthesis were upregulated in red 'Anjou'. The flesh of red 'Anjou' had higher concentrations of glucose, but lower activities of ATP-dependent phosphofructokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase and lower dark respiration. The peel of red 'Anjou' had higher activities of glutaminase, asparagine synthetase and asparaginase, and higher concentrations of asparagine, aspartate, alanine, valine, threonine and isoleucine. The effects of anthocyanin synthesis on primary metabolism in fruit peel are discussed.


Assuntos
Mutação , Fenóis/metabolismo , Pyrus/genética , Pyrus/metabolismo , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Antocianinas/metabolismo , Frutas/genética , Frutas/metabolismo , Frutas/efeitos da radiação , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Meristema/genética , Meristema/metabolismo , Meristema/efeitos da radiação , Oxirredutases/genética , Oxirredutases/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Pigmentação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estruturas Vegetais/genética , Estruturas Vegetais/metabolismo , Estruturas Vegetais/efeitos da radiação , Pyrus/efeitos da radiação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Luz Solar
6.
Can J Anaesth ; 61(5): 446-51, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24585232

RESUMO

PURPOSE: Intravenous leiomyomatosis is a rare disorder characterized by benign smooth-muscle tumours, termed leiomyomas, which originate from uterine leiomyomas or pelvic veins. Tumours may extend into the right-sided heart chambers, termed intracardiac leiomyomatosis (ICLM), and may be potentially life-threatening due to mechanical interference with cardiac structures or pulmonary arteries. While surgical excision is the optimal therapy, incomplete retrieval of a tumour or fatal retroperitoneal hemorrhage may occur. We present a case where intraoperative transesophageal ultrasound (TEU) guided complete removal of an intracardiac leiomyoma in a single-stage surgery solely through the right atrium without vein injury. CLINICAL FEATURES: A 46-yr-old female patient presented with a two-week history of exertional dyspnea, palpitations, and syncope. Preoperative imaging modalities revealed a continuous solid mass extending from the inferior vena cava (IVC) into the right atrium, and the patient subsequently underwent open heart surgery for tumour removal and definitive diagnosis. A systematic intraoperative TEU examination performed before resection showed that the serpentine tumour was free from any attachment to the IVC and the heart. Furthermore, the diameter of the intracardiac end of the tumour was wider than that of the IVC. Given these findings, the surgeons carefully drew the cord-like tumour out of the right atrium under close TEU monitoring without vein injury. Post-extraction TEU examination showed complete removal of the tumour. Microscopic examination of the specimen confirmed the diagnosis of intravenous leiomyomatosis. CONCLUSIONS: For cases with ICLM, intraoperative TEU plays a significant role in helping to plan the surgical approach, monitor the movement of the tumour and the IVC during the extraction, and assess the completeness of tumour resection.


Assuntos
Neoplasias Cardíacas/cirurgia , Leiomiomatose/cirurgia , Ultrassonografia de Intervenção/métodos , Neoplasias Vasculares/cirurgia , Dispneia/etiologia , Feminino , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Leiomiomatose/diagnóstico , Leiomiomatose/diagnóstico por imagem , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/diagnóstico por imagem , Veia Cava Inferior
7.
Am J Med Sci ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39186977

RESUMO

BACKGROUND: Prediabetes and diabetes are common and serious public health problems, and high blood glucose can lead to serious cardiovascular complications. The purpose of this article was to explore the link between CVH levels and the incidence of prediabetes and diabetes in people over 20 years old, and whether serum vitamin D status could alter this relationship. MATERIALS AND METHODS: Data, from six consecutive cycles of the NHANES database from 2007 to 2018 were combined, eligible participants were aged ≥20 years. After excluding missing data, a total of 19,992 subjects were enrolled in the study. Significant risk factors for prediabetes and diabetes were analyzed using univariate and multivariate logistic regression. Exploring the interaction of VD and CVH on prediabetes and diabetes based on multifactorial regression analysis. RESULTS: The prevalence of prediabetes among all participants was 36.15% and the prevalence of diabetes was 16.39%. CVH and vitamin D levels are influential factors in prediabetes and diabetes, and are negatively associated with the risk of developing prediabetes and diabetes. Compared with normoglycemia, poorer CVH and vitamin D deficiency only had a synergistic multiplicative interaction on the development of diabetes, and no significant interaction was observed for the development of prediabetes. Compared with prediabetes, poorer CVH and vitamin D deficiency still had a synergistic additive interaction on the development of diabetes. CONCLUSIONS: Although the cross-sectional study only determine the association and do not prove causality, the current results can be used to prompt people to improve their lifestyle and risk factors to prevent prediabetes or diabetes through higher CVH and adequate Vitamin D.

8.
Plants (Basel) ; 13(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38475568

RESUMO

Uridine diphosphate glycosyltransferases (UDP-GTs, UGTs), which are regulated by UGT genes, play a crucial role in glycosylation. In vivo, the activity of UGT genes can affect the availability of metabolites and the rate at which they can be eliminated from the body. UGT genes can exert their regulatory effects through mechanisms such as post-transcriptional modification, substrate subtype specificity, and drug interactions. Phoebe bournei is an economically significant tree species that is endemic to southern China. Despite extensive studies on the UGT gene family in various species, a comprehensive investigation of the UGT family in P. bournei has not been reported. Therefore, we conducted a systematic analysis to identify 156 UGT genes within the entire P. bournei genome, all of which contained the PSPG box. The PbUGT family consists of 14 subfamilies, consistent with Arabidopsis thaliana. We observed varying expression levels of PbUGT genes across different tissues in P. bournei, with the following average expression hierarchy: leaf > stem xylem > stem bark > root xylem > root bark. Covariance analysis revealed stronger covariance between P. bournei and closely related species. In addition, we stressed the seedlings with 10% NaCl and 10% PEG-6000. The PbUGT genes exhibited differential expression under drought and salt stresses, with specific expression patterns observed under each stress condition. Our findings shed light on the transcriptional response of PbUGT factors to drought and salt stresses, thereby establishing a foundation for future investigations into the role of PbUGT transcription factors.

9.
PeerJ Comput Sci ; 9: e1509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705662

RESUMO

Relation extraction is an important topic in information extraction, as it is used to create large-scale knowledge graphs for a variety of downstream applications. Its goal is to find and extract semantic links between entity pairs in natural language sentences. Deep learning has substantially advanced neural relation extraction, allowing for the autonomous learning of semantic features. We offer an effective Chinese relation extraction model that uses bidirectional LSTM (Bi-LSTM) and an attention mechanism to extract crucial semantic information from phrases without relying on domain knowledge from lexical resources or language systems in this study. The attention mechanism included into the Bi-LSTM network allows for automatic focus on key words. Two benchmark datasets were used to create and test our models: Chinese SanWen and FinRE. The experimental results show that the SanWen dataset model outperforms the FinRE dataset model, with area under the receiver operating characteristic curve values of 0.70 and 0.50, respectively. The models trained on the SanWen and FinRE datasets achieve values of 0.44 and 0.19, respectively, for the area under the precision-recall curve. In addition, the results of repeated modeling experiments indicated that our proposed method was robust and reproducible.

10.
J Hazard Mater ; 460: 132259, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37633018

RESUMO

Photodegradation process plays an important role in the natural attenuation of petroleum hydrocarbons (PHs) in oil contaminated soil. The photodegradation characteristics of PHs (C10-C40) in topsoil of crude oil contaminated soil irradiated by simulated sunlight in 280 d without microbial action were investigated. The results showed that photodegradation rate of PHs was increased with increasing the light intensity and decreased with increasing the initial concentration of PHs. Moreover, the photodegradation capacity of tested PHs was relevant to the length of carbon chain. The photodegradation rates of C10-C20 were higher than that of C21-C40 in photoperiod. C21-C40 showed an obvious trend of photodegradation after 56 d, although their photodegradation rates were less than 20% at the early stage. And, the redundancy analysis indicated that lighting time was the primary factor for photodegradation of PHs under abiotic conditions. The photodegradation rate was well interpreted by a two-stage, first-order kinetic law with a faster initial photolysis rate. The EPR spectrums showed that simulated solar irradiation accelerated the generation of superoxide radicals, which could react with PHs in soil. Also, the function groups in PHs polluted soil were changed after light exposure, which might imply the possible photodegradation pathway of PHs.

11.
Front Genet ; 13: 908289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783260

RESUMO

RNA, like DNA and proteins, has been discovered to undergo dynamic and reversible chemical alterations, increasing the diversity and functional complexity of the molecule. N-6-methyladenosine (m6A) RNA methylation serves as a bridge between transcription and translation and is critical for many diseases' progression. There is a complex interrelationship between m6A modifications and other epigenetic modifications. Their crosstalk significantly affects transcriptional outputs, translation, recruitment of chromatin modifiers, as well as the deployment of the m6A methyltransferase complex at target sites. This article outlines the potential function of m6A RNA methylation in epigenetics and summarizes its interactions with histone modifications.

12.
Cardiovasc Ther ; 2022: 7576388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812724

RESUMO

Purpose: An arteriovenous fistula (AVF) is the preferred vascular access mode for maintenance hemodialysis, and access stenosis and thrombosis are the primary causes of AVF dysfunction. This study is aimed at exploring the molecular mechanisms underlying AVF development and the roles of the heme oxygenase 1/peroxisome proliferator-activated receptor gamma (HO-1/PPAR-γ) pathway in AVF. Method: AVF model mice were established, and the vascular tissues from the arteriovenous anastomosis site were sent for mRNA sequencing. Differentially expressed mRNAs (DEmRNAs) were screened and subjected to functional analysis. Thereafter, the mice with HO-1 knockdown and coprotoporphyrin IX chloride (COPP) pretreatment were used to investigate the roles of the HO-1/PPAR-γ pathway in AVF. Results: By sequencing, 2514 DEmRNAs, including 1323 upregulated and 1191 downregulated genes, were identified. These DEmRNAs were significantly enriched in the PPAR signaling pathway, AMPK signaling pathway, glucagon signaling pathway, IL-17 signaling pathway, and Toll-like receptor signaling pathway. High expression of HO-1 and PPAR-γ reduced endothelial damage and intimal hyperplasia during AVF maturation. After AVF was established, the levels of transforming growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and reactive oxygen species (ROS) were significantly increased (P < 0.05), and HO-1 normal expression and COPP pretreatment evidently decreased their levels in AVF (P < 0.05). Additionally, AVF significantly upregulated HO-1 and PPAR-γ and downregulated MMP9, and COPP pretreatment and HO-1 normal expression further upregulated and downregulated their expression. Conclusion: The HO-1/PPAR-γ pathway may suppress intimal hyperplasia induced by AVF and protect the intima of blood vessels by regulating MMP9 and ROS, thus mitigating AVF dysfunction.


Assuntos
Fístula Arteriovenosa , Heme Oxigenase-1 , Proteínas de Membrana , Estresse Oxidativo , PPAR gama , Animais , Fístula Arteriovenosa/patologia , Citocinas/análise , Técnicas de Silenciamento de Genes , Heme Oxigenase-1/metabolismo , Hiperplasia/prevenção & controle , Inflamação , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , RNA Mensageiro , Espécies Reativas de Oxigênio/análise , Transdução de Sinais
13.
Front Psychol ; 12: 743997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721221

RESUMO

Entrepreneurship education complements vocational education in helping students develop their career prospects. This empirical study comprehensively analyzed sample data of 13,885 students from 40 "Double High-level Plan" higher vocational colleges in China using robust standard error regression analysis and other methods. The results showed that Entrepreneurship Practice (EP), Entrepreneurship Curriculum (EC), and Integration of Entrepreneurship Education and Professional Education (IEEPE) have a significant positive effect on Entrepreneurship Education Performance (EEP), with EP being the most important factor. Furthermore, ascribed factors (gender, household registration, only child or not, whether parents have entrepreneurial experience) and self-achieved factors (double high-level type, school area, subject major, whether to accept social entrepreneurship education) were found to affect students' perception of investment in entrepreneurship education. The study summarizes the existing problems of entrepreneurship education in "Double High-level Plan" higher vocational colleges and proposes four suggestions: pursue the integrated development of entrepreneurship education and "Double High-level" construction, advance both theoretical education and practical education, promote digital reform of the "three teaches" (teachers, teaching materials, and teaching methods), and develop entrepreneurship education in a comprehensive and balanced manner. This has certain theoretical and practical significance for the improvement of entrepreneurship education in other developing countries.

14.
Signal Transduct Target Ther ; 6(1): 223, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112762

RESUMO

CD38 is the main enzyme for nicotinamide adenine dinucleotide (NAD) degradation in mammalian cells. Decreased NAD levels are closely related to metabolic syndromes and aging-related diseases. Our study showed that CD38 deficiency significantly alleviated angiotensin II (Ang II)-induced vascular remodeling in mice, as shown by decreased blood pressures; reduced vascular media thickness, media-to-lumen ratio, and collagen deposition; and restored elastin expression. However, our bone marrow transplantation assay showed that CD38 deficiency in lymphocytes led to lack of protection against Ang II-induced vascular remodeling, suggesting that the effects of CD38 on Ang II-induced vascular remodeling might rely primarily on vascular smooth muscle cells (VSMCs), not lymphocytes. In addition, we observed that CD38 deficiency or NAD supplementation remarkably mitigated Ang II-induced vascular senescence by suppressing the biogenesis, secretion, and internalization of senescence-associated small extracellular vesicles (SA-sEVs), which facilitated the senescence of neighboring non-damaged VSMCs. Furthermore, we found that the protective effects of CD38 deficiency on VSMC senescence were related to restoration of lysosome dysfunction, particularly with respect to the maintenance of sirtuin-mediated mitochondrial homeostasis and activation of the mitochondria-lysosomal axis in VSMCs. In conclusion, our findings demonstrated that CD38 and its associated intracellular NAD decline are critical for Ang II-induced VSMC senescence and vascular remodeling.


Assuntos
ADP-Ribosil Ciclase 1/genética , Senescência Celular/genética , Hipertensão/genética , Glicoproteínas de Membrana/genética , Remodelação Vascular/genética , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Vesículas Extracelulares/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos
15.
Am J Transl Res ; 12(11): 7565-7580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33312389

RESUMO

OBJECTIVE: To investigate the difference between trimethylation of monocyte histone H3K4 and DNA methylation in acute rejection (AR) after renal transplantation in rats and reveal the epigenetic mechanism of the AR rats based on metabolomics. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated, and CD4 +CD25 + Treg cells were sorted by flow cytometry. The Foxp3 mRNA and protein levels of CD4 +CD25 + Treg cells were detected by real-time RT-PCR and Western blotting, respectively. High-throughput screening was applied to evaluate the H3K4 methylation of monocytes using chromatin immunoprecipitation with DNA microarray (ChIP-chip) and verified by ChIP with real-time PCR (ChIP-qPCR). Methylated DNA immunoprecipitation sequencing was combined with real-time PCR (MeDIP-qPCR) to detect the DNA methylation level of positive genes (ABCC4, Mef2d, Tbx1 and Eif6). Real-time quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein levels of positive genes. The difference in lipid metabolism in the blood of (non) acute rejection rats was analysed by HPLC/MS. RESULTS: AR rats showed an apparent increase in BUN and Cr levels, as well as IL-2, IL-10 and IFN-γ. Compared with non-AR rats, the expression of CD4 +CD25 + Treg cells and Foxp3 mRNA and protein were significantly lower in AR rats. AR rats also showed an increase in H3K4 trimethylation of CD4 +CD25 + Treg and decrease in DNA methylation. There were significant differences in the DNA methylation level of four positive genes between AR and non-AR rats (P<0.05), in addition to differences in the expression levels of mRNA and protein. Pathological examination of the transplanted kidney indicated that AR rats had more severe pathological injury of the kidney than the non-AR rats. There were significant increase in the contents of several phosphatidylcholines, lysophosphatidylcholine, free fatty acids and carnitine in AR rats which detected by HPLC/MS. CONCLUSION: H3K4 trimethylation increased in PBMCs in AR rats, while DNA methylation decreased, indicating the presence of epigenetic differences between AR and non-AR rats. Metabolomic studies indicated a significant increase in AR rats in the contents of several metabolites, such as phosphatidylcholines, lysophosphatidylcholine, free fatty acids and carnitine, suggesting an increasein phospholipase activity and leading to an energy metabolism imbalance with intensification of ß-oxidation. DNA methylation may be associated with an increase in phosphatidylcholines, lysophosphatidylcholine and free fatty acids in AR rats, which may further affect energy metabolism by enhancing the tricarboxylic acid cycle in AR rats.

16.
Exp Ther Med ; 20(1): 195-204, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32536991

RESUMO

Crystalized deposits of monosodium urate activate the Nod-like receptor protein 3 (NLRP3) inflammasome, resulting in kidney damage. The present study investigated whether the NLRP3 inflammasome is associated with the progression of hyperuricaemia and gouty nephropathy. Adult male patients were recruited at the Affiliated Baoan Hospital of Shenzhen and divided into three groups of 15 patients each: The control group, the hyperuricaemia group and the gouty nephropathy group. General characteristics and organ function indicators were also measured for each patient. NLRP3, apoptosis-associated speck like protein (ASC) and caspase-1 mRNA and protein expressions in peripheral blood mononuclear cells were detected. The expression of certain downstream inflammatory factors, including interleukin (IL)-1ß and IL-18 were also assessed in plasma. The results demonstrated that the concentration of uric acid and creatinine were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. NLRP3, ASC and caspase-1 mRNA and protein expression, and IL-1ß and IL-18 expression were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. In addition, ASC and caspase-1 mRNA and protein expression, and IL-1ß expression were higher in the gouty nephropathy group compared with the hyperuricaemia group. In conclusion, the present results supported the hypothesis that the NLRP3 inflammasome signalling pathway is associated with gouty nephropathy leading to initiation of the inflammatory response and causing renal damage.

17.
Int J Mol Med ; 44(1): 172-184, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059009

RESUMO

To determine the differences in plasma metabolism between healthy patients and patients with hyperuricaemia and gouty nephropathy, the present study identified differentially expressed metabolites associated with gouty nephropathy. Furthermore, the NLRP3 inflammasome signalling pathway in gouty nephropathy was explored, and the mechanism of hyperuricaemia­induced renal damage. Adult male patients examined between July 2016 and June 2017 were selected as the patient cohort for the present study from the Affiliated Bao'an Hospital of Shenzhen, Southern Medical University (Shenzhen, China). These patients were divided into three groups of 30 patients each: Control, hyperuricaemia and gouty nephropathy groups. The expression levels of NLRP3, ASC and caspase­1 mRNA and protein were detected in peripheral blood mononuclear cells, and the plasma levels of IL­1ß and IL­18. Ultra­performance liquid chromatography coupled with quadrupole time­of­flight mass spectrometry was used to determine differential levels of metabolites between patients from different groups, in order to identify potential biomarkers. The expression of the NLRP3 inflammasome in peripheral blood mononuclear cells, and the levels of IL­1ß and IL­18 in the plasma were increased in the gouty nephropathy group compared with the control and hyperuricaemia groups. In addition, 46 metabolites were identified as potential plasma metabolic biomarkers that were able to distinguish gouty nephropathy from hyperuricaemia. The majority of these metabolites were involved in lipid metabolism, in particular the activity of phospholipase Α2 and ß­oxidation. These data indicated that lipid metabolism and the NLRP3 inflammasome serve a pivotal role in gouty nephropathy. In addition, the results suggested that lipids may mediate the progression of gouty nephropathy through the activity of phospholipase A2, ß­oxidation and activation of the NLRP3 inflammasome.


Assuntos
Gota/metabolismo , Hiperuricemia/metabolismo , Inflamassomos/metabolismo , Nefropatias/metabolismo , Metabolismo dos Lipídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Gota/patologia , Humanos , Hiperuricemia/patologia , Nefropatias/patologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade
18.
Lab Anim ; 53(2): 160-168, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30049253

RESUMO

It is important to develop a feasible animal model of regional anesthesia other than sciatic nerve blockade for pharmacokinetic investigations of new local anesthetics or analgesia in upper extremity surgery. Herein, we explored a nerve stimulator (NS)-guided brachial plexus block (BPB) in a rat model. The anatomy of the brachial plexus in rats was delineated in cadavers, and various BPBs were examined. The puncture point was located 0.5-1.0 cm below the lateral one-third of the clavicle. The efficacy and safety of the NS-guided BPB were evaluated using an injection of 2% lidocaine or 0.5% bupivacaine in 16 live animals; saline injection was used as a control. Both sides of the brachial plexus were located successfully using the NS-guided technique. Sensory blockade (nociception assessment) and motor blockade (grasping and straightening tests) appeared after application of the two classical local anesthetics, but not normal saline. The motor and sensory blockade induced by bupivacaine exhibited a longer duration than that induced by lidocaine ( p < 0.05). All rats recovered uneventfully from general anesthesia and BPB. No abnormal results were found in pathological studies or behavioral observations. Thus, a rat model of NS-guided BPB was established, and BPB induced an overall reversible sensory and motor blockade in the thoracic limbs. Evaluation of the efficacy and safety demonstrated that this rat BPB model was feasible, reproducible, and safe.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio do Plexo Braquial/métodos , Bupivacaína/farmacologia , Lidocaína/farmacologia , Ratos/fisiologia , Animais , Cadáver , Feminino , Humanos , Masculino , Modelos Animais , Ratos Sprague-Dawley
19.
Orthopedics ; 41(5): e607-e614, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29940055

RESUMO

In this prospective, randomized, placebo-controlled study, the authors compared the analgesic efficacy of the single-shot adductor canal block (SS-ACB) vs the continuous adductor canal block (C-ACB) with intermittent boluses during the 72-hour postoperative period. Seventy-five patients randomly received the following: a single shot of 20 mL of 0.5% ropivacaine preoperatively followed by intermittent saline boluses at 12 hours and 24 hours postoperatively (SS-ACB group); 20 mL of 0.5% ropivacaine preoperatively and 12 hours and 24 hours postoperatively (C-ACB group); or saline preoperatively and postoperatively (control group). The primary outcome was visual analog scale pain scores with movement on postoperative day 1. The dynamic pain scores of the 2 ACB groups were equivalent and were lower than those of the control group on postoperative day 1. Compared with the control group, the 2 ACB groups were less likely to use opioids on the operative day and the first 2 postoperative days. The patients in the control group and the C-ACB group exhibited less quadriceps muscle strength than those in the SS-ACB group on postoperative day 1. The time required for an SS-ACB was markedly shorter than that required for an indwelling adductor canal catheter. Further, each adductor canal catheter cost $80. Patients who received a single block reported more satisfaction with their pain-relief treatment. Given the similar analgesic effect but better quadriceps muscle strength, easier execution, and higher patient satisfaction, the SS-ACB may be more suitable for total knee arthroplasty patients than the C-ACB. [Orthopedics. 2018; 41(5):e607-e614.].


Assuntos
Anestésicos Locais/administração & dosagem , Artroplastia do Joelho/métodos , Bloqueio Nervoso/métodos , Ropivacaina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Cateterismo , Método Duplo-Cego , Nervo Femoral/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Manejo da Dor , Dor Pós-Operatória , Satisfação do Paciente , Estudos Prospectivos , Músculo Quadríceps/fisiologia , Coxa da Perna , Ultrassonografia de Intervenção , Adulto Jovem
20.
Front Pharmacol ; 8: 623, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28955228

RESUMO

Osteosarcoma is a malignant musculoskeletal tumor that has high-rate morbidity and mortality worldwide. Alginate oligosaccharide (AOS), a natural product, has antitumor activities and may have therapeutic effects in osteosarcoma, the molecular mechanisms of which remain unclear. AOS was prepared from alginate sodium using alginate lyase. The fractions of AOS were further isolated by size-exclusion chromatography and verified by electrospray ionization mass spectrometry (ESI-MS). Osteosarcoma patients were enrolled in the study and assigned into two groups: AOS (AG, oral administration of 10-mg AOS daily) and control groups (CG, placebo). Preoperative and postoperative clinical data were investigated and analyzed. Four different degrees of polymerizations (DPs) were isolated and denominated as DP2, DP3, DP4, and DP5. Among these polymers, only DP5 showed antitumor functions on osteosarcoma cells. Before surgery and the outcome of primary end point after surgery, no significant differences were observed for clinical data and tumor size between the AG and CG groups (P > 0.05). After 2-year therapy, the mean tumor volume was 214.6 ± 145.7 c.c. in AG and 467.2 ± 225.3 c.c in CG (P < 0.01). The rate of local recurrence was 44.9 and 68.7% in AG and CG, respectively (P < 0.01). AOS treatment resulted in the increase in serum levels of SOD, GSH, HDL-C, and reduction in the levels of interleukin-1 (IL-1) beta and IL-6; the ratios of AST/ALT; and triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol LDL-C, and malondialdehyde (MDA) (P < 0.05). AOS reduces osteosarcoma progression, which is associated with improvement in antioxidant and anti-inflammatory capacities of patients, and may be used as a potential drug for osteosarcoma therapy.

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