RESUMEN
BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.
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Caveolina 1 , Dieta Alta en Grasa , Células Endoteliales , Endotelio Vascular , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III , Vasodilatación , Animales , Masculino , Ratones , Aorta/enzimología , Aorta/fisiopatología , Aorta/metabolismo , Aorta/efectos de los fármacos , Aorta/patología , Caveolina 1/metabolismo , Caveolina 1/deficiencia , Caveolina 1/genética , Células Cultivadas , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/fisiopatología , Células Endoteliales/enzimología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/fisiopatología , Endotelio Vascular/metabolismo , Endotelio Vascular/enzimología , Endotelio Vascular/efectos de los fármacos , Ratones Noqueados , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/enzimología , Obesidad/fisiopatología , Obesidad/metabolismo , Transducción de Señal , Esterol Esterasa/metabolismo , Esterol Esterasa/genética , Ubiquitinación , Vasodilatación/efectos de los fármacosRESUMEN
Members of the abscisic acid (ABA)-responsive element (ABRE) binding factor (ABF) and ABA-responsive element binding protein (AREB) families play essential roles in the regulation of ABA signaling pathway activity and shape the ability of plants to adapt to a range of stressful environmental conditions. To date, however, systematic genome-wide analyses focused on the ABF/AREB gene family in wheat are lacking. Here, we identified 35 ABF/AREB genes in the wheat genome, designated TaABF1-TaABF35 according to their chromosomal distribution. These genes were further classified, based on their phylogenetic relationships, into three groups (A-C), with the TaABF genes in a given group exhibiting similar motifs and similar numbers of introns/exons. Cis-element analyses of the promoter regions upstream of these TaABFs revealed large numbers of ABREs, with the other predominant elements that were identified differing across these three groups. Patterns of TaABF gene expansion were primarily characterized by allopolyploidization and fragment duplication, with purifying selection having played a significant role in the evolution of this gene family. Further expression profiling indicated that the majority of the TaABF genes from groups A and B were highly expressed in various tissues and upregulated following abiotic stress exposure such as drought, low temperature, low nitrogen, etc., while some of the TaABF genes in group C were specifically expressed in grain tissues. Regulatory network analyses revealed that four of the group A TaABFs (TaABF2, TaABF7, TaABF13, and TaABF19) were centrally located in protein-protein interaction networks, with 13 of these TaABF genes being regulated by 11 known miRNAs, which play important roles in abiotic stress resistance such as drought and salt stress. The two primary upstream transcription factor types found to regulate TaABF gene expression were BBR/BPC and ERF, which have previously been reported to be important in the context of plant abiotic stress responses. Together, these results offer insight into the role that the ABF/AREB genes play in the responses of wheat to abiotic stressors, providing a robust foundation for future functional studies of these genes.
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Estudio de Asociación del Genoma Completo , Triticum , Triticum/genética , Filogenia , Regulación de la Expresión Génica , Factores Estimuladores hacia 5'RESUMEN
Tube-like outgrowths from root epidermal cells, known as root hairs, enhance water and nutrient absorption, facilitate microbial interactions, and contribute to plant anchorage by expanding the root surface area. Genetically regulated and strongly influenced by environmental conditions, longer root hairs generally enhance water and nutrient absorption, correlating with increased stress resistance. Wheat, a globally predominant crop pivotal for human nutrition, necessitates the identification of long root hair genotypes and their regulatory genes to enhance nutrient capture and yield potential. This study focused on 261 wheat samples of diverse genotypes during germination, revealing noticeable disparities in the length of the root hair among the genotypes. Notably, two long root hair genotypes (W106 and W136) and two short root hair genotypes (W90 and W100) were identified. Transcriptome sequencing resulted in the development of 12 root cDNA libraries, unveiling 1180 shared differentially expressed genes (DEGs). Further analyses, including GO function annotation, KEGG enrichment, MapMan metabolic pathway analysis, and protein-protein interaction (PPI) network prediction, underscored the upregulation of root hair length regulatory genes in the long root hair genotypes. These included genes are associated with GA and BA hormone signaling pathways, FRS/FRF and bHLH transcription factors, phenylpropanoid, lignin, lignan secondary metabolic pathways, the peroxidase gene for maintaining ROS steady state, and the ankyrin gene with diverse biological functions. This study contributes valuable insights into modulating the length of wheat root hair and identifies candidate genes for the genetic improvement of wheat root traits.
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Transcriptoma , Triticum , Humanos , Perfilación de la Expresión Génica , Fenotipo , Agua , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/genéticaRESUMEN
AIM: To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. METHODS: A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. RESULTS: We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of -0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of -0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). CONCLUSIONS: Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.
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Citocinas/sangre , Células TH1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Adulto , Pueblo Asiatico , Complemento C3/metabolismo , Complemento C4/metabolismo , Femenino , Humanos , Interferón gamma/sangre , Interleucina-12/sangre , Interleucina-13/sangre , Interleucina-18/sangre , Interleucina-4/sangre , Interleucina-6/sangre , Lipocalina 2/sangre , Nefritis Lúpica/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Cumulus cells surrounding oocytes furnish nutritional support crucial for oocyte maturation in vitro, and thereby enhance oocyte quality significantly. Our previous studies affirmed the role of SIRT2 in regulation of mitochondrial function in sheep granulosa cells. However, the effect of SIRT2 action on mitophagy in these cells remain unclear. Here, RNA-seq was used to scrutinize pathways where differentially expressed genes (DEGs) are enriched following SIRT2 knockdown in cumulus cells. Prior to SIRT2 knock down, cumulus cells were treated with the mitophagy inhibitor Mdivi-1. Potential mechanisms by which SIRT2 affects apoptosis via mitophagy were explored. Results indicated that DEGs after SIRT2 knockdown were enriched in various pathways including mitochondria, mitophagy, and apoptosis. The expression levels of CASP3/CASP9 were significantly increased after mitophagy activation (P < 0.01), whereas inhibition of mitophagy had no effect on apoptosis (P > 0.05). Pretreatment of cumulus cells with Mdivi-1 prior to SIRT2 knockdown significantly reduced the expression of mitophagy-related genes, the number of autolysosomes, the expression of CASP3/CASP9, and the levels of Ca2+ and cytochrome C (P < 0.05). In addition, an improvement in mitochondrial morphology and increases in ATP levels and mitochondrial DNA (mtDNA) copy numbers were observed. Interestingly, double knockdown of SIRT2 and MAPK15 was found to reverse increased mitophagy and apoptosis activity caused by SIRT2 knockdown. Our findings indicate that SIRT2 modulate apoptosis in cumulus cells by regulating mitophagy, with MAPK15 likely playing a pivotal role in this process.
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Células del Cúmulo , Mitofagia , Femenino , Animales , Ovinos/genética , Mitofagia/genética , Células del Cúmulo/fisiología , Caspasa 3/metabolismo , Sirtuina 2/metabolismo , Oocitos/fisiología , Apoptosis , ADN MitocondrialRESUMEN
Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.
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Lesión Renal Aguda , Ácidos Cafeicos , Lipopolisacáridos , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Sepsis , Succinatos , Animales , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Ratones , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Masculino , Succinatos/farmacología , Succinatos/uso terapéutico , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células RAW 264.7 , Estrés Oxidativo/efectos de los fármacos , Inflamasomas/metabolismo , Ratones Endogámicos C57BL , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Glucólisis/efectos de los fármacos , Apoptosis/efectos de los fármacos , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Activación de Macrófagos/efectos de los fármacosRESUMEN
BACKGROUND: Skin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient's condition. Some patients will experience symptoms such as depression and insomnia due to skin pruritus, and simply scratching the skin lead to infection. Severely affected patients may even show suicidal tendency, endangering the physical and mental health of patients, and it is needed to give the effective treatment to patients. Hemodialysis is a common treatment for uremic pruritus, which can effectively relieve the pruritus symptoms of patients. The drugs can also relieve the symptoms and improve the degree of pruritus in patients. And some studies show that traditional Chinese medicine UCG combined with HFH in the treatment of uremic pruritus has a very good effect, Therefore, this study will systematically evaluate the clinical efficacy and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. METHODS: Use computer to search English and Chinese databases, English databases include: PubMed, Web of Science, EMbase, The Cochrane Library. Chinese databases include: CNKI, CBM, WanFang Data and VIP databases, collecting the RCT on the clinical effectiveness and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. The retrieval time is from the beginning of each database to May 1, 2021. In order to improve the retrieval rate of the literature, the references cited in the included research are also collected and screened. Set Chinese and English as the search language. Two members of the research group independently collected, included and excluded the literatures. In case of disagreement, consulting the third party to assist in the judgment. For the literature with missing data, the original author should be contacted as far as possible to obtain complete data. Two evaluators evaluate the bias risk of included studies according to the Cochrane Handbook bias risk assessment tool for RCT. RevMan 5.3 software is used for statistical analysis and the forest plot is drawn to show the outcome indicators and funnel plot is drawn to show the publication bias. RESULTS: This study evaluates the advantages and disadvantages of traditional Chinese medicine UCG combined with HFH and HFH alone in the treatment of uremic pruritus through the clinical effectiveness and safety-related indicators. CONCLUSION: This study will give a positive conclusion on the efficacy and safety of uremic clearance granule in the treatment of uremic pruritus, and the research results will be published in professional journals in the form of academic papers, thus benefiting more patients. ETHICS AND DISSEMINATION: This study belongs to meta-analysis and all data comes from academic papers published publicly in formal academic journals, so there are no ethical issues involved in this study and no ethical review or approval is required. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W8P5G.
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Medicamentos Herbarios Chinos/administración & dosificación , Fallo Renal Crónico/terapia , Prurito/terapia , Diálisis Renal/efectos adversos , Uremia/terapia , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Fallo Renal Crónico/complicaciones , Metaanálisis como Asunto , Prurito/diagnóstico , Prurito/etiología , Prurito/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento , Uremia/diagnóstico , Uremia/etiologíaRESUMEN
Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown etiology that predominantly affects East Asians, particularly Japanese with a prevalence of 0.00028. Research has shown that HLA-B54 and HLA-A11 are positively associated with this disease. HLA-A, -B, and -DR loci were analyzed using an oligonucleotide microarray in both Chinese patients with DPB and normal control subjects. The most marked difference between the patients and the controls was the decreased frequency of HLA-A2 (p=0.001, OR=0.12), which showed a negative association with the disease; however, there was no significant contribution of HLA-B loci. Interestingly, the frequency of HLA-A11 was increased (p=0.007, OR=3.9), in accordance with previous reports on Japanese and Koreans. In addition, the frequency of HLA-DRB5*010/020 slightly increased (p=0.049). The HLA-associated genes for DPB are located between the HLA-A and HLA-B loci. Differences in HLA-associated genes may partially explain differences in the incidence of DPB among different populations.
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Bronquiolitis/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Adulto , Anciano , Alelos , Pueblo Asiatico/etnología , Bronquiolitis/tratamiento farmacológico , Eritromicina/uso terapéutico , Femenino , Frecuencia de los Genes , Humanos , Hibridación in Situ/métodos , Masculino , Análisis por Micromatrices/métodos , Persona de Mediana Edad , Inhibidores de la Síntesis de la Proteína/uso terapéutico , Estudios RetrospectivosRESUMEN
Chemical forms of Cr, Cu, Mn, Ni, Pb and Zn in the surface sediments of Nansihu Lake and its main inflow rivers are determined by the BCR sequential extraction method. The chemical fractionation composition characteristics, pollution state and potential ecological effects of the heavy metals are discussed. Cr, Cu, Ni and Zn in the sediments of Sihe River, Jinghang Canal, Zhuzhaoxin River, Guangfu River, south area of the Upper Lakes, and Down Lakes mainly exist in residual fraction, which account for 80% - 90% of their content, mainly reflecting the natural characteristics of the heavy metals; but for the sediment of Old Canal, Guangfu River estuary, Baima River, nearly 80% of Cr, Cu, Ni and Zn exist in extractable fractions due to human pollution, especially with high oxidizable and acid extractable fractions content. Pb and Mn mainly exist in residual fraction and oxidizable fraction in the sediment of Nansihu Lake and its main inflow rivers, which account for 95% and 70% of the content of Pb and Mn, similar to other unpolluted sediments. With the mineralization and decomposition of organic matter and change of environment condition of the surface sediment, the extractable fractions of Cr, Cu, Ni, Zn in the polluted sediment can be reactivated, bringing on ecological harm to the water ecological system.