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Both carbon limitation and developmentally driven kernel failure occur in the apical region of maize (Zea mays L.) ears. Failed kernel development in the basal and middle regions of the ear often is neglected because their spaces usually are occupied by adjacent ovaries at harvest. We tested the spatial distribution of kernel losses and potential underlying reasons, from perspectives of silk elongation and carbohydrate dynamics, when maize experienced water deficit during silk elongation. Kernel loss was distributed along the length of the ear regardless of water availability, with the highest kernel set in the middle region and a gradual reduction toward the apical and basal ends. Water deficit limited silk elongation in a manner inverse to the temporal pattern of silk initiation, more strongly in the apical and basal regions of the ear than in the middle region. The limited recovery of silk elongation, especially at the apical and basal regions following rescue irrigation was probably due to water potentials below the threshold for elongation and lower growth rates of the associated ovaries. While sugar concentrations increased or did not respond to water deficit in ovaries and silks, the calculated sugar flux into the developing ovaries was impaired and diverged among ovaries at different positions under water deficit. Water deficit resulted in 58% kernel loss, 68% of which was attributable to arrested silks within husks caused by lower water potentials and 32% to ovaries with emerged silks possibly due to impaired carbohydrate metabolism.
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BACKGROUND: IgA nephropathy is the most common primary GN worldwide, with dominant deposition of IgA and co-deposits of complement component 3 (C3). Phenotypes and progression of IgA nephropathy varies among different ethnic populations, while patients with IgA nephropathy from Asia showed more severe clinical phenotypes, active kidney lesions, and rapid progression. Our previous genome-wide association study identified complement factor H ( CFH ) variant rs6677604, tightly linked with the deletion of CFH -related protein 3 and CFH -related protein 1 genes ( ΔCFHR3-1 ), as IgA nephropathy susceptible variant, and additionally revealed its effect on complement regulation in IgA nephropathy. METHODS: To further explore the effect of rs6677604 on IgA nephropathy progression, here we enrolled a Chinese IgA nephropathy cohort of 1781 patients with regular follow-up for analysis. The rs6677604 genotype was measured, and the genotype-phenotype correlation was analyzed using the t test, the chi-squared test, or the nonparametric test, and the association between rs6677604 genotype or mesangial C3 deposition and IgA nephropathy prognosis was analyzed using Kaplan-Meier analysis and Cox regression. RESULTS: We found that patients with rs6677604-GG genotype had a stronger intensity of mesangial C3 deposition than those with the rs6677604-AA/AG genotype. Patients with IgA nephropathy who had stronger intensity of C3 deposition manifested with more severe clinical and pathological manifestations, including lower eGFR and higher Oxford-M/S/T/C (mesangial hypercellularity, endocapillary cellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and crescent) scores. In the survival analysis, stronger intensity of mesangial C3 deposition, but not rs6677604-GG genotypes, was associated with poor long-term kidney outcome in IgA nephropathy. CONCLUSIONS: We found that in Chinese patients with IgA nephropathy, variant rs6677604 was associated with mesangial C3 deposition, and mesangial C3 deposition, but not rs6677604, was associated with IgA nephropathy severity and progression.
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Fator H do Complemento , Glomerulonefrite por IGA , Humanos , Progressão da Doença , Estudo de Associação Genômica Ampla , Mesângio Glomerular/metabolismo , Glomerulonefrite por IGA/patologia , Rim/patologia , Prognóstico , Fator H do Complemento/genéticaRESUMO
In addition to its pulmonary effects, COVID-19 has also been found to cause acute kidney injury (AKI), which has been linked to high mortality rates. In this review, we collected data from 20 clinical studies on post-COVID-19-related AKI and 97 cases of AKI associated with COVID-19 vaccination. Acute tubular injury was by far the most common finding in the kidneys of patients with COVID-19-related AKI. Among patients hospitalized for COVID-19, 34.0% developed AKI, of which 59.0%, 19.1%, and 21.9% were stage 1, 2, and 3, respectively. Though kidney disease and other adverse effects after COVID-19 vaccination overall appear rare, case reports have accumulated suggesting that COVID-19 vaccination may be associated with a risk of subsequent kidney disease. Among the patients with post-vaccination AKI, the most common pathologic findings include crescentic glomerulonephritis (29.9%), acute tubular injury (23.7%), IgA nephropathy (18.6%), ANCA-associated vasculitis (17.5%), minimal change disease (17.5%), and thrombotic microangiopathy (10.3%). It is important to note that crescentic glomerulonephritis appears to be more prevalent in patients who have newly diagnosed renal involvement. The proportions of patients with AKI stages 1, 2, and 3 after COVID-19 vaccination in case reports were 30.9%, 22.7%, and 46.4%, respectively. In general, clinical cases of new-onset and recurrent nephropathy with AKI after COVID-19 vaccination have a positive prognosis. In this article, we also explore the underlying pathophysiological mechanisms of AKI associated with COVID-19 infection and its vaccination by describing key renal morphological and clinical features and prognostic findings.
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With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT-PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients' prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT-PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.
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The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an exceptional setback to the global economy and health. Vaccination is one of the most effective interventions to markedly decrease severe illness and death from COVID-19. In recent years, there have been increasingly more reports of new acute kidney injury (AKI) after COVID-19 vaccination. Podocyte injury, IgA nephropathy, vasculitis, tubulointerstitial injury, and thrombotic microangiopathy appear to be the main pathological phenotypes. Nonetheless, whether the link between the COVID-19 vaccine and acute kidney disease (AKD) is causal or coincidental remains to be verified. Here, we generalize some hypotheses for the emergence of AKD and its pathogenesis in response to certain COVID-19 vaccines. In fact, the enormous benefits of mass vaccination against COVID-19 in preventing COVID-19 morbidity and mortality cannot be denied. The purpose of this review is to assist in the clinical assessment and management of AKD following COVID-19 vaccination.
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Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT-PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT-PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.
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Colon cancer (CC) is one of the most prevalent malignant tumours of the alimentary canal. It is unclear whether pyroptosis-related lncRNA expression is correlated with CC prognosis. We discovered 20 pyroptosis-related lncRNAs that were expressed differently in CC and normal colon tissues in our investigation. Based on differentially expressed genes (DEGs), we grouped all CC patients into two categories (Clusters 1 and 2). Cluster 1 was shown to be connected with a higher overall survival rate, upregulated expression of immune checkpoints, higher immunoscores, higher estimated scores, and immune cell infiltration. Using data from the Cancer Genome Atlas (TCGA), to create a multigene signature, the predictive significance of each lncRNA linked with pyroptosis for survival was assessed. A 9-lncRNA signature was established using the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all CC patients in the TCGA cohort were classified into low-risk or high-risk groups. The low-risk CC patients had a much greater chance of survival than those in the high-risk group. The risk score is an independent prognostic indicator for predicting survival. In addition, risk characteristics are linked to immune characteristics. In summary, pyroptosis-related lncRNAs can be used to predict CC prognosis and participate in tumour immunity.
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In recent years, multiple clinical trials have shown that sodium glucose cotransporter 1 (SGLT1) inhibitors have significant beneficial cardiovascular effects. This includes reducing the incidence of cardiovascular deaths and heart failure hospitalizations in people with and without diabetes, as well as those with and without generalized heart failure. The exact mechanism responsible for these beneficial effects is not completely understood. To explain the cardiovascular protective effects of SGLT1 inhibitors, several potential arguments have been proposed, including decreasing oxidative stress, regulating cardiac glucose uptake, preventing ischemia/reperfusion injury, alleviating the activation of cardiac fibroblasts, attenuating apoptosis, reducing intermittent high glucose-induced pyroptosis, ameliorating cardiac hypertrophy, attenuating arrhythmic vulnerabilities, and improving left ventricular systolic disorder. This article reviews the advantages and disadvantages of these mechanisms, and attempts to synthesize and prioritize mechanisms related to the reduction of clinical events.
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Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Animais , Cardiotônicos/farmacologia , HumanosRESUMO
BACKGROUND: The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent. METHODS: A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation). RESULTS: During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group. CONCLUSIONS: LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.
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Corticosteroides/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Leflunomida/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Leflunomida/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
A giant exchange bias (EB) of 9600 Oe was observed in polycrystalline Fe3O4/CoO layers at 10 K after 20 kOe field cooling, and was attributed to the strong exchange coupling formed by the interfacial spins between the polycrystalline Fe3O4 and the CoO layer. It was found that at 10 K, the magnetic-moment difference (ΔM) between the zero field cooling curves and field cooling curves first increases and then decreases with the change of the field, and it reaches the maximum value at a field of 20 kOe, which suggests that the interfacial spins can be tuned by the cooling field. Furthermore, other magnetic properties, including field dependence, temperature dependence, and training effects, were investigated, which further confirmed that the interfacial spins play an important role in the EB effect. This work provides a method to tune the magnitude of the EB effect and reveals the mechanism of the dependency of EB on interfacial spins, which could guide the design of giant-EB-effect materials.
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BACKGROUND: Mesangial collagen synthesis in renal glomeruli contributes to the pathogenesis of diabetic nephropathy (DN) which is one of the most serious complications of diabetes mellitus. However, the underlying mechanism of mesangial collagen synthesis is largely unknown. METHODS: The differential expression of CHOP and TRIM13 which is a well-defined E3 ubiquitin ligase was compared in renal biopsy samples from DN/normal renal tissues, in isolated glomeruli of diabetic/control mice, as well as in high glucose (HG) or TGF-ß1-stimulated renal mesangial cells. Then the relationship between TRIM13 and CHOP was explored using the ubiquitination assay. FINDINGS: We found that the expression of TRIM13 was downregulated in renal biopsies, isolated glomeruli of diabetic mice, and HG/TGF-ß1-stimulated renal mesangial cells, while the expression of CHOP was upregulated. An increased level of TRIM13 promoter methylation contributed to the deregulation of TRIM13 in renal glomeruli of DN. The ubiquitination assay confirmed that TRIM13 promoted ubiquitination and degradation of CHOP. Meanwhile, overexpressing TRIM13 attenuated DN-induced collagen synthesis and restored renal function in vitro and in vivo via downregulating CHOP. INTERPRETATION: Our findings demonstrated that overexpressed TRIM13 suppresses mesangial collagen synthesis in DN by promoting ubiquitination of CHOP, suggesting TRIM13 as a potential therapeutic target in treating DN.
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Colágeno/biossíntese , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Nefropatias Diabéticas/genética , Células Mesangiais/metabolismo , Fator de Transcrição CHOP/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Animais , Biópsia , Linhagem Celular , Metilação de DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/fisiopatologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Glucose/toxicidade , Humanos , Testes de Função Renal , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Camundongos Endogâmicos C57BL , Proteólise/efeitos dos fármacos , Proteínas com Motivo Tripartido/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND: The present study aims to compare the relative efficacy and safety of different uses of cyclophosphamide (CYC) in lupus nephritis (LN). METHODS: We searched the Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed for articles from the database till June 2018. RESULTS: 12 randomized controlled trials with 994 participants were included. The meta-analysis indicated that the short-interval lower-dose intravenous CYC regime remarkably reduced 24-hour proteinuria [mean difference (MD) -0.45; 95% confidence interval (CI) -0.62 to -0.27; I2 0%], incidence of major infections [odds ratio (OR) 0.62, 95% CI 0.40 to 0.95; I2 42%], gonadal toxicity (OR 0.41, 95% CI 0.27 to 0.62; I2 0%), and leukopenia (OR 0.55, 95% CI 0.33 to 0.94, I2 0%), while high-dose regime had an obvious lower probability of doubling of serum creatinine (Scr) level (OR 2.43; 95% CI 1.19 to 4.95; I2 0%). However, the difference in the complete and total remission rates between the two regimens was not observed. CONCLUSION: The result suggested that the short-interval lower-dose CYC regime remarkably reduced 24-hour proteinuria and the incidence of adverse events, while the long-course high-dose regime played a significant role in reducing the rate of doubling Scr level.
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Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Proteinúria/induzido quimicamente , Proteinúria/imunologia , Resultado do TratamentoRESUMO
OBJECTIVE: The present study aims to compare the relative efficacy and safety of jinshuibao (JSB) combined with angiotensinconverting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) in the treatment of diabetic kidney disease. METHODS: We searched EMBASE, MEDLINE, PubMed, China National Knowledge Internet, the Chinese Biomedical Database, and Wanfang database for articles from the building of the database to September 2018. RESULTS: Fifty-one randomized controlled trials with 3,955 participants were included. The meta-analysis indicated that compared with the controls, JSB combined with ACEI/ARB group could remarkably improve the overall response rate (odds ratio 4.91; 95% confidence interval [CI] 3.32-7.25) and reduce 24 h proteinuria (mean difference [MD] -0.16; 95% CI -0.19 to -0.13), urine albumin excretion ratio (MD -28.20; 95% CI -36.30 to -20.11), serum creatinine (MD -13.84; 95% CI -18.01 to -9.68), blood urea nitrogen (MD -1.00; 95% CI -1.36 to -0.63), systolic blood pressure (MD -4.57; 95% CI -6.78 to -2.37), diastolic blood pressure (MD -3.96; 95% CI -5.73 to -2.19), fasting blood glucose (MD -0.85; 95% CI -1.45 to -0.24), hemoglobin A1c (MD -0.52; 95% CI -0.83 to -0.21), serum total cholesterol (MD -0.53; 95% CI -0.86 to -0.20), and triglyceride (MD -0.53; 95% CI -0.55 to -0.51). CONCLUSIONS: JSB combined with ACEI/ARB in the treatment of diabetic kidney disease is superior to the single application of ACEI/ARB.
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Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cordyceps , Nefropatias Diabéticas/tratamento farmacológico , Terapia Combinada , Fermentação , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: It has been recognized that primary membranous nephropathy (MN) is related to an increased risk for thromboembolic complications. However, the current evidence supporting prophylactic and therapeutic anticoagulation is too weak to better meet the clinical needs of this patient population. The present review provides some suggestions to guide the decision on anticoagulant management in primary MN patients with a high risk of thrombosis or with thromboembolic complication. MATERIALS AND METHODS: We extracted relevant studies by searching the published literature using the Cochrane Library, Medline, PubMed and Web of Science from March 1968 to March 2018. Eligible publications included guidelines, reviews, case reports, and clinical trial studies that concerned the rational management of anticoagulation therapy in the primary MN population. The evidence was thematically synthesized to contextualize implementation issues. RESULTS: It was helpful for clinicians to make a decision for personalized prophylactic aspirin or warfarin in primary MN patients when serum albumin was < 3.2 g/dl to prevent arterial and venous thromboembolic events (VTEs). The treatment regimen for thromboembolic complications (VTEs, acute coronary syndrome and ischemic stroke) in primary MN was almost similar to that for the general population with thromboembolic events. It is noteworthy that patients should continue the previous primary MN treatment protocol during the entire treatment period until they achieve remission, the protocol is complete and the underlying diseases resolve. CONCLUSION: The utility of prophylactic aspirin or warfarin may have clinical benefits for the primary prevention of thromboembolic events in primary MN with hypoalbuminemia. It is necessary to perform large randomized controlled trials and to formulate relevant guidelines to support the present review.
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Anticoagulantes/farmacologia , Glomerulonefrite Membranosa , Inibidores da Agregação Plaquetária/farmacologia , Tromboembolia , Coagulação Sanguínea/efeitos dos fármacos , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Fatores de Risco , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Tromboembolia/terapiaRESUMO
Glomerular endothelial cell injury plays an important role in the development and progression of diabetic nephropathy (DN). The expression and function of klotho in glomerular endothelial cells remain unclear. Thus, this study aimed to investigate the expression and the functional role of klotho in DN progression in mice and in high glucose (HG)-induced cell injury of human renal glomerular endothelial cells (HRGECs) and the underlying mechanism. In this study, HRGECs were cultured with media containing HG to induce endothelial cell injury and db/db mice were used as DN model mice. Klotho was overexpressed or knocked down in HRECs to evaluate its role in HG-induced HRGECs injury. klotho-overexpressing adenovirus (rAAV-klotho) was injected into db/db mice via the tail vein to further validate the protective effect of klotho in DN. Decreased klotho expression was observed in DN patients, DN mice, and HG-exposed HRGECs. Furthermore, klotho overexpression significantly abolished the HG-induced HRGECs injury and activation of Wnt/ß-catenin pathway and RAAS. In contrast, klotho knockdown exerted the opposite effects. Moreover, klotho attenuated diabetic nephropathy in db/db mice, which was also associated with inhibition of the Wnt/ß-catenin pathway and RAAS. In conclusion, klotho attenuates DN in db/db mice and ameliorates HG-induced injury of HRGECs.
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Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Glucuronidase/metabolismo , Glomérulos Renais/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Rim/metabolismo , Proteínas Klotho , Camundongos , Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
Several recent reporters have indicated the potential role of long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in diabetic nephropathy (DN). However, these studies mainly focus on renal tubular epithelial cells HK-2, the role of MALAT1 in human renal glomerular endothelial cells (HRGECs) remains unclear. Hence, this study aimed to explore the role of MALAT1 in high glucose (HG)-induced HRGECs injury and the underlying epigenetic mechanism. Increased MALAT1 and decreased klotho expression were observed in both renal tissues from DN patients and HG-exposed HRGECs. Furthermore, MALAT1 expression was negatively correlated with klotho expression. Moreover, both MALAT1 knockdown and klotho overexpression significantly abolished the HG-induced HRGECs injury. Importantly, klotho overexpression reversed the MALAT1 overexpression-mediated enhancement of the HG-induced HRGECs injury. In addition, MALAT1 recruited G9a to elevate H3K9me1, which can bind to the klotho promoter and thus inhibited klotho transcription. In conclusion, MALAT recruits methyltransferase G9a to elevate H3K9me1 and epigenetically inhibits klotho expression, and thus mediates HG-induced glomerular endothelial cell injury. © 2019 IUBMB Life, 1-9, 2019.
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Nefropatias Diabéticas/patologia , Células Endoteliais/patologia , Epigênese Genética , Glucuronidase/antagonistas & inibidores , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Glomérulos Renais/patologia , RNA Longo não Codificante/genética , Células Cultivadas , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Glucose/farmacologia , Glucuronidase/genética , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/genética , Humanos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Proteínas Klotho , Edulcorantes/farmacologiaRESUMO
The kernel setting of maize varies greatly because of the timing and intensity of water deficits. This variation can limit leaf productivity (source), the translocation of assimilated sugars (flow), and yield formation (sink). To explain the decline in kernel setting of maize under water deficits from the perspective of source-flow-sink, a 3-year experiment was conducted under a rain shelter. Five water regimes were studied. One regime included well-irrigated (CK) treatment. Four regimes involved water deficits: irrigation was withheld during the 6- to 8-leaf stage (V6-8), the 9- to 12-leaf stage (V9-12), the 13-leaf stage to tasseling stage (V13-T), and the silking stage to blister stage (R1-2). Water deficit effects on kernel setting began when the water deficit occurred at V9 and became more significant with time. Kernel weight was reduced by 12 and 11% when there were water deficits during V9-12 and V13-T, respectively. This was the result of reduced leaf area (limited source) and an altered vascular bundle in the ear peduncles (limited assimilate flow). The reduced vascular bundle number, rather than the ear peduncle cross-sectional area, significantly affected the final kernel weight when exposed to a water deficit prior to the silking stage. The water deficits prior to and close to the flowering stage significantly reduced ear kernel number; that is, 14 and 19% less during V13-T and R1-2, respectively, compared with the kernel number during the CK treatment. This reflects a smaller sink under water deficit conditions. Additionally, ovary size was reduced the most in the V13-T water deficit compared with other treatments. After rewatering, the water deficit before or during flowering stage continued to have residual effects on grain-filling in the late growth period. The grain-filling rate decreased under the V9-12 water deficit; the grain-filling duration shortened under the R1-2 water deficit; and both negative effects occurred under the V13-T water deficit. This study clearly indicated that (1) the water deficit during the vegetative organ rapid growth period both limited leaf source development and assimilate flow and slowed down kernel development, and (2) the water deficit just before and during flowering reduced kernel sink. Deficits at both times could retard grain-filling and reduce maize yield. The results of the present study might guide irrigation practices in irrigated maize or inform the management of sowing time in rainfed maize, to desynchronize the water deficit and the plant's reactions to such deficits at different stages.