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The effect of changes in microbial community structure on the migration and release of toxic heavy metal (loid)s is often ignored in ecological restoration. Here, we investigated a multi-metal (mercury and thallium, Tl) mine waste slag. With particular focus on its strong acidity, poor nutrition, and high toxicity pollution characteristics, we added fish manure and carbonate to the slag as environmental-friendly amendments. On this basis, ryegrass, which is suitable for the remediation of metal waste dumps, was then planted for ecological restoration. We finally explored the influence of changes in microbial community structure on the release of Tl and As in the waste slag during vegetation reconstruction. The results show that the combination of fish manure and carbonate temporarily halted the release of Tl, but subsequently promoted the release of Tl and arsenic (As), which was closely related to changes in the microbial community structure in the waste slag after fish manure and carbonate addition. The main reason for these patterns was that in the early stage of the experiment, Bacillaceae inhibited the release of Tl by secreting extracellular polymeric substances; with increasing time, Actinobacteriota became the dominant bacterium, which promoted the migration and release of Tl by mycelial disintegration of minerals. In addition, the exogenously added organic matter acted as an electron transport medium for reducing microorganisms and thus helped to reduce nitrate or As (â ¤) in the substrate, which reduced the redox potential of the waste slag and promoted As release. At the same time, the phylum Firmicutes, including specific dissimilatory As-reducing bacteria that are capable of converting As into a more soluble form, further promoted the release of As. Our findings provide a theoretical basis for guiding the ecological restoration of relevant heavy-metal (loid) mine waste dumps.
Assuntos
Mercúrio , Mineração , Tálio , Mercúrio/análise , Mercúrio/metabolismo , Poluentes do Solo/análise , Poluentes do Solo/química , Metais Pesados/análise , Microbiota/efeitos dos fármacos , Resíduos Industriais/análise , Recuperação e Remediação Ambiental/métodos , Microbiologia do SoloRESUMO
Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy and extracellular matrix accumulation in vivo and in vitro. These effects delayed CKD progression. Immunoprecipitation assays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.
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Macrophytes are crucial in maintaining the equilibrium of aquatic ecosystems. However, the pattern of macrophyte-derived caffeic acid (CA) release under heavy metal stress is yet to be fully understood. More importantly, due to its functional groups, CA may be a precursor to the formation of disinfection by-products, posing threats to water ecology and even safety of human drinking water. This study analyzed the responses of CA released by Vallisneria natans (V. natans) and Pistia stratiotes (P. Stratiotes) when exposed to Cu2+ and Mn2+ stress. Additionally, the CA levels in two constructed wetland ponds were detected and the degradation kinetics of CA during chlorination were investigated. Results indicated that CA occurred in two constructed wetland ponds with the concentrations of 44.727⯵g/L (planted with V. natans) and 61.607⯵g/L (planted with P. Stratiotes). Notably, heavy metal stress could significantly affect CA release from V. natans and P. Stratiotes. In general, under Cu2+ stress, V. natans secreted far more CA than under Mn2+ stress, the level could reach up to 435.303⯵g/L. However, compared to V. natans, P. Stratiotes was less affected by Cu2+ and Mn2+ stress, releasing a maximum CA content of 55.582⯵g/L under 5â¯mg/L Mn2+ stress. Aquatic macrophytes secreted more CA in response to heavy metal stresses and protected macrophytes from harmful heavy metals. CA degradation followed the pseudo first-order kinetics model, and the chlorination of CA conformed to a second-order reaction. The reaction rate significantly accelerated as NaClO, pH, temperature and Br- concentration increased. A new pathway for CA degradation and a new DBP 2, 2, 3, 3-tetrachloropropanal were observed. These findings pointed at a new direction into the adverse effect of CA, potentially paving the way for new strategies to solve drinking water safety problems.
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Araceae , Ácidos Cafeicos , Água Potável , Metais Pesados , Poluentes Químicos da Água , Humanos , Ecossistema , Poluentes Químicos da Água/análise , Halogenação , Araceae/metabolismo , Metais Pesados/análiseRESUMO
Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics.
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Células Endoteliais da Veia Umbilical Humana , Fator Regulador 1 de Interferon , Interferon gama , Tricloroetileno , Fator de Necrose Tumoral alfa , Animais , Humanos , Camundongos , Injúria Renal Aguda/induzido quimicamente , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fator Regulador 1 de Interferon/metabolismo , Rim/efeitos dos fármacos , Tricloroetileno/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Feminino , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Previous observational studies have shown that immune cells play an important role in IgA nephropathy. However, the specific causal relationship between the two is inconsistent. METHODS: We used a two-sample mendelian randomization(MR) analysis to investigate the causal association between 731 immune cell signatures and IgA nephropathy in this study. Based on published GWAS data, immune cells were characterized by four immune types absolute cell (AC) counts, median fluorescence intensity (MFI), morphological parameters (MP), relative cell (RC) counts. Meanwhile, heterogeneity test, horizontal pleiotropy and sensitivity test were used to evaluate the robustness and reliability of the results. RESULTS: An important causal association was achieved for 14 RC traits/IgA nephropathy, 3 AC traits/IgA nephropathy, 10 MFI traits/IgA nephropathy, and 1 MP trait/IgA nephropathy. However, after false discovery rate (FDR) correction, only one immunophenotype was found to be protective against IgA nephropathy. The OR of herpesvirus entry mediator (HVEM) on terminally differentiated CD4+ T cell (maturation stages of T-cell panel) on IgA nephropathy risk was estimated to be 0.727 (95%CI: 0.624-0.847, p = 4.20e - 05, PFDR = 0.023) according to inverse variance weighting (IVW) method, and the weighted-median method yielded similar results (OR = 0.743, 95% CI: 0.596-0.927, p = 0.008). Although not statistically significant, the association was consistent with MR-Egger, simple mode and weighted mode. CONCLUSIONS: Our study further confirmed that immune cells play a complex and important role in the pathogenesis of IgA nephropathy, providing evidence for clinical research.
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Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA , Análise da Randomização Mendeliana , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/imunologia , Humanos , Polimorfismo de Nucleotídeo Único , Linfócitos T CD4-Positivos/imunologia , ImunofenotipagemRESUMO
Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Animais , Camundongos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Rim , Falência Renal Crônica/complicações , Túbulos Renais Proximais/metabolismo , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Araquidonato 12-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase/metabolismoRESUMO
Macrophage infiltration plays an important role in the progression of diabetic nephropathy (DN). Previously, we demonstrated that highglucose-stimulated macrophage-derived exosomes (HG-exo) induces proliferation and extracellular matrix accumulation in glomerular mesangial cells, but its effect on tubular cells is unclear. This study aimed to explore the role of HG-exo on renal tubular injury in DN. The results show that HG-exo could induce dysfunction, autophagy inhibition, and inflammation in mouse tubular epithelial cell (mTEC) and C57 mouse kidney. Moreover, miR-7002-5p was differentially expressed in HG-exo based on miRNAs sequencing and bioinformatics analysis. A dual-luciferase reporter assay confirmed that Atg9b was the direct target gene of miR-7002-5p. Further experimentation showed that miR-7002-5p inhibition in vivo and vitro reserves HG-exo effects. These results demonstrated that HG-exo carries excessive miR-7002-5p and inhibits autophagy through targeting Atg9b; this process then induces renal tubular dysfunction and inflammation. In conclusion, our study clarifies the important role of macrophage-derived exosomes in DN and is expected to provide new insight on DN prevention and treatment.
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Autofagia , Nefropatias Diabéticas , Exossomos , Proteínas de Membrana , MicroRNAs , Animais , Proteínas Relacionadas à Autofagia/genética , Nefropatias Diabéticas/genética , Células Epiteliais/citologia , Exossomos/genética , Inflamação/genética , Túbulos Renais/citologia , Macrófagos , Proteínas de Membrana/genética , Camundongos , MicroRNAs/genéticaRESUMO
The carnosinase dipeptidase 1 (CNDP1) gene has been reported as a susceptibility locus for the development of diabetic kidney disease (DKD). While the (CTG)5 allele affords protection in the Caucasian population, we have previously shown that this allele is less frequently present in the Chinese population and therefore a protective role for the (CTG)5 allele is difficult to demonstrate. In the present study, we sought to assess if carnosinase-1 (CN-1) concentrations in serum and/or urine are associated with progression of DKD and to what extent CN-1 influences diabetes-associated inflammation. From a total of 622 individuals that enrolled in our study, 247 patients had type 2 diabetes without DKD, 165 patients had DKD and 210 subjects served as healthy controls. Uni- and multivariate regression analyses were performed to identify potential factors predicting urinary albumin creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and CN-1 concentration in serum and urine. The results indicated that serum CN-1 indeed correlated with eGFR (p = 0.001). In addition, urinary CN-1 associated with eGFR and tubular injury indicator: urinary cystatin C (Cys-C) and urinary retinol-binding protein (RBP). Interestingly, serum CN-1 also positively correlated with inflammatory indicators: neutrophils and lymphocytes. With regard to this, a STZ injected C57BL/6 mice model with surgically made skin wound was established for the generation of skin inflammation. This animal model further proved that the expression of CN-1 in liver and kidney increased remarkably in diabetic mice with skin wound as compared to those without. In conclusion, serum and urinary CN-1 significantly related to the surrogates of impaired renal function in diabetic patients; besides, CN-1 expression might also be associated with the process of inflammation.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Camundongos , Animais , Diabetes Mellitus Tipo 2/complicações , Camundongos Endogâmicos C57BL , Rim/metabolismo , Inflamação , Biomarcadores/urinaRESUMO
Diabetic nephropathy (DN) can promote the occurrence of end-stage renal disease (ESRD). The injury of renal tubular epithelial cells is a significant reason for the occurrence of ESRD. A recent research demonstrated that ferroptosis was associated with renal tubular injury in DN. Ferroptosis is a kind of cell death brought on by the buildup of iron ions and lipid peroxidation brought on by ROS. Because carnosine (CAR) is a scavenger of iron ions and reactive oxygen species, we investigated whether CAR can improve DN by regulating ferroptosis. The results show that both CAR and Fer-1 significantly reduced kidney damage and inhibited ferroptosis in STZ mice. In addition, ferroptosis caused by HG or erastin (an inducer of ferroptosis) in human kidney tubular epithelial cell (HK2) was also rescued by CAR treatment. It was discovered that the protective effect of CAR against HG-induced ferroptosis was abolished when NRF2 was specifically knocked down in HK2 cells.
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Epigenetic changes are present in many physiological and pathological processes. The N6-methyladenosine (m6A) modification is the most common modification in eukaryotic mRNA. However, the role of m6A modification in diabetic nephropathy (DN) remains elusive. Here, we found that m6A modification was significantly upregulated in the kidney of type 1 and type 2 diabetic mice, which was caused by elevated levels of METTL3. Moreover, METTL3 is increased in podocyte of renal biopsy from patients with DN, which is related to renal damage. METTL3 knockout significantly reduced the inflammation and apoptosis in high glucose (HG)-stimulated podocytes, while its overexpression significantly aggravated these responses in vitro. Podocyte-conditional knockout METTL3 significantly alleviated podocyte injury and albuminuria in streptozotocin (STZ)-induced diabetic mice. Therapeutically, silencing METTL3 with adeno-associated virus serotype-9 (AAV9)-shMETTL3 in vivo mitigated albuminuria and histopathological injury in STZ-induced diabetic mice and db/db mice. Mechanistically, METTL3 modulated Notch signaling via the m6A modification of TIMP2 in an insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2)-dependent manner and exerted pro-inflammatory and pro-apoptotic effects. In summary, this study suggested that METTL3-mediated m6A modification is an important mechanism of podocyte injury in DN. Targeting m6A through the writer enzyme METTL3 is a potential approach for the treatment of DN.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Podócitos , Albuminúria/metabolismo , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Podócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Estreptozocina , Inibidor Tecidual de Metaloproteinase-2RESUMO
BACKGROUND: Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment. METHODS: A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients. RESULTS: The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera. CONCLUSION: Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Falência Renal Crônica , Diálise Peritoneal , Humanos , Microbioma Gastrointestinal/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , CogniçãoRESUMO
Objective: Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD). Methods: In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function. Results: The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm-1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: -3.71, 95% confidence interval: -7.09 to -0.33, p = 0.03). Conclusions: Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline.
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Disfunção Cognitiva , Microaneurisma , Diálise Peritoneal , Doenças Retinianas , Masculino , Humanos , Feminino , Hemorragia Retiniana , Estudos Transversais , Doenças Retinianas/epidemiologia , Doenças Retinianas/etiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Cognição , Diálise Peritoneal/efeitos adversosRESUMO
Direct revegetation is a promising strategy for phytostabilization of metal smelting slag sites. Slag comes into direct contact with root exudates when slag sites undergo direct revegetation. The slag particle size fractions are considered the key factor influencing the geochemical behaviour of potentially toxic elements (PTEs). However, the effects of root exudates on the geochemical behaviours of PTEs in various slag particle size fractions remain unclear. Here, the effects of simulated root exudates of perennial ryegrass (Lolium perenne) directly revegetated at a zinc smelting slag site on the distribution, bioavailability, and fractionation of PTEs (Cu, Pb, Zn, and Cd) in various slag particle size fractions were investigated. The results showed that PTEs mainly occurred in the <1 mm slag particles; the mass loads of PTEs in the <1 mm slag particles were higher than those in the >1 mm slag particles. The bioavailability of Cu, Zn, and Cd rather than Pb in the slag increased as the particle size decreased. There was a decrease in the <0.25 and 1-2 mm slag particles and an increase in the 0.25-0.5, 0.5-1, and >2 mm slag particles in the presence of root exudates. Root exudates enhanced the transformation of acid-soluble PTEs into other more stable fractions in various slag particle size fractions. Root exudates enhanced the aggregation of slag particles associated with the migration of PTEs, causing differences in the geochemical behaviour of PTEs in various slag particle size fractions. These findings are beneficial for understanding the geochemical behaviour of PTEs in metal smelting slags undergoing direct revegetation and provide an important basis for the guidance of environmental risk management of the revegetated metal smelting slag sites.
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Lolium , Zinco , Disponibilidade Biológica , Cádmio , Chumbo , Tamanho da Partícula , Exsudatos e TransudatosRESUMO
We investigated the effects of ultrasound-assisted ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) washing on heavy metal (HM) removal, residual HM mobility, and sewage sludge quality. EDTA and CA washing of sewage sludge successfully reduced the total concentration of HMs after one round of washing, but the mobility of residual HMs increased significantly. The eluate had a high concentration of HMs and nutrients (nitrogen, phosphorus, potassium, and total organic carbon), although the nutritional content of the sludge remained high. The three-phase ratio of the sludge after six rounds of washing by CA was closest to the ideal three-phase ratio, and the degree of influence on the physical structure of the soil after a land application was reduced, according to the fluctuation of generalized soil structure index (GSSI) and soil three-phase structure distance (STPSD) values. The results indicate that CA as an environmental-friendly washing agent can be the superior choice for sludge HM washing; single washing of sewage sludge may increase the mobility of residual HMs, so multiple washings should be considered for land application of sludge.
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Metais Pesados , Poluentes do Solo , Ácido Edético/química , Esgotos/química , Ácido Cítrico/química , Solo , Metais Pesados/química , Poluentes do Solo/análiseRESUMO
Organic amendments in aided phytostabilization of waste slag containing high levels of heavy metal (loid)s (HMs) are an important way to control the release of HMs in situ. However, the effects of dissolved organic matter (DOM) derived from organic amendments on HMs and microbial community dynamics in waste slag are still unclear. Here, the effect of DOM derived from organic amendments (cow manure) on the geochemical behaviour of HMs and the bacterial community dynamics in mercury (Hg)-thallium (Tl) mining waste slag were investigated. The results showed that the Hg-Tl mining waste slag without the addition of DOM continuously decreased the pH and increased the EC, Eh, SO42-, Hg, and Tl levels in the leachate with increasing incubation time. The addition of DOM significantly increased the pH, EC, SO42-, and arsenic (As) levels but decreased the Eh, Hg, and Tl levels. The addition of DOM significantly increased the diversity and richness of the bacterial community. The dominant bacterial phyla (Proteobacteria, Firmicutes, Acidobacteriota, Actinobacteriota, and Bacteroidota) and genera (Bacillus, Acinetobacter, Delftia, Sphingomonas, and Enterobacter) were changed in association with increases in DOM content and incubation time. The DOM components in the leachate were humic-like substances (C1 and C2), and the DOC content and maximum fluorescence intensity (FMax) values of C1 and C2 in the leachate decreased and first increased and then decreased with increasing incubation time. The correlations between HMs and DOM and the bacterial community showed that the geochemical behaviours of HMs in Hg-Tl mining waste slag were directly influenced by DOM-mediated properties and indirectly influenced by DOM regulation of bacterial community changes. Overall, these results indicated that DOM properties associated with bacterial community changes increased As mobilization but decreased Hg and Tl mobilization from Hg-Tl mining waste slag.
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Arsênio , Mercúrio , Metais Pesados , Animais , Bovinos , Tálio , Matéria Orgânica Dissolvida , Esterco , Substâncias Húmicas/análiseRESUMO
The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.
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Injúria Renal Aguda , Inibidor Tecidual de Metaloproteinase-2 , Adenosina Difosfato Ribose , Animais , Biomarcadores , Cisplatino/toxicidade , Inflamação , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Lipopolissacarídeos , Camundongos , Camundongos Knockout , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 µM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1ß as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg-1 · d-1, i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Glomérulos Renais/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Flavanonas/administração & dosagem , Injeções Intraperitoneais , Glomérulos Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Podócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To explore the technical specifications and clinical outcomes of thrombosed aneurysmal haemodialysis arteriovenous fistula (AVF) treated with ultrasound-guided percutaneous transluminal angioplasty combined with minimal aneurysmotomy. METHODS: This case series study included 11 patients who had thrombosed aneurysmal AVF and underwent salvage procedures over a 13-month period. All procedures were performed under duplex guidance. Minimal aneurysmotomy was performed, along with manual thrombectomy and thrombolytic agent infusion, followed by angioplasty to macerate the thrombus and sufficiently dilate potential stenoses. A successful procedure was defined as immediate restoration of flow through the AVF. RESULTS: The 11 patients (four males and seven females) had a mean age of 49.6 years ± 11.9 years. Six patients (54.5%) had two or more aneurysms. The mean aneurysm maximal diameter was 21.5 mm (standard deviation: ± 5.0 mm), and the mean thrombus length was 12.9 cm (8-22 cm). Ten (83.3%) of the 12 procedures were technically successful. The mean duration of operation was 150.9 minutes (standard deviation: ± 34.2 minutes), and mean postoperative AVF blood flow was 728.6 ml/min (standard deviation: ± 53.7 mi/min). The resumption of hemodialysis was successful in all 11 cases, with a clinical success rate of 100%. The primary patency rates were 90.0% and 75.0% at three and four months over a mean follow-up time of 6.3 months (3-12 months). The secondary patency rates were 90.4% at three and four months. CONCLUSION: A hybrid approach combining ultrasound-guided percutaneous transluminal angioplasty and minimal aneurysmotomy might be a safe and effective method for thrombosed aneurysmal AVF salvage.
Assuntos
Aneurisma , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Trombose , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgia , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
This study aimed to investigate the activating mechanism of the NLRP3 inflammasome in trichloroethylene-sensitized mice. In total, 88 BALB/c female mice were used to establish the trichloroethylene (TCE)-sensitized mouse model. Some of the mice received MitoTEMPO, MCC 950 or soluble recombinant CD59-Cys to inhibit mitochondrial reactive oxygen species (mtROS) production, NLRP3 assembly, or C5b-9 formation. Mouse tubular epithelial cell expression levels of NLRP3, ASC, Caspase 1, IL-1ß, IL-18 and mitochondrial antiviral signaling protein (MAVS) were detected by western blot. Mitochondrial numbers, membrane potential (ΔΨm) and mtROS were detected by using MitoScene Green II, JC-1 dye and MitoSOX Red indicator, respectively. Tubular epithelial cell calcium levels were detected by a Fluo-8 no wash calcium assay kit. Human kidney-2 (HK-2) cells were cultured and stimulated by C5b6 and normal human serum (NHS) to verify the role of C5b-9-induced mitochondrial ROS in activating NLRP3 inflammasome. Urine α1-MG, ß2-MG, and mtROS production and calcium levels were increased, while mitochondrial numbers were decreased in TCE-sensitized positive mice. After treatment with MitoTEMPO, renal tubular injury was alleviated, JC-1 fluorescence and mitochondrial numbers were significantly increased, and mitochondrial ROS were inhibited. The NLRP3 inflammasome was activated in TCE-sensitized positive mice, while Mito TEMPO inhibited MAVS expression and NLRP3 inflammasome activation. The in vitro studies proved that C5b-9 can induce mtROS release and activate the assembly of NLRP3 inflammasome in HK-2 cells. In conclusion, in TCE-sensitized positive mouse renal tubular epithelial cells, C5b-9 caused calcium influx and thus induced mitochondrial injury and mtROS overexpression, finally inducing MAVS expression and NLRP3 inflammasome activation and kidney injury.
Assuntos
Inflamassomos , Tricloroetileno , Animais , Antivirais , Benzimidazóis , Cálcio , Carbocianinas , Caspase 1 , Complexo de Ataque à Membrana do Sistema Complemento , Feminino , Humanos , Inflamassomos/metabolismo , Interleucina-18 , Rim/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Compostos Organofosforados , Piperidinas , Espécies Reativas de Oxigênio/metabolismo , Tricloroetileno/toxicidadeRESUMO
OBJECTIVE: To predict the risk factors for cardiovascular events within 5 years in patients with peritoneal dialysis-associated peritonitis and establish a nomogram for clinical prediction. METHODS: A prediction model was established by conducting an observational study in 150 patients with peritoneal dialysis-associated peritonitis obtained from the Information Database of AnHui Medical University Affiliated Hospital. The nomogram was constructed using the multivariate COX regression model. The C-index and the calibration plot were used to assess the discrimination and calibration of the prediction model. RESULTS: The elderly [HR = 2.453 (1.071-5.619)], history of cardiovascular events [HR = 2.296 (1.220-4.321)], alkaline phosphatase [HR = 1.004 (1.002-1.005)] and culture-positive [HR= 2.173 (1.009-4.682)] were identified as risk predictors of cardiovascular events, while serum albumin [HR = 0.396(0.170-0.924)] was identified as protective predictors of cardiovascular events. Combined with clinical studies, we constructed a nomogram based on the minimum value of the Akaike Information Criterion or Bayesian Information Criterion. The C index of the nomogram is 0.732, revealing great discrimination and appropriate calibration. Through the total score of the nomogram and the result of ROC, we classify patients into high-risk groups (cardiovascular events group) and low-risk groups (no cardiovascular events group). Cardiovascular events were significantly different for patients in the high-risk group compared to the low-risk group (HR = 3.862(2.202-6.772; p < 0.001). CONCLUSIONS: The current novel nomogram can accurately predict cardiovascular events in patients with peritonitis associated with peritoneal dialysis. However, external validation is required before the model can be used in clinic settings.