Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57.182
Filtrar
1.
Sci Rep ; 14(1): 15775, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982238

RESUMO

A three-dimensional convolutional neural network model was developed to classify the severity of chronic kidney disease (CKD) using magnetic resonance imaging (MRI) Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) imaging. Seventy-three patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2, CKD stage G4-5); 172 with moderate renal dysfunction (30 ≤ eGFR < 60 mL/min/1.73 m2, CKD stage G3a/b); and 76 with mild renal dysfunction (eGFR ≥ 60 mL/min/1.73 m2, CKD stage G1-2) participated in this study. The model was applied to the right, left, and both kidneys, as well as to each imaging method (T1-weighted IP/OP/WO images). The best performance was obtained when using bilateral kidneys and IP images, with an accuracy of 0.862 ± 0.036. The overall accuracy was better for the bilateral kidney models than for the unilateral kidney models. Our deep learning approach using kidney MRI can be applied to classify patients with CKD based on the severity of kidney disease.


Assuntos
Taxa de Filtração Glomerular , Rim , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Insuficiência Renal Crônica , Índice de Gravidade de Doença , Humanos , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Rim/diagnóstico por imagem , Rim/patologia , Idoso , Adulto , Aprendizado Profundo , Imageamento Tridimensional/métodos
2.
Ren Fail ; 46(2): 2375033, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967135

RESUMO

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.


Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Flavonas , Rim , Panax notoginseng , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica , Transdução de Sinais , Animais , Camundongos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Panax notoginseng/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Rim/patologia , Rim/efeitos dos fármacos , Astrágalo/química , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão
3.
Sci Signal ; 17(844): eadn6052, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980922

RESUMO

Inhibitors of the transforming growth factor-ß (TGF-ß) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-ß homologs has safety liabilities. TGF-ß1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-ß-binding proteins (LTBPs) present TGF-ß1 in the extracellular matrix, and TGF-ß1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-ß1 presented by LTBPs but did not bind to TGF-ß1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-ß1 that is not accessible on GARP- or LRRC33-presented TGF-ß1, explaining the antibody's selectivity for LTBP-complexed TGF-ß1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-ß1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-ß inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-ß1 as an approach for treating fibrosis.


Assuntos
Matriz Extracelular , Fibrose , Proteínas de Ligação a TGF-beta Latente , Fator de Crescimento Transformador beta1 , Fator de Crescimento Transformador beta1/metabolismo , Animais , Humanos , Proteínas de Ligação a TGF-beta Latente/metabolismo , Proteínas de Ligação a TGF-beta Latente/antagonistas & inibidores , Matriz Extracelular/metabolismo , Camundongos , Masculino , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/tratamento farmacológico , Progressão da Doença , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Camundongos Endogâmicos C57BL
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 501-507, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38952089

RESUMO

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.


Assuntos
Glomerulonefrite por IGA , Receptor Celular 1 do Vírus da Hepatite A , Camundongos Endogâmicos BALB C , Saponinas , Transdução de Sinais , Células Th1 , Células Th2 , Triterpenos , Animais , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/genética , Triterpenos/farmacologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/imunologia , Saponinas/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Camundongos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Interleucina-4/genética , Interleucina-4/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interferon gama/metabolismo , Interferon gama/genética , Masculino , Feminino
5.
J Biomed Mater Res B Appl Biomater ; 112(7): e35443, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968028

RESUMO

The aim of this work was to analyze the effects of long-term exposure to titanium dioxide (TiO2) micro- (MPs) and nanoparticles (NPs) (six and 12 months) on the biochemical and histopathological response of target organs using a murine model. Male Wistar rats were intraperitoneally injected with a suspension of TiO2 NPs (5 nm; TiO2-NP5 group) or MPs (45 µm; TiO2-NP5 group); the control group was injected with saline solution. Six and 12 months post-injection, titanium (Ti) concentration in plasma and target organs was determined spectrometrically (ICP-MS). Blood smears and organ tissue samples were evaluated by light microscopy. Liver and kidney function was evaluated using serum biochemical parameters. Oxidative metabolism was assessed 6 months post-injection (determination of superoxide anion by nitroblue tetrazolium (NBT) test, superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation, and paraoxonase 1). Titanium (Ti) concentration in target organs and plasma was significantly higher in the TiO2-exposed groups than in the control group. Histological evaluation showed the presence of titanium-based particles in the target organs, which displayed no structural alterations, and in blood monocytes. Oxidative metabolism analysis showed that TiO2 NPs were more reactive over time than MPs (p < .05) and mobilization of antioxidant enzymes and membrane damage varied among the studied organs. Clearance of TiO2 micro and nanoparticles differed among the target organs, and lung clearance was more rapid than clearance from the lungs and kidneys (p < .05). Conversely, Ti concentration in plasma increased with time (p < .05). In conclusion, neither serum biochemical parameters nor oxidative metabolism markers appear to be useful as biomarkers of tissue damage in response to TiO2 micro- and nanoparticle deposits at chronic time points.


Assuntos
Ratos Wistar , Titânio , Titânio/química , Animais , Masculino , Ratos , Nanopartículas Metálicas/química , Rim/metabolismo , Rim/patologia , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas/química , Fígado/metabolismo , Fígado/patologia
6.
Sci Rep ; 14(1): 15449, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965392

RESUMO

Hyperuricemia (HUA), a metabolic disease caused by excessive production or decreased excretion of uric acid (UA), has been reported to be closely associated with a variety of UA transporters. Clerodendranthus spicatus (C. spicatus) is an herbal widely used in China for the treatment of HUA. However, the mechanism has not been clarified. Here, the rat model of HUA was induced via 10% fructose. The levels of biochemical indicators, including UA, xanthine oxidase (XOD), adenosine deaminase (ADA), blood urea nitrogen (BUN), and creatinine (Cre), were measured. Western blotting was applied to explore its effect on renal UA transporters, such as urate transporter1 (URAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette super-family G member 2 (ABCG2). Furthermore, the effect of C. spicatus on plasma metabolites was identified by metabolomics. Our results showed that C. spicatus could significantly reduce the serum levels of UA, XOD, ADA and Cre, and improve the renal pathological changes in HUA rats. Meanwhile, C. spicatus significantly inhibited the expression of URAT1 and GLUT9, while increased the expression of ABCG2 in a dose-dependent manner. Metabolomics showed that 13 components, including 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PE, Tyr-Leu and N-cis-15-Tetracosenoyl-C18-sphingosine, were identified as potential biomarkers for the UA-lowering effect of C. spicatus. In addition, pathway enrichment analysis revealed that arginine biosynthesis, biosynthesis of amino acids, pyrimidine metabolism and other metabolic pathways might be involved in the protection of C. spicatus against HUA. This study is the first to explore the mechanism of anti-HUA of C. spicatus through molecular biology and metabolomics analysis, which provides new ideas for the treatment of HUA.


Assuntos
Hiperuricemia , Metabolômica , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ratos , Metabolômica/métodos , Ácido Úrico/sangue , Masculino , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Ratos Sprague-Dawley , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Xantina Oxidase/metabolismo , Modelos Animais de Doenças
7.
PLoS One ; 19(7): e0304387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968252

RESUMO

Lindane is a broad-spectrum insecticide widely used on fruits, vegetables, crops, livestock and on animal premises to control the insects and pests. The extensive use of pesticides and their residues in the soil and water typically join the food chain and thus accumulate in the body tissues of human and animals causing severe health effects. The study was designed to determine the toxicity effects of sub-lethal concentrations of lindane on hemato-biochemical profile and histo-pathological changes in Rohu (Labeo rohita). A significant increase in the absolute (p<0.05) and relative (p<0.05) weights was observed along with severe histo-pathological alterations in liver, kidneys, gills, heart and brain at 30µg/L and 45µg/L concentration of lindane. A significant (p<0.05) decrease in RBCs count, PCV and Hb concentration while a significant (p<0.05) increased leukocytes were observed by 30µg/L and 45µg/L concentrations of lindane at 45 and 60 days of the experiment. Serum total protein and albumin were significantly (p<0.05) decreased while hepatic and renal enzymes were significantly (p<0.05) increased due to 30µg/L and 45µg/L concentrations of lindane at days-45 and 60 of experiment compared to control group. The observations of thin blood smear indicated significantly increased number of erythrocytes having nuclear abnormalities in the fish exposed at 30µg/L and 45µg/L concentrations of lindane. ROS and TBARS were found to be significantly increased while CAT, SOD, POD and GSH were significantly decreased with an increase in the concentration and exposure time of lindane. The results showed that lindane causes oxidative stress and severe hematological, serum biochemical and histo-pathological alterations in the fish even at sub-lethal concentrations.


Assuntos
Cyprinidae , Hexaclorocicloexano , Inseticidas , Rim , Fígado , Animais , Hexaclorocicloexano/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Inseticidas/toxicidade , Cyprinidae/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/patologia , Brânquias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
8.
Ren Fail ; 46(2): 2371988, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38952291

RESUMO

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.


Assuntos
Ácido Clorogênico , Nefropatias Diabéticas , Fibrose , Rim , Metabolismo dos Lipídeos , Receptor Notch1 , Fator de Transcrição STAT3 , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Receptor Notch1/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Animais , Transdução de Sinais/efeitos dos fármacos , Fibrose/tratamento farmacológico , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Humanos , Camundongos , Masculino , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Linhagem Celular
9.
FASEB J ; 38(13): e23769, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38958951

RESUMO

Renal ischemia-reperfusion injury (IRI) is an integral process in renal transplantation, which results in compromised graft survival. Macrophages play an important role in both the early inflammatory period and late fibrotic period in response to IRI. In this study, we investigated whether scutellarin (SCU) could protect against renal IRI by regulating macrophage polarization. Mice were given SCU (5-50 mg/kg) by gavage 1 h earlier, followed by a unilateral renal IRI. Renal function and pathological injury were assessed 24 h after reperfusion. The results showed that administration of 50 mg/kg SCU significantly improved renal function and renal pathology in IRI mice. In addition, SCU alleviated IRI-induced apoptosis. Meanwhile, it reduced macrophage infiltration and inhibited pro-inflammatory macrophage polarization. Moreover, in RAW 264.7 cells and primary bone marrow-derived macrophages (BMDMs) exposed to SCU, we found that 150 µM SCU inhibited these cells to polarize to an inflammatory phenotype induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, SCU has no influence on anti-inflammatory macrophage polarization in vivo and in vitro induced by in interleukin-4 (IL-4). Finally, we explored the effect of SCU on the activation of the mitogen-activated protein kinase (MAPK) pathway both in vivo and in vitro. We found that SCU suppressed the activation of the MAPK pathway, including the extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38. Our results demonstrated that SCU protects the kidney against IRI by inhibiting macrophage infiltration and polarization toward pro-inflammatory phenotype via the MAPK pathway, suggesting that SCU may be therapeutically important in treatment of IRI.


Assuntos
Apigenina , Glucuronatos , Sistema de Sinalização das MAP Quinases , Macrófagos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Camundongos , Apigenina/farmacologia , Glucuronatos/farmacologia , Glucuronatos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células RAW 264.7 , Masculino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Apoptose/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/prevenção & controle , Inflamação/patologia
10.
Sci Rep ; 14(1): 15140, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956234

RESUMO

Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice.


Assuntos
Modelos Animais de Doenças , Camundongos Knockout , Nanopartículas , Doenças Renais Policísticas , Sirolimo , Animais , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Camundongos , Doenças Renais Policísticas/tratamento farmacológico , Doenças Renais Policísticas/metabolismo , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Nanopartículas/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Rim/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Sistemas de Liberação de Medicamentos , Masculino
11.
Clin Exp Med ; 24(1): 148, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960929

RESUMO

Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical prosthetic valves require long-term anticoagulant therapy. Nonetheless, warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical prosthetic valves constitute a special group among the entire anticoagulant population. The present study recorded two cases of patients who had undergone mechanical prosthetic valve surgery and were receiving warfarin therapy. They presented to the hospital with gross hematuria and progressive creatinine levels. Notably, their international normalized ratio (INR) did not exceed three. Subsequent renal biopsies confirmed WRN with IgA nephropathy. The two patients continued to receive warfarin as anticoagulation therapy and were prescribed oral corticosteroids and cyclophosphamide, which resulted in improved renal function during the follow-up. Based on a review of all relevant literature and the present study, we proposed a new challenge: must elevated INR levels be one of the criteria for clinical diagnosis of WRN? Perhaps some inspiration can be drawn from the present article.


Assuntos
Anticoagulantes , Varfarina , Humanos , Varfarina/efeitos adversos , Anticoagulantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Coeficiente Internacional Normatizado , Idoso , Glomerulonefrite por IGA , Biópsia , Injúria Renal Aguda/induzido quimicamente , Rim/patologia , Rim/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Corticosteroides/uso terapêutico , Corticosteroides/efeitos adversos , Corticosteroides/administração & dosagem
13.
Life Sci ; 351: 122813, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38857655

RESUMO

The cytoplasmic oligomer NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated in most inflammatory and autoimmune diseases. Here, we highlight the significance of NLRP3 in diverse renal disorders, demonstrating its activation in macrophages and non-immune tubular epithelial and mesangial cells in response to various stimuli. This activation leads to the release of pro-inflammatory cytokines, contributing to the development of acute kidney injury (AKI), chronic renal injury, or fibrosis. In AKI, NLRP3 inflammasome activation and pyroptotic renal tubular cell death is driven by contrast and chemotherapeutic agents, sepsis, and rhabdomyolysis. Nevertheless, inflammasome is provoked in disorders such as crystal and diabetic nephropathy, obesity-related renal fibrosis, lupus nephritis, and hypertension-induced renal damage that induce chronic kidney injury and/or fibrosis. The mechanisms by which the inflammatory NLRP3/ Apoptosis-associated Speck-like protein containing a Caspase recruitment domain (ASC)/caspase-1/interleukin (IL)-1ß & IL-18 pathway can turn on renal fibrosis is also comprehended. This review further outlines the involvement of dopamine and its associated G protein-coupled receptors (GPCRs), including D1-like (D1, D5) and D2-like (D2-D4) subtypes, in regulating this inflammation-linked renal dysfunction pathway. Hence, we identify D-related receptors as promising targets for renal disease management by inhibiting the functionality of the NLRP3 inflammasome.


Assuntos
Inflamassomos , Nefropatias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Animais , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/etiologia , Rim/patologia , Rim/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia
14.
Ren Fail ; 46(2): 2359642, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38860328

RESUMO

OBJECTIVES: Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. METHODS: Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. RESULTS: On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). CONCLUSIONS: Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.


Assuntos
Imagem de Difusão por Ressonância Magnética , Modelos Animais de Doenças , Ratos Sprague-Dawley , Obstrução Ureteral , Animais , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/fisiopatologia , Ratos , Imagem de Difusão por Ressonância Magnética/métodos , Masculino , Córtex Renal/diagnóstico por imagem , Córtex Renal/patologia , Rim/diagnóstico por imagem , Rim/patologia , Medula Renal/diagnóstico por imagem , Medula Renal/patologia
15.
J Zoo Wildl Med ; 55(2): 381-392, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38875194

RESUMO

Of the 202 species of Chamaeleonidae, 38.6% are globally threatened. Currently, nearly a thousand individual chameleons from 36 different species are kept in zoological institutions worldwide. The objectives of this study were to assess the main mortality causes of chameleons in zoological institutions, the prevalence of renal lesions at necropsy, and the environmental factors associated with renal lesions. An online survey was sent to 245 zoological institutions worldwide to collect information about species and sex distribution, necropsy results, and husbandry parameters. Necropsy reports of the last 10 yr were requested from participating institutions (n = 65) when available. Mortality causes were classified into three categories (open diagnosis, infectious, and noninfectious), and noninfectious causes were further subdivided into seven categories (renal, reproductive, myoarthroskeletal, digestive, ophthalmologic, denutrition/multisystemic, and neoplastic). The prevalence of renal lesions was recorded. Multiple linear regression models were used with the prevalence of renal diseases as the dependent variable, and exhibit minimum and maximum hygrometry; exhibit highest and coolest temperature; as well as minimum, mean, and maximum hygrometry of the geographical area as independent variables, combining all chameleon species with similar environmental requirements. Results were obtained for 14 species (n = 412 individuals). The main mortality causes were infectious (46.8%), noninfectious renal (11.4%), and noninfectious reproductive (10.7%) diseases, with all cases of fatal reproductive diseases reported in females. Of the individuals that underwent renal histopathology, 41.7% displayed renal lesions. There was a tendency towards higher renal lesion prevalence in zoos located in areas with lower mean hygrometry (P = 0.05). Further research studies about infectious, renal, and reproductive diseases of Chamaeleonidae are warranted.


Assuntos
Animais de Zoológico , Nefropatias , Lagartos , Animais , Nefropatias/veterinária , Nefropatias/mortalidade , Nefropatias/epidemiologia , Nefropatias/patologia , Feminino , Prevalência , Masculino , Rim/patologia
16.
Sci Immunol ; 9(96): eadd6774, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875317

RESUMO

Pro-inflammatory CD4+ T cells are major drivers of autoimmune diseases, yet therapies modulating T cell phenotypes to promote an anti-inflammatory state are lacking. Here, we identify T helper 17 (TH17) cell plasticity in the kidneys of patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis on the basis of single-cell (sc) T cell receptor analysis and scRNA velocity. To uncover molecules driving T cell polarization and plasticity, we established an in vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen and applied it to mouse models of glomerulonephritis and colitis. CRISPR-based gene targeting in TH17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (TH1) and regulatory T cells could be quantified. Furthermore, we show that iCROP-seq can facilitate the identification of therapeutic targets by efficient functional stratification of genes and pathways in a disease- and tissue-specific manner. These findings uncover TH17 to TH1 cell plasticity in the human kidney in the context of renal autoimmunity.


Assuntos
Análise de Célula Única , Células Th17 , Animais , Humanos , Camundongos , Células Th17/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/genética , Plasticidade Celular/imunologia , Plasticidade Celular/genética , Rim/imunologia , Rim/patologia , Camundongos Endogâmicos C57BL , Sistemas CRISPR-Cas , Colite/imunologia , Colite/genética , Inflamação/imunologia , Inflamação/genética , Feminino , Masculino , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/imunologia
17.
BMC Vet Res ; 20(1): 262, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890656

RESUMO

BACKGROUND: In recent years, anthropogenic activities have released heavy metals and polluted the aquatic environment. This study investigated the ability of the silica-stabilized magnetite (Si-M) nanocomposite materials to dispose of lead nitrate (Pb(NO3)2) toxicity in Nile tilapia and African catfish. RESULTS: Preliminary toxicity tests were conducted and determined the median lethal concentration (LC50) of lead nitrate (Pb(NO3)2) to Nile tilapia and African catfish to be 5 mg/l. The sublethal concentration, equivalent to 1/20 of the 96-hour LC50 Pb(NO3)2, was selected for our experiment. Fish of each species were divided into four duplicated groups. The first group served as the control negative group, while the second group (Pb group) was exposed to 0.25 mg/l Pb(NO3)2 (1/20 of the 96-hour LC50). The third group (Si-MNPs) was exposed to silica-stabilized magnetite nanoparticles at a concentration of 1 mg/l, and the fourth group (Pb + Si-MNPs) was exposed simultaneously to Pb(NO3)2 and Si-MNPs at the same concentrations as the second and third groups. Throughout the experimental period, no mortalities or abnormal clinical observations were recorded in any of the treated groups, except for melanosis and abnormal nervous behavior observed in some fish in the Pb group. After three weeks of sublethal exposure, we analyzed hepatorenal indices, oxidative stress parameters, and genotoxicity. Values of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), urea, and creatinine were significantly higher in the Pb-intoxicated groups compared to the control and Pb + Si-MNPs groups in both fish species. Oxidative stress parameters showed a significant decrease in reduced glutathione (GSH) concentration, along with a significant increase in malondialdehyde (MDA) and protein carbonyl content (PCC) concentrations, as well as DNA fragmentation percentage in the Pb group. However, these values were nearly restored to control levels in the Pb + Si-MNPs groups. High lead accumulation was observed in the liver and gills of the Pb group, with the least accumulation in the muscles of tilapia and catfish in the Pb + Si-MNPs group. Histopathological analysis of tissue samples from Pb-exposed groups of tilapia and catfish revealed brain vacuolation, gill fusion, hyperplasia, and marked hepatocellular and renal necrosis, contrasting with Pb + Si-MNP group, which appeared to have an apparently normal tissue structure. CONCLUSIONS: Our results demonstrate that Si-MNPs are safe and effective aqueous additives in reducing the toxic effects of Pb (NO3)2 on fish tissue through the lead-chelating ability of Si-MNPs in water before being absorbed by fish.


Assuntos
Peixes-Gato , Ciclídeos , Chumbo , Fígado , Nitratos , Estresse Oxidativo , Dióxido de Silício , Poluentes Químicos da Água , Animais , Chumbo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Dióxido de Silício/química , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Poluentes Químicos da Água/toxicidade , Nanocompostos/química , Nanocompostos/toxicidade , Quelantes/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Bioacumulação , Brânquias/efeitos dos fármacos , Brânquias/patologia , Dano ao DNA/efeitos dos fármacos
18.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891834

RESUMO

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary disorder that affects the kidneys, characterized by the development of an excessive number of fluid-filled cysts of varying sizes in both kidneys. Along with the progression of ADPKD, these enlarged cysts displace normal kidney tissue, often accompanied by interstitial fibrosis and inflammation, and significantly impair renal function, leading to end-stage renal disease. Currently, the precise mechanisms underlying ADPKD remain elusive, and a definitive cure has yet to be discovered. This review delineates the epidemiology, pathological features, and clinical diagnostics of ADPKD or ADPKD-like disease across human populations, as well as companion animals and other domesticated species. A light has been shed on pivotal genes and biological pathways essential for preventing and managing ADPKD, which underscores the importance of cross-species research in addressing this complex condition. Treatment options are currently limited to Tolvaptan, dialysis, or surgical excision of large cysts. However, comparative studies of ADPKD across different species hold promise for unveiling novel insights and therapeutic strategies to combat this disease.


Assuntos
Rim Policístico Autossômico Dominante , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/terapia , Rim Policístico Autossômico Dominante/patologia , Humanos , Animais , Rim/patologia , Rim/metabolismo , Modelos Animais de Doenças
19.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891942

RESUMO

While considerable attention has been devoted to respiratory manifestations, such as pneumonia and acute respiratory distress syndrome (ARDS), emerging evidence underlines the significance of extrapulmonary involvement. In this study, we examined 15 hospitalized patients who succumbed to severe complications following SARS-CoV-2 infection. These patients were admitted to the Sibiu County Clinical Emergency Hospital in Sibiu, Romania, between March and October 2021. All patients were ethnic Romanians. Conducted within a COVID-19-restricted environment and adhering to national safety protocols, autopsies provided a comprehensive understanding of the disease's multisystemic impact. Detailed macroscopic evaluations and histopathological analyses of myocardial, renal, hepatic, splenic, and gastrointestinal tissues were performed. Additionally, reverse transcription-quantitative polymerase chain reaction (rt-qPCR) assays and immunohistochemical staining were employed to detect the viral genome and nucleocapsid within the tissues. Myocardial lesions, including ischemic microstructural changes and inflammatory infiltrates, were prevalent, indicative of COVID-19's cardiac implications, while renal pathology revealed the chronic alterations, acute tubular necrosis, and inflammatory infiltrates most evident. Hepatic examination identified hepatocellular necroinflammatory changes and hepatocytic cytopathy, highlighting the hepatic involvement of SARS-CoV-2 infection. Splenic parenchymal disorganization was prominent, indicating systemic immune dysregulation. Furthermore, gastrointestinal examinations unveiled nonspecific changes. Molecular analyses detected viral genes in various organs, with immunohistochemical assays confirming viral presence predominantly in macrophages and fibroblasts. These findings highlighted the systemic nature of SARS-CoV-2 infection, emphasizing the need for comprehensive clinical management strategies and targeted therapeutic approaches beyond respiratory systems.


Assuntos
COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/genética , COVID-19/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Rim/virologia , Rim/patologia , Rim/metabolismo , Fígado/virologia , Fígado/patologia , Fígado/metabolismo , Adulto , Baço/virologia , Baço/patologia , Baço/metabolismo , Romênia , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Miocárdio/patologia , Miocárdio/metabolismo , Autopsia , Idoso de 80 Anos ou mais , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo
20.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892068

RESUMO

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.


Assuntos
Ceramidas , Nanopartículas Metálicas , Ratos Wistar , Titânio , Óxido de Zinco , Animais , Óxido de Zinco/toxicidade , Titânio/toxicidade , Titânio/efeitos adversos , Ratos , Ceramidas/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Masculino , Administração Oral , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...