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1.
Mol Med ; 29(1): 42, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013504

RESUMO

BACKGROUND: Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway. METHODS: Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined. RESULTS: We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro. CONCLUSION: Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.


Assuntos
Injúria Renal Aguda , Ferroptose , Traumatismo por Reperfusão , Animais , Camundongos , Proteínas Quinases Ativadas por AMP , Espécies Reativas de Oxigênio , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Traumatismo por Reperfusão/tratamento farmacológico , Ferro , Isquemia , Lipídeos
2.
Opt Express ; 31(9): 14308-14316, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157298

RESUMO

A 32×32 100 GHz silicon photonic integrated arrayed waveguide grating router (AWGR) is experimentally demonstrated for dense wavelength division multiplexing (DWDM) applications. The dimension of the AWGR is 2.57 mm×1.09 mm with a core size of 1.31 mm×0.64 mm. It exhibits 6.07 dB maximum channel loss non-uniformity with -1.66 dB best-case insertion loss and average channel crosstalk of -15.74 dB. In addition, in the case of 25 Gb/s signals, the device successfully realizes high-speed data routing. The AWG router provides clear optical eye diagrams and low power penalty at bit-error-rates of 10-9.

3.
Appl Opt ; 62(5): 1279-1284, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36821228

RESUMO

We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.19 dB on the operational waveband. Furthermore, the proposed device shows a great robustness to fabrication imperfection, with a waveguide width deviation of 50 nm and ambient temperature change from 0°C to 200°C. These properties make the design a potential candidate for ultrahigh-density photonic integration chips.

4.
Appl Opt ; 62(7): 1662-1666, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132910

RESUMO

Photonic antennas are critical in applications such as spectroscopy, photovoltaics, optical communications, holography, and sensors. Metal antennas are widely used because of their small size, but they are difficult to be compatible with a CMOS. All-dielectric antennas are easier to integrate with Si waveguides, but are generally larger in size. In this paper, we propose the design of a small-sized, high-efficiency semicircular dielectric grating antenna. The antenna's key size is only 2.37µm×4.74µm, and the emission efficiency reaches over 64% in the wavelength range from 1.16 to 1.61 µm. The antenna provides a new, to the best of our knowledge, approach for three-dimensional optical interconnections between different decks of integrated photonic circuits.

5.
Health Expect ; 26(3): 1368-1379, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37013625

RESUMO

INTRODUCTION: The level of physical activity of people undergoing haemodialyses is low, so understanding what factors underlie the motivation to be physically active in people undergoing haemodialyses is important. Therefore, this qualitative study aims to explore the different motivation types and corresponding basic psychological needs (BPNs) of people undergoing haemodialyses based on self-determination theory. METHODS: We adopted the objective sampling method to select 19 patients with the end-stage renal disease aged from 28 to 66 years old from a tertiary hospital in Xi'an. They underwent haemodialyses five to six times every 2 weeks for more than 3 months. Then, we conducted semistructured one-on-one interviews with 19 people undergoing haemodialyses using qualitative content analysis. All interviews were recorded, transcribed verbatim and analyzed on a thematic analysis. RESULTS: We analyzed four motivation types of patients, namely four themes, including entrenching in physical inactivity (Amotivation), breaking physical inactivity (Controlled motivation), finding one's way (Autonomous regulation) and enjoying the positive effects of physical activity (Intrinsic motivation). Each motivation is dominated by one or more BPNs. For example, inadequate Competence such as decreased physical function is the reason why the patient does not perform physical activities. Due to the lack of health education on physical activity, people undergoing haemodialyses often lack the motivation for controlled regulation. The motivation for self-regulation is generated by the patients' promotion of meeting BPNs, such as normal social interactions. The formation of patients' autonomous motivation can't be separated from the effective understanding felt by other patients, because their situations are similar. Enjoying physical activity promotes the formation of patients' intrinsic motivation and the maintenance of this behaviour. CONCLUSION: Perceived Competence, Relatedness and Autonomous Motivation are important determinants for physical activity in people undergoing haemodialyses. Patients need to internalize the changed values and skills, so as to generate the motivation of self-regulation, rather than external or controlled forms of motivation regulation, to better maintain behaviour change. PATIENT OR PUBLIC CONTRIBUTION: People undergoing haemodialyses were involved in the development of the interview topic guide to ensure all relevant topics were explored.


Assuntos
Exercício Físico , Motivação , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Exercício Físico/psicologia , Pesquisa Qualitativa
6.
Opt Express ; 30(26): 47326-47337, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558663

RESUMO

3D doping structure has significant advantages in modulation efficiency and loss compared with 2D modulator doping profiles. However, to the best of our knowledge, previous work on 3D simulation methods for interdigitated doping designs applied simplified models, which prohibited complex 3D doping. In this work, innovative omni junctions, based on the effective 3D Monte-Carlo method, are believed to be the first proposed for high-performance modulators. Simulation results show that the modulation efficiency reaches 0.88 V·cm, while the loss is only 16 dB/cm, with capacitance below 0.42 pF/mm. This work provides a modulator design with superior modulation efficiency and serviceability for high-speed datacom.

7.
Small ; 16(47): e2004654, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33136308

RESUMO

Catalytic generation of reactive oxygen species has been developed as a promising methodology for tumor therapy. Direct O2•- production from intratumor oxygen exhibits exceptional tumor therapeutic efficacy. Herein, this therapy strategy is demonstrated by a pH-responsive hybrid of porous CeO2 nanorods and sodium polystyrene sulfonate that delivers high oxidative activity for O2•- generation within acidic tumor microenvironments for chemodynamic therapy and only limited oxidative activity in neutral media to limit damage to healthy organs. The hydrated polymer-nanorod hybrids with large hydrodynamic diameters form nanoreactors that locally trap oxygen and biological substrates inside and improve the charge transfer between the catalysts and substrates in the tumor microenvironment, leading to enhanced catalytic O2•- production and consequent oxidation. Together with successful in vitro and in vivo experiments, these data show that the use of hybrids provides a compelling opportunity for the delivery selective chemodynamic tumor therapy.


Assuntos
Cério , Neoplasias , Estresse Oxidativo , Polímeros , Cério/química , Cério/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Polímeros/química , Microambiente Tumoral/efeitos dos fármacos
8.
J Autoimmun ; 97: 100-107, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30385082

RESUMO

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. The pathologic hallmark of IgAN is immune complex deposited in glomerular mesangium, which induces inflammation and affects the kidney's normal functions. The exact pathogenesis of IgAN, however, remains obscure. Further, in current clinical practice, the diagnosis relies on needle biopsy of renal tissue. Therefore, a non-invasive method for diagnosis and prognosis surveillance of the disease is highly desirable. To this end, we investigated the T cell receptor beta chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire in circulating lymphocytes and compared them with kidney infiltrating lymphocytes using immune repertoire high throughput sequencing. We found that some features of TCRB and IGH in renal tissues were remarkably different from that in the blood, including decreased repertoire diversity, increased IgA and IgG frequency, and more antigen-experienced B cells. The complementarity-determining region 3 (CDR3) length of circulating TCRB and IGH in IgAN patients was significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clonal selection. The IgA1 frequency in the blood of IgAN patients is significantly higher than that in other Nephropathy (NIgAN) patients and healthy control. Importantly we identified a set of TCRB and IGH clones, which can be used to distinguish IgAN from NIgAN and healthy controls with high accuracy. These results indicated that the TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for the diagnosis of IgAN. The characteristics of the kidney infiltrating and circulating lymphocytes repertoires shed light on IgAN detection, treatment and surveillance.


Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/etiologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adolescente , Adulto , Idoso , Regiões Determinantes de Complementaridade/imunologia , Regiões Determinantes de Complementaridade/metabolismo , Biologia Computacional/métodos , Suscetibilidade a Doenças , Feminino , Glomerulonefrite por IGA/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina G/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Int J Med Sci ; 11(10): 1001-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25076846

RESUMO

Bcrp1/ABCG2 is exclusively expressed in side population (SP) cells, however, it has not been fully elucidated whether it has an impact on the viability, proliferation and paracrine actions in kidney SP cells under oxygen-glucose deprivation (OGD) followed by reoxygenation. In this study, we found that 2-h OGD did not injure SP cells (sub-lethal OGD) but induced SP cells proliferation 48 and 72 h after reoxygenation; whereas 4-h OGD markedly injured the cells (lethal OGD) and led to apoptosis 24-72 h after reoxygenation. Fumitremorgin C, an inhibitor of ABCG2, attenuated both the proliferation and viability of SP cells. Sub-lethal and lethal OGD induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP cells, which was inhibited by Fumitremorgin C. Collectively, these findings provide evidence for a crucial role for the ABCG2 expression in the viability, proliferation and paracrine actions of kidney SP cells after OGD.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Glicemia/metabolismo , Sobrevivência Celular/fisiologia , Rim/metabolismo , Oxigênio/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Ciclo Celular/genética , Ciclo Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Células Cultivadas , Rim/citologia , Masculino , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Int J Clin Pharmacol Ther ; 52(2): 95-102, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24161158

RESUMO

OBJECTIVE: To compare the efficacy of mycophenolate mofetil (MMF)/prednisone to cyclophosphamide (CYC)/prednisone in the treatment of severe IgA nephropathy. METHODS: Patients (n = 84) with severe IgA nephropathy received either MMF/prednisone (MMF group) or CYC/prednisone (CYC group). The MMF induction dose was 1.5 g/d for 6 months and the maintenance dose was 0.75 - 1.0 g/day for 12 months. The CYC induction dose was 0.8 - 1.0 g/month for 6 months and the maintenance dose was 0.8 - 1.0 g/3 months for 12 months. Laboratory tests, clinical remission rate and side effects were investigated. RESULTS: After 18 months of treatment, the total effective rate in the MMF group was significantly higher than that of the CYC group. Patients' 24-hour urinary protein excretion in the MMF group was lower than the CYC group. Patients' plasma albumin and total protein in the MMF group was higher than the CYC group. MMF and prednisone reduced serum lipids, while in the CYC group serum lipids remained unchanged. There was also a lower incidence of adverse effects in the MMF group (4.76%) than in the CYC group (26.2%). CONCLUSION: Combination therapy with MMF and prednisone for severe IgA nephropathy achieved a higher remission rate compared to treatment with CYC and prednisone. This therapy also reduced the 24-hour urinary protein and serum lipids while increasing plasma albumin and improving renal function. The incidence of adverse effects was significantly lower in the MMF group compared to the CYC group. *These authors have contributed equally to this work.


Assuntos
Ciclofosfamida/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Ácido Micofenólico/análogos & derivados , Prednisona/administração & dosagem , Adulto , Ciclofosfamida/efeitos adversos , Quimioterapia Combinada , Feminino , Glomerulonefrite por IGA/sangue , Humanos , Lipídeos/sangue , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisona/efeitos adversos , Albumina Sérica/análise
11.
Clin Chim Acta ; 551: 117616, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37884118

RESUMO

BACKGROUND: Oxidized lipids are essential bioactive lipid mediators generated during infection that regulate oxidative stress and the inflammatory response, but their signatures in patients with sepsis-associated acute kidney injury (SA-AKI) are poorly understood. This study analyzed the oxidative lipidomics of plasma from patients with SA-AKI to reveal the underlying biomarkers and pathophysiological mechanisms involved in sepsis. MATERIALS: A total of 67 patients with SA-AKI and 20 age- and sex-matched healthy controls (HCs) participated in this prospective cohort study. Among the patients with SA-AKI, 14 cases had stage I-II AKI and 53 cases had stage III AKI. Oxidative lipidomic analysis of plasma samples was conducted using ultra performance liquid chromatography coupled with tandem mass spectrometric (UPLC-MS /MS) detection. RESULTS: Among 21 kinds of differentially oxidized lipids, 5(S),12(S)-DiHETE, 5-isoPGF2VI, 5,6-DiHETrE, 11,12-EET and 9,10-DiHOME showed the best performance. The prediction model incorporating them has shown highly sensitive and specific in distinguishing different stages of SA-AKI from HCs. The annotation of Kyoto Encyclopedia of Genes and Genomes illustrated that the overall downregulation of vascular smooth muscle contraction was closely related to the pathophysiological mechanism of SA-AKI. CONCLUSION: This study revealed alterations in the characteristic oxidized lipids in the plasma of SA-AKI patients, and these lipids had high diagnostic efficiency and potential targeted intervention value for SA-AKI.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Lipidômica , Estudos Prospectivos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Sepse/complicações , Estresse Oxidativo , Lipídeos
12.
Life Sci ; 322: 121671, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37023953

RESUMO

In diabetic kidney disease (DKD), the long-term hyperactivation of yes-associated protein (YAP)/transcriptional coactivator PDZ-binding motif (TAZ) in renal proximal tubule epithelial cells (RPTCs) plays an important role in progressive tubulointerstitial fibrosis. Sodium-glucose cotransporter 2 (SGLT2) is highly expressed in RPTCs, but its relationship with YAP/TAZ in tubulointerstitial fibrosis in DKD is still unknown. The purpose of this study was to clarify whether the SGLT2 inhibitor (SGLT2i) dapagliflozin could alleviate renal tubulointerstitial fibrosis in DKD by regulating YAP/TAZ. We examined 58 patients with DKD confirmed by renal biopsy and found that the expression and nuclear translocation of YAP/TAZ increased with the exacerbation of chronic kidney disease classification. In models of DKD, dapagliflozin showed similar effects to verteporfin, an inhibitor of YAP/TAZ, in reducing the activation of YAP/TAZ and downregulating the expression of their target genes, connective tissue growth factor (CTGF) and amphiregulin in vivo and in vitro. Silencing SGLT2 also confirmed this effect. Importantly, dapagliflozin showed a better effect than verteporfin in inhibiting inflammation, oxidative stress and fibrosis in the kidney in DKD rats. Taken together, this study proved for the first time that dapagliflozin delayed tubulointerstitial fibrosis at least partly by inhibiting YAP/TAZ activation, which further enriched the antifibrotic effect of SGLT2i.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Ratos , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Transdução de Sinais , Transportador 2 de Glucose-Sódio/metabolismo , Proteínas de Sinalização YAP , Verteporfina/farmacologia , Proteínas de Ciclo Celular/metabolismo , Fibrose
13.
Transpl Int ; 25(1): 118-26, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22017688

RESUMO

Activation of NF-κB pathway and co-stimulatory system CD40/CD40L promotes the inflammation, which plays a key role in the failure of islet graft. Therefore, the purpose of this study was to determine if simultaneous blockade of CD40/CD40L and IκB/NF-κB pathways could protect islet graft. Streptozocin-induced diabetic Wistar rats were transplanted intraportally with 2000 IEQ islets isolated from Sprague-Dawley rats. The rats were divided into five groups: nontreatment group, AdGFP-treated group, Ad-IκBα-treated group, Ad-sCD40LIg-treated group, and Ad-IκBα-IRES(2) -sCD40L-treated group. The islet graft mean survival time (MST), insulin expression of islet grafts, and the levels of cytokines in peripheral blood, were measured for the animals in each group. Our study confirmed that islet cells transfected with low doses of adenovirus could achieve high transfection efficiency, and would not affect the function of islet cells (P > 0.05). Splenocytes cultured with Ad-IκBα-IRES2-CD40L-transfected islets resulted in homospecific hyporesponsiveness. The islet graft MST (>100 d) in the Ad-IκBα-IRES2-sCD40L-treated group was dramatically prolonged compared with that in the nontreatment group (7.1 ± 1.16 d). In addition, TNF-α, IL-1ß, and IFN-γ were diminished in the Ad-IκBα-IRES2-sCD40L-treated group, which was commensurate with the reduced cellular infiltration (P < 0.01). Simultaneous blockade of the CD40/CD40L and IκB/NF-κB pathways could effectively extend the survival of islet grafts.


Assuntos
Antígenos CD40/biossíntese , Ligante de CD40/biossíntese , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , NF-kappa B/metabolismo , Animais , Linhagem Celular , Citocinas/biossíntese , Diabetes Mellitus Experimental , Sobrevivência de Enxerto , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Baço/citologia , Estreptozocina/farmacologia , Fatores de Tempo
14.
Front Physiol ; 13: 945827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117692

RESUMO

Acute kidney injury (AKI) is a complex clinical syndrome with multiple etiologies and pathogenesis, which lacks early biomarkers and targeted therapy. Recently, macrophage migration inhibitory factor (MIF) family protein have received increasing attention owing to its pleiotropic protein molecule character in acute kidney injury, where it performed a dual role in the pathological process. macrophage migration inhibitory factor and macrophage migration inhibitory factor-2 are released into the peripheral circulation when Acute kidney injury occurs and interact with various cellular pathways. On the one hand, macrophage migration inhibitory factor exerts a protective effect in anti-oxidation and macrophage migration inhibitory factor-2 promotes cell proliferation and ameliorates renal fibrosis. On the other hand, macrophage migration inhibitory factor aggravates renal injury as an upstream inflammation factor. Herein, we provide an overview on the biological role and possible mechanisms of macrophage migration inhibitory factor and macrophage migration inhibitory factor-2 in the process of Acute kidney injury and the clinical application prospects of macrophage migration inhibitory factor family proteins as a potential therapeutic target.

15.
Oxid Med Cell Longev ; 2022: 4326695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873795

RESUMO

Xanthine oxidase (XO) utilizes molecular oxygen as a substrate to convert purine substrates into uric acid, superoxide, and hydrogen peroxide, which is one of the main enzyme pathways to produce reactive oxygen species (ROS) during septic inflammation and oxidative stress. However, it is not clear whether XO inhibition can improve sepsis-induced renal hypoxia in sepsis-induced acute kidney injury (SI-AKI) mice. In this study, pretreatment with febuxostat, an XO-specific inhibitor, or kidney knockdown of XO by shRNA in vivo significantly improved the prognosis of SI-AKI, not only by reducing the levels of blood urea nitrogen, serum creatinine, tumor necrosis factor-α, interleukin-6, and interleukin-1ß in peripheral blood but also by improving histological damage and apoptosis, reducing the production of ROS, and infiltrating neutrophils and macrophages in the kidney. More importantly, we found that pharmacological and genetic inhibition of XO significantly improved renal hypoxia in SI-AKI mice by a hypoxia probe via fluorescence staining. This effect was further confirmed by the decrease in hypoxia-inducible factor-1α expression in the kidneys of mice with pharmacological and genetic inhibition of XO. In vitro, the change in XO activity induced by lipopolysaccharide was related to the change in hypoxia in HK-2 cells. Febuxostat and XO siRNA significantly relieved the hypoxia of HK-2 cells cultured in 2% oxygen and reversed the decrease in cell viability induced by lipopolysaccharide. Our results provide novel insights into the nephroprotection of XO inhibition in SI-AKI, improving cell hypoxia by inhibiting XO activity and reducing apoptosis, inflammation, and oxidative stress.


Assuntos
Injúria Renal Aguda , Sepse , Injúria Renal Aguda/etiologia , Animais , Febuxostat/farmacologia , Febuxostat/uso terapêutico , Hipóxia/complicações , Inflamação/tratamento farmacológico , Isquemia , Rim , Lipopolissacarídeos/farmacologia , Camundongos , Oxigênio/farmacologia , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sepse/complicações , Xantina Oxidase/metabolismo
16.
Front Physiol ; 13: 927794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277194

RESUMO

The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.

17.
Front Psychiatry ; 13: 992404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245863

RESUMO

Background: Self-management in patients with early chronic kidney disease (CKD) can effectively delay damage to renal function. However, with the continuous spread of COVID-19, patients cannot receive timely treatment, which can lead to different affects, resulting in ego depletion and serious challenges to self-management. This study aimed to investigate the mediating and suppressing roles of ego depletion on the relationship between positive and negative affect and self-management among patients with early CKD during the COVID-19 pandemic in China. Methods: A total of 383 patients with early CKD from three tertiary hospitals were enrolled by convenience sampling in our cross-sectional study from September 2021 to March 2022. Participants completed the Sociodemographic Questionnaire, Positive Affect and Negative Affect Scale, Self-Regulating Fatigue Scale and Chronic Kidney Disease Self-Management Instrument. A structural equation model was conducted to test the mediating and suppressing effects of ego depletion on the relationship between positive and negative affect and self-management. Results: The average score of the participants' self-management was 84.54 (SD: 19.72), and nearly 60% of them were at low and moderate levels. The mediating effect of positive affect on self-management through ego depletion was significant (ß = 0.248, 95% CI: 0.170 to 0.376), accounting for 53.22% of the total effect. The suppressing effect of negative affect on self-management through ego depletion was significant (ß = -0.191, 95% CI: -0.310 to -0.118), and the absolute value of the ratio of the suppressing effect to the direct effect was 66.55%. Conclusions: Ego depletion partially mediated the relationship between positive affect and self-management while suppressing the relationship between negative affect and self-management among patients with early CKD during the COVID-19 pandemic. The reduction of patients' ego depletion must be taken as the intervention target to improve self-management and delay the progression of CKD.

18.
Oxid Med Cell Longev ; 2022: 9035547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160707

RESUMO

In the treatment of malignant tumors, the effectiveness of cisplatin (CP) is limited by its nephrotoxicity, leading to cisplatin-induced acute kidney injury (CP-AKI). Polydatin (PD) has been demonstrated to regulate autophagy in tumors, sepsis, and diabetes. We have recently confirmed that PD attenuated CP-AKI by inhibiting ferroptosis, but it is not clear whether PD can regulate autophagy to protect from CP-AKI. The purpose of this study was to investigate the effect of PD on autophagy in CP-treated HK-2 cells and CP-AKI mouse models, exploring the role of sirtuin 6 (SIRT6) upregulated by PD. In this study, the blocking of autophagy flux was observed in both CP-treated HK-2 cells in vitro and CP-AKI mouse models in vivo, whereas this blocking was reversed by PD, which was characterized by the increase of autophagy microtubule-associated protein light chain 3 II expression and autophagolysosome/autophagosome ratio and the decrease of p62 expression. Furthermore, PD also significantly increased the expression of SIRT6 in vivo and in vitro. The protective effect of PD manifested by the stimulating of autophagy flux, with the reducing of inflammatory response and oxidative stress, which included downregulation of tumor necrosis factor-α and interleukin-1ß, decreased activity of myeloperoxidase and content of malondialdehyde, and increased activity of superoxide dismutase and level of glutathione, both in vivo and in vitro, was reversed by either inhibition of autophagy flux by chloroquine or downregulation of SIRT6 by OSS-128167. Taken together, the present findings provide the first evidence demonstrating that PD exhibited nephroprotective effects on CP-AKI by restoring SIRT6-mediated autophagy flux mechanisms.


Assuntos
Injúria Renal Aguda , Sirtuínas , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Apoptose , Autofagia , Cloroquina/farmacologia , Cisplatino/toxicidade , Glucosídeos , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Rim/patologia , Malondialdeído/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Peroxidase/metabolismo , Sirtuínas/metabolismo , Estilbenos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Front Psychiatry ; 13: 864727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664473

RESUMO

Recent studies have shown that coronavirus disease 2019 (COVID-19) aggravates anxiety in patients with maintenance hemodialysis (MHD), but it is still unclear how long this adverse effect will last. This study aims to investigate the impact of COVID-19 on the elevated anxiety symptoms of MHD patients 1 year after the outbreak. Assessment of elevated anxiety symptoms was performed on patients with MHD during early COVID-19 (February 17-February 29, 2020) and 1-year follow-up (March 1-March 13, 2021), and a total of 100 patients had completed face-to-face questionnaires at the first and 1-year follow-up. At the beginning of the outbreak, 40% of the patients with MHD had anxiety symptoms [self-rating anxiety scale (SAS) score ≥ 50], and 11% (SAS score: 60-69) and 2% (SAS score ≥ 70) of the patients had moderate and severe anxiety symptoms, respectively. Multivariate analysis shows that possibility of unaccompanied transfer, possibility of family members or themselves being infected in a hospital, added body temperature monitoring during dialysis, and increased medical procedures are the risk factors in elevated anxiety symptoms during early COVID-19. At the 1-year follow-up, the incidence of anxiety symptoms in the same group of patients declined to 28%, and all the patients had mild anxiety symptoms (SAS score: 50-59), which is significantly lower than that of the early COVID-19 pandemic with statistically significant difference (p = 0.003). Increased protective measures taken by the medical staves were the only risk factor in elevated anxiety symptoms during the 1-year follow-up. This study shows that COVID-19 has a direct impact on the deterioration of anxiety symptoms in patients with MHD. With the changes of the requirements for COVID-19 prevention and control, as well as the enhancement of propaganda and education of the pandemic and psychological care, the severity and risk factors of anxiety symptoms in the patients with MHD are changing. Thus, targeted interventions are suggested to improve the psychological endurance of the patients with MHD.

20.
Front Public Health ; 10: 1073409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703816

RESUMO

Background: Family function plays a pivotal role in self-management among patients with early chronic kidney disease (CKD), which has been especially important during the COVID-19 pandemic. Previous studies have investigated the relationships between family function and self-management using total scores through self-report questionnaires while ignoring the different components in both family function and self-management. The specific objective of this study was to explore the network structure of family function and self-management at the component level. Methods: A total of 360 patients with early CKD from three tertiary hospitals were enrolled in our cross-sectional survey from September to December 2021 in China. Components of family function were measured by the Family Adaptation Partnership Growth and Resolve Index, and components of self-management were measured by the Chronic Kidney Disease Self-management Instrument. Network analysis was used to establish the network structure. Results: Edges across the community of family function and self-management were mainly positive. Edges between F3 "Growth" and M1 "Self-integration", F2 "Partnership" and M3 "Seeking social support," F5 "Resolve" and M3 "Seeking social support" were the strongest. F3 "Growth" had the greatest positive bridge expected influence of family function community (0.12), and M3 "Seeking social support" had the greatest positive bridge expected influence of self-management community (0.16). Conclusion: We explored the potential pathways between different components of family function and self-management among patients with early CKD during the COVID-19 pandemic and found fine-grained relationships between them. The two nodes F3 "Growth" and M3 "Seeking social support" may provide a new idea from the perspective of family function for interventions to improve self-management.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Autogestão , Humanos , Estudos Transversais , Pandemias , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/epidemiologia
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