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1.
Heliyon ; 10(15): e35008, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170525

RESUMO

Ultra-low-head turbines can harness energy from previously deemed unsuitable sites, including natural and man-made locations like shallow estuaries, marine canals, and industrial waterways. Various hydro-turbine concepts were evaluated for their potential to extract power from these areas. These turbines can generate renewable energy for utilization in remotely located areas. A horizontal-axis screw turbine concept, horizontal and vertical Savonius turbine concepts, axial turbine concepts, and a gate turbine concept were investigated in the present study using computational fluid dynamic tools. Reynolds Averaged Navier Stokes equations with a shear stress transport model are used to calculate the flow field. The numerical methodology is then verified with previously published data. The turbine performances were compared and the design feasibility was analyzed to find the most effective turbine design which can extract the maximum energy. The gate turbine concept exhibited a significant power output with high efficiency while the screw turbine showed the lowest performance among the tested designs. The horizontal Savonius turbine displayed enhanced performance with an increment of 23.25 % compared to the screw turbine. An additional parametric study is conducted on the gate turbine namely, the number of runner blades, and the gate installation angle. The 3-bladed gate turbine installed at a 14° gate angle showed superior power output and efficiency than other hydrokinetic turbines.

2.
Circ Res ; 135(5): e114-e132, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38989585

RESUMO

BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.


Assuntos
Clorofilídeos , Imagem Multimodal , Fármacos Fotossensibilizantes , Placa Aterosclerótica , Porfirinas , Tomografia de Coerência Óptica , Animais , Placa Aterosclerótica/diagnóstico por imagem , Coelhos , Imagem Multimodal/métodos , Tomografia de Coerência Óptica/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Macrófagos/metabolismo , Nanomedicina Teranóstica/métodos , Camundongos , Masculino , Autofagia , c-Mer Tirosina Quinase/metabolismo , Apoptose
3.
Heliyon ; 10(11): e32233, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947451

RESUMO

In this work, three different twist angles of a micro helical insert in a T-shaped are studied numerically in order to evaluate the laminar steady flow behavior of Newtonian fluid in chaotic geometry. In the geometries under consideration, thermal mixing behavior is carried out using fluids having two distinct input temperatures. Under the influence of chaotic advection and low rates of Reynolds number, the second law of thermodynamics is controlled in terms of the entropy generation caused by hydrodynamic and thermal processes. The governing equations are numerically solved using the CFD Fluent code. Thus, the micromixer's configuration demonstrated a very significant improvement in mixing degree while minimizing friction and thermal irreversibilities. The synergy coefficient, which depicts the link between velocity and heat transfer in angle form, is analyzed and the results are provided.

4.
Nanomaterials (Basel) ; 14(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38607150

RESUMO

Broad adoption has already been started of MXene materials in various energy storage technologies, such as super-capacitors and batteries, due to the increasing versatility of the preparation methods, as well as the ongoing discovery of new members. The essential requirements for an excellent anode material for lithium-ion batteries (LIBs) are high safety, minimal volume expansion during the lithiation/de-lithiation process, high cyclic stability, and high Li+ storage capability. However, most of the anode materials for LIBs, such as graphite, SnO2, Si, Al, and Li4Ti5O12, have at least one issue. Hence, creating novel anode materials continues to be difficult. To date, a few MXenes have been investigated experimentally as anodes of LIBs due to their distinct active voltage windows, large power capabilities, and longer cyclic life. The objective of this review paper is to provide an overview of the synthesis and characterization characteristics of the MXenes as anode materials of LIBs, including their discharge/charge capacity, rate performance, and cycle ability. In addition, a summary of the potential outlook for developments of these materials as anodes is provided.

5.
Int J Pharm ; 654: 123951, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38423154

RESUMO

Previous studies have demonstrated the effects of theranostic agents on atherosclerotic plaques. However, there is limited information on targeted theranostics for photodynamic treatment of atherosclerosis. This study aimed to develop a macrophage-mannose-receptor-targeted photoactivatable nanoagent that regulates atherosclerosis and to evaluate its efficacy as well as safety in atherosclerotic mice. We synthesised and characterised D-mannosamine (MAN)-polyethylene glycol (PEG)-chlorin e6 (Ce6) for phototheranostic treatment of atherosclerosis. The diagnostic and therapeutic effects of MAN-PEG-Ce6 were investigated using the atherosclerotic mouse model. The hydrophobic Ce6 photosensitiser was surrounded by the hydrophilic MAN-PEG outer shell of the self-assembled nanostructure under aqueous conditions. The MAN-PEG-Ce6 was specifically internalised in macrophage-derived foam cells through receptor-mediated endocytosis. After laser irradiation, the MAN-PEG-Ce6 markedly increased singlet oxygen generation. Intravital imaging and immunohistochemistry analyses verified MAN-PEG-Ce6's specificity to plaque macrophages and its notable anti-inflammatory impact by effectively reducing mannose-receptor-positive macrophages. The toxicity assay showed that MAN-PEG-Ce6 had negligible effects on the biochemical profile and structural damage in the skin and organs. Targeted photoactivation with MAN-PEG-Ce6 thus has the potential to rapidly reduce macrophage-derived inflammatory responses in atheroma and present favourable toxicity profiles, making it a promising approach for both imaging and treatment of atherosclerosis.


Assuntos
Aterosclerose , Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Animais , Camundongos , Fotoquimioterapia/métodos , Manose , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Macrófagos , Aterosclerose/diagnóstico por imagem , Aterosclerose/tratamento farmacológico , Porfirinas/química , Linhagem Celular Tumoral
6.
Sci Rep ; 14(1): 437, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172402

RESUMO

Advanced inlet guide vane (IGV) and diffuser vane (DV) geometries were constructed in an effort to increase the energy performance of an axial-flow pump at the best efficiency point (BEP). DV setting angles were also investigated to increase energy performance at the off-design points. By integrating the advantages of an adjustable IGV, combinations of adjustable IGV and DV geometries were constructed and thoroughly analyzed by way of energy loss. The asymmetrical geometry of the IGV, upgraded through the use of a hydrofoil profile, resulted in higher hydraulic performance compared to that of the reference model. The efficiency and total head at the BEP increased significantly with the implementation of the new DV, by 1.456% and 5.756% over those of the reference model, respectively. Using the new DV reduced the unsteady turbulent flow behind the trailing edge of the DV under all flow rate conditions, resulting in a reduction in vibration and noise. The positive setting angles of the DV increased the energy performance in the high-flow-rate region, whereas the negative DV setting angles produced a good performance in the low-flow-rate region. Combining an adjustable IGV with an adjustable DV model resulted in a significant increase in the total head, with more optimal energy performance provided by the positive IGV setting angles. At the BEP and under high-flow-rate conditions, the low-velocity zone is closely related to high entropy generation. Furthermore, these high-entropy generation regions follow the trajectory of the low-velocity zones. However, the low-velocity zone is not strongly associated with the high-entropy generation region when operating under low-flow-rate conditions.

7.
Sci Rep ; 13(1): 3468, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859554

RESUMO

Inlet flow direction significantly affects the hydraulic performance of an axial-flow pump. Usually, the research papers ignore this phenomenon, resulting in discrepancies between simulation and experimental results. This study examines the influence of inflow direction in five cases (0%, 5%, 10%, 15%, and 30% pre-swirl intensities) to determine the relationship between the pre-swirl intensity and the hydraulic performance of the axial-flow pump. Based on this, changing the setting angle of the inlet guide vane (IGV) is proposed and thoroughly investigated to reduce the effect of inflow direction. In this study, the influence of clearances in IGV blades on hydraulic performance is also investigated in detail. Numerical simulations are performed using ANSYS-CFX and a shear stress transport reattachment modification (SST k-[Formula: see text]) turbulence model with small y+ values at all walls. Specifically, the hydraulic performance curves and internal flow characteristics, including contours and streamlines, are assessed and analyzed. The inflow direction significantly impacts the hydraulic efficiency of the axial-flow pump. Increased pre-swirl intensity causes more loss in the IGV passage. The internal flow field and performance are not affected by the clearance at the hub and shroud of the IGV. However, the tip clearance of the impeller causes a decrease in hydraulic efficiency due to the tip leakage vortex. By adjusting the setting angle of the IGV, the efficiency and head gradually increase from a negative to a positive setting angle. Additionally, 30° is considered the critical setting angle for IGV.

9.
Sci Rep ; 12(1): 21884, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536152

RESUMO

Acute thoracic aortic dissection is a life-threatening disease, in which blood leaking from the damaged inner layer of the aorta causes dissection between the intimal and adventitial layers. The diagnosis of this disease is challenging. Chest x-rays are usually performed for initial screening or diagnosis, but the diagnostic accuracy of this method is not high. Recently, deep learning has been successfully applied in multiple medical image analysis tasks. In this paper, we attempt to increase the accuracy of diagnosis of acute thoracic aortic dissection based on chest x-rays by applying deep learning techniques. In aggregate, 3,331 images, comprising 716 positive images and 2615 negative images, were collected from 3,331 patients. Residual neural network 18 was used to detect acute thoracic aortic dissection. The diagnostic accuracy of the ResNet18 was observed to be 90.20% with a precision of 75.00%, recall of 94.44%, and F1-score of 83.61%. Further research is required to improve diagnostic accuracy based on aorta segmentation.


Assuntos
Dissecção Aórtica , Dissecção da Aorta Torácica , Humanos , Redes Neurais de Computação , Aorta , Radiografia Torácica/métodos
10.
Nanomaterials (Basel) ; 12(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36079968

RESUMO

Recently, lithium-ion batteries (LIBs) have been widely employed in automobiles, mining operations, space applications, marine vessels and submarines, and defense or military applications. As an anode, commercial carbon or carbon-based materials have some critical issues such as insufficient charge capacity and power density, low working voltage, deadweight formation, short-circuiting tendency initiated from dendrite formation, device warming up, etc., which have led to a search for carbon alternatives. Transition metal oxides (TMOs) such as NiO as an anode can be used as a substitute for carbon material. However, NiO has some limitations such as low coulombic efficiency, low cycle stability, and poor ionic conductivity. These limitations can be overcome through the use of different nanostructures. This present study reviews the integration of the electrochemical performance of binder involved nanocomposite of NiO as an anode of a LIB. This review article aims to epitomize the synthesis and characterization parameters such as specific discharge/charge capacity, cycle stability, rate performance, and cycle ability of a nanocomposite anode. An overview of possible future advances in NiO nanocomposites is also proposed.

11.
Int J Biol Macromol ; 218: 384-393, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35902009

RESUMO

The M2-like phenotype of tumor-associated macrophages (TAMs) present in tumors promotes tumor growth and metastasis. Therefore, targeting M2-like TAMs is a potential strategy for cancer therapy. Herein, we fabricated a dextran sulfate-based nano-photosensitizer (dextran sulfate-conjugated chlorin e6, DS-Ce6) to specifically target M2-like TAMs for enhanced photodynamic therapy (PDT). DS-Ce6 was preferentially taken up by interleukin-4-derived M2 macrophages, which overexpressed scavenger receptor-A and selectively targeted macrophages in co-cultured 4T1 tumors/macrophages. The nano-photosensitizer also effectively induced the apoptosis of tumor cells in both monolayer co-culture and three-dimensional co-culture spheroids of tumors/macrophages under laser irradiation. Moreover, the nano-photosensitizer specifically targeted F4/80 and CD206 double-positive M2-like TAMs within tumor tissues. Therefore, the specifically targeted delivery of DS-Ce6 to M2-like TAMs prominently induced tumor apoptosis, leading to excellent phototherapeutic effects in 4T1 tumor-bearing mice after PDT, suggesting the potential of DS-Ce6 for specific targeting of M2-like TAMs and enhanced PDT.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Sulfato de Dextrana , Camundongos , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Macrófagos Associados a Tumor
12.
Nanomaterials (Basel) ; 12(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35745373

RESUMO

Lithium-ion batteries (LIBs) are undeniably the most promising system for storing electric energy for both portable and stationary devices. A wide range of materials for anodes is being investigated to mitigate the issues with conventional graphite anodes. Among them, TiO2 has attracted extensive focus as an anode candidate due to its green technology, low volume fluctuations (<4%), safety, and durability. In this review, the fabrication of different TiO2 nanostructures along with their electrochemical performance are presented. Different nanostructured TiO2 materials including 0D, 1D, 2D, and 3D are thoroughly discussed as well. More precisely, the breakthroughs and recent developments in different anodic oxidation processes have been explored to identify in detail the effects of anodization parameters on nanostructure morphology. Clear guidelines on the interconnected nature of electrochemical behaviors, nanostructure morphology, and tunable anodic constraints are provided in this review.

13.
Aging (Albany NY) ; 13(19): 22649-22665, 2021 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-34607314

RESUMO

Periostin plays a crucial role in fibrosis, which is involved in kidney aging. A few studies have shown that lipid metabolism is involved in kidney aging. We investigated the role of periostin in lipid metabolism during kidney aging. Renal function, fibrosis, and inflammatory markers were studied using urine, blood, and tissue samples from wild-type (WT) C57BL/6 mice and Postn-null mice of 2 and 24 months of age. Lipids were quantitatively profiled using liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring mode. Renal function was worse and tubular atrophy/interstitial fibrosis, periostin expression, and inflammatory and fibrotic markers were more severe in aged WT mice than in young WT mice. In aged Postn-null mice, these changes were mitigated. Thirty-five differentially regulated lipids were identified. Phosphatidylcholines, cholesteryl ester, cholesterol, ceramide-1-phosphate, and CCL5 expression were significantly higher in aged WT mice than in aged Postn-null mice. Particularly, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid differed strongly between the two groups. Lysophosphatidylcholine acyltransferase 2, which converts lysophosphatidylcholine to phosphatidylcholine, was significantly higher in aged WT mice than in aged Postn-null mice. Periostin expression in the kidneys increased with age, and periostin ablation delayed aging. Changes in lipids and their metabolism were found in Postn-null mice. Further research on the precise mechanisms of and relationships between lipid expression and metabolism, kidney aging, and periostin expression is warranted.


Assuntos
Envelhecimento/fisiologia , Moléculas de Adesão Celular/metabolismo , Rim/patologia , Metabolismo dos Lipídeos/genética , Animais , Moléculas de Adesão Celular/genética , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Distribuição Aleatória
14.
ACS Appl Mater Interfaces ; 13(37): 45097-45104, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34496563

RESUMO

A recent study found that magnetization curves for Y3Fe5O12 (YIG) slab and thick films (>20 µm thick) differed from bulk system curves by their longitudinal spin Seebeck effect in a Pt/YIG bilayer system. The deviation was due to intrinsic YIG surface magnetic anisotropy, which is difficult to adopt extrinsic surface magnetic anisotropy even when in contact with other materials on the YIG surface. This study experimentally demonstrates evidence for extrinsic YIG surface magnetic anisotropy when in contact with a diamagnetic graphene interlayer by observing the spin Seebeck effect, directly proving intrinsic YIG surface magnetic anisotropy interruption. We show the Pt/YIG bilayer system graphene interlayer role using large area single and multilayered graphenes using the longitudinal spin Seebeck effect at room temperature, and address the presence of surface magnetic anisotropy due to magnetic proximity between graphene and YIG layer. These findings suggest a promising route to understand new physics of spin Seebeck effect in spin transport.

15.
Kidney Res Clin Pract ; 40(4): 596-610, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34510856

RESUMO

BACKGROUND: Hepatocyte growth factor (HGF)/cMet pathway is necessary for repair and regeneration following acute kidney injury (AKI). We evaluated the clinical potential of plasma HGF and soluble cMet as prognostic biomarkers for severe AKI requiring continuous renal replacement therapy (CRRT). METHODS: One hundred thirty-six patients with severe AKI who participated in the VENUS (volume management under body composition monitoring in critically ill patients on CRRT) trial between 2017 and 2019 were enrolled in this study. We investigated associations between plasma HGF and cMet concentrations and all-cause mortality. RESULTS: Plasma HGF and soluble cMet levels were positively correlated. Patients were divided into three groups based on their HGF and soluble cMet concentrations. The day D 0, D2, and D7 highest concentration HGF groups had significantly higher in-hospital mortality after adjusting for sex, body mass index, Acute Physiology and Chronic Health Evaluation II, and age-adjusted Charlson comorbidity index score, especially on D7 (hazard ratio, 4.26; 95% confidence interval, 1.71-10.62; p = 0.002). D7 soluble cMet level was also associated with mortality. Receiver operating characteristic curve analysis indicated that D7 HGF and soluble cMet levels were best at predicting mortality. Addition of plasma HGF and soluble cMet to conventional prognostic indices significantly improved the predictive value for mortality on D7. However, plasma HGF and soluble cMet were not associated with fluid status. CONCLUSION: Plasma HGF and soluble cMet levels were significant predictors of the outcomes of severe AKI patients undergoing CRRT. There was no correlation between plasma HGF and soluble cMet levels and fluid balance.

16.
Clin Sci (Lond) ; 135(11): 1427-1444, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34061176

RESUMO

We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-ß1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1ß) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-ß1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-ß1/Smad pathway.


Assuntos
Injúria Renal Aguda/patologia , Insuficiência Renal Crônica/metabolismo , Proteína Smad7/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Fibrose/patologia , Humanos , Rim/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Crescimento Transformador beta/metabolismo
17.
Int J Mol Sci ; 22(1)2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33375356

RESUMO

Macrophage-derived foam cells play critical roles in the initiation and progression of atherosclerosis. Activated macrophages and foam cells are important biomarkers for targeted imaging and inflammatory disease therapy. Macrophages also express the dectin-1 receptor, which specifically recognizes ß-glucan (Glu). Here, we prepared photoactivatable nanoagents (termed Glu/Ce6 nanocomplexes) by encapsulating hydrophobic chlorin e6 (Ce6) within the triple-helix structure of Glu in aqueous condition. Glu/Ce6 nanocomplexes generate singlet oxygen upon laser irradiation. The Glu/Ce6 nanocomplexes were internalized into foam cells and delivered Ce6 molecules into the cytoplasm of foam cells. Upon laser irradiation, they induced significant membrane damage and apoptosis of foam cells. These results suggest that Glu/Ce6 nanocomplexes can be a photoactivatable material for treating atherogenic foam cells.


Assuntos
Aterosclerose/tratamento farmacológico , Células Espumosas/efeitos dos fármacos , Glucanos/farmacologia , Lasers , Nanopartículas/administração & dosagem , Porfirinas/farmacologia , Radiossensibilizantes/farmacologia , Animais , Apoptose , Aterosclerose/metabolismo , Aterosclerose/patologia , Clorofilídeos , Células Espumosas/metabolismo , Células Espumosas/patologia , Glucanos/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Nanopartículas/química , Fotoquimioterapia , Porfirinas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
18.
J Cell Mol Med ; 24(19): 11158-11169, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822114

RESUMO

The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below-median (Group 2) and above-median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary-cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)-α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria (P < .001). During the follow-up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr < 300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF-α treatment, the proliferation of mesangial cells and increased interleukin-8 and intercellular adhesion molecule-1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.


Assuntos
Glomerulonefrite por IGA/urina , Proteínas Proto-Oncogênicas c-met/urina , Adulto , Biomarcadores/urina , Creatinina/urina , Feminino , Glomerulonefrite por IGA/complicações , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Prognóstico , Proteinúria/complicações , Indução de Remissão
19.
Sci Rep ; 9(1): 14707, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605028

RESUMO

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.


Assuntos
Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/urina , Inositol/urina , Nefrose Lipoide/urina , Adulto , Idoso , Biomarcadores/urina , Linhagem Celular , Feminino , Taxa de Filtração Glomerular , Glomerulosclerose Segmentar e Focal/sangue , Humanos , Inositol/farmacologia , Inositol Oxigenase/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Pessoa de Meia-Idade , Ressonância Magnética Nuclear Biomolecular , Podócitos/efeitos dos fármacos , Prognóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue
20.
Sci Rep ; 9(1): 13495, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530851

RESUMO

Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-ß1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.


Assuntos
Anticorpos Monoclonais/farmacologia , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-met/agonistas , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Animais , Biomarcadores , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fibrose , Expressão Gênica , Humanos , Imuno-Histoquímica , Túbulos Renais Proximais/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia
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