RESUMEN
High soil salinity negatively affects plant growth and development, leading to a severe decrease in crop production worldwide. Here, we report that a secreted peptide, PAMP-INDUCED SECRETED PEPTIDE 3 (PIP3), plays an essential role in plant salt tolerance through RECEPTOR-LIKE KINASE 7 (RLK7) in Arabidopsis (Arabidopsis thaliana). The gene encoding the PIP3 precursor, prePIP3, was significantly induced by salt stress. Plants overexpressing prePIP3 exhibited enhanced salt tolerance, whereas a prePIP3 knockout mutant had a salt-sensitive phenotype. PIP3 physically interacted with RLK7, a leucine-rich repeat RLK, and salt stress enhanced PIP3-RLK7 complex formation. Functional analyses revealed that PIP3-mediated salt tolerance is dependent on RLK7. Exogenous application of synthetic PIP3 peptide activated RLK7, and salt treatment significantly induced RLK7 phosphorylation in a PIP3-dependent manner. Notably, MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6 were downstream of the PIP3-RLK7 module in salt response signaling. Activation of MPK3/6 was attenuated in pip3 or rlk7 mutants under saline conditions. Therefore, MPK3/6 might amplify salt stress response signaling in plants for salt tolerance. Collectively, our work characterized a novel ligand-receptor signaling cascade that modulates plant salt tolerance in Arabidopsis. This study contributes to our understanding of how plants respond to salt stress.
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Proteínas de Arabidopsis , Arabidopsis , Tolerancia a la Sal , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Plantas Modificadas Genéticamente , Estrés Salino/fisiología , Tolerancia a la Sal/fisiologíaRESUMEN
The regulation of intracellular pH in yeast (Saccharomyces cerevisiae) cells is critical for cell function and viability. In yeast, protons (H+) can be excreted from the cell by plasma membrane ATPase PMA1 and pumped into vacuoles by vacuolar H+-ATPase. Because PMA1 is critical to the survival of yeast cells, it is unknown whether other compensatory components are involved in pH homeostasis in the absence of PMA1. To elucidate how intracellular pH is regulated independently of PMA1, we employed a screening approach by exposing the yeast haploid deletion mutant library (ver 4.0) to the selective plant plasma membrane H+-ATPase inhibitor PS-1, which we previously reported. After repeated screenings and verification, we identified two proteins, Aly1 and Aly2, that play a role in the regulation of intracellular pH when PMA1 is deficient. Our research uncovers a new perspective on the regulation of intracellular pH related to PMA1 and also preliminarily reveals a role for Aly1 and Aly2 in the regulation of intracellular pH.
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BACKGROUND: Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT. RESULTS: By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI. CONCLUSIONS: We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window.
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Neoplasias del Colon , Terapia Fototérmica , Humanos , Animales , Ratones , Fototerapia , Carbono , Neoplasias del Colon/terapia , OroRESUMEN
The use of acoustic attractants may have the potential to guide native migratory species towards safe passage. Flower fish Ptychobarbus kaznakovi, a short-distance migratory fish whose population is in decline in the past decades, was exposed to three acoustic stimuli (feeding sound, ambient riverine noise and the pure tone 1000 Hz) to examine the phonotaxic responses using playbacks approaches in a fibreglass tank. The results showed that the flower fish showed significantly greater positive phonotaxis and swam towards the sound sources significantly faster in response to the feeding sounds than to ambient riverine noise and the pure tone during the 5-min exposure. Distribution experiments were conducted to study the preference of flower fish to the three sounds stimuli. The results showed that the experimental fish in feeding sound trials spent significant more time in areas closer to the sound sources than that in the pure tone and the ambient riverine noise trials, respectively. This study indicates that the feeding sounds may serve as potential acoustic attractants to guide flower fish to safe passage routes.
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Cyprinidae/fisiología , Conducta Alimentaria , Sonido , Estimulación Acústica , Animales , Señales (Psicología) , Ruido , NataciónRESUMEN
Analyte-responsive chromo-fluorogenic reactions under accessible conditions are important for designing small-molecule spectroscopic probes. We describe a series of newly constructed motifs based on the chromo-fluorogenic reaction between catechol derivatives (typically hydroxytyrosol, dopamine, and levodopa) and naphthoresorcin (NR) in aqueous solution under ambient conditions. The weakly absorptive and fluorogenic catechols/NR was converted to products having visible absorption and bright fluorescence within several minutes. The chromo-fluorophores produced from this reaction had a maximum absorbance at 458 nm and emission at 480 nm with high fluorescence quantum yields (30-84%). Inspired by the tyrosinase-catalyzed hydroxylation of monophenols to catechols, the tyrosinase-enabled chromo-fluorogenic reaction was verified by using monophenol (typically tyrosol) as the substrate. In this regard, a dual-readout tyrosinase activity assay was developed by virtue of the in situ "turn-on" optical signals. Furthermore, a test of tyrosinase inhibition, by using a common inhibitor kojic acid, demonstrated the potential of the chromo-fluorogenic reaction for developing other tyrosinase related assays and signal transduction.
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Catecoles/metabolismo , Colorantes Fluorescentes/metabolismo , Monofenol Monooxigenasa/metabolismo , Naftalenos/metabolismo , Resorcinoles/metabolismo , Agaricales/enzimología , Catecoles/química , Colorantes Fluorescentes/química , Estructura Molecular , Monofenol Monooxigenasa/análisis , Naftalenos/química , Resorcinoles/químicaRESUMEN
Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in individuals with diabetes, and it is the leading cause of end-stage renal disease (ESRD) worldwide. Stanniocalcin-1 (STC-1) is present in various tissues, and it has antioxidant and anti-apoptotic activities, which play a role in kidney protection, including diabetic nephropathy (DN). However, the mechanism that underlies these effects remains unknown. This study suggests that STC-1 ameliorates oxidative stress and cell apoptosis in the kidneys of db/db mice and high glucose (HG)-treated BUMPT cells by inhibiting Bnip3 expression through AMPK/Sirt3 pathway activation. In the clinic, DKD patients with high levels of STC-1 have a better prognosis than patients with low STC-1 levels. Thus, we concluded that STC-1 ameliorates renal injury in DN by inhibiting the expression of Bnip3 through the AMPK/SIRT3 pathway and that serum STC-1 is independently associated with DKD progression in patients with type 2 diabetes. As high STC-1 levels indicate a better prognosis, synthetic STC-1 may become a potential drug for the treatment of DKD patients.
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Proteínas Quinasas Activadas por AMP/metabolismo , Nefropatías Diabéticas/sangre , Glicoproteínas/sangre , Riñón/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Sirtuina 3/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/prevención & control , Femenino , Glicoproteínas/farmacología , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Transducción de Señal/efectos de los fármacosRESUMEN
Alkaline phosphatase (ALP) usually acts as a signal transmitter in enzyme-linked immunosorbent assay (ELISA); therefore, developing an attractive ALP activity assay, especially using a preferable substrate, would help improve the efficiency and convenience of ELISA in practical applications. Herein we have first prepared an original and creative substrate, named m-hydroxyphenyl phosphate sodium salt ( m-HPP), with a desirable dephosphorylation site for ALP. On the basis of the ALP-catalyzed hydrolysis of m-HPP to resorcinol and its subsequent specific nucleophilic reaction with dopamine, we have exploited a fluorometric and colorimetric dual-readout ALP activity assay and ALP-based ELISA system. Under the employed experimental conditions, highly sensitive and specific assay of ALP and cardiac troponin I (cTnI) has been accomplished in a straightforward way. Furthermore, the commendable sensing performance of our proposed ELISA in the determination of the cTnI level in diluted human serum unambiguously illustrates great potential in the early diagnosis of acute myocardial infarction.
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Fosfatasa Alcalina/metabolismo , Técnicas Biosensibles/métodos , Colorimetría , Ensayo de Inmunoadsorción Enzimática/métodos , Fluorometría , Fosfatasa Alcalina/antagonistas & inhibidores , Fosfatasa Alcalina/química , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Modelos Moleculares , Fosfatos/química , Fosfatos/metabolismo , Conformación Proteica , Troponina I/metabolismoRESUMEN
Inspired by the coreactive activity of carbon nanodots (CDs) and branched polyethylenimine (BPEI) toward electrochemiluminescence (ECL) of Ru(bpy)32+, a highly luminescent and self-enhanced ECL nanohybrid (Ru-BCDs) was synthesized through covalently linking BPEI-coated carbon dots (BCDs) with Tris (4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)32+). The composition and morphological characterization demonstrated that the spherical Ru-BCDs particles with 12.1 ± 1.4 nm diameter were obtained. The enhanced ECL property of Ru-BCDs was proved to originate from the dual coreactive contribution of BPEI and CDs as coreactants as well as the intramolecular electron transfer process, which could shorten the electron transfer path and minimize energy loss. A carbon nitride nanosheet (CNN) was utilized to stabilize the Ru-BCDs-modified glassy carbon electrode, which greatly improved the stability of solid-state ECL. By utilizing the affinity discrepancy of the CNN to single-stranded and double-stranded nucleic acids, a label-free and signal-on ECL biosensor was constructed for the determination of microRNA-133a (miR-133a), a potential biomarker of acute myocardial infarction. The designed biosensor exhibited good performance of miR-133a detection with a detection limit of 60 fM and could be used for the detection of real human serum with satisfactory results. The self-enhanced ECL nanohybrid with distinguished ECL efficiency holds a promising prospect in biosensing and bioimaging applications.
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Técnicas Biosensibles/métodos , Complejos de Coordinación/química , Sustancias Luminiscentes/química , MicroARNs/sangre , Puntos Cuánticos/química , Técnicas Electroquímicas/métodos , Electrodos , Humanos , Límite de Detección , Luminiscencia , Mediciones Luminiscentes/métodos , Polietileneimina/químicaRESUMEN
BACKGROUND: Focal and segmental glomerular sclerosis (FSGS) is a common cause of nephrotic syndrome and end-stage renal disease. It has been reported that overproduction of reactive oxygen species (ROS) and cell apoptosis are associated with the development of FSGS. Epigallocatechin-3-gallate (EGCG) is a bioactive constituent accounting for more than 50% of the total catechins in green tea, which have anti-oxidative and anti-apoptotic effects. Based on this, this study was designed to evaluate the renoprotective effect of EGCG treatment on Adriamycin-induced FSGS. -Methods: In C57BL/6 mice, Adriamycin nephropathy (AN) was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were given with EGCG (20 mg/kg body weight) or YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor-1α [HIF-1α], 50 mg/kg body weight) or both intraperitoneally. Both the EGCG and YC-1 were given on the day of Adriamycin injection and continued for 6 weeks. The animals were organized into the following 5 groups for the animal experiments: the control group, the AN group, the AN + EGCG group, the AN + YC-1 group and the AN + EGCG + YC-1 group. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. The HIF-1α and the angiopoietin-like 4 (ANGPTL4) expression were detected by Western blot, real-time PCR, immunohistochemistry or immunofluorescence. Dihydroethidium staining and NADPH oxidase 1 (Nox1) measurement were used to detect ROS production. Terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 measurement was used to detect cell apoptosis. RESULTS: When the animals were treated with Adriamycin, both the ROS production and TUNEL positive cells increased. Besides, the expression of HIF-1α, ANGPTL4, and caspase-3 were also up-regulated, while EGCG treatment could attenuate these changes. Interestingly, compared with treatment with YC-1 or EGCG alone, more pronounced inhibition of ANGPTL4, caspase-3 and Nox1 were obtained when YC-1 and EGCG were administered simultaneously. CONCLUSION: EGCG attenuates FSGS through the suppression of Oxidant Stress and apoptosis by targeting the HIF-1α/ANGPTL4 pathway.
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Antioxidantes/farmacología , Catequina/análogos & derivados , Glomeruloesclerosis Focal y Segmentaria/prevención & control , Estrés Oxidativo/efectos de los fármacos , Proteína 4 Similar a la Angiopoyetina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Catequina/farmacología , Modelos Animales de Enfermedad , Doxorrubicina/toxicidad , Técnica del Anticuerpo Fluorescente , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Etiquetado Corte-Fin in Situ , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Periplaneta americana is one of the ancient insect groups with the strongest vitality. Periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases. Although much progress has been made in the study about PAE, the role of the drug in renal disease is rarely reported, especially in renal fibrosis. This study was designed to evaluate the renoprotective effect of PAE treatment to renal fibrosis. METHOD: An in vivo, unilateral ureteral obstruction (UUO) mouse model was built. Then the mice were treated with PAE (100 mg/kg body weight) once daily by oral gavage, again starting on the day of UUO and continued for 1 week. At the end of 1 week, the mice were sacrificed; kidney samples were collected for further analysis. In vitro, Boston University mouse proximal tubular cells were plated in 35-mm dishes at a density of 0.3 * 106 cells/dish. Then the cells were treated with 5-ng/mL TGF-ß1 in serum-free DMEM medium for an indicated length of time. The experimental groups were pretreated with the indicated concentrations of PAE (0.3125 mg/mL). The cells were further cultured for 24 h, and then cells were monitored morphologically or collected for biochemical analyses. RESULTS: Both in vivo and vitro PAE inhibits the expression of FN and alpha-smooth muscle actin and suppresses renal fibrosis. Importantly, PAE protects against renal fibrosis by inhibiting Janus tyrosine kinase 2 (JAK)/signal transducer and activator of transcription 3 (STAT) tyrosine phosphorylation. CONCLUSION: PAE attenuates renal fibrosis through the suppression of the JAK2/STAT3 pathway.
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Fibrosis/prevención & control , Janus Quinasa 2/antagonistas & inhibidores , Riñón/patología , Periplaneta , Extractos Vegetales/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Actinas/biosíntesis , Animales , Células Cultivadas , Fibronectinas/biosíntesis , Masculino , Ratones , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.â© Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1ß, IL-18, IL-10 and adiponectin were determined. The levels of TGF-ß1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.â© Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1ß and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).â© Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
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Doxorrubicina , Glomeruloesclerosis Focal y Segmentaria , Xantonas/uso terapéutico , Animales , Modelos Animales de Enfermedad , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Riñón/efectos de los fármacos , Ratones , Ratones Endogámicos NOD , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Xantonas/farmacologíaRESUMEN
BACKGROUND/AIMS: Transforming growth factor ß 1 (TGFß1) plays a critical role in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs) during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. METHODS: Expression of TGFß1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO) in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFß1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. RESULTS: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFß1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. CONCLUSION: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.
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Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Ácidos Aminosalicílicos/farmacología , Animales , Bencenosulfonatos/farmacología , Cadherinas/genética , Cadherinas/metabolismo , Células Cultivadas , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis , Túbulos Renales/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/efectos de los fármacos , Proteína smad3/genética , Proteína smad3/metabolismo , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/veterinariaRESUMEN
BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS. METHODS: In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with RSV (40 mg/kg body weight) once daily by oral gavage, again starting on the day of adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. RESULTS: When treated with adriamycin, the expressions of C3aR, C5aR, sphingosine kinase 1 (Sphk1), and soluble urokinase-type plasminogen activator receptor (suPAR) were upregulated, while RSV treatment could inhibit the expressions of C3aR, C5aR, Sphk1, and suPAR, eventually leading to anti-inflammatory and anti-fibrosis conditions. CONCLUSION: RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.
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Doxorrubicina/farmacología , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Receptor de Anafilatoxina C5a/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Estilbenos/farmacología , Animales , Antiinflamatorios/farmacología , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Resveratrol , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Immunoglobulin (Ig) A nephropathy (IgAN) is the xFB01;nding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the 'mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN. METHODS: The aim of the study was to investigate the expression of all-trans-RA (ATRA) and BATF, and to identify their impact on IgA CSR in IgAN patients and rat animal models. Blood samples and tonsillar tissue specimens were obtained from 22 patients with IgAN and 24 patients with chronic tonsillitis as control. RESULTS: Immunohistochemical, RT-PCR and western blotting examination revealed that RA signaling and BATF productions are activated in IgAN patients compared with controls. Lipopolysaccharide and α-hemolytic streptococcus stimulation upregulated RA receptor (RAR) and BATF expression, promote IgA CSR and ATRA productions in tonsil mononuclear cells. RAR alpha (RARα) or BATF siRNA decreases IgA expression. We also built IgAN rat models and found that RARα, BATF and activation-induced cytidine deaminase were upregulated in the peripheral blood, spleen and BM. With ATRA (500 µg/kg body weight) treatment for 8 weeks, IgA deposition on glomeruli and mesangial cells proliferation increased. It also revealed that ATRA activated BATF and IgA CSR in vivo. CONCLUSION: These data point toward the role of RA signaling together with BATF in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with neoantigen results in impaired mucosal and systemic IgA responses.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/sangre , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/metabolismo , Tonsila Palatina/metabolismo , Tretinoina/sangre , Adolescente , Adulto , Animales , Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulina A/metabolismo , Cambio de Clase de Inmunoglobulina , Glomérulos Renales/metabolismo , Lipopolisacáridos , Masculino , Células Mesangiales/fisiología , Persona de Mediana Edad , Tonsila Palatina/inmunología , Cultivo Primario de Células , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor alfa de Ácido Retinoico/metabolismo , Transducción de Señal , Bazo/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Gentamicin-induced nephrotoxicity is one of the most common causes of acute kidney injury (AKI). The phenotypic alterations that contribute to acute kidney injury include inflammatory response and oxidative stress. Curcumin has a wide range biological functions, especially as an antioxidant. This study was designed to evaluate the renoprotective effects of curcumin treatment in gentamicin-induced AKI. METHODS: Gentamicin-induced AKI was established in female Sprague-Dawley rats. Rats were treated with curcumin (100 mg/kg body mass) by intragastric administration, once daily, followed with an intraperitoneal injection of gentamicin sulfate solution at a dose of 80 mg/kg body mass for 8 consecutive days. At days 3 and 8, the rats were sacrificed, and the kidneys and blood samples were collected for further analysis. RESULTS: The animals treated with gentamicin showed marked deterioration of renal function, together with higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the plasma as compared with the controls. Animals that underwent intermittent treatment with curcumin exhibited significant improvements in renal functional parameters. We also observed that treatment with curcumin significantly attenuated renal tubular damage, apoptosis, and oxidative stress. Curcumin treatment exerted anti-apoptosis and anti-oxidative effects by up-regulating Nrf2/HO-1 and Sirt1 expression. CONCLUSIONS: Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.
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Lesión Renal Aguda/prevención & control , Antibacterianos/química , Antiinflamatorios no Esteroideos/uso terapéutico , Curcumina/uso terapéutico , Gentamicinas/antagonistas & inhibidores , Riñón/efectos de los fármacos , Nefritis/prevención & control , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/metabolismo , Animales , Antibacterianos/efectos adversos , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Moléculas de Adhesión Celular/sangre , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Gentamicinas/efectos adversos , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/inmunología , Túbulos Renales/patología , Túbulos Renales/fisiopatología , Lipocalina 2 , Lipocalinas/sangre , Factor 2 Relacionado con NF-E2/agonistas , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Nefritis/inducido químicamente , Nefritis/inmunología , Nefritis/metabolismo , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas Sprague-Dawley , Sirtuina 1/química , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) is a specific pattern of chronic renal injury with progressive glomerular scarring. The phenotypic alterations that contribute to FSGS include inflammatory response and oxidative stress. Astaxanthin (ATX) has a broad range of biological functions, particularly antioxidant and anti-inï¬ammatory ones. This study was designed to evaluate the renoprotective effect of ATX treatment on Adriamycin-induced FSGS. METHODS: In Balb/c mice, Adriamycin nephropathy was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with ATX (50 mg/kg body weight) once daily by oral gavage, again starting on the day of Adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. RESULTS: Animals that underwent intermittent exposure to ATX treatment exhibited significant improvements in renal functional parameters as well as in glomerular and interstitial fibrosis compared to those undergoing saline treatment in FSGS mouse models. ATX treatment exerted anti-inflammatory and antioxidant effects by promoting Nrf2 expression and suppressing renal nucleotide-binding oligomerization domain-like receptor protein 3 inï¬ammasome activation. CONCLUSION: ATX might offer a ray of hope for ameliorating FSGS.
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Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Animales , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Creatinina/sangre , Doxorrubicina , Fibrosis , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomeruloesclerosis Focal y Segmentaria/patología , Interleucina-18/sangre , Interleucina-1beta/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos BALB C , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Xantófilas/farmacología , Xantófilas/uso terapéuticoRESUMEN
IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague-Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200 µg/kg/d intragastrically) from 12 to 28 weeks. At Week 28, the rats was sacrificed, kidneys and blood samples were collected for further analysis. Our data shown that IgAN rat model showed marked deterioration of proteinuria together with higher levels of the urine protein:creatinine ratio compared to the normal control. Animals that underwent intermittent exposure to triptolide treatment exhibited significant improvements in the functional parameters without severe side effects. Rats developing IgAN had profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, while triptolide treatment significantly attenuated it. We also observed that treatment with triptolide significantly decreases serum levels of IL-1ß and IL-18, and may exerted anti-inflammatory effects by down-regulating NLRP3 and TLR4 expression. Our study clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.
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Antiinflamatorios no Esteroideos/farmacología , Diterpenos/farmacología , Glomerulonefritis por IGA/tratamiento farmacológico , Fenantrenos/farmacología , Animales , Proteínas Portadoras/inmunología , Modelos Animales de Enfermedad , Compuestos Epoxi/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Glomerulonefritis por IGA/inducido químicamente , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/patología , Interleucina-18/inmunología , Interleucina-1beta/inmunología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas , Ratas Sprague-Dawley , Receptor Toll-Like 4/inmunologíaRESUMEN
The migration of Schizothorax prenanti, an ecologically important and commercially valuable species, is impeded by dams. Effective fishways would contribute to conservation of wild populations, and swimming performance data are necessary for fishway design. The swimming performance of S. prenanti was investigated at four temperatures (15, 19, 23, 27 °C), and numerical models were used to characterize the effect of temperature on swimming performance. As temperature increases, critical swimming speed (U crit) increases from 15 to 23 °C and then decreases significantly. The highest U crit (7.71 BL/s) occurs at 24 °C, as estimated by interpolation. Swimming efficiency was similar from 19 to 23 °C, but decreases significantly at 27 °C. The temperature range 15-23 °C is suitable for S. prenanti. However, the excess post-exercise oxygen consumption values of Q 10 for the four temperature increments indicate that 19-23 °C is the optimal range for swimming performance. Maximum tail beat amplitude increased >25 % (0.35-0.45 BL) over the temperature range considered, but variation of tail beat frequency was erratic. White muscle fiber begins to contribute to swimming at swimming speeds ~40 % U crit at the lower three temperatures, but increases to almost 60 % at 27 °C, and the contribution is relatively small. The results of this investigation advance the knowledge of fish metabolism while swimming provides data critical for fishway design.
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Cyprinidae/fisiología , Migración Animal/fisiología , Animales , China , Conservación de los Recursos Naturales , Ecosistema , Consumo de Oxígeno , Ríos , Natación/fisiología , TemperaturaRESUMEN
Smart agricultural (SA) technology has become a technological support for modern agriculture. By exploring the decision-making process and psychological motivation of farmers in adopting SA technology, it is conducive to achieving the popularisation of SA technology and promoting the modernisation of agriculture. Based on microscopic research data, a Structural Equation Model (SEM) is used to analyse the influencing factors and extent of cotton farmers' adoption of SA technologies, using Deconstructive Theory of Planned Behavior (DTPB) as the analytical framework. This was combined with in-depth interviews to further reveal the motivations and influencing mechanisms of cotton farmers' adoption of SA technologies. The results show that under the behavioural belief dimension, cotton farmers value the positive effect of perceived usefulness even though the risk of the technology itself has a dampening effect on adoption intentions. Under the normative belief dimension, superior influence influenced the willingness to adopt SA technologies to a greater extent than peer influence. Under the control belief dimension, factors such as self-efficacy and information channels influence willingness to adopt technology and behaviour. In addition, behavioural attitudes, subjective norms, and perceived behavioural control all contribute to cotton farmers' willingness to adopt SA technologies, and can also influence behaviour directly or indirectly through willingness to adopt. Policy and technology satisfaction positively moderate the transition from willingness to behaviour. Therefore, preferential policies are proposed to reduce the cost of adopting SA technologies; to continuously improve the level of SA technologies; to establish SA technology test plots to provide a reference base; and to increase knowledge training on SA and expand access to information.
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Agricultura , Tecnología , Encuestas y Cuestionarios , Agricultura/métodos , Intención , Actitud , Agricultores/psicologíaRESUMEN
INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix and usually associated with nephrotic range proteinuria. FSGS is a huge burden to society; however, the mechanisms remain unclear and treatment is still lacking. METHODS: Adriamycin nephropathy was induced by Adriamycin injection and some mice were also injected with Anti-miR-155-5p LNA or YC-1 (a pharmacological inhibitor of HIF-1). At 6 weeks, the mice were sacrificed, and kidneys, blood and urine samples were collected for further analysis. RESULTS: We demonstrated a significant increase of miR-155-5p in kidney tissues in Adriamycin-induced FSGS mouse models. We also found Adriamycin treatment led to the activation of HIF-1, and inhibition of HIF-1 using YC-1 partly prevented the induction of miR-155-5p. Functionally, anti-miR-155-5p attenuated kidney injury and delayed the progression of renal fibrosis. Further, anti-miR-155-5p also enhanced the expression of Nrf2 following Adriamycin treatment. Further, our luciferase microRNA target reporter assay verified Nrf2 as a direct target of miR-155-5p. Our further results indicated anti-miR-155-5p could suppress kidney oxidative stress and inflammation, also supporting Nrf2 was the direct target of miR-155-5p. Finally, we also found miR-155-5p did not increase in serum but significantly increased in urine, indicating urinary miR-155-5p may be useful for FSGS diagnosis. CONCLUSION: This study identified a HIF-1/miR-155-5p/Nrf2 axis which can promote kidney oxidative stress and inflammation, finally aggravating kidney injury and accelerating the progression of renal fibrosis in FSGS. Moreover, the increase in urinary miR-155-5p may be useful for the diagnosis of FSGS.