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1.
FASEB J ; 38(15): e23871, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39109498

RESUMEN

Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM-related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high-fat diet combined with a single streptozotocin injection in 7-week-old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end-products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE-RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Productos Finales de Glicación Avanzada , Inflamación , Estrés Oxidativo , Ratas Sprague-Dawley , Receptor para Productos Finales de Glicación Avanzada , Animales , Productos Finales de Glicación Avanzada/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Ratas , Inflamación/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Diabetes Mellitus Experimental/metabolismo , Osteoblastos/metabolismo , Remodelación Ósea
2.
J Neuroinflammation ; 19(1): 213, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050772

RESUMEN

BACKGROUND: Chronic kidney disease (CKD), characterized as renal dysfunction, is regarded as a major public health problem which carries a high risk of cardiovascular diseases. The purpose of this study is to evaluate the functional significance of Drp1 in hypercalcemia-associated neuronal damage following CKD and the associated mechanism. METHODS: Initially, the CKD mouse models were established. Next, RT-qPCR and Western blot analysis were performed to measure expression of Fis1 and Drp1 in CKD. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay were utilized to explore the relationship among Drp1, HIF-1α, EZH2, and ROS with primary cortical neurons isolated from neonatal mice. Next, CKD mice were subjected to calcitonin treatment or manipulation with adenovirus expressing sh-Drp1, so as to explore the effects of Drp1 on hypercalcemia-induced neuronal injury in CKD. TUNEL assay and immunofluorescence staining were performed to detect apoptosis and NeuN-positive cells (neurons) in prefrontal cortical tissues of CKD mice. RESULTS: It was found that hypercalcemia could induce neuronal injury in CKD mice. An increase of Fis1 and Drp1 expression in cerebral cortex of CKD mice correlated with mitochondrial fragmentation. Calcitonin suppressed Drp1/Fis1-mediated mitochondrial fragmentation to attenuate hypercalcemia-induced neuronal injury after CKD. Additionally, Drp1 could increase EZH2 expression through the binding of HIF-1α to EZH2 promoter via elevating ROS generation. Furthermore, Drp1 knockdown inhibited hypercalcemia-induced neuronal injury in CKD while overexpression of EZH2 could reverse this effect in vivo. CONCLUSION: Taken together, the key findings of the current study demonstrate the promotive role of Drp1 in mitochondrial fragmentation which contributes to hypercalcemia-induced neuronal injury in CKD.


Asunto(s)
Dinaminas/metabolismo , Hipercalcemia , Mitocondrias , Insuficiencia Renal Crónica , Animales , Apoptosis , Calcitonina/metabolismo , Calcitonina/farmacología , Modelos Animales de Enfermedad , Dinaminas/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Hipercalcemia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Mitocondrias/metabolismo , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Insuficiencia Renal Crónica/metabolismo
3.
J Mol Recognit ; 34(4): e2880, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33166010

RESUMEN

In this work, seven acrylonitrile derivatives were selected as potential inhibitors of fat and obesity-related proteins (FTO) by the aid of fluorescence spectroscopy, ultraviolet visible spectroscopy, molecular docking, and cytotoxicity methods. Results show that the interaction between 3-amino-2-(4-chlorophenyl)-3-phenylacrylonitrile (1a) and FTO was the strongest among these derivatives. Thermodynamic analysis and molecular modeling show that the main force between 1a and FTO is hydrophobic interaction. The cytotoxicity test showed that the IC50 value of 1a was 46.64 µmol/L, which indicated 1a had the smallest IC50 value and had the best inhibitory effect on the proliferation of leukemia K562 cells among the seven derivatives. Both our previous results and this work show that chlorine atoms play important role in the binding of small molecules and FTO. This work brings new information for the study of FTO inhibitors.


Asunto(s)
Acrilonitrilo/química , Acrilonitrilo/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/química , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Cloro/química , Acrilonitrilo/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Fluorescencia , Humanos , Células K562 , Modelos Moleculares , Espectrometría de Fluorescencia/métodos , Espectrofotometría Ultravioleta , Termodinámica
4.
Opt Express ; 29(8): 12195-12205, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33984984

RESUMEN

A novel laser-induced thermoelastic spectroscopy (LITES) sensor based on a polymer-coated quartz tuning fork (QTF) is reported. Two types of polymer films with different thicknesses are deposited on commercially available QTF to improve the conversion efficiency of laser energy deposition into vibration. CO2 was selected as the target analyte for validation measurements. The experimental results indicate that by introducing a polymer coating, a maximum gain factor of 3.46 and 3.21 is attained for the signal amplitude and signal-to-noise ratio (SNR), respectively, when compared to traditional LITES that using only a bare QTF. A minimum detectable concentration of 0.181% can be obtained, corresponding to a normalized noise equivalent absorption coefficient (NNEA) of 1.74×10-11 cm-1·W·Hz-1/2, and the measurement precision is approximately 0.06% with an averaging time of 200 s. Here, we show what we believe is the first demonstration of polymer coated QTF for LITES sensing, compared with custom QTF, the design has the virtues of lower cost, simple and easy-to-operate, is a promising new strategy for sensitive trace gas analysis.

5.
Opt Express ; 29(13): 20190-20204, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34266113

RESUMEN

Sensitive and broadband infrared sensors are required for security and medical applications, as few can rapidly and sensitively detect infrared without uncooled devices. Here, we report a wideband optical-detection strategy based on the thermoelastic effect of a coating-enhanced quartz tuning fork (QTF) and study the feasibility of using an atomic force probe operating in contact mode to monitor the vibration. Graphene oxide (GO) and polydimethylsiloxane (PDMS) coating were applied on the QTF's surface to improve the light absorption and the thermal-mechanical conversion efficiency. Experimental results showed that the bi-layer coatings yielded a maximum gain factor of 8 in response amplitude and signal-to-noise ratio (SNR) than that of a bare QTF, respectively. Lasers with wavelengths of 1512 nm and 10.6 µm were used as the typical representative light source to test the photoresponse of the QTF detector. The device displays a broadband photoresponse covering the near-infrared to mid-infrared range at room temperature, high performance with the maximum photoresponsivity of 85.76 V·mW-1, and 1σ detection limit of 0.056 µW; the lowest noise equivalent power (NEP) of 1.35 nW·Hz-1/2 and 43.9 ms response speed is also achieved. The preparation process of detector is simple and easy to implement; the resulting device exhibits high responsivity and wide wavelength response ranging at least from 1512 to 10600 nm, compared with custom QTF; and the surface coating strategy potentially enables the construction of a new class of low-cost photodetection sensors operated at room temperature.

6.
BMC Infect Dis ; 19(1): 19, 2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30616531

RESUMEN

BACKGROUND: Hand, foot and mouth disease (HFMD) is an infectious disease caused by enteroviruses that has a severely impair for those high incidence countries such as China.The current study aimed to investigate the epidemic pattern of HFMD by time and region in Northwestern China. METHODS: All reported HFMD cases from 2008 to 2015 were collected from local Disease Control and Prevention.The HFMD was diagnosed in accordance with the guidebook provided by the National Health and Family Planning Commission of the People's Republic of China. RESULTS: A total of 154,869 cases of probable HFMD were reported. The overall incidence of HFMD has been increased from 91.68 per 100/000 in 2008 to 335.64 per 100/000 in 2015.The case mortality is decreased from 0.014 per100/000 to 0.011 per 100/000 during the time period. Most HFMD (93.82%) occurred in children younger than 5 years. The seasonal peak of HFMD infections occurred in April-July and September-November and Central regions of Xi'an city were the major locations of the clusters (incidence rate 245.75/100,000; relative risk 1.19, P < 0.01). EVA71 was the predominant enterovirus serotype, accounting for 50.0% of all reported HFMD cases since 2011.The most susceptible group infected by HFMD was children younger than 5 years, especially boys. CONCLUSIONS: Incidence of HFMD has been increasing in the past few years, however, the case fatality is decreasing. Season and region shall be considered as influence factors in the prevention of HFMD.


Asunto(s)
Enfermedad de Boca, Mano y Pie/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , China/epidemiología , Ciudades , Enterovirus Humano A/clasificación , Enterovirus Humano A/patogenicidad , Epidemias , Femenino , Enfermedad de Boca, Mano y Pie/mortalidad , Enfermedad de Boca, Mano y Pie/virología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Mortalidad , Estaciones del Año , Serogrupo
7.
Int J Mol Sci ; 16(1): 1008-29, 2015 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-25569083

RESUMEN

Here we describe a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects. This work takes advantage of a large chemical biology data set comprising the effects of known, well-characterized reference agents on the cell surface levels of tissue factor (TF) in a primary human endothelial cell-based model of vascular inflammation, the BioMAP® 3C system. In previous work with the Environmental Protection Agency (EPA) for the ToxCast™ program, aryl hydrocarbon receptor (AhR) agonists and estrogen receptor (ER) antagonists were found to share an usual activity, that of increasing TF levels in this system. Since human exposure to compounds in both chemical classes is associated with increased incidence of thrombosis-related side effects, we expanded this analysis with a large number of well-characterized reference compounds in order to better understand the underlying mechanisms. As a result, mechanisms for increasing (AhR, histamine H1 receptor, histone deacetylase or HDAC, hsp90, nuclear factor kappa B or NFκB, MEK, oncostatin M receptor, Jak kinase, and p38 MAPK) and decreasing (vacuolar ATPase or V-ATPase) and mTOR) TF expression levels were uncovered. These data identify the nutrient, lipid, bacterial, and hypoxia sensing functions of autophagy as potential key regulatory points controlling cell surface TF levels in endothelial cells and support the mechanistic hypothesis that these functions are associated with thrombosis-related side effects in vivo.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Modelos Biológicos , Compuestos Orgánicos/toxicidad , Trombosis/etiología , Autofagia , Biomarcadores/metabolismo , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Estrógenos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Tromboplastina/metabolismo
8.
Front Physiol ; 15: 1346579, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660535

RESUMEN

Glycerophosphocholine (GPC) is a water-soluble small molecule found naturally in humans and foods such as milk and soybeans. It can activate the IIS pathway by regulating the expression of daf-2, ins-18 and daf-16 genes, sek-1 and skn-1 genes of MAPK pathway, sod-3, ctl-1, gst-4 and other antioxidant genes. GPC can relieve symptoms related to aging in organisms. The aim of this study was to probe the effects of GPC on the longevity and stress resistance of the entomopathogenic nematode (EPN) Steinernema kraussei 0657L strain. The results showed that the lifespan of S. kraussei 0657L was significantly prolonged by 50 mM GPC treatment, which was 54.55% longer than that of the control (0 mM GPC). GPC significantly inhibited reactive oxygen species (ROS) and lipofuscin accumulation, but the body size and fecundity of S. kraussei 0657L had little changed. At the same time, the longevity of S. kraussei 0657L exposed to heat shock and UV-B radiation was significantly prolonged than that with no external stress. GPC supplementation increased the activity of antioxidant enzymes and corresponding gene expression. Under treatment with 50 mM GPC, the activities of superoxide dismutase and catalase were increased by 1.90- and 4.13-fold, respectively, the expression of the sod-3 and ctl-1 genes was increased by 3.60- and 0.60-fold, respectively, and harmful reactive oxygen species were removed. In addition, the expression levels of the ins-18, skn-1, sek-1 and gst-4 genes related to the insulin/IGF-1 signaling pathway were upregulated 1.04-, 1.84-, 2.21- and 1.24-fold, respectively. These results indicate that GPC is mainly involved in the lifespan regulation of S. kraussei 0657L and plays an important role in resistance to external stress by activating the insulin/IGF-1 signaling pathway and downstream PI3K/MAPK kinase, creating a new idea for improving the commercial efficacy of S. kraussei. It also laid a theoretical foundation for its further efficient development and utilization in the field of biological control.

9.
Nutrients ; 16(16)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39203816

RESUMEN

Target values for 25-hydroxy vitamin D and 1,25(OH)2D or 1,25-dihydroxy vitamin D remain a topic of debate among clinicians. We analysed data collected from December 2012 to April 2020 from two cohorts. Cohort A, comprising 455,062 subjects, was used to investigate the relationship between inflammatory indicators (white blood cell [WBC] count and C-reactive protein [CRP]) and 25(OH)D/1,25(OH)2D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH)2D and mineral metabolism markers (phosphate, calcium, and intact parathyroid hormone [iPTH]). Quadratic models fit best for all tested correlations, revealing U-shaped relationships between inflammatory indicators and 25(OH)D and 1,25(OH)2D. Minimal CRP and WBC counts were observed at 1,25(OH)2D levels of 60 pg/mL and at 25(OH)D levels of 32 ng/mL, as well as of 42 ng/mL, respectively. iPTH correlated inversely with both 1,25(OH)2D and 25(OH)D, while phosphate as well as calcium levels positively correlated with both vitamin D forms. Calcium-phosphate product increased sharply when 25(OH)D was more than 50 ng/mL, indicating a possible risk for vascular calcification. Multiple regression analyses confirmed that these correlations were independent of confounders. This study suggests target values for 25(OH)D between 30-50 ng/mL and for 1,25(OH)2D between 50-70 pg/mL, based particularly on their associations with inflammation but also with mineral metabolism markers. These findings contribute to the ongoing discussion around ideal levels of vitamin D but require support from independent studies with data on clinical endpoints.


Asunto(s)
Calcio , Inflamación , Vitamina D , Humanos , Vitamina D/sangre , Vitamina D/análogos & derivados , Femenino , Masculino , Inflamación/sangre , Persona de Mediana Edad , Calcio/sangre , Hormona Paratiroidea/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adulto , Estudios de Cohortes , Biomarcadores/sangre , Anciano , Fosfatos/sangre , Fosfatos de Calcio/sangre , Recuento de Leucocitos , Deficiencia de Vitamina D/sangre
10.
Cardiorenal Med ; 14(1): 407-415, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39004070

RESUMEN

INTRODUCTION: Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases. However, there is a lack of clinical studies to clarify the prognostic significance of systemic periostin on all-cause mortality in patients with end-stage renal disease on hemodialysis. METHODS: 313 stable end-stage renal disease patients were recruited and followed for 5 years concerning all-cause mortality. At baseline, we collected blood samples and clinical data. Serum periostin concentrations were measured using a certified ELISA. RESULTS: The optimal cut-off value for serum periostin regarding all-cause mortality, calculated through receiver operating characteristic analysis, was 777.5 pmol/L. Kaplan-Meier survival analysis using this cut-off value demonstrated that higher periostin concentrations are linked to higher all-cause mortality (log-rank test: p = 0.002). Subgroup analysis revealed that serum periostin concentrations only affected all-cause mortality in male but not in female patients (p = 0.002 in male patients and p = 0.474 in female patients). Multivariate Cox regression analyses, adjusted for confounding factors, likewise showed that elevated serum periostin concentrations were positively associated with all-cause mortality in male (p = 0.028) but not in female patients on hemodialysis (p = 0.313). CONCLUSION: Baseline serum periostin is an independent risk factor for all-cause mortality in male patients with chronic renal disease on hemodialysis.


Asunto(s)
Moléculas de Adhesión Celular , Fallo Renal Crónico , Diálisis Renal , Humanos , Moléculas de Adhesión Celular/sangre , Femenino , Fallo Renal Crónico/terapia , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Anciano , Factores Sexuales , Pronóstico , Causas de Muerte/tendencias , Biomarcadores/sangre , Factores de Riesgo , Curva ROC , Estimación de Kaplan-Meier , Periostina
11.
Cell Signal ; 116: 111063, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38242267

RESUMEN

Chronic kidney disease (CKD) often culminates in hypercalcemia, instigating severe neurological injuries that are not yet fully understood. This study unveils a mechanism, where GSK343 ameliorates CKD-induced neural damage in mice by modulating macrophage polarization through the EZH2/MST1/YAP1 signaling axis. Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure. This molecular pathway introduced herein not only sheds light on the cellular machinations behind CKD-induced neurological harm but also paves the way for potential therapeutic interventions targeting the identified axis, especially considering the M2 macrophage polarization as a potential strategy to mitigate hypercalcemia-induced neural injuries.


Asunto(s)
Hipercalcemia , Piridonas , Insuficiencia Renal Crónica , Ratones , Animales , Macrófagos , Indazoles/farmacología , Insuficiencia Renal Crónica/complicaciones
12.
Environ Pollut ; 306: 119349, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35487467

RESUMEN

Increasing rates of commercialization and industrialization have led to the comprehensive evaluation of toxic effects of microplastics on crop plants. However, research on the impact of functionalized polystyrene nanoplastics on the toxicity of heavy metals remains limited. This study investigated the effects of polystyrene, carboxy-modified polystyrene, and amino-modified polystyrene on lead (Pb) toxicity in dandelion seedlings. The results showed that carboxy -modified polystyrene with a negative charge absorbed more Pb2+ than polystyrene and amino-modified polystyrene, and their maximum adsorption amounts were 5.328, 0.247, and 0.153 µg g-1, respectively. The hydroponic experiment demonstrated that single amino-modified polystyrene was more toxic to dandelion seedlings than polystyrene and carboxy-modified polystyrene. The presence of Pb2+ was found to increase antioxidant enzymes (superoxide dismutase and catalase) and non-antioxidant enzymes (glutathione and ascorbic acid) activities in response to excessive reactive oxygen species in dandelion leaves and roots treated with polystyrene and carboxy-modified polystyrene, while it did not change much when amino-modified polystyrene was added. Interestingly, compared with single Pb2+, the addition of amino-modified polystyrene with positive charges induced an obvious decrease in the above parameters; however, they declined slightly in the treatments with polystyrene and carboxy-modified polystyrene despite a stronger adsorption capacity for Pb2+. Similarly, the bioactive compounds, including flavonoids, polyphenols, and polysaccharides in dandelion, showed a scavenging effect on O2- and H2O2, thereby inhibiting the accumulation and reducing medicinal properties. This study found that the effects of microplastics on the uptake, distribution, and toxicity of heavy metals depended on the nanoparticle surface charge.


Asunto(s)
Metales Pesados , Taraxacum , Peróxido de Hidrógeno/farmacología , Plomo/toxicidad , Metales Pesados/farmacología , Microplásticos , Plásticos/farmacología , Poliestirenos/toxicidad , Plantones
13.
J Pharm Biomed Anal ; 207: 114426, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34689062

RESUMEN

Alcoholism is a severe threat to public health, and there are no adequate treatments for alcoholic liver disease. The aim of this study was to identify bioactive peptides derived from natural proteins that prevent acute alcohol-induced liver injury. We identified a peptide with the sequence Gly-Leu-hydroxyproline-Gly-Glu-Arg (GLpGER) from the hydrolysate of crucian carp swim bladder using size-exclusion chromatography and reversed-phase chromatography. The in vitro EC50 value of GLpGER to activate alcohol dehydrogenase (ADH) was 137.9 ± 9 µM. Molecular docking experiments indicated that the mechanism by which GLpGER activates ADH may be related to the formation of stable complexes with ADH active pockets through hydrogen bonding, and electrostatic and hydrophobic interactions. Oral administration of GLpGER one hour before acute alcohol ingestion significantly increased alcohol metabolism, manifesting as reduced incidence of the loss of righting reflex, increased alcohol tolerance time, shortened sobering time, and decreased blood alcohol concentration level. GLpGER restored liver ADH activity, maintained the typical morphology of hepatocytes, and reduced serum levels of alanine aminotransferase and aspartate aminotransferase. These findings suggest that GLpGER might reduce acute alcohol-induced liver injury and may have the potential to be developed as an anti-inebriation ingredient.


Asunto(s)
Carpas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Alcohol Deshidrogenasa , Animales , Nivel de Alcohol en Sangre , Etanol , Hígado , Ratones , Simulación del Acoplamiento Molecular , Péptidos , Vejiga Urinaria
14.
Biomed Pharmacother ; 156: 113947, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36411661

RESUMEN

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. METHODS: We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing. FINDINGS: Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p < 0.01 in all cases). Renal interstitial fibrosis and glomerulosclerosis was likewise decreased by 51% and 66.8%; respectively (p < 0.05 in all cases). 14 distinct kidney cell clusters could be identified by scRNA-seq. The polarization of M2 macrophages from state 1 (CD206-CD68- M2 macrophages) to state 5 (CD206+CD68+ M2 macrophages) was the main pro-fibrotic process, as CD206+CD68+ M2 macrophages highly expressed fibrosis-promoting genes and can convert into fibrocytes. Empagliflozin remarkably inhibited the expression of fibrosis-promoting (IFG1 and TREM2) and polarization-associated genes (GPNMB, LGALS3, PRDX5, and CTSB) in CD206+CD68+ M2 macrophages and attenuated inflammatory signals from CD8+ effector T cells. The inhibitory effect of empagliflozin on CD206+CD68+ M2 macrophages polarization was mainly achieved by affecting mitophagy and mTOR pathways. INTERPRETATION: We propose that the beneficial effects of empagliflozin on kidney function and morphology in 5/6 nephrectomyiced rats with established CKD are at least partially due to an inhibition of CD206+CD68+ M2 macrophage polarization by targeting mTOR and mitophagy pathways and attenuating inflammatory signals from CD8+ effector T cells. FUNDINGS: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Ratas , Animales , Activación de Macrófagos , Diabetes Mellitus Tipo 2/patología , Fibrosis , Riñón/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Nefrectomía , Serina-Treonina Quinasas TOR , Glicoproteínas de Membrana
15.
Water Res ; 203: 117541, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34416650

RESUMEN

Efficient removal of low-concentration refractory pollutants is a crucial problem to ensuring water safety. The use of heterogeneous catalysis of molecular imprinting technology combined with traditional catalysts is a promising method to improve removal efficiency. Presently, the research into molecular imprinting targeting catalysts focuses mainly on material preparation and performance optimization. However, more researchers are investigating other applications of imprinting materials. This review provides recent progress in photocatalyst preparation, electrocatalyst, and Fenton-like catalysts synthesized by molecular imprinting. The principle and control points of target catalysts prepared by precipitation polymerization (PP) and surface molecular imprinting (S-MIP) are introduced. Also, the application of imprinted catalysts in targeted degradation of drugs, pesticides, environmental hormones, and other refractory pollutants is summarized. In addition, the reusability and stability of imprinted catalyst in water treatment are discussed, and the possible ecotoxicity risk is analyzed. Finally, we appraised the prospects, challenges, and opportunities of imprinted catalysts in the advanced oxidation process. This paper provides a reference for the targeted degradation of refractory pollutants and the preparation of targeted catalysts.


Asunto(s)
Impresión Molecular , Contaminantes Químicos del Agua , Purificación del Agua , Catálisis , Aguas Residuales , Contaminantes Químicos del Agua/análisis
16.
Chemosphere ; 270: 128620, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33109356

RESUMEN

Adsorptive removal of dimethyl phthalate (DMP) in water combined with advanced oxidation processes (AOPs) has attracted interest. In this work, the adsorptive and catalytic properties of an Fe-based metal-organic framework (Fe-MOF-74) have been improved by molecular imprinting technique. The adsorption behaviors have been evaluated by the Freundlich and pseudo-second-order model. The results have shown that selective adsorption ability of the material for DMP was highly enhanced and chemisorption was dominating. A 1.5-fold increase in catalytic rate after being modified by molecular imprinting indicated that the selective adsorption is crucial. In the synergy of adsorption and catalysis, DMP was first specifically adsorbed on the surface of the material by hydrogen bonds and electrostatic interactions. Then, hydroxyl radicals and sulfate radicals, which were both generated via activation of persulfate (PS), catalytically oxidized DMP. The degradation rate can rapidly reach around 90% in 30 min and three possible degradation pathways were proposed. The molecular imprinting modified catalyst can be used for DMP effective degradation in water.


Asunto(s)
Impresión Molecular , Ácidos Ftálicos , Contaminantes Químicos del Agua , Adsorción , Catálisis , Oxidación-Reducción
17.
J Hazard Mater ; 411: 125194, 2021 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-33858121

RESUMEN

The poor water stability of metal-organic frameworks (MOFs) significantly hindered their catalytic application in advanced oxidation system. A protective outer layer was an effective strategy to solve this problem. However, the commonly used coating techniques are too complicated or too difficult to accurately control, thus, the applicability was relatively low. In this study, a water stable MOF core-SiO2 shell nanomaterial (Fe-MOF-74@SiO2) was synthesized by a facile hydrothermal method, and applied to activate persulfate (PS) for dimethyl phthalate (DMP) degradation. The catalyst water stability and DMP degradation in the system were investigated, suggesting that the SiO2-coated catalyst was more stable and exhibited higher DMP degradation efficiency over the pure MOF. It was found that pH had negligible effects on Fe-MOF-74@SiO2 + PS system, while, higher temperature facilitated the degradation of DMP. The activation mechanism was studied by quenching experiments combined with electron paramagnetic resonance, indicating that SO4⋅- played a major role in the activation of PS with Fe-MOF-74@SiO2 for DMP removal, while ⋅OH also involved in the catalytic process. Finally, possible DMP degradation pathways were proposed. These findings indicated that the core-shell structured Fe-MOF-74@SiO2 showed promise for DMP degradation by PS advanced oxidation system.

18.
Future Med Chem ; 13(17): 1475-1489, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34240624

RESUMEN

Studies have shown that the FTO gene is closely related to obesity and weight gain in humans. FTO is an N6-methyladenosine demethylase and is linked to an increased risk of obesity and a variety of diseases, such as acute myeloid leukemia, type 2 diabetes, breast cancer, glioblastoma and cervical squamous cell carcinoma. In light of the significant role of FTO, the development of small-molecule inhibitors targeting the FTO protein provides not only a powerful tool for grasping the active site of FTO but also a theoretical basis for the design and synthesis of drugs targeting the FTO protein. This review focuses on the structural characteristics of FTO inhibitors and discusses the occurrence of obesity and cancer caused by FTO gene overexpression.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/antagonistas & inhibidores , Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Neoplasias/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/farmacología , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Antineoplásicos/química , Inhibidores Enzimáticos/química , Humanos , Neoplasias/metabolismo , Bibliotecas de Moléculas Pequeñas/química
19.
Front Plant Sci ; 11: 241, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32210999

RESUMEN

Cyanobacteria have evolved various strategies to sense and adapt to biotic and abiotic stresses including active movement. Motility in cyanobacteria utilizing the type IV pili (TFP) is useful to cope with changing environmental conditions. The model cyanobacterium Synechocystis sp. PCC 6803 (hereafter named Synechocystis) exhibits motility via TFP called thick pili, and uses it to seek out favorable light/nutrition or escape from unfavorable conditions. Recently, a number of studies on Synechocystis thick pili have been undertaken. Molecular approaches support the role of the pilin in motility, cell adhesion, metal utilization, and natural competence in Synechocystis. This review summarizes the most recent studies on the function of thick pili as well as their formation and regulation in this cyanobacterium.

20.
Chemosphere ; 240: 124875, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31541899

RESUMEN

Adsorptive removal of phthalate esters from wastewater combined with their persulfate (PS) catalytic degradation has attracted the attention of many researchers. In this study, the adsorptive and catalytic properties of an MIL100 material obtained by a green synthetic route have been optimized by a surface molecular imprinting technique. Results have shown that there are two steps in the molecular imprinting process. A polymerization is first carried out in the internal channels of the material and the imprinting layer is then formed on the surface. The relative proportions of the starting materials for the synthesis have been optimized through the design of a three-dimensional response surface. The amount of pollutant adsorbed was increased fourfold after surface imprinting, reaching 13.6 mg g-1. The homogeneity of the recognition sites has been evaluated by dynamics calculations and the Freundlich equation. The selective adsorption ability of the material for diethyl phthalate was improved, and the process involved chemical adsorption. The catalytic properties of the material after imprinting were increased about 1.5-fold, indicating that selective adsorption is important. Such molecularly imprinted polymers may potentially serve as good functional materials for the removal of phthalate esters from wastewater.


Asunto(s)
Impresión Molecular/métodos , Ácidos Ftálicos/química , Aguas Residuales/química , Polímeros/química
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