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1.
BMC Cancer ; 23(1): 227, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36899319

RESUMEN

BACKGROUND: An early diagnosis of pancreatic cancer (PC) is extremely difficult because of the lack of sensitive liquid biopsy methods and effective biomarkers. We attempted to evaluate whether circulating inflammatory marker could complement CA199 for the detection of early-stage PC. METHODS: We enrolled 430 patients with early-stage PC, 287 patients with other pancreatic tumors (OPT), and 401 healthy controls (HC). The patients and HC were randomly divided into a training set (n = 872) and two testing sets (n1 = 218, n2 = 28). The receiver operating characteristic (ROC) curves were investigated to evaluate the diagnostic performance of circulating inflammatory markers ratios, CA199, and combinations of the markers ratios in the training set, which would then be validated in the two testing sets. RESULTS: Circulating fibrinogen, neutrophils, and monocytes in patients with PC were significantly higher while circulating albumin, prealbumin, lymphocytes, and platelets of patients with PC were significantly lower compared to those of HC and OPT (all P < 0.05). The fibrinogen-to-albumin (FAR), fibrinogen-to-prealbumin (FPR), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), and fibrinogen-to-lymphocyte (FLR) ratios were significantly higher while the prognostic nutrition index values (PNI) were lower in patients with PC than in HC and OPT (all P < 0.05). Combining the FAR, FPR, and FLR with CA199 exhibited the best diagnostic value for distinguishing patients with early-stage PC from HC with an area under the curve (AUC) of 0.964, and for distinguishing patients with early-stage PC from OPT with an AUC of 0.924 in the training sets. In the testing set, compared with HC, the combination markers had powerful efficiency for PC with an AUC 0.947 and AUC 0.942 when comparing PC with OPT. The AUC was 0.915 for the combination of CA199, FAR, FPR, and FLR for differentiating between patients with pancreatic head cancer (PHC) and other pancreatic head tumors (OPHT), and 0.894 for differentiating between patients with pancreatic body and tail cancer (PBTC) and other pancreatic body and tail tumors (OPBTT). CONCLUSION: A combination of FAR, FPR, FLR, and CA199 may serve as a potential non-invasive biomarker for differentiating early-stage PC from HC and OPT, especially early-stage PHC.


Asunto(s)
Neoplasias Pancreáticas , Prealbúmina , Humanos , Biomarcadores de Tumor , Linfocitos/química , Neoplasias Pancreáticas/patología , Neutrófilos/patología , Fibrinógeno/análisis , Estudios Retrospectivos , Pronóstico , Neoplasias Pancreáticas
2.
Ecotoxicol Environ Saf ; 256: 114913, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37062264

RESUMEN

The rapid development of nanotechnology has aroused considerable attentions toward understanding the effects of engineered nanomaterials (ENMs) on the propagation of antibiotic resistance. Molybdenum disulfide (MoS2) is an extensively used ENM and poses potential risks associated with environmental exposure; nevertheless, the role of MoS2 toward antibiotic resistance genes (ARGs) transfer remains largely unknown. Herein, it was discovered that MoS2 nanosheets accelerated the horizontal transfer of RP4 plasmid across Escherichia coli in a dose-dependent manner (0.5-10 mg/L), with the maximum transfer frequency 2.07-fold higher than that of the control. Integration of physiological, transcriptomics, and metabolomics analyses demonstrated that SOS response in bacteria was activated by MoS2 due to the elevation of oxidative damage, accompanied by cell membrane permeabilization. MoS2 promoted bacterial adhesion and intercellular contact via stimulating the secretion of extracellular polysaccharides. The ATP levels were maximally increased by 305.7 % upon exposure to MoS2, and the expression of plasmid transfer genes was up-regulated, contributing to the accelerated plasmid conjugation and increased ARG abundance in soil. Our findings highlight the roles of emerging ENMs (e.g., MoS2) in ARGs dissemination, which is significant for the safe applications and risk management of ENMs under the development scenarios of nanotechnology.


Asunto(s)
Antibacterianos , Molibdeno , Antibacterianos/farmacología , Molibdeno/farmacología , Genes Bacterianos , Suelo , Transferencia de Gen Horizontal , Farmacorresistencia Microbiana/genética , Escherichia coli , Plásmidos
3.
Immunol Cell Biol ; 100(3): 144-159, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35080788

RESUMEN

Bronchial asthma is divided into Th2 high, Th2 low and mixed types. The Th2 high type is dominated by eosinophils while the Th2 low type is divided into neutrophilic and paucigranulocytic types. Eosinophilic asthma has gained increased attention recently, and its pathogenesis and treatment are well understood. However, severe neutrophilic asthma requires more in-depth research because its pathogenesis is not well understood, and no effective treatment exists. This review looks at the advances made in asthma research, the pathogenesis of neutrophilic asthma, the mechanisms of progression to severe asthma, risk factors for asthma exacerbations, and biomarkers and treatment of neutrophilic asthma. The pathogenesis of neutrophilic asthma is further discussed from four aspects: Th17-type inflammatory response, inflammasomes, exosomes and microRNAs. This review provides direction for the mechanistic study, diagnosis and treatment of neutrophilic asthma. The treatment of neutrophilic asthma remains a significant challenge for clinical therapists and is an important area of future clinical research.


Asunto(s)
Asma , Neutrófilos , Asma/tratamiento farmacológico , Eosinófilos , Humanos , Inflamación/tratamiento farmacológico , Células Th17
4.
Environ Sci Technol ; 56(13): 9556-9568, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35576172

RESUMEN

Thorough investigations of the environmental fate and risks are necessary for the safe application of engineered nanomaterials. Nevertheless, the current understanding of potential transformations of MoS2 (an intensively studied two-dimensional nanosheet) upon interactions with ubiquitous environmentally relevant thiols (ERTs) in water is limited. This study revealed that two ERTs, l-cysteine and mercaptoacetic acid, could modify MoS2 by covalently grafting thiol groups on S atoms of 1T phases, improving the colloidal persistence and chemical stability of MoS2. Compared with the pristine form, MoS2-thiols with higher dispersity exhibited significantly mitigated envelopment and ultrastructural damage to microalgae. MoS2-triggered growth inhibition, upregulation of reactive oxygen species, photosynthetic injury, and metabolic perturbation in algae were remarkably attenuated by ERTs. The diminished capability for MoS2 to generate reactive intermediates and glutathione oxidation driven by ERTs caused the weakness of oxidative stress and negative effects. Additionally, molecular dynamics simulations demonstrated that ERTs altered the extent of the influence of MoS2 on the secondary structures and functions of adsorbed intracellular proteins, which also contributed to the lower phytotoxicity of MoS2. Our findings provide evidence for the crucial role of specific organic ligands in the risk of MoS2 in aquatic environments.


Asunto(s)
Molibdeno , Nanoestructuras , Disulfuros , Nanoestructuras/química , Nanoestructuras/toxicidad , Compuestos de Sulfhidrilo
5.
Pers Individ Dif ; 179: 110893, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36540084

RESUMEN

Confronting COVID-19 pandemic, one's health belief and behavior are essential to mental well-being. Thus conceived, this study applied the Health Belief Model to test the mediating effect of risk perception and coping strategies on the relationship between self-efficacy and mental health problems. Six hundred and eighteen participants aged 17-52 (117 males and 501 females) completed our web-based survey from February 7 to April 10, 2020. 12.6-15.1% of participants were affected by COVID-19 outbreak in varying degrees. The mediating effects of risk perception and active coping were significant, so was the serial mediating effect of risk perception and passive coping. Individuals with higher general self-efficacy were more likely to have lower risk perception, less passive coping strategies, more active coping strategies, and subsequently had less mental health problems. In conclusion, application of the HBM would help understand how mental health problems happen during an infectious disease epidemic, and the relationships among the HBM constructs need further investigation.

7.
Environ Sci Technol ; 54(21): 13888-13898, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33078945

RESUMEN

Microplastics (MPs) are ubiquitous in the environment and pose substantial threats to the water ecosystem. However, the impact of natural aging of MPs on their toxicity has rarely been considered. This study found that visible light irradiation with hydrogen peroxide at environmentally relevant concentration for 90 days significantly altered the physicochemical properties and mitigated the toxicity of polyamide (PA) fragments to infantile zebrafish. The size of PA particles was reduced from ∼8.13 to ∼6.37 µm, and nanoparticles were produced with a maximum yield of 5.03%. The end amino groups were volatilized, and abundant oxygen-containing groups (e.g., hydroxyl and carboxyl) and carbon-centered free radicals were generated, improving the hydrophilicity and colloidal stability of degraded MPs. Compared with pristine PA, the depuration of degraded MPs mediated by multixenobiotics resistance was much quicker, leading to markedly lower bioaccumulation in fish and weaker inhibition on musculoskeletal development. By integrating transcriptomics and transgenic zebrafish [Tg(lyz:EGFP)] tests, differences in macrophages-triggered proinflammatory effects, apoptosis via IL-17 signaling pathway, and antioxidant damages were identified as the underlying mechanisms for the attenuated toxicity of degraded MPs. This work highlights the importance of natural degradation on the toxicity of MPs, which has great implications for risk assessment of MPs.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Animales , Apoptosis , Ecosistema , Larva , Macrófagos , Nylons/toxicidad , Estrés Oxidativo , Plásticos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Pez Cebra
8.
Environ Sci Technol ; 54(19): 12295-12306, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-32852947

RESUMEN

The increasing applications of single-layer molybdenum disulfide (SLMoS2) pose great potential risks associated with environmental exposure. This study found that metallic-phase SLMoS2 with nanoscale (N-1T-SLMoS2, ∼400 nm) and microscale (M-1T-SLMoS2, ∼3.6 µm) diameters at 10-25 mg/L induced significant algal growth inhibition (maximum 72.7 and 74.6%, respectively), plasmolysis, and oxidative damage, but these alterations were recoverable. Nevertheless, membrane permeability, chloroplast damage, and chlorophyll biosynthesis reduction were persistent. By contrast, the growth inhibition (maximum 55.3%) and adverse effects of nano-sized semiconductive-phase SLMoS2 (N-2H-SLMoS2, ∼400 nm) were weak and easily alleviated after 96 h of recovery. N-1T-SLMoS2 (0.011 µg/h) and N-2H-SLMoS2 (0.008 µg/h) were quickly biodegraded to soluble Mo compared with M-1T-SLMoS2 (0.004 µg/h) and excreted by algae. Incomplete biodegradation of SLMoS2 (26.8-43.9%) did not significantly mitigate its toxicity. Proteomics and metabolomics indicated that the downregulation of proteins (50.7-99.2%) related to antioxidants and photosynthesis and inhibition of carbon fixation and carbohydrate metabolism contributed to the persistent phytotoxicity. These findings highlight the roles and mechanisms of the size and phase in the persistent phytotoxicity of SLMoS2, which has potential implications for risk assessment and environmental applications of nanomaterials.


Asunto(s)
Molibdeno , Nanoestructuras , Disulfuros/toxicidad , Molibdeno/toxicidad , Fotosíntesis
9.
Bull Environ Contam Toxicol ; 105(5): 790-797, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33037880

RESUMEN

Manure, soil, and vegetable samples were collected from different-sized livestock farms in Xinxiang, China. The residues of sulfadiazine, sulfamonomethoxine, and sulfamethoxazole were analyzed by high-performance liquid chromatography. The results indicated that the concentration ranges of the three total sulfonamides in manure, soil, and vegetables were 10.13-566.23 µg kg-1, 7.60-176.26 µg kg-1, and 0-32.70 µg kg-1, respectively. The mean concentrations were 219.71 µg kg-1, 70.73 µg kg-1, and 7.08 µg kg-1 for manure, soil, and vegetables, respectively. The mean concentrations in soil were lower than the ecotoxic effect trigger value (100 µg kg-1), indicating a low risk for organisms in soil. The concentrations of the three sulfonamides varied significantly in different types of vegetables and all were lower than the acceptable daily intake value (50 µg (kg day)-1). However, the potential ecotoxicity and danger to human and animal health via accumulation of the antibiotic in the food chain cannot be ignored.


Asunto(s)
Antibacterianos/análisis , Ganado , Estiércol/análisis , Contaminantes del Suelo/análisis , Suelo/química , Sulfonamidas/análisis , Verduras/química , Animales , China , Cromatografía Líquida de Alta Presión , Medición de Riesgo
10.
Environ Sci Technol ; 53(13): 7759-7769, 2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31198033

RESUMEN

Understanding environmental fate is a prerequisite for the safe application of nanoparticles. However, the fundamental persistence and environmental transformation of single-layer molybdenum disulfide (SLMoS2, a 2D nanosheet attracting substantial attention in various fields) remain largely unknown. The present work found that the dissolution of SLMoS2 was pH and dissolved oxygen dependent and that alterations in phase composition significantly occur under visible light irradiation. The 1T phase was preferentially oxidized to yield soluble species (MoO42- and SO42-), and the 2H phase remained as a residual. The transformed SLMoS2 exhibited a ribbon-like and multilayered structure and low colloidal stability due to the loss of surface charge. Dissolved oxygen competitively captured the electrons of SLMoS2 to generate superoxide radicals and accelerated the dissolution of nanosheets. Compared to pristine 1T-phase SLMoS2, the transformed 2H-phase SLMoS2 could not easily enter algal cells and induced a low developmental inhibition, oxidative stress, plasmolysis, photosynthetic toxicity and metabolic perturbation. The downregulation of amino acids and upregulation of unsaturated fatty acids contributed to the higher toxicity of 1T-phase SLMoS2. The dissolved ions did not induce apparent phytotoxicity. The connections between environmental transformation (phase change and ion release) and phytotoxicity provide insights into the safe design and evaluation of 2D nanomaterials.


Asunto(s)
Molibdeno , Oxígeno , Disulfuros , Luz
11.
Environ Sci Technol ; 53(24): 14700-14708, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31633338

RESUMEN

To comprehensively clarify human exposure to halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs) through dermal uptake and hand-to-mouth intake, skin wipe samples from four typical skin locations from 30 volunteers were collected. The total concentration of the target chemicals (24 HFRs and 16 PCBs) ranged from 203 to 4470 ng/m2. BDE-209 and DBDPE accounted for about 37 and 40% of ∑24HFRs, respectively, and PCB-41 and PCB-110 were the dominant PCB congeners, with proportion of 24 and 10%, respectively. Although exhibiting relatively lower concentrations of contaminants than bared skin locations, clothing-covered skin areas were also detected with considerable levels of HFRs and PCBs, indicating clothing to be a potentially significant exposure source. Significant differences in HFR and PCB levels and profiles were also observed between males and females, with more lower-volatility chemicals in male-bared skin locations and more higher-volatility compounds in clothing-covered skin locations of female participants. The mean estimated whole-body dermal absorption doses of ∑8HFRs and ∑16PCBs (2.9 × 10-4 and 6.7 × 10-6 mg/kg·d) were 1-2 orders of magnitude higher than ingestion doses via hand-to-mouth contact (6.6 × 10-7 and 3.1 × 10-7 mg/kg·d). The total noncarcinogenic health risk resulted from whole-body dermal absorption and oral ingestion to ∑7HFRs and ∑16PCBs were 5.2 and 0.35, respectively.


Asunto(s)
Contaminantes Ambientales , Retardadores de Llama , Bifenilos Policlorados , Vestuario , Monitoreo del Ambiente , Femenino , Éteres Difenilos Halogenados , Humanos , Masculino , Medición de Riesgo
12.
Environ Sci Technol ; 52(5): 2638-2648, 2018 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-29425036

RESUMEN

The environmental transformations of nanomaterials are correlated with their behaviors and ecological risks. The applications of single-layer molybdenum disulfide (SLMoS2) have rapidly developed in environmental fields, but the potential transformations and biological effects of SLMoS2 remain largely unknown. This study revealed that humic acid (HA, over 10 mg/L) induced the scrolling of SLMoS2 with light irradiation over a 56-day incubation. The colloidal stability of SLMoS2 increased, and the aggregation ratio decreased from 0.59 ± 0.07 to 0.08 ± 0.01 nm/min after HA hybridization. Besides, compared with pristine SLMoS2, the chemical dissolution rate of SLMoS2 was up to 4.6-fold faster with HA exposure. These results demonstrate that HA affects the environmental fate and transformations of SLMoS2. SLMoS2-HA possessed a significantly widened direct band gap (2.06 eV) compared with that of SLMoS2 (1.8 eV). SLMoS2 acted as an electronic acceptor from HA, resulting in the separation of electron-hole pairs. Consequently, SLMoS2-HA exhibited stronger peroxidase-like catalytic activity, which was approximately 2-fold higher than that of SLMoS2. Moreover, the morphology and layered structure of SLMoS2 changed, and the damage SLMoS2 inflicted on microalgae was significantly reduced. This work provides insights into the behaviors and related biological risks of SLMoS2 in aqueous environments.


Asunto(s)
Sustancias Húmicas , Nanoestructuras , Disulfuros , Molibdeno
13.
Ecotoxicol Environ Saf ; 159: 221-231, 2018 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-29753824

RESUMEN

The effects of graphene oxide (GO) carbon nanomaterials on ecosystems have been well characterized, but the toxicity of GO at predicted environmental concentrations to living organisms at the protein level remain largely unknown. In the present work, the adverse effects and mechanisms of GO at predicted environmental concentrations were evaluated by integrating proteomics and standard analyses for the first time. The abundances of 243 proteins, including proteins involved in endocytosis (e.g., cltcb, arf6, capzb and dnm1a), oxidative stress (e.g., gpx4b, sod2, and prdx1), cytoskeleton assembly (e.g., krt8, krt94, lmna and vim), mitochondrial function (e.g., ndufa10, ndufa8, cox5aa, and cox6b1), Ca2+ handling (e.g., atp1b2a, atp1b1a, atp6v0a1b and ncx4a) and cardiac function (e.g., tpm4a, tpm2, tnni2a.1 and tnnt3b), were found to be notably altered in response to exposure 100 µg/L GO. The results revealed that GO caused malformation and mortality, likely through the downregulation of proteins related to actin filaments and formation of the cytoskeleton, and induced oxidative stress and mitochondrial disorders by altering the levels of antioxidant enzymes and proteins associated with the mitochondrial membrane respiratory chain. Exposure to GO also increased the heart rate of zebrafish larvae and induced pericardial edema, likely by changing the expression of proteins related to Ca2+ balance and cardiac function. This study provides new proteomic-level insights into GO toxicity against aquatic organisms, which will greatly benefit our understanding of the bio-safety of GO and its toxicity at predicted environmental concentrations.


Asunto(s)
Grafito/toxicidad , Nanoestructuras/toxicidad , Óxidos/toxicidad , Pez Cebra , Animales , Frecuencia Cardíaca/efectos de los fármacos , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Larva/metabolismo , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteómica , Pez Cebra/anomalías , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismo
14.
Environ Sci Technol ; 51(14): 7861-7871, 2017 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-28614664

RESUMEN

Developmental toxicity is a critical issue in nanotoxicity. However, very little is known about the effects of graphene oxide (GO, a widely used carbon material) at predicted environmental concentrations on biological development or the specific molecular mechanisms. The present study established that the development of zebrafish embryos exposed to trace concentrations (1-100 µg/L) of GO was impaired because of DNA modification, protein carbonylation and excessive generation of reactive oxygen species (ROS), especially the superoxide radical. Noticeably, there was a nonmonotonic response of zebrafish developmental toxicity to GO at µg/L to mg/L levels. Transcriptomics analysis revealed that disturbing collagen- and matrix metalloproteinase (MMP)-related genes affected the skeletal and cardiac development of zebrafish. Moreover, metabolomics analysis showed that the inhibition of amino acid metabolism and the ratios of unsaturated fatty acids (UFAs) to saturated fatty acids (SFAs) contributed to the above developmental toxicity. The present work verifies the developmental toxicity of GO at trace concentrations and illustrates for the first time the specific molecular mechanisms thereof. Because of the potential developmental toxicity of GO at trace concentrations, government administrators and nanomaterial producers should consider its potential risks prior to the widespread environmental exposure to GO.


Asunto(s)
Daño del ADN , Contaminantes Ambientales/toxicidad , Grafito/toxicidad , Animales , Embrión no Mamífero , Óxidos , Especies Reactivas de Oxígeno , Pez Cebra/embriología
15.
Conscious Cogn ; 55: 172-178, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28886467

RESUMEN

Previous researches have shown that people with higher fluid intelligence are more likely to detect the unexpected stimuli. The current study systematically explored the relationship between fluid intelligence and sustained inattentional blindness in children. In Experiment 1, we measured one hundred and seventy-nine 7-to-14-year-old children's fluid intelligence and sustained inattentional blindness. The results showed that fluid intelligence was negatively related to sustained inattentional blindness only in 7-to-8-year-old children. In Experiment 2, we explored sustained inattentional blindness in sixty children with high Raven's scores. We found that compared with children who have average Raven's scores aged 11-to-12 years old, children with high Raven's scores were unable to better avoid sustained inattentional blindness. In general, this research implies that the relation between fluid intelligence and sustained inattentional blindness is weak. Fluid intelligence could predict sustained inattentional blindness only when children do not have enough perceptual capacities to complete the primary task.


Asunto(s)
Atención/fisiología , Desarrollo Infantil/fisiología , Inteligencia/fisiología , Percepción Visual/fisiología , Adolescente , Niño , Femenino , Humanos , Masculino , Percepción de Movimiento/fisiología , Reconocimiento Visual de Modelos/fisiología
16.
EMBO Rep ; 15(5): 566-75, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24671035

RESUMEN

Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho-mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Mitofagia/fisiología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia , Hipoxia de la Célula , Células HeLa , Humanos , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Mitocondrias/fisiología , Proteínas Mitocondriales/genética , Mutación , Fosforilación , Unión Proteica , Proteínas Serina-Treonina Quinasas/biosíntesis , Regulación hacia Arriba
17.
Int J Mol Sci ; 17(4): 515, 2016 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-27058536

RESUMEN

Cisatracurium besylate is an ideal non-depolarizing muscle relaxant which is widely used in clinical application. However, some studies have suggested that cisatracurium besylate can affect cell proliferation. Moreover, its specific mechanism of action remains unclear. Here, we found that the number of GFP-LC3 (green fluoresent protein-light chain 3) positive autophagosomes and the rate of mitochondria fracture both increased significantly in drug-treated GFP-LC3 and MitoDsRed stable HeLa cells. Moreover, cisatracurium promoted the co-localization of LC3 and mitochondria and induced formation of autolysosomes. Levels of mitochondrial proteins decreased, which were reversed by the lysosome inhibitor Bafinomycin A1. Similar results with evidence of dose-dependent effects were found in both HeLa and Human Umbilical Vein Endothelial Cells (HUVECs). Cisatracurium lowered HUVEC viability to 0.16 (OD490) at 100 µM and to 0.05 (OD490) after 48 h in vitro; it increased the cell death rate to 56% at 100 µM and to 60% after 24 h in a concentration- and time-dependent manner (p < 0.01). Cell proliferation decreased significantly by four fold in Atg5 WT (wildtype) MEF (mouse embryonic fibroblast) (p < 0.01) but was unaffected in Atg5 KO (Knockout) MEF, even upon treatment with a high dose of cisatracurium. Cisatracurium induced significant increase in cell death of wild-type MEFs even in the presence of the apoptosis inhibitor zVAD. Thus, we conclude that activation of both the autophagic cell death and cell apoptosis pathways contributes to cisatracurium-mediated cell injury.


Asunto(s)
Apoptosis/efectos de los fármacos , Atracurio/análogos & derivados , Autofagia/efectos de los fármacos , Bloqueantes Neuromusculares/efectos adversos , Animales , Atracurio/efectos adversos , Línea Celular , Proliferación Celular/efectos de los fármacos , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteolisis/efectos de los fármacos
18.
J Biol Chem ; 289(15): 10691-10701, 2014 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-24573672

RESUMEN

Mitophagy receptors mediate the selective recognition and targeting of damaged mitochondria by autophagosomes. The mechanism for the regulation of these receptors remains unknown. Here, we demonstrated that a novel hypoxia-responsive microRNA, microRNA-137 (miR-137), markedly inhibits mitochondrial degradation by autophagy without affecting global autophagy. miR-137 targets the expression of two mitophagy receptors NIX and FUNDC1. Impaired mitophagy in response to hypoxia caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression vectors lacking the miR-137 recognition sites at their 3' UTR. Conversely, miR-137 also suppresses the mitophagy induced by fundc1 (CDS+3'UTR) but not fundc1 (CDS) overexpression. Finally, we found that miR-137 inhibits mitophagy by reducing the expression of the mitophagy receptor thereby leads to inadequate interaction between mitophagy receptor and LC3. Our results demonstrated the regulatory role of miRNA to mitophagy receptors and revealed a novel link between miR-137 and mitophagy.


Asunto(s)
Autofagia , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Proteínas Mitocondriales/metabolismo , Regiones no Traducidas 3' , Animales , Hipoxia de la Célula , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Vectores Genéticos , Células HEK293 , Células HeLa , Humanos , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Fagosomas/metabolismo
19.
J Nanosci Nanotechnol ; 14(6): 4313-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24738389

RESUMEN

Lutetium oxide nanocrystals codoped with Tm3+ and Yb3+ have been successfully synthesized via adjusting the pH values of the precursor solution in a hydrothermal method followed by a subsequent calcination process. The samples were systematically characterized by X-ray diffraction, field-emission scanning microscopy, Fourier transform infrared transmittance spectroscopy, and upconversion luminescent spectra. The experimental results show that the pH values of the precursor solution have great effects on the structural, morphological, and upconversion luminescent properties of Lu2O3:2%Yb3+, 0.2%Tm3+ nanocrystals. The as-formed lutetium oxide precursors could transform to cubic Lu2O3 with the same morphology and a slight shrinkage in size after a calcination process. The upconversion emission intensity of Lu2O3:2%Yb3+, 0.2%Tm3+ nanocrystals obtained from the precursor solution with pH = 9 is the strongest. The enhancement of the upconversion luminescence is suggested to be the consequence of reducing the number of OH- groups and the enlarged nanocrystals size. Strong blue and weak red emissions from the prepared nanocrystals were observed under 980 nm laser excitation, which were attributed to the 1G4 --> 3H6 and 1G4 --> 3F4 transitions of Tm3+ ion, respectively.


Asunto(s)
Lutecio/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Óxidos/síntesis química , Tulio/química , Agua/química , Iterbio/química , Cristalización/métodos , Calor , Rayos Infrarrojos , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de Superficie
20.
ACS Appl Mater Interfaces ; 16(36): 48470-48480, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39186605

RESUMEN

Solar-driven interfacial evaporation technology is a novel and efficient desalination process that helps alleviate the global shortage of freshwater resources. We developed a Janus evaporator assembled from cotton hydrogel, hydrophilic polyester fabric (PF), and Hydrophobic Wood (PW). By doping graphene oxide and TiO2 as light-absorbing materials within the hydrogel, we achieved a high absorptivity of over 90% across the entire solar spectrum. The hydrophilically modified PF, combined with the PW substrate, provided robust water transport and reduced thermal losses. Subsequent optical path simulations using TracePro74 software verified that the sawtooth light-trapping design of the wood substrate increased multiple light reflections and absorption (compared to a flat structure), enhancing light absorption capabilities. The sawtooth interface also enlarged the evaporation area, further boosting evaporation performance. The cleverly designed evaporator exhibited an evaporation rate of 1.722 kg m-2 h-1 and an efficiency of 83.1% under 1 sun irradiation. Additionally, after applying polydimethylsiloxane to the single surface of the photothermal hydrogel for low surface energy treatment, the resulting Janus structure demonstrated asymmetric wettability that prevented salt ions from accumulating on the irradiated interface. After 8 h of continuous evaporation in saline water (10 wt %), only slight salt crystallization occurred at the edges. The evaporator maintained long-term stability during a 15 day cyclic test, and the produced freshwater fully met the relevant drinking water standards. The components of the evaporator are characterized by simple fabrication, low cost, and eco-friendliness, offering significant application potential in the global context of energy conservation and emission reduction initiatives.

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