RESUMEN
Ozonation is universally used during water treatment but can form hazardous brominated disinfection byproducts (Br-DBPs). While sunlight exposure is advised to reduce the risk of Br-DBPs, their phototransformation pathways remain insufficiently understood. Here, sunlight irradiation was found to reduce adsorbable organic bromine by 63%. Applying high-resolution mass spectrometry, the study investigated transformations of dissolved organic matter in sunlit-ozonated reclaimed water, revealing the number and abundance of assigned formulas decreased after irradiation. The Br-DBPs with O/C < 0.6 and MW > 400 Da were decreased or removed after irradiation, with the majority being CHOBr compounds. The peak intensity reduction ratio of CHOBr compounds correlated positively with double bound equivalent minus oxygen ratios but negatively with O/C, suggesting that photo-susceptible CHOBr compounds were highly unsaturated. Mass difference analysis revealed that the photodegradation pathways were mainly oxidation aligned with debromination. Three typical CHOBr molecular structures were resolved, and their photoproducts were proposed. Toxicity estimates indicated decreased toxicity in these photoproducts compared to their parent compounds, in line with experimentally determined values. Our proposed phototransformation pathways for Br-DBPs enhance our comprehension of their degradation and irradiation-induced toxicity reduction in reclaimed water, further illuminating their transformation under sunlight in widespread environmental scenarios.
Asunto(s)
Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Desinfección/métodos , Desinfectantes/análisis , Desinfectantes/química , Desinfectantes/toxicidad , Halogenación , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodosRESUMEN
Glucose 6-phosphate isomerase (G6PI) is an indicator to assist in diagnosis of rheumatoid arthritis (RA) and monitor the disease. It also plays a key role in proliferating RA synovial tissues, pannus formation, and invasion and destruction of articular cartilage. In this study, we synthesized nanoparticles targeting G6PI (siG6PI-MSN) using mesoporous silica nanocarriers (MSN) and small interfering RNA (siRNA), followed by identifying the characteristics and functions, and preliminarily exploring their application in the treatment of RA in vivo with a type II collagen-induced arthritis (CIA) rat model. It showed that the synthetic functionalized carrier had a regular pore structure and a specific volume and surface area. No obvious hemolysis or toxicity of the carrier was found when its concentration was below 100 µg/ml. Cytological results in vitro suggested that siG6PI-MSN significantly inhibited G6PI expression and reduced the ability of proliferation, migration, and invasion of FLSs, compared with the siNC-MSN group. In vivo results in the CIA rat model showed that the arthritis index and degree of joint swelling among rats in the siG6PI-MSN-treatment group were significantly lower than those in the control group. Moreover, the number of FLSs in Synovium and the levels of TNF α and IL-1 ß were also significantly decreased in the siG6PI-MSN group. Histopathology of the synovial tissue and cartilage revealed siG6PI-MSN treatment significantly reduced the pathological manifestations of arthritis. In conclusion, siG6PI-MSN effectively suppresses the proliferation and invasive growth of synovial tissue and improve joint swelling and inflammatory infiltration, thereby preventing joint damage in RA. This carrier may be a new therapeutic measure for RA, with potential social and economic benefits.
Asunto(s)
Artritis Experimental , Artritis Reumatoide , Sinoviocitos , Animales , Ratas , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Reumatoide/patología , Movimiento Celular , Glucosa-6-Fosfato Isomerasa/metabolismo , Glucosa-6-Fosfato Isomerasa/farmacología , ARN Interferente Pequeño/metabolismo , Membrana Sinovial/metabolismoRESUMEN
OBJECTIVES: To study the intellectual level and the factors influencing the intelligence in children aged 6-16 years with attention deficit hyperactivity disorder (ADHD). METHODS: A retrospective study was conducted on 2 861 children who were diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition between October 2014 and September 2022 at Henan Children's Hospital. The Wechsler Intelligence Scale for Children-Fourth Edition was used to assess the intellectual levels of the ADHD children. Based on intelligence quotient (IQ) scores, the intellectual levels were classified into five categories: borderline (70-79), low average (80-89), average (90-109), high average (110-119), and superior (≥120). The intellectual levels among the children of different genders, grades, and parental education levels were compared. RESULTS: Among the 2 861 ADHD children, 569 (19.89%) were classified as borderline, 846 (29.57%) as low average, 1 304 (45.58%) as average, 111 (3.88%) as high average, and 31 (1.08%) as superior. The boys had lower scores in working memory, processing speed, and overall IQ than the girls (P<0.05). There were significant differences in perceptual reasoning, working memory, processing speed, and overall IQ scores among different grade groups (P<0.05). The scores in language comprehension, perceptual reasoning, working memory, processing speed, and overall IQ were found to be associated with parental education level in ADHD children (P<0.05). CONCLUSIONS: The proportion of ADHD children with low average and borderline intellectual levels is relatively high. The IQ level of ADHD children is influenced by gender, grade level and parental education level.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Humanos , Masculino , Niño , Femenino , Estudios Retrospectivos , Inteligencia , Pruebas de Inteligencia , CogniciónRESUMEN
Today, a lot of attention is being paid to the pre-miRNAs/miRNAs or activity of Dicer due to their important functions in various physiological processes. Especially, the intrinsic relationship among these associated targets is of significant importance for more in-depth research on the mechanism of disease formation and early diagnosis. Herein, a strategy for simultaneous bioanalysis of miRNAs/pre-miRNAs and Dicer enzyme based on the self-designed multi-path nucleic acid amplification technology was proposed. Typically, in the presence of pre-miRNA-155, it can hybridize with Helper to generate a structure with two new toeholds, one of which could react with H1, H2, and H3, performing a modified CHA reaction with obvious fluorescence responses of FAM, and another of which could hybridize with H4, H5, and H6 to construct the [H4-H5-H6]n DNA nanosphere with obvious fluorescence responses of Cy5. Similarly, miRNA-155 could just hybridize with H1, H2, and H3 to generate the same modified CHA reaction with obvious fluorescence responses of FAM. Due to the successful multi-path nucleic acid amplification, the proposed bioanalysis strategy could be successfully employed for miRNA-155 and pre-miRNA-155 analysis in the range from 500 pM to 100 nM and 1 to 300 nM, respectively. The proposed strategy could be applied to explore another inter-related nucleic acid relationship also, providing great potential in bioanalysis of various nucleic acids.
Asunto(s)
Técnicas Biosensibles , MicroARNs , Ácidos Nucleicos , Límite de Detección , MicroARNs/química , MicroARNs/genética , Técnicas de Amplificación de Ácido Nucleico , Ribonucleasa III/genéticaRESUMEN
INTRODUCTION: As the main source of informal care in China, family members bear a tremendous caregiving burden, particularly in relation to older people with dementia (PwDs). However, the continuous caregiving trajectory of family caregivers was unclear. OBJECTIVES: To investigate the trajectory of PwDs' family caregivers' struggles from home care to institutional care, and identify the common tipping points leading to institutional care from their perspectives. METHODS: An ethnographic study was conducted in a long-term care institution in Chengdu, China, from 2019 to 2020. Face-to-face, semi-structured interviews were carried out with 13 family members (i.e. 5 spouses and 8 adult children) of older PwDs during family caregivers' visits. The interviews were recorded and transcribed, after which the transcripts were analysed using thematic analysis. RESULTS: The family caregivers' experiences before and after the PwDs' institutionalization fell into two distinctive parts, and three subthemes about their caregiving experiences in each period were identified: the mental stress, the physical care burden, and the social and emotional pressure connected to home-based care; the moral pressure and emotional torment, the financial burden, and new worries after institutionalization. The tipping points in between the two stages were major changes or incidents related to the PwDs' status. Variations in the spouse and older children's care experiences also emerged. CONCLUSION: Our study provides a nuanced analysis of the trajectory of family caregiving for PwDs. The plight of family caregivers at all stages should be recognized and supported with adequate medical and social resources, with a further consideration of the caregivers' relationships with the older PwDs.
Asunto(s)
Demencia , Servicios de Atención de Salud a Domicilio , Anciano , Humanos , Cuidadores/psicología , Demencia/diagnóstico , Demencia/terapia , Familia/psicología , Estrés Psicológico/diagnósticoRESUMEN
The erythropoietin-producing human hepatocellular receptor EPH receptor B6 (EPHB6) is a receptor tyrosine kinase that has been shown previously to control catecholamine synthesis in the adrenal gland chromaffin cells (AGCCs) in a testosterone-dependent fashion. EPHB6 also has a role in regulating blood pressure, but several facets of this regulation remain unclear. Using amperometry recordings, we now found that catecholamine secretion by AGCCs is compromised in the absence of EPHB6. AGCCs from male knockout (KO) mice displayed reduced cortical F-actin disassembly, accompanied by decreased catecholamine secretion through exocytosis. This phenotype was not observed in AGCCs from female KO mice, suggesting that testosterone, but not estrogen, contributes to this phenotype. Of note, reverse signaling from EPHB6 to ephrin B1 (EFNB1) and a 7-amino acid-long segment in the EFNB1 intracellular tail were essential for the regulation of catecholamine secretion. Further downstream, the Ras homolog family member A (RHOA) and FYN proto-oncogene Src family tyrosine kinase (FYN)-proto-oncogene c-ABL-microtubule-associated monooxygenase calponin and LIM domain containing 1 (MICAL-1) pathways mediated the signaling from EFNB1 to the defective F-actin disassembly. We discuss the implications of EPHB6's effect on catecholamine exocytosis and secretion for blood pressure regulation.
Asunto(s)
Glándulas Suprarrenales/enzimología , Catecolaminas/metabolismo , Células Cromafines/enzimología , Exocitosis , Receptor EphB6/metabolismo , Transducción de Señal , Glándulas Suprarrenales/citología , Animales , Catecolaminas/genética , Células Cromafines/citología , Efrina-B1/genética , Efrina-B1/metabolismo , Femenino , Masculino , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-fyn/genética , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Receptor EphB6/genética , Caracteres Sexuales , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
OBJECTIVES: Epigallocatechin gallate (EGCG) is the main bioactive component of polyphenols in tea, which has a variety of biological effects. The neurologic injury caused by cerebral ischemia/reperfusion (I/R) is closely related to the inflammatory reaction. The pro-inflammatory factor interleukin-1ß (IL-1ß) and the anti-inflammatory factor interleukin-10 (IL-10) play important roles in the regulation of inflammatory reaction. This study aims to explore the effect of EGCG on water content, myeloperoxidase (MPO) activity, IL-1ß and IL-10 in brain tissues of rats suffered cerebral I/R injury. METHODS: Middle cerebral artery occlusion model of SD rats was established by suture embolic method. After ischemia for 1.5 h, the nylon thread was pulled out and reperfusion was performed for 24.0 h. SD rats were randomly divided into 5 groups: a sham group, an I/R group, a EGCG1 group (I/R+12.5 mg/kg EGCG), a EGCG2 (I/R+25.0 mg/kg EGCG), and a EGCG3 group (I/R+50.0 mg/kg EGCG). The sham group was the same as the I/R group except that the middle cerebral artery was not blocked. The water content in brain tissues of rats was measured by dry and wet weight method, and MPO activity was detected by colorimetry. The levels of IL-1ß and IL-10 mRNA were determined by RT-PCR, and the contents of IL-1ß and IL-10 were determined by ELISA. In addition, primary cultured cortical neurons of SD rats were randomly divided into 3 groups: a control group, an oxygen-glucose deprivation/reperfusion (OGD/R) group, and an OGD/R+EGCG group (OGD/R+50.0 µmol/L EGCG). The effects of EGCG on the levels of IL-1ß and IL-10 protein in neurons were assessed by Western blotting. RESULTS: Compared with the sham group, water content, MPO activity, the contents of IL-1ß and IL-10 were significantly increased (P<0.05 or P<0.01), the mRNA expression of IL-1ß and IL-10 were obviously up-regulated (both P<0.01) in cerebral tissues of rats in the I/R group. Compared with the I/R group, water content and MPO activity in cerebral tissues of rats were significantly decreased (both P<0.01), the content of IL-1ß (P<0.01) were significantly decreased and IL-10 (P<0.01) were significantly increased in the EGCG3 group. Compared with the I/R group, the mRNA expression of IL-1ß was obviously down-regulated and the mRNA expression of IL-10 was obviously up-regulated in the EGCG2 and the EGCG3 group (P<0.05 or P<0.01). Compared with the control group, the protein levels of IL-1ß and IL-10 in neurons were significantly increased in the OGD/R group (both P<0.01). Compared with the OGD/R group, the protein expression of IL-1ß was obviously down-regulated and the protein expression of IL-10 was obviously up-regulated in neurons in the OGD/R+EGCG group (both P<0.01). CONCLUSIONS: EGCG can inhibit the inflammatory reaction induced by cerebral I/R, which may be related to down-regulating the expression of pro-inflammatory factor IL-1ß and up-regulating anti-inflammatory factor IL-10.
Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Animales , Isquemia Encefálica/tratamiento farmacológico , Catequina/análogos & derivados , Infarto de la Arteria Cerebral Media , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoRESUMEN
Inflammatory cytokine-induced cell apoptosis is important for initiation and progression of chronic heart failure (CHF). Non-coding RNAs, including long non-coding RNAs and microRNAs, have emerged as critical regulators of this pathological process. The role in regulating inflammation and induction to cell apoptosis in CHF is not well understood. This study found CHF patients had elevated serum miR-939-5p, with greater increase in New York Heart Association (NYHA) I-II patients than in NYHA III-IV. Moreover, miR-939-5p was positively correlated with B-type natriuretic peptide (BNP) in NYHA III-IV patients, while not in NYHA I-II. Further study showed miR-939-5p mimics promoted cell proliferation and inhibited inflammatory cytokine-induced apoptosis of HUVECs and H9C2, while inhibition of endogenous miR-939-5p produced the opposite effects. Induced nitric oxide synthase (iNOS) and tumour necrosis factor α (TNFα) were identified as target genes of miR-939-5p. Additionally, lncRNA-NOS2P3 acted as an endogenous sponge RNA to inhibit miR-939-5p expression, regulate the expression of iNOS/TNFα and control inflammation-induced cells apoptosis. These suggest that CHF patients exhibited elevated serum miR-939-5p level especially in NYHA I-II grades. And lnc-NOS2P3-miR-939-5p-iNOS/TNFα pathway regulated inflammatory cytokine-induced endothelial and myocardial cells apoptosis and provided a promising strategy for diagnosis and treatment of CHF.
Asunto(s)
Apoptosis , Regulación de la Expresión Génica , Insuficiencia Cardíaca/genética , Células Endoteliales de la Vena Umbilical Humana/patología , MicroARNs/genética , Miocardio/patología , ARN Largo no Codificante/genética , Transducción de Señal , Apoptosis/genética , Secuencia de Bases , Enfermedad Crónica , Citocinas/metabolismo , Insuficiencia Cardíaca/sangre , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/genética , Inflamación/patología , MicroARNs/sangre , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Largo no Codificante/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The aim of this study was to evaluate the use of a novel porous silica carrier, AEROPERL® 300 Pharma (AP), to improve the in vitro release and oral bioavailability of puerarin (PUE) in solid dispersions (SDs). PUE-AP SD formulations with different ratios of drug to silica (RDS) were prepared by the solvent method. The scanning electron microscopy (SEM) results indicated that the dispersion of PUE improved as the concentration of AP was increased. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed that PUE mostly existed in an amorphous state in the SDs. The rate of drug dissolution from the SDs was significantly higher than that from the PUE powder (p < 0.05). The in vitro drug release percentage from the PUE-AP SDs increased as the RDS was reduced. The oral bioavailability of PUE from the SDs improved when using AP, as indicated by AUC(0-∞), which was 2.05 and 2.01 times greater than that of the PUE (API) and PVP K30 SDs, respectively (p < 0.05). The drug content, in vitro release profiles, and the amorphous state of PUE in the PUE-AP SDs showed no significant changes after being stored at room temperature for 6 months or under accelerated conditions (40 ± 2°C, 75 ± 5% relative humidity) for 3 months. AP has a high pore volume, large specific surface area, excellent flowability, and hydrophilic properties, making it capable of improving the dissolution and bioavailability of poorly water-soluble drugs.
Asunto(s)
Portadores de Fármacos , Isoflavonas/administración & dosificación , Dióxido de Silicio/química , Animales , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Composición de Medicamentos/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Isoflavonas/farmacocinética , Masculino , Microscopía Electrónica de Rastreo , Porosidad , Povidona/química , Difracción de Polvo , Ratas , Ratas Sprague-Dawley , SolubilidadRESUMEN
OBJECTIVE: To explore the effect of epigallocatechin gallate (EGCG) on oxidative stress and Nrf2/HO-1 pathway in neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R).â© Methods: Primary cultured cerebral cortical neurons were prepared from Sprague-Dawley rats, and the OGD/R cell model was established. After pretreatment with EGCG at different concentrations (12.5, 25.0, 50.0 or 100.0 µmol/L), the neurons were subjected to OGD/R. The cell viability, reactive oxygen species (ROS) level and malondialdehyde (MDA) content were assessed after reperfusion. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. The expression of Nrf2 protein in nucleus, HO-1 mRNA and protein were detected.â© Results: OGD/R treatment reduced the cell viability, elevated ROS level and MDA content, decreased SOD and GSH-Px activities. The expression of Nrf2 protein in nucleus, HO-1 mRNA and protein were increased (P<0.01). Pretreatment with EGCG promoted the survival of neurons exposed to OGD/R, decreased ROS level and MDA content while increased SOD and GSH-Px activities. The levels of Nrf2 protein in nucleus, HO-1 mRNA and protein were upregulated (P<0.01).â© Conclusion: EGCG can reduce the oxidative stress of neurons subjected to OGD/R, which may be related to activation of Nrf2/HO-1 signal pathway and enhancement of the antioxidant ability of neurons.
Asunto(s)
Catequina/análogos & derivados , Glucosa , Factor 2 Relacionado con NF-E2 , Neuronas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxígeno , Animales , Catequina/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/prevención & controlRESUMEN
To evaluate the effectiveness of epigallocatechin gallate (EGCG) in inhibiting corneal neovascularization in rat alkaline burn model. Corneal neovascularization model was induced by sodium hydroxide alkaline burn injury in SD rats. Rats were randomly divided into two groups and were given intraperitoneal injection with EGCG or PBS per day for up to 14 days respectively. Corneal inflammation and neovascularization area were assessed on days 3, 7, and 14 after cauterization with digital photographs. Vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) mRNA levels were measured by reverse transcription-polymerase chain reaction (qRT-PCR). The nuclear transfactor-Κb (NF-κB) subunit P65 protein was assayed by immunohistochemistry. The differences of corneal inflammation scores between two groups were significant. The area of CNV between two groups had no significant difference on day 3 but have significant difference on days 7 and 14.The PDEF mRNA expression in EGCG group was significantly higher and the expression of VEGF mRNA was lower than those in PBS group. The results of immunohistochemistry showed from day 7, expression of NF-κB P65protein was suppressed considerably in EGCG group. This study demonstrates that EGCG inhibits corneal neovascularization in a rat model induced by alkali burn.
Asunto(s)
Catequina/análogos & derivados , Neovascularización de la Córnea/prevención & control , Animales , Quemaduras Químicas/fisiopatología , Catequina/farmacología , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , Neovascularización de la Córnea/fisiopatología , Proteínas del Ojo/biosíntesis , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/prevención & control , Masculino , Proteínas de Neoplasias/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ratas , Serpinas/biosíntesis , Hidróxido de Sodio , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
A proton (perfluorosulfonic acid, PFSA) and electron (polyaniline, PANI) conductor polymer costabilized Pt catalyst (Pt-PFSA/C@PANI) is synthesized to improve the long-term stability of polymer electrolyte membrane fuel cells (PEMFCs). The prepared catalyst not only displays comparable oxygen reduction reaction (ORR) activity, but significantly higher electrochemical stability than commercial porous carbon nanosphere supported Pt catalysts (Pt/C). This robust electrochemical property can be due to the result of PFSA and PANI. PANI as protector inhibits carbon nanospheres from corrosion of carbon supports in harsh chemical and electrochemical conditions. Meanwhile, PFSA wrapped Pt NPs (Pt@PFSA) can also anchor Pt NPs on C@PANI to avoid aggregation and detachment of Pt NPs, due to the increased metal-support interaction caused by the strong electrostatic attraction between PANI and PFSA with corresponding positive and negative charges. Significantly, after coating PANI on carbon supports (C@PANI), almost all micropores in the surface of carbon disappear, effectively avoiding the embedding of Pt nanopaticles into micropores. Furthermore, the triple-phase boundary toward ORR catalysis can be facilitated by PFSA as proton conductor (solid electrolyte). These are of benefit to increase utilization of Pt noble metals and ORR activity of our new catalysts.
RESUMEN
Improving the long-term stability of metal catalysts is crucial to developing polymer electrolyte fuel cells (PEFCs). In this work, we first report an inorganic (TiO2)-organic (perfluorosulfonic acid, PFSA) costabilized Pt catalyst supported on graphene nanosheets (GNS) (Pt-PFSA-TiO2/GNS). Herein, TiO2, as a robust wall, impedes the collision between the metal nanoparticles (NPs) in plane along the horizontal x and y axes, while PFSA mainly anchors the metal NPs to constrain detachment along the vertical z axis. The resulting catalyst displays higher oxygen reduction reaction (ORR) activity in comparison to that of commercial Pt/C. Significantly, the stability is particularly better than that of only PFSA- or TiO2-decorated catalysts (Pt-PFSA/GNS or Pt-TiO2/GNS) and far better than that of Pt/C. After 6000 potential cycles, the half-wave potential (E1/2) of Pt-PFSA-TiO2/GNS decreases by only 16 mV, far less than that of Pt/C (56 mV). The excellent electrochemical property of Pt-PFSA-TiO2/GNS is predominantly attributed to the synergistic effect of PFSA and TiO2 in costabilizing the Pt NP by anchoring and blocking Pt NPs in all three spatial directions. The structural dynamics and mechanism of enhanced properties are also discussed.
RESUMEN
An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.
Asunto(s)
Elastasa de Leucocito/sangre , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/sangre , alfa 1-Antitripsina/sangre , Adulto , Glucemia/metabolismo , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Fibrosis , Humanos , Inflamación/sangre , Resistencia a la Insulina , Hígado/enzimología , Masculino , Neutrófilos/citología , Enfermedad del Hígado Graso no Alcohólico/enzimología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
Gastric cancer (GC) is one of the most common cancers and lethal malignancies in the world. Discovering novel biomarkers that correlate with GC may provide opportunities to reduce the severity of GC. As one of Notch receptor family members in mammals, Notch4 plays an important role in carcinogenesis of several tumors. However, the precise function and mechanism of Notch4 in GC remain undefined. To address this question, we investigated whether Notch4 could be involved in GC progression. We found that Notch4 was activated by overexpressing exogenous intracellular domain of Notch4 (ICN4), and Notch4 activation promoted GC growth in vitro and in vivo, while Notch4 inhibition using ICN4 siRNA had opposite effects. In addition, Notch4 activation induced expression and activation of Wnt1, ß-catenin and downstream target genes, c-Myc and cyclin D1, in GC cells, while Notch4 inhibition had opposite effects. Moreover, ß-catenin depletion by siRNA attenuated cell proliferation induced by Notch4 activation. Therefore, our results revealed that Notch4 activates Wnt1/ß-catenin signaling to regulate GC growth.
Asunto(s)
Adenocarcinoma/patología , Proteínas Proto-Oncogénicas/metabolismo , Receptores Notch/metabolismo , Neoplasias Gástricas/patología , Vía de Señalización Wnt , Adenocarcinoma/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Trasplante de Neoplasias , Receptor Notch4 , Neoplasias Gástricas/metabolismo , Análisis de Matrices Tisulares , Regulación hacia Arriba , beta Catenina/metabolismoRESUMEN
OBJECTIVE: To explore the effect of hepatocyte growth factor (HGF) on inducible nitric oxide synthase (iNOS), NO and interleukin-1ß (IL-1ß) in the cerebrum of rats subjected to cerebral ischemia/reperfusion (I/R). METHODS: Sprague-Dawley rats were randomly divided into 5 groups: a sham group, an I/R group,an HGF1 group, an HGF2 group, and an HGF3 group. The latter 3 groups were respectively injected 15, 30 and 60 µg/kg HGF. The focal cerebral I/R model was established by sutureoccluded method. After 1.5 h ischemia followed by 24 h reperfusion, the iNOS activity and NO content in the ischemic cerebral tissue were assessed. The expression of iNOS mRNA and IL-1ß mRNA was detected. The level of iNOS protein and IL-1ß content were determined. In addition, cultured cerebral cortical neurons in vitro were exposed to I/R. Then the expression of iNOS and IL-1ß protein in the neurons was detected, and NO content was assessed. RESULTS: The iNOS activity and NO content in the ischemic cerebral tissue were increased. The expression of iNOS mRNA and IL-1ß mRNA was upregulated. The level of iNOS protein and IL- 1ß content were increased. Administration of HGF decreased the iNOS activity and NO content, and downregulated the expression of iNOS mRNA, IL-1ß mRNA, iNOS protein and IL-1ß content in the ischemic cerebral tissue. HGF decreased the expression of IL-1ß, iNOS protein and NO content in the cortical neurons exposed to I/R in vitro. CONCLUSION: HGF can inhibit the expression of IL-1ß and decrease the expression of iNOS and content of NO, which is probably one of the mechanisms mediating the protection of HGF against cerebral ischemia injury.
Asunto(s)
Cerebro/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Interleucina-1beta/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Daño por Reperfusión/metabolismo , Animales , Isquemia Encefálica/metabolismo , Cerebro/patología , Regulación hacia Abajo , Ratas , Ratas Sprague-Dawley , Regulación hacia ArribaRESUMEN
This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.
Asunto(s)
Trastorno de Personalidad Antisocial , Personalidad , Humanos , Maquiavelismo , Trastornos de la Personalidad , Narcisismo , AnsiedadRESUMEN
Permanganate is a common preoxidant applied in water treatment to remove organic pollutants and to reduce the formation of disinfection by-products. However, the effect of permanganate preoxidation on the transformation of dissolved effluent organic matter (dEfOM) and on the formation of unknown chlorinated disinfection by-products (Cl-DBPs) during chlorination remains unknown at molecular level. In this work, the molecular changes of dEfOM during permanganate preoxidation and subsequent chlorination were characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Permanganate preoxidation was found to decrease the DBE (double bond equivalent) and AImod (modified aromaticity index) of the dEfOM. The identity and fate of over 400 unknown Cl-DBPs during KMnO4-chlorine treatment were investigated. Most Cl-DBPs and the precursors were found to be highly unsaturated aliphatic and phenolic compounds. The Cl-DBPs precursors with lower H/C and lower O/C were preferentially removed by permanganate preoxidation. Additionally, permanganate preoxidation decreased the number of unknown Cl-DBPs by 30% and intensity of unknown Cl-DBPs by 25%. One-chlorine-containing DBPs were the major Cl-DBPs and had more CH2 groups and higher DBEw than Cl-DBPs containing two and three chlorine atoms. 60% of the Cl-DBPs formation was attributed to substitution reactions (i.e., +Cl-H, +2Cl-2H, +3Cl-3H, +ClO-H, +Cl2O3-2H). This work provides detailed molecular level information on the efficacy of permanganate preoxidation on the control of overall Cl-DBPs formation during chlorination.
Asunto(s)
Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Desinfección/métodos , Materia Orgánica Disuelta , Halogenación , Cloro/análisis , Purificación del Agua/métodos , Contaminantes Químicos del Agua/análisis , Desinfectantes/químicaRESUMEN
Low-pressure mercury lamps emitting at 254 nm (UV254) are used widely for disinfection. However, subsequent exposure to visible light results in photoreactivation of treated bacteria. This study employed a krypton chloride excimer lamp emitting at 222 nm (UV222) to inactivate E. coli. UV222 and UV254 treatment had similar E. coli-inactivation kinetics. Upon subsequent irradiation with visible light, E. coli inactivated by UV254 was reactivated from 2.71-log to 4.75-log, whereas E. coli inactivated by UV222 showed negligible photoreactivation. UV222 treatment irreversibly broke DNA strands in the bacterium, whereas UV254 treatment primarily formed nucleobase dimers. Additionally, UV222 treatment caused cell membrane damage, resulting in wizened, pitted cells and permeability changes. The damage to the cell membrane was mainly due to the photolysis of proteins and lipids by UV222. Furthermore, the photolysis of proteins by UV222 destroyed enzymes, which blocked photoreactivation and dark repair. The multiple damages can be further evidenced by 4.0-61.1 times higher quantum yield in the photolysis of nucleobases and amino acids for UV222 than UV254. This study demonstrates that UV222 treatment damages multiple sites in bacteria, leading to their inactivation. Employing UV222 treatment as an alternative to UV254 could be viable for inhibiting microorganism photoreactivation in water and wastewater.
RESUMEN
OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: Forty-six TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, colour Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesions were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analyses identified that extra-thyroidal extension (odds ratio [OR], 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: P = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm) + 2.957 × (if aspect ratio ≥ 0.91) + 2.819 × (if extra-thyroidal extension). The prediction model had a good discrimination performance for TCPTC: the area under the receiver-operator-characteristic curve, sensitivity, and specificity were 0.928, 0.848, and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923, and 0.926, respectively. CONCLUSION: Ultrasound has the potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extra-thyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful in predicting TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC was a supplement to preoperative cytological diagnosis and molecular diagnosis of PTC subtypes.