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Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0-12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks.
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Contaminantes Ambientales , Bifenilos Policlorados , Lactante , Femenino , Humanos , Leche Humana/química , Contaminantes Ambientales/análisis , Bifenilos Policlorados/análisis , Espectrometría de Masas , LípidosRESUMEN
By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7' and C-10'; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 µM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.
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Antineoplásicos , Chaetomium , Cromonas , Ensayos de Selección de Medicamentos Antitumorales , Policétidos , Xylariales , Cromonas/química , Cromonas/farmacología , Cromonas/aislamiento & purificación , Policétidos/química , Policétidos/farmacología , Policétidos/aislamiento & purificación , Estructura Molecular , Xylariales/química , Chaetomium/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Técnicas de Cocultivo , Proliferación Celular/efectos de los fármacosRESUMEN
(-)-Guaiol is a sesquiterpenoid found in many traditional Chinese medicines with potent antitumor activity. However, its therapeutic effect and mechanism in non-small cell lung cancer (NSCLC) have not been fully elucidated. In this study, (-)-Guaiol was found to induce immunogenic cell death (ICD) in NSCLC in vitro. Using (-)-Guaiol in vivo, we found that (-)-Guaiol could suppress tumor growth, increase dendritic cell activation, and enhance T-cell infiltration. Vaccination experiments suggest that cellular immunoprophylaxis after (-)-Guaiol intervention can suppress tumor growth. Previous studies have found that (-)-Guaiol induces apoptosis and autophagy in NSCLC. Apoptosis and autophagy are closely related to ICD. To explore whether autophagy and apoptosis are involved in (-)-Guaiol-induced ICD, we used inhibitors of apoptosis and autophagy. The results showed that the release of damage-associated molecular patterns (DAMPs) was partly reversed after inhibition of apoptosis and autophagy. In conclusion, these results suggested that the (-)-Guaiol triggers immunogenic cell death and inhibits tumor growth in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Muerte Celular Inmunogénica , Línea Celular Tumoral , Apoptosis , AutofagiaRESUMEN
BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.
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Propofol , Humanos , Ratones , Animales , Propofol/farmacología , Hipoxia , Células Endoteliales de la Vena Umbilical Humana , Miocitos Cardíacos , Estrés Oxidativo , Apoptosis/fisiología , Chaperonina con TCP-1RESUMEN
In view of the practical application, it is imperative to develop efficient, exercisable, and visible light driven water pollution treatment materials. Herein, a high-efficiency green photocatalytic membrane for water pollution treatment is proposed and fabricated conveniently. Firstly, silver phosphate (Ag3PO4) nanoparticles with controlled morphology were prepared by simple liquid-phase precipitation method, and then a hierarchical structured Ag3PO4@polylactic acid (PLA) composite nanofiber membrane was prepared by electrospinning. Using electrospun PLA nanofiber membrane as a carrier of photocatalysts can significantly improve the dispersion of Ag3PO4nanoparticles, and increase the contact probability with pollutants and photocatalytic activity. The prepared PLA@Ag3PO4composite membrane was used to degrade methylene blue (MB) and tetracycline hydrochloride (TC) under visible light irradiation. The results showed that the removal ratio of pollutants on Ag3PO4@PLA composite nanofiber membrane was 94.0% for MB and 82.0% for TC, demonstrating an outstanding photocatalytic activity of composite membrane. Moreover, the PLA nanofiber membrane is a self-supported and biodegradable matrix. After five cycles, it can still achieve 88.0% of the initial photocatalytic degradation rate towards MB, showing excellent recyclability. Thus, this composite nanofiber membrane is a high-efficiency and environmental-friendly visible light driven water pollution treatment material that could be used in real applications.
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BACKGROUND: To investigate the effect of intravenous injection of dexmedetomidine combined with parecoxib sodium on sedation and anxiety and stress response of tracheal intubation in patients undergoing functional endoscopic sinus surgery. METHODS: One hundred twenty patients undergoing endoscopic sinus surgery were randomly divided into four groups: group DP, group D, group P and group N. The blood pressure (BP), heart rate (HR), blood oxygen saturation (SPO2), EEG, bispectral index (BIS), Ramsay sedation score and state anxiety questionnaire (SAI) were recorded before administration (T0), 10 min (T1), 20 min (T2) and 30 min (T3) after administration. After 30 min, endotracheal intubation was performed after anesthesia induction. The BP, HR, SPO2 were recorded 1 min before intubation (T4), intubation (T5), 3 min (T6) after intubation, 5 min (T7) after intubation, and blood samples were collected from patients before administration and after intubation 2 min to detect serum cortisol (Cor), adrenalin (E) norepinephrine (NE) and blood glucose (BS). RESULTS: There was no significant difference in Ramsay sedation score before anesthesia, but the Ramsay sedation score in group DãDP was significantly higher than that in group P and group N, the BIS, BP, HR and anxiety scores were significantly lower than those in the group P and group N (p < 0.05). There was no significant difference in Ramsay sedation score, BIS value, anxiety score and BP, HR between group D and group DP (p > 0.05). Compared with T4, there was no significant difference in BIS and BP, HR in group D, group DP and group P (p > 0.05), but the BIS, BP and HR in group N were significantly higher than T4, (p < 0.05). Three minutes after intubation there was no statistical difference in the changes of Cor, E, NE and BS values compared with before intubation in group P and group DP (p > 0.05), but the changes of Cor, E, NE and BS values were significantly lower than that in group N (p < 0.05). Compared with T0, the values of NE, E, Cor, BS decreased in group D, DP and P at T4, group DP decreased more significantly than group D (p < 0.05). while the NE, E, Cor, BS of T6 are at the same level as the base value. In group N, the NE, E, Cor, BS of T4 were at the same level of T0, but significantly higher at T6.And at T6, NE and E in group D, P and N were significantly different from those in group DP (p < 0.05). CONCLUSION: Preoperative intravenous infusion of dexmedetomidine combined with parecoxib sodium by functional nasal endoscopy can not only calm and resist anxiety, but also better prevent stress response of endotracheal intubation, which is a safe and effective way of preoperative medication. TRIAL REGISTRATION: ChiCTR-OPN-17010444 . Prospectively registered on 16 January 2017.
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Ansiedad/tratamiento farmacológico , Sedación Consciente , Dexmedetomidina/administración & dosificación , Intubación Intratraqueal , Isoxazoles/administración & dosificación , Senos Paranasales/cirugía , Estrés Psicológico/prevención & control , Adulto , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Serine plays critically important roles in tumorigenesis. Homo sapiens 3-phosphoglycerate dehydrogenase (PHGDH) catalyzes the first committed step for the synthesis of glucose-derived serine via the phosphoserine pathway and has been associated with a wide variety of cancers, including breast cancer, melanoma, colon cancer, glioma, nasopharyngeal carcinoma, cervical adenocarcinoma, etc. Azacoccone E, an aza-epicoccone derivative from the culture of Aspergillus flavipes, exhibited effective inhibitory activity against PHGDH in vitro. The microscale thermophoresis (MST) method and the cellular thermal shift assay (CETSA) confirmed that azacoccone E directly bound to PHGDH. And the cell-based experiments showed that this compound was selectively toxic to PHGDH-dependent cancer cells and could cause apoptosis. Further biochemical assays revealed that it was a noncompetitive inhibitor with respect to the substrate of 3-PG and exhibited a time-dependent inhibition. Furthermore, molecular docking demonstrated that azacoccone E coordinated in an allosteric site of PHGDH with low binding energy. Therefore, azacoccone E can be considered as a possible drug candidate targeting at PHGDH for treatment of cancers.
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Antineoplásicos/farmacología , Compuestos Aza/farmacología , Inhibidores Enzimáticos/farmacología , Fosfoglicerato-Deshidrogenasa/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Compuestos Aza/síntesis química , Compuestos Aza/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Células HeLa , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Fosfoglicerato-Deshidrogenasa/metabolismo , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
An efficient, environmentally friendly and high-yielding route from inexpensive starting materials to 1,2-dihydroquinolines has been developed. This procedure proceeded via a cascade Friedel-Crafts-type reaction and 6-endo-trig hydroamination under the catalysis of FeCl3·6H2O, involving the formation of two new σ (C-C and C-N) bonds in a single operation for the construction of a 1,2-dihydroquinoline skeleton in good to excellent yields.
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Alquinos/química , Aminas/química , Cloruros/química , Compuestos Férricos/química , Propanoles/química , Quinolinas/síntesis química , Catálisis , Modelos Moleculares , Estructura Molecular , Quinolinas/químicaRESUMEN
AIM: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into control group, model group and G-Rg1 treatment group. G-Rg1 was administered to rats by intraperitoneal injection. Renal interstitial fibrosis in the model group was developed by UUO in rats. Renal function was estimated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. The ER stress was assessed with glucose-regulated protein (GRP) 78 expression, and the proapoptotic response was detected with CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 expressions by Western Blot. The number of apoptotic cells was determined by Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) analysis. RESULTS: UUO for 14 days aggravated renal function, renal damage and renal interstitial fibrosis, activated ER stress response (induction of GRP78 protein), enhanced the proapoptotic response (increase in CHOP and caspase-12 proteins) and increased the number of apoptotic cells (shown by the TUNEL assay). Treatment with G-Rg1 significantly ameliorates the renal pathological lesions and decreases expressions of ER stress-associated proteins and the level of apoptotic cells in kidneys. CONCLUSION: G-Rg1 suppresses renal cell apoptotic and fibrotic process partly through inhibition of ERS- and UPR-related apoptotic pathway in the kidneys after UUO.
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Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Ginsenósidos/administración & dosificación , Riñón/patología , Obstrucción Ureteral/patología , Animales , Nitrógeno de la Urea Sanguínea , Caspasa 12/genética , Creatinina/sangre , Proteínas de Choque Térmico/genética , Etiquetado Corte-Fin in Situ/métodos , Masculino , Ratas , Ratas Sprague-Dawley , Factor de Transcripción CHOP/genéticaRESUMEN
This study aims to understand how socioeconomic status and the family environment impact students' academic achievement through the mediation of parental involvement in rural China. To achieve this, a cross-sectional design was adopted, and a total of 525 parents of rural junior high school students from S province in southwest China were surveyed. The proposed conceptual framework was tested by structural equation modeling. The results claimed that both socioeconomic status and the family environment are important factors affecting the academic achievement of rural students, and the role of the family environment is more pronounced. Furthermore, parental involvement has a significant mediating effect between socioeconomic status and academic achievement, especially between the family environment and academic achievement. The findings highlighted the importance of the family environment and parental involvement to compensate for the negative impact of disadvantaged family socioeconomic status on academic achievement.
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The development of environmentally friendly, degradable piezoelectric materials is of great significance for the environment. Poly(L-lactic acid) (PLLA) is a promising piezoelectric material as a degradable material. Here, we have introduced a series of ionic liquids (ILs) into PLLA spinning solution, and the PLLA/IL composite nanofiber membranes are prepared by electrospinning method. When the conductivity of the spinning solution is below 400 µS·cm-1, the addition of ILs, especially [EMIm][PF6], can significantly improve the morphology and piezoelectric properties of the PLLA/IL composite nanofiber membrane with the output voltage of 2.3 V under the pressure of 5 N, which is 4 times that of the PLLA nanofiber membrane. The improvement of the piezoelectric properties of PLLA/IL nanofiber membrane may be due to the high dipole moment generated by the C=O dipole after the interaction between the O atom in C=O on the PLLA molecular chain and the [EMIm]+ cation in the IL. This work has elucidated the effects of ILs on the properties of spinning solution and the piezoelectric properties of PLLA, which can provide a theoretical basis for the selection of the preparation system of piezoelectric polymer and inspire the development of environmentally friendly flexible piezoelectric materials.
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Estrogen-induced intrahepatic cholestasis (IHC) is a mild but potentially serious risk and urges for new therapeutic targets and effective treatment. Our previous study demonstrated that RORγt and CXCR3 signaling pathway of invariant natural killer T (iNKT) 17 cells play pathogenic roles in 17α-ethinylestradiol (EE)-induced IHC. Ursodeoxycholic acid (UDCA) and 18ß-glycyrrhetinic acid (GA) present a protective effect on IHC partially due to their immunomodulatory properties. Hence in present study, we aim to investigate the effectiveness of UDCA and 18ß-GA in vitro and verify the accessibility of the above targets. Biochemical index measurement indicated that UDCA and 18ß-GA presented efficacy to alleviate EE-induced cholestatic cytotoxicity. Both UDCA and 18ß-GA exhibited suppression on the CXCL9/10-CXCR3 axis, and significantly restrained the expression of RORγt in vitro. In conclusion, our observations provide new therapeutic targets of UDCA and 18ß-GA, and 18ß-GA as an alternative treatment for EE-induced cholestasis.
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Colestasis , Ácido Glicirretínico , Células T Asesinas Naturales , Receptores CXCR3 , Ácido Ursodesoxicólico , Colestasis/inducido químicamente , Colestasis/tratamiento farmacológico , Etinilestradiol/toxicidad , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/uso terapéutico , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Transducción de Señal , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/uso terapéutico , Animales , RatonesRESUMEN
The higher viscosity and lower pH in lysosomes of cancer cells highlight their potential as biomarkers for cancer. Therefore, the development of acid-activated viscosity fluorescent probes is significant for the early diagnosis and treatment of cancer. Based on this, we have designed and synthesized a near-infrared fluorescent probe based on the 2-(2-hydroxyphenyl)benzothiazole (HBT) group, namely HBTH, to monitor the viscosity changes within lysosomes. It has been demonstrated that HBTH was extremely sensitive to viscosity, with a strong linear relationship between fluorescence intensity and log(viscosity) within the range of (logη) = 0-3.06 (a correlation coefficient of 0.98), proving its capability for quantitative viscosity measurement. In particular, the most obvious fluorescence enhancement of HBTH was only efficiently triggered by the combined effect of low pH and high viscosity. Furthermore, HBTH can rapidly localize to lysosomes by wash-free procedure at a low concentration (100 nM) and achieve high-fidelity imaging within 20 s. It can also monitor the dynamic processes of lysosomes in cells, viscosity changes under drug stimuli, and lysosomal behavior during mitophagy. Importantly, HBTH is capable of identifying tumors in tumor-bearing nude mice through in vivo imaging. These features make HBTH a powerful tool for the early diagnosis and treatment of cancer.
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BACKGROUND: Lipid droplets (LDs) polarity is intricately linked to diverse biological processes and diseases. The visualization of LDs-polarity is of vital importance but challenging due to the lack of high-specificity, high-sensitivity and large-Stokes shift probes for real-time tracking LDs-polarity in biological systems. RESULTS: Four D-π-A based fluorescent probes (TPA-TCF1-TPA-TCF4) have been developed by combining tricyanofuran (an electron acceptor, A) and triphenylamine (an electron donor, D) derivatives with different terminal groups. Among them, TPA-TCF1 and TPA-TCF4 exhibit excellent polar sensitivity, large Stokes shift (≥182 nm in H2O), and efficient LDs targeting ability. In particular, TPA-TCF4 is capable of monitoring the change of LDs-polarity during ferroptosis, inflammation, apoptosis of cancer cell, and fatty liver. SIGNIFICANCE: All these features render TPA-TCF4 a versatile tool for pharmacodynamic evaluation of anti-cancer drugs, in-depth understanding of the biological effect of LDs on ferroptosis, and medical diagnosis of LDs-polarity related diseases.
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Hígado Graso , Ferroptosis , Colorantes Fluorescentes , Inflamación , Gotas Lipídicas , Gotas Lipídicas/química , Gotas Lipídicas/metabolismo , Humanos , Ferroptosis/efectos de los fármacos , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Colorantes Fluorescentes/química , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Estructura MolecularRESUMEN
BACKGROUND: The early growth response-1 (Egr-1) gene is upregulated after an ischemia-reperfusion (IR) challenge and upregulates target genes, such as proinflammatory cytokines. Ischemic postconditioning (IPostC) attenuates lung IR injury and reduces the systemic inflammatory response by activating heme oxygenase-1 (HO-1). However, the role of Egr-1 in IPostC protection against lung IR injury and inflammation and its interplay with HO-1 in IPostC protection is unknown. MATERIALS AND METHODS: Sprague-Dawley rats or cultured A549 cells were subjected to IR or hypoxia/reoxygenation with or without IPostC or hypoxic postconditioning in the presence or absence of Egr-1 inhibition using Egr-1 antisense oligodeoxyrinonucleotide or Egr-1 small interfering RNA transfection. Lung injury was assessed by measuring the lung wet/dry weight ratio, histologic change, and malondialdehyde content. The amount of lactate dehydrogenase release in culture medium was detected to evaluate cell injury. The protein expression of Egr-1, interleukin (IL)-1ß, and HO-1 was assessed by Western blot. RESULTS: Inhibition of Egr-1 significantly attenuated lung IR injury and the inflammation response caused by IR or hypoxia/reoxygenation, as shown by the alleviated lung pathologic changes, decreased pulmonary malondialdehyde content, wet/dry ratio, reduced release of the cytokines tumor necrosis factor-α, IL-6, and IL-8 in the bronchoalveolar lavage, and reduced Egr-1, IL-1ß, and HO-1 protein expression and HO-1 activity. IPostC or hypoxic postconditioning reduced the postischemic Egr-1 expression and conferred similar protection against lung IR injury as Egr-1 inhibition. CONCLUSIONS: Egr-1 plays an important role in regulating the HO-1 production induced by IR or hypoxia/reoxygenation. Thus, downregulation of Egr-1 expression might represent one of the major mechanisms whereby IPostC confers protection against pulmonary IR insult.
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Citocinas/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Poscondicionamiento Isquémico , Pulmón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Biomarcadores/metabolismo , Western Blotting , Línea Celular Tumoral , Regulación hacia Abajo , Proteína 1 de la Respuesta de Crecimiento Precoz/antagonistas & inhibidores , Hemo Oxigenasa (Desciclizante)/metabolismo , Humanos , Pulmón/metabolismo , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
Objective:The purpose of this study was to investigate the clinical characteristics and risk factors of adult recurrent acute infectious epiglottitis. Methods:All patients diagnosed with acute infectious epiglottitis hospitalized in the Department of Otolaryngology, Hai'an People's Hospital, Nantong University from January 2012 to December 2019 were included. Results:The recurrence rate of 331 adult patients with acute infectious epiglottitis was 4.2% ï¼14/331ï¼, including 10 cases of once recurrence and 4 cases of twice recurrence. The onset time of all patients was within 48 hours. The most common main complaint in the recurrent group was sore throat ï¼42.9%ï¼, and dysphagia in the non-recurrent group ï¼42.0%ï¼. The frequency of drinking in recurrent group was higher than that in non-recurrent group ï¼P=0.009ï¼. The incidence of chronic obstructive pulmoriary diseaseï¼COPDï¼, diabetes, cyst and gastroesophageal reflux disease/laryngopharyngeal reflux disease in recurrent group was higher than that in non-recurrent group. There was no significant difference in other clinical features, treatment and prognosis between the two groups except tongue tonsil infection under laryngoscope. Multivariate analysis showed that frequent drinking ï¼more than twice a weekï¼, COPD, diabetes, cysts and lingual tonsillar infection were the risk factors for recurrence. Conclusion:Adult acute infectious epiglottitis has a proportion of single or multiple recurrence. Frequent drinking, COPD, diabetes, cyst and lingual tonsillar infection are the risk factors for the recurrence.
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Quistes , Epiglotitis , Reflujo Laringofaríngeo , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Adulto , Epiglotitis/diagnóstico , Epiglotitis/terapia , Factores de Riesgo , Enfermedad AgudaRESUMEN
A mild, modular and efficient synthetic method with broad substrate scope was developed for aspulvinones. Nine natural aspulvinones were synthesized, six of which were for the first time. The aldol condensation delivered Z-configuration products predominantly in MeCN. Meanwhile, alkoxy exchange occurred in MeOH and EtOH. Aspulvinone O and E, and substrate 49, 50, and 51 exhibited modest anti-SARS-CoV-2 activity in a high-throughput screening and enzyme kinetics assay.
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Since the COVID-19 pandemic, polypropylene melt-blown nonwovens (MBs) have been widely used in disposable medical surgical masks and medical protective clothing, seriously threatening the environment. As a bio-based biodegradable polymer, polylactic acid (PLA) has attracted great attention in fabricating MBs. However, there are still issues with the undesirable spinnability of PLA and the limited filtration and antibacterial performance of PLA MBs. Herein, a high-efficiency, low-resistance, and antibacterial PLA filter is fabricated by melt-blown spinning and electret postprocessing technology. The irradiation technique is used to tune PLA chain structure, improving its spinnability. Further, silica (SiO2) nanoparticles are added to enhance the charge storage stability of PLA MBs. With a constant airflow rate of 32 L min-1, the PLA-based MBs exhibit a high particulate filtration efficiency of 94.8 ± 1.5%, an ultralow pressure drop of 14.1 ± 1.8 Pa, and an adequate bacterial filtration efficiency of 98 ± 1.2%, meeting the medical protective equipment standard. In addition, the zinc oxide (ZnO) masterbatches are doped into the blend and the antibacterial rate of PLA-based MBs against Escherichia coli and Staphylococcus aureus is higher than 99%. This successful preparation and modification method paves the way for the large-scale production of PLA MBs as promising candidates for high-efficacy and antibacterial filters.
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Flexible conductive films based on light-to-heat conversion are promising for the next-generation electronic devices. A flexible waterborne polyurethane composite film (PU/MA) with excellent photothermal conversion performance was obtained by combination of PU and silver nanoparticle decorated MXene (MX/Ag). The silver nanoparticles (AgNPs) uniformly decorated on the MXene surface by γ-ray irradiation induced reduction. Because of the synergistic effect of MXene with outstanding light-to-heat conversion efficiency and the AgNPs with plasmonic effect, the surface temperature of the PU/MA-II (0.4%) composite with lower MXene content increased from room temperature to 60.7 °C at 5 min under 85 mW cm-2 light irradiation. Besides, the tensile strength of PU/MA-II (0.4%) increased from 20.9 MPa (pure PU) to 27.5 MPa. The flexible PU/MA composite film shows great potential in the field of thermal management of flexible wearable electronic devices.
RESUMEN
Propofol (2,6-diisopropylphenol) is an anaesthetic agent with anti-oxidant properties. The aim of the present study was to determine whether propofol can protect pulmonary epithelial (A549) cells against lipopolysaccharide (LPS)-induced cell death and, if so, the mechanisms involved. The effects of LPS alone and in combination with propofol on A549 cell death were investigated. Cell viability was determined using the colourimetric 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic A549 cells were detected by flow cytometry, as propidium iodide-negative and annexin-V-positive cells, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL). Mitochondrial membrane potential (MMP), caspase 9 activity, Ca(2+) concentrations and reactive oxygen species (ROS) were analysed by immunofluorescent methods. Aconitase 2 (ACO2), microtubule-associated light chain 3 (LC3) and beclin-1 levels were evaluated using reverse transcription-polymerase chain reaction and/or western blot analysis. Exposure of A549 cells to 1-50 µg/mL LPS for 3-24 h resulted in the concentration- and time-dependent induction of cell death. Cell apoptosis accounted for approximately 77% of cell death induced by LPS. Propofol (5-150 µmol/L) concentration-dependently inhibited LPS-induced A549 cell death. This protective effect of propofol was accompanied by prevention of LPS-induced mitochondrial dysfunction (reductions in MMP, ACO2 expression and ATP) and was associated with the inhibition of LPS-induced activation of apoptotic signals (caspase 9 activity, ROS overproduction and Ca(2+) accumulation). In addition, propofol blocked LPS-induced overexpression of the autophagy-associated proteins LC3 and beclin-1. The data indicate that propofol protects A549 cells against LPS-induced apoptosis, and probably autophagy, by blocking LPS-induced activation of ROS/caspase 9 pathways and upregulation of LC3 and beclin-1, respectively.