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A three-dimensional (3D) microstructural volume is reconstructed from a stack of two-dimensional sections which was obtained by serial sectioning coupled with electron back scattering diffraction (EBSD) mapping of a 316L austenitic stainless steel. A new alignment algorithm named linear translation by minimising the indicator (LTMI) is proposed to reduce the translational misalignments between adjacent sections by referencing to coherent twin boundaries which are flat and lying on {111} planes. The angular difference between the measured orientation of a flat twin boundary and that of the {111} plane is used as an indicator of the accuracy of the alignment operations. This indicator is minimised through linear translations of the centroids of triangular facets, which constitute grain boundaries at a distance not restricted by the in-plane step size of the EBSD maps. And hence the systematic trend in the translational misalignments can be effectively reduced. The LTMI alignment procedure proposed herein effectively corrects the misalignments remained by other methods on a 3D-EBSD data prepared using serial sectioning methods. The accuracy in distinguishing between coherent and incoherent twin boundaries is significantly improved.
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Chemotherapy resistance is a major obstacle to effective cancer treatment, and promotion of ferroptosis can suppress cisplatin resistance in tumor cells. TCF12 plays a suppressive role in oral squamous cell carcinoma (OSCC), but whether it participates in the regulation of cisplatin resistance by modulating ferroptosis remains unclear. Here, we found that TCF12 expression was decreased in OSCC cells compared with normal oral cells, and it was reduced in cisplatin (DDP)-resistant OSCC cells compared with parental cells. Moreover, overexpression of TCF12 sensitized DDP-resistant cells to DDP by promoting ferroptosis. Intriguingly, silencing TCF12 reversed the promotion effect of the ferroptosis activator RSL3 on ferroptosis and DDP sensitivity, and overexpressing TCF12 antagonized the effect of the ferroptosis inhibitor liproxstatin-1 on ferroptosis and DDP resistance. Mechanically, TCF12 promoted ubiquitination of SLC7A11 and decreased SLC7A11 protein stability through transcriptional repression of OTUB1, thereby facilitating ferroptosis. Consistently, SLC7A11 overexpression neutralized the promotion effect of TCF12 on ferroptosis and DDP sensitivity. Additionally, upregulation of TCF12 hindered the growth of mouse OSCC xenografts and enhanced the DDP sensitivity of xenografts by inducing ferroptosis. In conclusion, TCF12 enhanced DDP sensitivity in OSCC cells by promoting ferroptosis, which was achieved through modulating SLC7A11 expression via transcriptional regulation of OTUB1.
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OBJECTIVE: METTL3 (methyltransferase-like protein 3)-mediated N6-methyladenosine modification is the most abundant RNA modification on eukaryote mRNAs and plays a crucial role in diverse physiological and pathological processes. However, whether N6-methyladenosine modification has function in thrombosis is unknown. This study aims to determine the role of METTL3 in the endothelial cells-mediated thrombosis. Approach and Results: RNA-sequencing and real-time quantitative PCR revealed that the expression of PAI-1 (plasminogen activator inhibitor-1) was downregulated in METTL3 knockdown human umbilical vein endothelial cells. In vitro experiments showed that METTL3 suppressed fibrinolysis. Mechanically, RNA methylation sequencing and meRIP-quantitative real-time PCR showed that METTL3 catalyzed N6-methyladenosine modification on 3' UTR of JUN mRNA. Western blotting analysis showed that METTL3 promoted JUN protein expression. Chromatin immunoprecipitation analysis demonstrated that JUN bound to the PAI-1 promoter in human umbilical vein endothelial cells. Furthermore, mice challenged with lipopolysaccharide resulted in higher METTL3 expression in vessels. Endothelial-specific knockdown of Mettl3 decreased expression of active PAI-1 in plasma and attenuated fibrin deposition in livers and lungs during endotoxemia. CONCLUSIONS: Our study reveals that METTL3-mediated N6-methyladenosine modification plays a crucial role in fibrinolysis and is an underlying target for the therapy of thrombotic disorders.
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Endotelio Vascular/metabolismo , Fibrinólisis , Metiltransferasas/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Proteínas de Unión al ARN/metabolismo , Trombosis/metabolismo , Regiones no Traducidas 3' , Animales , Regulación hacia Abajo , Genes jun , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARN , Regulación hacia ArribaRESUMEN
Current research has widely applied heteroatom doping for the promotion of catalyst activity in peroxymonosulfate (PMS) systems; however, the relationship between heteroatom doping and stimulated activation mechanism transformation is not fully understood. Herein, we introduce nitrogen and sulfur doping into a Co@rGO material for PMS activation to degrade tetracycline (TC) and systematically investigate how heteroatom doping transformed the activation mechanism of the original Co@rGO/PMS system. N was homogeneously inserted into the reduced graphene oxide (rGO) matrix of Co@rGO, inducing a significant increase in the degradation efficiency without affecting the activation mechanism transformation. Additionally, S doping converted Co3O4 to Co4S3 in Co@rGO and transformed the cooperative oxidation pathway into a single non-radical pathway with stronger intensity, which led to a higher stability against environmental interferences. Notably, based on density functional theory (DFT) calculations, we demonstrated that Co4S3 had a higher energy barrier for PMS adsorption and cleavage than Co3O4, and therefore, the radical pathway was not easily stimulated by Co4S3. Overall, this study not only illustrated the improvement due to the heteroatom doping of Co@rGO for TC degradation in a PMS system but also bridged the knowledge gap between the catalyst structure and degradation performance through activation mechanism transformation drawn from theoretical and experimental analyses.
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Nitrógeno , Peróxidos , Antibacterianos , Cobalto , Grafito , Nitrógeno/química , Óxidos , Peróxidos/química , Azufre , TetraciclinaRESUMEN
Soy sauce, a dark-colored seasoning, is added to enhance the sensory properties of foods. Soy sauce can be consumed as a condiment or added during the preparation of food. There are 3 types of soy sauce: fermented, acid-hydrolyzed vegetable protein (acid- HVP), and mixtures of these. 3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminants formed during the preparation of soy sauce and was found to be a by-product of acid-HVP-produced soy sauce in 1978. 3-MCPD has been reported to be carcinogenic, nephrotoxic, and reproductively toxic in laboratory animal testing and has been registered as a chemosterilant for rodent control. 3-MCPD is classified as a possible carcinogenic compound, and the maximum tolerated limit in food has been established at both national and international levels. The purpose of this review is to provide an overview on the detection of 3-MCPD in soy sauce, its toxic effects, and the potential methods to reduce its concentration, especially during the production of acid-HVP soy sauce. The methods of quantification are also critically reviewed with a focus on efficiency, suitability, and challenges encountered in analysis.
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BACKGROUND: Acute myeloid leukemia (AML) recurrence is largely a result of multidrug resistance (MDR). We aimed to examine the role of 14-3-3ζ in AML chemosensitivity using HL-60 and vincristine-resistant HL-60/VCR cells. METHODS: The effects of 14-3-3ζ siRNA on the growth and cell cycle progression of HL-60 and HL-60/VCR cells were determined. The effect of 14-3-3ζ siRNA on topotecan (TPT)-induced apoptosis was evaluated by several assays. RESULTS: Compared to HL-60 cells, HL-60/VCR cells had increased 14-3-3ζ mRNA and protein expression. Increased mdr-1 mRNA as well as mdr-1, Bcl-2 and Mcl-1 protein expression were observed in HL-60/VCR cells. In both HL-60 and HL-60/VCR cells, 14-3-3ζ was observed in the cytoplasm and nuclear compartments. 14-3-3ζ siRNA significantly reduced HL-60 and HL-60/VCR cell growth after 48 h and increased the proportion of cells in the G0/G1 phase. Moreover, 14-3-3ζ siRNA significantly increased the sensitivity of both HL-60 and HL-60/VCR cells to TPT, possibly through the inhibition of Bcl-2, Mcl-1 and mdr-1 protein expression. CONCLUSIONS: Silencing of 14-3-3ζ increased the sensitivity of both sensitive and resistant HL-60 cells to TPT-induced apoptosis, possibly through altering the expression of apoptosis-associated proteins, suggesting that it may be a potential target for MDR AML.
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Proteínas 14-3-3/fisiología , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Regulación Leucémica de la Expresión Génica , Células HL-60/enzimología , Proteínas de Neoplasias/fisiología , Proteínas 14-3-3/antagonistas & inhibidores , Proteínas 14-3-3/biosíntesis , Proteínas 14-3-3/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/fisiología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Perfilación de la Expresión Génica , Células HL-60/efectos de los fármacos , Humanos , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/biosíntesis , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , ARN Interferente Pequeño/farmacología , Fracciones Subcelulares/metabolismo , Inhibidores de Topoisomerasa I/farmacología , Topotecan/farmacología , Vincristina/farmacologíaRESUMEN
Objective: This study investigated how anticipated instrumental support sources and intergenerational support influence depressive symptoms in older Chinese adults. Methods: We employed binary logistic regression on data from 7,117 adults aged ≥60 in the 2018 China Health and Retirement Longitudinal Study, controlling for gender, marital status, and self-rated health. Results: 38.89% of respondents exhibited depressive symptoms. Anticipated support from spouse and children, spouse only, children only, or other sources showed 52, 25, 46, and 40% lower odds of depression, respectively, compared with no anticipated support. Those providing financial support had 36% higher odds of depression than those without exchanges. However, those receiving financial support, receiving instrumental support, and receiving and providing financial and emotional support had 19, 14, 23, and 24% lower odds of depression. Conclusion: Different anticipated instrumental support sources and intergenerational support influenced depression odds in older adults, suggesting potential benefits in promoting such support systems.
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Depresión , Jubilación , Niño , Humanos , Persona de Mediana Edad , Anciano , Depresión/epidemiología , Depresión/psicología , Estudios Longitudinales , China/epidemiología , Modelos LogísticosRESUMEN
Transition-metal sulfide is considered to be an admirable transformational electrode material due to low cost, large specific capacity, and good reversibility in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). Herein, the reduced graphene oxide-wrapped open bimetallic sulfide (NiS2-Co3S4@rGO) nanocage, derived from nickel-cobalt Prussian blue, was obtained by two-step calcination. There are luxuriant pore structures in the nanocage composite with a specific surface area of 85.28 m2 g-1, which provides plentiful paths for rapid transmission of Li+/Na+ and alleviates the volume stress caused by insertion and extraction of alkali metal ions. The excellent interface combination of bimetallic sulfide wrapped in reduced graphene oxide improves the conductivity and overall performance of the battery. Thanks to the special interface engineering, the open NiS2-Co3S4@rGO nanocage composite displays rapid lithium storage properties with an average diffusion coefficient of 8.5 × 10-13 cm2 s-1. Moreover, after 300 cycles, the reversible capacity of the composite is 1113.2 mAh g-1 at 1 A g-1. In SIBs, the capacity of the open NiS2-Co3S4@rGO composite is 487.9 mAh g-1 when the current density is 5 A g-1. These preeminent performances demonstrate the enormous development prospects of bimetallic sulfide nanocage as anode material in LIBs and SIBs.
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Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.
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Temperatura Corporal , Nocicepción , Canales Catiónicos TRPV , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Animales , Ratones , Regulación Alostérica/efectos de los fármacos , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Temperatura Corporal/efectos de los fármacos , Analgésicos/farmacología , Masculino , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Dolor/metabolismo , Dolor/tratamiento farmacológicoRESUMEN
The chemical shift of fluoxetine hydrochloride appears at delta 14.15 in 19F NMR analysis. The delta moved upfield slightly from 14.158 to 14.145 when the concentration of solution became diluted from 2.00 to 0.05 mmol x L(-1). Spiking test was suggested to confirm the existence of the compound for qualitative analysis. 19F NMR detection sensitivity test illustrated that a concentration of 17 mg in 1 L water could be detected while the sample was scanned 500 times with optimum parameters. In quantitative analysis, standard curve of concentration versus fluorine signal intensity was proposed to determine the amount of fluoxetine. Long capillary tube containing trifluoroacetic acid was used as internal standard for the integration measurements and straight line was obtained with good fitting. Direct additions of trifluoroethanol to fluoxetine solutions gave a poorer standard curve.
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Fluoxetina/análisis , Fluoxetina/química , Espectroscopía de Resonancia Magnética , Flúor/química , Estructura Molecular , Ácido Trifluoroacético/análisisRESUMEN
Current research focused on developing multiple active species in peroxymonosulfate (PMS) system to degrade contaminants, but deepening concern lacks over why cooperation of those active species facilitated a faster degradation. Here, we employed Co3O4, rGO and Co3O4@rGO composite to activate PMS for tetracycline (TC) degradation, and detected crucial factors toward highest performance of Co3O4@rGO/PMS system. Batch experiments exhibited a satisfactory TC degradation efficiency under Co3O4@rGO/PMS, complete degraded 50 mg/L TC within 20 min. Analytical tests discovered that radical active species generated by Co3O4/PMS and non-radical species by rGO/PMS were successfully co-existed in Co3O4@rGO/PMS system, significantly improving the performance of TC removal. Subsequently, a combination of density functional theory (DFT) calculation and intermediates analysis revealed that, in Co3O4@rGO/PMS system, the cooperation rather than independent effect of radical and non-radical active species expanded TC degradation pathways, enhancing the degradation performance. Furthermore, decent adaptability, stability, and recyclability toward affecting factors variation of Co3O4@rGO/PMS demonstrated it as a potent and economical system to degrade TC. Overall, this study developed a novel Co3O4@rGO/PMS system with a cooperative oxidation pathway for highly efficient TC removal, and managed to clarify why this oxidation pathway achieved high efficiency through a combination of theoretical and experimental method.
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Peróxidos , Tetraciclina , Cobalto , ÓxidosRESUMEN
Microplastics (the term for plastics at sizes of <5 mm) might be introduced into the environment from domestic or agricultural activities or from the breakdown of plastic pieces, particles, and debris that are bigger in size. Their presence in the aquatic environment has caused accumulation problems, as microplastics do not easily break down and can be digested by some aquatic organisms. This study was conducted to screen and monitor the level of microplastic pollution in polychaete worms using pyrolysis−gas chromatography/mass spectrometry (Py-GC/MS). The study was conducted in Setiu Wetlands, Malaysia from November 2015 to January 2017 at five-month intervals and covered all monsoon changes. Results from physical and visual analyses indicated that a total number of 371.4 ± 20.2 items/g microplastics were retrieved from polychaete for all seasons, in which, the majority comprised transparent microplastics (49.87%), followed by brown with 138.3 ± 13.6 items/g (37.24%), 21.7 ± 1.9 items/g for blue (5.84%), and 12.9 ± 1.1 items/g for black (3.47%), while the remaining were green and grey-red colors. Statistical analysis using Kruskal−Wallis showed insignificant differences (p > 0.05) between the sampling station and period for the presence of a microplastics amount. Most of the microplastics were found in fiber form (81.5%), whereas the remaining comprised fragment (18.31%) and film (0.19%) forms. Further analysis with Py-GC/MS under a selective ion monitoring mode indicated that pyrolytic products and fragment ions for a variety of polymers, such as polyvinyl chloride, polypropylene, polyethylene, polyethylene terephthalate, polyamide, and polymethylmethacrylate, were detected. This study provides an insightful application of Py-GC/MS techniques for microplastics monitoring, especially when dealing with analytical amounts of samples.
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BACKGROUND: The findings of previous studies remain controversial on the optimal management required for effective seizure control after surgical excision of arteriovenous malformations (AVMs). We evaluated the efficacy of additional bipolar electrocoagulation on the electrically positive cortex guided by intraoperative electrocorticography (ECoG) for controlling cerebral AVMs-related epilepsy. CLINICAL MATERIAL AND METHODS: Sixty consecutive patients with seizure due to cerebral AVMs, who underwent surgical excision of cerebral AVMs and intraoperative ECoG, were assessed. The AVMs and surrounding hemosiderin stained tissue were completely removed, and bipolar electrocoagulation was applied on the surrounding cerebral cortex where epileptic discharges were monitored via intraoperative ECoG. Patients were followed up at three to six months after the surgery and then annually. We evaluated seizure outcome by using Engel's classification and postoperative complications. RESULTS: Forty-nine patients (81.6%) were detected of epileptic discharges before and after AVMs excision. These patients underwent the removal of AVMs plus bipolar electrocoagulation on spike-positive site cortex. After electrocoagulation, 45 patients' epileptic discharges disappeared, while four obviously diminished. Fifty-five of 60 patients (91.7%) had follow-up lasting at least 22 months (mean 51.1 months; range 22-93 months). Determined by the Engel Seizure Outcome Scale, 39 patients (70.9%) were Class I, seven (12.7%) Class II, five (9.0%) Class III, and four (7.2%) Class IV. CONCLUSION: Even after the complete removal of AVM and surrounding gliotic and hemosiderin stained tissue, a high-frequency residual spike remained on the surrounding cerebral cortex. Effective surgical seizure control can be achieved by carrying out additional bipolar electrocoagulation on the cortex guided by the intraoperative ECoG.
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Corteza Cerebral/fisiología , Corteza Cerebral/cirugía , Electrocoagulación/métodos , Convulsiones/patología , Convulsiones/cirugía , Adolescente , Adulto , Anciano , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/cirugía , Niño , Electroencefalografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To explore the application of intracranial electrodes (IE) for temporal lobe epilepsy (TLE) surgery and assess the clinical utility of intracranial video electroencephalography (IVEEG). METHODS: The clinical data of 60 TLE patients undergoing implantation of IE were reviewed retrospectively. Cortical subdural strip, grids and depth electrodes were implanted by sphenotresia, bone disc craniotomy or stereotactic technology. RESULTS: The implanted electrodes were as follows: frontal-temporal lobe cortical strip (n = 34), frontal-anterior temporal-occipitotemporal lobe cortical strip (n = 7), bilateral temporal lobe cortical strip (n = 7), combined temporal lobe strip & depth (n = 7), anterior temporal-occipitotemporal junction cortical strip (n = 3) and combined strip & grid (n = 2). The following procedures were performed: anterior temporal lobectomy (ATL) (n = 50), combined ATL & frontal focal cortical resection (n = 7), combined ATL & callosotomy (n = 1) and combined neocortex epileptogenic focus resection & amygdalohippocampectomy (n = 2). CONCLUSION: IVEEG is effective and important for the localization of epileptogenic focus in patients with intractable temporal lobe epilepsy.
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Electroencefalografía/métodos , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/cirugía , Adolescente , Adulto , Niño , Electrodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Fluorine (F) is widely dispersed in the environment and frequently used in industry and agriculture with a high migration ability. Thus, it is essential to understand the leaching characteristic of F in soil from industry and agriculture sources. Several sources of F pollutants in soil, including fertilizers, pesticides, phosphogypsum, and atmospheric deposition, were selected to investigate leaching characteristics of F in soil by leaching experiments. The addition of phosphate fertilizer and compound fertilizer (N:P:K = 20:10:15) enhanced the leachability of F in soil and the proportion of F leached out from soil treated by these fertilizers were 0.25% and 0.24%, respectively. However, unanticipated lower leachability of F appeared in compound fertilizer (N:P:K = 17:17:17), nitrogen fertilizer, dipterex, fluoroglycofen, fluopimomide, simulative dry deposition (YF3), and phosphogypsum loaded soils compared with additive-absent treatment. Although phosphogysum had a high F concentration, minimum proportion of F released (0.18%) was observed in phosphogypsum-coverd soil. The amounts of F leaching-out from surface soils (0-25 cm) treated with nitrogen fertilizer decreased 1.03 kg ha-1 comparing with blank control. Soil with phosphate fertilizer leached 5.47 kg F ha-1 a year, having the highest environment risk to deeper soil and groundwater. However, phosphogypsum and dry deposition of airbone F chemical had few effects on F leaching in soil. F-containing materials from agricultural process may leach more F from surface soils than industrial sources.
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Plaguicidas , Contaminantes del Suelo , Agricultura , Sulfato de Calcio , Fertilizantes/análisis , Flúor , Nitrógeno , Fósforo , Suelo , Contaminantes del Suelo/análisisRESUMEN
Based on data of daily precipitation, temperature, sunshine hours, relative humidity, wind speed and vapor pressure of 70 meteorological stations from 1960 to 2019 in Shanxi Province, the Penman-Monteith model was applied to calculate the reference evapotranspiration (ET0). The spatiotemporal variations of ET0 as well as the ET0 in different climatic zones and at different altitudes were quantitatively analyzed. The results showed that the mean annual ET0 decreased from west to east in 1960-2019. A jumping point was detected in 1982, with the mean annual ET0 increased both in 1960-1982 and 1983-2019. The monthly and ten-day changes of ET0 showed single peak curves. The variation of ET0 in different climatic zones was as follows: ET0 in temperate and semi-arid areas was higher than that in warm temperate and semi-humid areas and warm temperate and semi-arid areas in spring, summer, autumn and the whole year, while in winter, the highest ET0 was in warm temperate and semi-humid areas. ET0 varied with altitudes, with ET0 in <660 m altitude areas being higher than that in other altitudes in summer, autumn, winter and the whole year.
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Productos Agrícolas , Transpiración de Plantas , China , Temperatura , VientoRESUMEN
BACKGROUND: The aim of the present study was to investigate the synergistic effects and interactive mechanisms of Shufeng Jiedu Capsule (SFJDC) combined with oseltamivir in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) induced by the influenza A virus (IAV). METHODS: The extraction of SFJDC was analyzed by UHPLC/ESI Q-Orbitrap Mass Spectrometry. Human bronchial epithelial cells were isolated from COPD (DHBE) bronchial tissues, co-cultured with IAV for 24â¯h, and were subsequently treated with SFJDC and/or oseltamivir. Cell viability was detected by MTT assay. A rat model of COPD with IAV infection was established and treated with SFJDC and/or oseltamivir. Interleukin (IL)-1ß and IL-18 in serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, mRNA and protein levels of NLRP3 inflammasome pathway were measured by quantitative real-time PCR and Western blotting, respectively. RESULTS: SFJDC and/or oseltamivir, at their optimal concentrations, had no significant cytotoxicity against DHBEs. The levels of NLRP3-inflammasome-associated components were significantly elevated after cells were inoculated with IAV, whereas the mRNA and protein levels of these components were significantly decreased after treatment with SFJDC and/or oseltamivir in vitro. Moreover, in vivo, the combination of SFJDC and oseltamivir improved survival rates, attenuated clinical symptoms, induced weight gain, alleviated lung damage, and significantly reduced IL-1ß and IL-18 levels in serum and BALF, as well as reduced the expression levels of NLRP3-associated components and viral titers in lung homogenates. CONCLUSION: SFJDC combined with oseltamivir treatment significantly attenuated IAV-induced airway inflammation and lung viral titers. Hence, our findings may provide a novel therapeutic strategy for IAV-induced respiratory infection.
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Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Oseltamivir/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/virología , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/virología , Animales , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Bronquios/virología , Líquido del Lavado Bronquioalveolar/virología , Línea Celular , Técnicas de Cocultivo/métodos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/virología , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/virología , Gripe Humana/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/virología , Masculino , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/virología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Carga Viral/efectos de los fármacosRESUMEN
The interaction between microglia and astrocytes significantly influences neuroinflammation. Microglia/astrocytes, part of the neurovascular unit (NVU), are activated by various brain insults. The local extracellular and intracellular signals determine their characteristics and switch of phenotypes. Microglia and astrocytes are activated into two polarization states: the pro-inflammatory phenotype (M1 and A1) and the anti-inflammatory phenotype (M2 and A2). During neuroinflammation, induced by stroke or lipopolysaccharides, microglia are more sensitive to pathogens, or damage; they are thus initially activated into the M1 phenotype and produce common inflammatory signals such as IL-1 and TNF-α to trigger reactive astrocytes into the A1 phenotype. These inflammatory signals can be amplified not only by the self-feedback loop of microglial activation but also by the unique anatomy structure of astrocytes. As the pathology further progresses, resulting in local environmental changes, M1-like microglia switch to the M2 phenotype, and M2 crosstalk with A2. While astrocytes communicate simultaneously with neurons and blood vessels to maintain the function of neurons and the blood-brain barrier (BBB), their subtle changes may be identified and responded by astrocytes, and possibly transferred to microglia. Although both microglia and astrocytes have different functional characteristics, they can achieve immune "optimization" through their mutual communication and cooperation in the NVU and build a cascaded immune network of amplification.
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Astrocitos/inmunología , Encéfalo/fisiología , Microglía/inmunología , Inflamación Neurogénica/inmunología , Neuronas/fisiología , Acoplamiento Neurovascular/fisiología , Animales , Humanos , Mediadores de Inflamación/metabolismoRESUMEN
Quantifiable levels of 3-chloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) were found in domestically manufactured soy-based sauces. Selected commercial foods in the Malaysian market (n = 43) were analyzed for their 3-MCPD and 1,3-DCP contents using a validated gas chromatography-mass spectrometry technique. The 3-MCPD and 1,3-DCP contents of the analyzed food samples varied from not detectable levels to 0.1223 ± 0.0419 mg kg-1 and not detectable levels to 0.025 ± 0.0041 mg kg-1, respectively. High concentrations of 3-MCPD, exceeding Malaysia's maximum tolerable limit of 0.02 mg kg-1, were found in chicken seasoning cubes (mean = 0.0898 ± 0.0378 mg kg-1). Monte Carlo simulation-based health risk assessment revealed that 3-MCPD and 1,3-DCP intakes in the 50th, 95th, and 99th percentiles were lower than 4 µg kg-1 bw day-1, the limit recommended by JECFA in 2016. Hence, it was concluded that the exposure of Malaysian citizens to chloropropanols through soy sauce consumption does not present a health risk.
Asunto(s)
Carcinógenos/análisis , Alimentos de Soja/análisis , alfa-Clorhidrina/análogos & derivados , alfa-Clorhidrina/análisis , Adolescente , Adulto , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Malasia , Masculino , Persona de Mediana Edad , Método de Montecarlo , Medición de RiesgoRESUMEN
BACKGROUND: Magnetic resonance elastography (MRE) is a recently developed imaging technique that can directly visualize and quantitatively measure tissue elasticity. PURPOSE: To evaluate the safety of brain MRE on human subjects. MATERIAL AND METHODS: The study included 20 healthy volunteers. MRE sequence scan (drive signal not applied to external force actuator) and MRE study were separately performed on each volunteer at an interval of more than 24 hours. The heart rate and blood pressure of each volunteer were measured immediately before and after MRE sequence scan and MRE study. Electroencephalography (EEG) was also performed within 2 hours after each scan. The volunteers were asked about their experience of the two scans. Randomized-block analysis of variance (ANOVA) was used to analyze the data of blood pressure and heart rate. Paired t test was used to analyze the data of the two EEG examinations. The volunteers were followed up 1 week after the examination. RESULTS: All procedures were performed on each volunteer, and no one complained of obvious discomfort. No related adverse events were reported during follow-up. There was no statistically significant difference in heart rate or blood pressure. There was a statistically significant difference (P<0.05) in EEG results in the right temporoparietal region. Increased power was found in the theta, delta, alpha, and beta2 bands. No brain injury was detected by the EEG examinations. CONCLUSION: Based on the study results, brain MRE examinations are safe to perform on human subjects.