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Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.
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Citocinas , Inflamação , Macrófagos , Neutrófilos , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Neutrófilos/metabolismo , Neutrófilos/imunologia , Macrófagos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Citocinas/metabolismo , Mutação/genética , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2/deficiênciaRESUMO
In this study, a cascade nanobioreactor was developed for the highly sensitive detection of methyl parathion (MP) in food samples. The simultaneous encapsulation of acetylcholinesterase (AChE) and choline oxidase (CHO) in a zeolitic imidazole ester backbone (ZIF-8) effectively improved the stability and cascade catalytic efficiency of the enzymes. In addition, glutathione-stabilized gold nanoclusters (GSH-AuNCs) were encapsulated in ZIF-8 by ligand self-assembly, conferring excellent fluorescence properties. Acetylcholine (ATCh) is catalyzed by a cascade of AChE/CHO@ZIF-8 as well as Fe(II) to generate hydroxyl radicals (·OH) with strong oxidizing properties. The ·OH radicals then oxidize Au(0) in GSH-AuNCs@ZIF-8 to Au(I), resulting in fluorescence quenching. MP, as an inhibitor of AChE, hinders the cascade reaction and thus restores the fluorescence emission, enabling its quantitative detection. The limit of detection of the constructed nanobioreactor for MP was 0.23 µg/L. This MOF-based cascade nanobioreactor has great potential for the detection of trace hazards.
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Nanopartículas Metálicas , Estruturas Metalorgânicas , Metil Paration , Acetilcolinesterase , Acetilcolina , Ouro , Limite de DetecçãoRESUMO
AIM: To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution. METHODS: Ten Sprague Dawley rats as the control group. Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d, then divided rats into three groups: dry eye group with no treatment (DED group, n=10); phosphate buffer saline treated group (PBS group, n=10); diquafosol treated group (DQS group, n=10). Clinical changes were observed by tear production test, fluorescein staining, tear break-up time (TBUT) test, corneal confocal microscope and ocular surface comprehensive analyzer. Eyeballs were collected on day 10 of treatment for hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and alcian blue staining. TUNEL assay, polymorphonuclear (PMN) and mucin 1 (MUC1) immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy. RESULTS: Compared with DED and PBS groups, tear production (7.26±0.440 vs 4.07±0.474 mm; 7.26±0.440 vs 3.74±0.280 mm; all P<0.01) and TBUT (7.37±0.383s vs 1.49±0.260s; 7.37±0.383s vs 1.42±0.437s; all P<0.01) were significantly increased in DQS group. HE, PAS, and alcian blue staining and MUC1 immunofluorescence showed mucins and conjunctival goblet cells density (8.45±0.718 vs 5.21±0.813 cells/0.1 mm2; 8.45±0.718 vs 5.36±0.615 cells/0.1 mm2; all P<0.01) increased in DQS group. Confocal microscopy, PMN immunofluorescence and TUNEL staining showed inflammatory infiltration and corneal epithelial cells apoptosis decreased in DQS group. The increased number of microvilli in corneal epithelial and the recovered cell junction were observed in DQS group. CONCLUSION: PI instillation can induce goblet cells and mucin loss, epithelial cell apoptosis and inflammation, which are consistent with the pathological manifestations of dry eye. Diquafosol can repair the ocular surface damage caused by PI, reduce corneal inflammation, inhibit corneal epithelial cell apoptosis, promote mucin secretion and maintain tear film stability.
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Hard-to-cook (HTC) is a textural defect that delays the softening of common bean seeds during cooking. While this defect is commonly associated with conventionally stored beans, soaking/cooking of beans in CaCl2 solutions or sodium acetate buffer can also prolong the cooking time of beans due to formation of Ca2+ crosslinked pectin retarding bean softening during cooking. In this study, the role of the cell wall-bound Mg2+/Ca2+ content and the degree of pectin methyl esterification (DM) was quantified, as important factors for bean texture-related changes stipulated in the pectin-cation-phytate hypothesis, the most plausible hypothesis of HTC development. Evaluation of texture changes during cooking of conventionally aged beans (35 °C and 83% RH for up to 20 weeks), beans soaked/cooked in CaCl2 solutions (0.01 to 0.1 M) or soaked in 0.1 M sodium acetate buffer (pH 4.4) revealed large bean-to-bean variations. Therefore a texture-based classification approach was used to better capture the relation between texture characteristics and cell wall polymer, in particular pectin, related changes. While cell wall-bound Ca2+ and pectin DM did not change/were not related to the texture variation during cooking of fresh beans, increased cell wall-bound Ca2+ and decreased pectin DM were associated with prolonged conventional storage of beans and their texture changes during subsequent cooking (due to pectin cross linking, retarding its solubilization during cooking). Exogenously added Ca2+ from pre-treating beans in CaCl2 solutions promoted to a great extent the cell wall-bound Ca2+ during soaking but even more so during cooking, complementing the harder texture associated with these beans during cooking (compared to conventionally stored and fresh beans). Similarly, free Ca2+ endogenously generated by phytase-catalysed phytate hydrolysis (beans treated by acetate buffer) promoted crosslinking of pectin by Ca2+ (cell wall-bound Ca2+), delaying softening of beans during cooking.
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Phaseolus , Phaseolus/química , Cloreto de Cálcio , Ácido Fítico/análise , Acetato de Sódio/análise , Temperatura Alta , Culinária , Pectinas/química , Verduras , Cátions , Parede Celular/químicaRESUMO
Objective:To compare the clinical effect of transaxillary non-inflatable endoscopic surgery and traditional open thyroid surgery in the treatment of PTC. Methods:A retrospective analysis was performed on 342 patients with PTC treated in the Otorhinolaryngology Department of Qilu Hospital of Shandong University from December 2020 to December 2022. There were 73 males and 269 females, aged 16-72 years, who underwent unilateral non-inflatable transaxillary endoscopic thyroid surgeryï¼endoscopic groupï¼ and unilateral traditional open thyroid surgeryï¼open groupï¼. There were 108 patients in the endoscopic group and 234 in the open group. Results:The endoscopic group was lower in ageï¼37.1±9.4 vs 43.5±11.2ï¼ years and BMIï¼23.4±3.4 vs 25.7±3.8 ï¼kg/m² than that in the open group, and the difference was statistically significantï¼t was 5.53, 5.67 respectively, P<0.01ï¼. There was no significant difference in hospitalization days between the two groupsï¼P>0.05ï¼. The logarithmic curve of the operation time showed a smooth downward trend, and the overall operation time of the endoscopic group was relatively consistent. There was no significant difference in intraoperative blood loss between the endoscopic groupï¼13.3±3.2ï¼ mL and the open groupï¼14.7±6.3ï¼ mLï¼P>0.05ï¼, but the operation timeï¼130.1±37.9ï¼ min was longer than that in the open groupï¼57.4±13.7ï¼ min, and the difference was statistically significantï¼t=19.40, P<0.01ï¼. There was no significant difference in complications such as temporary recurrent laryngeal nerve injury within 3 days after operation between the two groupsï¼P>0.05ï¼. The aesthetic satisfaction score of the surgical incision and the incision concealment effect score in the endoscopic group were higher than those in the open group, and the difference was statistically significantï¼P<0.05ï¼. Conclusion:Compared with traditional open thyroidectomy, transaxillary non-inflatable endoscopic thyroidectomy has more advantages in the concealment and aesthetics of postoperative incision. Although the former has longer operation time and more drainage, it is still a safe and feasible surgical method with good postoperative clinical effect.
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Neoplasias da Glândula Tireoide , Masculino , Feminino , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Pescoço , Tireoidectomia/métodos , Endoscopia/métodosRESUMO
To establish the HTC defect development, the cooking kinetics of seeds of ten bean accessions (belonging to seven common bean market classes), fresh and conventionally aged (35 °C, 83% RH, 3 months) were compared to those obtained after soaking in specific salt solutions (in 0.1 M sodium acetate buffer at pH 4.4, 41 °C for 12 h, or 0.01 M CaCl2 at pH 6.2, 25 °C for 16 h and subsequently cooking in CaCl2 solution, or deionised water). The extent of phytate (inositol hexaphosphate, IP6) hydrolysis was evaluated to better understand the role of endogenous Ca2+ in the changes of the bean cooking kinetics. A significant decrease in the IP6 content was observed after conventional ageing and after soaking in a sodium acetate solution suggesting phytate hydrolysis (release of endogenous Ca2+). These changes were accompanied by an increase in the cooking time of the beans. Smaller changes in cooking times after soaking in a sodium acetate solution (compared to conventionally aged beans) was attributed to a lower ionisation level of the COOH groups in pectin (pH 4.4, being close to pKa value of pectin) limiting pectin Ca2+ cross-linking. In beans soaked in a CaCl2 solution, the uptake of exogenous cations increased the cooking times (with no IP6 hydrolysis). The change in cooking time of conventionally aged beans was strongly correlated with the extent of IP6 hydrolysis, although two groups of beans with low or high IP6 hydrolysis were distinguished. Comparable trends were observed when soaking in CaCl2 solution (r = 0.67, p = 0.14 or r = 0.97, p = 0.03 for two groups of beans with softer or harder texture during cooking). Therefore a test based on the Ca2+ sensitivity of the cooking times, implemented through a Ca2+ soaking experiment followed by cooking can be used as an accelerated test to predict susceptibility to HTC defect development during conventional ageing. On the other hand, a sodium acetate soaking experiment can be used to predict IP6 hydrolysis of conventionally aged bean accessions and changes of cooking times for these bean accessions (with exception of yellow bean-KATB1).
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Phaseolus , Phaseolus/química , Manipulação de Alimentos , Ácido Fítico , Acetato de Sódio , Cloreto de Cálcio , Culinária , Pectinas/químicaRESUMO
The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.
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In this work, a "turn off-on" fluorescent sensor was developed for highly sensitive determination of tert-butylhydroquinone (TBHQ) based on an Fe(III)-based metal-organic framework (Fe-MOF). An Fe-MOF with an octahedral structure was synthesized via a simple hydrothermal method using ferric chloride hexahydrate and 2-aminoterephthalic acid (NH2-BDC) as raw materials. The fluorescence of Fe-MOF is extremely weak owing to ligand-to-metal charge transfer (LMCT) and internal filtration effect (IFE). When the system contained TBHQ, the binding of TBHQ to Fe(III) inhibited the LMCT of the fluorescent ligand NH2-BDC to Fe(III), releasing the fluorescence of NH2-BDC and thus restoring the fluorescence. With this as the basis, a rapid, sensitive, and selective fluorescence sensor is developed for the detection of TBHQ. Under the optimal conditions, TBHQ showed good linearity with fluorescence intensity in the range of 0-1.5 × 102 µmol L-1 and a detection limit of 0.0030 µmol L-1 (S/N = 3). The selectivity, reproducibility, and stability of the developed Fe-MOF-based sensors are comprehensively studied. Finally, the practicality of the method is verified by examining the detection of TBHQ in soybean oil; the results are consistent with those obtained using conventional high-performance liquid chromatography.
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Corantes , Compostos Férricos , Ligantes , Reprodutibilidade dos Testes , ÓleosRESUMO
Parity-time (PT) symmetry challenges the long-held theoretical basis that only Hermitian operators correspond to observable phenomena in quantum mechanics. Non-Hermitian Hamiltonians satisfying PT symmetry also have a real-valued energy spectrum. In the field of inductor-capacitor (LC) passive wireless sensors, PT symmetry is mainly used for improving performance in terms of multi-parameter sensing, ultrahigh sensitivity, and longer interrogation distance. For example, the proposal of both higher-order PT symmetry and divergent exceptional points can utilize a more drastic bifurcation process around exceptional points (EPs) to accomplish a significantly higher sensitivity and spectral resolution. However, there are still many controversies regarding the inevitable noise and actual precision of the EP sensors. In this review, we systematically present the research status of PT-symmetric LC sensors in three working areas: exact phase, exceptional point, and broken phase, demonstrating the advantages of non-Hermitian sensing concerning classical LC sensing principles.
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Registros , Feminino , Gravidez , Humanos , ParidadeRESUMO
This study reports the development of a Tb-metal-organic framework (Tb-MOF)-based fluorescent platform for the detection of propyl gallate (PG). The Tb-MOF using 5-boronoisophthalic acid (5-bop) as the ligand exhibited multiple emissions at 490, 543, 585, and 622 nm under an excitation wavelength of 256 nm. The fluorescence of Tb-MOF was selectively and significantly weakened in the presence of PG due to the special nucleophilic reaction between the boric acid of Tb-MOF and o-diphenol hydroxyl of PG, and the combined effect of static quenching and internal filtering. Furthermore, this sensor enabled the determination of PG within seconds in a wide linear range of 1-150 µg/mL, and with a low detection limit of 0.098 µg/mL, and high specificity against other phenolic antioxidants. This work provided a new route for the sensitive and selective determination of PG in soybean oil, thus was perspective to monitor and reduce the risk of PG overuse.
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Estruturas Metalorgânicas , Galato de Propila , Limite de Detecção , Corantes Fluorescentes , ÓleosRESUMO
BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.
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Suplementos Nutricionais , Ácido Fólico , Criança , Feminino , Gravidez , Humanos , Estudos Transversais , China , Ácido Fólico/uso terapêutico , Cuidado Pré-Natal , Cuidado Pré-ConcepcionalRESUMO
Utilization of common beans is greatly hampered by the hard-to-cook (HTC) defect induced by ageing of the beans under adverse storage. Large bean-to-bean variations exist in a single batch of beans. Therefore, a texture-based bean classification approach was applied in this detailed study on beans with known textures, to gain in-depth insights into the role of the pectin-cation-phytate mechanism in relation to the texture changes during subsequent cooking of Red haricot fresh and aged beans. For the first time, a correlation between the texture (exhibited after cooking) of a single bean seed before ageing (fresh) and its texture after ageing was established. Furthermore, scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS) based in situ cell wall associated mineral quantification revealed that the cell wall associated Ca concentration was significantly positively correlated with the texture of both fresh and aged cooked Red haricot bean cotyledons, with ageing resulting in a significant enrichment of Ca at the cell wall. These additional Ca cations originate from intracellular phytate hydrolysis during ageing, which was shown to affect the texture distribution of aged beans during cooking significantly. The relocation of the mineral cations from the cell interior to the cell wall occurs mainly during storage rather than subsequent soaking of the cotyledons. In addition, the pectin-cation-phytate hypothesis of HTC was further confirmed by demethylesterification of the cell wall pectin and increased pectin-Ca interactions upon ageing of the cotyledons, finally leading to HTC development of the cotyledon tissue.
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Fabaceae , Pectinas , Pectinas/química , Ácido Fítico/análise , Temperatura Alta , Culinária/métodos , Fabaceae/química , Minerais/análise , Cátions , Verduras , Parede Celular/químicaRESUMO
During adverse postharvest storage of Red haricot beans, the inositol phosphate content, particularly InsP6, decreased significantly, along with a significant increase in InsP5. Using a texture-based classification approach, the InsP6 content in cotyledons was shown an indicator for the extent of hard-to-cook (HTC) development during bean aging. This textural defect development was predominated by storage-induced InsP6 degradation, rather than phytate interconversions during soaking. Ca cations, released during storage, did not leach out significantly during subsequent soaking, suggesting that they were bound with the cell wall pectin in cotyledons, while Mg cations were mostly leached out into the soaking water due to their weak binding capacity to the pectin, and the cell membrane damages developed during HTC. Results obtained herein provide evidence for the pectin-cation-phytate mechanism in textural hardening (and its distribution after cooking) of common beans, and call for a more detailed Ca-relocation study during postharvest storage, soaking and cooking.
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Phaseolus , Phaseolus/química , Ácido Fítico/análise , Sementes/química , Temperatura Alta , Culinária/métodos , Pectinas/química , Minerais/análiseRESUMO
As one of the most popular beverages, green tea has attracted much interest for its beneficial effects on human health. However, the toxicity of green tea and its underlying mechanism are still poorly understood. Here, we evaluated the effect of green tea and its constituents on development by exposing zebrafish embryos to them. Morphologic results demonstrated that 0.1% and 0.2% green tea increased mortality, delayed epiboly of gastrulation, and shortened body length. Green tea altered the expression pattern of dlx3, cstlb, myod, and papc and decreased the expression levels of wnt5 and wnt11, suggesting that green tea disturbed convergence and extension movement through the downregulation of wnt5 and wnt11. The increased expression of the dorsal gene chordin and reduced expression of wnt8 and its target genes vox and vent in embryos exposed to 0.1% and 0.2% green tea indicated that green tea could affect dorsoventral differentiation by inhibiting the wnt8 signaling pathway. Additionally, green tea could inhibit epiboly progression by disrupting F-actin organization or removing F-actin in vegetal yolks during gastrulation. However, no malformation was caused by exposure to the five catechins and gallic acid individually. The mixture of constituents showed a similar effect to green tea solution on the embryos, such as smaller eyes and head, shorter body length, and slower heart rate, which indicated that the effect of green tea solution on embryo development was mainly due to the comprehensive effect of multiple components in the green tea solution.
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Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Humanos , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Actinas/metabolismo , Chá/metabolismo , Desenvolvimento EmbrionárioRESUMO
Cell wall material was isolated from selected non-aged and aged Red haricot bean cotyledons using a texture-based classification approach. Pectin-depleted residual cell wall fractions were obtained by sequential pectin extraction and were characterized to investigate in situ cell wall related molecular changes upon ageing during adverse storage of the beans. Particularly, involvement of phenolic compounds in cell wall strengthening during the ageing process, resulting in the hard-to-cook defect, was evaluated. Results show that ageing induces substantial changes at a cell-wall-structural level in the Aged sample compared to the Non-aged sample, with mainly vanillin, 4-hydroxybenzoic acid and 4-hydroxybenzaldehyde covalently bound with sugar side-chains of pectin and/or involved in lignification-like mechanisms. FT-IR spectroscopy coupled with chemometric analysis reveals that lignin-like phenolic-cell wall polymers, which are known to reinforce cell wall structure, are present in the cell wall polysaccharide network of the Aged sample, and are therefore contributing factors to the hard-to-cook development during Red haricot bean ageing.
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Phaseolus , Espectroscopia de Infravermelho com Transformada de Fourier , Parede Celular , Polissacarídeos , Carboidratos da Dieta , Verduras , Pectinas , FenóisRESUMO
Acute lung injury (ALI) is an inflammatory response which causes serious damages to alveolar epithelia and vasculature, and it still remains high lethality and mortality with no effective treatment. Based on the inflammatory homing of platelets and cell membrane cloaking nanotechnology, in this study we developed a biomimetic anti-inflammation nanoparticle delivery system for ALI treatment. PM@Cur-RV NPs were designed by combining the poly (lactic-co-glycolic acid) nanoparticles (NPs) coated with platelet membrane vesicles (PM) for the purpose of highly targeting delivery of curcumin (Cur) and resveratrol (RV) to inflammatory lungs. PM@Cur-RV NPs showed good biocompatibility and biosafety both in vitro and in vivo. Accumulation of NPs into lung tract was observed after inhaled NPs. Remarkably, the inhalation of PM@Cur-RV NPs effectively inhibited lung vascular injury evidenced by the decreased lung vascular permeability, and the reduced proinflammatory cytokine burden in an ALI mouse model. The analysis of infiltrated macrophages in the lungs showed that the Cur-RV-modulated macrophage polarized towards M2 phenotype and the decreased histone lactylation might contribute to their anti-inflammation effects. Together, this work highlights the potential of inhalation of biomimetic nanoparticle delivery of curcumin and resveratrol for the treatment of pulmonary diseases.
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In recent years, immune checkpoint inhibitors (ICIs) have greatly improved the survival rate of non-small cell lung cancer (NSCLC) patients without driver mutation. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations have greater heterogeneity in immune microenvironment characteristics such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB). Whether ICIs is suitable for NSCLC patients with EGFR mutation has been controversial. Clinical studies have shown that immunomonotherapy has no significant effect on patients with EGFR mutant NSCLC. ICIs combined with chemotherapy and antiangiogenic drugs show good survival benefits. This paper overviews the clinical research and related mechanism of ICIs single drug or combination therapy inadvanced NSCLC patients with EGFR mutation.â©.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Microambiente TumoralRESUMO
To extend the applications of glutinous rice bran, a by-product of the glutinous rice processing industry, soluble dietary fibers (SDF) isolated from Chinese white (WSDF) and black (BSDF) glutinous rice bran were compared for their structures, physicochemical properties, and hypoglycemic activities in this study. Results showed that BSDF had higher glucose content while lower rhamnose, arabinose, xylose, and mannose contents, similar molecular weight, and a particular presence of anthocyanin compared to WSDF. Owing to the smaller particle size, higher viscosity, and more abundant network structures, BSDF had higher glucose adsorption capacity and retarding glucose diffusion ability than WSDF. The evaluations in vitro kinetics showed that addition of BSDF in starch led to a smaller glucose absorption rate constant and expected glucose index than WSDF, although BSDF showed lower α-amylase inhibitory ability. Interactions between the SDF and α-amylase, which were mediated by van der Waals force and hydrogen bond (WSDF-α-amylase) and hydrophobic interaction (BSDF-α-amylase), induced partial transformation of α-amylase from α-helix and ß-sheet to ß-turn and random coil. In summary, both WSDF and BSDF could be used as natural food additives for the reduction of postprandial blood glucose level and the enhancement of antioxidant activity in food products, while BSDF may show better efficacy.
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Oryza , Fibras na Dieta/farmacologia , Glucose/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Oryza/química , alfa-AmilasesRESUMO
In this study, two chemical bean seed hardening methods were used to investigate the changes in cooking behavior associated with Ca2+ transport and phytate hydrolysis to better understand their role in the pectin-cation-phytate hypothesis. The texture evolution of fresh and hardened red kidney beans was evaluated, hardening being induced by soaking or in a CaCl2 solution (0.01 M, 0.05 M, 0.1 M) or sodium acetate buffer (0.1 M, pH 4.4, 41 °C). The beans soaked in a CaCl2 solution at higher concentrations or in sodium acetate buffer for a longer time exhibited a delayed cooking behavior. This study also explored the bio-chemical changes (calcium content in different bean substructures, phytate content and the pectin degree of methylesterification (DM) in the cotyledons) occurring in the beans during chemical hardening and cooking. The Ca2+ concentrations in the whole beans and cotyledons of beans soaked and cooked in CaCl2 solutions significantly increased while inositol hexaphosphate IP6 content showed no significant changes. This indicates that the delayed texture drop in this case results from the influx of exogenous Ca2+ in the cotyledons and seed coats during cooking while the IP6 was not hydrolyzed and did not release endogenous Ca2+. For beans soaked in sodium acetate buffer, phytate profiling showed increased hydrolysis of IP6 with longer soaking time, suggesting the migration of endogenous Ca2+ released from phytate hydrolysis contributing to the delayed cooking of these beans. These results indicate that both an exogenous Ca2+ influx during soaking and cooking and an endogenous Ca2+ replacement resulting from phytate hydrolysis can play an important role in the hardening of beans. In neither of the cases, a significant change in pectin DM was observed during chemical hardening, therefore limiting the delayed cooking to the role of Ca2+ transport. The outcome of both cases is inline with the basic principles of the pectin-cation-phytate hypothesis whereby pectin DM changes are hardly involved and different mechanisms of release/transport are involved.
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Phaseolus , Ácido Fítico , Cálcio/análise , Cloreto de Cálcio , Cátions , Manipulação de Alimentos/métodos , Temperatura Alta , Hidrólise , Pectinas/química , Phaseolus/química , Ácido Fítico/análise , Sementes/química , Acetato de Sódio/análise , Água/químicaRESUMO
Purpose: The purpose of this study was to introduce a novel dry eye rat model induced by aerosol exposure of particulate matter (PM). Methods: A total of 30 female Sprague Dawley (SD) rats divided into 3 groups: the control group, the low-level exposed group, and the high-level exposed group. The rats in the experience groups were directly exposed to PM samples in the exposure chamber over 14 days. The clinical observation, including tear volume, corneal fluorescein staining, breakup time (BUT), inflammation index, corneal irregularity score, and corneal confocal microscopy. Eyeballs were collected on day 14 for hematoxylin and eosin (H&E) staining and PAS staining. TUNEL assay, CD45, and Ki67 immunostaining was performed and corneal ultrastructural changes were detected by electron microscopy. IL-1ß, TNF-α, IFN-γ, and NF-κB Western blot analysis were used to observe the possible pathogenesis. Results: In the PM-treated groups, the number of layers in the corneal epithelium and corneal nerve fiber length were significantly decreased compared with that of the control group. The number of corneal epithelial microvilli and chondriosome/desmosomes were drastically reduced in PM-treated groups. Confocal microscopy and CD45 immunohistochemistry showed inflammatory cell infiltration in the PM-treated groups. PM caused apoptosis of corneal and conjunctival epithelial cells while leading to abnormal epithelial cell proliferation, meanwhile, conjunctival goblet cells in the PM-treated group were also significantly reduced. PM significantly increased the levels of IL-1ß, TNF-α, IFN-γ, and p-NF-κB-p65 in the cornea. Conclusions: Aerosol exposure of PM can reduce the stability of tear film and cause the change of ocular surface, which is similar to the performance of human dry eye, suggesting a novel animal model of dry eye.