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1.
World Neurosurg ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001411

RESUMO

BACKGROUND: A pressure wire offers a dynamic tool to assist in the measurement of the pressure gradient and assessment of the functional significance of stenosis. The author presents a patient with idiopathic intracranial hypertension(IIH) who was diagnosed with cerebral venous sinus stenosis (CVSS). Venography accompanied by pressure measurement was utilized to guide the stent placement for CVSS. CASE DESCRIPTION: A 27-year-old woman was referred to our hospital with a chief complaint of headache and neckache lasting for seven weeks, with an 8-day history of binocular diplopia and blurred vision. Magnetic resonance venography (MRV) and digital subtraction angiography (DSA) showed a filling defect in the right transverse sinus. A pressure wire was used before endovascular treatment and showed that the pressure gradient was 10mmHg, which meets the surgical indication. After a stent was placed, no pressure gradient was recorded by the pressure wire. CONCLUSIONS: This is the first report of use of a pressure wire for CVSS. The finding suggests that use of a pressure wire can be a new approach in the diagnosis and treatment of CVSS.

2.
Opt Lett ; 45(3): 682-685, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004284

RESUMO

Phase memory is an effect in which the interaction between a coherent pump beam and a nonlinear crystal generates photon pairs via the spontaneous parametric down-conversion process, then the down-converted photons (signal and idler) can carry the phase information of the pump beam. There has been much research on the memory of the dynamic phase so far; however, there is no report on the memory of non-dynamic phase, to the best of our knowledge. Here we acquire a Pancharatnam-Berry (PB) geometric phase in a physical system when light travels along a trajectory in polarization-state space. Induced coherence occurs in a cascaded scheme composed of two nonlinear crystals, when the idler photons in both crystals are aligned to be indistinguishable. A NOON ($N\; = \;{2}$N=2) state is established when blocking the two idler photons. We explore the PB geometric phase memory of the NOON state and induced coherence. We find that the first-order interference of the two-photon state or signal photons can be controlled by introducing the PB geometric phase to the pump light. This may facilitate precise control of the phase of the down-converted photons.

3.
Medicine (Baltimore) ; 99(7): e19179, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049851

RESUMO

RATIONALE: Polyglandular autoimmune syndromes (PAS) are a heterogeneous group of rare diseases characterized by the association of at least 2 organ-specific autoimmune disorders, concerning both the endocrine and nonendocrine organs. Type III is defined as the combination of autoimmune thyroid disease and other autoimmune conditions (other than Addison disease), and is divided into 4 subtypes. We describe a patient with Hashimoto thyroiditis, adult-onset Still disease, alopecia, vasculitis, antineutrophil cytoplasmic antibody (ANCA)-mediated crescentic glomerulonephritis, and hyperparathyroidism. Co-occurrence of these 5 diseases allowed us to diagnose PAS type IIIc. The rare combination of these different diseases has not been reported before. PATIENT CONCERNS: A 51-year-old woman was admitted in April, 2019 after the complaint of an enlarged thyroid. She was diagnosed with Hashimoto thyroiditis at the age of 36. At age 40, she was diagnosed with an adult-onset Still disease. Three months before admission, she experienced renal insufficiency. After admission, she was diagnosed with hyperparathyroidism. DIAGNOSIS: Renal biopsy revealed renal vasculitis and crescentic nephritis. Antineutrophil cytoplasmic autoantibody showed that human perinuclear ANCA and myeloperoxidase ANCA were positive. Therefore, the patient was diagnosed with vasculitis and ANCA-mediated crescentic glomerulonephritis. After admission, parathyroid single-photon emission computed tomography/computed tomography fusion image demonstrated the presence of hyperparathyroidism. INTERVENTIONS: The patient was treated with high-dose methylprednisolone pulse therapy (0.1 g/d) for vasculitis and ANCA-mediated crescentic glomerulonephritis, calcium and vitamin D3 (600 mg/d elemental calcium [calcium carbonate] and 2.5 µg/d active vitamin D3) for hyperparathyroidism, and levothyroxine sodium (50 ug/d) for Hashimoto thyroiditis. OUTCOMES: Up to now, serum thyroid-stimulating hormone, total triiodothyronine, total thyroxine, free triiodothyronine, and free thyroxine were within the normal ranges. Patient's renal function did not deteriorate. LESSONS: We report a patient with Hashimoto thyroiditis, adult-onset Still disease, alopecia, vasculitis, ANCA-mediated crescentic glomerulonephritis, and hyperparathyroidism, which is a very rare combination. We present this case as evidence for the coexistence of several different immune-mediated diseases in the clinical context of a PAS IIIc.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 160-164, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027270

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of microRNA-195 in patients with diffuse large B cell lymphoma(DLBCL). METHODS: Sixty patients with DLBCL were selected from nearly four years in our hospital, and at the same time 30 healthy people with physical examination of the same period and with the same age in our hospital were choosed as control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the miR-195 expression of the patients and controls, the relationship between miR-195 expression and clinicopathological characteristics of DLBCL and survival time of patients was analyzed. RESULTS: The expression level of miR-195 in DLBCL patients was significantly lower than that in the controls (P<0.001). The expression level of miR-195 closely related with tumor diameter, IPI score and Ann Arbor stage of patients with DLBCL. Overall survival(OS) time of DLBCL patients with highly expressed miR-195 was significantly longer than that of patients with low expression (P<0.001). CONCLUSION: miR-195 expression decrease in DLBCL patients, and miR-195 closely relates with tumor characteristics of patients with DLBCL. DLBCL patients with higher expression of miR-195 show longer overall survival time.

5.
Chemistry ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011778

RESUMO

Supercapacitors have attracted tremendous research interest since they are expected to achieve battery-level energy density while having long calendar life and short charging time. In this work, we have successfully assembled a novel asymmetric supercapacitor using NiCo2S4 nanosheets and spinous Fe2O3 nanowires modified hollow melamine foam (MF) decorated with polypyrrole (PPY) as positive and negative electrodes, respectively. Owning to the well-designed nanostructure and the suitable matching of electrode materials, the assembled asymmetric supercapacitors (ASC) exhibits an extended operation voltage window of 1.6 V with the energy density of 20.1 W h kg-1 at a power density of 159.4 kW kg-1. Moreover, the ASC shows stable cycling stability with 81.3% retention after 4000 cycles and a low internal resistance Rs of 1.03 Ω. Additionally, a 2.5 V LED indicator can be lit up by three ASCs connected in series, evidencing the practical application potential of the assembled energy storage system. The excellent electrochemical performances should be credited to the significant enhancement of the specific surface area, charge transport and mechanical stability resulted from the unique 3D-morphology.

6.
Medicine (Baltimore) ; 99(5): e18851, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000386

RESUMO

BACKGROUND: The pathogenesis of cervical spondylotic is degenerative changes of the cervical intervertebral disc, or bone hyperplasia of the posterior and hook joints, and instability of the joints of the cervical vertebrae. It causes the nerve roots to be stimulated and oppressed. The clinical manifestations are the sensation, movement, and reflex disorder of the cervical spinal nerve roots that are stimulated and oppressed, especially the numbness and pain of the neck, shoulders, upper limbs, and fingers. In this systematic review, we aimed to evaluate the efficacy and safety of acupuncture and chiropractic in the treatment of cervical spondylotic. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, Embase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to September 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the RevMan 5.3 and Stata 13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of cervical spondylotic. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture and chiropractic for cervical spondylotic. Because all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process trial.


Assuntos
Terapia por Acupuntura , Manipulação Quiroprática , Radiculopatia/terapia , Humanos , Radiculopatia/etiologia , Espondilose/complicações
7.
Food Chem ; 315: 126268, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32018083

RESUMO

Starch digestion in pulse cellular matrices is primarily determined by the hindrance of cell walls limiting enzyme diffusion as well as the retention of starch granular structure. However, the effect of hydrothermal treatment on structure and digestion properties of entrapped pulse starches is not fully elucidated. In present study, we reported the variations in structure and enzyme susceptibility of pulse cells isolated at 60 °C followed by heated at 70, 80, 90, 100 °C, which were higher than the starch gelatinization temperature. Based on the thermal and crystalline properties, entrapped starches in pulse cells were not fully gelatinized even treated at 100 °C. Whilst, the digestion of entrapped pulse starches increased with higher temperature, but still much lower than the isolated starch treated at the same temperature. In addition to physical barriers (intact cell wall) and starch structural features (partial ordered crystalline structure), the soluble/insoluble proteinaceous materials in cells also synergistically reduced the starch digestibility.

8.
Chemosphere ; 248: 126053, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32041067

RESUMO

Nitrogen-containing carbon materials (NCC-x) are promising metal-free catalysts for activation of peroxymonosulfate (PMS) to treat with aqueous organic pollutants. In this study, NCC-x were synthesized via a facile thermal polymerization method using urea and terephthalaldehyde as precursors. This method was derived from the polymerization method of graphitic carbon nitride (g-C3N4) and the reaction between the precursors was based on Schiff base chemistry. Compared with the synthesis of g-C3N4 using urea as the precursor, formation of a melamine ring was inhibited and the cyano groups were produced in NCC-x during the polymerization process. The obtained NCC-x catalysts had high specific surface areas, many graphite-nitrogen active sites, and high degrees of graphitization, thus exhibiting excellent activities for the degradation of bisphenol A via PMS activation. This study introduces a convenient method to obtain a highly efficient nitrogen-containing carbon PMS activator and the results are useful for the development of bisphenol A treatment by PMS activation using carbon-containing materials.

9.
JCI Insight ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027623

RESUMO

Recent studies have presented compelling evidence that it is not tissue-resident, but rather monocyte-derived alveolar macrophages (TR-AMs vs. Mo-AMs) are essential to development of experimental lung fibrosis. However, whether Apolipoprotein E (ApoE), which is produced abundantly by Mo-AMs in the lung, plays a role in the pathogenesis is unclear. In this study, we found that pulmonary ApoE was almost exclusively produced by Mo-AMs in mice with bleomycin induced lung fibrosis. We showed although ApoE was not necessary for developing maximal fibrosis in bleomycin injured lung, it was required for the resolution of this pathology. We found that ApoE directly bound to Collagen I and mediated Collagen I phagocytosis in vitro and in vivo, and this process was dependent on low density lipoprotein receptor-related protein 1 (LPR1). Furthermore, interference of ApoE/LRP1 interaction impaired the resolution of lung fibrosis in bleomycin treated wild-type mice. In contrast, supplementation of ApoE promoted this process in ApoE-/- animals. In conclusion, Mo-AM derived ApoE is beneficial to the resolution of lung fibrosis, supporting the notion that Mo-AMs may have distinct functions in different phases of lung fibrogenesis. The findings also suggest a novel therapeutic target for treating lung fibrosis, to which effective remedies remain scarce.

10.
Sci Rep ; 10(1): 2070, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034196

RESUMO

Non-small cell lung cancer (NSCLC) is featured with complex genomic alterations. Molecular profiling of large cohort of NSCLC patients is thus a prerequisite for precision medicine. We first validated the detection performance of a next-generation sequencing (NGS) cancer hotspot panel, OncoAim, on formalin-fixed paraffin-embedded (FFPE) samples. We then utilized OncoAim to delineate the genomic aberrations in Chinese NSCLC patients. Overall detection performance was powerful for mutations with allele frequency (MAF) ≥ 5% at >500 × coverage depth, with >99% sensitivity, high specificity (positive predictive value > 99%), 94% accuracy and 96% repeatability. Profiling 422 NSCLC FFPE samples revealed that patient characteristics, including gender, age, lymphatic spread, histologic grade and histologic subtype were significantly associated with the mutation incidence of EGFR and TP53. Moreover, RTK signaling pathway activation was enriched in adenocarcinoma, while PI(3)K pathway activation, oxidative stress pathway activation, and TP53 pathway inhibition were more prevalent in squamous cell carcinoma. Additionally, novel co-existence (e.g., variants in BRAF and PTEN) and mutual-exclusiveness (e.g., alterations in EGFR and NFE2L2) were found. Finally, we revealed distinct mutation spectrum in TP53, as well as a previously undervalued PTEN aberration. Our findings could aid in improving diagnosis, prognosis and personalized therapeutic decisions of Chinese NSCLC patients.

11.
Br J Pharmacol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034757

RESUMO

BACKGROUND AND PURPOSE: Immunotherapeutic intervention is one of the most promising strategies for the prevention and treatment of Alzheimer's disease (AD). Although they showed great success in AD mouse models, the clinical trials of many immune approaches failed due to low efficacy and safety. Thus, an animal model which can show the potential side effects of vaccines or antibodies is urgently needed. In this study, we generated EAE/AD mice by crossing APP/PS1 mice with experimental autoimmune encephalomyelitis (EAE) mice. We then investigated the efficacy and safety of two vaccines, the immunogens of which were Aß1-42 aggregates (Aß42 vaccine) and an oligomer-specific conformational epitope (AOE1 vaccine), respectively. EXPERIMENTAL APPROACH: EAE/AD mice were immunized with the Aß42 vaccine or AOE1 vaccine five times at biweekly intervals. After the final immunization, the cognitive function of the mice was evaluated by the Morris water maze, Y-maze, and object recognition tests. Neuropathological changes in the mouse brains were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay. KEY RESULTS: In contrast to previous findings in conventional AD animal models, Aß42 immunization promoted neuroinflammation, enhanced Aß levels and plaque burden, and failed to rescue cognitive deficits in EAE/AD mice. By contrast, AOE1 immunization dramatically attenuated neuroinflammation, reduced Aß levels, and improved cognitive performance in EAE/AD mice. CONCLUSIONS AND IMPLICATIONS: These results suggest that the EAE/AD mouse model can exhibit the potential side effects of AD immune approaches that conventional AD animal models fail to display. Furthermore, strategies specifically targeting Aß oligomers may be safe and show clinical benefit for AD treatment.

12.
Int J Biol Macromol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057848

RESUMO

The functional properties and physiological functions of whey protein isolate (WPI) decreased near its isoelectric point (PI). The Maillard reaction covalently binding polysaccharides to proteins is an effective method to improve the functional activities of proteins. WPI-inulin conjugates were prepared by wet-heating method at 70 °C for 2 h, 4 h and 6 h, respectively. New bonds at higher molecular zone appearing at SDS-PAGE, decreased free amino acid content and new formed CN bonds in FT-IR of conjugates compared with WPI confirmed the formation of the covalent bonds between WPI and inulin. As the increase of the reaction time, both the brown intensity and fluorescence intensity of WPI-inulin conjugates became higher. Amino acid contents, Circular dichroism analysis and SEM analysis presented the primary structure, secondary structure and surface structure change of protein after covalent with inulin. Emulsion properties of emulsion activity (EAI) and emulsion stability (ES) of WPI-inulin conjugates were assessed and both showed significantly enhanced compared with WPI at range of pH 3 to pH 7. AAPH+ scavenging test and ORAC measurement also revealed that covalent binding with inulin enhanced the antioxidant activities of WPI. This work presented the conjugation with inulin successfully enhanced the functional properties of WPI.

13.
Int J Biol Macromol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057851

RESUMO

Nitroreductase (NTR), a member of the flavoenzyme family, could react with nicotinamide adenine dinucleotide by reducing nitro to amino at hypoxic tumor, which can be monitored by some fluorescent probes in vivo. Here, molecular docking and molecular dynamics simulation techniques were used to explore the molecular mechanisms between NTR and probes. The results showed that formation of hydrogen bond in 1F5V-13 between A@His215 and B@Ser41 with 74.53% occupancy might be the main reason for the decrease of probe fluorescence emission in experiment. Moreover, Probe 16 was rotated by nearly 60 degrees with respect to the position of other probes in protein binding pocket, deforming the protein active pocket, changing the hydrogen bond formation, which leads to the fluorescence performance of 16 with electron donor and electron acceptor groups was superior to other probes in experiment. The deformation of protein active pocket and the formation of intramolecular hydrogen bonds revealed the difference in performance of NTR fluorescent probe at molecular level, which provide theoretical guidance for latter design of fluorescent probes with better performance.

14.
Anal Chem ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030974

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, which is demanding powerful diagnosis tools. Although the traditionally used serological biomarker alpha-fetoprotein (AFP), cannot meet the accuracy requirements of disease diagnosis, its isoform alpha-fetoprotein L3 (AFP-L3) ratio in total AFP is emerging as a highly specific alternative for the accurate diagnosis. The routine electrophoretic blotting methods for analyzing AFP-L3 isoform ratio are reliable but often lack of speediness, sensitivity or accuracy. Herein, an elemental mass spectrometric strategy was established to simultaneously detect total AFP and AFP-L3 for the accurate HCC diagnosis. The metal isotopes inside colloidal gold nanoparticles (AuNPs) and colloidal silver nanoparticles (AgNPs) reporters were used to sensitively detect total AFP and AFP-L3, respectively. AFP-L3 and total AFP were accurately and simultaneously detected with the limits of detection (LODs) of 0.1 ng mL-1 and 0.2 ng mL-1, respectively. The proposed method was successfully validated in a series of human serum samples. The assay procedure was greatly simplified and less time-consuming for the AFP-L3 isoform ratio evaluation, when compared to clinical routine chromatographic/electrophoretic methods. Thanks to the highly multiplex ability of mass spectrometry, the proposed method possesses great potential for the analysis of multiple isoforms of various disease biomarkers.

15.
Food Funct ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043503

RESUMO

Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggregates of HTT, which leads to neuronal dysfunction and death. Therapies to lower mutant HTT (mHTT) and its aggregates appear to be the most promising strategies. Ellagic acid (EA) has been marketed as a dietary supplement with various claimed benefits and neuroprotective effects on several neurodegenerative disorders, while its effect on mHTT pathology is still unknown. Here we reported that EA significantly attenuated motor and cognitive deficits in R6/2 mice. Moreover, EA significantly lowered mHTT levels, reduced neuroinflammation, rescued synapse loss, and decreased oxidative stress in R6/2 mouse brains. These findings indicated that EA has promising therapeutic potential for HD treatment.

16.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32053943

RESUMO

The phenolic profiles, hypoglycemic activity, and molecular mechanism of the effect on type 2 diabetes mellitus (T2DM) of four highland barley varieties were investigated in the present study. The fundamental phenolics in highland barley were ferulic acid, naringin, and catechin, which mainly existed in bound form. These varieties showed favorable hypoglycemic activity via inhibition of α-glucosidase and α-amylase activities, enhancement of glucose consumption, glycogen accumulation and glycogen synthase 2 (GYS2) activity, and down-regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities. Specifically, ZQ320 variety exhibited the strongest hypoglycemic activity compared to the other varieties. Highland barley phenolics could inhibit gluconeogenesis and motivate glycogen synthesis via down-regulating the gene expression of G6Pase, PEPCK, and glycogen synthase kinase 3ß (GSK3ß), while activating the expression of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), serine/threonine kinase (Akt), GYS2, and glucose transporter type 4 (GLUT4). Therefore, phenolics from highland barley could be served as suitable candidates for therapeutic agent in T2DM to improve human health.

17.
Chem Commun (Camb) ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016209

RESUMO

Small-sized semiconducting polymer dots (Pdots) provide better tissue and subcellular penetration while minimizing unspecific interactions, and make the fast clearance of Pdots from human bodies possible by urinary excretion. We employ a powerful and scalable technology, flash nanoprecipitation, to prepare Pdots with small sizes (hydrodynamic diameters ∼10 nm).

18.
Int Immunopharmacol ; 81: 106258, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044660

RESUMO

While imiquimod (IMQ) has been widely used in dermatology, its side effect manifested as dermatitis couldn't be ignored. However, the underlying mechanism has not been fully understood. Considering the clinical features of IMQ-related dermatitis similar to pseudo-allergic reaction and the presence of large numbers of mast cell in tissues treated with IMQ, the possibility that IMQ-related dermatitis mediated by mast cell-specific Mas-related G protein-coupled receptor X2 (MRGPRX2) should be addressed. To investigate the role of MRGPRX2 in vivo, MrgprB2, the mice homology of human MRGPRX2, was detected in IMQ-induced dermatitis mouse model. Histopathological changes including mast cell degranulation and footpad swelling were assayed in wild-type and MrgprB2-/- mice. The results showed that IMQ application induced dermatitis and footpad swelling with inflammatory cells infiltration plus mast cell activation in the skin of wild-type mice but reduced significantly in MrgprB2-/- mice. Further, compared to wild-type mice, serum histamine and inflammatory cytokine levels were compromised in MrgprB2-/- mice treated with IMQ, while the serum IgE level didn't change significantly. In vitro studies, levels of mediators released from murine peritoneal mast cells (MPMCs) after IMQ treatment were increased in a dose-dependent manner, which were much mild in MPMCs from MrgprB2-/- mice. Intracellular Ca2+ concentration was increased in a dose dependent manner after IMQ treatment both in MrgprB2-HEK293 and MRGPRX2-HEK293 cells. Moreover, ß-hexosaminidase released after IMQ treatment was blocked by siRNA directed at the MRGPRX2 receptor in LAD2 cells. In summary, MrgprB2 /MRGPRX2 mediate mast cell activation and participate in IMQ-related dermatitis.

19.
Toxicol Appl Pharmacol ; : 114921, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061592

RESUMO

Angioedema may occur during local anesthetic (LA) injection in the perioperative period. Histaminergic angioedema is the most common form of angioedema. It has been reported that LA is a potential exogenous ligand for histamine receptor 1 (H1R). Whether H1R participates in LA-induced angioedema is still controversial. By using a constructed H1R high-expressed cell model, siRNA transfection, pharmacologic means, and genetically modified animal models, here we showed that H1R mediated LA-induced hyperpermeability. LA with uncycled N-methyl scaffold in the side chain (procaine, tetracaine and lidocaine) had a better strength of drug-H1R affinity than that for LA with cycled N atom (bupivacaine and ropivacaine) by the molecular docking assay and equilibrium dissociation constant (KD values) obtained from the cell membrane chromatography (CMC) relative standard method. Procaine, tetracaine, and lidocaine triggered big calcium mobilization in H1R-HEK293 cells and human umbilical vein endothelial cells (HUVECs) but much weaker in NC-HEK293 cells or H1R knockdown HUVECs. Besides, the results of transendothelial resistance measurement, paracellular flux assay and immunofluorescence showed that procaine induced H1R-dependent hyperpermeability, which involved in PLCγ/IP3R/PKC, ERK1/2, Akt signaling pathways, downstream vascular endothelial cadherin (VE-cad) destabilization. Furthermore, H1R gene knockout prevented paw swelling and vascular leakage caused by procaine, tetracaine, and lidocaine in vivo. This study supported a key role of H1R in LA-induced angioedema, and suggested that in the design of LA structure, the ring formation of the N-methyl scaffold on the side chain can properly avoid the angioedema.

20.
Molecules ; 25(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952185

RESUMO

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan.

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