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1.
Int J Biol Macromol ; 271(Pt 2): 132592, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38820905

RESUMO

Torreya grandis wax (TGW), a new nut wax and by-product of refined Torreya grandis oil, lacks sufficient research and application. In this study, the gelling behavior in diacylglycerol (DAG) and chemical compositions of TGW were investigated. Compared with four typical natural waxes, TGW exhibited the lowest critical gelling concentration (Cg, 1 %wt) in DAG. The results performed that TGW-DAG oleogels at Cg possessed the highest G'LVR and G″, highest critical stress, good thermal stability, moderate viscosity recovery, and osc. yields stress, indicating strong gel. The microstructure and correlation analysis revealed that excellent gelling behaviors of TGW-DAG oleogels were due to the solid three-dimensional network formed by rod-like TGW crystal, and the higher hydrocarbon compound (HC) content and HC/wax ester in TGW. Formulation optimization suggested that oleogel containing 3.2 % TGW and 1.0 % diosgenin (DSG) better mimicked the characteristics of shortening in terms of hardness, adhesiveness, spreadability. The bread prepared with TGW/DSG-DAG oleogel owned uniform and dense pores, the best moisture retention capability, and soft and firm taste, demonstrating that TGW/DSG-DAG oleogel was a good shortening substitute. Therefore, this study provides the systematically fundamental knowledge of TGW and develops DSG-TGW-DAG oleogels as promising shortening substitutions.


Assuntos
Diglicerídeos , Géis , Compostos Orgânicos , Ceras , Ceras/química , Diglicerídeos/química , Compostos Orgânicos/química , Géis/química , Viscosidade , Reologia
2.
Nat Commun ; 15(1): 3759, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704384

RESUMO

Millimeter-scale soft continuum robots offer safety and adaptability in transluminal procedures due to their passive compliance, but this feature necessitates interactions with surrounding lumina, leading to potential medical risks and restricted mobility. Here, we introduce a millimeter-scale continuum robot, enabling apical extension while maintaining structural stability. Utilizing phase transition components, the robot executes cycles of tip-based elongation, steered accurately through programmable magnetic fields. Each motion cycle features a solid-like backbone for stability, and a liquid-like component for advancement, thereby enabling autonomous shaping without reliance on environmental interactions. Together with clinical imaging technologies, we demonstrate the capability of navigating through tortuous and fragile lumina to transport microsurgical tools. Once it reaches larger anatomical spaces such as stomach, it can morph into functional 3D structures that serve as surgical tools or sensing units, overcoming the constraints of initially narrow pathways. By leveraging this design paradigm, we anticipate enhanced safety, multi-functionality, and cooperative capabilities among millimeter-scale continuum robots, opening new avenues for transluminal robotic surgery.


Assuntos
Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Desenho de Equipamento , Robótica/instrumentação , Robótica/métodos , Campos Magnéticos , Microcirurgia/instrumentação , Microcirurgia/métodos , Animais , Magnetismo
3.
Reprod Sci ; 31(3): 832-839, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37831368

RESUMO

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Previous studies have suggested that metabolites may play a pivotal mediating role in the progression of phenotypic variations. Although several metabolites had been identified as potential markers for PCOS, the relationship between blood metabolites and PCOS was not comprehensively explored. Previously, Pickrell et al. designed a robust approach to infer evidence of a causal relationship between different phenotypes using independently putative causal SNPs. Our previous paper extended this approach to make it more suitable for cases where only a few independently putative causal SNPs were identified to be significantly associated with the phenotypes (i.e., metabolites). When the most significant SNPs in each independent locus (the independent lead SNPs) with p-values of < 1 × 10-5 were used, 3 metabolites (2-tetradecenoyl carnitine, threitol, 1-docosahexaenoylglycerophosphocholine) causally influencing PCOS and 2 metabolites (asparagine and phenyllactate) influenced by PCOS were identified, (relative likelihood r < 0.01). Under a less stringent threshold of r < 0.05, 7 metabolites (trans-4-hydroxyproline, glutaroyl carnitine, stachydrine, undecanoate, 7-Hoca, N-acetylalanine and 2-hydroxyisobutyrate) were identified. Taken together, this study can provide novel insights into the pathophysiological mechanisms underlying PCOS; whether these metabolites can serve as biomarkers to predict PCOS in clinical practice warrants further investigations.


Assuntos
Hiperandrogenismo , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/genética , Estudo de Associação Genômica Ampla , Fenótipo , Carnitina
4.
Food Chem Toxicol ; 183: 114200, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029872

RESUMO

2-tert-butyl-1,4-benzoquinone (TBBQ), a degradation product of lipid antioxidant Tert-Butylhydroquinone (TBHQ), is a new hazardous compound in foods. This study investigated whether co-ingestion of dietary protein and TBBQ can alleviate the toxicity of TBBQ. The results indicated that soy protein isolate, whey protein isolate, and rice protein significantly reduced the residual amount of TBBQ during simulated gastrointestinal digestion. This result was attributed to the excellent elimination capacity of the released amino acids for TBBQ through formation of adducts. Among 20 amino acids, histidine, lysine, glycine, and cysteine showed better elimination capacity for TBBQ; they can eliminate 92.1%, 89.4%, 86.1%, and almost 100%, respectively, in 5 min at pH 8.0. Further study indicated that amino acids with lower ionization constant exhibited greater TBBQ elimination capacity. In addition, incubation of the cells with 50 µM TBBQ for 12 h decreased the cell viability to 28.95 ± 3.25%; while amino acids intervention was involved in the alleviation of TBBQ cytotoxicity via decreasing ROS. Particularly, cysteine showed 100 times more TBBQ detoxifying capacity than other amino acids. This work could provide a theoretical basis for the potential application of amino acids for detoxifying TBBQ in the food industry.


Assuntos
Aminoácidos , Cisteína , Cisteína/farmacologia , Proteínas Alimentares , Digestão
5.
Food Sci Biotechnol ; 32(14): 2043-2055, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37860735

RESUMO

Gardenia jasminoides Ellis, a representative for "homology of medicine and food", can be used to produce pigment and edible oil. Here, aqueous enzymatic extraction (AEE) combined with puffing pre-treatment was explored to prepare oil from gardenia seeds. Both wet-heating puffing (WP) at 90 °C and dry-heating puffing (DP) at 1.0 MPa facilitated the release of free oil by AEE, resulting in the highest free oil yields (FOY) of 21.8% and 23.2% within 3 h, much higher than that of un-puffed group. Additionally, active crocin and geniposide were also completely released. The FOY obtained was much higher than mechanical pressing method (10.44%), and close to solvent extraction (25.45%). Microstructure analysis indicated that gardenia seeds expanded by dry-heating puffing (1.0 MPa) had a larger, rougher surface and porous structure than other groups. Overall, AEE coupled with puffing pre-treatment developed is an eco-friendly extraction technology with high efficiency that can be employed to oil preparation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01319-9.

6.
Food Chem X ; 18: 100679, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37179978

RESUMO

D2O-assisted moisture analysis of edible oils was investigated. The acetonitrile extract of the oil samples was split into two parts. The spectrum of one part was taken as is, another was recorded after addition of excess D2O. Changes in spectral absorption of the H-O-H bending band (1600-1660 cm-1) was used to calculate moisture in oil samples. To effectively depleting absorption of water in the acetonitrile extract, a 30-fold excess of D2O is required. The typical OH-containing constituents in oil did not show significant interference on the H/D exchange. Validation experiments by using five oils with five levels of moisture spiked (50-1000 µg/g) suggested that the prediction tracked the spiked amounts well. The results of variance analysis indicate that there is no difference in terms of analytical methods and oil types used (p < 0.001). The D2O method developed is generally applicable to the accurate analysis of moisture at trace levels (<100 µg/g) in edible oils.

7.
Food Chem ; 414: 135681, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36827778

RESUMO

Emulsification is the practical limitation of aqueous enzymatic extractions of Camellia oils. This study aimed to investigate the influence and demulsification mechanisms of isopropanol ultrasonic pretreatments and Ca2+ additions on aqueous enzymatic extractions of Camellia oils. Combining isopropanol ultrasonic pretreatments with Ca2+ flow additions obtained the highest free oil recovery (78.03 %) and lowest emulsion content (1.5 %). Results indicated that the superior demulsification performance originated from the decrease in emulsion stabilities and formations. First, demulsification pretreatments reduced the oil (14.69 %) and solid (13.21 %) fractions in emulsions to decrease the stability of as-formed emulsions. Meanwhile, isopropanol ultrasonic pretreatments extracted tea saponins (0.38 mg/mL) and polysaccharides (0.23 mg/mL), while Ca2+ combined with protein isolates (5.82 mg/mL), tea saponins (7.48 mg/mL) and polysaccharides (0.78 mg/mL) to form precipitates and reduce emulsion formation. This work could promote the practical application of aqueous enzymatic extractions of Camellia oils and enlighten the rise of advanced demulsification pretreatments.


Assuntos
Camellia , Camellia/metabolismo , 2-Propanol , Óleos de Plantas/metabolismo , Emulsões , Ultrassom , Sementes/metabolismo , Chá
8.
Food Chem ; 413: 135663, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36796264

RESUMO

This study aimed to evaluate the influence of gelation and unsaturated fatty acids on the reduced extent of lipolysis between diosgenin (DSG)-based oleogels and oils with various unsaturated fatty acids. Overall, the lipolysis of oleogels was significantly lower than oils. The highest reduced extent of lipolysis (46.23 %) was obtained in linseed oleogels (LOG) while sesame oleogels possessed the lowest (21.17 %). It was suggested LOG discovered the strong van der Waals force to induce the robust gel strength and tight cross-linked network and then increase the contact difficulty between lipase and oils. Correlation analysis revealed that C18:3n-3 was positively correlated with hardness and G' while C18:2n-6 was negative. Thus, the effect on the reduced extent of lipolysis with abundant C18:3n-3 was most significant while that rich in C18:2n-6 was least. These discoveries provided a deepening insight into DSG-based oleogels with various unsaturated fatty acids to design desirable properties.


Assuntos
Ácidos Graxos Insaturados , Óleos de Plantas , Óleos de Plantas/química , Compostos Orgânicos/química , Digestão , Ácidos Graxos
9.
Nat Commun ; 12(1): 6311, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728629

RESUMO

Machine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice.


Assuntos
Inteligência Artificial/normas , Neoplasias Colorretais/patologia , Aprendizado Profundo/normas , Neoplasias Pulmonares/patologia , Aprendizado de Máquina Supervisionado/normas , Neoplasias Colorretais/classificação , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática , Redes Neurais de Computação , Curva ROC
10.
Food Funct ; 11(5): 4193-4201, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32352125

RESUMO

tert-Butyl-p-benzoquinone (TBBQ), a metabolite of tert-butylhydroquinone from food, has cytotoxicity, the underlying mechanism of which is not clear. In this study, the viability of RAW 264.7 cells exposed to TBBQ at concentrations of 0.5-10 µg mL-1 was assayed by MTT. Results suggest that TBBQ decreased the viability in a dose-dependent manner. Monodansylcadaverine (MDC) staining results indicate the occurrence of autophagy induced by TBBQ, which was manifested by activation of LC3-II concurrent with the increased levels of Beclin1 and reduced levels of p62. Elevated lipid peroxide and decreased SOD activity by TBBQ exposure suggest the overproduction of ROS, which may account for the increase in the genotoxic stress protein p53. Both upregulation of p53 and reduction of Akt levels inhibited mTOR, which activated autophagy. Addition of 3-MA counteracted the impact of TBBQ on ATG proteins and cell viability. All of these results suggest that TBBQ induces autophagy of RAW 264.7 cells principally by inhibition of the Akt/mTOR signaling pathway, and they implicate ROS in this regulation.


Assuntos
Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética , Células RAW 264.7 , Espécies Reativas de Oxigênio , Serina-Treonina Quinases TOR/genética
11.
Biosci Biotechnol Biochem ; 84(6): 1239-1249, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32141401

RESUMO

The use of anthocyanins are limited by their chemical properties. Recent evidence suggests Cyanidin-3-O-glucoside (C3 G) liposomes via the ethanol injection method exhibit improved stability. In the current study, the characterization and cell absorption of C3 G liposomes were explored via transmission electron microscopy and flow cytometry. The internalization of the C3 G liposomes across the gastric epithelial cell monolayer (GES-1 cells) were investigated. Results showed that the particle size and encapsulation efficiency were 234 ± 9.35 nm and 75.0% ± 0.001, respectively. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content were used to evaluate the antioxidant activity of C3 G liposomes. The C3 G liposomes can obviously increased T-AOC and decreased the MDA content.Collectively, C3 G liposomes protected human GES-1 cells from gastric mucosal injury induced by H2O2 by activating the related antioxidant pathway. Our research could provide a new effective treatment strategy for the absorption of stomach drugs.Abbreviations: C3G: Cyanidin-3-O-glucoside; LP: Liposome; GES-1 cells: Human gastric epithelial cell lines; FBS: Fetal Bovine Serum; PBS: Phosphate-buffered saline; PC: Phosphatidylcholine; CH: Cholesterol; MDA: Malondialdehyde; TEM: Transmission electron microscope; FCM: Flow cytometry; FITC: Fluorescein isothiocyanate; DAPI: 4', 6-diamidino-2phenylidole; FT-IR: Fourier Transform infrared spectroscopy; PFA: Paraformaldehyde.


Assuntos
Absorção Fisiológica/efeitos dos fármacos , Antocianinas/metabolismo , Antocianinas/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Células Epiteliais/metabolismo , Mucosa Gástrica/citologia , Lipossomos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Humanos , Peróxido de Hidrogênio/farmacologia , Microscopia Eletrônica de Transmissão , Tamanho da Partícula
12.
ACS Appl Mater Interfaces ; 12(1): 1913-1923, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31802656

RESUMO

Mechanical phenotyping of complex cellular structures gives insight into the process and function of mechanotransduction in biological systems. Several methods have been developed to characterize intracellular elastic moduli, while direct viscoelastic characterization of intracellular structures is still challenging. Here, we develop a needle tip viscoelastic spectroscopy method to probe multidimensional mechanical phenotyping of intracellular structures during a mini-invasive penetrating process. Viscoelastic spectroscopy is determined by magnetically driven resonant vibration (about 15 kHz) with a tiny amplitude. It not only detects the unique dynamic stiffness, damping, and loss tangent of the cell membrane-cytoskeleton and nucleus-nuclear lamina but also bridges viscoelastic parameters between the mitotic phase and interphase. Self-defined dynamic mechanical ratios of these two phases can identify two malignant cervical cancer cell lines (HeLa-HPV18+, SiHa-HPV16+) whose membrane or nucleus elastic moduli are indistinguishable. This technique provides a quantitative method for studying mechanosensation, mechanotransduction, and mechanoresponse of intracellular structures from a dynamic mechanical perspective. This technique has the potential to become a reliable quantitative measurement method for dynamic mechanical studies of intracellular structures.


Assuntos
Permeabilidade da Membrana Celular/efeitos da radiação , Mecanotransdução Celular/genética , Biologia de Sistemas , Substâncias Viscoelásticas/química , Células HeLa/ultraestrutura , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/patogenicidade , Humanos , Mecanotransdução Celular/efeitos da radiação , Análise Espectral , Vibração/efeitos adversos , Substâncias Viscoelásticas/efeitos adversos
13.
Sci Rep ; 9(1): 10432, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320706

RESUMO

Retrospective studies have found that left upper lobectomy (LUL) may be a new risk factor for stroke, and the potential mechanism is pulmonary vein thrombosis, which more likely develops in the left superior pulmonary vein (LSPV) stump. The LSPV remaining after left pneumonectomy is similar to that remaining after LUL. However, the association between left pneumonectomy, LUL, and postoperative stroke remains unclear. Thus, we sought to analyze whether both LUL and left pneumonectomy are risk factors for postoperative stroke. We prospectively included consecutive patients who underwent resection between November 2016 and March 2018 at our institution with 6 months of follow-up. Baseline demographic and clinical data were taken. A logistic regression model was used to determine independent predictors of postoperative stroke. In our study, 756 patients who underwent an isolated pulmonary lobectomy procedure were screened; of these, 637 patients who completed the 6-month follow-up were included in the analysis. Multivariable logistic regression analysis adjusted for common risk factors showed that the LUL and left pneumonectomy were independent predictors of stroke (odds ratio, 18.12; 95% confidence interval, 2.12-155.24; P = 0.008). Moreover, diabetes mellitus also was a predictor of postoperative stroke. In conclusion, both LUL and left pneumonectomy are significant risk factors for postoperative stroke.


Assuntos
Pulmão/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/cirurgia , Fatores de Risco
14.
J Biosci Bioeng ; 128(6): 716-722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31208799

RESUMO

Aqueous enzymatic extraction of Camellia sinensis oil was studied. The results suggested that saponin removal pretreatment assisted by ultrasound was effective in decreasing emulsification and in enhancing the free oil recovery. After 70% isopropanol extraction for 30 min under ultrasound, the residue of C. sinensis seeds was further hydrolyzed with free cellulase and Alcalase for 5 h, and calcium ions were concurrently added during enzymatic hydrolysis (nCa2+: nsaponin = 1:2), and free oil recovery up to 94.14% was obtained. Separate immobilization and co-immobilization of Alcalase and cellulase were performed by alginate entrapment combined with glutaraldehyde crosslinking. Specific activity and recovery of activity for Alcalase and cellulase were acceptable. After immobilization, Alcalase and cellulase exhibited higher activity at a wider pH and temperature range. Reuse experiments of immobilized enzymes were conducted. The deactivation kinetics immobilized enzymes were simulated and half-life of immobilized enzyme was estimated. The results indicated that a magnetic supporter facilitated the recovery of immobilized enzymes from tea seed slurry, and that immobilized Alcalase and cellulase had good reusability.


Assuntos
Camellia sinensis/química , Celulase/metabolismo , Camellia sinensis/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Glutaral/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Óleos de Plantas/química , Óleos de Plantas/metabolismo , Sementes/química , Sementes/metabolismo , Temperatura
15.
Bone ; 125: 25-29, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31077850

RESUMO

Leptin, a small polypeptide hormone secreted by the adipocytes, controls body weight and gonadal function by binding to a special receptor located in the hypothalamus. Observational studies have demonstrated a controversial association between leptin and bone mineral density (BMD), and functional studies of the relationship between leptin and BMD still largely vary by different studies. Using SNPs strongly associated with leptin levels in 52,140 individuals, we conducted a two-sample Mendelian randomization study to identify whether genetically lowered leptin levels were associated with BMD by using an inverse-variance weighted method, a weighted median method, MR-Egger and Robust Adjusted Profile Score. We found that circulating leptin levels may causally decrease lumbar spine BMD (effect size = -0.45, 95% CI: -0.82, -0.083; p value = 0.016). The association estimates of circulating leptin levels on femoral neck, forearm and total body BMD were not significant. Our study suggests that genetically predicted higher circulating leptin was associated with lower LS-BMD.


Assuntos
Densidade Óssea/fisiologia , Leptina/sangue , Análise da Randomização Mendeliana/métodos , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética
16.
Brain Res Bull ; 144: 180-186, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30529367

RESUMO

Accumulated evidence has recently demonstrated that spinal cord injury (SCI) can lead to chronic damage in a wide range of brain regions. Neuregulin 1 (Nrg1) signaling has been broadly recognized as an important mechanism contributing to neural differentiation and regeneration. We here studied the effect of SCI on Nrg1 signaling in prefrontal cortex (PFC) and hippocampus (HIP) in a mouse model. As was indicated by the increased levels of GFAP and Iba-1, our results demonstrated that SCI significantly induced activation of astrocytes and microglial cells in both PFC and HIP. In addition, both western blot and morphological assay demonstrated that Nrg1 was altered in both regions at 8 weeks post SCI, which was accompanied with decreased phosphorylation levels of its cognitive receptors Neu and ErbB4. Our combined results indicated that SCI can influence Nrg1 signaling, which may contribute to the worsening of pathophysiological changes in major brain regions during SCI. These results also suggested that exogenous Nrg1 treatment may have a therapeutic role in counteracting SCI-induced brain damage.


Assuntos
Neuregulina-1/metabolismo , Córtex Pré-Frontal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Receptor ErbB-4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lobo Temporal/metabolismo
17.
Inorg Chem ; 57(9): 5669-5676, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29676900

RESUMO

Two gallium-based borates, K3Ba3Li2Ga4B6O20F (I) and Rb3Ba3Li2Ga4B6O20F (II), have been successfully grown in the M2O (M = K, Rb)-LiF-B2O3 flux. They can be recognized as the element cosubstitutions of Sr for K/Rb and Ba and of Be for Li and Ga from Sr2Be2(BO3)2O (SBBO), which uses poisonous beryllium oxide during the synthesis and crystal growth process and also exhibits the problem of structural instability. The isostructural borates crystallize into the noncentrosymmetric space group P6̅2 c, with a = 8.6398(12) Å and c = 16.827(3) Å for I and a = 8.7214(12) Å and c = 17.180(3) Å for II. In the structures, the basic anionic units are the BO3 triangles and GaO4 and LiO3F tetrahydra. These anionic units bond together through O atoms, forming the infinitely extended ∞2[LiGa2B3O12]8- single layer at the ab plane. The adjacent layers are further coupled to the ∞2[Li2Ga4B6O20F]9- double layers by means of bridged O and F atoms. Then the adjacent double layers are strongly joined together via O atoms of the GaO4 tetrahedra to form a three-dimensional skeleton, with K/Rb and Ba atoms occupying the network for charge balance. I and II have considerable second-harmonic-generation responses of about 0.7 and 0.5 as large as that of KH2PO4, respectively. In addition, the first-principles calculations were conducted to confirm that they address the structural instability issues in SBBO.

18.
J Virol ; 90(5): 2332-44, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26656705

RESUMO

UNLABELLED: High-mobility group box 1 (HMGB1) protein is a highly conserved nuclear protein involved in multiple human diseases, including infectious diseases, immune disorders, metabolic disorders, and cancer. HMGB1 is comprised of two tandem HMG boxes (the A box and the B box) containing DNA-binding domains and an acidic C-terminal peptide. It has been reported that HMGB1 enhances viral replication by binding to viral proteins. However, its role in hepatitis C virus (HCV) replication is unknown. Here, we show that HMGB1 promoted HCV replication but had no effect on HCV translation. RNA immunoprecipitation experiments indicated that the positive strand, not the negative strand, of HCV RNA interacted with HMGB1. HCV infection triggered HMGB1 protein translocation from the nucleus to the cytoplasm, in which it interacted with the HCV genome. Moreover, the A box of HMGB1 is the pivotal domain to interact with stem-loop 4 (SL4) of the HCV 5' untranslated region. Deletion of the HMGB1 A box abrogated the enhancement of HCV replication by HMGB1. Our data suggested that HMGB1 serves as a proviral factor of HCV to facilitate viral replication in hepatocytes by interaction with the HCV genome. IMPORTANCE: Hepatitis C virus (HCV) is a major global health threat, affecting more than 170 million people infection worldwide. These patients are at high risk of developing severe liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Currently, no vaccine is available. Many host factors may be implicated in the pathogenesis of HCV-related diseases. In this study, we found a novel HCV RNA-binding protein, HMGB1, that promotes HCV RNA replication. Moreover, SL4 in the 5' untranslated region of the HCV genome is the key region for HMGB1 binding, and the A box of HMGB1 protein is the functional domain to interact with HCV RNA and enhance viral replication. HMGB1 appears to play an important role in HCV-related diseases, and further investigation is warranted to elucidate the specific actions of HMGB1 in HCV pathogenesis.


Assuntos
Regiões 5' não Traduzidas , Proteína HMGB1/metabolismo , Hepacivirus/fisiologia , Interações Hospedeiro-Patógeno , RNA Viral/metabolismo , Replicação Viral , Linhagem Celular , Hepatócitos/virologia , Humanos , Ligação Proteica
19.
Mediators Inflamm ; 2015: 716315, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26146465

RESUMO

It has been reported that IFN-λs inhibit HCV replication in vitro. But the mechanisms of how IL-28A conducts antiviral activity and the functions of IL-28A-induced ISGs (IFN-stimulated genes) are not fully understood. In this study, we found that IL-28A has the antiviral effect on HCV life cycle including viral replication, assembly, and release. IL-28A and IFN-α synergistically inhibit virus replication. EPSTI1 (epithelial-stromal interaction 1), one of IL-28A-induced ISGs, plays a vital role in IL-28A-mediated antiviral activity. Furthermore, forced expression of EPSTI1 effectively inhibits HCV replication in the absence of interferon treatment, and knockdown of EPSTI1 contributes to viral enhancement. EPSTI1 can activate PKR promoter and induce several PKR-dependent genes, including IFN-ß, IFIT1, OAS1, and RNase L, which is responsible for EPSTI1-mediated antiviral activity.


Assuntos
Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Interleucinas/farmacologia , Proteínas de Neoplasias/fisiologia , 2',5'-Oligoadenilato Sintetase/fisiologia , Células Cultivadas , Hepacivirus/fisiologia , Humanos , Interferon-alfa/farmacologia , Regiões Promotoras Genéticas , Montagem de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , eIF-2 Quinase/genética , eIF-2 Quinase/fisiologia
20.
PLoS One ; 9(4): e94501, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24727952

RESUMO

The interaction between hepatitis C virus (HCV) and human hepatic innate antiviral responses is unclear. The aim of this study was to examine how human hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A protein was examined by real-time PCR or immunofluorescence respectively. The mechanisms of HCV-induced IFN-ß and apoptosis were explored. Our data showed that HLCZ01 cells supported the entire HCV lifecycle and IFN-ß and interferon-stimulated genes (ISGs) were induced in HCV-infected cells. Viral infection caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942 forced expression in HLCZ01 cells decreased ISG12a expression and subsequently suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942 expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a-mediated apoptosis. All the data indicated that innate host response is intact in HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which human hepatocytes respond to HCV infection.


Assuntos
Apoptose , Hepacivirus/fisiologia , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proteína DEAD-box 58 , RNA Helicases DEAD-box/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Imunológicos , Transdução de Sinais/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia
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