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Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.
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In the course of clinical treatment for anti-tumor, the combination of traditional Chinese medicine (TCM) and other treatment schemes can reduce toxicity and increase efficiency. The purpose of this paper is to find out the key TCM and effective components for the treatment of non-small cell lung cancer (NSCLC) and analyze its therapeutic mechanism by analyzing the prescription of TCM combined with chemotherapy for NSCLC. Firstly, the prescriptions of TCM in the randomized controlled trials combined with chemotherapy for NSCLC were collected, and the core TCM was screened by frequency statistics, association rule analysis, and cluster analysis. Then, the intersection targets of the potential effects of NSCLC and core Chinese medicine were collected, and PPI analysis and enrichment analysis were performed on the intersection targets to screen the core targets, components, and pathways. The core components were verified by molecular docking and cell experiments. In this study, 269 prescriptions were collected, among which the frequency of medication for Astragalus membranaceus (HQ, in Chinese), Wolfiporia cocos (FL, in Chinese), and Atractylodes macrocephala (BZ, in Chinese) was over 100. Association rule analysis showed that they were highly correlated and clustered into the same category in cluster analysis. Their core components were quercetin, kaempferol, and isorhamnetin. The molecular docking results of the core components with the core targets AKT1 and EGFR obtained by PPI network analysis showed that they could bind stably. KEGG analysis screened 110 pathways including PI3K-Akt; the results of CCK-8 showed that quercetin, kaempferol, and isorhamnetin could effectively inhibit the proliferation of A549 cells, and isorhamnetin had the best inhibitory effect. Isorhamnetin can inhibit the migration and invasion of A549 cells, induce apoptosis and G1 phase arrest, and decrease the expression of P-PI3K and P-AKT in A549 cells. In a word, the key TCM for the treatment of NSCLC includes HQ, FL, and BZ. and its key components quercetin, kaempferol, and isorhamnetin have potential therapeutic effects on NSCLC according to the research results.
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Currently, large amounts of agricultural solid wastes have caused serious environmental problems. Agricultural solid waste is made into biochar by pyrolysis, which is an effective means of its disposal. As the prepared biochar has a good adsorption capacity, it is often used to treat pollutants in water, such as heavy metals and pharmaceuticals. PRO is an emerging contaminant in the environment today. However, there are limited studies on the interaction between biochars with PRO. Thus, in this study, we investigate the adsorption of PRO onto the biochars derived from three different feedstocks. The order of adsorption capacity was corn stalk biochar (CS, 10.97 mg/g) > apple wood biochar (AW, 10.09 mg/g) > rice husk biochar (RH, 8.78 mg/g). When 2 < pH < 9, the adsorption capacity of all the biochars increased as the pH increased, while the adsorption decreased when pH > 9, 10 and 10.33 for AW, CS and RH, respectively. The adsorption of PRO on biochars was reduced with increasing Na+ and Ca2+ concentrations from 0 to 200 mg·L-1. The effects of pH and coexisting ions illustrated that there exist electrostatic interaction and cation exchange in the process. In addition, when HA concentration was less than 20 mg/L, it promoted the adsorption of PRO on the biochars; however, when the concentration was more than 20 mg/L, its promoting effect was weakened and gradually changed into an inhibitory effect. The adsorption isotherm data of PRO by biochars were best fitted with the Freundlich model, indicating that the adsorption process is heterogeneous adsorption. The adsorption kinetics were fitted well with the pseudo-second-order model. All the results can provide new information into the adsorption behavior of PRO and the biochars in the aquatic environment and a theoretical basis for the large-scale application of biochar from agricultural solid wastes.
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Thermal-denatured whey protein-milk fat emulsion gels with different degrees of pre-emulsification were prepared by pre-emulsifying milk fat with thermal-denatured whey protein and used in the preparation of reduced-sodium processed cheeses. The effect of the thermal-denatured whey protein pre-emulsification process on the texture and microstructure of reduced-sodium processed cheeses was evaluated by studying the composition, color, texture, functional properties, microstructure and sensory analysis of the processed cheeses. The results showed that compared with cheese without pre-emulsified fat (1.5% ES control), the moisture content of cheese with pre-emulsified 100% fat (1.5% ES100) increased by 5.81%, the L* values increased by 7.61%, the hardness increased by 43.24%, and the free oil release decreased by 38%. The microstructure showed that the particle size of fat was significantly reduced, and the distribution was more uniform. In addition, compared with the cheese added with 3% emulsifying salt (3% ES control), the amount of emulsifying salt in the 1.5% ES100 decreased by 50%, but the fat distribution of the two kinds of cheese tended to be consistent, and there was no obvious change in texture characteristics and meltability. Sensory scores increased with the increase in pre-emulsification degree. Overall, the pre-emulsification of milk fat with thermal-denatured whey protein can reduce the sodium content of processed cheese and improve its quality.
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Human beings have made significant progress in the medical field since antibiotics were widely used. However, the consequences caused by antibiotics abuse have gradually shown their negative effects. Antibacterial photodynamic therapy (aPDT) has the ability to resist drug-resistant bacteria without antibiotics, and as it is increasingly recognized that nanoparticles can effectively solve the deficiency problem of singlet oxygen produced by photosensitizers, the application performance and scope of aPDT are gradually being expanded. In this study, we used a biological template method to reduce Ag+ to silver atoms in situ with bovine serum albumin (BSA) rich in various functional groups in a 50 °C water bath. The aggregation of nanomaterials was inhibited by the protein's multistage structure so that the formed nanomaterials have good dispersion and stability. It is unexpected that we used chitosan microspheres (CMs) loaded with silver nanoparticles (AgNPs) to adsorb methylene blue (MB), which is both a pollutant and photosensitive substance. The Langmuir adsorption isothermal curve was used to fit the adsorption capacity. The exceptional multi-bond angle chelating forceps of chitosan make it have a powerful physical adsorption capacity, and dehydrogenated functional groups of proteins with negative charge can also bond to positively charged MB to form a certain amount of ionic bonds. Compared with single bacteriostatic materials, the bacteriostatic capacity of the composite materials adsorbing MB under light was significantly improved. This composite material not only has a strong inhibitory effect on Gram-negative bacteria but also has a good inhibitory effect on the growth of Gram-positive bacteria poorly affected by conventional bacteriostatic agents. In conclusion, the CMs loaded with MB and AgNPs have some possible applications in the purification or treatment of wastewater in the future.
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The self-assembling behavior of peptides and derivatives is crucial in the natural process to construct various architectures and achieve specific functions. However, the surface or interfacial self-assembly, in particular, on the surface of micro- or nanoparticles is even less systematically investigated. Here, uniform porous CaCO3 microparticles were prepared with different charged, hydrophobic and hydrophilic surfaces to assess the self-assembling behavior of dipeptides composed of various sequences. Experimental results indicate that dipeptides with a negative charge in an aqueous solution preferred to self-assemble on the hydrophobic and positively charged surface of CaCO3 particles, which can be ascribed to the electrostatic and hydrophobic interaction between dipeptides and CaCO3 particles. Meanwhile, the Logâ¯p (lipid-water partition coefficient) of dipeptides has a significant effect on the self-assembling behavior of dipeptides on the surface of porous CaCO3; dipeptides with high Logâ¯p preferred to self-assemble on the surface of CaCO3 particles, resulting in the improved cell internalization efficiency of particles with low cytotoxicity. After loading with a model drug (doxorubicin), the particles show obvious antitumor activity in animal experiments and can reduce Dox side effects effectively.
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Dipéptidos , Nanopartículas , Animales , Porosidad , Péptidos , Doxorrubicina/farmacología , Doxorrubicina/química , Nanopartículas/química , AguaRESUMEN
Taurine (Tau) is a special sulphur-containing amino acid and has been widely used as a dietary supplement. Although Tau exists in lymphocytes in large quantities, the physiological significance of Tau to modulate human immunity is unknown. In the present study, we first found that Tau regulates the B-cell receptor (BCR)-mediated signal transduction and induces the B cells activation. The IgG production of mice after ovalbumin immunization was also increased by Tau administration. Moreover, the isothermal titration calorimetry and surface plasmon resonance analysis have shown that Tau specifically bound to the IgG2a-BCR. The Tau could bind to IgG F(ab')2 regions via fluorescence spectroscopy analysis. In the molecular docking analysis, Tau bound to the framework regions (FRs) of variable region of the heavy chains (VH ) and in the light chains (VL ) of IgG2a-BCR. Our results suggested that Tau could improve the activation of B cells by interaction with the VH /VL FRs of BCR.
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Cadenas Pesadas de Inmunoglobulina , Región Variable de Inmunoglobulina , Animales , Ratones , Humanos , Cadenas Ligeras de Inmunoglobulina/química , Cadenas Ligeras de Inmunoglobulina/metabolismo , Taurina , Simulación del Acoplamiento Molecular , Receptores de Antígenos de Linfocitos B , Inmunoglobulina GRESUMEN
Poor rate capability, the biggest barrier to potential applications of electrochemical actuators (ECAs), is primarily resulted from symmetric electrochemical reactions. This makes it extremely difficult for ECAs to actuate above 1 Hz while maintaining sufficient displacement retainability compared with their actuations at relatively low frequencies, particularly when working in liquids. Here, tungsten trisulfide (WS3) assisted tungsten disulfide nano onions are synthesized through a one-step laser-assisted strategy. Using the irreversibility of WS3 in adsorbing hydrogen in an acidic solution, the electrochemical reaction of tungsten sulfide nano onions is tailored to realize an asymmetric redox reaction for breaking the symmetry of the electrical double layer and battery-like process. Experiments demonstrate that the ECA's response rate (0.24 mm-1 s-1) is at least 10 times faster than that of the previously reported ECAs. Moreover, this ECA can actuate at 30 Hz and reaches top performance in liquids at 4 Hz with long-term durability (>90% after 23 000 cycles), which is comparable to that of electromagnetic and electrothermal actuators. To understand the electrochemical actuation of tungsten sulfide from the atomic scale to the macroscopic scale, density functional theory calculations are conducted and an electrochemomechanical coupling model is proposed. A new generation of subvolt electric-driven actuators used in underwater robotics can be developed by modulating the electrochemical response and chemomechanical coupling effect.
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Soil microbial biofilms (SMBs) are a biological community of soil bacteria and their accumulative extracellular polymeric substances (EPS), which are the initial status and the most important components of biological soil crusts. SMBs, as the most common mode of soil bacterium survival, not only greatly contribute to the survival of free-living cells, but also stick to soil particles and roots, performing a variety of important ecological functions. Based on the structure and composition analysis of SMBs, we gave a summary of eco-physiological functions of SMBs involving soil quality and plant health. SMBs have higher metabolic activity than free-living cells. It promotes EPS secretion and organic turnover, which is important for soil fertility, pollutant decomposition, and aggregate formation. SMBs help improve plant nutrient utilization and stress resistance through the synergy of microorganisms, promotion of plant growth, promoting substance secretion and immobilization of EPS. In the future, it will be critical to uncover the micro-mechanisms underlying SMBs' eco-physiological functions and to screen functional soil bacterium strains.
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Microbiología del Suelo , Suelo , Bacterias , Biopelículas , Raíces de Plantas/microbiología , PlantasRESUMEN
The abuse of fluoroquinolones (FQs) antibiotics leads to bacterial resistance and environmental pollution, so it is of great significance to verify the decomposition mechanism for eliminating antibiotic efficiently and conveniently. The effects of various environmental factors and the fleroxacin (FLE) photodegradation mechanisms were investigated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), UV-Vis absorption spectroscopy, fluorescence spectroscopy and quantum chemical calculation. Six possible photodegradation reaction paths on T1 (excited triplet state) were proposed and simulated. The departure of the piperazine ring and the substitution of F atom at C-6 position by OH group were determined as the main reactions based on the reaction rates and energy barriers of each path. The multi-pathway reactions resulted in the fastest photodegradation rates of FLE at pH 6-7 than other pH conditions. NaN3 would promote FLE photodegradation by inhibiting the reverse reaction of the separation process of F atom at C-8 and the generation of biphenyl molecules, which was a novel and distinctive phenomenon in this report. ·OH would rapidly combine with the free radicals generated in photolysis processes and made a great contribution to FLE photodegradation. Ca2+, Mg2+ and Ba2+ could stabilize the carboxyl group to impede the photo-competitive process of the decarboxylation reaction, while NO3- could generate reactive oxygen species to promote photodegradation.
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Fleroxacino , Contaminantes Químicos del Agua , Antibacterianos/química , Fleroxacino/química , Fluoroquinolonas , Cinética , Fotólisis , Piperazinas , Especies Reactivas de Oxígeno , Contaminantes Químicos del Agua/químicaRESUMEN
The large conjugated system and the d orbitals of metallic phthalocyanines (MPcs) are easily triggered by solvent molecules and light to cause variations in photo-physical and photo-chemical properties. To clarify the novel properties of photo-excited MPcs in solvents, the steady/transient state spectral data were collected to investigate four MPc templates, including FePc, ZnPc, CoPc and AlClPc. The Q bands of FePc and CoPc were prone to redshift, while the peaks of ZnPc and AlClPc tended to blueshift in various solvents compared with that in DMSO. With xenon lamp irradiation, the characteristic absorption peak intensity of FePc and ZnPc in DMSO decreased gradually and then increased after being subjected to dark condition. The transient absorption spectra and kinetic data illustrated that photo-excited FePc and CoPc produced relatively short lifetime transient intermediates. The positive absorption at 650 nm in the Q bands of FePc and CoPc could be assigned to the d-π* electron transition in transient intermediates with unpaired d-orbital electron in the open shell configuration of Fe2+ and Co2+. The above studies were of great significance for the application of solvent-triggered and photo-induced novel properties of MPcs.
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Corrole and oxaporphyrin have been successfully synthesized and applied in many research fields such as organic photoelectronics and sensors with the unique photophysical and chemical properties. However, the low synthesis yields of oxacorrole drive researchers turning their attention to theoretical studies for more reasonable molecular structure as the appeal of energy conservation and green chemistry. Corroles, oxacorroles (OC) and dioxacorroles (DOC), a total of 14 molecules, are calculated to systematically explore their structures, intramolecular hydrogen bonds, molecular aromatic and absorption spectral properties influenced by the inner O atoms positions with density functional theory (DFT) and time-dependent density functional theory (TDDFT). The smaller NICS(1)ZZ values of oxacorrole (-35.23 ppm to -33.54 ppm) and dioxacorrole (-34.91 ppm to -33.24) than these of corroles (-32.97 ppm and -33.12 ppm) indicate that the O atoms attendances can increase the molecular aromaticity. The gradually increasing energy gaps of H-8 to H-3 from Corrole1 and Corrole2 to DOC series and the larger charge of CO (+0.208e-+0.380e) than that of CN (+0.065e-+0.177e) illustrate that the substitution of O can reduce the degeneracy degree of energy levels and change the charge distributions. With Hirshfeld method, the molecular orbital contributions of H-1, HOMO, LUMO and L+1 exhibit the regular effects of O atoms positions on orbital energy and electron absorption spectra. For series 1, 23O is beneficial to the red shift of electron absorption spectra. These theoretical conclusions manifest that OC1-23 and DOC1-1 possess the excellent absorption characteristics in the visible region, which can be used as potential materials in the fields of photoelectric materials.
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Oxígeno , Porfirinas , Modelos Teóricos , Estructura Molecular , Porfirinas/químicaRESUMEN
BACKGROUND: Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. METHODS: Forty patients with both-column acetabular fractures were recruited in the randomized prospective case-control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, nâ=â20; conventional method group, nâ=â20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. RESULTS: The operation and instrumentation times in the 3D printing group were significantly shorter (130.8â±â29.2âmin, tâ=â-7.5, Pâ<â0.001 and 32.1â±â9.5âmin, tâ=â-6.5, Pâ<â0.001, respectively) than those in the conventional method group. The amount of blood loss and blood transfusion in the 3D printing group were significantly lower (500 [400, 800] mL, Mann-Whitney Uâ=â74.5, Pâ<â0.001 and 0 [0,400] mL, Mann-Whitney Uâ=â59.5, Pâ<â0.001, respectively) than those in the conventional method group. The number of the approach performed in the 3D printing group was significantly smaller than that in the conventional method group (pararectus + Kocher-Langenbeck [K-L] approach rate: 35% vs. 85%; χâ=â10.4, Pâ<â0.05). The time of intra-operative fluoroscopy in the 3D printing group was significantly shorter than that in the conventional method group (4.2â±â1.8 vs. 7.7â±â2.6âs; tâ=â-5.0, Pâ<â0.001). The post-operative fracture reduction quality in the 3D printing group was significantly better than that in the conventional method group (good reduction rate: 80% vs. 30%; χâ=â10.1, Pâ<â0.05). The hip joint function (based on the Harris score 1 year after the operation) in the 3D printing group was significantly better than that in the conventional method group (excellent/good rate: 75% vs. 30%; χâ=â8.1, Pâ<â0.05). The complication was similar in both groups (5.0% vs. 25%; χâ=â3.1, Pâ=â0.182). CONCLUSIONS: The use of a pre-operative virtual simulation and 3D printing technology is a more effective method for treating both-column acetabular fractures. This method can shorten the operation and instrumentation times, reduce blood loss, blood transfusion and the time of intra-operative fluoroscopy, and improve the post-operative fracture reduction quality. CLINICAL TRAIL REGISTRATION: No.ChiCTR1900028230; http://www.chictr.org.cn.
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Acetábulo/lesiones , Simulación por Computador , Fracturas Óseas/cirugía , Impresión Tridimensional , Adulto , Transfusión Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/terapia , Estudios ProspectivosRESUMEN
Despite being one of the most studied proteins in biology, the photolysis mechanism of myoglobin heme affected by endogenous substances free amino acids is still in controversy. The transient absorption and kinetic processes of photo-excited myoglobin in three forms and the effects of free excited tryptophan on redox reaction of myoglobin were monitored by laser flash photolysis. With dual energy superposition of direct light irradiation and indirect energy transferred from the free excited tryptophan, the variation value in optical density (ΔOD) of MetMb increased by 66.7%, from 0.9 to 1.5. The ΔOD value of MbO2 in ferrous form increased from 0.9 to 1.25, while the ΔOD value of DeoxyMb increased from 0.75 to 1.2. The decay time of excited DeoxyMb was prolonged obviously with the excited tryptophan, while the decay time of excited MbO2 and MetMb was shortened significantly. The excited tryptophan could promote laser induced reaction processes of myoglobin in different forms by intermolecular energy transfer to one final similar photo reaction state. The possible photo induced reaction mechanisms of DeoxyMb, MbO2, MetMb with and without free tryptophan were also proposed.
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Core fucosylation catalyzed by core fucosyltransferase (Fut8) contributes to the progressions of epithelial ovarian cancer (EOC). Copper transporter 1 (CTR1), which contains one N-glycan on Asn15 , mediates cellular transport of cisplatin (cDDP), and plays an important role in the process of cDDP-resistance in EOC. In the present study, we found that the core fucosylation level elevated significantly in the sera of cDDP-treated EOC patients. The in vitro assays also indicate that core fucosylation of CTR1 was significantly upregulated in cDDP-resistant A2780CP cells compared to the cDDP-sensitive A2780S cells. Intriguingly, the hyper core fucosylation suppressed the CTR1-cDDP interactions and cDDP-uptake into A2780CP cells. Conversely, contrast to the Fut8+/+ mouse ovarian epithelial cells, the Fut8-deleted (Fut8-/- ) cells obviously showed higher cDDP-uptake. Furthermore, the recovered core fucosylation induced the suppression of cDDP-uptake in Fut8-restored ovarian epithelial cells. In addition, the core fucosylation could regulate the phosphorylation of cDDP-resistance-associated molecules, such as AKT, ERK, JNK, and mTOR. Our findings suggest that the core fucosylation of CTR1 plays an important role in the cellular cDDP-uptake and thus provide new strategies for improving the outcome of cDDP based chemotherapy of EOC.
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Carcinoma Epitelial de Ovario/tratamiento farmacológico , Proteínas de Transporte de Catión/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos , Fucosa/metabolismo , Fucosiltransferasas/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Proteínas de Transporte de Catión/química , Ciclo Celular , Proliferación Celular , Transportador de Cobre 1 , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Células Tumorales CultivadasRESUMEN
A simple method combing Mn(2+) doping with a hierarchical structure was developed for the improvement of thin-film sensors and efficient detection of the explosives relevant to improvised explosive devices (IEDs). ZnS hierarchical nanospheres (HNs) were prepared via a solution-based route and their sensing performances were manipulated by Mn(2+) doping. The responses of the sensors based on ZnS HNs towards 8 explosives generally increase firstly and then decrease with the increase of the doped Mn(2+) concentration, reaching the climate at 5% Mn(2+). Furthermore, the sensory array based on ZnS HNs with different doping levels achieved the sensitive and discriminative detection of 6 analytes relevant to IEDs and 2 military explosives in less than 5 s at room temperature. Importantly, the superior sensing performances make ZnS HNs material interesting in the field of chemiresistive sensors, and this simple method could be a very promising strategy to put the sensors based on thin-films of one-dimensional (1D) nanostructures into practical IEDs detection.
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With the particular conjugation structure in the heme prosthetic group, Cyt c shows unusual functions similar to chlorophyll while irradiated by specific wavelength of UV-Vis lights. To further reveal mechanism of the photo-irradiation of Cyt c, we then studied various external factors that may influence the photo induced process. The absorbance intensity increase of band (317 nm) and Q band (520 nm and 549 nm)indicated Cyt c in phosphate-buffered saline within N2 atmosphere was photoreduced to Fe(II) Cyt c. Irradiated by 410 nm, the photoreduction process was facilitated by Met. But Trp, Tyr and Phe impeded the process due to their light absorbance abilities. In addition, the results of fluorescence and CD spectra indicated that the microenvironment polarity of Trp residue varied during the photoreduction process. And the secondary structure of Cyt c changed with lower α-helix/ßsheet ratio. The photoreduction mechanism of Cyt c was intramolecular electron transfer and porphyrin cation radicals were generated. The protein structure of Cyt c changed as well as part of the photoreduction.
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Citocromos c/química , Citocromos c/efectos de la radiación , Animales , Caballos , Fotólisis , Conformación Proteica , Estabilidad Proteica , Espectrofotometría UltravioletaRESUMEN
Ag recognition and Ab production in B cells are major components of the humoral immune response. In the current study, we found that the core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) was required for the Ag recognition of BCR and the subsequent signal transduction. Moreover, compared with the 3-83 B cells, the coalescing of lipid rafts and Ag-BCR endocytosis were substantially reduced in Fut8-knockdown (3-83-KD) cells with p31 stimulation and then completely restored by reintroduction of the Fut8 gene to the 3-83-KD cells. Indeed, Fut8-null (Fut8(-/-)) mice evoked a low immune response following OVA immunization. Also, the frequency of IgG-producing cells was significantly reduced in the Fut8(-/-) spleen following OVA immunization. Our results clearly suggest an unexpected mode of BCR function, in which the core fucosylation of IgG-BCR mediates Ag recognition and, concomitantly, cell signal transduction via BCR and Ab production.
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Formación de Anticuerpos/inmunología , Antígenos/inmunología , Linfocitos B/inmunología , Inmunoglobulina G/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Secuencia de Aminoácidos , Animales , Linfocitos B/metabolismo , Secuencia de Bases , Sitios de Unión/genética , Western Blotting , Células Cultivadas , Endocitosis/inmunología , Citometría de Flujo , Fucosa/inmunología , Fucosa/metabolismo , Fucosiltransferasas/deficiencia , Fucosiltransferasas/genética , Fucosiltransferasas/inmunología , Glicosilación , Inmunoglobulina G/genética , Inmunoglobulina G/metabolismo , Microdominios de Membrana/inmunología , Microdominios de Membrana/metabolismo , Ratones Endogámicos ICR , Ratones Noqueados , Datos de Secuencia Molecular , Ovalbúmina/inmunología , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal/inmunología , Bazo/inmunología , Bazo/metabolismoRESUMEN
As we all known, the instantaneous reaction between protein and ligands are very important to adjust the normal playing of biological function. And nitric oxide interactions with iron are the most important biological reactions in which NO participates. Unlike carbon monoxide or oxygen, NO can also bind reversibly to ferric iron. In this paper, UV-Vis absorption and CD spectra were used to study coordination reaction process between horse heart metMb and NO, to demonstrate the coordination reaction mechanism and to explore the influencing factors of metMb with NO. The experimental results showed that metMb could react with NO, and obtained three new peaks at 420 nm, 534 and 568 nm, respectively, which implied metMb and NO have reacted and generated a new complex-nitrosylmetmyoglobin (metMbNO). Then as time went on, NO concentration decreased in the solution, and the Fe-N bond fractured under the attack of H2O, then NO leaves slowly from metMbNO, and met-Mb was regenerated. In this experiment, we also found that external conditions such as buffer medium, ionic strength, pH, temperature, etc, had an important influence on the coordination reaction between metMb and NO. It was favorable for the coordination reaction, when the 0.01 mol x L(-1) phosphate buffer. solution is near neutral condition, the temperature is 280 K, the coordination reaction could reach equilibrium at a fastest speed. In addition, the CD date show that NO only reacts with Fe atom in the center of heme and has less effect on the secondary structuers of protein. The research of metMb and NO played an important role to further study the function of NO. Especially the establish of equilibrium reaction mechanism between NO and heme protein has an important research value on maintaining the balance of NO in vivo and keeping the normal function in the body's cells.
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Metamioglobina/química , Óxido Nítrico/química , Animales , Hemo/química , Caballos , Concentración de Iones de Hidrógeno , Hierro/química , Soluciones , TemperaturaRESUMEN
Magnetic polymer microspheres (MPMs) using glycidylmethacrylate (GMA) as a functional monomer were synthesized in the presence of Fe3O4 nanoparticles via dispersion polymerization. After polymerization, the magnetic polymer microbeads were modified with ethylenediamine (EDA). The obtained ethylenediamine-functionalized magnetic microspheres (EDA-MPMs) were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), vibrating-sample magnetometer (VSM) and Fourier transform infrared (FT-IR) spectroscopy. Then the EDA-MPMs were applied as adsorbents for the removal of Cr(VI) from aqueous solution. Langmuir equation was appropriate to describe the experimental data. The maximum adsorption capacities obtained from the Langmuir model were 236.9, 242.1 and 253.2 mg/g at 298, 308 and 318 K, respectively. The Cr(VI) adsorption equilibrium was established within 120 min and the adsorption kinetics was compatibly described by the pseudo-second order equation. The thermodynamic parameters (ΔG°, ΔH°, ΔS°) of the sorption process revealed that the adsorption was spontaneous and was an endothermic process. The regeneration study demonstrated that the EDA-MPMs could be repeatedly utilized with no significant loss of adsorption efficiency.