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1.
Anal Chim Acta ; 1182: 338940, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34602204

RESUMO

We develop an electrochemical sensor by using 2D-transition metal dichalcogenides (TMD), specifically MoS2, and nanoparticles stabilized with cucurbit[8]uril (CB[8]) incorporated together with them. Two different nanoparticles are assayed: diamond nanoparticles (DNPs) and gold nanoparticles (AuNp). 0D materials, together with TMD, provide increased conductivity and active surface while the macrocycle CB[8] affords selectivity towards the guest methyl viologen (MV2+), also named paraquat. Glassy Carbon (GC) electrodes are modified by drop-casting of suspensions of MoS2, followed by either a CB[8]-DNPs hybrid dispersion or a CB[8]-AuNp suspension. Atomic force microscopy is employed for the morphological characterization of the electrochemical sensor surface while cyclic voltammetry and electrochemical impedance spectroscopy techniques allow the electrochemical characterization of the sensor. The well-stablished signals of CB[8]-encapsulated MV2+ arise in voltammetric measurements when the macrocycle modifies the 0D-materials. Once the sensor construction and differential pulse voltammetry parameters have been optimized for quantification purposes, calibration procedures are performed with the platform GC/MoS2/CB[8]-DNPs. This sensing platform shows linear relations between peak intensity and the MV2+ concentration in the linear concentration range of (0.73-8.0) · 10-6 M with a limit of detection of 2.2 · 10-7 M. Analyses of river water samples fortified with MV2+ at the µM level shows recoveries of 100% with RSD values of 6.4% (n = 3).


Assuntos
Dissulfetos , Nanopartículas Metálicas , Hidrocarbonetos Aromáticos com Pontes , Ouro , Imidazóis , Paraquat
2.
Sensors (Basel) ; 21(18)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34577327

RESUMO

Toxic and nontoxic volatile organic compound (VOC) gases are emitted into the atmosphere from certain solids and liquids as a consequence of wastage and some common daily activities. Inhalation of toxic VOCs has an adverse effect on human health, so it is necessary to monitor their concentration in the atmosphere. In this work, we report on the fabrication of inorganic nanotube (INT)-tungsten disulfide, paper-based graphene-PEDOT:PSS sheet and WS2 nanotube-modified conductive paper-based chemiresistors for VOC gas sensing. The WS2 nanotubes were fabricated by a two-step reaction, that is oxide reduction and sulfurization, carried out at 900 °C. The synthesized nanotubes were characterized by FE-SEM, EDS, XRD, Raman spectroscopy, and TEM. The synthesized nanotubes were 206-267 nm in diameter. The FE-SEM results show the length of the nanotubes to be 4.5-8 µm. The graphene-PEDOT:PSS hybrid conductive paper sheet was fabricated by a continuous coating process. Then, WS2 nanotubes were drop-cast onto conductive paper for fabrication of the chemiresistors. The feasibility and sensitivity of the WS2 nanotube-modified paper-based chemiresistor were tested in four VOC gases at different concentrations at room temperature (RT). Experimental results show the proposed sensor to be more sensitive to butanol gas when the concentration ranges from 50 to 1000 ppm. The limit of detection (LOD) of this chemiresistor for butanol gas was 44.92 ppm. The WS2 nanotube-modified paper-based chemiresistor exhibits good potential as a VOC sensor with the advantages of flexibility, easy fabrication, and low fabrication cost.


Assuntos
Nanotubos , Compostos Orgânicos Voláteis , Dissulfetos , Humanos , Limite de Detecção , Tungstênio
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474905

RESUMO

Bioreducible polyethylenimines (SSPEIs) are promising non-viral carriers for cancer gene therapy. However, the availability of significant gene transfection activity by SSPEIs remains a challenge. Herein, an essential step was taken to ascertain whether or not the disulfide bonds of SSPEIs play a critical role in promoting significant gene transfection activity in different tissues. Initially, a disulfide-linked linear polyethylenimine (denoted as SSLPEI) consisting of one 5.0 kDa LPEI main chain and three disulfide-linked 5.7 kDa LPEI grafts was designed and prepared to possess similar molecular weight with commercialized 25 kDa LPEI as a positive control. The SSLPEI could induce superior in vitro transfection activity in different cells to the LPEI control as well as low cytotoxicity. Notably, such enhanced in vitro transfection effect by the SSLPEI was more marked in type-II alveolar epithelial cells compared to different cancer cells. In a Balb/c nude mouse model bearing SKOV-3 tumor, the SSLPEI caused parallel level of transgene expression with the LPEI control in the tumor but significantly higher level in the mouse lung. Furthermore, the SSLPEI and LPEI groups afforded an identical antitumor efficacy against the SKOV-3 tumor via intravenous delivery of a shRNA for silencing VEGF expression in the tumor. However, via intravenous delivery of an interleukin-12 (IL-12) gene into metastatic lung cancers in a C57BL/6 mouse model, the SSLPEI group exerted markedly higher IL-12 expression level in the mouse lung and peripheral blood as compared to the LPEI group, thereby boosting IL-12 immunotherapy against the lung metastasis with longer medium survival time. The results of this work elicit that the disulfide bonds of SSPEIs play a pivotal role in enhancing gene transfection activity selectively in the lung tissue rather than solid tumor, enabling high translational potential of SSPEIs for non-viral gene therapy against metastatic lung cancers.


Assuntos
Neoplasias Pulmonares , Polietilenoimina , Animais , Dissulfetos , Terapia Genética , Interleucina-12/genética , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos C57BL , Transfecção
4.
Int J Clin Pract ; 75(11): e14838, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519144

RESUMO

OBJECTIVE: We aimed to investigate the effects of hypotensive anaesthesia on oxidative stress with serum thiol/disulphide balance in patients undergoing elective septoplasty procedures under general anaesthesia. METHODS: Seventy-two patients between the ages of 18-60, with a physical condition I -II, according to the American Society of Anesthesiologists, were included in this prospective observational study. Septoplasty was chosen for standard surgical stress. According to the maintenance of anaesthesia, patients were divided into the groups as Hypotensive Anaesthesia (n = 40) and Normotensive Anaesthesia (n = 32). Serum thiol/disulphide levels were measured by the method developed by Erel & Neselioglu. RESULTS: The native thiol and total thiol values of both groups measured at the 60th min intraoperatively were significantly lower than the preoperative values (both P < .01). Intraoperatively, at the 60th min, there was no significant difference in terms of post-native thiol and post-total thiol levels between hypotensive and normotensive anaesthesia groups (P = .68 and .81, respectively). Age >40 years and female gender were found to have a significant effect on dynamic oxidative stress (P = .002 and .001, respectively). CONCLUSION: This pilot study has found that hypotensive anaesthesia had no adverse effect on dynamic thiol/disulphide balance in elective surgeries.


Assuntos
Anestesia , Dissulfetos , Adolescente , Adulto , Feminino , Homeostase , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Projetos Piloto , Compostos de Sulfidrila , Adulto Jovem
5.
Int J Clin Pract ; 75(11): e14872, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34525247

RESUMO

AIMS: In this study, we aimed to investigate the anti-inflammatory and antioxidant effects of intravenous ibuprofen by using the C-reactive protein level and thiol/disulfide homeostasis as the oxidative stress marker. MATERIALS AND METHODS: This study was conducted on 70 patients aged between 30 and 65 who were scheduled for elective laparoscopic hysterectomy. The patients were divided into two groups to receive either pre-emptive 800mg of intravenous ibuprofen plus 1000 mg of intravenous paracetamol (Group IP) or only 1000 mg of intravenous paracetamol as a control group (Group P). The blood samples for thiol/disulfide homeostasis were collected as follows: before induction of anesthesia (T0), before pneumoperitoneum (T1), following postdeflation and discontinuation of anesthesia (T2), and postoperative 24th hour (T3). Simultaneous blood samples for C-reactive protein (CRP) were also collected. The pre- and postoperative urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were measured. RESULTS: A total of 69 patients were included in the study. The patient's characteristics and intraoperative variables were comparable between groups (P > .05). The number of patients requiring rescue analgesia, the total amount of analgesic used, Visual Analog Scale (VAS) scores, and postoperative side effects were significantly lower in Group IP (P < .001). The decrease in native and total thiol levels at T1, T2, and T3 measurement points was significant in Group IP (P < .001). In both groups, the comparison to baseline values demonstrated no significant changes in terms of disulfide level (P > .05). The simultaneous CRP levels indicated a significant increase at the postoperative 24 hour in both groups (P < .001). The difference between groups was insignificant (P > .05). There was a significant increase in urea and creatinine levels in patients of Group IP (P < .05). CONCLUSION: The pre-emptive administration of ibuprofen provided effective pain control after gynecologic laparoscopy. However, ibuprofen changed the thiol/disulfide homeostasis in favor of oxidation and had no beneficial effect in surgically induced oxidative stress.


Assuntos
Ibuprofeno , Laparoscopia , Adulto , Idoso , Proteína C-Reativa , Dissulfetos , Feminino , Homeostase , Humanos , Inflamação , Pessoa de Meia-Idade , Estresse Oxidativo , Compostos de Sulfidrila
6.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500571

RESUMO

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR's cardioprotective impact and protected rats from developing ISO-induced myocardial infarction.


Assuntos
Compostos Alílicos/farmacologia , Cardiotônicos/farmacologia , Carvedilol/farmacologia , Dissulfetos/farmacologia , Alho/química , Coração/diagnóstico por imagem , Isoproterenol/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Modelos Animais de Doenças , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502071

RESUMO

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion.


Assuntos
Antígeno B7-H1/metabolismo , Dissulfetos/farmacologia , Periodontite/metabolismo , Ácidos Sulfínicos/farmacologia , Linfócitos T/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-H1/química , Sítios de Ligação , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL6/genética , Quimiocina CXCL6/metabolismo , Dissulfetos/química , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ligação Proteica , Ácidos Sulfínicos/química , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
ACS Nano ; 15(9): 14492-14508, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34478266

RESUMO

Recent advances in supramolecular chemistry research have led to the development of artificial chemical systems that can form self-assembled structures that imitate proteins involved in the regulation of cellular function. However, intracellular polymerization systems that operate inside living cells have been seldom reported. In this study, we developed an intramitochondrial polymerization-induced self-assembly system for regulating the cellular fate of cancer cells. It showed that polymeric disulfide formation inside cells occurred due to the high reactive oxygen species (ROS) concentration of cancer mitochondria. This polymerization barely occurs elsewhere in the cell owing to the reductive intracellular environment. The polymerization of the thiol-containing monomers further increases the ROS level inside the mitochondria, thereby autocatalyzing the polymerization process and creating fibrous polymeric structures. This process induces dysfunction of the mitochondria, which in turn activates cell necroptosis. Thus, this in situ polymerization system shows great potential for cancer treatment, including that of drug-resistant cancers.


Assuntos
Dissulfetos , Neoplasias , Neoplasias/tratamento farmacológico , Polimerização
9.
J Synchrotron Radiat ; 28(Pt 5): 1309-1320, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34475280

RESUMO

X-ray-based techniques are a powerful tool in structural biology but the radiation-induced chemistry that results can be detrimental and may mask an accurate structural understanding. In the crystallographic case, cryocooling has been employed as a successful mitigation strategy but also has its limitations including the trapping of non-biological structural states. Crystallographic and solution studies performed at physiological temperatures can reveal otherwise hidden but relevant conformations, but are limited by their increased susceptibility to radiation damage. In this case, chemical additives that scavenge the species generated by radiation can mitigate damage but are not always successful and the mechanisms are often unclear. Using a protein designed to undergo a large-scale structural change from breakage of a disulfide bond, radiation damage can be monitored with small-angle X-ray scattering. Using this, we have quantitatively evaluated how three scavengers commonly used in crystallographic experiments - sodium nitrate, cysteine, and ascorbic acid - perform in solution at 10°C. Sodium nitrate was the most effective scavenger and completely inhibited fragmentation of the disulfide bond at a lower concentration (500 µM) compared with cysteine (∼5 mM) while ascorbic acid performed best at 5 mM but could only reduce fragmentation by ∼75% after a total accumulated dose of 792 Gy. The relative effectiveness of each scavenger matches their reported affinities for solvated electrons. Saturating concentrations of each scavenger shifted fragmentation from first order to a zeroth-order process, perhaps indicating the direct contribution of photoabsorption. The SAXS-based method can detect damage at X-ray doses far lower than those accessible crystallographically, thereby providing a detailed picture of scavenger processes. The solution results are also in close agreement with what is known about scavenger performance and mechanism in a crystallographic setting and suggest that a link can be made between the damage phenomenon in the two scenarios. Therefore, our engineered approach might provide a platform for more systematic and comprehensive screening of radioprotectants that can directly inform mitigation strategies for both solution and crystallographic experiments, while also clarifying fundamental radiation damage mechanisms.


Assuntos
Ácido Ascórbico/química , Cristalografia por Raios X/métodos , Cisteína/química , Sequestradores de Radicais Livres/química , Nitratos/química , Dissulfetos/química , Estrutura Molecular , Espalhamento a Baixo Ângulo , Soluções/química , Temperatura
10.
Langmuir ; 37(36): 10720-10731, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34473512

RESUMO

The two characteristic absorption peaks of semiconducting two-dimensional tungsten disulfide (WS2) are red-shifted after integrating with gold nanocube (AuNC) arrays. The amount of the red shift is reduced when the AuNCs are coated with a high concentration of Pd. A negligible shift was observed in the absorption peaks of WS2 when smaller amounts of Pd are introduced to the surface of AuNCs. Conversely, the photoluminescence (PL) of WS2 is blue-shifted when measured on top of AuNCs and AuNCs coated with different amounts of Pd. AuNC-Pd Janus nanoparticles are prepared by depositing Pd atoms asymmetrically on AuNCs assembled into 2-D arrays on the surface of a glass substrate by the chemical reduction of Pd ions. Due to the large AuNC or AuNC-Pd/WS2 Schottky barrier, the plasmon-induced hot electron transfer (PHET) from AuNCs and AuNCs coated with a high concentration of Pd is responsible for the red shift of the absorption spectrum of WS2. Introducing a lower concentration of Pd to AuNCs increases the Schottky barrier further due to the formation of the Au-Pd equilibrium Fermi level of lower energy, reducing the efficiency of PHET. The effect of Pd on the Fermi level of AuNCs vanishes at high Pd deposition. Pauli blocking and phase-space filling are responsible for the blue shift of PL of WS2 on top of AuNCs and AuNCs coated with Pd. The Pauli blocking effect is directly proportional to the PHET efficiency. This explains the significant blue shift of PL of WS2 after integrating with AuNCs and AuNCs coated with a high concentration of Pd. Additionally, depositing Pd onto AuNCs elongates the lifetime of the hot electrons and enhances the PHET efficiency.


Assuntos
Ouro , Nanoestruturas , Dissulfetos , Paládio
11.
J Hazard Mater ; 416: 126043, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492890

RESUMO

The transformation of Ag+ is strongly correlated with its risks in aquatic environment. Considering the wide application of molybdenum disulfide (MoS2) and the inevitable release into the environment, the effects of MoS2 on Ag+ transformation and toxicity are of great concerns. This study revealed the pH-dependent reduction of Ag+ (0.5 mM) to Ag nanoparticles (AgNPs) by MoS2 (50 mg/L) and solar irradiation obviously accelerates the AgNPs formation (2.638 mg/L per day, pH=7.0) compared with dark condition (0.637 mg/L per day), ascribing to the electrons capture from electron-hole pairs of MoS2 by Ag+. Ionic strengths and natural organic matter decreased the AgNPs yield. Metallic 1 T phase of MoS2 primarily participated in AgNPs formation and was oxidized to soluble ions (MoO42-) due to the oxygen generation in valance band. The above processes also occurred between Ag+ and MoS2 at environmentally relevant concentrations. Further, photoinduced transformation of Ag+ by MoS2 (10-100 µg/L) significantly lowered its toxicity to freshwater algae. The AgNPs formation on MoS2 reduced the bioavailability of Ag+ to algae, which was the mechanism for attenuated Ag+ toxicity. The provided data are helpful for better understanding the roles of MoS2 on the environmental fates and risks of metal ions under natural conditions.


Assuntos
Nanopartículas Metálicas , Prata , Dissulfetos , Água Doce , Íons , Nanopartículas Metálicas/toxicidade , Molibdênio/toxicidade , Prata/toxicidade
12.
Redox Biol ; 46: 102107, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509915

RESUMO

Soluble epoxide hydrolase (sEH), an enzyme that broadly regulates the cardiovascular system, hydrolyses epoxyeicosatrienoic acids (EETs) to their corresponding dihydroxyeicosatrienoic acids (DHETs). We previously showed that endogenous lipid electrophiles adduct within the catalytic domain, inhibiting sEH to lower blood pressure in angiotensin II-induced hypertensive mice. As angiotensin II increases vascular H2O2, we explored sEH redox regulation by this oxidant and how this integrates with inhibition by lipid electrophiles to regulate vasotone. Kinetics analyses revealed that H2O2 not only increased the specific activity of sEH but increased its affinity for substrate and increased its catalytic efficiency. This oxidative activation was mediated by formation of an intra-disulfide bond between C262 and C264, as determined by mass spectrometry and substantiated by biotin-phenylarsinate and thioredoxin-trapping mutant assays. C262S/264S sEH mutants were resistant to peroxide-induced activation, corroborating the disulfide-activation mechanism. The physiological impact of sEH redox state was determined in isolated arteries and the effect of the pro-oxidant vasopressor angiotensin II on arterial sEH redox state and vasodilatory EETs indexed in mice. Angiotensin II induced the activating intra-disulfide in sEH, causing a decrease in plasma EET/DHET ratios that is consistent with the pressor response to this hormone. Although sEH C262-C264 disulfide formation enhances hydrolysis of vasodilatory EETs, this modification also sensitized sEH to inhibition by lipid electrophiles. This explains why angiotensin II decreases EETs and increases blood pressure, but when lipid electrophiles are also present, that EETs are increased and blood pressure lowered.


Assuntos
Epóxido Hidrolases , Compostos de Sulfidrila , Animais , Dissulfetos , Epóxido Hidrolases/genética , Epóxido Hidrolases/metabolismo , Peróxido de Hidrogênio , Camundongos , Oxirredução , Estresse Oxidativo
13.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34551978

RESUMO

Human metapneumovirus (HMPV) is a major cause of respiratory disease worldwide, particularly among children and the elderly. Although there is no licensed HMPV vaccine, promising candidates have been identified for related pneumoviruses based on the structure-based stabilization of the fusion (F) glycoprotein trimer, with prefusion-stabilized F glycoprotein trimers eliciting significantly higher neutralizing responses than their postfusion F counterparts. However, immunization with HMPV F trimers in either prefusion or postfusion conformations has been reported to elicit equivalent neutralization responses. Here we investigate the impact of stabilizing disulfides, especially interprotomer disulfides (IP-DSs) linking protomers of the F trimer, on the elicitation of HMPV-neutralizing responses. We designed F trimer disulfides, screened for their expression, and used electron microscopy (EM) to confirm their formation, including that of an unexpected postfusion variant. In mice, IP-DS-stabilized prefusion and postfusion HMPV F elicited significantly higher neutralizing responses than non-IP-DS-stabilized HMPV Fs. In macaques, the impact of IP-DS stabilization was more measured, although IP-DS-stabilized variants of either prefusion or postfusion HMPV F induced neutralizing responses many times the average titers observed in a healthy human cohort. Serological and absorption-based analyses of macaque responses revealed elicited HMPV-neutralizing responses to be absorbed differently by IP-DS-containing and by non-IP-DS-containing postfusion Fs, suggesting IP-DS stabilization to alter not only the immunogenicity of select epitopes but their antigenicity as well. We speculate the observed increase in immunogenicity by IP-DS trimers to be related to reduced interprotomer flexibility within the HMPV F trimer.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Dissulfetos/química , Epitopos/imunologia , Glicoproteínas/imunologia , Metapneumovirus/imunologia , Mutação , Animais , Glicoproteínas/genética , Humanos , Imunização , Macaca , Metapneumovirus/genética , Camundongos , Regiões Promotoras Genéticas
14.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361695

RESUMO

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.


Assuntos
Antioxidantes/uso terapêutico , Curcuma/química , Curcumina/uso terapêutico , Dissulfetos/uso terapêutico , Alho/química , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Ácidos Sulfínicos/uso terapêutico , Animais , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Contagem de Ovos de Parasitas , Praziquantel/uso terapêutico , Esquistossomose mansoni/parasitologia , Resultado do Tratamento
15.
J Food Sci ; 86(9): 4026-4036, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34409609

RESUMO

Allicin, a chemical found in functional foods, has a variety of beneficial bioactivities but the unpleasent odor and unstability hinder its applications. Isolating products from cyclodextrin (CD) complexation, using ß-CD and its derivatives, is usually a time and energy-consuming process. Herein, a high-efficiency and eco-friendly preparation method of an inclusion (allicin@α-CD) formed by allicin and α-CD was designed, which turned liquid allicin into crystal particles with high-speed stirring (10,000 r/min) at 25°C for 10 min in water. In vivo and in vitro masking evaluations showed that the inclusion particles could decrease the unpleasant odor of allicin. Molecular docking and experimental characterization results illustrated that the main reason of odor masking was due to the disulfide and thiocarbonyl groups of allicin being partially encapsulated by the cavity of α-CD. Compared with the physical mixture, the stability of allicin in allicin@α-CD at 60°C for 10 days was 33-fold improved. Overall, this efficient strategy of inclusion provided a promising approach for the industrialization of allicin-related formulations. PRACTICAL APPLICATION: In this study, an environmentally friendly method of α-CD inclusion without the use of organic reagents was designed to solidify and stabilize allicin, which effectively masked the unpleasant odor and taste of allicin. It has contributed greatly to improving the compliance of consumers and provided a new and effective approach to broaden the application of allicin.


Assuntos
Aditivos Alimentares , Tecnologia de Alimentos , Odorantes , alfa-Ciclodextrinas , Cristalização , Dissulfetos/química , Aditivos Alimentares/química , Aditivos Alimentares/normas , Tecnologia de Alimentos/métodos , Humanos , Simulação de Acoplamento Molecular , Odorantes/análise , Solubilidade , Ácidos Sulfínicos/química , alfa-Ciclodextrinas/química
16.
Int J Clin Pract ; 75(11): e14713, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34374172

RESUMO

AIM: Trauma is the most common cause of death in childhood. Tissue damage, ischaemia-reperfusion injury and inflammatory response are mainly responsible for increasing free oxygen radicals. In this study, we aimed to investigate the use of thiol-disulphide and ischaemia-modified albumin levels as a diagnostic laboratory parameter in trauma children. METHODS: Of 202 children, 101 were hospitalised in the paediatric surgical intensive care unit with trauma, and 101 were healthy children. Levels of native thiol (-SH), total thiol (SH + SS), dynamic disulphide (SS), dynamic disulphide (SS)/total thiol (SH + SS), albumin and ischaemic modified albumin (IMA) were measured from the sera of patients and healthy volunteers. For statistical analyses, SPSS 17.0 was used. Mann-Whitney U and paired correlation tests were used where appropriate. P < .05 was considered significant. RESULTS: The mean age of the patients in the trauma group (boys: 61 girls: 40) was 7.88 years and the control group was 8.00 years. In the trauma group, 86 children were exposed to blunt trauma, 15 children had penetrating trauma and 54 patients had multiple trauma. Surgical procedures were performed on 17 patients. In the trauma group, native thiol, total thiol, dynamic disulphide/total thiol, albumin and IMA levels were significantly lower than that of the control (P < .001), and their dynamic disulphide (P = .001) was higher compared with the control. There was no difference thiol-disulphide parameters in trauma groups sub-division as surgery (n = 17) vs follow-up (n = 84) groups or multiple trauma (n = 54) vs isolated organ trauma (n = 47) groups or penetrating (n = 15) or blunt trauma (n = 86) groups. CONCLUSION: Thiol-disulphide balance and IMA levels show changes in favour of oxidative stress in children with trauma; however, it cannot be used as a laboratory marker that helps to show the system and organ affected by the trauma and to decide the surgical intervention.


Assuntos
Dissulfetos , Compostos de Sulfidrila , Biomarcadores , Criança , Feminino , Homeostase , Humanos , Masculino , Estresse Oxidativo , Albumina Sérica , Albumina Sérica Humana
17.
J Org Chem ; 86(17): 11987-11997, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34374284

RESUMO

A cheap iron-catalyzed C-C bond cleavage/thiolation and selenylation of cycloalkyl hydroperoxides are presented. This redox-neutral protocol provides efficient access to diverse distal keto-functionalized thioethers and selenium compounds. Remarkably, only some amounts of disulfides are required for this transformation.


Assuntos
Peróxido de Hidrogênio , Ferro , Catálise , Dissulfetos , Sulfetos
18.
Nat Commun ; 12(1): 5082, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426584

RESUMO

Gram-positive bacteria can resist large mechanical perturbations during their invasion and colonization by secreting various surface proteins with intramolecular isopeptide or ester bonds. Compared to isopeptide bonds, ester bonds are prone to hydrolysis. It remains elusive whether ester bonds can completely block mechanical extension similarly to isopeptide bonds, or whether ester bonds dissipate mechanical energy by bond rupture. Here, we show that an ester-bond containing stalk domain of Cpe0147 is inextensible even at forces > 2 nN. The ester bond locks the structure to a partially unfolded conformation, in which the ester bond remains largely water inaccessible. This allows the ester bond to withstand considerable mechanical forces and in turn prevent complete protein unfolding. However, the protecting effect might be reduced at non-physiological basic pHs or low calcium concentrations due to destabilizing the protein structures. Inspired by this design principle, we engineer a disulfide mutant resistant to mechanical unfolding under reducing conditions.


Assuntos
Proteínas de Bactérias/química , Ésteres/química , Fenômenos Mecânicos , Dissulfetos/química , Microscopia de Força Atômica , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Domínios Proteicos , Água/química
19.
Chemistry ; 27(55): 13840-13845, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34398482

RESUMO

There have been several attempts to construct supramolecular chemical systems that mimic the phase transitions in living systems. However, most of these phase transitions are one-to-one and induced by one stimulus or chemical; there have been few reports on the pathway-dependent phase transition of supramolecular self-assemblies in multi-step. To induce multistep phase transitions, molecular crystals were prepared that contained a cationic amphiphile bearing azobenzene and disulfide groups. A reducing agent caused the crystals to become vesicles, and adjacent, non-touching vesicles fused under UV and subsequent visible light. Adding a reducing agent to the worm-like aggregates that were generated after UV irradiation of the original crystals resulted in the growth of sheet-like aggregates. 1 H NMR and fluorescence anisotropy measurements showed that a series of phase transitions was induced by changes in the phase structures from molecular conversions of the reactive amphiphiles. The multiple pathway-dependent phase transitions of supramolecular self-assemblies can provide a methodology for developing new stimuli-responsive materials that exhibit the desirable properties under specific circumstances from a systems chemistry viewpoint.


Assuntos
Compostos Azo , Dissulfetos , Transição de Fase , Raios Ultravioleta
20.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445305

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, TNF-α, NFκB p65, Iκß, TGF-ß, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-ß were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1ß, and Cd68 in the lung. In addition, TGF-ß, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-ß. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dissulfetos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Citocinas/genética , Citocinas/metabolismo , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos , Ratos Wistar , Proteína Smad5/genética , Proteína Smad5/metabolismo
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