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1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 17-23, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016672

RESUMO

OBJECTIVE: To evaluate the hemostasis of plasma aminothiols in different subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 177 patients, aged 62 (55-68) years, admitted in the first 8-24 hours since IS onset. The pathogenetic subtype of IS was clarified according to the results of clinical and instrumental examination by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Determination of the total plasma aminothiols levels, their reduced forms and redox status was performed using the ultra-efficient Acquity H-Class UPLC liquid chromatograph (Waters, CSHA). RESULTS: Large-artery atherosclerosis was diagnosed in 24.3% patients, cardioembolic stroke in 20.3%, lacunar stroke in 55.4%. Significant differences in total levels of cysteine (Cys), glutathione (Gsh) and homocysteine (Hcy) were identified in patients with different IS subtypes. Patients with large-artery atherosclerosis and lacunar stroke showed the highest level of Hcy, patients with cardioembolic stroke had the lowest levels of Cys and Gsh. CONCLUSION: Total levels of plasma aminothiols are associated with different subtypes of IS.


Assuntos
Aterosclerose , Isquemia Encefálica/complicações , Cisteína , Glutationa , Homocisteína , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/sangue , Cisteína/sangue , Glutationa/sangue , Homocisteína/sangue , Humanos , Pessoa de Meia-Idade , Oxirredução
3.
Oxid Med Cell Longev ; 2020: 6401341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014275

RESUMO

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.


Assuntos
Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Dieta Cetogênica/métodos , Cetonas/administração & dosagem , Pneumonia Viral/terapia , Ácido 3-Hidroxibutírico/metabolismo , Imunidade Adaptativa , Animais , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Metabolismo Energético , Humanos , Imunidade Inata , Cetonas/metabolismo , Oxirredução , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
4.
Water Sci Technol ; 82(5): 967-983, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33031074

RESUMO

An easy-to-use, pollution-free and reusable beaded NiOx(OH)y catalyst for improving hypochlorite oxidation was prepared by impregnating the mixture of persulfate and alkali over alumina and then reduced it with Ni2+. The effects of catalyst preparation conditions and reaction parameters on NaClO conversion rate and Ni2+ dissolution rate were studied. Impregnating the γ-Al2O3 beads in PS/OH- mixed solution with 0.59 M PS and PS/OH- molar ratio of 1.1, and then reducing with 0.8 M Ni2+ solution is the best condition for preparing catalyst. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The best catalytic layer is characterized by high content of chemisorbed oxygen which can be converted into atomic oxygen. The hypochlorite conversion rate increased with the catalyst dosage and reuse times, and decreased with available chlorine, while pH of hypochlorite solution had little effect on the conversion rate. After running stably for 120 h in continuous flow test, the chemisorbed oxygen content in the optimal catalytic layer decreased slightly. Atomic oxygen plays an important role in the decolorization of dye solution by NaClO/NiOx(OH)y system. The oxidant consumption cost of this process is much cheaper than Fenton reagent. The prepared catalyst has great potential in hypochlorite decomposition and wastewater treatment.


Assuntos
Ácido Hipocloroso , Águas Residuárias , Catálise , Oxirredução , Difração de Raios X
5.
Water Sci Technol ; 82(5): 998-1008, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33031076

RESUMO

The feasibility of an advanced oxidation process based upon sodium persulfate (SPS) activated simultaneously by heat (50 °C) and nanoscale zero-valent iron (nZVI) on benzene removal was investigated. The experimental results strongly showed the synergistic effect of thermal and nZVI activation to SPS and benzene removal was enhanced with the increase of SPS/nZVI/benzene molar ratio. Specifically, 94% of benzene could be removed in 1 hr at 50 °C at the SPS/nZVI/benzene molar ratio of 10/5/1. The radical scavenger tests and electron paramagnetic resonance (EPR) analysis confirmed that SO4•- was the predominant species contributing to benzene degradation. Further, the effects of the solution matrix on benzene elimination were investigated. The results indicated that benzene destruction in the thermally activated SPS/nZVI system performed better under acidic conditions, and the high concentration of both Cl- and HCO3- had adverse effects on benzene elimination. The test for the performance of benzene degradation in the actual groundwater demonstrated that benzene could be degraded entirely at SPS/nZVI/benzene molar ratio of 40/40/1 at 50 °C, indicating that the synergistic catalysis of thermal and nZVI activation to SPS is exploitable and the thermally activated SPS/nZVI system can be applicable to the remediation of benzene contaminated groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Benzeno , Ferro , Oxirredução , Poluentes Químicos da Água/análise
6.
J Environ Manage ; 263: 110403, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32883479

RESUMO

In this study, we prepared Ti4O7 porous electrodes with continuous layered structures characterized by different layer-to-layer distance (from 2 to 10 µm) but the same total void fraction (88-90%), to modulate the electrodes' permeability and the volumetric electrochemical surface area (from 90 to 840 cm2 cm-3). These platforms were evaluated as anodes in the electro-oxidation (EO) of bentazon in a three-electrode cell under galvanostatic conditions, operated both in traditional batch (TB) or batch recycle flow-through (BRFT) modes. The performance was significantly enhanced when the liquid was recirculated through the lamellar structure of the electrodes. In BRFT mode, the electrode interlayer gap was found to be a key factor to control the bentazon and total organic carbon (TOC) conversions. For the best conditions evaluated (BRFT, 10 µm-interlayered Ti4O7 electrodes with a volumetric surface area of 90 cm2 cm-3), the effect of the applied current (1 or 3 mA) and liquid flow rate (10, 12 or 14 mL. min-1) was investigated. Specific energy consumption (SEC) values were estimated to reveal the performance of each of the EO treatments from an energetic point of view. The use of 10 µm-interlayered Ti4O7 electrodes at 1 mA in BRFT mode at a flow rate of 14 mL min-1 showed the best results, yielding 85% bentazon removal, 57% mineralization and SEC values of 0.006 kWh.gTOC-1 after 6 h of treatment. This contribution highlights the use of layered Ti4O7 electrodes as a promising strategy for intensifying EO processes, pointing to a trade-off between the accessibility to the internal electrode structure and the volumetric electrode surface area to enhance the contact between the target molecules and the hydroxyl radicals physisorbed on the electrode surface, while minimizing simultaneously the energy requirements.


Assuntos
Titânio , Poluentes Químicos da Água/análise , Benzotiadiazinas , Eletrodos , Oxirredução
7.
Sci Total Environ ; 741: 140502, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887006

RESUMO

Landfill leachate contains high concentrations of complex organic matter (OM) that can severely impact the ecological environment. If landfill leachate is to be treated using a combined "biological + advanced treatment" process, the molecular information of OM must be investigated to optimize the operation parameters of the combined process and maximize the removal of organic pollutants. This study applied ultra-high resolution mass spectroscopy to investigate the degradation and transformation characteristics of refractory OM in mature landfill leachate at the molecular level (m/z = 150-800) during biological treatment (i.e., semi-aerobic aged refuse biofilter, SAARB) and subsequent chemical oxidation (i.e., the Fenton process and ozonation). After SAARB treatment, the polycyclic aromatics (aromatic index, AI > 0.66) and polyphenol (0.66 ≥ AI > 0.50) contents increased, and the highly unsaturated phenolic compounds (AI ≤ 0.50 and H/C < 1.5), which have a high bioavailability, were mostly removed. Compared with raw leachate, SAARB effluent (i.e., SAARB leachate) contained fewer organics with short carbon chains, more organics with long carbon chains, an elevated condensation degree for organics and, thus, a considerably reduced biodegradability. Although both the Fenton and ozonation processes could remove many of the polycyclic aromatics and polyphenols, ozone produced considerable amounts of aliphatic compounds with high bioavailability. Compared to ozonation, the Fenton process utilized the hydroxyl radical to non-selectively react with OM and produced better mineralization results.


Assuntos
Resíduos de Alimentos , Ozônio , Eliminação de Resíduos , Poluentes Químicos da Água/análise , Peróxido de Hidrogênio , Oxirredução
8.
Sci Total Environ ; 740: 140152, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32927549

RESUMO

This is the first study to investigate ethylenediamine-N,N'-disuccinic acid (EDDS)/photo-Fenton process to polish real wastewater containing pesticides for possible water reuse. To this end, simultaneous degradation of pesticides ametrine, atrazine, imidacloprid and tebuthiuron was evaluated in distilled water (DW) and in sewage treatment plant (STP) effluent at initial pH 6.0. Several operational parameters (Fe3+-EDDS concentration, Fe3+-EDDS molar ratio, EDDS addition patterns and radiation source) were evaluated. 80-98% removal of target pesticides were obtained in DW using 30 µmol L-1 of Fe3+-EDDS with a molar ratio of 1:2 (300 µmol L-1 of H2O2). In addition, the proposed Fe3+-EDDS photo-Fenton at pH 6 was more efficient than classic photo-Fenton at pH 2.7 (30-84% removal). Experiments conducted in the presence of radical trapping agents (2-propanol or chloroform) revealed that HO• was the most active radical during treatment. Matrix composition strongly affected the degradation of target pesticides as a six-fold higher concentration of reagents (180 µmol L-1 of Fe3+-EDDS and 1800 µmol L-1 of H2O2) was needed to reach the same efficiency in STP compared to DW. Even so, first order rate constants corresponding to the degradation of pesticides in DW (k = 0.098-0.85 min-1) were nearly two-fold higher than in STP (k = 0.079-0.49 min-1) under the same radiation source (black-light or solar radiation). Finally, acute toxicity towards Vibrio fischeri and Drosophila melanogaster flies, and antibacterial activity assessed for Escherichia coli were eliminated after the application of the proposed treatment, thus indicating environmental safety for either discharge or reuse of treated wastewater for crop irrigation in agriculture.


Assuntos
Anti-Infecciosos , Praguicidas , Poluentes Químicos da Água/análise , Animais , Drosophila melanogaster , Peróxido de Hidrogênio , Ferro , Oxirredução
9.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3565-3574, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893545

RESUMO

Quercetin is a kind of typical flavonoid, mainly found in various vegetables, fruits and Chinese herbs that are consumed daily, with the functions of anti-oxidation, anti-tumor, prevention and treatment of cardiovascular and cerebrovascular diseases. Quercetin is a natural compound with defined anti-tumor activity. Due to its low bioavailability and poor water solubility, quercetin has limitations in clinical application. The quercetin derivatives with good solubility, high bioavailability, metabolic stability, and low toxicity have been obtained through modification of quercetin structure. In recent years, a large number of quercetin ethers, esters, complexes, C-4 carbonyloxy substituted derivatives, A,B-ring modified compounds and other derivatives have been synthesized and tested for in vitro anticancer activity. The quercetin derivatives with anti-tumor activity synthesized in the last 5 years were reviewed in this paper.


Assuntos
Neoplasias , Quercetina , Disponibilidade Biológica , Humanos , Oxirredução , Solubilidade
10.
J Environ Sci (China) ; 97: 11-18, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933725

RESUMO

It is known that many kinds of fermentative antibiotics can be removed by temperature-enhanced hydrolysis from production wastewater based on their easy-to-hydrolyze characteristics. However, a few aminoglycosides are hard to hydrolyze below 100°C because of their stability expressed by high molecular energy gap (ΔE). Herein, removal of hard-to-hydrolyze kanamycin residue from production wastewater by hydrothermal treatment at subcritical temperatures was investigated. The results showed the reaction temperature had a significant impact on kanamycin degradation. The degradation half-life (t1/2) was shortened by 87.17-fold when the hydrothermal treatment temperature was increased from 100°C to 180°C. The t1/2 of kanamycin in the N2 process was extended by 1.08-1.34-fold compared to that of the corresponding air process at reaction temperatures of 140-180°C, indicating that the reactions during hydrothermal treatment process mainly include oxidation and hydrolysis. However, the contribution of hydrolysis was calculated as 75%-98%, which showed hydrolysis played a major role during the process, providing possibilities for the removal of kanamycin from production wastewaters with high-concentration organic matrices. Five transformation products with lower antibacterial activity than kanamycin were identified using UPLC-QTOF-MS analysis. More importantly, hydrothermal treatment could remove 97.9% of antibacterial activity (kanamycin EQ, 1,109 mg/L) from actual production wastewater with CODCr around 100,000 mg/L. Furthermore, the methane production yield in anaerobic inhibition tests could be increased about 2.3 times by adopting the hydrothermal pretreatment. Therefore, it is concluded that hydrothermal treatment as a pretreatment technology is an efficient method for removing high-concentration hard-to-hydrolyze antibiotic residues from wastewater with high-concentration organic matrices.


Assuntos
Canamicina , Águas Residuárias , Anaerobiose , Hidrólise , Metano , Oxirredução , Temperatura
11.
J Environ Sci (China) ; 97: 110-119, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32933726

RESUMO

FeVO4/CeO2 was applied in the electro-Fenton (EF) degradation of Methyl Orange (MO) as a model of wastewater pollution. The results of the characterization techniques indicate that FeVO4 with triclinic structure and face-centered cubic fluorite CeO2 maintained their structures during the nanocomposite synthesis. The effect of applied current intensity, initial pollutant concentration, initial pH, and catalyst weight was investigated. The MO removal reached 96.31% and chemical oxygen demand (COD) removal 70% for 60 min of the reaction. The presence of CeO2 in the nanocomposite plays a key role in H2O2 electro-generation as a significant factor in the electro-Fenton (EF) system. The metal leaching from FeVO4/CeO2 was negligible (cerium 4.1%, iron 4.3%, and vanadium 1.7%), which indicates that the active species in the nanocomposite are strongly interacting with each other and are stable. The performance of the nanocatalyst in real wastewaters, salty, and binary systems was acceptable and the pollutions were removed efficiently. The synergistic effect between V, Fe, and Ce could be account as the reason for the respectable function of FeVO4/CeO2. The electron transfer proceeds via Haber-Weiss mechanism. A degradation pathway was proposed through by-products analysis using gas chromatography-mass spectrometry (GC-MS) technique. The pseudo-first-order kinetic model described the obtained experimental results (R2 = 0.9906). The electro-Fenton system efficiency was improved by adding persulfate. The nanocomposite preserved almost its efficiency after six cycles. The obtained results demonstrate that the synergistic catalyst (FeVO4/CeO2) has the capability to introduce as a promising replacement of conventional catalysts in the electro-Fenton processes with brilliant proficiency.


Assuntos
Nanocompostos , Poluentes Químicos da Água/análise , Catálise , Peróxido de Hidrogênio , Ferro , Oxirredução , Águas Residuárias
12.
Anticancer Res ; 40(9): 5159-5170, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878804

RESUMO

BACKGROUND/AIM: The aim of this study was to elucidate the possibility of sensitizing colon cancer cells to the chemotherapeutic drug SN38 and investigate its mechanism of action after combined treatment with electroporation (EP). MATERIALS AND METHODS: Cells were treated with SN38, EP and their combination for 24/48 h. The cell viability, actin cytoskeleton integrity, mitochondrial superoxide, hydroperoxides, total glutathione, phosphatidyl serine expression, DNA damages and expression of membrane ABC transporters were analyzed using conventional analytical tests. RESULTS: The combination of EP and SN38 affected cell viability and cytoskeleton integrity. This effect was accompanied by: (i) high production of intracellular superoxide and hydroperoxides and depletion of glutathione; (ii) increased DNA damage and apoptotic/ferroptotic cell death; (iii) changes in the expression of membrane ABC transporters - up-regulation of SLCO1B1 and retention of SN38 in the cells. CONCLUSION: The anticancer effect of the combined treatment of SN38 and EP is related to changes in the redox-homeostasis of cancer cells, leading to cell death via apoptosis and/or ferroptosis. Thus, electroporation has a potential to increase the sensitivity of cancer cells to conventional anticancer therapy with SN38.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Oxirredução , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Imunofluorescência , Glutationa/metabolismo , Humanos , Modelos Biológicos , Espécies Reativas de Oxigênio/metabolismo
13.
Nat Commun ; 11(1): 4722, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948764

RESUMO

Precisely controlled deuterium labeling at specific sites of N-alkyl drugs is crucial in drug-development as over 50% of the top-selling drugs contain N-alkyl groups, in which it is very challenging to selectively replace protons with deuterium atoms. With the goal of achieving controllable isotope-labeling in N-alkylated amines, we herein rationally design photocatalytic water-splitting to furnish [H] or [D] and isotope alkanol-oxidation by photoexcited electron-hole pairs on a polymeric semiconductor. The controlled installation of N-CH3, -CDH2, -CD2H, -CD3, and -13CH3 groups into pharmaceutical amines thus has been demonstrated by tuning isotopic water and methanol. More than 50 examples with a wide range of functionalities are presented, demonstrating the universal applicability and mildness of this strategy. Gram-scale production has been realized, paving the way for the practical photosynthesis of pharmaceuticals.


Assuntos
Aminas/química , Aminas/metabolismo , Luz , Semicondutores , Alquilação , Aminas/farmacologia , Catálise , Deutério , Oxirredução , Preparações Farmacêuticas , Prótons , Água , Difração de Raios X
16.
Chemosphere ; 258: 127393, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947669

RESUMO

UV/chlorine and chlorination processes have drawn great interests of water treatment utilities for oxidation and disinfection purposes. This work proposed a restricted chlorine-dosing strategy for UV/chlorine and post-chlorination under different pH and UV irradiation conditions by comprehensively assessing the oxidation of natural organic matter (NOM), formation of 9 haloacetic acids (HAA9) and bromate, and alteration of toxicity. During UV/chlorine with restricted chlorine doses, the oxidation of NOM chromophores (i.e., ΔUVA254) showed an apparent dependence on cumulative exposures of free available chlorine (CTFAC); Meanwhile, HAA9 formation was determined by CTFAC values and could be linearly correlated with ΔUVA254 irrespective of pH and UV irradiation wavelength. Irradiated by 254 nm LP-Hg lamp, the faster chlorine photolysis produced relatively higher steady-state concentrations of Cl• and HO• species but resulted in lower CTFAC. Reducing CTFAC values by operation parameters (pH, UV wavelength and irradiation fluence) could mitigate HAA9 formation during UV/chlorine at a specific chlorine dose. Additionally, high bromide concentration and acidic pH promoted more bromo-HAAs formation, and the presence of NOM significantly suppressed bromate formation. Analogous to ozonation, the UV/chlorine pre-oxidation could reduce the HAA9 formation potentials during post-chlorination at mildly alkaline pH. The photobacterium bioassay further demonstrated that although the UV/chlorine treatment might have increased the acute toxicity, the post-chlorination treatment could polish the acute toxicity to the level of chlorination alone. These results suggest that with the restricted chlorine-dosing strategy, the trade-off between oxidation/disinfection efficiency and DBPs formation can be controlled by monitoring CTFAC and ΔUVA254 values during UV/chlorine treatment.


Assuntos
Purificação da Água/métodos , Bromatos , Brometos/efeitos da radiação , Cloro , Desinfecção , Halogenação , Concentração de Íons de Hidrogênio , Oxirredução , Fotólise , Raios Ultravioleta , Poluentes Químicos da Água/análise , Purificação da Água/normas
17.
Chemosphere ; 258: 127343, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947672

RESUMO

Hydroxyl radicals (OH) have robust non-selective oxidizing properties to effectively degrade organic pollutants. However, graphitic carbon nitride (g-C3N4) is restricted to directly generate OH due to its intrinsic valence band. In this study, we report a facile environmental-friendly self-modification strategy to synthesize reduced graphitic carbon nitride (RCN), with nitrogen vacancies and CN functional groups. The incorporation of CN enabled to downshift the valence band level, which endowed RCN with the capacity to directly generate OH via h+. Experimental and instrumental analyses revealed the critical roles of nitrogen vacancies and CN groups in the modification of the RCN band structure to improve its visible light absorption and oxidizing capacity. With these superior properties, the RCN was significantly enhanced for the photocatalytic degradation of DCF under visible light irradiation. The self-modification strategy articulated in this study has strong potential for the creation of customized g-C3N4 band structures with enhanced oxidation performance.


Assuntos
Diclofenaco/química , Grafite/química , Compostos de Nitrogênio/química , Catálise , Luz , Oxirredução , Processos Fotoquímicos
18.
Anticancer Res ; 40(9): 4843-4856, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878772

RESUMO

Aberrant fatty acid (FA) metabolism has long been recognized in colorectal cancer (CRC) cells. Since de novo lipogenesis is required for CRC tumour growth and survival, the inhibition of FA metabolism is a promising potential therapeutic target. Inhibition of the opposite process, ß-oxidation of FAs, has also showed promising results in many CRC models. For patients with CRC, both FA synthesis and ß-oxidation inhibitors are promising potential therapeutic options as monotherapies or as combination therapies with other anticancer agents. In this review, we discuss recent reports concerning inhibitors of FA synthesis and ß-oxidation in various CRC models. The exact mechanisms of action of the selected compounds described in this review remain unknown and require precise evaluation before the development of new successful therapies for CRC is possible.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Inibidores Enzimáticos/farmacologia , Ácidos Graxos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos
19.
Yakugaku Zasshi ; 140(9): 1095-1099, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879241

RESUMO

The lens of the eye is an avascular and anuclear tissue that serves to focus objects on the retina. Cataract is opacity within the clear lens that changes the transparency and refractive index of the lens causing significant visual impairments. These impairments can severely restrict the ability to carry out daily activities. Cataracts is common among elderly person occurring in more than 80% of patients aged 80 or older. Notably, we have recently identified key compounds that are effective against cataract formation. Presbyopia is also an ocular disease that typically develops in people over the age of 45 while affecting almost 100% of people over the age of 65. Recent research suggests that age-related changes in hydrostatic pressure of the lens controlled by Na/K ATPase contribute to the development of presbyopia. In the lens, Na/K ATPase has been shown to be regulated by transient receptor potential cation channels, vanilloid 1 (TRPV1) and 4, thus suggesting the potential role of TRPV1 and TRPV4 in the development of presbyopia. This review article summarizes data obtained from our laboratory with my colleagues highlighting the critical role of aquaporin 0 (AQP0) in maintaining a healthy lens redox environment, key molecules that delay the onset of cataract in vivo, as well as potential mechanisms of lens hydrostatic pressure control that may be associated with presbyopia.


Assuntos
Aquaporinas/fisiologia , Catarata/tratamento farmacológico , Catarata/etiologia , Desenvolvimento de Medicamentos , Proteínas do Olho/fisiologia , Pressão Hidrostática , Cristalino/metabolismo , Oxirredução , Presbiopia/etiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/fisiologia , Canais de Cátion TRPV/fisiologia
20.
Yakugaku Zasshi ; 140(9): 1119-1128, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879244

RESUMO

Humans are exposed to various xenobiotic electrophiles on a daily basis. Electrophiles form covalent adducts with nucleophilic residues of proteins. Redox signaling, which consists of effector molecules (e.g., kinases and transcription factors) and redox sensor proteins with low pKa cysteine residues, is involved in cell survival, cell proliferation, quality control of cellular proteins and oxidative stress response. Herein, we showed that at a low dose, xenobiotic electrophiles selectively modified redox sensor proteins through covalent modification of their reactive thiols, resulting in activation of a variety of redox signaling pathways. However, increasing the dose of xenobiotic electrophiles caused non-selective and extensive modification of cellular proteins involved in toxicity. Of interest, reactive sulfur species (RSS), such as hydrogen sulfide (H2S), cysteine persulfide (CysSSH), glutathione persulfide (GSSH) and even synthetic polysulfide (e.g., Na2S4), readily captured xenobiotic electrophiles, forming their sulfur adducts, which was associated with inactivation of the electrophiles. Our findings suggest that an adaptive response through redox signaling activation and RSS-mediated electrophile capturing is involved in the regulation of electrophilic stress.


Assuntos
Cisteína/análogos & derivados , Dissulfetos/metabolismo , Glutationa/análogos & derivados , Sulfeto de Hidrogênio/metabolismo , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Cisteína/metabolismo , Glutationa/metabolismo , Humanos , Compostos de Sulfidrila/metabolismo , Xenobióticos/metabolismo
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