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1.
Talanta ; 236: 122859, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635243

RESUMO

The sensitivity and selectivity of electrochemical analysis are challenging due to the materials used for electrode modification as well as electrical conductivity, catalytic activity and recognition ability of the working electrode. In this work, a portable 3D-printed electrochemical electrode clamp was designed and applied in combination with the developed covalent organic framework (COF DQTP)-modified pencil graphite electrode (DQTP/PGE). The ß-ketoenamine-linked COF DQTP synthesized by 1,3,5-triformylphloroglucinol (TP) and 2,6-diaminoanthraquinone (DQ) through solvothermal method is a porous crystalline with excellent conductivity and large periodic π-arrays, coupled with commercial available pencil graphite electrode to fabricate a disposable sensor for simultaneous determination of environmental endocrine disruptors bisphenol A and bisphenol S. The DQTP/PGE sensor exhibited high electrical conductivity and catalytic activity, and a good linearity was obtained in a range of 0.5-30 µM for two bisphenols with a detection limit of 0.15 µM (S/N = 3). Moreover, the sensor showed a reproducible and stable response over one month with negligible interference, and an accepted recovery with real food packaging samples.


Assuntos
Grafite , Estruturas Metalorgânicas , Compostos Benzidrílicos , Eletrodos , Fenóis , Sulfonas
2.
J Hazard Mater ; 421: 126744, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34333408

RESUMO

To meet the rising global demand for water, it is necessary to develop membranes capable of efficiently purifying contaminated water sources. Herein, we report a series of novel polysulfone (PSf)/GO-vanillin nanofiltration membranes highly permeable, selective, and fouling resistant. The membranes are composed of two-dimensional (2D) graphite oxide (GO) layers embedded with vanillin as porogen and PSf as the base polymer. There is a growing interest in addressing the synergistic effect of GO and vanillin on improving the permeability and antifouling characteristics of membranes. Various spectroscopic and microscopic techniques were used to perform detailed physicochemical and morphological analyses. The optimized PSf16/GO0.15-vanillin0.8 membrane demonstrated 92.5% and 25.4% rejection rate for 2000 ppm magnesium sulphate (MgSO4) and sodium chloride (NaCl) solutions respectively. Antifouling results showed over 99% rejection for BSA and 93.57% flux recovery ratio (FRR). Experimental work evaluated the antifouling characteristics of prepared membranes to treat landfill leachate wastewater. The results showed 84-90% rejection for magnesium (Mg+2) and calcium (Ca+2) with 90.32 FRR. The study experimentally demonstrated that adding GO and vanillin to the polymeric matrix significantly improves fouling resistance and membrane performance. Future research will focus on molecular sieving for industrial separations and other niche applications using mixed matrix membranes.


Assuntos
Grafite , Purificação da Água , Benzaldeídos , Membranas Artificiais , Óxidos , Polímeros , Sulfonas
3.
J Hazard Mater ; 421: 126788, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34364204

RESUMO

Development of efficient absorbent materials for oil spillage clean-up and environmental pollution remediation is highly desired but remains a challenge. In this work, superhydrophobic/superoleophilic polysulfone based ZIF-7 composite (SPZ) foams were fabricated via chemical modification of polysulfone and integrating with hydrophobic coin-shaped ZIF-7 particles. The synergistic approaches provided the SPZ foams with high porosity, low density and superhydrophobic/superoleophilic features (θwater=162.3°, θoil=0°) and outstanding self-cleaning property. The as-prepared SPZ foams exhibited highly selective absorption capacity (up to 3800 wt%) for various kinds of oils and organic solvents. Furthermore, the SPZ foams still maintained 95.2% of its pristine absorption capacity and the θwater remained at 143.6° after ten absorption/distillation cycles. The SPZ foam showed outstanding separation ability towards different types of emulsions with separation efficiency all above 97%. The high oil/water separation efficiency and robust reusability made the SPZ foams promising absorbent in dealing with practical oil spills.


Assuntos
Poluição por Petróleo , Água , Interações Hidrofóbicas e Hidrofílicas , Óleos , Polímeros , Sulfonas
4.
Food Chem ; 367: 130758, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391995

RESUMO

This study evaluated the chemical behaviour of Bisphenol S (BPS) and determined its bioaccessibility after human ingestion using a standardised in vitro gastrointestinal digestion protocol and an analytical method based on high-pressure liquid chromatography coupled with a photodiode array and tandem mass spectrometry. The effects of different factors such as gastric pH, enzymes, and food matrix on the solubility and chemical stability of BPS were studied to evaluate their contribution to its bioaccessibility. The results highlighted that BPS was available at the end of the digestion process in the range of 50-80%, and was susceptible to absorption at the intestinal level. The effect of pH was not significant as a single factor. The presence of enzymes slightly decreased the bioaccessibility of BPS in the intestinal phase with gastric pH increase. Additionally, a soy drink reduced BPS bioaccessibility by up to 5% after oral intake. Finally, a few BPS degradation products were found in non-bioaccessible fractions at different pH values.


Assuntos
Fenóis , Espectrometria de Massas em Tandem , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Digestão , Humanos , Sulfonas
5.
Chemosphere ; 286(Pt 1): 131616, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34325268

RESUMO

Membrane fouling is one of the challenging bottleneck problems in waste water treatment by membrane process. The present study constructed a nanofiltration membrane based on the zinc oxide nanoparticle (n-ZnO) integrated Poly(ether ether sulfone) (PEES) membranes. The developed membranes were characterized by X-ray diffraction (XRD), attenuated total reflectance - fourier transform infrared spectroscopy (AT-FTIR), atomic force microscopy (AFM) and scanning electron microscope (SEM) coupled with energy dispersive X-ray (EDX) analysis. Pure water flux, contact angle, molecular weight cut-off, mean pore size and porosity were determined to investigate the influence of n-ZnO on the properties of the membranes. The characterization showed asymmetric configuration of membranes after n-ZnO incorporation. This incorporation also enhanced the hydrophilicity of PEES membrane. The fouling-resistant potential of the membranes was investigated by the model foulant humic acid (HA) and an enhanced anti-fouling irreversible property with a corresponding flux recovery rate of 92.43 % was noted for the prepared membrane. The rejection performance and permeability of HA was 98.03 % and 166.73 L m-2 h-1, respectively, owing to the hydrophilic nature of ZnO particles. Further, modified PEES membrane exhibited superior separation performance for monovalent and divalent anions. PEES/n-ZnO hybrid membrane assisted nanofiltration is an effective process for the improvement of membrane performance and anti-fouling property, demonstrating its immense use in water reclamation.


Assuntos
Incrustação Biológica , Nanopartículas , Óxido de Zinco , Incrustação Biológica/prevenção & controle , Éter , Éteres , Membranas Artificiais , Sulfonas
6.
Chemosphere ; 286(Pt 2): 131797, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426121

RESUMO

A photocatalyst composed of Zn-TiO2 and Cu-TiO2 through simple physical mixing was used to activate persulfate(PS) for Bisphenol S (BPS) degradation. Zn-TiO2 and Cu-TiO2 were prepared with a sol gel method and were characterized by X-ray diffraction (XRD), Raman, Transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The two catalysts have shown an obvious synergistic effect in the photocatalytic degradation process. When 5 mM persulfate and 0.3 g/L catalyst were used, the removal rate of mixed catalyst (0.2 g/L Zn-TiO2 and 0.1 g/L Cu-TiO2) is 100 % in 18 min, which is significantly better than that of 0.3 g/L Zn-TiO2(58 %) and 0.3 g/L Cu-TiO2(90 %). Typically, the effects of various operation parameters, including the ratio of Cu-TiO2/Zn-TiO2, catalyst dosage, persulfate dosage, initial concentration of BPS, and initial solution pH, were examined. Reactive oxygen species (ROS) in the UV/mixed catalyst/PS process was identified by scavenger and electron paramagnetic resonance (EPR) tests. The superoxide radicals generated by both Zn-TiO2 and the hydrolysis of persulfate in the system could accelerate the Cu (II)/Cu(I) redox cycles and results in the synergistic effect. This study proposed a new and effective way to improve the reaction by simply combining two catalysts, and unraveled the mechanism behind the synergistic effect, which could provide new ideas to use the catalyst more effectively for wastewater treatment or other areas.


Assuntos
Titânio , Zinco , Catálise , Fenóis , Sulfonas , Difração de Raios X
7.
J Agric Food Chem ; 69(44): 12974-12984, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34723494

RESUMO

Fluensulfone (FSF) becomes increasingly popular because of its nonfumigation application method. However, studies on the metabolic mechanism of FSF in plants are lacking. Here, tomato seedling was cultivated in hydroponic media to investigate the connection among FSF's metabolism in tomato, the regulation of tomato endogenous glycosides, and the elimination of hydrogen peroxide in tomato cells. The accumulation of FSF was only detected in the lower stems of tomatoes; FSF was mainly metabolized into S-glycosylated conjugates in the roots, and the roots were the tissues with the highest metabolite content; and no FSF and metabolites were detected in the upper leaves. In response to FSF stress (2 mg/L for 7 d), the content of sugar and glycosides in the stems of tomato seedlings significantly increased. The amount of some compounds on the pathway related to glucose was affected by FSF. The three precursor compounds (homomethioine, isoleucine, and l-tyrosine) in the pathway of glucosinolate biosynthesis increased significantly under the stress of FSF, which indicates that FSF may compete with them for UGT74B1. Besides, FSF-induced flavonoid glycosides may play a role in the process of removing hydrogen peroxide. This research provides inspiration for the fate of many xenobiotics containing sulfonyl groups in plants.


Assuntos
Lycopersicon esculentum , Glicosilação , Plântula , Sulfonas , Tiazóis
8.
J Environ Manage ; 300: 113809, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649317

RESUMO

A highly efficient nanofiltration membrane should exhibit high separation performance in removing divalent salts and organic solutes, as well as high permeation to meet practical separation and purification applications in aqueous media. Here, we designed a series of hybrid multilayer thin film membranes filled with the structurally and morphologically different nanofillers such as hexagonal boron nitride (HBN) nanosheets and metal-organic framework (MOF) nanoparticles, consisting of 3 and 6 layer pairs of polyelectrolyte through the layer-by-layer self-assembly technique (LBL) and characterized them in terms of dye and salt separation, as well as permeation. The rejection performance and permeability of the designed membranes manifested that HBN nanosheets were more effective than MOF nanoparticles in achieving a high-performance membrane. As compared to the bare multilayer thin film membrane, the addition of HBN nanosheets within the negatively-charged layers of the multilayer thin film membrane consisting of 6 bilayers resulted in good retention of up to 93% and 92% for acid blue (ACB) and bromophenol blue (BPB) dye molecules, respectively. Besides, this membrane exhibited 60% and 45% improvement in the water flux for ACB and BPB solutions, respectively, while the rejection of the sulfate ions maintained an acceptable value around 78%. Furthermore, it was found that this HBN-embedded hybrid multilayer membrane had superior potential for the removal of coherent foulant compared to all samples.


Assuntos
Padrões Moleculares Associados a Patógenos , Polímeros , Membranas Artificiais , Sulfonas
9.
Nutrients ; 13(10)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34684621

RESUMO

Interventions to decrease inflammation and improve metabolic function hold promise for the prevention of obesity-related diseases. Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates antioxidant and anti-inflammatory effects. Improvements in measures of metabolic health have been observed in mouse models of obesity and diabetes following MSM treatment. However, the effects of MSM on obesity-related diseases in humans have not been investigated. Therefore, the purpose of this investigation was to determine whether MSM supplementation improves cardiometabolic health, and markers of inflammation and oxidative status. A randomized, double-blind, placebo-controlled design was utilized with a total of 22 overweight or obese adults completing the study. Participants received either a placebo (white rice flour) or 3 g MSM daily for 16 weeks. Measurements occurred at baseline and after 4, 8, and 16 weeks. Outcome measures included fasting glucose, insulin, blood lipids, blood pressure, body composition, metabolic rate, and markers of inflammation and oxidative status. The primary finding of this work shows that high-density lipoprotein cholesterol was elevated at 8 and 16 weeks of daily MSM consumption compared to baseline, (p = 0.008, p = 0.013). Our findings indicate that MSM supplementation may improve the cholesterol profile by resulting in higher levels of high-density lipoprotein cholesterol.


Assuntos
HDL-Colesterol/sangue , Dimetil Sulfóxido/farmacologia , Obesidade/sangue , Sulfonas/farmacologia , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Dieta , Dimetil Sulfóxido/sangue , Exercício Físico , Feminino , Fibrose , Humanos , Inflamação/sangue , Inflamação/patologia , Masculino , Oxirredução , Sulfonas/sangue
10.
Behav Neurol ; 2021: 9536054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539935

RESUMO

Background: The purpose of this meta-analysis was to assess the clinical efficacy of etoricoxib in comparison with traditional NSAIDs for postoperative pain after third molar surgery. Methods: The quality of studies found in PubMed and Google Scholar was evaluated with Cochrane Collaboration's risk of bias tool. Data on total consumption of rescue analgesics, number of patients using rescue analgesics, global assessment of study treatments, and adverse effects were extracted exclusively from high-quality clinical trials. Each meta-analysis was performed with the Review Manager Software 5.3 for Windows. Results: The qualitative analysis showed that etoricoxib has better analgesic activity when compared with ibuprofen (2 clinical trials) and diclofenac (1 clinical trial). A similar analgesic efficacy between etoricoxib and nonselective Cox-2 NSAIDs was informed in 3/8 studies (2 compared to ibuprofen and 1 to naproxen sodium). Moreover, the number of patients requiring rescue analgesics in the postoperative period showed a statistical difference in favor of etoricoxib when compared to NSAIDs. Conclusion: Etoricoxib significantly reduces the number of patients needing rescue analgesics compared to NSAIDs after third molar surgery.


Assuntos
Dente Serotino , Sulfonas , Analgésicos , Etoricoxib , Humanos , Dente Serotino/cirurgia , Piridinas/uso terapêutico , Sulfonas/uso terapêutico
11.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502095

RESUMO

Sphingosine-1-phosphate (S1P) synthesized by sphingosine kinase (SPHK) is a signaling molecule, involved in cell proliferation, growth, differentiation, and survival. Indeed, a sharp increase of S1P is linked to a pathological outcome with inflammation, cancer metastasis, or angiogenesis, etc. In this regard, SPHK/S1P axis regulation has been a specific issue in the anticancer strategy to turn accumulated sphingosine (SPN) into cytotoxic ceramides (Cers). For these purposes, there have been numerous chemicals synthesized for SPHK inhibition. In this study, we investigated the comparative efficiency of dansylated PF-543 (DPF-543) on the Cers synthesis along with PF-543. DPF-543 deserved attention in strong cytotoxicity, due to the cytotoxic Cers accumulation by ceramide synthase (CerSs). DPF-543 exhibited dual actions on Cers synthesis by enhancing serine palmitoyltransferase (SPT) activity, and by inhibiting SPHKs, which eventually induced an unusual environment with a high amount of 3-ketosphinganine and sphinganine (SPA). SPA in turn was consumed to synthesize Cers via de novo pathway. Interestingly, PF-543 increased only the SPN level, but not for SPA. In addition, DPF-543 mildly activates acid sphingomyelinase (aSMase), which contributes a partial increase in Cers. Collectively, a dansyl-modified DPF-543 relatively enhanced Cers accumulation via de novo pathway which was not observed in PF-543. Our results demonstrated that the structural modification on SPHK inhibitors is still an attractive anticancer strategy by regulating sphingolipid metabolism.


Assuntos
Ceramidas/biossíntese , Inibidores Enzimáticos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Pirrolidinas/química , Sulfonas/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Compostos de Dansil/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/toxicidade , Humanos , Metanol/química , Esfingosina/metabolismo , Especificidade por Substrato , Suínos
12.
J Phys Chem B ; 125(40): 11242-11255, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34586817

RESUMO

A many-body polarizable force field (PFF) was developed for molecular dynamics (MD) simulations of sulfone-based solvents and lithium salts. Development of the polarizable force field included parameterization of atomic polarizabilities, electrostatic interactions, and van der Waals interactions of electrolyte components. 1λ6-thiolane-1,1-dione or sulfolane (SLF) compound was selected as one of the most appropriate solvents for high-voltage battery electrolytes. Atomic polarizabilities for the sulfolane solvent and lithium salts were obtained by means of a combination of quantum mechanics (QM) and molecular mechanics (MM) approaches using the isotropic atomic dipole polarizable (IADP) model. High-quality atomic polarizabilities were refined for 10 atomic types. Intermolecular interactions of Li+ ions with SLF were parameterized to reproduce the binding energies at the MP2/aug-cc-pvDZ level of theory in the gas phase. Intermolecular interactions of Li+ ions with polyatomic anions, such as nitrate [NO3]-, tetrafluoroborate [BF4]-, perchlorate [ClO4]-, hexafluorophosphate [PF6]-, bis(fluorosulfonyl)imide [FSI]-, and bis(trifluoromethylsulfonyl)imide [TFSI]-, were parameterized employing a similar methodology. A series of molecular dynamics simulations was performed for sulfolane-based electrolytes at several different lithium salt concentrations. Thermodynamic, structural, and transport properties were evaluated to validate the force field parameters against available simulation and experimental data. Transport properties of sulfolane were significantly improved as compared with those obtained from MD simulations using a nonpolarizable force field (NFF). A newly developed polarizable potential was shown to reproduce Li+ ion dynamics as a function of salt concentration. Faster diffusion of Li+ ions, among other electrolyte components, was obtained for high salt concentration electrolytes.


Assuntos
Lítio , Simulação de Dinâmica Molecular , Eletrólitos , Íons , Sais , Solventes , Sulfonas
13.
J Hazard Mater ; 416: 126126, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492920

RESUMO

Biomass-derived heteroatom-doped porous carbon-based materials are emerging as low-cost adsorbents for removing common pollutants, although the adsorption performance is still unsatisfactory and the main adsorption mechanisms are still controversial. Herein, we report a facile and general method for fabricating biomass-derived N/S dual-doped hierarchically porous carbon adsorbent (MZ-NSPC). The MZ-NSPC material exhibits excellent adsorption capacity (295.8 mg/g for bisphenol F (BPF), 308.7 mg/g for bisphenol S (BPS)), short equilibrium time (30 min), and good reusability (the decline efficiency < 6.15% after five times). The remarkable adsorption performance originates from a large BET surface area, hierarchically porous structure, and N/S heteroatoms dual-doping. Combined with comparative experiments and density functional theory (DFT) calculations, we revealed that the doped N, S heteroatoms played a synergistic effect which promoted the adsorption performance and adsorption sites are mainly the oxidized-S and pyridinic-N. Importantly, for BPF, the proportion contribution of different mechanisms followed the order of hydrophobic interaction > π-π interaction > hydrogen bonding interaction. However, adsorption mechanism of BPS was mainly controlled by π-π interaction. This work not only promotes the development of low-cost and sustainable heteroatom-doped carbon-based materials, but also systematically studies adsorption mechanism of heteroatom-doped carbon-based materials for bisphenols.


Assuntos
Carbono , Compostos Benzidrílicos , Biomassa , Fenóis , Porosidade , Sulfonas
16.
Molecules ; 26(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34500807

RESUMO

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson's disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.


Assuntos
Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Estirenos/farmacologia , Sulfonas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Células Cultivadas , Inflamação/metabolismo , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estirenos/síntese química , Estirenos/química , Sulfonas/síntese química , Sulfonas/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
PLoS One ; 16(9): e0257477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555055

RESUMO

GPR40 (FFAR1) is a promising target for the managing type 2 diabetes (T2D). The most advanced GPR40 agonist TAK-875 exhibited satisfactory glucose-lowering effects in phase II and III studies. However, the phase III studies of TAK-875 revealed drug-induced liver injury (DILI). It is unknown whether DILI is a consequence of a specific GPR40 agonist or is an inherent feature of all GPR40 agonists. CPL207280 is a novel GPR40 agonist that improves diabetes in Zucker Diabetic Fatty (ZDF) rats, Goto Kakizaki (GK) rats and db/db mice. In this report, the DILI-related toxicity of CPL207280 was compared directly with that of TAK-875. In vitro studies evaluating hepatic biliary transporter inhibition, mitochondrial function, and metabolic profiling were performed in hepatocytes from different species. The long term toxicity of CPL207280 was studied in vivo in rats and monkeys. Activity of CPL207280 was one order of magnitude lesser than that of TAK-875 for the inhibition of bile acid transporters. CPL207280 had a negligible effect on the hepatic mitochondria. In contrast to TAK-875, which was metabolized through toxic glucuronidation, CPL207280 was metabolized mainly through oxidation. No deleterious hepatic effects were observed in chronically treated healthy and diabetic animals. The study presents promising data on the feasibility of creating a liver-safe GPR40 agonist. Additionally, it can be concluded that DILI is not a hallmark of GPR40 agonists; it is linked to the intrinsic properties of an individual agonist.


Assuntos
Benzofuranos , Hipoglicemiantes , Sulfonas , Animais , Glicemia , Diabetes Mellitus Tipo 2 , Masculino , Camundongos , Ratos
18.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576228

RESUMO

Human Angiogenin (hANG, or ANG, 14.1 kDa) promotes vessel formation and is also called RNase 5 because it is included in the pancreatic-type ribonuclease (pt-RNase) super-family. Although low, its ribonucleolytic activity is crucial for angiogenesis in tumor tissues but also in the physiological development of the Central Nervous System (CNS) neuronal progenitors. Nevertheless, some ANG variants are involved in both neurodegenerative Parkinson disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Notably, some pt-RNases acquire new biological functions upon oligomerization. Considering neurodegenerative diseases correlation with massive protein aggregation, we analyzed the aggregation propensity of ANG and of three of its pathogenic variants, namely H13A, S28N, and R121C. We found no massive aggregation, but wt-ANG, as well as S28N and R121C variants, can form an enzymatically active dimer, which is called ANG-D. By contrast, the enzymatically inactive H13A-ANG does not dimerize. Corroborated by a specific cross-linking analysis and by the behavior of H13A-ANG that in turn lacks one of the two His active site residues necessary for pt-RNases to self-associate through the three-dimensional domain swapping (3D-DS), we demonstrate that ANG actually dimerizes through 3D-DS. Then, we deduce by size exclusion chromatography (SEC) and modeling that ANG-D forms through the swapping of ANG N-termini. In light of these novelties, we can expect future investigations to unveil other ANG determinants possibly related with the onset and/or development of neurodegenerative pathologies.


Assuntos
Esclerose Amiotrófica Lateral/genética , Doença de Parkinson/genética , Ribonuclease Pancreático/química , Esclerose Amiotrófica Lateral/metabolismo , Cromatografia , Cristalografia por Raios X , Dimerização , Variação Genética , Humanos , Modelos Moleculares , Mutação , Doença de Parkinson/metabolismo , Fosforilação , Conformação Proteica , Domínios Proteicos , Ribonuclease Pancreático/metabolismo , Ribonucleases/metabolismo , Sulfonas/química
19.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576160

RESUMO

Collagen XV (Col XV), a basement membrane (BM) component, is highly expressed in adipose tissue, and studies have found that Col XV is related to extracellular matrix (ECM) remodeling involving in adipose tissue fibrosis and inflammation. Furthermore, the ECM is essential for maintaining normal development and tissue function. In this study, we found that Col XV is related to the endoplasmic reticulum stress (ERS) and inflammation of adipose tissue. Moreover, we found that overexpression of Col XV in mice could cause macrophages to infiltrate white adipose tissue (iWAT). At the same time, the expression of the ERS sensor IRE1α (Inositol-Requiring Enzyme-1α) was significantly up-regulated, which intensified the inflammation of adipose tissue and the polarization of M1 macrophages after the overexpression of Col XV in mice. In addition, after overexpression of Col XV, the intracellular Ca2+ concentration was significantly increased. Using focal adhesion kinase (FAK) inhibitor PF573228, we found that PF-573228 inhibited the phosphorylation of FAK and reversed the upward trend of Col XV-induced protein expression levels of IRE1α, C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). After treatment with IRE1α inhibitor STF-083010, the results showed that the expression of adipocyte inflammation-related genes interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) significantly were decreased. Our results demonstrate that Col XV induces ER-stress in adipocytes by activating the Integrinß1/FAK pathway and disrupting the intracellular Ca2+ balance. At the same time, Col XV regulates the inflammation induced by ER stress in adipocytes by promoting IRE1α/XBP1 (X-Box binding protein 1) signaling. Our study provides new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM.


Assuntos
Tecido Adiposo/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Inflamação/metabolismo , Células 3T3-L1 , Animais , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/genética , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Imuno-Histoquímica , Inflamação/genética , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinolonas/farmacologia , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonas/farmacologia
20.
Chem Commun (Camb) ; 57(72): 9140-9143, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498639

RESUMO

The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.


Assuntos
Piperidinas/síntese química , Estirenos/química , Sulfonas/química , Triptaminas/síntese química , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Piperidinas/química , Triptaminas/química
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