Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 176
Filtrar
1.
J Atheroscler Thromb ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38325861

RESUMO

AIMS: Identifying patients with vulnerable plaque who have poor prognosis among those with coronary artery disease (CAD) is crucial to deciding future therapeutic interventions. We previously reported that male CAD patients with low anti-apolipoprotein B-100 autoantibody (anti-apoB-100 Ab) levels were at an increased risk of developing unstable plaque lesions. This study focused on the autoantibodies against lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, which is another risk factor for atherosclerosis, and investigated their association with plaque characteristics. METHODS: We measured serum anti-LPL Ab levels using a homemade enzyme-linked immunosorbent assay in 80 male CAD patients. Coronary plaque properties were evaluated using iMAP®-intravascular ultrasound. RESULTS: Serum anti-LPL Ab levels were not correlated with plaque burden but were significantly negatively and positively correlated with fibrotic and necrotic plaques, respectively. High-risk patients with low anti-apoB-100 Ab levels were divided into groups according to their anti-LPL Ab levels. The group with high anti-LPL Ab levels exhibited more necrotic plaques and fewer fibrotic plaques as well as higher remnant-like lipoprotein particle levels than the group with low anti-LPL Ab levels. CONCLUSIONS: Serum anti-LPL Ab levels can serve as a marker of plaque instability in CAD patients and can help identify higher-risk cases when combined with anti-apoB-100 Ab levels.

2.
Antimicrob Agents Chemother ; 68(1): e0095523, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38092678

RESUMO

The newly emerged pathogen, Candida auris, presents a serious threat to public health worldwide. This multidrug-resistant yeast often colonizes and persists on the skin of patients, can easily spread from person to person, and can cause life-threatening systemic infections. New antifungal therapies are therefore urgently needed to limit and control both superficial and systemic C. auris infections. In this study, we designed a novel antifungal agent, PQA-Az-13, that contains a combination of indazole, pyrrolidine, and arylpiperazine scaffolds substituted with a trifluoromethyl moiety. PQA-Az-13 demonstrated antifungal activity against biofilms of a set of 10 different C. auris clinical isolates, representing all four geographical clades distinguished within this species. This compound showed strong activity, with MIC values between 0.67 and 1.25 µg/mL. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes composed of soybean phosphatidylcholine (SPC), 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP), and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt (DSPE-PEG 2000), and characterized by biophysical and spectral techniques. These PQA-Az-13-loaded liposomes displayed a mean size of 76.4 nm, a positive charge of +45.0 mV, a high encapsulation efficiency of 97.2%, excellent stability, and no toxicity to normal human dermal fibroblasts. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models. These initial results suggest that molecules like PQA-Az-13 warrant further study and development.


Assuntos
Antifúngicos , Candida , Humanos , Antifúngicos/farmacologia , Candida auris , Lipossomos , Testes de Sensibilidade Microbiana , Biofilmes
4.
J Control Release ; 363: 536-549, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37776905

RESUMO

The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.


Assuntos
Nanopartículas , Distribuição Tecidual , Trato Gastrointestinal , Administração Oral , Preparações Farmacêuticas
5.
Mol Pharm ; 20(8): 4297-4306, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37491730

RESUMO

Adsorption of gut relevant biomolecules onto particles after oral administration of solid oral dosage forms is expected to form a "gastrointestinal corona", which could influence solution-mediated solid-state transformations on exposure of drug particles to gastrointestinal fluids. Low-frequency Raman (LFR) spectroscopy was used in this study to investigate in situ solid-state phase transformations under biorelevant temperature and pH conditions along with the presence of biomolecules. Melt-quenched amorphous indomethacin was used as a model solid particulate, and its solid-state behavior was evaluated at 37 °C and pH 1.2-6.8 with or without the presence of typical bile salt/phospholipid mixtures emulating fed-state conditions. Overall, a change in the solid-state transformation pathway from amorphous to crystalline drug was observed, where an intermediate ε-form that initially formed at pH 6.8 was suppressed by the addition of endogenous gastrointestinal biomolecules. These solid-state changes were corroborated using time-resolved synchrotron small- and wide-angle X-ray scattering (SAXS/WAXS). Additionally, the bile salt and phospholipid mixture partly prevented the otherwise strong aggregation between drug particles at more acidic conditions (pH ≤ 4.5) and helped to shift the balance against the intrinsic hydrophobicity of indomethacin as well as the plasticization effect brought about by the physiological temperature (i.e., the stickiness arising from the supercooled liquid state at 37 °C). The overall results highlight the importance of evaluating the impact that endogenous biomolecules may have on the solid-state characteristics of drug molecules in dissolution media, where analytical tools such as LFR spectroscopy can serve as an attractive avenue for accessing time-resolved solid-state information on time-scales that are difficult to achieve with other techniques such as X-ray diffraction.


Assuntos
Indometacina , Fosfolipídeos , Preparações Farmacêuticas , Difração de Raios X , Cristalização , Espalhamento a Baixo Ângulo , Solubilidade , Indometacina/química
6.
Endocrinology ; 164(3)2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36534970

RESUMO

We have previously reported that ß-aminoisobutyric acid (BAIBA), a muscle-derived exercise mimetic, had anti-inflammatory and reactive oxygen species (ROS) scavenging effects in vascular endothelial cells through the enhanced expression of peroxisome proliferator-activated receptor gamma coactivator-1ß (PGC-1ß). Although BAIBA also increased the expression of estrogen-related receptor α (ERRα), the roles of ERRα in vascular endothelial cells have yet to be fully elucidated. Here, we found that human aortic endothelial cells (HAECs) infected with ERRα-expressing adenovirus had significantly decreased mRNA levels of tumor necrosis factor α-stimulated proinflammatory molecules. However, ERRα overexpression had little effect on the mRNA levels of PGC-1ß, peroxisome proliferator-activated receptors, and almost all ROS scavenging molecules, except for superoxide dismutase 2. ERRα expression significantly decreased NFκB reporter activities in a dose-dependent manner with unaltered IκBα phosphorylation levels but with a significant increase in the mRNA levels of PDZ and LIM domain protein 2 (PDLIM2) and copper metabolism gene MURR1 domain-containing protein (COMMD1), which enhance the ubiquitination and degradation of NFκB. Also, PDLIM2 and COMMD1 mRNA levels were upregulated in BAIBA-treated HAECs. Finally, we identified the ERRα-response element in the COMMD1 promoter region (-283 to -29 bp). These results indicated that ERRα exerted anti-inflammatory effects in vascular endothelial cells through COMMD1-mediated attenuation of NFκB activity, which could be an atheroprotective mechanism of physical exercise.


Assuntos
Células Endoteliais , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , NF-kappa B/metabolismo , Inflamação , RNA Mensageiro , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas com Domínio LIM/metabolismo , Receptor ERRalfa Relacionado ao Estrogênio
7.
RSC Adv ; 12(32): 20519-20522, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35919172

RESUMO

This work presents a novel filter paper-based method using surface-enhanced Raman spectroscopy (SERS), for detecting polystyrene nanoplastics (PSNPs). The SERS system used a simple mixture of spherical Au nanoparticles (AuNPs) and 20 nm nanoplastics deposited onto a filter paper which offered a detection limit of 10 µg mL-1 with a sample volume of 50 µL, and in a rare case 5.0 µg mL-1 (with four aliquits of 50 µL).

8.
J Cardiovasc Pharmacol ; 80(4): 583-591, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35900901

RESUMO

ABSTRACT: Chronic low-grade inflammation and excess mineralocorticoid receptor (MR) activation are well-known pathological conditions of metabolic syndrome (MetS). To elucidate the crosstalk between inflammation and MR signaling, we focused on serum/glucocorticoid-regulated kinase 1 (SGK1) in vascular endothelial cells. We treated human aortic endothelial cells (HAECs) with esaxerenone (ESX), a novel nonsteroidal highly selective MR antagonist, or spironolactone (SPL), a classic competitive MR antagonist, followed by stimulation with tumor necrosis factor (TNF)-α. ESX at therapeutic concentrations attenuated the long-term induction of TNF-α-stimulated inflammatory molecules in HAEC, whereas SPL had only a minor effect at 10 µM. We found long-term TNF-α-stimulated induction of SGK1 mRNA and protein levels in HAEC and that ESX pretreatment significantly decreased SGK1 mRNA and protein levels at both the basal and the TNF-α-stimulated conditions, whereas SPL had no effect on SGK1 mRNA and protein levels. In addition, the TNF-α-induced nuclear factor kappa-light-chain-enhancer of activated B cell activity was suppressed by the treatment with ESX, and it was abrogated by SGK1 overexpression. These results indicated that ESX has direct anti-inflammatory effects in HAEC via the blocking of long-term TNF-α-induced SGK1 activation and that SGK1 could be a key molecule linking cytokine-induced vascular chronic inflammation and MR activation.


Assuntos
Espironolactona , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/farmacologia , Citocinas , Células Endoteliais/metabolismo , Glucocorticoides/farmacologia , Humanos , Inflamação/patologia , NF-kappa B/metabolismo , Pirróis , RNA Mensageiro , Receptores de Mineralocorticoides/genética , Espironolactona/farmacologia , Sulfonas , Fator de Necrose Tumoral alfa/farmacologia
9.
J Pept Sci ; 28(10): e3413, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35445486

RESUMO

Cheap artificial light harvesting systems, which competently harvest solar energy and promote efficient energy transfer, are highly sought after in the renewable sector. We report the synthesis of self-assembled peptide-porphyrin fibers (SJ 6) fabricated with iron(III) oxide (Fe3 O4 ) nanoparticles as feasible electron acceptors. Charge-complementarity between the negatively charged peptide (20E) and the protonated Zn-tetraphenyl porphyrin (ZnTPyP) led to an ordered assembly of the ZnTPyP molecules, enabling efficient light harvesting. X-ray diffraction data indicates a more ordered structure in SJ 6 compared to 20E and ZnTPyP. The incorporation of Fe3 O4 nanoparticles into SJ 6 showed significant fluorescence quenching, indicating efficient electron flow from the donor to the acceptor. The SJ 6-nFe3 O4 system performed the light reaction of photosynthesis as confirmed by the reduction of 1 mM NAD+ to 0.180 mM NADH upon exposure to visible light (Xe lamp λ > 420 nm) for 1 h. The photochemical regeneration of NADH using the SJ 6-nFe3 O4 system was coupled to glutamate dehydrogenase-catalyzed conversion of α-ketoglutarate to L-glutamate. These results confirm the successful synthesis of an artificial light harvesting peptide-porphyrin system with Fe3 O4 nanoparticles as promising low-cost electron separators.


Assuntos
Nanopartículas Metálicas , Nanofibras , Porfirinas , Compostos Férricos , Luz , NAD/química , Óxidos , Peptídeos , Porfirinas/química
10.
Biointerphases ; 16(4): 041001, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34241329

RESUMO

Plastic waste is ubiquitously spread across the world and its smaller analogs-microplastics and nanoplastics-raise particular health concerns. While biological impacts of microplastics and nanoplastics have been actively studied, the chemical and biological bases for the adverse effects are sought after. This work explores contributory factors by combining results from in vitro and model mammalian membrane experimentation to assess the outcome of cell/nanoplastic interactions in molecular detail, inspecting the individual contribution of nanoplastics and different types of protein coronae. The in vitro study showed mild cytotoxicity and cellular uptake of polystyrene (PS) nanoplastics, with no clear trend based on nanoplastic size (20 and 200 nm) or surface charge. In contrast, a nanoplastic size-dependency on bilayer disruption was observed in the model system. This suggests that membrane disruption resulting from direct interaction with PS nanoplastics has little correlation with cytotoxicity. Furthermore, the level of bilayer disruption was found to be limited to the hydrophilic headgroup, indicating that transmembrane diffusion was an unlikely pathway for cellular uptake-endocytosis is the viable mechanism. In rare cases, small PS nanoplastics (20 nm) were found in the vicinity of chromosomes without a nuclear membrane surrounding them; however, this was not observed for larger PS nanoplastics (200 nm). We hypothesize that the nanoplastics can interact with chromosomes prior to nuclear membrane formation. Overall, precoating PS particles with protein coronae reduced the cytotoxicity, irrespective of the corona type. When comparing the two types, the extent of reduction was more apparent with soft than hard corona.


Assuntos
Nanopartículas , Coroa de Proteína , Animais , Microplásticos , Nanopartículas/toxicidade , Tamanho da Partícula , Plásticos , Poliestirenos
11.
J Environ Manage ; 296: 113163, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34229137

RESUMO

This work reports an environmentally benign and readily scalable process for production of akaganéite (ß-FeOOH) nanocomposites by using abundant gallic acid or grape seed tannins and urea. Influences from those phytochemicals on the properties of ß-FeOOH nanocomposites were investigated by X-ray powder diffraction, Fourier transform infrared spectroscopy, Thermogravimetric analysis, Scanning electron microscopy, Transmission electron microscopy, UV-Vis spectroscopy and Photoluminescence. The addition of 0.1% (w/v) grape seed tannins or gallic acid (640 mg L-1) solution yielded single-crystalline ß-FeOOH nanocomposites with reduced dimensions, increased porosities and BET surface area, and no oxidized impurities such as hematite (Fe2O3) were formed. The added grape seed tannins (S0.8) or gallic acid together with less urea (0.8 M) produced ß-FeOOH nanocomposites with higher activities as peroxidase mimics compared to those prepared with only urea (C0.8). Moreover, S0.8 was more efficient in methylene blue (MB) discoloration compared to C0.8 at all three pH values of 4, 7 and 11, and the S0.8-mediated MB degradation pathways at pH 4 and 7 were different from those at pH 11 due to the generation of different predominant oxidants. The overall MB discoloration efficacies by S0.8 at pH 4, 7 and 11 were combinative effects of both physical adsorption and chemical reactions. These ß-FeOOH nanocomposites possess great potential as peroxidase mimics for facile monitoring of excess hydrogen peroxide and applications in environmental remediation.


Assuntos
Azul de Metileno , Nanocompostos , Compostos Férricos , Peroxidase , Peroxidases
12.
Clin Chim Acta ; 516: 142-148, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33571485

RESUMO

BACKGROUND: Mac-2 binding protein (Mac-2BP) is used as a serum biomarker of nonalcoholic steatohepatitis, considered to be a liver phenotype of metabolic syndrome (MetS). In this study, we investigated the serum Mac-2BP concentrations-correlated MetS-related clinical parameters in vivo, and the underlying mechanism in vitro. MATERIALS & METHODS: We enrolled 54 healthy Japanese men who underwent health examination at Osaka University Health Care Center in this study. Physical and serum biochemical parameters were obtained from all the subjects. In the cultured HepG2 cells, the effects of interferon (IFN)-γ on the expression of Mac-2BP, apolipoprotein (apo) A-I, and ATP binding cassette transporter A1 (ABCA1) were studied. RESULTS: Serum Mac-2BP concentrations correlated negatively with HDL-C, and positively with body mass index and systolic blood pressure in univariate analysis. These results suggested the association between Mac-2BP and MetS, although none of these 3 parameters had significant correlation with serum Mac-2BP concentrations in multivariate analysis. In HepG2 cells, IFN-γ stimulation resulted in the increased Mac-2BP and the decreased ABCA1 and apo A-I mRNA concentrations, while Mac-2BP had no effects on ABCA1 and apo A-I concentrations. CONCLUSIONS: The serum Mac-2BP concentrations are negatively correlated with HDL-C concentrations in healthy subjects, as a result of chronic inflammation.


Assuntos
Apolipoproteína A-I , Transportador 1 de Cassete de Ligação de ATP/genética , HDL-Colesterol , Humanos , Masculino
13.
Adv Colloid Interface Sci ; 288: 102337, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385776

RESUMO

Multiple international agencies have recently raised environmental and health concerns regarding plastics in nanoforms (nanoplastics), but there is insufficient knowledge of their properties to allow for an accurate risk assessment to be conducted and any risks managed. For this reason, research into the toxicity of nanoplastics has focused strongly on documenting their impacts on biological organisms. One scope of this review is to summarise the recent findings on the adverse effects on biological organisms and strategies which can be adopted to advance our understanding of nanoplastic properties and their toxicity. Specifically, a mechanistic approach has already been employed in nanotoxicology, which focuses on the cause-and-effect relationships to establish a tool that predicts the biological impacts based on nanoparticle characteristics. Identifying the chemical and biological bases behind the observed biological effects (such as in vitro cellular response) is a major challenge, due to the intricate nature of nanoparticle-biological molecule complexes and an unawareness of their interaction with other biological targets, particularly at interfacial level. An exemplary case includes protein corona formation and ecological molecule corona (eco-corona) for nanoplastics. Therefore, the second scope of this review is to discuss recent findings and importance of (for both non-plastic and plastic nanoparticles) coronae formation and structure. Finally, we discuss the opportunities provided by model system approaches (model protein corona and lipid bilayer) to deepen the understanding of the above-mentioned perspectives, and corroborate the findings from in vitro experiments.


Assuntos
Microplásticos , Nanopartículas , Plásticos , Poliestirenos
14.
J Atheroscler Thromb ; 28(10): 1025-1034, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33191364

RESUMO

AIMS: Cardiovascular diseases (CVD) are a global leading cause of mortality. However, few biomarkers are available to predict future coronary plaque rupture. We have recently demonstrated that low levels of anti-apolipoprotein B-100 autoantibody (anti-apo B-100 Ab) correlated with an increased CVD risk in Japanese patients with diabetes. In the present study, we examined the relationship between serum anti-apo B-100 Ab levels and coronary plaque characteristics in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We conducted iMAP®-intravascular ultrasound (IVUS) in 88 Japanese male patients undergoing elective PCI, and the five consecutive slices of IVUS images at the center of the most stenotic culprit lesion were used for identifying the plaque characteristics. The serum levels of anti-apo B-100 Ab against synthetic peptides (p45 or p210) were measured using a homemade enzyme-linked immunosorbent assay. RESULTS: Serum IgG levels of anti-apo B-100 Ab against both native p45 and p210 (IgG N-p45 and IgGN-p210) and malondialdehyde (MDA)-modified p45 and p210 (IgGMDA-p45 or IgGMDA-p210) showed a negative correlation with plaque burden in total male patients undergoing elective PCI. Additionally, both IgGN-p45 and IgGN-p210, but neither IgGMDA-p45 nor IgGMDA-p210, correlated negatively with necrotic and positively with fibrotic components of iMAP®-IVUS plaque characteristics in the patients with <1 month statin treatment before elective PCI ("statin-untreated" group). There was no significant correlation between anti-apo B-100 Ab and any plaque characteristics in the patients with statin treatment for 1 month or more before elective PCI ("statin-treated" group). CONCLUSION: Measuring serum levels of anti-apo B-100 Ab might be helpful in the evaluation of unstable coronary plaque in male CVD patients without statin treatment.


Assuntos
Apolipoproteína B-100/imunologia , Autoanticorpos/imunologia , Placa Aterosclerótica/patologia , Idoso , Autoanticorpos/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/imunologia
15.
J Atheroscler Thromb ; 28(11): 1204-1213, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33191365

RESUMO

AIM: Adiponectin (APN) exhibits different atheroprotective effects, and we have previously reported that APN function is modulated by its binding proteins, E-selectin ligand 1, Mac-2 binding protein, and cystatin C. In the present study, we aimed to identify a novel atheroprotective mechanism of APN via C-C motif chemokine 2 (CCL2). METHODS: We conducted iMAP®-intravascular ultrasound (IVUS) in 111 Japanese male patients with stable angina. The plaque characteristics were determined where "plaque burden" [(EEM CSA - lumen CSA)/(EEM CSA)×100 (%)] >50%, and their correlation with serum CCL2 and APN levels was analyzed. Using western blot analysis, the effects of APN on the biological effects of CCL2 were examined in their mutual binding by co-immunoprecipitation assay, the monocyte migration, and the phosphorylation of MAP kinases. RESULTS: In a clinical study, we found that the percentage of plaque in the culprit lesion was correlated positively with serum CCL2 and negatively with serum APN levels, with significance. We identified CCL2 as a novel APN-binding serum protein using immunoprecipitation and western blot analysis. CCL2-induced phosphorylation of MAP kinases and monocyte migration was significantly attenuated by APN in vitro. CONCLUSION: The opposite association of APN and CCL2 on the percentage of coronary plaque might be caused by their direct interaction and competitive functions on monocyte migration.


Assuntos
Adiponectina/farmacologia , Biomarcadores/metabolismo , Quimiocina CCL2/antagonistas & inibidores , Placa Aterosclerótica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimento Celular , Proliferação de Células , Quimiocina CCL2/metabolismo , Feminino , Seguimentos , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Prognóstico
16.
FASEB J ; 34(12): 15805-15821, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33040408

RESUMO

Voltage-gated proton channels (Hv1/VSOP), encoded by Hvcn1, are important regulator of reactive oxygen species (ROS) production in many types of immune cells. While in vitro studies indicate that Hv1/VSOP regulates ROS production by maintaining pH homeostasis, there are few studies investigating the functional importance of Hv1/VSOP in vivo. In the present study, we first show that Hv1/VSOP is functionally expressed in liver resident macrophage, Kupffer cells, regulating the hepatic oxidative stress in vivo. Our immunocytochemistry and electrophysiology data showed that Hvcn1 is specifically expressed in Kupffer cells, but not in hepatocytes. Furthermore, Hvcn1-deficiency drastically altered the hepatic oxidative stress. The Hvcn1-deficient mice showed high blood glucose and serum insulin but normal insulin sensitivity, indicating that these phenotypes were not linked to insulin resistance. Transcriptome analysis indicated that the gene expression of glycogen phosphorylase (Pygl) and Glucose-6-phosphatase, catalytic subunit (G6pc) were upregulated in Hvcn1-deficient liver tissues, and quantitative PCR confirmed the result for Pygl. Furthermore, we observed higher amount of glucose-6-phosphate, a key sugar intermediate for glucose in Hvcn1-deficient liver than WT, suggesting that glucose production in liver is accelerated in Hvcn1-deficient mice. The present study sheds light on the functional importance of Kupffer cells in hepatic oxidative stress and its potential relationship with glucose metabolism.


Assuntos
Glucose/metabolismo , Canais Iônicos/metabolismo , Células de Kupffer/metabolismo , Fígado/metabolismo , Estresse Oxidativo/fisiologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prótons , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/fisiologia
17.
Aquat Toxicol ; 228: 105645, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33010639

RESUMO

The toxicity of heavy metals commonly impacts the survival of crustacean and bivalve larvae in hatchery culture, and this has led to the widespread use of EDTA to decrease this toxicity. Since EDTA has a very poor biodegradability leading to potential persistent environmental effects, alternative methods to prevent heavy metal toxicity to shellfish larvae are needed. EDDS is a biodegradable potential alternative to EDTA for this application and was tested as a treatment of the seawater used for rearing aquaculture Greenshell™ mussel (Perna canaliculus) larval embryos in this study. Mussel embryos reared with EDTA or EDDS had significantly better survival than without. The concentrations and spatial distributions of heavy metals in D-veliger larvae as determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and X-ray Fluorescence Microscopy (XFM) suggested that chelating agents increased the levels of calcium in larvae while they reduced the concentration of zinc. In addition, where decreased accumulation of the other heavy metals was not observed, chelating agents affected their distribution within the larvae, especially for copper and arsenic. This is the first study to test the use of EDDS for aquaculture hatchery application and shows that EDDS is an effective biodegradable alternative to EDTA that can mitigate the effects of heavy metals for shellfish larval rearing.


Assuntos
Aquicultura , Quelantes/farmacologia , Perna (Organismo)/crescimento & desenvolvimento , Animais , Biodegradação Ambiental/efeitos dos fármacos , Larva/efeitos dos fármacos , Metais/análise , Microscopia de Fluorescência , Perna (Organismo)/efeitos dos fármacos , Água do Mar/química , Análise de Sobrevida , Poluentes Químicos da Água/toxicidade
18.
Biointerphases ; 15(5): 051002, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32948094

RESUMO

A major challenge in understanding nanoplastic toxicity (or nanoparticles in general) lies in establishing the causal relationships between its physical properties and biological impact. This difficulty can be attributed to surface alterations that follow the formation of a biological complex around the nanoplastic, as exemplified by protein coronae. The protein corona is known to be responsible for the biological response elicited, although its own structure and attributes remain unknown. We approach this knowledge gap by independently studying the structure of soft and hard coronae using neutron scattering techniques. We investigated the formation and the structure of corona proteins (human serum albumin and lysozyme) and the resulting protein corona complexes with polystyrene nanoplastics of different sizes (20 and 200 nm) and charges. Soft corona complexes (regardless of protein type) adopted a structure where the nanoplastics were surrounded by a loose protein layer (∼2-3 protein molecules thick). Hard corona complexes formed fractal-like aggregates, and the morphology of which is known to be harmful to cellular membranes. In most cases, hard-corona coated nanoplastics also formed fractal-like aggregates in solution. Nanoplastic size affected the structures of both the protein corona and the intrinsic protein: more significant conformational change was observed in the hard corona proteins around smaller nanoparticles compared to larger ones, as the self-association forces holding the nanoplastic/protein complex together were stronger. This also implies that protein-dependent biochemical processes are more likely to be disrupted by smaller polystyrene nanoplastics, rather than larger ones.


Assuntos
Muramidase/química , Nanoestruturas/química , Poliestirenos/química , Coroa de Proteína/química , Albumina Sérica Humana/química , Dicroísmo Circular , Muramidase/metabolismo , Tamanho da Partícula , Agregados Proteicos , Estrutura Secundária de Proteína , Albumina Sérica Humana/metabolismo
19.
Soft Matter ; 16(28): 6563-6571, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32588868

RESUMO

Increased water solubility and long-range intermolecular ordering have been introduced into the fluorescent organic molecule thiophene-diketopyrrolopyrrole (TDPP) via its conjugation to the octapeptide HEFISTAH, which is derived from the protein-protein ß-interface of the homo-tetramer protein diaminopimelate decarboxylase. The octapeptide, and its TDPP mono- and cross-linked conjugates were synthesised using 9-fluorenylmethoxycarbonyl (Fmoc) based solid-phase peptide synthesis (SPPS). Unlike the unmodified peptide, the resulting mono-linked and cross-linked peptides showed a fibrous morphology and formed hydrogels at 4 wt% in water at neutral pH, but failed to assemble at pH 2 and pH 9. Further peptide characterization showed that the TDPP organic core enhances peptide self-assembly and that both peptides assembled into fibers with a parallel ß-sheet structure. Furthermore, UV-vis spectroscopic analysis suggests that the TDPP molecules form H-type aggregates where the chromophores are likely to be co-facially packed, but rotationally and/or laterally offset from one another. This intermolecular coupling indicates that π-π stacking interactions are highly likely - a favourable sign for charge transport. The enhanced aqueous solubility and self-assembling properties of the TDPP-peptide conjugates allowed the successful preparation of thin films. Atomic force microscopy, X-ray diffraction and UV-vis spectroscopic analysis of these thin films revealed that the hybrid materials retained a fibrous morphology, ß-sheet structures and strong intermolecular coupling between neighbouring TDPP molecules. These results open an exciting avenue for bio-organic materials development, through structural and electronic tuning of the TDPP core.


Assuntos
Peptídeos , Pirróis , Hidrogéis , Concentração de Íons de Hidrogênio , Cetonas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA