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1.
Am J Physiol Endocrinol Metab ; 326(4): E537-E544, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38477876

RESUMO

There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the KATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances.NEW & NOTEWORTHY We show that the bitter substance, denatonium benzoate (DB), stimulates insulin, glucagon, somatostatin, and GLP-1 secretion from pancreatic islets, independent of glucose, and that DB augments insulin release via the KATP channel, bitter taste receptor signaling, and intraislet GLP-1 secretion. Exposure to a high dose of DB (5 mM) induces cellular apoptosis in pancreatic islets. Therefore, clinical use of bitter substances to improve glucose homeostasis may have unintended negative impacts beyond the gut.


Assuntos
Ilhotas Pancreáticas , Compostos de Amônio Quaternário , Paladar , Camundongos , Animais , Glucagon/farmacologia , Insulina/farmacologia , Glucose/farmacologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Somatostatina/farmacologia , Trifosfato de Adenosina/farmacologia
2.
Int J Pharm ; 653: 123878, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38325622

RESUMO

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC. The present research involved the design and preparation of a hybrid nanoparticle system (LPNs) specifically targeting macrophages at the colonic site. This was achieved by electrostatically adsorbing HA onto positively charged lipid-polymer hybrid nanoparticles (HA-LPNs). The prepared HA-LPNs exhibited a rounded morphology and a narrow size distribution. In vitro, the anti-inflammatory efficacy of Mag-HA-LPNs (which control levels of the pro-inflammatory cytokines NO, IL-6 and TNF-α) was assessed in RAW 264.7 cells. Analysis by flow cytometry and fluorescence microscopy demonstrated increased cellular uptake through HA/CD44 interaction. As expected, Mag-HA-LPNs was found to effectively increased colon length and reduced DAI scores in DSS-treated mice. This effect was achieved by regulating the inflammatory cytokines level and promoting the restoration of the colonic mucosal barrier through increased expression of Claudin-1, ZO-1 and Occludin. In this study, we developed an efficient and user-friendly delivery method for the preparation of HA-functionalized PLGA nanoparticles, which are intended for oral delivery of Mag. The findings suggest that these HA-LPNs possess the potential to serve as a promising approach for direct drug delivery to the colon for effective treatment of UC.


Assuntos
Compostos de Bifenilo , Colite Ulcerativa , Colite , Lignanas , Nanopartículas , Compostos de Amônio Quaternário , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Ácido Hialurônico , Colo/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Colite/tratamento farmacológico , Sulfato de Dextrana , Camundongos Endogâmicos C57BL
3.
New Microbiol ; 46(4): 361-366, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38252047

RESUMO

The in vitro antimicrobial activity of the active ingredient in antimicrobial magistral drug formulations and plant extracts used in folk medicine were investigated comparatively. Borax, sulfur colloid, hydrogen peroxide, benzoic acid, rivanol, brilliant green and plant extracts as active ingredients, namely: Helianthus tuberosus tuber-H2O (aqueous extract), Cydonia oblonga leaves-H2O, Allium porrum whole plant-H2O, Cistus laurifolius leaves-EtOH, Solanum muricalum-H2O, and Fumaria cilicica leaves-EtOH were studied to determine their antimicrobial activity against different bacteria and fungi (S. pyogenes, S. aureus, S. epidermidis, E. faecalis, K. pneumonia, H. influenza, P. aeruginosa, A. baumannii, E. coli, Candida albicans, C. tropicalis, C. parapsilosis, C. krusei) by using the microdilution method. The active ingredients and plant extracts showed different activities as MIC between 1->128 µg/mL. Brilliant green and rivanol as active ingredients had MIC values of 1 µg/mL against all tested microorganisms. C. oblonga leaves-H2O as well as C. laurifolius leaves-EtOH as plant extracts were indicated as having the highest antimicrobial effect in MIC value of 16 µg/ml against A. baumannii and S. pyogenes, respectively. On the other hand, F. cilicica leaves-EtOH and C. laurifolius leaves-EtOH showed the highest antifungal activity (MIC; 16 µg/mL).


Assuntos
Anti-Infecciosos , Plantas Medicinais , Compostos de Amônio Quaternário , Humanos , Etacridina , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Etanol , Extratos Vegetais/farmacologia
4.
ACS Infect Dis ; 9(12): 2471-2481, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-37950691

RESUMO

Survival of foodborne Gram-negative bacteria during osmotic stress often leads to multidrug resistance development. However, despite the concern, how osmoadaptation alters drug penetration across the Gram-negative bacterial cell envelope has remained inconclusive for years. Here, we have investigated drug permeation and accumulation inside hypo-osmotically shocked Escherichia coli. Three different quaternary ammonium compounds (QACs) are used as cationic amine-containing drug representatives; they also serve as envelope permeability indicators in different assays. Propidium iodide fluorescence reveals cytoplasmic accumulation and overall envelope permeability, while crystal violet sorption and second harmonic generation (SHG) spectroscopy reveal periplasmic accumulation and outer membrane permeability. Malachite green sorption and SHG results reveal transport across both the outer and inner membranes and accumulation in the periplasm as well as cytoplasm. The findings are found to be complementary to one another, collectively revealing enhanced permeabilities of both membranes and the periplasmic space in response to hypo-osmotic stress in E. coli. Enhanced permeability leads to faster QACs transport and higher accumulation in subcellular compartments, whereas transport and accumulation both are negligible under isosmotic conditions. The QACs' transport rates are found to be highly influenced by the osmolytes used, where phosphate ion emerges as a key facilitator of transport across the periplasm into the cytoplasm. E. coli is found viable, with morphology unchanged under extreme hypo-osmotic stress; i.e., it adapts to the situation. The outcome shows that the hypo-osmotic shock to E. coli, specifically using phosphate as an osmolyte, can be beneficial for drug delivery.


Assuntos
Escherichia coli , Compostos de Amônio Quaternário , Escherichia coli/metabolismo , Pressão Osmótica , Membrana Celular/metabolismo , Permeabilidade , Compostos de Amônio Quaternário/análise , Compostos de Amônio Quaternário/metabolismo , Fosfatos/metabolismo
5.
Mol Immunol ; 164: 66-78, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979473

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury involves inflammatory necrosis of liver cells as a significant pathological mechanism. Catapol possesses anti-inflammatory activity that is extracted from the traditional Chinese medicine, Rehmannia glutinosa. METHODS: The liver function and histopathology, Oxidative stress, and aseptic inflammatory responses were assessed in vivo, and the strongest dose group was selected. For mechanism, the expression of miR-410-3p, HMGB1, and TLR-4/NF-κB signaling pathways was detected. The dual luciferase assay can verify the targeting relationship between miR-410-3p and HMGB1. Knockdown of miR-410-3p in L02 cells is applied in interference experiments. RESULTS: CAT pre-treatment significantly decreased the liver function markers alanine and aspartate aminotransferases and reduced the areas of hemorrhage and necrosis induced by hepatic I/R injury. Additionally, it reduced the aseptic inflammatory response and oxidative stress, with the strongest protective effect observed in the high-dose CAT group. Mechanistically, CAT downregulates HMGB1, inhibits TLR-4/NF-κB signaling pathway activation, and reduces inflammatory cytokines TNF-α, and IL-1ß. In addition, the I/R-induced downregulation of microRNA-410-3p was inhibited by CAT pre-treatment in vivo and in vitro. HMGB1 was identified as a potential target of microRNA-410-3p using a dual-luciferase reporter assay. Knockdown of microRNA-410-3p abolished the inhibitory effect of CAT on HMGB1, p-NF-κB, and p-IκB-α protein expression. CONCLUSIONS: Our study showed that CAT pre-treatment has a protective effect against hepatic I/R injury in rats. Specifically, CAT attenuates the aseptic inflammatory response to hepatic I/R injury in vivo and in vitro by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway via the microRNA-410-3p.


Assuntos
Proteína HMGB1 , Fígado , Compostos de Amônio Quaternário , Traumatismo por Reperfusão , Animais , Ratos , Apoptose , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Necrose , NF-kappa B/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/uso terapêutico , Inflamação/tratamento farmacológico
6.
Res Microbiol ; 174(1-2): 103992, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36122890

RESUMO

New drugs are urgently required for the treatment of infections due to an increasing number of new strains of diseases-causing pathogens and antibiotic-resistant bacteria. A library of drugs approved by Food and Drug Administration was screened for efficacy against Vibrio vulnificus using antimicrobial assays. We found that otilonium bromide showed potent antimicrobial activity against V.vulnificus and had a synergistic effect in combination with antibiotics. Field emission transmission electron microscope images revealed that otilonium bromide caused cell division defects in V.vulnificus. Moreover, it significantly inhibited V.vulnificus swarming motility and adhesion to host cells at concentrations lower than the minimum inhibitory concentration. To investigate its inhibitory action mechanisms, we examined the effect of otilonium bromide on the expression levels of several proteins crucial for V.vulnificus growth, motility, and adhesion. It decreased the protein expression levels of cAMP receptor protein and flagellin B, but not HlyU or OmpU. In addition, otilonium bromide significantly decreased the expression levels of outer membrane protein TolCV1, thus inhibiting RtxA1 toxin secretion and substantially reducing V.vulnificus cytotoxicity to host cells. Collectively, these findings suggest that otilonium bromide may be considered as a promising candidate for treating V.vulnificus infections.


Assuntos
Vibrioses , Vibrio vulnificus , Humanos , Vibrio vulnificus/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Compostos de Amônio Quaternário/metabolismo , Compostos de Amônio Quaternário/farmacologia , Testes de Sensibilidade Microbiana , Vibrioses/microbiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-36429408

RESUMO

Disinfectants are used intensively to control and prevent healthcare-associated infections. With continuous use and exposure to disinfectants, bacteria may develop reduced susceptibility. The study aimed to check the hygiene of devices in the physiotherapy department. For isolated bacterial strains, we aimed to determine the minimum inhibitory concentration of five different disinfectant wipe products currently in use. Microbiological environmental sampling in four various institutions in four different cities from two counties was performed, followed by CFU calculation and identification using matrix-assisted laser desorption and ionization with time-of-flight analyzer mass spectrometry (MALDI-TOF). The sampling was performed on three different occasions: before patient use, after patient use, and after disinfection. The susceptibility of isolates to three different alcohol-based and three different quaternary ammonium compounds (QAC) disinfectant wipes was examined by determining the minimal inhibitory concentrations (MIC). We identified 27 different bacterial species from 11 different genera. Gram-positive bacteria predominated. The most abundant genera were Staphylococcus, Micrococcus, and Bacillus. The average MIC values of alcohol-based disinfectants range between 66.61 and 148.82 g/L, and those of QAC-based disinfectants range between 2.4 and 3.5 mg/L. Distinctive strains with four-fold increases in MIC values, compared to average values, were identified. The widespread use of disinfectants can induce a reduction in the susceptibility of bacteria against disinfectants and affect the increase in the proportion of antibiotic-resistant bacteria. Therefore, it is urgent to define clear criteria for defining a microorganism as resistant to disinfectants by setting epidemiological cut-off (ECOFF) values and standardizing protocols for testing the resistance of microorganisms against disinfectants.


Assuntos
Desinfetantes , Humanos , Desinfetantes/farmacologia , Compostos de Amônio Quaternário/farmacologia , Testes de Sensibilidade Microbiana , Higiene , Etanol , Bactérias , Modalidades de Fisioterapia
8.
Oper Dent ; 47(6): 640-647, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36251544

RESUMO

OBJECTIVE: The objective of this in vitro study was to evaluate the effects of potassium iodide on dentin discoloration and ion penetration into the pulp chamber after application of silver diamine fluoride (SDF). METHODS: Proximal surfaces of extracted one-rooted sound human teeth were polished to obtain flat dentin and treated with 17% EDTA for two minutes. Each tooth was then fixed to a test tube. The specimens were distributed into five groups according to the treatment: SDF (Advantage Arrest, Elevate Oral Care); SDF-KI (SSKI, Upsher-Smith); RV-SDF (Riva Star, SDI); and RV-SDFKI. The CIE L*a*b* color value for each proximal dentin was assessed using a colorimeter (CR200, Konica-Minolta) at baseline, after two minutes, 10 minutes, and 24 hours, and ΔE compared to baseline was calculated. Subsequently, the water-filled tube was inverted to collect the ions that had penetrated from the tooth surface into the pulp chamber. Silver, iodide, and fluoride in the pulp were measured using trace element analysis (ISMat) and fluoride ion-selective electrode (Orion, Thermo Scientific) at days 1, 2, 7, and 14. RESULTS: Dentin in both SDF-KI groups showed no visual change in color whereas the groups using only SDF exhibited gradual staining. The time, the treatment and their interaction had a significant effect on ΔE (p<0.001). The fluoride concentrations at day 1 and day 14 for group SDF and KI were significantly lower compared to SDF (p=0.044). There was a difference between control groups and other groups in silver and iodine (p<0.05), whereas there was no significant difference among groups with treatment after 14 days (p>0.05). CONCLUSION: The application of KI after SDF treatment could significantly reduce the dentin staining. The pulpal fluoride concentration in the groups using SDF-KI was lower compared to the ones using SDF only, whereas there was no difference observed in iodide and silver among the groups with treatment.


Assuntos
Cárie Dentária , Iodeto de Potássio , Humanos , Iodeto de Potássio/uso terapêutico , Iodeto de Potássio/farmacologia , Fluoretos/farmacologia , Iodetos/farmacologia , Dentina , Fluoretos Tópicos/farmacologia , Compostos de Amônio Quaternário/farmacologia
9.
Environ Sci Pollut Res Int ; 29(42): 63294-63303, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35449334

RESUMO

For the past few years, the environmental safety problems of radioactive nuclides caused wide public concern. In this work, the dodecyl trimethyl ammonium bromide-modified silicon dioxide composite (DTAB/SiO2) was synthesized for the elimination of uranium. The dodecyl trimethyl ammonium bromide can decorate the surface of the silicon dioxide and change its surface topography, which can offer more active sites and functional groups for the combination of U(VI). The removal capacity of U(VI) on DTAB/SiO2 reached 78.1 mg/g, which was greater than that of the silicon dioxide nanopowder. In the adsorption process, the surface oxygen-containing functional groups formed surface complexation with uranium. The results may provide helpful content to eliminate U(VI) and expand the application of surfactant in radioactive nuclide cleanup.


Assuntos
Urânio , Adsorção , Brometos , Oxigênio , Compostos de Amônio Quaternário , Dióxido de Silício/química , Tensoativos , Urânio/química
10.
J Mater Chem B ; 10(15): 2865-2874, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35266482

RESUMO

The emergence of drug resistance and superbugs poses a devastating threat to public health and can even lead to death. Thus, it is significant to develop a novel antibacterial agent to combat bacterial infections. Herein, we developed quaternary ammonium salt (QAS) modified near-infrared carbon dots (RCDs-C35), which possesses synergistic antibacterial performance under 808 nm irradiation. This nanocomposite exhibits excellent photothermal performance and the photothermal conversion efficiency (PCE) could reach 35%. Generally speaking, the bacterial membrane sensitivity to hyperthermia would be enhanced after QAS caused the initial damage, and thus it can more easily cause bacterial inactivation after irradiation. In vitro and in vivo experiments indicated that the RCDs-C35 exhibit excellent biocompatibility, predominant synergistic antibacterial performance, and the capability of promoting wound healing. The antibacterial ratio against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) could reach 99.5% and 99.8%, respectively, after 808 nm irradiation. Additionally, the cellular imaging indicated that the RCDs-C35 could be used as a fluorescent probe in bioimaging. Therefore, RCDs-C35 with synergistic antibacterial performance and inherent luminescence possess great potential for application in the biomedical field.


Assuntos
Hipertermia Induzida , Staphylococcus aureus , Antibacterianos/farmacologia , Carbono/farmacologia , Escherichia coli , Compostos de Amônio Quaternário/farmacologia
11.
Int J Mol Sci ; 23(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35163609

RESUMO

1H spin-lattice relaxation experiments have been performed for a series of ionic liquids including bis(trifluoromethanesulfonyl)imide anion and cations of a varying alkyl chain length: triethylhexylammonium, triethyloctylammonium, decyltriethylammonium, dodecyltriethylammonium, triethyltetradecylammonium, and hexadecyltriethylammonium. The relaxation studies were carried out in abroad frequency range covering three orders of magnitude, from 10 kHz to 10 MHz, versus temperature. On the basis of a thorough, quantitative analysis of this reach data set, parameters characterizing the relative, cation-cation, translation diffusion (relative diffusion coefficients and translational correlation times), and rotational motion of the cation (rotational correlation times) were determined. Relationships between these quantities and their dependence on the alkyl chain length were discussed in comparison to analogous properties of molecular liquids. It was shown, among other findings, that the ratio between the translational and rotational correlation times is smaller than for molecular liquids and considerably dependent on temperature. Moreover, a comparison of relative and self-diffusion coefficients indicate correlated translational dynamics of the cations.


Assuntos
Líquidos Iônicos/química , Compostos de Amônio Quaternário/química , Difusão , Espectroscopia de Ressonância Magnética , Relaxamento , Temperatura
12.
J Colloid Interface Sci ; 615: 386-394, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35149352

RESUMO

Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.


Assuntos
Hipertermia Induzida , Nanotubos , Neoplasias , Calixarenos , Linhagem Celular Tumoral , Ouro/química , Nanotubos/química , Óxido Nítrico , Fototerapia , Compostos de Amônio Quaternário
13.
J Dairy Sci ; 105(3): 2228-2241, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34998571

RESUMO

We evaluated the effects of supplemental calcium ammonium nitrate (CAN) fed to dairy cows on dry matter (DM) intake, nutrient digestibility, milk quality, microbial protein synthesis, and ruminal fermentation. Six multiparous Holstein cows at 106 ± 14.8 d in milk, with 551 ± 21.8 kg of body weight were used in a replicated 3 × 3 Latin square design. Experimental period lasted 21 d, with 14 d for an adaptation phase and 7 d for sampling and data collection. Cows were randomly assigned to receive the following treatments: URE, 12 g of urea/kg of DM as a control group; CAN15, 15 g of CAN/kg of DM; and CAN30, 30 g of CAN/kg of DM. Supplemental CAN reduced DM intake (URE 19.0 vs. CAN15 18.9 vs. CAN30 16.5 kg/d). No treatment effects were observed for apparent digestibility of DM, organic matter, crude protein, ether extract, and neutral detergent fiber; however, CAN supplementation linearly increased nonfiber carbohydrate digestibility. Milk yield was not affected by treatments (average = 23.1 kg/d), whereas energy-corrected milk (ECM) and 3.5% fat-corrected milk (FCM) decreased as the levels of CAN increased. Nitrate residue in milk increased linearly (URE 0.30 vs. CAN15 0.33 vs. CAN30 0.38 mg/L); however, treatments did not affect nitrite concentration (average: 0.042 mg/L). Milk fat concentration was decreased (URE 3.39 vs. CAN15 3.35 vs. CAN30 2.94%), and the proportion of saturated fatty acids was suppressed by CAN supplementation. No treatment effects were observed on the reducing power and thiobarbituric acid reactive substances of milk, whereas conjugated dienes increased linearly (URE 47.6 vs. CAN15 52.7 vs. CAN30 63.4 mmol/g of fat) with CAN supplementation. Treatments had no effect on microbial protein synthesis; however, molar proportion of ruminal acetate and acetate-to-propionate ratio increased with CAN supplementation. Based on the results observed, supplementing CAN at 30 g/kg of DM should not be recommended as an optimal dose because it lowered DM intake along with ECM and 3.5% FCM, although no major changes were observed on milk quality and ruminal fermentation.


Assuntos
Leite , Nitratos , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Digestão , Ingestão de Alimentos , Feminino , Fermentação , Lactação , Leite/química , Nitratos/farmacologia , Compostos de Amônio Quaternário , Rúmen/metabolismo
14.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166287, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626772

RESUMO

Oxidative stress and lipid peroxidation are major causes of skin injury induced by ultraviolet (UV) irradiation. Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis. We generated UV irradiation-induced skin injury mice model to examine the accumulation of the lipid peroxides and iron. Lipid peroxides 4-HNE, the oxidative enzyme COX2, the oxidative DNA damage biomarker 8-OHdG, and the iron level were increased in UV irradiation-induced skin. The accumulation of iron and lipid peroxidation was also observed in UVB-irradiated epidermal keratinocytes without actual ongoing ferroptotic cell death. Ferroptosis was triggered in UV-irradiated keratinocytes stimulated with ferric ammonium citrate (FAC) to mimic the iron overload. Although GPX4 protected UVB-injured keratinocytes against ferroptotic cell death resulted from dysregulation of iron metabolism and the subsequent increase of lipid ROS, keratinocytes enduring constant UVB treatment were markedly sensitized to ferroptosis. Nicotinamide mononucleotide (NMN) which is a direct and potent NAD+ precursor supplement, rescued the imbalanced NAD+/NADH ratio, recruited the production of GSH and promoted resistance to lipid peroxidation in a GPX4-dependent manner. Taken together, our data suggest that NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced skin diseases or disorders.


Assuntos
Glutationa/genética , Ferro/metabolismo , Estresse Oxidativo/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Pele/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/farmacologia , Aldeídos/farmacologia , Animais , Ciclo-Oxigenase 2/genética , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Compostos Férricos/farmacologia , Ferroptose/efeitos dos fármacos , Ferroptose/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Peróxidos Lipídicos/farmacologia , Camundongos , Mononucleotídeo de Nicotinamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Compostos de Amônio Quaternário/farmacologia , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Raios Ultravioleta/efeitos adversos
15.
Int J Nanomedicine ; 16: 7181-7194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712048

RESUMO

PURPOSE: The aim was to evaluate the antimicrobial potential of AgNPs synthesized with Artemisia argyi leaf extract and investigate the antimicrobial synergistic effects of AgNPs combined with domiphen and provide an efficient and broad-spectrum combination drug strategy. METHODS: AgNPs synthesized with Artemisia argyi leaf extract were studied using UV-vis spectroscopy, FTIR spectroscopy and particle size analysis. Then, Artemisia argyi leaf extract-synthesized AgNPs and domiphen were tested against Acinetobacter baumannii (ATCC 19606), Staphylococcus aureus (ATCC 6538), Escherichia coli (8099) and Candida albicans (ATCC 10231), respectively. Then, we explore synergistic antimicrobial effect and synergistic anti-biofilm effect through combined drug susceptibility test and combined drug minimum biofilm eradication concentration (MBEC50) test. RESULTS: Characteristic absorption bands of AgNPs were found near 430 nm in the UV-vis spectrum. Particle size analysis results revealed that the average particle size of Artemisia argyi leaf extract-synthesized AgNPs was 77.6 nm. Artemisia argyi leaf extract-synthesized AgNPs showed high antimicrobial activity against the above four strains. Minimum inhibitory concentration (MIC) of Artemisia argyi leaf extract-synthesized AgNPs against strains was 1 µg/mL for Acinetobacter baumannii, 2 µg/mL for Staphylococcus aureus, Escherichia coli and Candida albicans. MBEC50 of Artemisia argyi leaf extract-synthesized AgNPs against strains was 2 µg/mL for Acinetobacter baumannii, 4 µg/mL for Staphylococcus aureus, 1/2 µg/mL for Escherichia coli and 2 µg/mL for Candida albicans. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effect and synergistic anti-biofilm effect. Fractional inhibitory concentration (FIC) was ≤0.5. CONCLUSION: Artemisia argyi leaf extract-synthesized AgNPs had antimicrobial activity against the above four strains. The combination of Artemisia argyi leaf extract-synthesized AgNPs and domiphen has synergistic antimicrobial effects to reduce the dosage of each antimicrobial drugs. Artemisia argyi leaf extract-synthesized AgNPs and domiphen have synergistic anti-biofilm effects.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Compostos de Amônio Quaternário , Prata/farmacologia
16.
ACS Appl Mater Interfaces ; 13(36): 43820-43829, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34460222

RESUMO

Biomimetic membrane materials have been widely explored and developed for drug loading and tissue engineering applications due to their excellent biocompatibility and abundant reaction sites. However, novel cytomembrane mimics have been lacking for a long time. In this study, black phosphorus (BP) was used as the foundation for a new generation of promising cytomembrane mimics due to its multiple similarities to cytomembranes. Inspired by the dual function of endotoxins on membranes, we prepared a BP-based cytomembrane mimic with controllable antibacterial ability via electrostatic interaction between BP and [1-pentyl-1-quaternary ammonium-3-vinyl-imidazole]Br ([PQVI]Br). The release of PQVI could be manipulated in different conditions by adjusting the electrostatic force, thereby achieving controllable antibacterial ability. This report confirms the possibility of using BP as a new material to mimic cytomembranes and provides a new concept of controllable antibacterial action based on endotoxins.


Assuntos
Antibacterianos/farmacologia , Preparações de Ação Retardada/química , Imidazóis/farmacologia , Membranas Artificiais , Fósforo/química , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/química , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Imidazóis/química , Testes de Sensibilidade Microbiana , Compostos de Amônio Quaternário/química
17.
Food Chem Toxicol ; 156: 112527, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34464636

RESUMO

Ferric citrate has been used to treat hyperphosphatemia, a prevalent symptom in patients with chronic kidney disease while ferric ammonium citrate (FAC), a more dissolvable format, is widely used as food additive. However, excess iron is associated with osteoporosis. Dietary soybean products have been shown to prevent the progression of osteoporosis. In this study, a group of peptides, referred as P3, was identified from the enzymolysis of soybean protein isolates, and its biological functions were investigated. The results showed that MC3T3-E1 cell cycle progression from G0/G1 to S phase was accelerated by P3 treatment. MC3T3-E1 cell proliferation was enhanced by P3 via ERK1/2 activation. Importantly, P3 treatment abolished the antiproliferative effect of FAC on MC3T3-E1 cell. In addition, P3 treatment increased the expression of ALP, COL-1, OCN, consequently promoting the differentiation and mineralization of MC3T3-E1 cells via activation of p38 MAPK pathway. Consequently, P3 treatment was able to reverse the inhibitory effect of FAC on osteoblasts differentiation and mineralization. Our findings suggest P3, as a dietary supplement, has a potential therapeutic function to attenuate the adverse effects of FAC on bone metabolism and to prevent osteoporosis progression.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Compostos Férricos/toxicidade , Osteoblastos/efeitos dos fármacos , Compostos de Amônio Quaternário/toxicidade , Proteínas de Soja/farmacologia , Células 3T3 , Animais , Sistema de Sinalização das MAP Quinases , Camundongos , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
J Am Chem Soc ; 143(28): 10565-10570, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232661

RESUMO

Aerobic alcohol oxidations catalyzed by transition metal salts and aminoxyls are prominent examples of cooperative catalysis. Cu/aminoxyl catalysts have been studied previously and feature "integrated cooperativity", in which CuII and the aminoxyl participate together to mediate alcohol oxidation. Here we investigate a complementary Fe/aminoxyl catalyst system and provide evidence for "serial cooperativity", involving a redox cascade wherein the alcohol is oxidized by an in situ-generated oxoammonium species, which is directly detected in the catalytic reaction mixture by cyclic step chronoamperometry. The mechanistic difference between the Cu- and Fe-based catalysts arises from the use iron(III) nitrate, which initiates a NOx-based redox cycle for oxidation of aminoxyl/hydroxylamine to oxoammonium. The different mechanisms for the Cu- and Fe-based catalyst systems are manifested in different alcohol oxidation chemoselectivity and functional group compatibility.


Assuntos
Álcoois/química , Óxidos N-Cíclicos/química , Compostos Férricos/química , Nitratos/química , Compostos de Amônio Quaternário/síntese química , Catálise , Estrutura Molecular , Oxirredução , Compostos de Amônio Quaternário/química
19.
Molecules ; 26(14)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34299617

RESUMO

Oligomeric surfactants display the novel properties of low surface activity, low critical micellar concentration and enhanced viscosity, but no CO2 switchable oligomeric surfactants have been developed so far. The introduction of CO2 can convert tertiary amine reversibly to quaternary ammonium salt, which causes switchable surface activity. In this study, epoxidized soybean oil was selected as a raw material to synthesize a CO2-responsive oligomeric surfactant. After addition and removal of CO2, the conductivity analyzing proves that the oligomeric surfactant had a good response to CO2 stimulation. The viscosity of the oligomeric surfactant solution increased obviously after sparging CO2, but returned to its initial low viscosity in the absence of CO2. This work is expected to open a new window for the study of bio-based CO2-stimulated oligomeric surfactants.


Assuntos
Dióxido de Carbono/química , Glycine max/química , Óleo de Soja/química , Tensoativos/química , Aminas/química , Micelas , Compostos de Amônio Quaternário/química , Viscosidade , Água/química
20.
Int J Med Sci ; 18(8): 1899-1909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746607

RESUMO

The morbidity and mortality rates associated with non-small-cell lung carcinoma (NSCLC) are increasing every year, placing new demands on existing therapies and drugs. Ammonium ferric citrate (AFC) is often used as a food additive for iron supplementation; however, to our knowledge, no studies have investigated whether AFC can induce ferroptosis in NSCLC. In this study, we demonstrated that specific concentrations of AFC effectively inhibit the proliferation and invasion of lung cancer cell lines in vitro using a cell proliferation inhibition test, a transwell assay, and flow cytometry analysis of cell cycle and apoptosis. In addition, AFC significantly induced oxidative stress injury in lung cancer cell lines. A quantitative polymerase chain reaction assay showed that AFC markedly reduced the expression levels of cell growth factors, negative regulators of ferroptosis, and autophagy regulators. Lastly, a protein-protein interaction analysis revealed that glutathione peroxidase 4 (GPX4) exerted its biological role through the regulation of the GSS/GSR complex and downstream GGT family proteins. When the expression of GPX4 changes, its biological activities, such as the glutathione metabolic process, cellular biosynthetic process, cellular response to chemical stimulus, and antioxidant activity, change accordingly, thereby affecting the survival quality and physiological and biochemical activities of cells. Overall, this study verifies that AFC has the biological activity of activating oxidative stress injury in NSCLC cell lines, leading to a decrease in their autophagy and inducing ferroptosis. We also confirmed that the GPX4-GSS/GSR-GGT axis is a crucial target of AFC-induced ferroptosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Compostos Férricos/farmacologia , Ferroptose/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Amônio Quaternário/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/uso terapêutico , Glutationa Redutase/metabolismo , Glutationa Sintase/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Compostos de Amônio Quaternário/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , gama-Glutamiltransferase/metabolismo
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