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 farmacológicoRESUMO
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/microbiologiaRESUMO
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 FisioterapiaRESUMO
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/farmacologiaRESUMO
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/farmacologiaRESUMO
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 adversosRESUMO
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/químicaRESUMO
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/metabolismoRESUMO
Silver diamine fluoride (SDF) is commonly used to arrest caries lesions, especially in early childhood caries. Recently, it was suggested that SDF can be combined with potassium iodide (KI) to minimize the discoloration of demineralized dentine associated with SDF application. However, the antibacterial efficacy of SDF alone or combined with KI on in-situ biofilm is unknown. Hence, we compared the anti-plaque biofilm efficacy of two different commercially available SDF solutions, with or without KI, using an in-situ biofilm, analysed using viability real-time PCR with propidium monoazide (PMA). Appliance-borne in-situ biofilm samples (n = 90) were grown for a period of 6 h in five healthy subjects who repeated the experiment on three separate occasions, using a validated, novel, intraoral device. The relative anti-biofilm efficacy of two SDF formulations; 38.0% Topamine (SDFT) and 31.3%, Riva Star (SDFR), KI alone, and KI in combination with SDFR (SDFR+KI) was compared. The experiments were performed by applying an optimized volume of the agents onto the biofilm for 1min, mimicking the standard clinical procedure. Afterwards the viability of the residual biofilm bacteria was quantified using viability real-time PCR with PMA, then the percentage of viable from total bacteria was calculated. Both SDF formulations (SDFT and SDFR) exhibited potent antibacterial activities against the in-situ biofilm; however, there was non-significant difference in their efficacy. KI alone did not demonstrate any antibacterial effect, and there was non-significant difference in the antibacterial efficacy of SDF alone compared to SDF with KI, (SDFT v SDFR/KI). Thus, we conclude that the antibacterial efficacy of SDF against plaque biofilms is not modulated by KI supplements. Viability real-time PCR with PMA was successfully used to analyze the viability of naturally grown oral biofilm; thus, the same method can be used to test the antimicrobial effect of other agents on oral biofilms in future research.
Assuntos
Antibacterianos/farmacologia , Azidas/farmacologia , Biofilmes/classificação , Iodeto de Potássio/farmacologia , Propídio/análogos & derivados , Compostos de Amônio Quaternário/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Compostos de Prata/farmacologia , Adulto , Biofilmes/efeitos dos fármacos , Calibragem , Feminino , Fluoretos Tópicos/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Propídio/farmacologiaRESUMO
Ionic liquids are increasingly used for their superior properties. Four water-immiscible ionic liquids (butyltriethylammonium bis(trifluoromethylsulfonyl)imide, octyltriethylammonium bis(trifluoromethylsulfonyl)imide, dodecyltriethylammonium bis(trifluoromethylsulfonyl)imide, butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and their water miscible precursors (bromides) were synthesized in a microwave reactor and by conventional heating. The best conditions for microwave-assisted synthesis concerning the yield and the purity of the product are proposed. The heating in the microwave reactor significantly shortened the reaction time. Biocide and ecotoxic effects of synthesized ionic liquids and their precursors were investigated. All tested compounds had at least a little effect on the growth or living of microorganisms (bacteria or mold). The precursor dodecyltriethylammonium bromide was found to be the strongest biocide, but posed a risk to the aquatic environment due to its relatively high EC50 value in the test with Vibrio fischeri. We assumed that apart from the alkyl chain length, the solubility in water, duration of action, or type of anion can influence the final biocide and ecotoxic effect.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Líquidos Iônicos/síntese química , Líquidos Iônicos/farmacologia , Aliivibrio fischeri/efeitos dos fármacos , Compostos de Amônio/química , Antibacterianos/síntese química , Antifúngicos/síntese química , Antifúngicos/química , Avaliação Pré-Clínica de Medicamentos/métodos , Ecotoxicologia/métodos , Imidazóis/química , Micro-Ondas , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/farmacologiaRESUMO
The aim of this study was to evaluate the effect of silver diamine fluoride and grape seed extract on the microstructure and mechanical properties of carious dentin following exposure to acidic challenge. Ninety-eight molars with occlusal caries were used. In the control group the specimens were kept in distilled water. In the GSE group, the specimens were immersed in 6.5% grape seed extract solution for 30 minutes. In the SDF group, the specimens were immersed in 30% SDF solution for 4 minutes. In the GSE+SDF group, the specimens were immersed in 6.5% grape seed extract solution for 30 minutes and then exposed to 30% SDF solution for 4 minutes. All the groups underwent pH cycling model for 8 days. Microhardness measurements were taken at the baseline before surface treatments and after pH cycling. Elastic modulus was measured, after pH cycling. In the control group, the final hardness was significantly lower than the initial hardness (P = 0.001). In the SDF group, the final hardness was significantly higher than the initial hardness (P < 0.001). There was no significant difference between the initial and final hardness values in the GSE and GSE + SDF groups (p = 0.92, p = 0.07). The H1-H0 in the SDF group was significantly higher than the other groups (P<0.05). Moreover, elastic modulus of the experimental groups except GSE+SDF group was significantly higher than control. The highest mean elastic modulus was detected in the SDF group (P<0.001). The use of SDF and GSE prior to the acid challenge improved mechanical properties. Microstructural investigation, using scanning electron microscope showed dentin structure protection against acid challenges with SDF treatment and collagen matrix stabilization with GSE treatment. However combined use of these agents was not beneficious.
Assuntos
Ácidos/efeitos adversos , Dentina/efeitos dos fármacos , Extrato de Sementes de Uva/farmacologia , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Compostos de Amônio Quaternário/farmacologia , Compostos de Prata/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Dentina/ultraestrutura , Módulo de Elasticidade/efeitos dos fármacos , Fluoretos Tópicos/farmacologia , HumanosRESUMO
Two randomized block designs were performed to evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on enteric methane production, nutrient digestibility, liver mineral concentration, and performance of beef cattle consuming bahiagrass hay (Paspalum notatum; ad libitum) and sugar cane molasses [1.07 kg/d; dry matter basis]. Experiment 1, used 25 crossbred steers [335 ± 46 kg of initial body weight (BW)] with a 2 × 2 + 1 factorial arrangement of treatments for two 20 d periods. Factors were nonprotein nitrogen (NPN) source (350 mg/kg BW of nitrate or 182 mg/kg BW of urea), BSS (0 or 58.4 mg/kg BW), and a negative control (NCTRL; bahiagrass hay and molasses only). Steers were re-randomized for a second period (n = 10/treatment total). Intake, apparent total tract digestibility and enteric methane were evaluated. Experiment 2 used 75 crossbred heifers in 25 pens (3 heifers/pen; 279 ± 57 kg of initial BW), consuming the same diet and treatments as experiment 1, to determine liver mineral concentration and growth performance over 56 d. Orthogonal contrasts were used to evaluate the effects of NPN (NCTRL vs. others), source of NPN (NS; urea vs. eCAN), BSS, and NS × BSS. For experiment 1, no interactions were observed for any variables, nor were there any effects of NPN on total tract digestibility of nutrients, except for crude protein. Digestibility of all nutrients was reduced (P ≤ 0.021) for steers consuming eCAN compared with urea. There was no effect (P > 0.155) of BSS on digestibility of nutrients; however, BSS reduced (P = 0.003) apparent S retention. Enteric CH4 emission (g/kg BW0.75) was decreased (P = 0.051) by 11% with the addition of eCAN compared with urea. For experiment 2, no NS × BSS interactions (P ≥ 0.251) were observed to affect liver mineral concentration; however, the addition of BSS decreased liver concentration of Cu (P = 0.002) while increasing Fe concentration (P = 0.016). There was an NS × BSS interaction (P = 0.048) where heifers consuming eCAN and BSS had lesser final BW compared with heifers consuming urea and BSS. While eCAN may be a viable resource for mitigating enteric CH4 production of forage-fed cattle, the negative effects on digestibility should be considered. Furthermore, BSS, at the amount provided, appears to have no negative effects on digestibility of nutrients in forage-fed cattle; however, there may be deleterious impacts on performance depending upon what nitrogen source is supplied.
Assuntos
Bismuto/farmacologia , Bovinos/fisiologia , Suplementos Nutricionais/análise , Metano/metabolismo , Minerais/análise , Nitratos/farmacologia , Compostos Organometálicos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Salicilatos/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Digestão/efeitos dos fármacos , Feminino , Trato Gastrointestinal/metabolismo , Fígado/metabolismo , Masculino , Melaço , Nutrientes/metabolismo , Paspalum , Distribuição Aleatória , Saccharum , Ureia/metabolismoRESUMO
We reported for the first time that cationic pillar[6]arene (cPA6) could tightly bind to peptide polymer (MW~20-50 kDa), an artificial substrate for tyrosine (Tyr) phosphorylation, and efficiently inhibit Tyr protein phosphorylation through host-guest recognition. We synthesized a nanocomposite of black phosphorus nanosheets loaded with cPA6 (BPNS@cPA6) to explore the effect of cPA6 on cells. BPNS@cPA6 was able to enter HepG2 cells, induced apoptosis, and inhibited cell proliferation by reducing the level of Tyr phosphorylation. Furthermore, BPNS@cPA6 showed a stronger ability of inhibiting cell proliferation in tumor cells than in normal cells. Our results revealed the supramolecular modulation of enzymatic Tyr phosphorylation by the host-guest recognition of cPA6.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Antineoplásicos/administração & dosagem , Cátions/administração & dosagem , Cátions/farmacologia , Portadores de Fármacos/química , Células Hep G2 , Humanos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fósforo/química , Compostos de Amônio Quaternário/administração & dosagem , Tirosina/metabolismoRESUMO
A replicated 5 × 5 Latin square design with a 2 × 2 + 1 factorial arrangement of treatments was used to determine the effects of bismuth subsalicylate (BSS) and encapsulated calcium ammonium nitrate (eCAN) on ruminal fermentation of beef cattle consuming bahiagrass hay (Paspalum notatum) and sugarcane molasses. Ten ruminally cannulated steers (n = 8; 461 ± 148 kg of body weight [BW]; average BW ± SD) and heifers (n = 2; 337 ± 74 kg of BW) were randomly assigned to one of five treatments as follows: 1) 2.7 g/kg of BW of molasses (NCTRL), 2) NCTRL + 182 mg/kg of BW of urea (U), 3) U + 58.4 mg/kg of BW of BSS (UB), 4) NCTRL + 538 mg/kg of BW of eCAN (NIT), and 5) NIT + 58.4 mg/kg of BW of BSS (NITB). With the exception of NCTRL, all treatments were isonitrogenous. Beginning on day 14 of each period, ruminal fluid was collected and rectal temperature was recorded 4× per day for 3 d to determine ruminal changes every 2 h from 0 to 22 h post-feeding. Ruminal gas cap samples were collected at 0, 3, 6, 9, and 12 h on day 0 of each period followed by 0 h on days 1, 2, 3, and 14. Microbial N flow was determined using Cr-Ethylenediaminetetraacetic acid, YbCl3, and indigestible neutral detergent fiber for liquid, small particle, and large particle phases, respectively. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts were used to evaluate the effects of nonprotein nitrogen (NPN) inclusion, NPN source, BSS, and NPN source × BSS. There was no treatment effect (P > 0.05) on concentrations of H2S on day 0, 1, 2, or 14; however, on day 3, concentrations of H2S were reduced (P = 0.018) when NPN was provided. No effect of treatment (P = 0.864) occurred for ruminal pH. There was an effect of NPN source on total concentrations of VFA (P = 0.011), where a 6% reduction occurred when eCAN was provided. There were effects of NPN (P = 0.001) and NPN source (P = 0.009) on the concentration of NH3-N, where cattle consuming NPN had a greater concentration than those not consuming NPN, and eCAN reduced the concentration compared with urea. Total concentrations of VFA and NH3-N were not affected (P > 0.05) by BSS. There was an effect of BSS (P = 0.009) on rectal temperature, where cattle not consuming BSS had greater temperatures than those receiving BSS. No differences for NPN, NPN source, nor BSS (P > 0.05) were observed for microbial N flow. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared with urea, and BSS has limited effects on fermentation.
Assuntos
Bismuto/farmacologia , Bovinos/fisiologia , Suplementos Nutricionais/análise , Nitratos/farmacologia , Compostos Organometálicos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Salicilatos/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Digestão/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Masculino , Melaço , Nitrogênio/metabolismo , Paspalum , Rúmen/efeitos dos fármacos , Rúmen/metabolismo , Saccharum , Ureia/metabolismoRESUMO
OBJECTIVES: The main goal of this study was to investigate the effectiveness of SDF and its individual components, silver (Ag+) and fluoride (F-) ions, in preventing enamel demineralization using biofilm and chemical models. METHODES: Polished human enamel specimens were assigned to five treatment groups (nâ¯=â¯18 per group): SDF (38 %); SDF followed by application of a saturated solution of potassium iodide (SDFâ¯+â¯KI); silver nitrate (AgNO3; silver control, 253,900â¯ppm Ag+); potassium fluoride (KF; fluoride control, 44,800â¯ppm F); deionized water (DIW). Treatments were applied once to sound enamel. In the biofilm model, specimens were demineralized by aerobic overnight incubation using cariogenic bacteria isolated from human saliva in brain heart infusion supplemented with 0.2 % sucrose for three days. In the chemical model, enamel specimens were immersed in a demineralizing solution containing 0.1â¯M lactic acid, 4.1â¯mM CaCl2, 8.0â¯mM KH2PO4, 0.2 % Carbopol 907, pH adjusted to 5.0 for five days. Vickers surface microhardness was used to determine the extent of enamel demineralization. Data were analyzed using one-way ANOVA. RESULTS: In the chemical model, there was no statistically significant difference between SDF and SDFâ¯+â¯KI in preventing coronal caries (pâ¯<â¯0.0001). In the biofilm model, SDFâ¯+â¯KI was significantly less effective in preventing demineralization than SDF (pâ¯<â¯0.0001). In both models, SDF and SDFâ¯+â¯KI were superior in their ability to prevent caries lesion formation than AgNO3 and DIW. CONCLUSION: KI application after SDF treatment appears to impair SDF's ability to prevent biofilm-mediated but not chemically induced demineralization. CLINICAL SIGNIFICANCE: SDF may be a viable option in preventing primary coronal caries.
Assuntos
Cárie Dentária , Desmineralização do Dente , Biofilmes , Cariostáticos , Cárie Dentária/prevenção & controle , Fluoretos Tópicos , Humanos , Compostos de Amônio Quaternário/farmacologia , Compostos de Prata , Desmineralização do Dente/prevenção & controleRESUMO
Objective: To investigate the caries prevention effect of silver diamine fluoride (SDF) with a carbon dioxide (CO2) laser (λ = 10,600 nm) on dentin. Method: Human dentin slices (n = 10) were prepared and allocated to the following treatments: Group 1 (SDF)-slices received an SDF application. Group 2 (laser)-slices were irradiated with a CO2 laser. Group 3 (laser + SDF)-slices were irradiated with a CO2 laser, followed by an SDF application. Group 4 (negative control)-slices had no treatment. All of the slices were subjected to pH cycling for cariogenic challenge. Lesion depth, nanohardness, and chemical and morphological changes were assessed by microcomputed tomography (micro-CT), nanoindentation, and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), respectively. Results: micro-CT determined lesion depths for groups 1-4 were 27 ± 6, 138 ± 32, 17 ± 5, and 182 ± 49 µm, respectively (p < 0.001; group 3 < group 1 < groups 2 and 4). The nanohardness values for groups 1-4 were 456 ± 109, 288 ± 5, 444 ± 142, and 258 ± 76 MPa, respectively (p = 0.003; groups 2 and 4 < groups 1 and 3). EDS determined that the calcium-to-phosphorus molar ratio for groups 1-4 were 1.26 ± 0.12, 1.07 ± 0.19, 1.37 ± 0.08, and 0.80 ± 0.17, respectively (p < 0.001; group 4 < group 2 < groups 1 and 3). SEM evidenced no ablation or cracking on the lased dentin surfaces. The treated dentin showed a relatively more intact and smoother surface morphology compared with the untreated dentin. Conclusions: SDF can reduce dentin demineralization against cariogenic challenge, and the caries preventive effect of SDF is further enhanced through CO2 laser irradiation.
Assuntos
Cárie Dentária/prevenção & controle , Dentina/efeitos dos fármacos , Dentina/efeitos da radiação , Lasers de Gás , Terapia com Luz de Baixa Intensidade , Compostos de Amônio Quaternário/farmacologia , Compostos de Prata/farmacologia , Dentina/ultraestrutura , Fluoretos Tópicos/farmacologia , Humanos , Microscopia Eletrônica de Varredura , Técnicas de Cultura de TecidosRESUMO
Refractory root canal infection of human teeth is the primary cause of dental treatment failure. Enterococcus faecalis is the major cause of refractory root canal infection. In the present study, poly(D,L-lactic-co-glycolide) (PLGA) submicron particles were used as carriers to deliver an antimicrobial quaternary ammonium silane (code-named K21) as well as calcium and phosphorus elements. The release profiles, antibacterial ability against E. faecalis, extent of infiltration into dentinal tubules, biocompatibility and in vitro mineralization potential of the particles were investigated. In addition, the antimicrobial effects of the particles against E. faecalis infection were evaluated in vivo in the teeth of beagle dogs. The encapsulated components were released from the PLGA particles in a sustained-release manner. The particles also displayed good biocompatibility, in vitro mineralization ability and antibacterial activity against E. faecalis. The particles could be driven into dentinal tubules of dentin slices by ultrasonic activation and inhibited E. faecalis colonization. In the root canals of beagle dogs, PLGA submicron particles loaded with K21, calcium and phosphorus demonstrated strong preventive effects against E. faecalis infection. The system may be developed into a new intracanal disinfectant for root canal treatment.
Assuntos
Cálcio/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Tamanho da Partícula , Fósforo/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Silanos/farmacologia , Dente/microbiologia , Animais , Antibacterianos/farmacologia , Linhagem Celular , Cães , Feminino , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Eletricidade Estática , Fosfatase Ácida Resistente a Tartarato/metabolismo , Dente/diagnóstico por imagem , Dente/patologiaRESUMO
Trace amines have been reported to be neuromodulators of monoaminergic systems. Trace amines receptor 5 (TAAR5) is expressed in several regions of mice central nervous system, such as amygdala, arcuate nucleus and ventromedial hypothalamus, but very limited information is available on its functional role. The purpose of this study is to examine the effect of TAAR5 agonist alpha-NETA on the generation of mismatch negativity (MMN) analogue in C57BL/6 mice. Event-related potentials have been recorded from awake mice in oddball paradigms before and after the alpha-NETA administration. Alpha-NETA has been found to decrease N40 MMN-like difference, which resulted from the increased response to standard stimuli. An opposite effect has been found for the P80 component: the amplitude increased in response both to standard and deviant stimuli. A significant increase in N40 peak latency after the alpha-NETA administration has been found. This may suggest a reduced speed of information processing similar to the increase in P50 and N100 components latencies in schizophrenia patients. These results provide new evidence for a role of TAAR5 in cognitive processes.
Assuntos
Estimulação Acústica/métodos , Potenciais Evocados Auditivos/fisiologia , Compostos de Amônio Quaternário/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/fisiologia , Vigília/fisiologia , Animais , Eletroencefalografia/métodos , Potenciais Evocados Auditivos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos de Amônio Quaternário/química , Vigília/efeitos dos fármacosRESUMO
BACKGROUND Iron overload is a prominent characteristic of liver injury, but there is no effective treatment at present. Qizhufang (ZSF) is a Chinese herbal formula showed anti-HBV activities, improved liver function, and anti-fibrosis effect. ZSF showed a series of liver-protection functions, but whether ZSF can relieve hepatic iron overload is still unclear. MATERIAL AND METHODS Ferric ammonium citrate (FAC) was used to construct iron-overloaded LO2 cells. The cell apoptosis and proliferation were measured by flow cytometry and CCK-8 assay, respectively. ROS level was analyzed by fluorescence probe. RNA and protein expressions were assessed by real-time PCR and Western blot. RESULTS FAC upregulated apoptosis rate, ROS level, and expression of hepcidin and p-STAT3, but suppressed proliferation and expression of DMT1, FPN1, and CP in LO2 cells. However, Qizhufang (ZSF) reversed the effect of FAC. We also found that hepcidin overexpression suppressed the expressions of DMT1, FPN1, and CP, which were reversed by ZSF. Additionally, STAT3 inhibitor AG490 suppressed hepcidin expression. Moreover, exogenous IL-6 reversed the effect of ZSF on apoptosis rate, ROS level, and the expression of hepcidin, DMT1, FNP1, CP, and p-STAT3. CONCLUSIONS Qizhufang (ZSF) can ameliorate iron overload-induced injury by suppressing hepcidin via the STAT3 pathway in LO2 cells.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Medicamentos de Ervas Chinesas/metabolismo , Compostos Férricos/farmacologia , Hepcidinas/metabolismo , Humanos , Interleucina-6/metabolismo , Ferro/metabolismo , Sobrecarga de Ferro/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Medicina Tradicional Chinesa , Compostos de Amônio Quaternário/farmacologia , Espécies Reativas de Oxigênio , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
The potential contribution of trace amines (TA) to the pathophysiology of neuropsychiatric disorders makes it interesting to examine the effect of TA receptor ligands on schizophrenia biomarkers. We studied the effect of systemic administration of a putative Trace Amine-Associated Receptor 5 (TAAR5) agonist, alpha-NETA (2-(alpha-naphthoyl) ethyltrimethylammonium iodide), on the amplitude of the N40 event related potentials component and on the sensory gating (SG) index in C57BL/6 mice. It was found that low doses of alpha-NETA (2.5â¯mg/kg and 5â¯mg/kg) do not elicit a significant effect on the parameters of the N40 component and the SG index. However, the higher dose of alpha-NETA (10â¯mg/kg) induces a significant effect on the N40 component, but since a decrease in amplitude is observed on both the first and second stimuli in the pair, the SG index does not change. Thus, alpha-NETA administration causes a steady decrease in the N40 amplitude in response to both the first and second stimuli in the paired-click paradigm, and an increase in the N40 peak latency.