RESUMO
Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of MÏller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and MÏller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.
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This study is designed to obtain recombinant human acetylcholinesterase (rhAChE) and apply it in screening acetylcholinesterase inhibitors. The rhAChE was overexpressed in HEK293 cells transfected by plasmid of pCMV-AChE with the cationic liposome and rhAChE was found to be secreted into cell culture medium. AChE activity was assayed according to modified Ellman method to obtain kinetic parameters. IC so50 values for donepezil compounds of rhAChE were calculated to determine their activities of inhibition. The results showed that Km value was 151.9 micromol.L-1 donepezil inhibited rhAChE in a mixed competitive-noncompetitive way (Ki= 16.03 nmol.L-1, Ki = 18.36 nmol.L-1) and that most new compounds tested exhibited high activities of inhibition on rhAChE. The study suggests that rhAChE is available to be applied in screening AChE inhibitors in vitro.
Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/análise , Indanos/análise , Piperidinas/análise , Acetilcolinesterase/genética , Inibidores da Colinesterase/farmacologia , Donepezila , Células HEK293 , Humanos , Indanos/farmacologia , Concentração Inibidora 50 , Cinética , Piperidinas/farmacologia , Plasmídeos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , TransfecçãoRESUMO
Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.
Assuntos
Ferro , Ferro/farmacologia , Ferro/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Ácidos Graxos/metabolismo , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Óxido Ferroso-Férrico/química , Percepção de Quorum/efeitos dos fármacosRESUMO
This study aimed to determine whether regular recruitment maneuvers (RMs) are essential for obese patients (OPs) undergoing elective laparoscopic bariatric surgery (LBS) during intraoperative ventilation with individualized positive end-expiratory pressure (PEEP). Patients were randomly assigned to two arms: the RM + PEEP-EIT arm consisted of individualized PEEP titrated by electrical impedance tomography (EIT) with two regular RMs and the PEEP-EIT arm consisted of individualized PEEP titrated by EIT without additional RMs. For these two arms together, EIT-guided PEEP varied among individuals. The partial pressure of oxygen in arterial blood to fractional inspired oxygen (PaO2 /FiO2 ) ratio in the RM + PEEP-EIT arm was higher than that in the PEEP-EIT arm at 1 h after pneumoperitoneum (p = 0.024) and at the end of surgery (p = 0.035). There was no great difference in the PaO2 /FiO2 ratio between these two arms when measured 5 min prior to postanesthesia care unit (PACU) departure and on postoperative day 1. Compared with the PEEP-EIT arm, patients in the RM + PEEP-EIT arm had significantly higher intraoperative dynamic respiratory system compliance (p < 0.001) but consumed more vasopressors (p = 0.036). Postoperative pulmonary complications occurred in 1 of 29 patients in the RM + PEEP-EIT arm compared with 2 of 31 patients in the PEEP-EIT arm. Regular lung RMs can improve intraoperative oxygenation and respiratory system compliance among OPs undergoing LBS with EIT-guided individual PEEP. However, the improvement might disappear before leaving the PACU, and regular RMs resulted in more vasopressor consumption.
Assuntos
Cirurgia Bariátrica , Respiração com Pressão Positiva , Impedância Elétrica , Humanos , Obesidade/complicações , Obesidade/cirurgia , Oxigênio , Respiração com Pressão Positiva/métodos , Complicações Pós-OperatóriasRESUMO
Extracellular ATP and its ultimate degradation product adenosine are potent extracellular signaling molecules that elicit a variety of pathophysiological pathways in retina through the activation of P2 and P1 purinoceptors, respectively. Excessive build-up of extracellular ATP accelerates pathologic responses in retinal diseases, whereas accumulation of adenosine protects retinal cells against degeneration or inflammation. This mini-review focuses on the roles of ATP and adenosine in three types of blinding diseases including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Several agonists and antagonists of ATP receptors and adenosine receptors (ARs) have been developed for the potential treatment of glaucoma, DR and AMD: antagonists of P2X7 receptor (P2X7R) (BBG, MRS2540) prevent ATP-induced neuronal apoptosis in glaucoma, DR, and AMD; A1 receptor (A1R) agonists (INO-8875) lower intraocular pressure in glaucoma; A2A receptor (A2AR) agonists (CGS21680) or antagonists (SCH58261, ZM241385) reduce neuroinflammation in glaucoma, DR, and AMD; A3 receptor (A3R) agonists (2-Cl-lB-MECA, MRS3558) protect retinal ganglion cells (RGCs) from apoptosis in glaucoma.
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BACKGROUND: While the influence of meteorology on carbon monoxide (CO) poisoning has been reported, few data are available on the association between air pollutants and the prediction of CO poisoning. Our objective is to explore meteorological and pollutant patterns associated with CO poisoning and to establish a predictive model. RESULTS: CO poisoning was found to be significantly associated with meteorological and pollutant patterns: low temperatures, low wind speeds, low air concentrations of sulfur dioxide (SO2) and ozone (O38h), and high daily temperature changes and ambient CO (r absolute value range: 0.079 to 0.232, all P values < 0.01). Based on the above factors, a predictive model was established: "logitPj = aj - 0.193 * temperature - 0.228 * wind speed + 0.221 * 24 h temperature change + 1.25 * CO - 0.0176 * SO2 + 0.0008 *O38h; j = 1, 2, 3, 4; a1 = -4.12, a2 = -2.93, a3 = -1.98, a4 = -0.92." The proposed prediction model based on combined factors showed better predictive capacity than a model using only meteorological factors as a predictor. CONCLUSION: Low temperatures, wind speed, and SO2 and high daily temperature changes, O38h, and CO are related to CO poisoning. Using both meteorological and pollutant factors as predictors could help facilitate the prevention of CO poisoning.
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The aim of this study was to obtain the soluble protein of human pregnane X receptor ligand binding domain (PXRLBD) through the coexpression of PXRLBD and 88 amino acids of steroid receptor coactivator-1 (SRC88) and apply the protein to constructing a new model of screening PXR ligands. Expression plasmid of pETDuet-1-SRC88-PXRLBD was constructed and transformed into Escherichia coli Rosetta (DE3) to coexpress PXRLBD and SRC88 via induction by IPTG at low temperature. Then an equilibrium dialysis model was constructed to study the interaction between PXRLBD and drugs including clotrimazole and dexamethasone, using HPLC as the analysis method. The results showed that the soluble protein of PXRLBD was obtained and the HPLC data indicated that clotrimazole bound to PXRLBD, while dexamethasone did not bind to PXRLBD, which indicated the successful establishment of a new method for studying the interaction between PXR and drugs. The new method may be useful in the screening of PXR ligands in vitro.
Assuntos
Clotrimazol/metabolismo , Dexametasona/metabolismo , Diálise/métodos , Histona Acetiltransferases/metabolismo , Receptores de Esteroides/metabolismo , Fatores de Transcrição/metabolismo , Interações Medicamentosas , Escherichia coli/genética , Escherichia coli/metabolismo , Histona Acetiltransferases/genética , Humanos , Ligantes , Coativador 1 de Receptor Nuclear , Plasmídeos , Receptor de Pregnano X , Ligação Proteica , Receptores de Esteroides/genética , Fatores de Transcrição/genética , Transformação GenéticaRESUMO
Effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on growth performance, blood metabolites, immune traits, and tissue chromium in finishing pigs were investigated. A total of 160 crossbred barrows (66.06 ± 1.01 kg initial weight) were randomly divided into four groups, each group with four pens, ten pigs per pen. Pigs were fed on the same basal diet supplemented with 0 (the control), 100, 200, and 400 µg/kg Cr from Cr-CNP. All pigs were given free access to feed and water. Eight pigs from each treatment were selected to collect blood and tissue samples after 35 days on trial for analysis of blood metabolites and immune traits and tissue chromium. The results of feeding trial showed that there were no significant difference in growth performance between control and Cr-CNP-treated groups. The supplementation of Cr-CNP decreased serum glucose (P < 0.001) in a linear and quadratic manner. Serum immunoglobulins A and M were linearly increased in Cr-CNP-treated groups (P < 0.001), and serum complement 4 in Cr-CNP-treated groups was also linearly increased (P < 0.05). Cr-CNP supplementation linearly increased the chromium content in the blood, longissimus muscle, heart, liver, kidney, and pancreas (P < 0.001). These results suggested that dietary supplementation of Cr as Cr-CNP affects serum glucose, influences immune status, and increases the tissue chromium content of blood, muscle, and selected organs in finishing pigs.