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1.
Artigo em Inglês | MEDLINE | ID: mdl-34048349

RESUMO

With the rapid development of swarm intelligence, the consensus of multiagent systems (MASs) has attracted substantial attention due to its broad range of applications in the practical world. Inspired by the considerable gap between control theory and engineering practices, this article is aimed at addressing the mean square consensus problems for stochastic dynamical nonlinear MASs in directed networks by designing proportional-integral (PI) protocols. In light of the general algebraic connectivity, consensus underlying PI protocols for a directed strongly connected network is investigated, and due to the M-matrix approaches, consensus with PI protocols for a directed network containing a spanning tree is studied. By constructing appropriate Lyapunov functions, combining with the stochastic analysis technique and LaSalle's invariant principles, some sufficient conditions are derived under which the stochastic dynamical MASs realize consensus in mean square. Numerical simulations are finally presented to illustrate the validity of the main results.

2.
Sci Total Environ ; 789: 147778, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34051498

RESUMO

Controlled-release urea (CRU) fertilizer application has been shown to improve crop yield and nitrogen (N) use efficiency. However, its effects when mixed with conventional urea fertilizer on soil aggregate stability, humic acid (HA) molecular composition and crop N uptake remain unclear. Soil and plant samples were collected from a long-term (2008-2019) experiment on field maize (Zea mays L., 'Zhengdan 958') which included two types of fertilizers [conventional urea fertilizer (CUF), blended CUF with CRU fertilizer (CRF)], four N application rates (0, 150, 300 and 450 kg ha-1), each in three replicates. The results showed that at 300 kg N ha-1, compared to CUF treatment, the CRF treatment significantly improved soil aggregate characteristics [aggregate content with particle size larger than 0.25 mm (R0.25) by 9.6%, mean weight diameter by 19.8%, and geometric mean diameter by 21.7%]. CRF treatment also increased HA content by 5.5%, fulvic acid (FA) by 5.5%, lignin-like molecules by 0.94 times, and protein-like molecules by 3.69 times. At grain-filling stage, CRF treatments significantly increased the sum of soil NH4+-N and NO3--N content by 23.3-24.5%, sap bleeding rate by 12.8-18.2% and N delivery rate through bleeding sap by 60.6-87.7% compared to CUF treatments at the same N application rate. At the same rate of N application, the CRF treatments significantly improved the average yield during three growing seasons by 9.4-14.0% in contrast with CUF treatments. The regression equations showed that the maximum yield was 8294 kg ha-1 for CUF at the application rate of 312 kg N ha-1 while it was 9890 kg ha-1 for CRF at the application rate of 286 kg N ha-1. We conclude that the long-term application of CRF changed the HA molecular structure, enhanced the water stable aggregates, improved crop N uptake, and increased economically viable maize yield.

3.
Phytomedicine ; 87: 153586, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34044253

RESUMO

BACKGROUND: Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases. PURPOSE: The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis. STUDY DESIGN: Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin. METHODS: Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA, qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury. RESULTS: The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1ß (IL-1ß) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA, SOD, and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro. CONCLUSIONS: These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.

4.
Sci Total Environ ; 788: 147747, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34034193

RESUMO

This study used a chemical transport model to investigate the response of secondary inorganic aerosols (SIA) to chemical processes and its precursor emissions over northern and southern city-clusters of China in January 2014. Unexpectedly, SIA concentrations with low levels of precursor emissions were much higher over the southern regions than those over the northern region with high levels of precursor emissions, based on ground observations and high-precision simulations. The sensitivity analysis of chemical processes suggests that the gas-phase chemistry was a critical factor determining the SIA pattern, especially the higher efficiency of nitrogen conversion to nitrate in southern cities controlled by favorable meteorological elements than that in northern city. However, the heterogeneous process led to the decrease of SIA in southern regions by 3% to 36% and the increasing of SIA in NCP by 26.9%, mainly attributing to the impact on nitrate. The reason was that sulfate enhancement by the heterogeneous reactions can compete ammonia (NH3) and the excessive nitric acid converted into nitrogen oxide (NOx), leading to nitrate decrease in southern regions under NH3-deficient regimes. Moreover, through sensitivity experiments of precursor emission reduction by 20%, NH3 control was found to be the most effective for reducing SIA concentrations comparing to sulfur dioxide (SO2) and NOx reduction and a more remarkable decrease of SIA was in southern regions by 10% to 15% than that in northern region by 6.7%. The effect of the synergy control of precursors emission varied in different city-clusters, inferring that the control strategy aimed at improving air quality should be implemented based on specific characteristics of precursors emission in different regions of China.

5.
Eur J Med Chem ; 219: 113433, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33878564

RESUMO

Due to the threat of escalating multi-drug resistant gram-negative bacteria to human health and life, novel antimicrobial agents against gram-negative pathogens are urgently needed. As antimicrobial peptides are not prone to induce bacteria resistance, they are believed to be one kind of promising class of potential antimicrobial agent candidates to combat multi-drug resistant bacteria for long-term use. Jelleine-1, first isolated from the royal jelly of honeybees, is a typical amphiphilic antimicrobial peptide and shows broad antimicrobial spectrum and negligible toxicity. To promote its antimicrobial activity and extend its potential of clinical use against multi-drug resistant gram-negative bacteria, novel analogs of jelleine-1 were designed, synthesized and their antimicrobial functions and toxicity were examined in this study. Our results showed that fine tuning of the cationic charge, polarity, and basicity of the sequence through amino acids substitution at position 3, 5, 7 and maintaining position 1, 4, 6, 8 unchanged could improve the bioactivity of jelleine-1 significantly. Meanwhile, we also found that the substitution of phenylalanine by tryptophan also could improve the antimicrobial activity of jelleine-1. Among all the analogs, analog 15, which is enriched in arginine and leucine, showed the most potent antimicrobial activity against both gram-negative and gram-positive bacteria, especially to multi-drug resistant Pseudomonas aeruginosa in vivo and in vitro. In addition, analog 15 also showed potent inhibition of the formation of multi-drug resistant P. aeruginosa biofilm and negligible toxicity, which was certified by MTT, hemolysis, blood assay, and biochemical analysis.

6.
J Colloid Interface Sci ; 596: 257-266, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839352

RESUMO

The room and low-temperature performances of solid-state lithium batteries are crucial to expand their practical application. Polyethylene oxide (PEO) has received great attention as the most representative polymer electrolyte matrix. However, most PEO-based solid-state batteries need to operate at high temperature due to low room temperature ionic conductivity. Improving the ionic conductivity by adding plasticizers or reducing the crystallinity of PEO often compromises its mechanical strength. Here, an amorphous PEO-based composite solid-state electrolyte is obtained by ultraviolet (UV) polymerizing PEO and methacryloyloxypropyltrimethoxy silane (KH570)-modified SiO2 which demonstrates both satisfactory mechanical performance and high ionic conductivity at room (3.37 × 10-4 S cm-1) and low temperatures (1.73 × 10-4 S cm-1 at 0 °C). In this electrolyte, the crystallinity of PEO is reduced through cross-linking, and therefore provides a fast Li+ ions transfer area. Moreover, the KH570-modified SiO2 inorganic particles promote the dissociation of lithium salts by Lewis acid centers to increase the ionic conductivity. Importantly, this kind of cross-linking networks endows the final electrolyte much higher mechanical strength than the pure PEO polymer electrolyte or PEO-inorganic filler blended systems. The solid-state LiFePO4/Li cell assembled with this electrolyte exhibits excellent cycling performance and high capacity at room and low temperatures.

7.
Inorg Chem ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710864

RESUMO

Single-crystal structures of five lanthanide-erythritol complexes are reported. The analysis of the chemical compositions and scrutinization of structural features in the single-crystal data of the complexes led us to find that unexpected deprotonation occurs on the OH group of erythritol of three complexes. Considering these complexes were prepared in acidic environments, where spontaneous ionization on an OH group is suppressed, we suggest metal ions play an important role in promoting the proton transfer. To find out why the chemically inert OH is activated, the single-crystal structures of 63 rare-earth complexes containing organic ligands with multiple hydroxyl groups (OLMHs) were surveyed. The formation of µ2-bridges turns out to be directly relevant to the occurrence of deprotonation. When an OH group from an OLMH molecule participates in the formation of a µ2-bridge, the polarization ability of the metal ions becomes strong enough to promote the deprotonation on the OH group. The above structural characteristics may be useful in the rational design of catalysts that can activate the chemically inert OH group and promote the relevant chemical conversions.

8.
Int J Nanomedicine ; 16: 1345-1360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633450

RESUMO

Purpose: Despite the extensive development of antibacterial biomaterials, there are few reports on the effects of materials on the antibacterial ability of the immune system, and in particular of neutrophils. In this study, we observe differences between the in vivo and in vitro anti-infective efficacies of silver nanoparticles (AgNPs). The present study was designed to further explore the mechanism for this inconsistency using ex vivo models and in vitro experiments. Methods: AgNPs were synthesized using the polyol process and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The antibacterial ability of AgNPs and neutrophils was tested by the spread-plate method. The infected air pouch model was prepared to detect the antimicrobial ability of AgNPs in vivo. Furthermore, blood-AgNPs-bacteria co-culture model and reactive oxygen species (ROS) measurement were used to evaluate the effect of AgNPs to neutrophil-mediated phagocytosis and ROS production. Results: The antibacterial experiments in vitro showed that AgNPs had superior antibacterial properties in cell compatible concentration. While, AgNPs had no significant antibacterial effect in vivo, and pathological section in AgNPs group indicated less neutrophil infiltration in inflammatory site than S. aureus group. Furthermore, AgNPs were found to reduce the phagocytosis of neutrophils and inhibit their ability to produce ROS and superoxide during ex vivo and in vitro experiments. Conclusion: This study selects AgNPs as the representative of inorganic nano-biomaterials and reveals the phenomenon and the mechanism underlying the significant AgNPs-induced inhibition of the antibacterial ability of neutrophils, and may have a certain enlightening effect on the development of biomaterials in the future. In the fabrication of antibacterial biomaterials, however, attention should be paid to both cell and immune system safety to make the antibacterial properties of the biomaterials and innate immune system complement each other and jointly promote the host's ability to resist the invasion of pathogenic microorganisms.


Assuntos
Antibacterianos/farmacologia , Sistema Imunitário/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Nanopartículas Metálicas/química , Neutrófilos/citologia , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Neutrófilos/efeitos dos fármacos , RNA/metabolismo , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacos , Superóxidos/metabolismo
9.
Curr Drug Metab ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33568030

RESUMO

BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 µM, 8.63 µM and 29.0 µM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.

10.
Reprod Toxicol ; 100: 74-82, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33453333

RESUMO

The panel of suitable reference genes in the fetal liver have not been reported. In this study, five commonly used reference genes (GAPDH, ß-actin, Rn18 s, Rpl13a, and Rps29) were firstly selected as candidates. Bestkeeper, GeNorm, and NormFinder software were then used to screen out the panel of suitable reference genes of male and female fetal rat liver under physiological and prenatal dexamethasone exposure (PDE) conditions. Finally, we verified the reliability of the screened panel of reference genes by standardizing sterol regulatory element binding protein 1c (SREBP1c) expression with different reference genes. The results showed that GAPDH + Rn18 s and GAPDH + Rpl13a were respectively the panel of suitable reference genes in male and female rat fetal liver under the physiological model, while Rn18 s + Rps29 and GAPDH + Rn18 s were respectively under the PDE model. The results showed that different reference genes affected the statistical results of SREBP1c expression, and the screened panel of suitable reference genes under the PDE model had smaller intragroup differences, when compared with other reference genes under physiological and PDE models. In conclusion, we screened and determined that the panel of suitable reference genes were GAPDH + Rn18 s and Rn18 s + Rps29 in the male rat fetal liver under physiological and PDE models, while they were GAPDH + Rpl13a and GAPDH + Rn18 s in the females, and confirmed that the selection of the panel of suitable reference genes in the fetal liver had gender differences and pathological model specificity.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33411110

RESUMO

PURPOSE: Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety. METHODS: The metabolic stability of rivaroxaban in the presence of human liver microsomes (HLMs) and recombinant CYPs was systematically evaluated to estimate the participation of various CYP isoforms. Furthermore, the catalytic efficiency of CYP isoforms was compared via metabolic kinetic studies of rivaroxaban with recombinant CYP isoenzymes, as well as via CYP-specific inhibitory studies. Additionally, docking simulations were used to illustrate molecular interactions. RESULTS: Multiple CYP isoforms were involved in the hydroxylation of rivaroxaban, with decreasing catalytic rates as follows: CYP2J2 > 3A4 > 2D6 > 4F3 > 1A1 > 3A5 > 3A7 > 2A6 > 2E1 > 2C9 > 2C19. Among the CYPs, 2J2, 3A4, 2D6, and 4F3 were the four major isoforms responsible for rivaroxaban metabolism. Notably, the intrinsic clearance of rivaroxaban catalyzed by CYP2J2 was nearly 39-, 64-, and 100-fold that catalyzed by CYP3A4, 2D6, and 4F3, respectively. In addition, rivaroxaban hydroxylation was inhibited by 41.1% in the presence of the CYP2J2-specific inhibitor danazol, which was comparable to the inhibition rate of 43.3% by the CYP3A-specific inhibitor ketoconazole in mixed HLMs. Furthermore, molecular simulations showed that rivaroxaban is principally bound to CYP2J2 by π-alkyl bonds, carbon-hydrogen bonds, and alkyl interactions. CONCLUSION: CYP2J2 dominated the hydroxylation of rivaroxaban, which may provide new insight into clinical drug interactions involving rivaroxaban.

12.
Biochem Pharmacol ; 185: 114420, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33460628

RESUMO

Epidemiological studies have shown that nonalcoholic fatty liver disease (NAFLD) has an intrauterine developmental origin. We aimed to demonstrate that NAFLD is caused by prenatal dexamethasone exposure (PDE) in adult male rat offspring and to investigate the intrauterine programming mechanism. Liver samples were obtained on gestational day (GD) 21 and postnatal week (PW) 28. The effects and epigenetic mechanism of dexamethasone were studied with bone marrow mesenchymal stem cells (BMSCs) hepatoid differentiated cells and other cell models. In the PDE group, lipid accumulation increased, triglyceride synthesis-related gene expression increased, and oxidation-related gene expression decreased in livers of adult male rat offspring. In utero, hepatic triglyceride synthesis increased and oxidative function decreased in PDE fetal male rats. Moreover, low hepatic miR-122 expression, high Yin Yang-1 (YY1) expression and angiotensin-converting enzyme 2 (ACE2)-Mas receptor (MAS1) signaling pathway inhibition were observed before and after birth. At the cellular level, dexamethasone (100-2500 nM) elevated the intracellular triglyceride content, increased triglyceride synthesis-related gene expression and decreased oxidation-related gene expression. Dexamethasone treatment also decreased miR-122 expression, increased YY1 expression and inhibited the ACE2-MAS1 signaling pathway. Interference or overexpression of glucocorticoid receptor (GR), miR-122, YY1 and ACE2 could reverse the changes in downstream gene expression. In summary, PDE could induce NAFLD in adult male rat offspring. The programming mechanism included inhibition of miR-122 expression after GR activation, and dexamethasone increased hepatocyte YY1 expression; these effects resulted in ACE2-MAS1 signaling pathway inhibition, which led to increased hepatic triglyceride synthesis and decreased oxidative function. The increased triglyceride synthesis and decreased oxidative function of hepatocytes caused by low miR-122 expression due to dexamethasone could continue postnatally, eventually leading to NAFLD in adult rat offspring.

13.
Oxid Med Cell Longev ; 2021: 7467156, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33510841

RESUMO

Nephrotoxicity is a common complication of cisplatin chemotherapy and, thus, limits the clinical application of cisplatin. In this work, the effects of catalpol (CAT), a bioactive ingredient extracted from Rehmannia glutinosa, on cisplatin-induced nephrotoxicity and antitumor efficacy were comprehensively investigated. Specifically, the protective effect of CAT on cisplatin-induced injury was explored in mice and HK-2 cells. In vivo, CAT administration strikingly suppressed cisplatin-induced renal dysfunction, morphology damage, apoptosis, and inflammation. In vitro, CAT induced activation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), improved mitochondrial function, and decreased generation of cellular reactive oxygen species (ROS), leading to a reduction in inflammation and apoptosis, which ultimately protected from cisplatin-induced injury. However, the beneficial effects of CAT were mostly blocked by coincubation with compound C. Furthermore, molecular docking results indicated that CAT had a higher affinity for AMPK than other AMPK activators such as danthron, phenformin, and metformin. Importantly, CAT possessed the ability to reverse drug resistance without compromising the antitumor properties of cisplatin. These findings suggest that CAT exerts positive effects against cisplatin-induced renal injury through reversing drug resistance via the mitochondrial-dependent pathway without affecting the anticancer activity of cisplatin.

14.
Toxicology ; 449: 152664, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359579

RESUMO

As a synthetic glucocorticoid, dexamethasone has been widely used in the clinical treatment of premature birth and related pregnant diseases, but its clinical use is still controversial due to developmental toxicity. This study aimed to confirm the proliferation inhibitory effect of pregnant dexamethasone exposure (PDE) on fetal liver development and elucidate its molecular mechanism. In vitro studies, we found that dexamethasone inhibited hepatocyte proliferation through autophagy activated by glucocorticoid receptor (GR)-forkhead protein O1 (FOXO1) pathway. Subsequently, in vivo, we confirmed in a PDE rat model that male fetal liver proliferation was inhibited, and the expression of the GR-FOXO1 pathway and autophagy were increased. Taken together, PDE induces autophagy by activating the GR-FOXO1 pathway, which leads to fetal liver proliferation inhibition and dysplasia in offspring rats. This study confirmed that dexamethasone activates cell autophagy in utero through the GR-FOXO1 pathway, thereby inhibiting hepatocyte proliferation and liver development, which provides theoretical basis for understanding the developmental toxicity of dexamethasone and guiding the rational clinical use.


Assuntos
Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dexametasona/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Autofagia/fisiologia , Proliferação de Células/fisiologia , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Desenvolvimento Fetal/fisiologia , Glucocorticoides/toxicidade , Fígado/embriologia , Fígado/patologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Wistar
15.
Brain Res Bull ; 168: 45-51, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33370588

RESUMO

BACKGROUND: Prostaglandin E2 (PGE2) binds to four receptor subtypes (EP1, EP2, EP3 and EP4) and plays an important role in response to stress. However, the identity of the receptor(s) responsible for PGE2 regulation of neuronal activity and signaling through activation of the hypothalamic-pituitary-adrenal (HPA) axis under immobilization stress is unknown. PURPOSE: The present study aimed to investigate the role of the hypothalamic PGE2 receptors in the activation of the HPA axis and neuronal activity in a rat model of stress. METHODS: Stress was induced by immobilization of the animals, after which the stress-induced profile of PGE2 receptor signaling in the rat hypothalamus was determined by real-time polymerase chain reaction and immunohistochemistry. The effect of a selective EP3 receptor antagonist on corticosterone concentrations and c-Fos immunoreactivity was measured. RESULTS: Expression of EP2 and EP3 receptor genes, but not EP1 and EP4, was increased following immobilization stress. The EP3 receptor was localized to the paraventricular nucleus (PVN) of the hypothalamus, and the integrated density of the EP3 receptor was increased after immobilization stress. Rats given L-798,106, a selective antagonist of the EP3 receptor, showed significant attenuation of stress-increased serum corticosterone levels. EP3 antagonist also significantly suppressed the increase in the gene expression of c-Fos and the number of c-Fos-immunoreactive cells in the PVN of the hypothalamus following immobilization stress. CONCLUSIONS: These results suggest that immobilization stress may result in increased activation of the HPA axis and neuronal activity through regulating the function of the EP3 receptor.

16.
J Pept Sci ; : e3294, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33283388

RESUMO

With the extensive use of antibiotics in medicine, agriculture and food chemistry, the emergence of multi-drug resistant bacteria become more and more frequent and posed great threats to human health and life. So novel antimicrobial agents were urgently needed to defend the resistant bacteria. Jelleine-I was a small antimicrobial peptide (AMP) with eight amino acids in its sequence. It was believed to be an ideal template for developing antimicrobial agents. In the present study, the possible action mode against both gram-negative bacteria and gram-positive bacteria and in vivo antimicrobial activity was explored. Our results showed that Jelleine-I exhibits its antimicrobial activity mainly by disrupting the integrity of the cell membrane, which would not be affected by the conventional resistant mechanism. It also aims at some intracellular targets such as genomic DNA to inhibit the growth of microbes. In addition, the result of in vivo antimicrobial activity experiment showed that Jelleine-I performed a good therapeutic effect toward the mice with Escherichia coli infected peritonitis. Notably, Jelleine-I has negligible cytotoxicity toward the tested mammalian cells, indicating excellent cell selectivity between prokaryotic cells and eurkayotic cells. In summary, our results showed that Jelleine-I would be a potential candidate to be developed as a novel antimicrobial agent.

17.
Phytother Res ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141989

RESUMO

Puerarin is an isoflavone isolated from Pueraria lobata (Willd.) Ohwi. In the present study, reversal effect and underlying mechanisms of puerarin on multidrug resistance (MDR) were investigated in K562/ADR cells. K562/ADR cells exhibited adriamycin (ADR) resistance and higher levels of MDR1 expression compared with K562 cells. Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells. The expression levels of MDR1 were down-regulated by puerarin in K562/ADR cells. Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF-α-induced NF-κB activation. The phosphorylation of IκB-α was significantly suppressed by puerarin. In silico docking analyses suggested that puerarin well matched with the active sites of IκB-α. Moreover, a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment. The significant increase in LC3-II and beclin-1 was also observed, indicating autophagy induction by puerarin in K562/ADR cells. Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells. Finally, puerarin inhibited phosphorylation of Akt and JNK. In conclusion, puerarin-sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of NF-κB pathway and autophagy induction via Akt inhibition.

18.
Eur J Pharmacol ; : 173653, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068587

RESUMO

Chronic alcohol assumption has been recognized as a major cause of alcoholic liver disease (ALD), which ranges from alcoholic steatohepatitis to fibrosis and hepatocellular carcinoma. Alcoholic liver disease has become the leading cause of liver-related health problem in the world. Herewith, effective therapeutic strategy for alcoholic liver disease is necessary. Yangonin (Yan), a bioactive compound extract from Kava, has been reported to exert hepatoprotective effects via Farnesoid X receptor (FXR) activation. The present study aims to investigate whether Yan ameliorated the ethanol-stimulated liver injury and further to elucidate the mechanisms in vivo and in vitro. Yan improved cell viabilities via cell count kit-8 (CCK-8) methods and obviously reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG) levels. We detected miR-194 levels in ethanol-induced LO2 cells and male C57BL/6 mice by quantitative real-time PCR. Also, the effects of miR-194 on modulating cellular senescence via targeting FXR were further verified. The cellular senescence markers p16, p21, telomerase activity and senescence-related ß-galactosidase (SA-ß-gal) were evaluated by quantitative real-time PCR and Western blot. Also, LO2 cells or liver tissues were stained with special primary antibodies and 4',6'-Diamidino-2-phenylindole (DAPI). The cell cycle was detected by flow cytometry. We observed that Yan significantly inhibited ethanol-induced cellular senescence via FXR activation (P < 0.05). Our results demonstrate that Yan significantly reduced the cellular markers p16, p21 and Hmga1 expression and inhibited the cell cycle arrest (P < 0.05). MiR-194 was upregulated in the alcoholic liver disease, which was significantly suppressed by Yan (P < 0.05). Moreover, miR-194 mimic inhibited FXR expression in vitro. In summary, these aggregated data demonstrate that Yan alleviates chronic ethanol-induced liver injury through inhibition of cellular senescence via regulating miR-194/FXR axis.

19.
Sci Rep ; 10(1): 18382, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093537

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

20.
Sci Rep ; 10(1): 18384, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093575

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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