RESUMO
The regulation of bacterial quorum sensing (QS) has been used to inhibit biofouling in wastewater treatment plants and the formation of biofilms. In contrast to traditional QS regulation strategies, this study aimed to obstruct the transmembrane transport process of QS signals to decrease their extracellular accumulation. Three phytochemicals, astragaloside IV, eugenol, and baicalin were selected, their effects on biofilm formation by Pseudomonas aeruginosa PA14 were studied, and the mechanisms determined. The inhibition efficiency of biofilm formation by 50 mg/L astragaloside IV, 1 mg/L eugenol, and 1 mg/L baicalin were 37%, 26%, and 26%, respectively. Confocal laser scanning microscopy and analysis of extracellular polymeric substances indicated that the three inhibitors affected the structure and composition of the biofilms. Furthermore, bacterial motility and a variety of QS-related virulence factors were suppressed by the inhibitor treatment due to changes in bacterial QS. Notably, the three inhibitors all decreased the extracellular concentration of the QS signaling molecule 3-oxo-C12-homoseine lactone by affecting the function of efflux pump MexAB-OprM. This indirectly interfered with the bacterial QS system and thus inhibited biofilm formation. In conclusion, this study revealed the inhibitory effects and inhibition mechanism of three phytochemicals on efflux pump and QS of P. aeruginosa and realized the inhibition on biofilm formation. We update the efflux pump inhibitor library and provide a new way for biofilm contamination control.
Assuntos
Percepção de Quorum , Saponinas , Eugenol/farmacologia , Biofilmes , Saponinas/farmacologia , Antibacterianos/farmacologia , Proteínas de BactériasRESUMO
The sediments of water bodies are not only pollutants sink but also sources of pollution. The assessment for the whole-sediment toxicity is still challenging research. Although the application of immobilized algal bead could overcome the practical difficulties in sediment toxicity assay, the weak growth and reduced sensitivity of algae inside the bead restricted its application. In this study, a sediment toxicity test was developed using immobilized sediment and Chlorella vulgaris. The immobilized sediment was prepared by mixing 2 g freeze-dried sediment and 15-mL 3% (w/v) alginate and hardened in a 4% (w/v) CaCl2 solution. Based on a C. vulgaris growth inhibition test and using the immobilized sediment, the median effective concentration value (EC50) of the spiked Cu and diuron was 506.23 and 2.37 mg/kg respectively, lower than that of using immobilized algae (719.62 and 3.12 mg/kg respectively). The Cu and diuron concentrations in the corresponding overlying water from the spiked immobilized and free sediment showed that sediment pollutants' diffusion capacity was not decreased after immobilization. By using the immobilized sediment in algae toxicity bioassay, the changes in the sediment toxicity of a polluted river before and after dredging was evaluated. The C. vulgaris growth inhibition in sediment A decreased from 81.94% to 8.43%; sediment B remained unchanged; sediment C stimulated the growth of C. vulgaris before dredging (-15.56%), but inhibited the algae growth after dredging (26.88%), and sediment D decreased growth inhibition from 32.66% to -12.60%.
Assuntos
Chlorella vulgaris/efeitos dos fármacos , Sedimentos Geológicos/química , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Alginatos/química , Cloreto de Cálcio/química , Chlorella vulgaris/crescimento & desenvolvimento , Cobre/análise , Cobre/toxicidade , Diurona/análise , Diurona/toxicidade , Rios/química , Poluentes Químicos da Água/análiseRESUMO
A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus.
Assuntos
Imunidade Adaptativa/genética , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Anfioxos/genética , Anfioxos/imunologia , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/imunologia , Proteína Quinase C-theta/genética , Proteína Quinase C-theta/imunologia , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica/veterinária , Anfioxos/enzimologia , Filogenia , Proteína Quinase C-delta/química , Proteína Quinase C-theta/química , Alinhamento de Sequência/veterináriaRESUMO
CONTEXT: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the other targets of CE still need to be identified with more efficient probes. OBJECTIVE: This study investigates CE analogue (CEA) as one clickable activity-based probe for use in exploring anti-apoptotic CE targets. MATERIALS AND METHODS: Pretreatment of HUVECs with CEA (1.25 µM) for 8 hr, followed by ox-LDL stimulation for 24 h. Flow cytometry analysis and JC-1 staining assays were performed The kinetic constant measurements were tested by the Biacore T200, CM5 Sensor Chip which was activated by using sulpho-NHS/EDC. Ligands were dissolved and injected with a concentration of 12.5, 6.25, 3.125, 1.56, 0.78 and 0 µM. RESULTS: CEA was confirmed to possess an anti-apoptotic effect. The probable targets of CE/CEA were calculated, and as one of the higher scores proteins (Fit values: 0.88/0.86), Hsp90 properly got our attention. Molecular modelling study showed that both CE and CEA could bind to Hsp90 with the similar interaction, and the docking scores (S value) were -7.61 and -7.33. SPR assay provided more evidence to prove that CEA can interact with Hsp90 with the KD value 11.7 µM. DISCUSSION AND CONCLUSIONS: Our results suggest that clickable probe CEA could alleviate ox-LDL induced apoptosis by a similar mechanism of anti-apoptotic CE, and afforded the possibility of identifying additional anti-apoptotic targets of CE.
Assuntos
Apoptose/efeitos dos fármacos , Química Click , Modelos Moleculares , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Proteínas de Choque Térmico HSP90/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipoproteínas LDL/metabolismo , Simulação de Acoplamento Molecular , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/farmacologia , Saponinas/administração & dosagemRESUMO
To verify the applicability of identifying Microcystis aeruginosa by matrix-assisted laser desorption-ionization-time-of-flight mass spectrometry (MALDI-TOF MS), mixed and field samples were employed to study the sensitivity and the analysis power, respectively. Series diluted samples and artificially mixed samples by the M. aeruginosa NIES-843 strain were designed to verify the sensitivity. The lowest detection limit was 1.955 × 106 cells in pure samples, while for mixed samples, the lowest detection limit and ratio of NIES-843 strain were 2.88 × 106 cells and 33.7%, respectively. The results provided a reference for the reasonable volume of the water sample in which the M. aeruginosa could be detected. Ribosomal protein biomarkers for identifying M. aeruginosa which were successfully detected from the field samples in Taihu Lake, indicated that the identification of M. aeruginosa by MALDI-TOF MS could be applied in field samples. Furthermore, different genetic types of M. aeruginosa strains were also detected at different locations in Taihu Lake, which revealed the diversity of M. aeruginosa and the detection power of MALDI-TOF MS at the strain level for the field samples. The sensitivity and detection power in the analysis of M. aeruginosa by the MALDI-TOF MS demonstrated the applicability of this method in routine environmental monitoring.
Assuntos
Monitoramento Ambiental/métodos , Microcystis/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This article would summarize the use status and research progress of Zha-xun by various ethnic groups all over the world, and the results show that it has various synonyms but most of them imply its most characteristic feature-outflow from the rock; Zha-xun resources are distributed in various places of the world, and its bearing spots are closely related to the geological structure; there are sharp arguments on the origins of Zha-xun, mainly including the minerals origin, biological fossils origin, biological origin, etc. Zha-xun has multiple functions and is mainly used to treat stomach disease, liver disease and rheumatoid arthritis in China, and premature ejaculation, impotence, vaginitis embolism in foreign countries. "Iron" Zha-xun is used into medicines both at home and abroad. According to ancient materia medica texts, it was mainly classified into five types, including gold Zha-xun, silver Zha-xun, copper Zha-xun, iron Zha-xun and lead Zha-xun mainly based on the predominance of color rather than the minerals contained. It is commonly believed by the domestic and foreign scholars that humic acid is the main medicinal part of Zha-xun, and their studies have found that it has a variety of pharmacological activities such as anti-ulcer, anti-inflammatory, liver protection, analgesia, immune regulation, increasing sexual desire and fertility, antioxidation, antibacterial, antidiabetic, antiepileptic, antipsychotic, etc. This paper provides a scientific basis for the rational utilization of Zha-xun resources.
Assuntos
Materia Medica , Medicina Tradicional Tibetana , China , Humanos , Masculino , Medicina Tradicional , PesquisaRESUMO
This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.
Assuntos
Mineração de Dados , Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Tibetana/normas , Prescrições de MedicamentosRESUMO
BACKGROUND: BrdU is a commonly used reagent in cell proliferation assays, and WST-1 measurement is widely used to detect cell viability. However, no previous study has formally reported the combination of the two assays, which may be used to detect the proliferation and viability simultaneously. In this study, we examined the effect of adding BrdU 2 h prior to the WST-1 assay and tried to test the possibility of the combined detection using rat airway smooth muscle cells. RESULTS: The WST-1 measurements obtained from the combined detection were consistent with those obtained from the separate detection, which suggested that the addition of BrdU 2 h prior to the WST-1 analysis did not affect the WST-1 results. The BrdU measurements obtained from the combined detection also demonstrated the same trend as that obtained from the separate detection, and dosages of 200, 400 and 800 ng/ml testing reagent significantly inhibited the proliferation of rat airway smooth muscle cells. CONCLUSIONS: Our study suggests that the BrdU and WST-1 measurements can be applied simultaneously without mutual interference, which may increase the efficacy and consistency of these measurements to a certain extent.
Assuntos
Bromodesoxiuridina/farmacologia , Proliferação de Células/fisiologia , Miócitos de Músculo Liso/fisiologia , Avaliação da Tecnologia Biomédica/métodos , Sais de Tetrazólio/farmacologia , Traqueia/citologia , Animais , Calgranulina B/administração & dosagem , Sobrevivência Celular/fisiologia , Ensaio de Imunoadsorção Enzimática , Cultura Primária de Células , Ratos , Kit de Reagentes para Diagnóstico , Traqueia/crescimento & desenvolvimentoRESUMO
Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.
Assuntos
Antibacterianos , Ciprofloxacina , Desnitrificação , Ciprofloxacina/farmacologia , Antibacterianos/farmacologia , Paracoccus denitrificans/metabolismoRESUMO
A highly efficient aerobic denitrifying microbe was isolated from sewage sludge by using a denitrifier enrichment strategy based on decreasing carbon content. The microbe was identified as Pseudomonas mendocina HITSZ-D1 (hereafter, D1). Investigation of the conditions under which D1 grew and denitrified revealed that it performed good growth and nitrate removal performance under a wide range of conditions. In particular, D1 rapidly removed all types of inorganic nitrogen without accumulation of the intermediate products nitrite and nitrous oxide. Overall, D1 showed a total nitrogen removal efficiency >96% at a C/N ratio of 8. The biotransformation modes and fates of three typical types of inorganic nitrogen were also assessed. Moreover, D1 had significantly higher denitrification efficiency and enzyme activities than other aerobic denitrifying microbes (Paracoccus denitrificans, Pseudomonas aeruginosa, and Pseudomonas putida). These results suggest that D1 has great potential for treating wastewater containing high concentrations of nitrogen.
Assuntos
Nitritos , Pseudomonas mendocina , Nitritos/metabolismo , Pseudomonas mendocina/metabolismo , Esgotos , Desnitrificação , Nitratos/metabolismo , Nitrogênio/metabolismo , Nitrificação , AerobioseRESUMO
The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,ß-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
Assuntos
Benzofuranos/química , Benzofuranos/síntese química , Química Farmacêutica/métodos , Imunossupressores/farmacologia , Linfócitos T/efeitos dos fármacos , Amidas/química , Desenho de Fármacos , Humanos , Ligação de Hidrogênio , IMP Desidrogenase/antagonistas & inibidores , Imunossupressores/uso terapêutico , Concentração Inibidora 50 , Modelos Químicos , Relação Estrutura-Atividade , Linfócitos T/imunologiaRESUMO
Current research focused on developing multiple active species in peroxymonosulfate (PMS) system to degrade contaminants, but deepening concern lacks over why cooperation of those active species facilitated a faster degradation. Here, we employed Co3O4, rGO and Co3O4@rGO composite to activate PMS for tetracycline (TC) degradation, and detected crucial factors toward highest performance of Co3O4@rGO/PMS system. Batch experiments exhibited a satisfactory TC degradation efficiency under Co3O4@rGO/PMS, complete degraded 50 mg/L TC within 20 min. Analytical tests discovered that radical active species generated by Co3O4/PMS and non-radical species by rGO/PMS were successfully co-existed in Co3O4@rGO/PMS system, significantly improving the performance of TC removal. Subsequently, a combination of density functional theory (DFT) calculation and intermediates analysis revealed that, in Co3O4@rGO/PMS system, the cooperation rather than independent effect of radical and non-radical active species expanded TC degradation pathways, enhancing the degradation performance. Furthermore, decent adaptability, stability, and recyclability toward affecting factors variation of Co3O4@rGO/PMS demonstrated it as a potent and economical system to degrade TC. Overall, this study developed a novel Co3O4@rGO/PMS system with a cooperative oxidation pathway for highly efficient TC removal, and managed to clarify why this oxidation pathway achieved high efficiency through a combination of theoretical and experimental method.
Assuntos
Peróxidos , Tetraciclina , Cobalto , ÓxidosRESUMO
Water environmental pollution caused by spent batteries is a nonignorable environmental issue. In this study, the early life stage of zebrafish was employed to assess the environmental risk of spent batteries after exposure to 0, 1%, 2%, 5% and 10% spent battery extract for 120 h. Our results clearly indicated that spent battery extract can significantly decrease the survival rate, hatching rate and body length and increase heart rate. Moreover, spent battery extract exposure-induced zebrafish larvae generate oxidative stress and inhibit the mRNA transcriptional levels of heat shock protein (HSP70) and metallothionein (MT) genes. These results showed that the spent batteries not only affected the survival and development performance of zebrafish at an early life stage but also caused oxidative stress and interfered with the detoxification of zebrafish. This study provided novel insight into spent battery induced toxicity in the early life stage of fish.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Biomarcadores/metabolismo , Embrião não Mamífero/metabolismo , Larva , Estresse Oxidativo , Extratos Vegetais , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Two new species of the genus Ricanula Melichar, 1898 within the family Ricaniidae (Hemiptera: Fulgoromorpha) from China are described and illustrated: R. curva sp. nov. and R. peronata sp. nov. Ricania cacaonis Chou et Lu, 1977 is redescribed and transferred to genus Ricanula. Ricanula pulverosa (Stl, 1865) is re-illustrated.
Assuntos
Hemípteros , Animais , ChinaRESUMO
The judgment and assessment of remediation effect on urban black-odor river still depend on the physical-chemical parameters and lack in ecological safety effects. A set of combined biological toxicity tests were applied to evaluate the ecological effects of one urban black-odor river before and after the remediation. The special growth rate of Chlorella vulgaris and mortality rate of Daphnia magna were used to assess acute toxicity. The Salmonella Typhimurium/Reverse Mutation Assay was applied to test the mutagenicity. The tests by C. vulgaris growth showed that there was no inhibition before and after remediation by overlying water, in contrast promoted the growth of C. vulgaris. The tests by D. magna showed slight toxicity on site 3# before remediation and nontoxic after remediation. The mutagenicity of organic extracts from overlying water at all sampling sites were positive before remediation, but were eliminated after remediation except from 3 of 4 sites on TA98 strain. The addition of the liver microsomal S9 induced the positive mutagenicity on site 4# compared to S9 absence. The results clarified the applicable and the importance of the biological toxicity tests on assessing the remediation effect and potential ecological risk of urban black-odor river.
Assuntos
Odorantes , Rios , Poluentes Químicos da Água/toxicidade , Animais , China , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/crescimento & desenvolvimento , Cidades , Daphnia/efeitos dos fármacos , Monitoramento Ambiental , Recuperação e Remediação Ambiental , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Testes de ToxicidadeRESUMO
OBJECTIVE: To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice. METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay. RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01). CONCLUSION: Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.
Assuntos
Terapia por Acupuntura , Asma/imunologia , Asma/terapia , Linfócitos T CD4-Positivos/imunologia , Animais , Asma/sangue , Asma/fisiopatologia , Citocinas/sangue , Feminino , Inflamação/patologia , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos Endogâmicos BALB C , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Hipersensibilidade Respiratória/fisiopatologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Bronchial asthma is a chronic airway inflammatory disease which has three main pathological features: airway hyperresponsiveness (AHR), airway remodelling, and chronic inflammation. Acupuncture is known to be an effective integrative medical therapy that has been used in the treatment of several chronic diseases, including bronchial asthma. The aim of the current study was to evaluate the effects of acupuncture on inflammation and regulation of the IL-33/ST2 pathway in a mouse model of asthma. METHODS: The murine asthma model was established by both injection and inhalation of ovalbumin (OVA). Within 24 hours of the last OVA challenge, lung function was assessed by measurement of the airway resistance (RL) and lung dynamic compliance (Cdyn). Pulmonary tissues were collected for the detection of pathological changes and mucus secretion. Serum levels of tumour necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-33 and sST2 (secreted ST2) were detected by ELISA. Th17 cell proportions and counts in bronchoalveolar lavage fluid (BALF) were analysed by flow cytometry. RESULTS: The results showed that AHR, chronic inflammation and mucus secretion were significantly suppressed by acupuncture treatment. RL decreased while Cdyn increased after acupuncture treatment. There was an apparent decrease in the serum concentrations of certain pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-33, and an increase in sST2 level compared with untreated asthmatic mice. Acupuncture also reduced the CD4 +IL-17A+ cell proportion and counts in BALF. CONCLUSION: Acupuncture effectively protects lung function and attenuates airway inflammation in the OVA-induced mouse model of asthma, which supports the role of acupuncture as a potential therapy in asthma treatment.
Assuntos
Terapia por Acupuntura , Asma/imunologia , Asma/terapia , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Interleucina-33/imunologia , Animais , Asma/induzido quimicamente , Asma/genética , Modelos Animais de Doenças , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-33/genética , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversosRESUMO
Ultraviolet absorbing chemicals (UV filters) are widely used in personal care products for protecting human skin and hair from damage by UV radiation. Although these substances are released into the environment during production and consumption processes, little is known about their genotoxicity effects. Our previous studies have shown that benzophenone-type UV filters exhibited acute toxicity on three species of aquatic organisms. Mutagenesis by benzophenone (BP) and benzophenone-1(BP-1) was tested in the present study by the Salmonella typhimurium/reverse mutation assay (Ames assay). All the positive reverse mutations occurred in the absence of the S9 liver extract system for both chemicals. From BP, positive mutation effects on the TA102 strain at doses of 0.05 µg/plate and 0.5 µg/plate were detected. From BP-1, positive mutation effects on the TA97 strain at doses of 0.05 µg/plate and 0.5 µg/plate, and on the TA100 strain at a dose of 0.5 µg/plate, were detected. A mixture of BP and BP-1 exhibited mutagenicity on the TA97 and TA100 strains. For the TA97 strain, the positive mutation results were detected at 10% and 50% of the mixture. For the TA100 strain, the results were detected when the mixture was at 5% and 10%. In the mixture at 5%, the concentrations of BP and BP-1 were 3.5 µg/plate and 14 µg/plate, respectively. In the 10% mixture, the doses of BP and BP-1 were 7 µg/plate and 28 µg/plate, respectively. In the 50% mixture, the doses of BP and BP-1 were 35 µg/plate and 140 µg/plate, respectively. The mixture test results suggested that there was antagonism in mutagenicity between BP and BP-1.
Assuntos
Benzofenonas/efeitos adversos , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/efeitos adversos , Salmonella typhimurium/efeitos dos fármacos , Protetores Solares/efeitos adversos , Raios Ultravioleta/efeitos adversos , Bioensaio , Monitoramento Ambiental/métodos , HumanosRESUMO
Premature ovarian failure (POF) results from a number of disorders. The POF model is primarily based on chemotherapeutic injury, and hence is not suitable for assessing the effects of chronic stress on ovarian function. Therefore, improved animal models are required to analyze the effects of chronic stress on ovarian reserve. The feasibility of the chronic unpredictable mild stress (CUMS) method for establishing a model of POF was examined. The depressive behavior exhibited by rats was evaluated with the open field and sucrose preference tests. Vaginal smears were obtained for assessment of the estrous cycle. The ovarian reserve of the animals was evaluated using the estrous cycle, ovarian histology and serum levels of gonadotropin releasing hormone (GnRH), folliclestimulating hormone (FSH), estradiol (E2), and antiMüllerian hormone (AMH). Compared with the control group, body weight, time spent in the center, horizontal movement, vertical frequency, consumption of sucrose, sucrose preference, number of small follicles from the rats, and serum E2, AMH and GnRH levels were significantly decreased in the CUMS group (all P<0.05). However, the estrous cycle was prolonged significantly (P<0.05) and serum FSH levels were increased significantly (P<0.01). These results suggested that the CUMS model rats exhibited depressionlike behaviors. CUMS may induce psychological stress and decrease ovarian reserve in female rats. Thus, the CUMS model may be used to assess the effects of chronic stress on female reproductive function.
Assuntos
Depressão , Ovário/patologia , Insuficiência Ovariana Primária/etiologia , Estresse Psicológico/complicações , Animais , Hormônio Antimülleriano/sangue , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Hormônio Liberador de Gonadotropina/sangue , Reserva Ovariana , Insuficiência Ovariana Primária/patologia , Insuficiência Ovariana Primária/psicologia , RatosRESUMO
There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than ß2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin- and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than ß2-agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma.