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1.
Eur J Med Chem ; 187: 111941, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821989

RESUMO

Threonyl-tRNA synthetase (ThrRS) is a key member of the aminoacyl-tRNA synthetase (aaRS) family that plays essential roles in protein biosynthesis, and ThrRS inhibitors have potential in the therapy of multiple diseases, such as microbial infections and cancers. Based on a unique tRNA-amino acid dual-site inhibitory mechanism identified recently with the herb-derived prolyl-tRNA synthetase (ProRS) inhibitor halofuginone (HF), a series of compounds have been designed and synthesized by employing a fragment-based target hopping approach to simultaneously target the tRNAThr and l-threonine binding pockets of ThrRS. Among them, compound 30d showed an IC50 value of 1.4 µM against Salmonella enterica ThrRS (SeThrRS) and MIC values of 16-32 µg/mL against the tested bacterial strains. The cocrystal structure of SeThrRS in complex with 30d was determined at high resolution, revealing that 30d simultaneously occupies both binding pockets for the nucleotide A76 of tRNAThr and l-threonine in an ATP-independent manner, a novel mechanism compared to all other reported ThrRS inhibitors. Our study provides a new class of ThrRS inhibitors, and more importantly, it presents the first experimental evidence that the tRNA-amino acid dual-site inhibitory mechanism could apply to other aaRSs beyond ProRS, thus providing great opportunities for designing new mechanistic inhibitors for aaRS-based therapeutics.

2.
Antioxid Redox Signal ; 32(1): 18-34, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642335

RESUMO

Aims: Neuronal nitric oxide synthase (nNOS) and nitric oxide (NO) signaling have been implicated in learning, memory, and underlying long-lasting synaptic plasticity. In this study, we aimed at detecting whether nNOS is a target protein of SUMOylation in the hippocampus and its contributions to hippocampal long-term potentiation (LTP) of synaptic transmission. Results: We showed that N-methyl-d-aspartate receptor-dependent neuronal activity enhancement induced the attachment of small ubiquitin-like modifier 1 (SUMO1) to nNOS. Protein inhibitor of activated STAT3 (PIAS3) promoted SUMO1 conjugation at K725 and K739 on nNOS, which upregulated NO production and nNOS S1412 phosphorylation (activation). In addition, the N-terminus (amino acids 43-86) of PIAS3 bound nNOS directly. Tat-tagged PIAS3 segment representing amino acids 43-86, a cell-permeable peptide containing PIAS3 residues 43-86, suppressed activity-induced nNOS SUMOylation by disrupting PIAS3-nNOS association. It also decreased LTP-related expression of Arc and brain-derived neurotrophic factor and blocked signaling via extracellular signal-regulated kinase (ERK) 1/2 and Elk-1 in the hippocampus. More importantly, PIAS3-mediated nNOS SUMOylation was required for activity-regulated ERK1/2 activation in nNOS-positive neurons and hippocampal LTP induction. Innovation and Conclusion: These findings indicated that network activity-regulated nNOS SUMOylation underlies excitatory synaptic LTP by facilitating nNOS-NO-ERK1/2 signal cascades.

3.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3463-3472, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621233

RESUMO

A total of six treatments, including continuous conventional tillage (CT), rotary tillage (RT), subsoiling (ST), no-tillage (NT), conventional-no tillage (CT-NT) and subsoiling-no tillage (ST-NT), were conducted to examine the effects of different tillage types on soil aggregates distribution and stability of irrigated sierozem on continuous 8-year-tillage maize fields in the Gansu Yellow River irrigated area in 2014-2017. The results showed that the aggregation and stability of large aggregates in 0-40 cm soil layer were increased by NT and ST-NT treatments, while the size distribution and stability in plough layer were significantly decreased by CT and RT treatments due to strong soil disturbance. Compared with RT, the mechanical stability of aggregates under dry sieving NT was the best. The contents of >0.25 mm aggregate (R0.25), mean weight diameter (MWD) and geometric mean diameter (GMD) increased by 5.8%, 8.0%, and 13.0%, respectively, and fractal dimension (D) decreased by 3.6%. The water-stable aggregates in ST-NT was the best, with R0.25, MWD and GMD increased by 55.3%, 15.1% and 8.7%, respectively, and D value decreased by 0.8%. The percentage of aggregate destruction (PAD) and unstable aggregate index (ELT) of NT and ST-NT treatments were the lowest. PAD was reduced by 5.9% and 7.7% compared with RT, ELT was reduced by 5.8% and 7.2%, respectively. All the results indicated that the subsoiling-notillage (ST-NT) rotation mode was more conducive to the enhancement of soil aggregate content and stability and consistent with the local farmers operating habits, which would be an ideal tillage method and had certain application value for the sustainable agricultural development in this area.


Assuntos
Rios , Solo , Agricultura , China , Zea mays
4.
J Immunol Methods ; 474: 112668, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31525367

RESUMO

Cell-mediated cytotoxicity is a critical function of the immune system in mounting defense against pathogens and cancers. Current methods that allow direct evaluation of cell-mediated cytotoxicity suffer from a wide-range of drawbacks. Here, we present a novel strategy to measure cytotoxicity that is direct, sensitive, rapid, and highly adaptable. Moreover, it allows accurate measurement of viability of both target and effector cells. Target cells are fluorescently labeled with a non-toxic, cell-permeable dye that covalently binds to cell proteins, including nuclear proteins. The labeled target cells are incubated with effector cells to begin killing. Following the killing reaction, the cell mixture is incubated with another dye that specifically stains proteins of dead cells, including nuclear proteins. In the final step, cell nuclei are released by Triton X-100, and analyzed by flow cytometry. This results in four nuclear staining patterns that separate target and effector nuclei as well as nuclei of live and dead cells. Analyzing nuclei, instead of cells, greatly reduces flow cytometry errors caused by the presence of target-effector cell aggregates. Target killing time can often be reduced to 2 h and the assay can be done in a high throughput format. We have successfully validated this assay in a variety of cytotoxicity scenarios including those mediated by NK-92 cells, Chimeric Antigen Receptor (CAR)-T cells, and Tumor Infiltrating Lymphocytes (TIL). Therefore, this technique is broadly applicable, highly sensitive and easily administered, making it a powerful tool to assess immunotherapy-based, cell-mediated cytotoxicity.

5.
Immunotherapy ; 11(15): 1315-1323, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31478418

RESUMO

Aim: Allergic rhinitis (AR) is a common disease. The therapeutic efficacy of AR needs to be improved. This study aims to evaluate the effects of local administration of probiotic extracts on inhibiting experimental AR. Methods: Epithelial cells (ECs) were primed by exposing to Clostridium butyricum extracts (CBe) in the culture to upregulate the expression of IL-10. A mouse AR model was developed to assess the therapeutic potential of CBe in AR. Results: CBe markedly induced the expression of IL-10 in ECs. Co-culture of naive B cells with CBe-primed ECs significantly increased IL-10 expression in the B cells (iB10 cells). The iB10 cells showed immune suppressive function in suppressing effector CD4+ T-cell proliferation. Treatment with nasal drops containing CBe efficiently inhibited experimental AR in mice. Conclusion: Local administration of CBe can efficiently inhibit experimental AR.

6.
Front Psychol ; 10: 1755, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456708

RESUMO

Employee voice is the discretionary communication of ideas, suggestions, or concerns to benefit the organization. Employee voice is important for both organizations and employees. As such, this study examined the relationship between supervisor behavior and voice, by exploring the positive influences of supervisor developmental feedback on employee voice at the episode level. Further, this study explored the underlying mediators of positive affect and perceived rapport in the relationship between supervisor developmental feedback and employee voice, based on social exchange theory. The study collected 310 matched data points, collected across 62 employees for five consecutive days, using an experience sampling method with mobile surveys. Day-level supervisor developmental feedback positively related to day-level employee voice. Positive affect and perceived rapport with supervisors mediated the relationship between supervisor developmental feedback and employee voice at the episode level. The findings extend the antecedents of voice and examined the social exchange process at a within-person level.

7.
Org Biomol Chem ; 17(28): 6854-6859, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31263819

RESUMO

The anti-malarial drug artemisinin (ART) possesses potent anti-inflammatory activity, yet its underlying mechanism of action has remained elusive. Here we employed quantitative chemical proteomics to in situ profile the cellular targets of ART and identified heat shock protein 90 (HSP90) as a direct target. Further study revealed that ART suppressed the production of nitric oxide (NO) in macrophages via inhibiting the interaction between HSP90 and inducible NO synthase (iNOS).


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artemisininas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteômica , Animais , Anti-Inflamatórios não Esteroides/química , Artemisininas/química , Células Cultivadas , Proteínas de Choque Térmico HSP90/análise , Hibridização in Situ Fluorescente , Camundongos , Células RAW 264.7
8.
Sheng Li Xue Bao ; 71(3): 454-462, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31218336

RESUMO

Neural stem cell therapy, as a new therapeutic method for neural diseases, has aroused a wide concern for over 20 years since neural stem cells were first found in 1992. Ischemic stroke is highly concerned because of its high incidence, mortality and disability rates. Because the brain has a limited ability to repair itself, to improve neural function and promote neural regeneration may help to prevent occurrence and development of neurological diseases. It is noteworthy that some stroke patients showed an ability to repair brain several months after the stroke happened, suggesting an existence of endogenous nerve repair in these patients. The research advances in functions of endogenous neural stem cells in neural regeneration and the related regulators after ischemic stroke are summarized in this review to provide new views of the mechanism of neural functional recovery after ischemic stroke.


Assuntos
Isquemia Encefálica/terapia , Regeneração Nervosa , Células-Tronco Neurais/citologia , Acidente Vascular Cerebral/terapia , Humanos
9.
Huan Jing Ke Xue ; 40(4): 1779-1787, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087919

RESUMO

Construction of cascade reservoirs in Lancang River had a certain influence on the ecological water environment of the basin, dividing the water into natural reaches and reservoir reaches. To explore the impact of the cascade reservoirs on the ecological environment, the nutrient and the chlorophyll a distribution data were measured in the natural reaches, reservoir reaches, and tributaries in June 2017. The results showed that the TN ranged from 0.37 to 1.22 mg·L-1, with an average of 0.70 mg·L-1, and the TP ranged from 0.01 to 0.19 mg·L-1, with an average of 0.04 mg·L-1. One-way ANOVA analysis showed significant spatial differences in the TN, with the TN concentration following the order tributaries > reservior reaches > natural reaches. However, the TP concentration did not show a significant trend. The chlorophyll a concentration varied from 2.6 to 10.2 µg·L-1, with a mean of 5.8 µg·L-1. Pearson correlation analysis showed significant relationships between the chlorophyll a concentration and the TP, water temperature, and Zeu/Zmix. The relationship between chlorophyll a and Zeu/Zmix was particularly significant, which indicated the Zeu/Zmix caused by thermal stratification may be the key factor influencing the growth of phytoplankton.


Assuntos
Clorofila A/análise , Monitoramento Ambiental , Rios/química , China , Nitrogênio/análise , Fósforo/análise
10.
Ying Yong Sheng Tai Xue Bao ; 30(1): 224-232, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30907544

RESUMO

A field experiment was conducted to examine the effects of subsoiling 35 cm with maize straw returning, subsoiling 35 cm without maize straw returning, and rotary tillage without maize straw returning on soil compaction, soil bulk density, soil infiltration, soil water content in 0-100 cm depth, nutrients uptake and production of maize on sierozem in the Gansu Yellow River irrigated area in 2015-2017. Compared with subsoiling 35 cm without maize straw returning and rotary tillage without maize straw returning, subsoiling 35 cm with maize straw returning significantly decreased the soil compaction and soil density in 0-40 cm depth. Compared with that in 2015 (before experiment), soil compaction and soil bulk density in subsoiling 35 cm with straw returning was decreased by 42.6% and 7.0%, respectively, after harvest in 2017. Compared with other treatments, subsoiling 35 cm with straw returning had the lowest variation of soil compaction (6.1%) and soil bulk density (3.2%) in 0-40 cm depth before sowing and after harvest in 2016 and 2017. The soil infiltration rate in subsoiling 35 cm with straw returning was significantly improved by 33.6% compared with rotary tillage without maize straw returning. Subsoiling 35 cm with straw retention could significantly increase soil water content and decrease water variation in 0-100 cm soil depth in spring (before maize sowing) and autumn (after maize harvest). Compared with rotary tillage without maize straw returning, water storage in subsoiling 35 cm with straw retention was increased by 15.5% and 5.6% in spring and autumn, respectively. The water use efficiency was enhanced by 32.4%. Furthermore, subsoiling 35 cm with straw retention could increase maize economic yield and biomass yield by 25.6% and 33.3%, compared with rotary tillage without straw retention. Subsoilng and straw retention could promote nutrient absorption, with N, P2O5 and K2O uptake increased by 49.6%, 51.5% and 37.6%, compared with rotary tillage. Overall, our results suggested that subsoiling 35 cm straw retention could improve soil characteristics, stabilize the phy-sical properties of the plough layer, increase soil water content in the 0-100 cm soil layer, and reduce water variation in spring and autumn. Consequently, it was the best management to promote the water and nutrient utilization of maize and achieve high yield. Our findings could provide theoretical basis for further research on the construction technology of the plough layer in Gansu irrigation area.


Assuntos
Agricultura/métodos , Zea mays , China , Rios , Solo/química , Triticum
11.
Phytomedicine ; 55: 214-221, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668431

RESUMO

BACKGROUND: Swertia chirayita, has been commonly used under the name "Zang-yin-chen" for the treatment of liver infections, inflammation, abdominal pain, and bacterial infection in traditional Tibetan medicine. However, the bioactive components with anti-inflammatory activities and underlying mechanisms remain poorly evaluated. STUDY DESIGN/METHODS: Repeated column chromatography yielded two main xanthones from petroleum ether (PE) and ethyl acetate fractions of whole plants of S. chirayita, and their structures were determined as bellidifolin (1) and swerchirin (2) on the basis of spectroscopic data and literature analysis. The anti-inflammatory activities and mechanisms of anti-inflammation of these two isolated xanthones were determined via enzyme-linked immunosorbent assay (ELISA) and western blot in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages in vitro. RESULTS: Anti-inflammation assay demonstrated that 1 and 2 inhibit the production of the pro-inflammatory cytokines interleukin-6 (IL-6) and TNF-α in LPS-stimulated RAW 264.7 macrophages. Xanthone 1 also potently inhibited the production of prostaglandin E2 (PGE2) by suppressing the protein expression of cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Western blot showed that the phosphorylation of c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPKs were remarkably attenuated by 1 in a concentration-dependent manner. Particularly, Compound 1 suppressed the phosphorylation of the inhibitor κB kinase-ß (IKK-ß), Akt, and p65 subunit of nuclear factor-kappaB (NF-κB). CONCLUSION: The potent suppressive effects of 1 from S. chirayita on inflammatory mediators by blocking the expression of COX-2 and phosphorylation of Akt, IKK-ß, MAPK and NF-κB, activation in LPS-stimulated macrophages suggest that 1 can be a preventive therapeutic candidate for the management of inflammatory-mediated immune disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/efeitos dos fármacos , Inflamação/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Swertia/química , Xantonas/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , China , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Macrófagos/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Células RAW 264.7/efeitos dos fármacos , Xantonas/uso terapêutico
12.
Cell Signal ; 54: 46-58, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30481562

RESUMO

As G-protein-coupled receptors (GPCRs), 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 2 (OX2R) regulate the levels of the cellular downstream molecules. The heterodimers of different GPCRs play important roles in various of neurological diseases. Moreover, 5-HT1AR and OX2R are involved in the pathogenesis of neurological diseases such as depression with deficiency of hippocampus plasticity. However, the direct interaction of the two receptors remains elusive. In the present study, we firstly demonstrated the heterodimer formation of 5-HT1AR and OX2R. Exchange protein directly activated by cAMP (Epac) cAMP bioluminescence resonance energy transfer (BRET) biosensor analysis revealed that the expression levels of cellular cAMP significantly increased in HEK293T cells transfected with the two receptors compared with the 5-HT1AR group. Additionally, the cellular level of calcium was upregulated robustly in HEK293T cells co-transfected with 5-HT1AR and OX2R group after agonist treatment. Furthermore, western blotting data showed that 5-HT1AR and OX2R heterodimer decreased the levels of phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element-binding protein (CREB). These results not only unraveled the formation of 5-HT1AR and OX2R heterodimer but also suggested that the heterodimer affected the downstream signaling pathway, which will provide new insights into the function of the two receptors in the brain.

13.
J Ethnopharmacol ; 231: 275-282, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496840

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yan-Hou-Qing (YHQ), a Chinese medicine formula containing fourteen kinds of materials, has been designed for pharyngitis and cough treatment in Oriental medicine. In the present study, the anti-allergic effects and underlying mechanisms of YHQ in inhibition of airway hyper responsiveness (AHR) was explored in an ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: BALB/c mice were sensitized by OVA and cholera toxin (CT) and challenged with OVA intranasally to induce allergic asthma mouse model. YHQ (200 mg/kg) was orally administered for 3 weeks from week-2 after OVA sensitization. The AHR and histological changes of lung tissues were evaluated by whole-body barometric plethysmography analysis and hematoxylin and eosin (H&E) staining, respectively. The serum concentration of OVA-specific IgE and T helper 2 (Th2) cytokines (IL-4 and IL-13) were determined by enzyme-linked immune sorbent assay (ELISA). Flow cytometry was performed to evaluate the percentage of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the spleen. RESULTS: The elevated AHR responses, heavier inflammatory cell infiltration and Th2 cytokines in allergic asthma group indicated Ovalbumin-induced asthmatic mouse models were built successfully. Compared to allergic asthma group, OVA-induced AHR responses and eosinophil infiltration in lung were improved significantly, and the productions of OVA-specific IgE and Th2 cytokines, IL-4 and IL-13, in the serum were also reduced dramatically after the treatment of YHQ. Moreover, YHQ treatment significantly increased the percentage of CD4+CD25+Foxp3+ Treg in OVA-induced allergic asthma mouse model. CONCLUSIONS: YHQ improves the allergic asthma related symptoms via promotion of CD4+CD25+Foxp3+ Treg and suppression of Th2 responses in mouse model, suggesting YHQ can be used as a potent agent to alleviate allergic asthma related symptoms.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Alérgenos , Animais , Antiasmáticos/farmacologia , Asma/sangue , Asma/imunologia , Toxina da Cólera , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Imunoglobulina E/sangue , Interleucina-13/sangue , Interleucina-4/sangue , Camundongos Endogâmicos BALB C , Ovalbumina , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
14.
Huan Jing Ke Xue ; 39(5): 2126-2134, 2018 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965512

RESUMO

A field survey was carried out to investigate the diffusive fluxes of nitrogen and phosphorus from sediment in the natural river areas and cascaded reservoirs in the Lancang River Basin from February through March in 2017. In the natural river areas, the mean value of total nitrogen (TN) concentrations in the sediment pore water was about 15.254 mg ·L-1, and the total phosphorus (TP) was only 0.654 mg ·L-1; while in the reservoirs, the mean value of TN and TP were 6.577 mg ·L-1 and 1.432 mg ·L-1, respectively. Both nutrients in the overlying water were less than that in the sediment pore water. The mean diffusive flux of total dissolved nitrogen (DTN) was almost 2.117 mg ·(m2 ·d)-1 in the natural river areas, and the mean value of total dissolved phosphorus (DTP) was 0.044 mg ·(m2 ·d)-1, while the mean value of DTN and DTP were 0.785 mg ·(m2 ·d)-1 and 0.053 mg ·(m2 ·d)-1 in the reservoirs, respectively. The TN content reaches the maximum in the overlying water-interstitial water vertical surface sediments. It was concluded that cascaded hydropower had greatly changed the nutrient exchange between the sediment and overlying water. Different hydrodynamics and varied chemical environments in the sediment could be additional causes.

15.
Huan Jing Ke Xue ; 39(8): 3649-3659, 2018 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-29998671

RESUMO

In order to explore the bacterioplankton diversity community structure in the Lancang River basin, as well as to study the relationship between the bacterial diversity and environmental factors, MiSeq high-throughput sequencing was used to analyze and compare the bacterial diversity and community composition of samples in February 2017. Furthermore, Pearson correlation analysis and redundancy analysis (RDA) were used to identify the key environmental factors for the change of bacterial community structure in the natural river and reservoirs of the Lancang river. The results show that the ACE index and Shannon index of the natural river are higher than those of the reservoir, and the main environmental factors causing the diversity of planktonic bacteria in natural river and reservoir segments are water temperature (WT), dissolved oxygen (DO), turbidity (Tur), permanganate index, pH, and total nitrogen (TN). Overall, 26772 optimized reads were obtained from samples based on the high-throughput sequencing of the V3 and V4 region of the 16S rRNA gene. The bacterial species detected in these samples cover 45 phyla and 965 genera. Taxonomic assignment analysis indicated that Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria are the abundant phyla. Among them, the Proteobacteria content is relatively rich, accounting for 36%-94% of the bacterial community. The predominant groups are α-Proteobacteria, ß-Proteobacteria, and γ-Proteobacteria, at the genus level, with Proteobacteria ratios of 0.39%-21.56%, 0.39%-55.80% and 31.09%-99.18%, respectively. The environmental factors affecting the community structure of planktonic bacteria are different in natural river and reservoir. DO and Tur are the key environmental factors affecting the community structure of planktonic bacteria in the natural river, while the community structure of planktonic bacteria in reservoirs is mainly affected by WT, permanganate index, and TN.


Assuntos
Bactérias/classificação , Biodiversidade , Plâncton/classificação , Rios/microbiologia , China , Filogenia , RNA Ribossômico 16S
16.
Int J Immunopathol Pharmacol ; 32: 2058738418785739, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29983082

RESUMO

Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells and the underlying mechanism. H2O2 treatment decreased the viability of SH-SY5Y cells, induced apoptosis, and decreased superoxide dismutase activity. Orexin-A attenuated these effects, indicating that it protects SH-SY5Y cells against H2O2-induced oxidative damage. Pre-treatment with Orexin-A also attenuated H2O2-induced increases in phosphorylation of MEK1/2 and ERK1/2. Moreover, these effects of Orexin-A were reduced in the presence of the PI3K inhibitor LY294002. Finally, pre-treatment with LY294002 abrogated attenuation of the H2O2-induced decrease in cell viability and increase in caspase-3/7 activity by Orexin-A. These results show that the PI3K/MEK1/2/ERK1/2 signaling pathway is involved in the neuroprotective effects of Orexin-A against H2O2-induced oxidative damage in SH-SY5Y cells. Our findings provide insight into the neuroprotective effects of Orexin-A and the underlying mechanism, which will be useful for the treatment of nervous system diseases.


Assuntos
Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Orexinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Oxidantes/toxicidade
17.
Org Lett ; 20(10): 3092-3095, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29741384

RESUMO

Dysiarenone (1), a dimeric C21 meroterpenoid featuring an unprecedented 2-oxaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] carbon skeleton, was isolated from the marine sponge Dysidea arenaria. The structure of 1 was determined by HRMS and NMR spectroscopic analyses coupled with ECD calculations. Dysiarenone showed inhibitory activities against COX-2 expression and the production of prostaglandin E2 with an IC50 value of 6.4 µM in LPS-stimulated RAW264.7 macrophages.


Assuntos
Dysidea/química , Animais , Ciclo-Oxigenase 2 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Terpenos
18.
Food Chem ; 263: 155-162, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29784301

RESUMO

Ganoderma fungi have long been used as a famous traditional medicine and food in country of East Asia. In this work, two new farnesyl phenolic compounds, ganoduriporols A and B (1 and 2), were isolated from the fruiting bodies of Ganoderma duripora, and their structures were elucidated using various spectroscopic methods. Anti-inflammatory activities were assayed and evaluated for the two compounds. Ganoduriporols A and B exhibited dose-dependent anti-inflammatory effects in RAW 264.7 cells. Furthermore, ganoduriporol A was demonstrated to inhibit the production of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) through the suppression of COX-2, MAPK and NF-κB signaling pathway in LPS-induced macrophage cells. These results suggested that these two new farnesyl phenolic compounds and the fruiting body of G. duripora could serve as anti-inflammatory agents for medicinal use or functional food.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Ganoderma/química , Fenóis/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Sci Total Environ ; 634: 205-213, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29627543

RESUMO

Eutrophication has become a severe environmental problem in some tributaries of the Three Gorges Reservoir (TGR) in China. A two-year field investigation of nutrients, oxygen stable isotopes (δ18O), and hydrogen stable isotopes (δD) was performed from January 2010 to December 2011 to determine the sources of nutrients in Xiangxi Bay (XXB). The results showed that nitrogen, phosphorus and silicon varied seasonally depending on hydrodynamic changes. The bottom-layer intrusive density current decreased nitrogen and silicon concentrations and increase phosphorus concentrations in XXB, while the middle-layer intrusive density current increased nitrogen and silicon concentrations and decrease phosphorus concentrations. The differences in δ18O and δD among the Yangtze River (YR), XXB and the region upstream of XXB were significant, and according to the tracer method, the estimated contribution ratios of nitrogen, phosphorus and silicon from the YR to XXB were much larger than those from the region upstream of XXB. These findings suggest that water quality in the TGR can be improved by reducing the pollution load throughout the upstream basin of the YR but not through decentralized efforts in only one or two tributary basins.


Assuntos
Monitoramento Ambiental , Eutrofização , Nitrogênio/análise , Fósforo/análise , Poluentes Químicos da Água/análise , Baías/química , China
20.
Eur J Med Chem ; 149: 129-138, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29499485

RESUMO

Twenty-eight compounds with a new scaffold were designed and synthesized by assembling fragments derived from known agents such as stilbenes and piperazinyl pyrimidines. Many strategies have been explored to improve the druggability of these series of compounds, such as increasing the distance between two benzene rings in the scaffold and introducing functional groups at designated positions. These compounds were validated for their anti-neuroinflammatory activity in BV2 cells. Experimental results reveal that the most active compound 8b can inhibit nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) production with IC50 values of 1.0, 2.6, and 0.5 µM, respectively. The compound can also significantly modulate the MAPK pathways through inhibiting the phosphorylation of JNK, ERK1/2, and p38 MAPK without disturbing NF-κB pathway. Parallel artificial membrane permeation assay demonstrated that the most active compound can overcome the blood-brain barrier (BBB). Therefore, this compound can be a promising lead for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/síntese química , Doença de Alzheimer/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Sistema Nervoso Central/patologia , Desenho de Drogas , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Fosforilação/efeitos dos fármacos , Pirimidinas/síntese química , Estilbenos/síntese química , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese
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