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1.
Sci Rep ; 10(1): 3708, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111963

RESUMO

The incidence of intervertebral disc (IVD) degeneration disease, caused by changes in the osmotic pressure of nucleus pulposus (NP) cells, increases with age. In general, low back pain is associated with IVD degeneration. However, the mechanism and molecular target of low back pain have not been elucidated, and there are no data suggesting specific biomarkers of low back pain. Therefore, the research aims to identify and verify the significant gene biomarkers of low back pain. The differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database, and the identification and analysis of significant gene biomarkers were also performed with various bioinformatics programs. A total of 120 patients with low back pain were recruited. Before surgery, the degree of pain was measured by the numeric rating scale (NRS), which enables comparison of the pain scores from individuals. After surgery, IVD tissues were obtained, and NP cells were isolated. The NP cells were cultured in two various osmotic media, including iso-osmotic media (293 mOsm/kg H2O) to account for the morbid environment of NP cells in IVD degeneration disease and hyper-osmotic media (450 mOsm/kg H2O) to account for the normal condition of NP cells in healthy individuals. The relative mRNA expression levels of CCL5, OPRL1, CXCL13, and SST were measured by quantitative real-time PCR in the in vitro analysis of the osmotic pressure experiments. Finally, correlation analysis and a neural network module were employed to explore the linkage between significant gene biomarkers and pain. A total of 371 DEGs were identified, including 128 downregulated genes and 243 upregulated genes. Furthermore, the four genes (CCL5, OPRL1, SST, and CXCL13) were identified as significant gene biomarkers of low back pain (P < 0.001) based on univariate linear regression, and CCL5 (odds ratio, 34.667; P = 0.003) and OPRL1 (odds ratio, 19.875; P < 0.001) were significantly related to low back pain through multivariate logistic regression. The expression of CCL5 and OPRL1 might be correlated with low back pain in patients with IVD degeneration disease caused by changes in the osmotic pressure of NP cells.

2.
Environ Int ; 138: 105617, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32155513

RESUMO

While PM2.5 (particles with aerodynamic diameter less than 2.5 µm) concentrations in China are beginning to decline because of pollution abatement measures, ozone (O3) concentrations continue to rise. In this study, we have used a Monte Carlo approach to estimate breathing-rate adjusted (BRA) population exposure to ozone and its oxidation products based on hourly O3 measurements collected in 2017 from monitoring stations in 333 Chinese cities. The median measured outdoor O3 concentration in these cities was 31 ppb, while the median calculated indoor concentrations of ozone and ozone-derived oxidation products were 7.5 ppb and 21 ppb, respectively. The median BRA O3 exposure concentration was 12 ppb, ranging from 2.2 ppb to 18 ppb among the cities. Eastern and central cities had higher exposure concentrations, while northeastern and western cities had lower. On average, the residents of these cities spent 88% of their time indoors. Consequently, even with breathing rate adjustments, indoor O3 exposure averaged 50% of the total O3 exposure nationwide. The median BRA exposure concentration for ozone-derived products was 18 ppb, ranging from 4.5 ppb to 32 ppb among the cities. On average, BRA exposure concentrations were 1.6 times larger for oxidation products than for ozone, while seasonal variations of exposure concentrations were smaller for oxidation products than for ozone. As many of the products of indoor ozone chemistry are toxic, the health consequences of exposure to such products should be further investigated.

3.
Fish Shellfish Immunol ; 100: 317-323, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32173450

RESUMO

Largemouth bass ulcerative syndrome virus (LBUSV) is an important virus induce the mortality of largemouth bass (Micropterus Salmoides). In this study, we reported a single-walled carbon nanotubes (SWCNTs) containing LBUSV major capsid protein (MCP) subunit vaccine (SWCNTs-MCP) which was evaluated for its protective effect on largemouth bass by immersion immunization. We found an elevation in serum antibody levels, enzyme activities, complement C3 content and immune-related genes (IgM, TGF-ß, IL-1ß, IL-8, TNF-α and CD4) expression, in the SWCNTs-MCP immunized groups compared with the pure MCP group. The survival rates for control group, pure MCP protein groups (40 mg L-1) and four SWCNTs-MCP groups (5 mg L-1, 10 mg L-1, 20 mg L-1 and 40 mg L-1) were 0%, 27.78%, 30.56%, 50.00%, 66.67% and 80.56%, respectively. The results suggests that with the assistance of SWCNTs, the immune protection of the SWCNTs-MCP group (40 mg L-1) increased up 52.78%-80.1% compared with pure MCP group (40 mg L-1). Our results demonstrate that the single-walled carbon nanotube subunit vaccine can be used as a new immunization method against LBUSV showing protection following challenge with LBUSV. Taken together, our results demonstrate that the single-walled carbon nanotube subunit vaccine can be used as a new method against LBUSV and have a high immune protection during the largemouth bass farm.

4.
J Agric Food Chem ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32129993

RESUMO

The protective effect and mechanism of action of p-coumaric acid for alleviating palmitic acid (PA)-induced hepatocyte injury were investigated using a PA-induced human hepatoma cell (HepG2)-based hepatocellular injury model and MTT cell viability determinations. Additionally, reduced glutathione content and catalase activity were detected using commercial kits, while intracellular lipid accumulation and total triglyceride content were measured using Oil Red O staining and a triglyceride quantification kit, respectively. Meanwhile, levels of proteins (fatty acid synthase, sterol regulatory element-binding protein-1, stearoyl-CoA desaturase-1) and proliferator-activated receptor-α mRNA were determined using western blotting and real-time quantitative polymerase chain reaction, respectively. After p-coumaric acid targets were identified using network pharmacological analysis, cyclooxygenase-2 (COX-2) expression was assessed via western blotting, while prostaglandin E2 accumulation was measured via an enzyme-linked immunosorbent assay. Notably, PA-treated hepatocytes exhibited increased viability (87.3 ± 2.2% vs 65.5 ± 2.5% for untreated cells), with reduced intracellular lipid accumulation reflecting promotion of lipolysis and fatty acid ß-oxidation; this protective effect may depend on inhibition of both PA-induced HepG2 cell COX-2 expression and PGE2 accumulation.

5.
Opt Express ; 28(4): 5179-5188, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32121743

RESUMO

In this paper, pure silk protein was extracted from Bombyx mori silks and fabricated into a new kind of disordered bio-microfiber structure using electrospinning technology. Coherent random lasing emission with low threshold was achieved in the silk fibroin fibers. The random lasing emission wavelength can be tuned in the range of 33 nm by controlling the pump location with different scattering strengths. Therefore, the bio-microfiber random lasers can be a wide spectral light source when the system is doped with a gain or energy transfer medium with a large fluorescence emission band. Application of the random lasers of the bio-microfibers as a low-coherence light source in speckle-free imaging had also been studied.

6.
Chaos ; 30(1): 013110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32013499

RESUMO

The swing equation plays a central role in the model and analysis of power system dynamics, including small-signal stability and transient stability. As it has the same form as that in a variety of different disciplines, such as the forced pendulum in mechanics, the classical mechanistic description of superconducting Josephson junctions in physics, and the classical second-order phase-locking loop in electronics, it has aroused general interest in science and engineering. In this paper, its approximate solution of the limit cycle is obtained by means of the incremental harmonic balance (IHB) method. It is found that the trouble of a more distorted limit cycle when the parameters are closer to the homoclinic bifurcation curve can be easily solved by incorporating higher order harmonics in the IHB method. In this way, we can predict the homoclinic bifurcation curve perfectly. In addition, the method is extended to study a generalized swing equation including excitation voltage dynamics.

7.
Immunopharmacol Immunotoxicol ; 42(2): 110-118, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32066303

RESUMO

Objective: This paper aims to investigate the dynamic changes of the T-cell receptor (TCR) ß complementarity-determining region 3 (CDR3) repertoire during cyclophosphamide or Cytoxan (CTX) damage or inhibition of bone marrow hematopoiesis caused by a reduction of peripheral blood white blood cells (WBCs) in BALB/c mice.Methods: We analyze TCR CDR3 repertoire of BALB/c mice including (1) NS control group (2) CTX damage group (3) CTX damage + GM-CSF recovery group (4) CTX damage + auto-recovery group.Results: The number of WBCs in the CTX group is significantly lower than that in the NS group and after GM-CSF injection, the GM-CSF group is higher than that in the NS group. The diversity of the CTX damage group is the highest and there is a significant difference in high-frequency clonal proliferation between the CTX damage group and CTX damage + GM-CSF recovery group compared with the NS control group. In addition, the numbers of unique productive CDR3 overlapping numbers in the four experimental groups are similar.Conclusions: These data reveal that CTX significantly reduced the number of WBCs and ratio of high-frequency TCR CDR3 sequences, and indirectly increased the diversity of the TCR CDR3 repertoire. GM-CSF quickly restored the number of WBCs, and partially restored changes in the TCR CDR3 repertoire induced by CTX. Results from monitoring the dynamic changes of the TCR CDR3 repertoire can be used to assess the effects of CTX and GM-CSF on the function of peripheral blood T cells and to explore the possible underlying mechanisms.

8.
Stem Cell Res Ther ; 11(1): 87, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102682

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent mesenchymal cells present in various adult tissues. MSCs secrete exosomes as regulators of the tumor niche, with involvement in tumorigenesis and metastasis. The regulatory role of microRNAs (miRs or miRNAs) in MSCs via targeting cyclin E1 (CCNE1) or cyclin E2 (CCNE2) has been extensively reported. Since exosomes are considered as protective and enriched sources of shuttle miRNAs, we hypothesized that exosomal transfer of miR-144 from bone marrow-derived MSCs (BMMSCs) would affect the development of non-small cell lung cancer (NSCLC) cells by targeting CCNE1 and CCNE2. METHODS: We first quantified the levels of miR-144, CCNE1, and CCNE2 in NSCLC tissues and cell lines and then undertook gain- and loss-of-function studies of miR-144, CCNE1, and CCNE2 to investigate their roles in the biological characteristics of NSCLC in vitro. NSCLC cells (A549) were exposed to exosomes derived from MSCs, and cell proliferation and colony formation rate were determined using in vitro assays. Finally, effects of BMMSC-derived exosomal miR-144 on tumor development were studied in vivo. RESULTS: In NSCLC tissues and cell lines, miR-144 was expressed poorly and CCNE1 and CCNE2 were expressed highly. Artificially elevating miR-144 inhibited cell proliferation, colony formation, and the number of S phase-arrested cells in NSCLC by downregulating CCNE1 and CCNE2. Additionally, BMMSC-derived exosomal miR-144 led to restrained NSCLC cell proliferation and colony formation. These inhibitory effects of BMMSC-derived exosomes carrying miR-144 on NSCLC were confirmed by experiments in vivo. CONCLUSION: Collectively, these findings revealed inhibitory effects of BMMSC-derived exosomal miR-144 on NSCLC progression, which were mediated by downregulation of CCNE1 and CCNE2.

9.
Adv Mater ; 32(11): e1907365, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022975

RESUMO

Tumor-lymph node (LN) metastasis is the dominant prognostic factor for tumor staging and therapeutic decision-making. However, concurrently visualizing metastasis and performing imaging-guided lymph node surgery is challenging. Here, a multiplexed-near-infrared-II (NIR-II) in vivo imaging system using nonoverlapping NIR-II probes with markedly suppressed photon scattering and zero-autofluorescence is reported, which enables visualization of the metastatic tumor and the tumor metastatic proximal LNs resection. A bright and tumor-seeking donor-acceptor-donor (D-A-D) dye, IR-FD, is screened for primary/metastatic tumor imaging in the NIR-IIa (1100-1300 nm) window. This optimized D-A-D dye exhibits greatly improved quantum yield of organic D-A-D fluorophores in aqueous solutions (≈6.0%) and good in vivo performance. Ultrabright PbS/CdS core/shell quantum dots (QDs) with dense polymer coating are used to visualize cancer-invaded sentinel LNs in the NIR-IIb (>1500 nm) window. Compared to clinically used indocyanine green, the QDs show superior brightness and photostability (no obvious bleaching even after continuous laser irradiation for 5 h); thus, only a picomolar dose is required for sentinel LNs detection. This combination of dual-NIR-II image-guided surgery can be performed under bright light, adding to its convenience and appeal in clinical use.

10.
Toxins (Basel) ; 12(2)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012831

RESUMO

Slow lorises are enigmatic animal that represent the only venomous primate lineage. Their defensive secretions have received little attention. In this study we determined the full length sequence of the protein secreted by their unique brachial glands. The full length sequences displayed homology to the main allergenic protein present in cat dander. We thus compared the molecular features of the slow loris brachial gland protein and the cat dander allergen protein, showing remarkable similarities between them. Thus we postulate that allergenic proteins play a role in the slow loris defensive arsenal. These results shed light on these neglected, novel animals.

11.
Nat Commun ; 11(1): 928, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066721

RESUMO

FOXM1, a known transcription factor, promotes cell proliferation in a variety of cancer cells. Here we show that Foxm1 is required for survival, quiescence and self-renewal of MLL-AF9 (MA9)-transformed leukemia stem cells (LSCs) in vivo. Mechanistically, Foxm1 upregulation activates the Wnt/ß-catenin signaling pathways by directly binding to ß-catenin and stabilizing ß-catenin protein through inhibiting its degradation, thereby preserving LSC quiescence, and promoting LSC self-renewal in MLL-rearranged AML. More importantly, inhibition of FOXM1 markedly suppresses leukemogenic potential and induces apoptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xenograft mice. Thus, our study shows a critical role and mechanisms of Foxm1 in MA9-LSCs, and indicates that FOXM1 is a potential therapeutic target for selectively eliminating LSCs in MLL-rearranged AML.

12.
Plant Cell Physiol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065633

RESUMO

The SNAT enzyme participates in biosynthesis of melatonin, which is reported to regulate thermotolerance in many plants. However, the mechanistic basis of this regulation remains unclear. Here, we identified the SlSNAT gene, which is responsible for melatonin biosynthesis in tomato. SlSNAT expression levels were three-fold and five-fold higher in SlSNAT over-expression lines OX-2 and OX-6 respectively. The melatonin levels were three-fold and four-fold higher than those in wild type. The melatonin levels decreased 50% when the expression of SlSNAT was downregulated to 40%. Overexpression of SlSNAT in tomato plants provided significantly enhanced thermotolerance with better growth performance in PS II maximum photochemical quantum yield (Fv/Fm) and alleviated heat injury. Both exogenous melatonin treatment and endogenous melatonin manipulation by SlSNAT overexpression decreased the levels of ROS accumulation and decreased Fv/Fm. The SlSNAT over expression line showed protected RuBisCO (Ribulose bisphosphate carboxylase oxygenase) proteins and upregulated response of heat transcription factors and heat shock proteins under heat stress. HSP40, a DnaJ-type chaperone, was found to interact with SlSNAT in chloroplast. Down regulation of HSP40 showed lower melatonin synthesis under heat stress. HSP40 functions as a chaperone to protect the SNAT enzyme during melatonin synthesis under heat stress. HSP40 interacted with SlSNAT, together participated in melatonin related thermotolerance regulation in tomato.

13.
Phys Chem Chem Phys ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32104817

RESUMO

The structure and stability of two-dimensional hydrogen hydrate were investigated in this work using density functional theory. The results are in line with expectations that the occupied cages are more stable after their confinement between two parallel hydrophobic sheets. The four two-dimensional hydrogen hydrate crystals - BLHH-I, BLHH-II, BLHH-III and BLHH-IV - that we predicted were much more stable in a restricted environment than in a free environment, even close to or exceeding conventional hydrogen hydrates. Besides, we found that the stability of two-dimensional hydrates is inversely related to the increase in temperature. Our work highlights that two-dimensional hydrates provide a new research idea in the field of hydrogen storage.

14.
Biomed Eng Online ; 19(1): 12, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070352

RESUMO

BACKGROUND: Bone defects are often combined with the risk of infection in the clinic, and artificial bone substitutes are often implanted to repair the defective bone. However, the implant materials are carriers for bacterial growth, and biofilm can form on the implant surface, which is difficult to eliminate using antibiotics and the host immune system. Magnesium (Mg) was previously reported to possess antibacterial potential. METHODS: In this study, Mg was incorporated into poly(lactide-co-glycolic acid) (PLGA) to fabricate a PLGA/Mg scaffold using a low-temperature rapid-prototyping technique. All scaffolds were divided into three groups: PLGA (P), PLGA/10 wt% Mg with low Mg content (PM-L) and PLGA/20 wt% Mg with high Mg content (PM-H). The degradation test of the scaffolds was conducted by immersing them into the trihydroxymethyl aminomethane-hydrochloric acid (Tris-HCl) buffer solution and measuring the change of pH values and concentrations of Mg ions. The antibacterial activity of the scaffolds was investigated by the spread plate method, tissue culture plate method, scanning electron microscopy and confocal laser scanning microscopy. Additionally, the cell attachment and proliferation of the scaffolds were evaluated by the cell counting kit-8 (CCK-8) assay using MC3T3-E1 cells. RESULTS: The Mg-incorporated scaffolds degraded and released Mg ions and caused an increase in the pH value. Both PM-L and PM-H inhibited bacterial growth and biofilm formation, and PM-H exhibited higher antibacterial activity than PM-L after incubation for 24 and 48 h. Cell tests revealed that PM-H exerted a suppressive effect on cell attachment and proliferation. CONCLUSIONS: These findings demonstrated that the PLGA/Mg scaffolds possessed favorable antibacterial activity, and a higher content of Mg (20%) exhibited higher antibacterial activity and inhibitory effects on cell attachment and proliferation than low Mg content (10%).

15.
Food Chem Toxicol ; 138: 111187, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061728

RESUMO

The objective of this study was to determine the immunotoxic effects of deoxynivalenol (DON) in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed a control diet or diet containing 1.0 or 3.0 mg DON/kg, or 3.0 mg DON/kg plus 0.05% modified HSCAS for 4 weeks. Compared to the control, the DON diets decreased serum porcine circovirus antibody titer and the dermal hypersensitivity response to OVA at day 21 or 28. DON also induced focal necrosis and proliferation of cortical lymphocytes and apoptosis and increased the total antioxidant capacity and reduced glutathione, protein carbonyl concentrations in thymus. DON increased thymus mRNA, protein and (or) enzyme levels, cytokines (IL-6, IL-10, and TNF-α) and apoptosis-related genes (Caspase-3), while hematopoietic cell kinase (HCK) decreased. Intriguingly, the modified HSCAS alleviated the DON-induced changes on serum antibody titer, and thymic histopathology, apoptosis, redox status, inflammation and apoptosis signaling. In conclusion, these findings help to explain the toxic effects and mechanisms of DON and demonstrated the modified HSCAS adsorbent could be used to reduce the toxicity of DON in weaning piglets.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32079130

RESUMO

Understanding factors influencing groundwater quality is critical to the development of best management practices at the large watershed scale. In this study, the shallow groundwater (10-20 m depth) in the Su-Xi-Chang region, eastern China, was investigated as part of a monitoring program from 2007 to 2008 to analyze the regional groundwater quality as well as the hydrogeochemical processes and their controlling factors. Conventional physicochemical water parameters (pH, turbidity, electrical conductivity, dissolved oxygen, total phosphorus), major cations (Na+, Ca2+, Mg2+ and NH4+) and anions (Cl-, NO3- and SO42-) were measured. Hydrochemical methods and multivariate statistical methods were applied to analyze the hydrogeochemical signatures, origins, the similarities among the variables and to identify the main pollution sources in the groundwater. The results showed that (1) the concentrations of TDS (224.89-1086.70 mg/L) and turbidity (0.1-18.60 NTU) were higher than the class II groundwater quality standards in China and the WHO drinking water standards, (2) there were extremely high concentrations of ammonia (0.01-32.90 mg/L), with a mean value of 0.72 mg/L and (3) the nitrate concentrations (average value of 22.07 mg/L) exceeded the class III groundwater quality standards. The study also provided evidence that weathering, dissolution of carbonate, halite and silicate and cation exchange were the possible primary hydrogeochemical control mechanisms in the groundwater. The sources of ammonia, total phosphorus, sulfates and nitrates included rock-water interactions and anthropogenic activities. The groundwater administration of pollution sinks and sources, long-term legal frameworks and economic incentives should be improved to optimize watershed scale management in the context of rapid development in China.

17.
Nat Prod Res ; : 1-6, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081038

RESUMO

One new long-chain ester derivative of trans-ferulic acid 1 and one natural tirucallane-type triterpenoid 2, together with forty known compounds (3-42), were isolated from the barks of Melia azedarach. Their structures were established on the basis of spectroscopic data interpretation. Compounds 7, 9, 10, 12, 13 showed significant inhibitory activities against PTP1B with IC50 values of 13.82 ± 1.29 µM, 13.29 ± 2.26 µM, 20.27 ± 0.52 µM, 24.36 ± 1.25 µM, 15.23 ± 0.6 µM, respectively.

18.
Environ Res ; 183: 109201, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32050128

RESUMO

BACKGROUND: Asthma is a major public health concern throughout the world. Numerous researches have shown that the spatial-temporal patterns of asthma are inconsistent, leading to the suggestion that these patterns are determined by multiple factors. This study aims to detect spatial-temporal clusters of asthma and analyze socio-ecological factors associated with the asthma hospitalization rate in Guangxi, China. METHODS: Asthma hospitalization and socio-ecological data for 88 counties/municipal districts in Guangxi, China in 2015 was collected. Space-time scan statistics were applied to identify the high-risk periods and areas of asthma hospital admissions. We further used GeoDetector and Spearman correlation coefficient to investigate the socio-ecological factors associated with the asthma hospitalization rates. RESULTS: There were a total of 7804 asthma admissions in 2015. The high-risk period was from April to June. The age groups of 0-4 and ≥65 years were both at the highest risk, with hospital admission rates of 45.0/105 and 46.5/105, respectively. High-risk areas were found in central and western Guangxi with relative risk (RR) values of asthma hospitalizations greater than 2.0. GDP per capita and altitude were positively associated with asthma hospitalizations, while air pressure and wind speed had a negative association. The explanatory powers of these factors (i.e., GDP per capita, altitude, air pressure, wind speed) were 22%, 20%, 14% and 10%, respectively. CONCLUSIONS: The GDP per capita appears to have the strongest correlation with asthma hospitalization rates. High-risk areas were identified in central and western Guangxi characterized by high GDP per capita. These findings may be helpful for authorities developing targeted asthma prevention policies for high-risk areas and vulnerable populations, especially during high-risk periods.

19.
Life Sci ; 245: 117337, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31972205

RESUMO

BACKGROUND: Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive. MAIN METHODS: Y1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed. RESULTS: We demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH. CONCLUSION: Our findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng.


Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Proteína de Ligação a CREB/metabolismo , Corticosterona/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Ginsenosídeos/farmacologia , Receptor Tipo 2 de Melanocortina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Córtex Suprarrenal/citologia , Córtex Suprarrenal/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Camundongos , Pregnenolona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Sci Total Environ ; 713: 136600, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958726

RESUMO

Acid rain has been one of the major environmental problems in industrial countries. While it may affect the litter decomposition, a highly important microbial-driven biogeochemical process, knowledge about the impact of acid rain on litter-decomposing microbial communities and their functions remains unclear. Therefore, this experiment was conducted to investigate how acid rain treatments would alter microbial communities and their functions during litter decomposition of three major commodity crops (maize, rice, and soybean) for six months from June to December 2018. We used litterbag method to determine litter decomposition,while the phospholipid fatty acid (PLFA) and fluorometric methods were used to reveal changes in the litter-adhering microbial community parameters and activities of enzymes involved in the litter decomposition and nutrient release (including carbon [C], nitrogen [N], and phosphorus [P]), respectively. Our results showed that microbial community composition and functions were significantly different among litter types, but not significantly altered by acid rain treatments during the experimental period. The enzyme activities significantly correlated with each other, thus suggesting that microbial requirements for C, N, and P were coupled together during litter decomposition. Moreover, the enzyme activities, at large, did not correlate to microbial community composition, thus indicating the asymmetric relationship between microbial community structure and functions. Our results imply that crop litter type and substrate availability determined the microbial community composition and functions, while litter-inhabiting microbial communities demonstrated substantial resilience under acid rain pressure throughout the experimental period. These results also predict that litter (crop residues) decomposition may not be altered by acid rains in the subtropical agroecosystem, due to relatively high resilience of litter-decomposing microbial communities.

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