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1.
Soft Matter ; 19(3): 497-501, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36538008

RESUMO

Fluorescent protein biomaterials have important applications such as bioimaging in pharmacological studies. Self-assembly of proteins, especially into fibrils, is known to produce fluorescence in the blue band. Capable of self-assembly into nanofibers, we have shown we can modulate its aggregation into mesofibers by encapsulation of a small hydrophobic molecule. Conversely, azobenzenes are hydrophobic small molecules that are virtually non-fluorescent in solution due to their highly efficient photoisomerization. However, they demonstrate fluorogenic properties upon confinement in nanoscale assemblies by reducing the non-radiative photoisomerization. Here, we report the fluorescence of a hybrid protein-small molecule system in which azobenzene is confined in our protein assembly leading to fiber thickening and increased fluorescence. We show our engineered protein Q encapsulates AzoCholine, bearing a photoswitchable azobenzene moiety, in the hydrophobic pore to produce fluorescent mesofibers. This study further investigates the photocontrol of protein conformation as well as fluorescence of an azobenze-containing biomaterial.


Assuntos
Compostos Azo , Proteínas , Conformação Proteica , Compostos Azo/química
2.
Anticancer Drugs ; 30(8): 838-845, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31415285

RESUMO

Clinical drug resistance to platinum-based chemotherapy is considered a major impediment in the successful treatment of non-small-cell lung cancer (NSCLC). The nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway regulates the oxidative stress response, and in many cancer types, the high constitutive expression of NRF2 leads to proliferation and chemoresistance. Ginsenoside Rd (GS-Rd) is the main active component of ginsenosides. Here, GS-Rd was found to inhibit the proliferation of A549 lung cancer cells and induce G0/G1 phase arrest. We established cisplatin (DDP)-resistant A549 cell lines (A549/DDP). The half maximal inhibitory concentrations of DDP, gemcitabine, and adriamycin were much higher in A549/DDP cells than in A549 cells. The A549/DDP cell lines developed multidrug resistance, accompanied by activation of multidrug resistance protein 1 and multidrug resistance-associated protein 1, as well as NRF2 and its target genes. Treatment with GS-Rd inhibited the NRF2 pathway and significantly sensitized A549/DDP cells to therapeutic drugs. In addition, NRF2 knockdown attenuated the synergistic effects of GS-Rd in both A549 and A54/DDP cells. Taken together, these data show that NRF2 plays an important role in acquired drug resistance in NSCLC, and GS-Rd may ameliorate this chemoresistance by downregulating the NRF2 pathway. This study demonstrates that the NRF2 pathway may serve as a therapeutic target in NSCLC, and ginseng compounds may be effective for the treatment of this disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular , Proliferação de Células , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células Tumorais Cultivadas
3.
New Phytol ; 218(3): 1036-1048, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29512165

RESUMO

Rhizosphere priming effects (RPEs) play a central role in modifying soil organic matter mineralization. However, effects of tree species and intraspecific competition on RPEs are poorly understood. We investigated RPEs of three tree species (larch, ash and Chinese fir) and the impact of intraspecific competition of these species on the RPE by growing them at two planting densities for 140 d. We determined the RPE on soil organic carbon (C) decomposition, gross and net nitrogen (N) mineralization and net plant N acquisition. Differences in the RPE among species were associated with differences in plant biomass. Gross N mineralization and net plant N acquisition increased, but net N mineralization decreased, as the RPE on soil organic C decomposition increased. Intraspecific competition reduced the RPE on soil organic C decomposition, gross and net N mineralization, and net plant N acquisition, especially for ash and Chinese fir. Microbial N mining may explain the overall positive RPEs across species, whereas intensified plant-microbe competition for N may have reduced the RPE with intraspecific competition. Overall, the species-specific effects of tree species play an important role in modulating the magnitude and mechanisms of RPEs and the intraspecific competition on soil C and N dynamics.


Assuntos
Carbono/metabolismo , Nitrogênio/metabolismo , Rizosfera , Solo/química , Árvores/fisiologia , Bactérias/crescimento & desenvolvimento , Biomassa , Dióxido de Carbono/metabolismo , Minerais/metabolismo , Desenvolvimento Vegetal , Raízes de Plantas/fisiologia , Brotos de Planta/fisiologia , Especificidade da Espécie
4.
Biomacromolecules ; 19(5): 1614-1624, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29601728

RESUMO

Osteoarthritis (OA) results from degenerative and abnormal function of joints, with localized biochemistry playing a critical role in its onset and progression. As high levels of all- trans retinoic acid (ATRA) in synovial fluid have been identified as a contributive factor to OA, the synthesis of de novo antagonists for retinoic acid receptors (RARs) has been exploited to interrupt the mechanism of ATRA action. BMS493, a pan-RAR inverse agonist, has been reported as an effective inhibitor of ATRA signaling pathway; however, it is unstable and rapidly degrades under physiological conditions. We employed an engineered cartilage oligomeric matrix protein coiled-coil (CccS) protein for the encapsulation, protection, and delivery of BMS493. In this study, we determine the binding affinity of CccS to BMS493 and the stimulator, ATRA, via competitive binding assay, in which ATRA exhibits approximately 5-fold superior association with CccS than BMS493. Interrogation of the structure of CccS indicates that ATRA causes about 10% loss in helicity, while BMS493 did not impact the structure. Furthermore, CccS self-assembles into nanofibers when bound to BMS493 or ATRA as expected, displaying 11-15 nm in diameter. Treatment of human articular chondrocytes in vitro reveals that CccS·BMS493 demonstrates a marked improvement in efficacy in reducing the mRNA levels of matrix metalloproteinase-13 (MMP-13), one of the main proteases responsible for the degradation of the extracellular cartilage matrix compared to BMS493 alone in the presence of ATRA, interleukin-1 beta (IL-1ß), or IL-1 ß together with ATRA. These results support the feasibility of utilizing coiled-coil proteins as drug delivery vehicles for compounds of relatively limited bioavailability for the potential treatment of OA.


Assuntos
Benzoatos/administração & dosagem , Portadores de Fármacos/química , Nanofibras/química , Osteoartrite/tratamento farmacológico , Estilbenos/administração & dosagem , Motivos de Aminoácidos , Benzoatos/química , Benzoatos/farmacologia , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Peptídeos/química , Receptores do Ácido Retinoico/agonistas , Estilbenos/química , Estilbenos/farmacologia
5.
Biomacromolecules ; 18(9): 2688-2698, 2017 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-28686014

RESUMO

An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 µg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , RNA Interferente Pequeno/química , Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Lipídeos/química , Células MCF-7
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(8): 800-4, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25140771

RESUMO

OBJECTIVE: To study the clinical significance of tidal breathing lung function test in 1-4 years old children with wheezing diseases. METHODS: A total of 141 1-4 years old children with wheezing diseases were enrolled as the observed groups (41 cases of asthma, 54 cases of asthmatic bronchitis, and 46 cases of bronchopneumonia). Thirty children without respiratory diseases were enrolled as the control group. All the recruits underwent tidal breathing lung function test. The observed groups underwent bronchial dilation test, and tidal breathing flow volume (TBFV) parameters were evaluated before and after bronchial dilation test. RESULTS: The observed groups showed obstructive ventilatory disorder (65%) according to the TBFV loop, and their ratio of time to peak tidal expiratory flow (TPTEF) to total expiratory time (TE) and ratio of volume to peak expiratory flow (VPEF) to total expiratory volume (VE) were significantly lower than in the control group (P<0.05). The asthma subgroup had significantly improved TPTEF/TE and VPEF/VE after bronchial dilation test (P<0.05). Taking an improvement rate of ≥ 15% either for TPTEF/TE or for VPEF/VE as an indicator of positive bronchial dilation test, the bronchial dilation test had a sensitivity of 47% and a specificity of 84% in diagnosing asthma in 1-4 years old children. The positive rate was 28% among the children in the asthma subgroup with an TPTEF/TE ratio of ≥ 23% before bronchial dilation test, versus 65% in those with an TPTEF/TE ratio of <23%. CONCLUSIONS: Obstructive ventilatory disorder is the main impairment of tidal breathing lung function in 1-4 years old children with wheezing diseases. Tidal breathing bronchial dilation test can reflect a reversal of airway obstruction to a certain extent. The sensitivity of bronchial dilation test for the diagnosis of asthma is not satisfactory in 1-4 years old children with wheezing diseases, but this test has a relatively high diagnostic value in children with severe airway obstruction.


Assuntos
Bronquite/diagnóstico , Respiração , Testes de Função Respiratória/métodos , Sons Respiratórios/diagnóstico , Asma/diagnóstico , Asma/fisiopatologia , Bronquite/fisiopatologia , Broncopneumonia/diagnóstico , Broncopneumonia/fisiopatologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Sons Respiratórios/efeitos dos fármacos , Sons Respiratórios/fisiopatologia
7.
Front Plant Sci ; 15: 1345189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425793

RESUMO

Introduction: While no tillage (NT) can significantly influence soil structure stratification compared to conventional tillage (CT), a comprehensive understanding of the degree of root trait plasticity and trade-offs of lateral roots of crops at various growth stages along a deep soil profile in response to NT remains elusive. This knowledge gap is important for understanding soil resource acquisition strategies and yield of crops. Methods: We systematically investigated the traits of lateral roots at jointing and flowering stages in a long-term (12 years) experiment in Northeast China where maize (Zea mays) has been continuously planted under CT and NT with or without maize residue mulch on soil surface. We also measured soil penetration resistance and bulk density. Results: Soil penetration resistance was reduced at the jointing stage, and was increased at the flowering stage under NT especially at a depth of 10 - 40 cm. Root length density decreased under NT across the two growth stages by on average 22%. In contrast, specific root length and diameter showed greater plasticity, ranging from -14% to 20% and from -11% to 8%, respectively, relative to those under CT. Discussion: These responses could be attributed to changes in root length proportions with different diameters associated with differences in soil penetration resistance between tillage practices. The negative relationships between root traits were stronger under CT than NT, and became weaker from the jointing stage to the flowering stage. To the best of our knowledge, for the first time, our study provides empirical evidence for pivotal root trait plasticity and trade-offs across growth stages as key indicators of changes in soil structure and resources in response to NT. These insights contribute to a better understanding of soil resource acquisition strategies of crops under NT.

8.
Pharmgenomics Pers Med ; 16: 629-643, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37383675

RESUMO

Background: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated. Methods: Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo. Results: A total of 36 DEGs were identified. AQP8, HMGCS2, and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2, and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees. Conclusion: AQP8, HMGCS2, and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.

9.
Chin J Integr Med ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085388

RESUMO

OBJECTIVE: To investigate the role of ginsenoside Rd (GRd) in acute myeloid leukemia (AML) cell differentiation. METHODS: AML cells were treated with GRd (25, 50, 100 and 200 µg/mL), retinoic acid (RA, 0.1g/L) and PD98059 (20 mg/mL) for 72 h, cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays, and cell cycle was detected by flow cytometry. Cell morphology and differentiation were observed by Wright-Giemsa staining, peroxidase chemical staining and cellular immunochemistry assay, respectively. The protein expression levels of GATA binding protein 1 (GATA-1), purine rich Box-1 (PU.1), phosphorylated-extracellular signal-related kinase (p-ERK), ERK, phosphorylated-glycogen synthase kinase-3ß (p-GSK3ß), GSK3ß and signal transducer and activator of transcription 1 (STAT1) were detected by Western blot. Thirty-six mice were randomly divided into 3 groups using a random number table: model control group (non-treated), GRd group [treated with 200 mg/(kg·d) GRd] and homoharringtonine (HTT) group [treated with 1 mg/(kg·d) HTT]. A tumor-bearing nude mouse model was established, and tumor weight and volume were recorded. Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining. WT1 and GATA-1 expressions were detected by immunohistochemical staining. RESULTS: The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest (p<0.05). GRd treatment induced leukemia cell differentiation, showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation (p<0.05). GRd treatment elicited upregulation of p-ERK, p-GSK-3ß and STAT1 expressions in cells, and reversed the effects of PD98059 on inhibiting the expressions of peroxidase, GATA-1 and PU.1 (P<0.05). After GRd treatment, tumor weight and volume of mice were decreased, and tumor cells underwent massive apoptosis and necrosis (P<0.05). WT1 level was decreased, and GATA-1 level was significantly increased in subcutaneous tumor tissues (P<0.05 or P<0.01). CONCLUSION: GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3ß signaling pathway.

10.
Front Plant Sci ; 13: 927435, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812934

RESUMO

Photosynthetically derived carbon (C) is allocated belowground, allowing plants to obtain nutrients. However, less is known about the amount of nutrients acquired relative to the C allocated belowground, which is referred to as C efficiency for nutrient acquisition (CENA). Here, we examined how C efficiency for nitrogen (N) and phosphorus (P) acquisition varied between ryegrass (Lolium perenne) and clover (Trifolium repens) with and without P fertilization. A continuous 13C-labeling method was applied to track belowground C allocation. Both species allocated nearly half of belowground C to rhizosphere respiration (49%), followed by root biomass (37%), and rhizodeposition (14%). With regard to N and P, CENA was higher for clover than for ryegrass, which remained higher after accounting for relatively low C costs associated with biological N2 fixation. Phosphorus fertilization increased the C efficiency for P acquisition but decreased the C efficiency for N acquisition. A higher CENA for N and P in clover may be attributed to the greater rhizosphere priming on soil organic matter decomposition. Increased P availability with P fertilization could induce lower C allocation for P uptake but exacerbate soil N limitation, thereby making N uptake less C efficient. Overall, our study revealed that species-specific belowground C allocation and nutrient uptake efficiency depend on which nutrient is limited.

11.
Org Lett ; 24(4): 1083-1087, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35060731

RESUMO

An efficient Ni-catalyzed hydrodifluoroalkylation of unactivated alkenes with bromodifluoroacetate by using PhSiH3 as hydride source was developed. The transformation affords aliphatic difluorides with anti-Markovnikov regioselectivity. A wide range of highly remote alkenes, simple alkenes, drug molecules, commercially available CF2 precursors, and even nonfluorinated substrates are competent in this reaction under mild conditions, demonstrating the practicability of the strategy. Moreover, mechanistic studies indicated that the difluoroalkyl radical might be a key intermediate to this transformation.

12.
Biochem Biophys Res Commun ; 407(3): 593-8, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21426903

RESUMO

In this paper, we determine the mutant W203F structure of TFsß-glucanase, which contains aromatic residue Trp203 at the active site of the enzyme. Residue Trp203 is stacked with the glucose product of cellotriose. Further analysis reveals that two extra calcium ions and a Tris molecule bind to the mutant structure. A Tris molecule, bound to the catalytic residues of Glu56 and Glu60, was found at the position normally taken by substrate binding at the -1 subsite. In addition, a second Ca(2+) ion was found near the residues Phe152 and Glu154 on the protein's surface, and a third one near the active site residue Asp202. Kinetic experiments reveal that both Tris and imidazole are competitive inhibitors, while calcium is a noncompetitive inhibitor for TFsß-glucanase. The two types of enzymatic inhibition are first-time descriptions for the glycosyl hydrolase family 16.


Assuntos
Cálcio/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/química , Trometamina/farmacologia , Cálcio/química , Domínio Catalítico/genética , Cátions Bivalentes/química , Cátions Bivalentes/farmacologia , Cristalografia por Raios X , Fibrobacter/enzimologia , Glicosídeo Hidrolases/genética , Imidazóis/química , Imidazóis/farmacologia , Mutação , Paenibacillus/enzimologia , Trometamina/química , Triptofano/química , Triptofano/genética
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 13(11): 870-2, 2011 Nov.
Artigo em Zh | MEDLINE | ID: mdl-22099193

RESUMO

OBJECTIVE: To study the prognosis of childhood asthma and the factors influencing asthmatic attacks and prognosis. METHODS: The medical data of 212 children with asthma who were followed up for more than 5 years were retrospectively studied. RESULTS: During the 5-year follow up, asthmatic attacks termination was found in 121 cases (57.1%) and asthma persistence was observed in 91 cases. Respiratory tract infections were found as the major factors inducing asthmatic attacks (71.7%), followed by inhaled allergens (17.0%).The children with asthma induced by respiratory tract infections had a higher remission rate of asthmatic attacks (61.2%) than those induced by allergens (41.7%) or exercises (26.3%). Three risk factors for asthma persistence were identified: concurrent allergic rhinitis and eczema, parental asthma and allergy-induced wheezing. CONCLUSIONS: The 5-year follow-up study demonstrated that asthmatic attacks stopped in the majority of children with asthma. Respiratory tract infections may be the major factors inducing acute asthma attacks. The children with asthma induced by respiratory infections may experience a better outcome. Atopic children or children with the genetic background of atopy are at high risks for the development of persistent asthma.


Assuntos
Asma/etiologia , Asma/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Infecções Respiratórias/complicações , Estudos Retrospectivos , Fatores de Risco
14.
Am J Transl Res ; 11(5): 2742-2753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217850

RESUMO

Ankylosing spondylitis (AS) is a type of rheumatic inflammatory disease. miRNAs participate in the process of regulating inflammatory response and bone differentiation. Herein, we aimed to test the effect of miR-495 on AS. The serum and tissues were obtained from traumatic fracture (health) and AS patients. The human fibroblast-like synovial (HFLS) cells were extracted from AS tissues. The contents of inflammatory factors and dishevelled 2 (DVL-2) were examined using enzyme-linked immunosorbent assay (ELISA). The ossification factors were detected by immunohistochemistry assay. Osteoclast was assessed by tartaric acid acid phosphatase (TRAP) assay. The cell viability and luciferase activity were measured using cell counting kit-8 (CCK-8) and dual-luciferase reporter system. The levels of factors were evaluated using quantitative real-time PCR (qRT-PCR) and western blotting. DVL-2 was a target gene for miR-495, according to the MicroRNA.org website and luciferase activity assay. The expressions of miR-495 and DVL-2 were negative corrected in AS. miR-495 and si-DVL-2 did not affect the cell viability. miR-495 and si-DVL-2 obviously inhibited inflammatory response by down-regulating tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 levels, and facilitated bone differentiation by up-regulating osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) levels in HFLS cells. Besides, miR-495 and si-DVL-2 increased the expression of wnt3a, runt-related transcription factor 2 (RUNX-2) and ß-catenin and reduced the phosphorylation of ß-catenin. Collectively, miR-495 depressed inflammatory response and promoted bone differentiation of HFLS cells, and this was accompanied by mediating wnt/ß-catenin/Runx-2 pathway by targeting DVL-2.

15.
Mol Med Rep ; 19(4): 2627-2635, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720115

RESUMO

MicroRNA (miR)­155 has a crucial role in various cellular functions, including differentiation of hematopoietic cells, immunization, inflammation and cardiovascular diseases. The present study aimed to investigate the roles and mechanisms of miR­155 in treatment­resistant depression (TRD). A Cell Counting Kit­8 assay and flow cytometry were performed to assess the cell viability and apoptosis of microglial cells, respectively. Western blotting and reverse transcription­quantitative polymerase chain reaction assays were used to evaluate the associated protein and mRNA expression, respectively. The results revealed that miR­155 reduced the cell viability of BV­2 microglial cells, and miR­155 enhanced the expression levels of pro­inflammatory cytokines in BV­2 microglial cells. Furthermore, conditioned medium from miR­155­treated microglia decreased the cell viability of HT22 hippocampal cells. miR­155­treated microglia increased the apoptosis of neuronal hippocampal cells by modulating the expression levels of apoptosis regulator Bax, apoptosis regulator Bcl­2, pro­caspase­3 and cleaved­caspase­3. The cell cycle distribution was disrupted by miR­155­treated microglia through induction of S phase arrest. Furthermore, the overexpression of suppressor of cytokine signaling 1 reversed the pro­apoptotic effect of activated microglia on hippocampal neuronal cells. In conclusion, the present results suggested that miR­155 mediated the inflammatory injury in hippocampal neuronal cells by activating the microglial cells. The potential effects of miR­155 on the activation of microglial cells suggest that miR­155 may be an effective target for TRD therapies.


Assuntos
Inflamação/etiologia , Inflamação/metabolismo , MicroRNAs/genética , Microglia/imunologia , Microglia/metabolismo , Células Piramidais/metabolismo , Animais , Apoptose/genética , Ciclo Celular/genética , Sobrevivência Celular/genética , Células Cultivadas , Citocinas/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Camundongos , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/metabolismo
16.
Chin J Integr Med ; 25(12): 902-910, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31802424

RESUMO

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.


Assuntos
Anemia Aplástica/tratamento farmacológico , Ginsenosídeos/farmacologia , Hematopoese/efeitos dos fármacos , Panax , Saponinas/farmacologia , Linfócitos T/efeitos dos fármacos , Anemia Aplástica/sangue , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C
17.
Biomed Pharmacother ; 102: 959-965, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29710551

RESUMO

Aplastic anemia (AA) is usually treated with immunosuppressive agents, but their efficacy and safety are not satisfactory. Panax notoginseng saponins (PNS) promote the proliferation of hematopoietic stem/progenitor cells. This study aimed to examine the effects of leaf PNS (LPNS) on hematopoiesis and T cells in mouse models of AA. The experiments were performed in normal mice and AA mice (controls, cyclosporine, and low, medium, and high doses of LPNS). Hematopoietic cells were counted using colony formation assays. The proportions of T cells were measured by flow cytometry. The ERK1/2, T-bet, GATA-3, FOXP3, and RORγ proteins were assessed by western blotting. Cytokines were measured using a cytometric bead array. AA mice showed impaired hematopoiesis, high activation of T cells, and decreased expression of T-bet, GATA-3, and FOXP3. LPNS attenuated the inflammation observed in AA mice, and significantly increased the number of hematopoietic progenitor cells. The proportions of Th2 and regulatory T cells and the protein levels of P-ERK1/2, GATA-3, and FOXP3 were increased in the AA + LPNS mice compared with the AA mice. In contrast, LPNS decreased the proportions of Th1 and Th17 cells and the protein expression of T-bet. LPNS and cyclosporine had similar effects, but of different amplitudes. These results suggest that LPNS have dual activities in AA: 1) promoting the proliferation of hematopoietic progenitor cells; and 2) modulating T cell immune functions, an activity similar to that of cyclosporine. Additional studies are necessary to confirm those results before clinical use.


Assuntos
Anemia Aplástica/tratamento farmacológico , Imunidade , Panax notoginseng/química , Folhas de Planta/química , Saponinas/uso terapêutico , Anemia Aplástica/patologia , Animais , Contagem de Células Sanguíneas , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Citocinas/metabolismo , Feminino , Hemoglobinas/metabolismo , Imunidade/efeitos dos fármacos , Terapia de Imunossupressão , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo
18.
Environ Sci Pollut Res Int ; 25(29): 29325-29334, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30121766

RESUMO

Fruit shell residue from Xanthoceras sorbifolia was investigated as a potential biosorbent to remove crude oil from aqueous solution. The shell powder and its carbonized material were compared while assessing various factors that influenced oil removal capacity. The structure and sorption mechanism were characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The oil removal capacity of the raw material (75.1 mg g-1) was better than the carbonized material (49.5 mg g-1). The oil removal capacity increased with greater saponin content, indicating that hydrophobic and lipophilic surface characteristics of the saponins improved adsorption by the raw X. sorbifolia shell. An orthogonal experimental design was used to optimize the adsorption. Using 4 g L-1 of raw X. sorbifolia shell (particle size of < 0.15 mm), the highest crude oil removal efficiency was obtained using an initial oil concentration of 400 mg L-1, adsorption temperature of 30 °C, adsorption time of 10 min at a shaking speed of 150 rpm. The adsorption of crude oil onto X. sorbifolia shell was best described using a pseudo-second-order kinetic model. Raw X. sorbifolia shell material was more efficient than the carbonized material at crude oil removal from aqueous solution. This was attributable to the functional groups of saponins in raw X. sorbifolia shell. This study highlights that some agricultural and forest residues could be a promising source of low-cost biosorbents for oil contaminants from water-without requiring additional processing such as carbonization.


Assuntos
Petróleo , Sapindaceae/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Carbono/química , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura , Modelos Químicos , Tamanho da Partícula , Soluções/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Água/química , Poluentes Químicos da Água/química , Purificação da Água/instrumentação , Purificação da Água/métodos
19.
Chin J Integr Med ; 24(3): 200-206, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28432529

RESUMO

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot. RESULTS: In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05). CONCLUSIONS: PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Ciclofosfamida/efeitos adversos , Ginsenosídeos/uso terapêutico , Hematopoese/efeitos dos fármacos , Células Mieloides/patologia , Panax/química , Pancitopenia/tratamento farmacológico , Saponinas/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Transcrição GATA1/metabolismo , Ginsenosídeos/farmacologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células Mieloides/efeitos dos fármacos , Pancitopenia/induzido quimicamente , Pancitopenia/patologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(2): 304-8, 2007 Apr.
Artigo em Zh | MEDLINE | ID: mdl-17478941

RESUMO

OBJECTIVE: To observe the effects of endothelial cells from umbilical cord blood (UCB) on the amplification of human early hematopoietic cells from UCB in vitro. METHODS: Endothelial cells from UCB were cultured by the optimized medium of endothelial cells. There were 2 experiment groups: cytokines group (SCF+IL-3+IL-6+GM-CSF, CKs group) and noncontact group (endothelial cell layer with CKs without contacting the CD34+ cells group). CD34+ cells from UCB were isolated by MiniMACS. After the cells in the CKs group and the noncontact group were cultured for 7 days, the amplifying folds of early hematopoietic cells were assayed. RESULTS: Early hematopoietic cells from UCB were expanded in the CKs group or the noncontact group. The amplifying folds of the noncontact group on early hematopoietic cells were significantly more than those of the CKs group. CONCLUSION: The amplification effect of the noncontact group on early hematopoietic cells is superior to that of the CKs group.


Assuntos
Células Endoteliais/citologia , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Antígenos CD34/análise , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Meios de Cultura/farmacologia , Citocinas/farmacologia , Células Endoteliais/metabolismo , Sangue Fetal/metabolismo , Citometria de Fluxo , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imuno-Histoquímica
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