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1.
J Exp Bot ; 71(1): 435-449, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31616940

RESUMO

Soluble carbohydrates not only directly affect plant growth and development but also act as signal molecules in processes that enhance tolerance to cold stress. Raffinose family oligosaccharides (RFOs) are an example and play an important role in abiotic stress tolerance. This study aimed to determine whether galactinol, a key limiting factor in RFO biosynthesis, functions as a signal molecule in triggering cold tolerance. Exposure to low temperatures induces the expression of galactinol synthase (AnGolS1) in Ammopiptanthus nanus, a desert plant that survives temperatures between -30 °C to 47 °C. AnGolS1 has a greater catalytic activity than tomato galactinol synthase (SlGolS2). Moreover, SlGolS2 is expressed only at low levels. Expression of AnGolS1 in tomato enhanced cold tolerance and led to changes in the sugar composition of the seeds and seedlings. AnGolS1 transgenic tomato lines exhibited an enhanced capacity for ethylene (ET) signaling. The application of galactinol abolished the repression of the ET signaling pathway by 1-methylcyclopropene during seed germination. In addition, the expression of ERF transcription factors was increased. Galactinol may therefore act as a signal molecule affecting the ET pathway.

2.
Oral Oncol ; 95: 157-163, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31345384

RESUMO

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy worldwide, with a high mortality. The prognosis of OSCC remains unsatisfactory; the dysregulated immune system plays an important role in the pathogenesis of OSCC. Myeloid-derived suppressor cells (MDSCs) have been identified as immune-suppressive cells in multiple tumor types. The aim of this study was to clarify the underlying immunoregulatory mechanism of MDSC in patients with OSCC. MATERIALS AND METHODS: Flow cytometry was used to analyze the phenotype of MDSC among peripheral blood mononuclear cells (PBMCs) from patients with OSCC and healthy control subjects. The correlation between MDSC frequency and the disease index of patients with OSCC was evaluated. T cell proliferation experiment was used to evaluate the immunosuppressive function of MDSC. RESULTS: Patients with OSCC exhibited significantly higher levels of PMN-MDSCs than did healthy controls. In the co-culture assay, T cell proliferation and IFN-γ production were abrogated by the addition of PMN-MDSCs in a dose-dependent manner. The levels of reactive oxygen species were higher for PMN-MDSCs derived from patients with OSCC than for those from normal individuals. p-STAT3 levels, a key activator of MDSCs, was higher in OSCC-related PMN-MDSCs than in those from healthy controls. Both of these effects were reversed by NAC (an ROS inhibitor) and JSI-124 (a p-STAT3 inhibitor). Finally, PMN-MDSC levels were positively related to histological differentiation, nodal metastasis, and recurrence. CONCLUSION: PMN-MDSCs were elevated in OSCC patients, with strong immune-suppressive effects via p-STAT3/reactive oxygen species, providing a new direction for therapeutic strategies.

3.
Org Lett ; 21(13): 5351-5356, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31247782

RESUMO

The first catalytic α-alkylation reaction of benzyl sulfides and 1,3-dithianes with styrenes and conjugated dienes was developed under mild conditions by using a readily available Brønsted base potassium bis(trimethylsilyl)amide (KHMDS) as catalyst. The reaction displayed good functional group tolerance, high efficiency, and excellent chemoselectivity. A series of desired alkylation products were obtained in good to high yield. Preliminary mechanism studies suggested that two of the potassium amide catalyst molecules worked together in the catalytic cycle.

4.
Zhongguo Gu Shang ; 32(4): 377-382, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31027418

RESUMO

As a common soft tissue disease, the mechanism of tendinopathy has not been clarified and is lack of effective treatment method. Change of tissue fibrosis is the one of the main pathological features. Transforming growth factor beta 1 (TGF-ß1), which is one of the important factor, participated in fibrosis. Inconsonant expressions of TGF-ß1 could be found in tendinopathy. The studies are still controversial, but the vast majority of studies had showed that TGF-ß1 was abnormal, and it is given priority to increase, which means that TGF-ß1 plays an important role in the process of tendinopathy. In the process of tendon injuries and repairs, the time of TGF-ß1 increasing is inconsistent. The time for TGF-ß1 plays a significant role has not been determined. TGF-ß1 has abnormal expressions in both tendinopathy and tendon repairs, which are two opposite processes. Thus, it may not be a one-way adjustment factor, but has a pleiotropic. Recent studies showed that TGF-ß1 was considered as binding to receptor and transferring signal into the cell. Now there are three different receptors are found. The classical pathway of TGF-ß1 in intracellular signal transduction is mainly through activation of Smad pathway. In the same time, there are also some non-classical pathways. TGF-ß1 could break balance of extracellular matrix, which may be a reason to cause tendinopathy. But the regulations of TGF-ß1 on the extracellular matrix are complex and diverse, further studies are required. Existing researches showed that the performance of treatments on tendinopathy is unsatisfied by blocking TGF-ß1 downstream pathway. Therefore, it is a good way to study the upstream mechanism of produce TGF-ß1. It may be an effective method to find new targets to inhibit the development of tendinopathy better by finding the original source of TGF-ß1.


Assuntos
Tendinopatia , Fibrose , Humanos , Transdução de Sinais , Fator de Crescimento Transformador beta1
5.
Curr Protein Pept Sci ; 20(8): 817-822, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843487

RESUMO

Autophagy entails the removal of dysfunctional components to maintain cellular homeostasis. Over the years, studies of autophagy demonstrated its complex physiological and pathological roles in the liver. Apart from regulation of normal metabolic functions such as glycogenolysis, glycogenesis, and ß-oxidation, autophagy also contributes to the modulation of various liver diseases. In this review, we provide a concise overview of the role of autophagy in regulating hepatic metabolism in healthy conditions and various chronic liver diseases. A well-rounded understanding of the role of autophagy may provide insight for future medical advancements in the field of hepatology.


Assuntos
Autofagia , Inflamação/patologia , Cirrose Hepática/patologia , Fígado/patologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Crônica , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hepatite Crônica/metabolismo , Hepatite Crônica/patologia , Hepatite Viral Humana/metabolismo , Hepatite Viral Humana/patologia , Humanos , Inflamação/metabolismo , Fígado/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia
6.
Medicine (Baltimore) ; 98(7): e14518, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762790

RESUMO

Little research has been done about the effects of allogeneic blood transfusion (ABT) on the recurrence and prognosis in the cases with childhood acute lymphocytic leukemia (cALL). In order to provide a basis for clinical safe blood transfusion, the data of 163 cases with cALL were retrospectively analyzed to explore the issue.The data of 163 cases with cALL between 2006 and 2011 were retrospectively analyzed. According to the frequency of blood transfusion, the 163 cases were divided into 4 groups including non-transfusion group, 1 to 10-time transfusion group, 11 to 25-time transfusion group, and >25-time transfusion group. Survival rates were compared with Log-Rank test. Cox regression analysis was used in the effects of risk factors on recurrence and death.ABT was performed in 152 cases with cALL (93.25%). In low-risk and intermediate-and-high risk cALL, the survival rate significantly decreased in all transfusion groups compared with that in non-transfusion group (all P < .01). Cox regression analysis showed that >25-time transfusion was an independent prognosis index of recurrence (odds ratio [OR] = 3.015, 95% confidence interval [CI]: 1.368-6.646) and death (OR = 3.979, 95% CI: 1.930-8.207) in cALL.Frequency of ABT appears to affect the recurrence and death in cALL. We should be careful with blood transfusion and avoid unnecessary blood transfusion as far as possible in the cases with cALL.


Assuntos
Transfusão de Sangue Autóloga/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Pré-Escolar , Protocolos Clínicos , Feminino , Humanos , Lactente , Masculino , Prognóstico , Recidiva , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
7.
ACS Appl Mater Interfaces ; 11(11): 10578-10588, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30802029

RESUMO

Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.


Assuntos
Materiais Biocompatíveis/química , MicroRNAs/metabolismo , Pró-Fármacos/química , Proteína ADAM17/metabolismo , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular , Quitosana/química , Regulação para Baixo/efeitos dos fármacos , Portadores de Fármacos/química , Sinergismo Farmacológico , Fluoruracila/química , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/química , Nanopartículas/química , Nanopartículas/toxicidade , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
8.
Artif Cells Nanomed Biotechnol ; 46(sup3): S661-S670, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30307317

RESUMO

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas , Nanopartículas , Pectinas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Pectinas/química , Pectinas/farmacocinética , Pectinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Arthritis Res Ther ; 20(1): 168, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30075733

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. The dysregulated immune system plays an important role in the pathogenesis of AS. Myeloid-derived suppressor cells (MDSCs) play a key immunoregulatory role in autoimmune arthritis. The aim of this study was to clarify the underlying immunoregulatory mechanism of MDSCs in patients with AS. METHODS: Flow cytometry was used to analyze the phenotype of MDSCs among peripheral blood mononuclear cells (PBMCs) from 46 patients with AS and 46 healthy control subjects. The correlation between MDSC frequency and the disease index of patients with AS was evaluated. A T cell proliferation experiment was used to evaluate the immunosuppressive function of MDSCs. RESULTS: Polymorphonuclear (PMN) and monocytic (M)-MDSCs were significantly elevated in the PBMCs of patients with AS, when compared with levels in healthy controls. Additionally, M-MDSC levels correlated positively with the clinical index of AS, including the Bath ankylosing spondylitis disease activity index (BASDAI) score, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. M-MDSCs derived from patients with AS suppressed T cell responses, and this effect was dependent on the induction of arginase-I. Furthermore, AS-derived M-MDSCs showed high levels of phosphorylated STAT3. Stattic, a STAT3-specific inhibitor, and STAT3-targeted siRNA abrogated the immunosuppressive function of M-MDSCs. Inhibition of STAT3 signaling also resulted in decreased arginase-I activity. CONCLUSIONS: STAT3/arginase-I signaling plays an important role in both the expansion and activation of M-MDSCs in patients with AS. This information may be beneficial in developing novel therapeutic strategies for preventing AS.


Assuntos
Arginase/metabolismo , Células Supressoras Mieloides/imunologia , Fator de Transcrição STAT3/metabolismo , Espondilite Anquilosante/imunologia , Adulto , Feminino , Humanos , Masculino , Células Supressoras Mieloides/metabolismo , Transdução de Sinais/imunologia , Espondilite Anquilosante/sangue , Subpopulações de Linfócitos T/imunologia
10.
Ying Yong Sheng Tai Xue Bao ; 29(6): 1983-1989, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29974709

RESUMO

We analyzed the growth, leaf chlorophyll content, and photosynthetic parameters of a tomato leaf yellowing mutant (Y55) induced by ethyl methane sulfonate (EMS) from the cultivar "Heinz 1706" (WT). Results showed that the plant height, stem diameter, and fresh mass of Y55 significantly . The contents of chlorophyll a, chlorophyll b, carotenoid, total chlorophyll and the chlorophyll a/b ratio of the mutant were significantly lower than those of WT. The contents of all precursor materials of chlorophyll synthesis, especially porphyrinogen III and those involved in the chlorophyll biosynthesis pathway, were significantly lower in Y55 than those in WT. Moreover, the net photosynthesis (Pn), transpiration rate (Tr), intercellular CO2 concentration (Ci), and conductance to H2O (gs) significantly in Y55. The maximum photosynthetic rate, CO2 saturation and compensation point, and light saturation and compensation point. The Fv/Fm significantly, whereas the Fo significantly in Y55. The photosynthetic electron production and electron transport rates of PSII and PSI also significantly decreased. The total photosynthetic pigment molecules (No) and the minimum average lifetime of photosynthetic pigment molecules in the excited state (τmin) significantly in Y55. All these results suggest that blocking the synthesis of porphyrinogen III ould decrease the chlorophyll content in the mutant Y55. Furthermore, the reduced amount of leaf pigment could affect photosynthesis in leaves and slow down the growth of mutant plants.


Assuntos
Clorofila/análise , Lycopersicon esculentum/genética , Mutação , Fotossíntese , Clorofila A , Metanossulfonato de Etila , Lycopersicon esculentum/fisiologia , Folhas de Planta
11.
J Exp Med ; 215(8): 2157-2174, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30049704

RESUMO

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient (ICAM-1-/- ) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1-/- mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1-/- mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.


Assuntos
Imunidade Inata , Molécula 1 de Adesão Intercelular/metabolismo , Linfócitos/metabolismo , Alternaria/fisiologia , Animais , Fator de Transcrição GATA3/metabolismo , Humanos , Imunidade Inata/efeitos dos fármacos , Interleucina-33/farmacologia , Antígeno-1 Associado à Função Linfocitária/metabolismo , Linfócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Pneumonia/imunologia , Pneumonia/microbiologia , Pneumonia/patologia , Ligação Proteica/efeitos dos fármacos
12.
Stem Cell Reports ; 11(1): 258-273, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29937143

RESUMO

The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favoring myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSC quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche.


Assuntos
Ciclo Celular/genética , Diferenciação Celular/genética , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Molécula 1 de Adesão Intercelular/genética , Nicho de Células-Tronco , Biomarcadores , Biologia Computacional/métodos , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Neovascularização Fisiológica/genética , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(4): 295-297, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29658454

RESUMO

OBJECTIVE: To investigate the clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis (MAHS) in children. METHODS: A retrospective analysis was performed for the primary diseases, clinical features, and prognosis of 24 children with MAHS. RESULTS: Among the 24 children, 11 (46%) had MAHS induced by tumor and 13 (54%) had chemotherapy-associated MAHS. As for primary diseases, 17 children had acute leukemia, 6 had lymphoma, and 1 had neuroblastoma. The most common clinical manifestations were pyrexia, respiratory symptoms, and hepatosplenomegaly. The most common laboratory abnormalities were hemocytopenia, elevated serum ferritin, and elevated lactate dehydrogenase. Of the 24 children, 22 were treated according to the HLH-2004 protocol and 2 gave up treatment; 18 children died, 1 was lost to follow-up, and 5 survived. The survival time ranged from 3 days to 2 years and 4 months (median 28 days). CONCLUSIONS: Children with MAHS have various clinical features and extremely poor treatment outcomes.


Assuntos
Linfo-Histiocitose Hemofagocítica/mortalidade , Neoplasias/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 77-82, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397822

RESUMO

OBJECTIVE: To screen and identify potential biomarkers specific for T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Sera were collected from 20 newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients and 20 T-ALL patients. Proteins were extracted, purified and digested with trypsin. All specimens were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) in a data-dependent mode. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression of serum soluble L-selectin (sL-selectin). RESULTS: A total of 468 proteins were identified from distinct peptides. Compared with B-ALL group, 31 proteins were significantly differentially up-regulated while 7 proteins were significantly down-regulated in T-ALL group, sL-selectin was the higher up-regulated in these differential expression proteins. The overexpression of sL-selectin in T-ALL was verified by ELISA. CONCLUSION: There are the differentially expressed proteins between T-ALL and B-ALL, and the sL-selectin is specific for T-ALL, which can not only become a new biomarker for the diagnosis and prognosis of T-ALL, but also can be used as a potential target for therapy of this leukemia.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Biomarcadores , Humanos , Proteômica , Linfócitos T , Espectrometria de Massas em Tandem
15.
Angew Chem Int Ed Engl ; 57(27): 8245-8249, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29394001

RESUMO

Direct functionalization of the benzylic C-H bond of diarylmethanes is an important strategy for the synthesis of diarylmethine-containing compounds. However, the methods developed to date for this purpose require a stoichiometric amount (usually more) of either a strong base or an oxidant. Reported here is the first catalytic benzylic C-H bond addition of diarylmethanes to styrenes and conjugated dienes. A potassium zincate complex, generated from potassium benzyl and zinc amide, acts as a catalyst and displays good activity and chemoselectivity. Considering the atom economy of the reaction and the ready availability of the catalyst, this reaction constitutes a practical, efficient method for diarylalkane synthesis.

16.
Nat Med ; 24(2): 224-231, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29334374

RESUMO

Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy. Here, we report that MDSCs with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins. MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with strong upregulation of an antimicrobial gene network, and had potent antibacterial activity. MDSCs played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low weight, who are prone to NEC, had lower MDSC levels and suppressive activity than did infants with normal weight. Thus, the transitory presence of MDSCs may be critical for regulation of inflammation in newborns.


Assuntos
Enterocolite Necrosante/metabolismo , Recém-Nascido de muito Baixo Peso/metabolismo , Inflamação/genética , Células Supressoras Mieloides/metabolismo , Animais , Animais Recém-Nascidos , Calgranulina A/genética , Calgranulina B/genética , Dinoprostona/genética , Enterocolite Necrosante/genética , Enterocolite Necrosante/patologia , Regulação da Expressão Gênica/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Lactoferrina/genética , Lactoferrina/metabolismo , Camundongos , Células Supressoras Mieloides/patologia , Óxido Nítrico/genética , Óxido Nítrico/metabolismo
17.
Angew Chem Int Ed Engl ; 57(6): 1650-1653, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29281163

RESUMO

The benzylic functionalization of alkylpyridines is an important pathway for pyridine derivatives synthesis. The reaction partners, however, were mostly limited to highly reactive polar electrophiles. Herein, we report a potassium amide-catalyzed selective benzylic C-H bond addition of alkylpyridines to styrenes. Potassium bis(trimethylsilyl)amide (KHMDS), a readily available Brønsted base, showed excellent catalytic activity and chemoselectivity. A series of alkylpyridine derivatives, including benzylic quaternary carbon substituted pyridines, were obtained in good to high yield. Preliminary mechanistic studies revealed that the deprotonation equilibrium is probably responsible for the excellent selectivity.

18.
Dalton Trans ; 47(3): 684-692, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29099525

RESUMO

Visible-light-driven organic transformations have received much attention because of their low cost, relative safety, and environmental friendliness. In this work, we report a series of Bi2S3@ZIF-8 core-shell heterostructures prepared using a simple and efficient self-assembly process. The photocatalytic activity was evaluated using the photocatalytic degradation of Rhodamine B (RhB) under visible-light irradiation and the results show that the core-shell Bi2S3@ZIF-8 heterostructure can remarkably enhance the photocatalytic efficiency at room temperature compared to pristine Bi2S3 nanorods. In addition, the Bi2S3@ZIF-8 composite with a Bi/Zn molar ratio of 1/10 demonstrates good structural stability after the degradation experiment and its photocatalytic activity remains at about 95% after the five recycling tests. The improved photocatalytic performance can be attributed to the larger specific surface area, increased light absorption, and more efficient separation of photogenerated electron-hole pairs due to the combined effects of Bi2S3 and ZIF-8. Moreover, the synergistic photocatalysis mechanism was investigated.

19.
Chem Cent J ; 11(1): 116, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29150749

RESUMO

The interaction of paeoniflorin with human serum albumin (HSA) was investigated using fluorescence, UV-vis absorption, circular dichroism (CD) spectra and molecular docking techniques under simulative physiological conditions. The results clarified that the fluorescence quenching of HSA by paeoniflorin was a static quenching process and energy transfer as a result of a newly formed complex (1:1). Paeoniflorin spontaneously bound to HSA in site I (subdomain IIA), which was primarily driven by hydrophobic forces and hydrogen bonds (ΔH° = - 9.98 kJ mol-1, ΔS° = 28.18 J mol-1 K-1). The binding constant was calculated to be 1.909 × 103 L mol-1 at 288 K and it decreased with the increase of the temperature. The binding distance was estimated to be 1.74 nm at 288 K, showing the occurrence of fluorescence energy transfer. The results of CD and three-dimensional fluorescence spectra showed that paeoniflorin induced the conformational changes of HSA. Meanwhile, the study of molecular docking also indicated that paeoniflorin could bind to the site I of HSA mainly by hydrophobic and hydrogen bond interactions.

20.
J Zhejiang Univ Sci B ; 18(7): 635-648, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28681588

RESUMO

OBJECTIVE: To evaluate the possible photoprotection mechanisms of cyclic and linear electron flux (CEF and LEF) under specific high temperature and high light (HH) stress. METHODS: Six-leaf-stage tomato seedlings ("Liaoyuanduoli", n=160) were divided into four parts: Part 1, served as control under 25 °C, 500 µmol/(m2·s); Part 2, spayed with distilled water (H2O) under 35 °C, 1000 µmol/(m2·s) (HH); Part 3, spayed with 100 µmol/L diuron (DCMU, CEF inhibitor) under HH; Part 4, spayed with 60 µmol/L methyl viologen (MV, LEF inhibitor) under HH. Energy conversion, photosystem I (PSI), and PSII activity, and trans-thylakoid membrane proton motive force were monitored during the treatment of 5 d and of the recovering 10 d. RESULTS: HH decreased photochemical reaction dissipation (P) and the maximal photochemical efficiency of PSII (Fv/Fm), and increased the excitation energy distribution coefficient of PSII (ß); DCMU and MV aggravated the partition imbalance of the excitation energy (γ) and the photoinhibition degree. With prolonged DCMU treatment time, electron transport rate and quantum efficiency of PSI (ETRI and YI) significantly decreased whereas acceptor and donor side limitation of PSI (YNA and YND) increased. MV led to a significant decline and accession of yield of regulated and non-regulated energy YNPQ and YNO, respectively. Membrane integrity and ATPase activity were reduced by HH stress, and DCMU and MV enhanced inhibitory actions. CONCLUSIONS: The protective effects of CEF and LEF were mediated to a certain degree by meliorations in energy absorption and distribution as well as by maintenance of thylakoid membrane integrity and ATPase activity.


Assuntos
Temperatura Alta , Luz , Lycopersicon esculentum/fisiologia , Fotossíntese , Adenosina Trifosfatases/metabolismo , Clorofila/metabolismo , Transporte de Elétrons , Elétrons , Fluorescência , Concentração de Íons de Hidrogênio , Lycopersicon esculentum/efeitos da radiação , Complexo de Proteína do Fotossistema I/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Plântula/fisiologia , Plântula/efeitos da radiação , Tilacoides/metabolismo , Fatores de Tempo
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