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1.
Nano Lett ; 24(15): 4454-4461, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38572779

RESUMO

Colloidal quantum well (CQW) based light emitting diodes (LEDs) possess extra-high theoretical efficiency, but their performance still lags far behind conventional LEDs due to severe exciton quenching and unbalanced charge injection. Herein, we devised a gradient composition CdxZn1-xS shell to address these issues. The epitaxial shell with gradient composition was achieved through controlling competition between Cd2+ and Zn2+ cations to preferentially bind to the anions S2-. Thus, exciton quenching was suppressed greatly by passivating defects and reducing nonradiative recombination, thereby achieving near-unity photoluminescence quantum yield (PLQY). The gradient energy level of the shell reduced the hole injection barriers and increased the hole injection efficiency to balance the charge injection of LEDs. As a result, the LEDs achieved a high external quantum efficiency (EQE) of 22.83%, luminance of 111,319 cd/m2 and a long operational lifetime (T95@100 cd/m2) over 6,500 h, demonstrating the state-of-the-art performance for the CQW based LEDs.

2.
J Biol Chem ; 298(3): 101718, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35151688

RESUMO

Peripheral myelination is a complicated process, wherein Schwann cells (SCs) promote the formation of the myelin sheath around the axons of peripheral neurons. Fibroblasts are the second resident cells in the peripheral nerves; however, the precise function of fibroblasts in SC-mediated myelination has rarely been examined. Here, we show that exosomes derived from fibroblasts boost myelination-related gene expression in SCs. We used exosome sequencing, together with bioinformatic analysis, to demonstrate that exosomal microRNA miR-673-5p is capable of stimulating myelin gene expression in SCs. Subsequent functional studies revealed that miR-673-5p targets the regulator of mechanistic target of the rapamycin (mTOR) complex 1 (mTORC1) tuberous sclerosis complex 2 in SCs, leading to the activation of downstream signaling pathways including mTORC1 and sterol-regulatory element binding protein 2. In vivo experiments further confirmed that miR-673-5p activates the tuberous sclerosis complex 2/mTORC1/sterol-regulatory element binding protein 2 axis, thus promoting the synthesis of cholesterol and related lipids and subsequently accelerating myelin sheath maturation in peripheral nerves. Overall, our findings revealed exosome-mediated cross talk between fibroblasts and SCs that plays a pivotal role in peripheral myelination. We propose that exosomes derived from fibroblasts and miR-673-5p might be useful for promoting peripheral myelination in translational medicine.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina , MicroRNAs , Bainha de Mielina , Células de Schwann , Proteína de Ligação a Elemento Regulador de Esterol 2 , Proteína 2 do Complexo Esclerose Tuberosa , Esclerose Tuberosa , Exossomos/genética , Exossomos/metabolismo , Fibroblastos/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Bainha de Mielina/metabolismo , Células de Schwann/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Esteróis/metabolismo , Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo
3.
Theor Appl Genet ; 136(6): 146, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37258797

RESUMO

KEY MESSAGE: QTgw.saas-5B was validated as a major thousand-grain weight-related QTL in a founder parent used for wheat breeding and then precisely mapped to a 0.6 cM interval. Increasing the thousand-grain weight (TGW) is considered to be one of the most important ways to improve yield, which is a core objective among wheat breeders. Chuanmai42, which is a wheat cultivar with high TGW and a high and stable yield, is a parent of more than 30 new varieties grown in southwestern China. In this study, a Chuanmai42-derived recombinant inbred line (RIL) population was used to dissect the genetic basis of TGW. A major QTL (QTgw.saas-5B) mapped to the Xgwm213-Xgwm540 interval on chromosome 5B of Chuanmai42 explained up to 20% of the phenotypic variation. Using 71 recombinants with a recombination in the QTgw.saas-5B interval identified from a secondary RIL population comprising 1818 lines constructed by crossing the QTgw.saas-5B near-isogenic line with the recurrent parent Chuannong16, QTgw.saas-5B was delimited to a 0.6 cM interval, corresponding to a 21.83 Mb physical interval in the Chinese Spring genome. These findings provide the foundation for QTgw.saas-5B cloning and its use in molecular marker-assisted breeding.


Assuntos
Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico , Triticum/genética , Fenótipo , Melhoramento Vegetal , Grão Comestível/genética , China , Cromossomos de Plantas/genética
4.
Macromol Rapid Commun ; 44(24): e2300451, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37795776

RESUMO

Lithium-sulfur (Li-S) battery features a high theoretical energy density, but the shuttle of soluble polysulfides between the two electrodes often results in a rapid capacity decay. Herein, a straightforward electrostatic adsorption strategy based on a cross-linked polyimidazolium separator as a snaring shield of polysulfides is reported, which suppresses the undesirable migration of polysulfides to the anode. The porous ionic network (PIN)-modified carbon nanotubes (CNTs) are successfully prepared and coated onto a commercial porous polypropylene membrane in a vacuum-filtration step. The favorable affinity of the imidazolium ring toward polysulfide via the polar interaction and the electrostatic effect of ions mitigates the undesirable shuttle of polysulfides in the electrolyte, improving the Li─S battery in terms of rate performance and cycling life. Compared to the reference PIN-free CNT-coated separator, the PIN/CNT-coated one has an increased initial capacity of 1.3 folds (up to 1394.8 mAh g-1 for PIN/CNT/PP-3) at 0.1 C.


Assuntos
Lítio , Nanotubos de Carbono , Porosidade , Íons , Enxofre
5.
Bioorg Chem ; 141: 106875, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37757670

RESUMO

Photodynamic therapy (PDT) is a clinically approved treatment for cancer due to its high spatiotemporal selectivity and non-invasive modality. However, its therapeutic outcomes are always limited to the severe hypoxia environment of the solid tumor. Herein, two novel photosensitizers HY and HYM based on naturally antitumor alkaloids ß-carboline were designed and synthesized. Through a series of experiments, we found HY and HYM can produce type II ROS (singlet oxygen) after light irradiation. HYM had higher singlet oxygen quantum yield and molar extinction coefficient than HY, as well as type I PDT behavior, which further let us find that HYM could exhibit robust phototoxicity activities in both normoxia and hypoxia. Meanwhile, HYM showed tumor-selective cytotoxicity with minimal toxicity toward normal cells. Notably, thanks to HYM's hypoxia-tolerant type I/II PDT and tumor selective chemotherapy, HYM showed synergistic inhibitory effect on tumor growth (inhibition rate > 91%). Our research provides a promising photosensitizer for hypoxia-tolerant chemo-photodynamic therapy, and may also give a novel molecular skeleton for photosensitizer design.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Carbolinas/farmacologia , Carbolinas/uso terapêutico , Linhagem Celular Tumoral
6.
J Nanobiotechnology ; 21(1): 111, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36973764

RESUMO

Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.


Assuntos
Artrite Reumatoide , Fibroínas , Humanos , Hidrogéis , Fibroínas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia , Artrite Reumatoide/metabolismo
7.
Angew Chem Int Ed Engl ; 62(34): e202306039, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37314932

RESUMO

Development of thermosets that can be repeatedly recycled via both chemical route (closed-loop) and thermo-mechanical process is attractive and remains an imperative task. In this work, we reported a triketoenamine based dynamic covalent network derived from 2,4,6-triformylphloroglucinol and secondary amines. The resulting triketoenamine based network does not have intramolecular hydrogen bonds, thus reducing its π-electron delocalization, lowering the stability of the tautomer structure, and enabling its dynamic feature. By virtue of the highly reversible bond exchange, this novel dynamic covalent bond enables the easy construction of highly crosslinked and chemically reprocessable networks from commercially available monomers. The as-made polymer monoliths exhibit high mechanical properties (tensile strength of 79.4 MPa and Young's modulus of 571.4 MPa) and can undergo a monomer-network-monomer (yields up to 90 %) recycling mediated by an aqueous solution, with the new-generation polymer capable of restoring the material strength to its original state. In addition, owing to its dynamic nature, a catalyst-free and low-temperature reprogrammable covalent adaptable network (vitrimer) was achieved. The design concept reported herein can be applied to the development of other novel vitrimers with high repressibility and recyclability, and sheds light on future design of sustainable polymers with minimal environmental impact.

8.
Nano Lett ; 21(7): 3007-3015, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33797927

RESUMO

Brain injuries are devastating central nervous system diseases, resulting in cognitive, motor, and sensory dysfunctions. However, clinical therapeutic options are still limited for brain injuries, indicating an urgent need to investigate new therapies. Furthermore, the efficient delivery of therapeutics across the blood-brain barrier (BBB) to the brain is a serious problem. In this study, a facile strategy of dual site-selective functionalized (DSSF) poly(ß-amino esters) was developed using bio-orthogonal chemistry for promoting brain nerve regeneration. Fluorescence colocalization studies demonstrated that these proton-sponge DSSF poly(ß-amino esters) targeted mitochondria through electrostatic interactions. More importantly, this delivery system could effectively accumulate in the injured brain sites and accelerate the recovery of the injured brain. Finally, this DSSF poly(ß-amino esters) platform may provide a new methodology for the construction of dual regioselective carriers in protein/peptide delivery and tissue engineering.


Assuntos
Ésteres , Regeneração Nervosa , Barreira Hematoencefálica , Encéfalo , Engenharia Tecidual
9.
Cell Immunol ; 360: 104262, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33373818

RESUMO

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC.


Assuntos
Exossomos/metabolismo , Proteínas Ligadas por GPI/metabolismo , Imunoterapia Adotiva/métodos , Animais , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Exossomos/imunologia , Feminino , Proteínas Ligadas por GPI/efeitos dos fármacos , Humanos , Imunoterapia/métodos , Masculino , Mesotelina , Camundongos , Camundongos Endogâmicos NOD , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
10.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805568

RESUMO

Despite the existence of many attempts at nerve tissue engineering, there is no ideal strategy to date for effectively treating defective peripheral nerve tissue. In the present study, well-aligned poly (L-lactic acid) (PLLA) nanofibers with varied nano-porous surface structures were designed within different ambient humidity levels using the stable jet electrospinning (SJES) technique. Nanofibers have the capacity to inhibit bacterial adhesion, especially with respect to Staphylococcus aureus (S. aureus). It was noteworthy to find that the large nano-porous fibers were less detrimentally affected by S. aureus than smaller fibers. Large nano-pores furthermore proved more conducive to the proliferation and differentiation of neural stem cells (NSCs), while small nano-pores were more beneficial to NSC migration. Thus, this study concluded that well-aligned fibers with varied nano-porous surface structures could reduce bacterial colonization and enhance cellular responses, which could be used as promising material in tissue engineering, especially for neuro-regeneration.


Assuntos
Antibacterianos/farmacologia , Nanofibras/química , Células-Tronco Neurais/citologia , Engenharia Tecidual/métodos , Animais , Antibacterianos/química , Materiais Biocompatíveis/química , Diferenciação Celular , Movimento Celular , Proliferação de Células , Escherichia coli/efeitos dos fármacos , Expressão Gênica , Camundongos , Células-Tronco Neurais/fisiologia , Poliésteres/química , Porosidade , Staphylococcus aureus/efeitos dos fármacos , Engenharia Tecidual/instrumentação , Alicerces Teciduais , Difração de Raios X
11.
Molecules ; 26(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34641427

RESUMO

O-GlcNAcylation is a nutrient-driven post-translational modification known as a metabolic sensor that links metabolism to cellular function. Recent evidences indicate that the activation of O-GlcNAc pathway is a potential pro-survival pathway and that acute enhancement of this response is conducive to the survival of cells and tissues. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-ß-d-pyranoside (SalA-4g), is a salidroside analogue synthesized in our laboratory by chemical structure-modification, with a phenyl ring containing a para-methoxy group and a sugar ring consisting of N-acetylglucosamine. We have previously shown that SalA-4g elevates levels of protein O-GlcNAc and improves neuronal tolerance to ischemia. However, the specific target of SalA-4g regulating O-GlcNAcylation remains unknown. To address these questions, in this study, we have focused on mitochondrial network homeostasis mediated by O-GlcNAcylation in SalA-4g's neuroprotection in primary cortical neurons under ischemic-like conditions. O-GlcNAc-modified mitochondria induced by SalA-4g demonstrated stronger neuroprotection under oxygen glucose deprivation and reoxygenation stress, including the improvement of mitochondrial homeostasis and bioenergy, and inhibition of mitochondrial apoptosis pathway. Blocking mitochondrial protein O-GlcNAcylation with OSMI-1 disrupted mitochondrial network homeostasis and antagonized the protective effects of SalA-4g. Collectively, these data demonstrate that mitochondrial homeostasis mediated by mitochondrial protein O-GlcNAcylation is critically involved in SalA-4g neuroprotection.


Assuntos
Acetilglucosamina/análogos & derivados , Metabolismo Energético , Isquemia/prevenção & controle , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Acetilglucosamina/farmacologia , Animais , Glucose/metabolismo , Glicosilação , Homeostase , Isquemia/metabolismo , Isquemia/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Oxigênio/metabolismo , Processamento de Proteína Pós-Traducional , Ratos , Ratos Sprague-Dawley
12.
J Nat Prod ; 83(10): 3041-3049, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33026807

RESUMO

The natural products piperlongumine and piperine have been shown to inhibit cancer cell proliferation through elevation of reactive oxidative species (ROS) and eventually cell death, but only have modest cytotoxic potencies. A series of 14 novel phenylallylidenecyclohexenone analogues based on piperlongumine and piperine therefore were designed and synthesized, and their pharmacological properties were evaluated. Most of the compounds produced antiproliferative activities against five human cancer cells with IC50 values lower than those of piperlongumine and piperine. Among these, compound 9m exerted the most potent antiproliferative activity against drug-resistant Bel-7402/5-FU human liver cancer 5-FU resistant cells (IC50 = 0.8 µM), which was approximately 10-fold lower than piperlongumine (IC50 = 8.4 µM). Further, 9m showed considerably lower cytotoxicity against LO2 human normal liver epithelial cells compared to Bel-7402/5-FU. Mechanistically, compound 9m inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, reduced mitochondrial transmembrane potential (MTP), and induced autophagy in Bel-7402/5-FU cells via regulation of autophagy-related proteins LC3, p62, and beclin-1. Finally, 9m activated significantly the p38 signaling pathways and suppressed the Akt/mTOR signaling pathways. In conclusion, 9m could be a promising candidate for the treatment of drug-resistant cancer cells and, as such, warrants further investigation.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Benzodioxóis/farmacologia , Dioxolanos/farmacologia , Proteína Oncogênica v-akt/efeitos dos fármacos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Tiorredoxina Redutase 1/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Alcaloides/síntese química , Alcaloides/química , Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Benzodioxóis/síntese química , Benzodioxóis/química , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dioxolanos/síntese química , Dioxolanos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/química , Alcamidas Poli-Insaturadas/síntese química , Alcamidas Poli-Insaturadas/química , Espécies Reativas de Oxigênio
13.
J Neuroinflammation ; 16(1): 85, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30981278

RESUMO

BACKGROUND: Astrocytes have been shown to produce several pro- and anti-inflammatory cytokines to maintain homeostasis of microenvironment in response to vast array of CNS insults. Some inflammation-related cytokines are responsible for regulating such cell events. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that can be inducibly expressed in the lesioned spinal cord. Unknown is whether MIF can facilitate the production of immunosuppressive factors from astrocytes to tune milieu following spinal cord injury. METHODS: Following establishment of contusion SCI rat model, correlation of PGE2 synthesis-related protein levels with that of MIF was assayed by Western blot. ELISA assay was used to detect production of PGE2, TNF-α, IL-1ß, and IL-6. Immunohistochemistry was performed to observe colocalization of COX2 with GFAP- and S100ß-positive astrocytes. The primary astrocytes were treated by various inhibitors to validate relevant signal pathway. RESULTS: The protein levels of MIF and COX2, but not of COX1, synchronously increased following spinal cord injury. Treatment of MIF inhibitor 4-IPP to the lesion sites significantly reduced the expression of COX2, mPGES-1, and as a consequence, the production of PGE2. Astrocytes responded robustly to the MIF interference, by which regulated MAPK/COX2/PGE2 signal pathway through coupling with the CD74 membrane receptor. MIF-induced production of PGE2 from astrocytes was able to suppress production of TNF-α, but boosted production of IL-1ß and IL-6 in LPS-activated macrophages. CONCLUSION: Collectively, these results reveal a novel function of MIF-mediated astrocytes, which fine-tune inflammatory microenvironment to maintain homeostasis. These suggest an alternative therapeutic strategy for CNS inflammation.


Assuntos
Astrócitos/efeitos dos fármacos , Dinoprostona/metabolismo , Inflamação/etiologia , Inflamação/patologia , Fatores Inibidores da Migração de Macrófagos/farmacologia , Traumatismos da Medula Espinal/complicações , Animais , Animais Recém-Nascidos , Antígenos de Diferenciação de Linfócitos B/metabolismo , Astrócitos/química , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Indóis/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Sprague-Dawley , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Medula Espinal/citologia
14.
J Mater Sci Mater Med ; 30(7): 85, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292746

RESUMO

Pancreatic transplantation remains the only cure for diabetes, but the shortage of donors limits its clinical application. Whole organ decellularized scaffolds offer a new opportunity for pancreatic organ regeneration; however inadequate endothelialization and vascularization can prevent sufficient transport of oxygen and nutrient supplies to the transplanted organ, as well as leading unwanted thrombotic events. In the present study, we explored the re-endothelialization of rat pancreatic acellular scaffolds via circulation perfusion using human skin fibroblasts (FBs) and human umbilical vein endothelial cells (HUVECs). Our results revealed that the cell adhesion rate when these cells were co-cultured was higher than under control conditions, and this increase was associated with increased release of growth factors including VEGF, FGFb, EGF, and IGF-1 as measured by ELISA. When these recellularized organs were implanted in vivo for 28 days in rat dorsal subcutaneous pockets, we found that de novo vasculature formation in the co-culture samples was superior to the control samples. Together these results suggest that endothelial cell and FB co-culture enhances the re-endothelialization and vascularization of pancreatic acellular scaffolds.


Assuntos
Técnicas de Cultura de Células , Células Endoteliais/citologia , Fibroblastos/citologia , Pâncreas/fisiologia , Alicerces Teciduais , Animais , Adesão Celular , Técnicas de Cocultura , Fator de Crescimento Epidérmico/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Oxigênio/química , Perfusão , Proteômica , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Clin Exp Hypertens ; 40(6): 518-523, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29200319

RESUMO

Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.


Assuntos
Povo Asiático/genética , DNA Mitocondrial/genética , Hipertensão/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Filogenia , Fatores de Risco
16.
Luminescence ; 31(5): 1130-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26748824

RESUMO

The binding of isorhamnetin to bovine liver catalase (BLC) was first investigated at 302, 310 and 318 K at pH 7.4 using spectroscopic methods including fluorescence spectra, circular dichroism (CD) and UV-vis absorption. Spectrophotometric observations are rationalized mainly in terms of a static quenching process. The binding constants and binding sites were evaluated by fluorescence quenching methods. Enzymatic activity of BLC in the absence and presence of isorhamnetin was measured using a UV/vis spectrophotometer. The result revealed that the binding of isorhamnetin to BLC led to a reduction in the activity of BLC. The positive entropy change and enthalpy change indicated that the interaction of isorhamnetin with BLC was mainly driven by hydrophobic forces. The distance r between the donor (BLC) and acceptor (isorhamnetin) was estimated to be 2.99 nm according to fluorescence resonance energy transfer. Fluorescence, synchronous fluorescence, and CD spectra showed no obvious change in the conformation of BLC upon the binding of isorhamnetin. In addition, the influence of pH on the binding of isorhamnetin to BLC was investigated and the binding ability of the drug to BLC deceased under other pH conditions (pH 9.0, 6.5, 5.0, 3.5, or 2.0) as compared with that at pH 7.4. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Catalase/química , Fígado/enzimologia , Quercetina/análogos & derivados , Animais , Catalase/metabolismo , Bovinos , Dicroísmo Circular , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Quercetina/química , Quercetina/metabolismo , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
17.
J Tradit Chin Med ; 35(6): 685-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26742315

RESUMO

OBJECTIVE: To ascertain if total flavonoids of Guangzao (Fructus Choerospondiatis) (TFFC) extracted from Guangzao (Fructus Choerospondiatis) can inhibit angiotensin II-induced proliferation of cardiac fibroblasts (CFs). METHODS: CFs were cultured by the differential attachment method. A model of cell proliferation was established by stimulation with Ang II. Cardiac fibroblasts growth was determined using a hemocytometer. Cell proliferation was detected by methyl thiazole tetrazolium. Lactate dehydrogenase activity was measured by chemical colorimetric method. RESULTS: Proliferation of TFFC-treated (25, 50, 100 mg/L) fibroblasts was significantly less than that of cells in the angiotensin II group (P < 0.01), and TFFC inhibited proliferation in a dose-dependent manner. These inhibitory effects were partly blocked by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ). CONCLUSION: TFFC inhibited angiotensin II-induced proliferation of cardiac fibroblasts via a mechanism that probably involves activation of the NO-cyclic guanosine monophosphate signaling pathway.


Assuntos
Anacardiaceae/química , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Coração/efeitos dos fármacos , Animais , Células Cultivadas , Fibroblastos/metabolismo , Flavonoides/farmacologia , Frutas/química , Coração/fisiopatologia , Ratos , Transdução de Sinais/efeitos dos fármacos
18.
Toxicol Appl Pharmacol ; 277(3): 259-69, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24726522

RESUMO

Salidroside is proven to be a neuroprotective agent of natural origin, and its analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-ß-d-pyranoside (named SalA-4g), has been synthesized in our lab. In this study, we showed that SalA-4g promoted neuronal survival and inhibited neuronal apoptosis in primary hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to ischemia by transient middle cerebral artery occlusion (MCAO), respectively, and that SalA-4g was more neuroprotective than salidroside. We further found that SalA-4g elevated glucose uptake in OGD-injured primary hippocampal neurons and increased the expression and recruitment of glucose transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4g triggered the phosphorylation of CREB, and increased the expression of PKA RII in primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and blocked the protective effects of SalA-4g. Moreover, SalA-4g was noted to inhibit intracellular Ca(2+) influx and calpain1 activation in OGD-injured primary hippocampal neurons. Our results suggest that SalA-4g neuroprotection might be mediated by increased glucose uptake and elevated GLUT3 expression through calpain1/PKA/CREB pathway.


Assuntos
Acetilglucosamina/análogos & derivados , Isquemia Encefálica/tratamento farmacológico , Transportador de Glucose Tipo 3/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acetilglucosamina/química , Acetilglucosamina/farmacologia , Acetilglucosamina/uso terapêutico , Animais , Isquemia Encefálica/complicações , Calpaína/genética , Calpaína/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 3/genética , Hipocampo/citologia , Camundongos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/etiologia
19.
Yao Xue Xue Bao ; 49(1): 136-41, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24783519

RESUMO

This study aims to investigate the effect of total flavones of Fructus Chorspondiatis (TFFC) on the mRNA and protein expression of collagen type I and III of rat cardiac fibroblasts (CFs) induced by angiotensin II (Ang II), and explore its anti-myocardial fibrosis molecular mechanism. Neonatal rat CFs were prepared from Sprague-Dawley rats (1-3 d after birth). The expression of collagen type I and III mRNA and protein were measured by RT-PCR and Western blotting, respectively. The study showed that stimulation of neonatal rat CFs with 100 nmol.L-1 of Ang II for 72 h resulted in a significant increase of the expression of collagen type I and III mRNA and protein. The changes on the expression level were blocked by TFFC. The results demonstrated that TFFC can inhibit myocardial fibrosis induced by Ang II in rats, which is probably associated with the collagen type I and III mRNA and protein levels up-regulated by Ang II, and TFFC was shown to decrease the expression levels of collagen type I and III mRNA and protein.


Assuntos
Anacardiaceae/química , Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Fibroblastos/metabolismo , Flavonas/farmacologia , Angiotensina II/farmacologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/citologia , Flavonas/administração & dosagem , Flavonas/isolamento & purificação , Frutas/química , Miocárdio/citologia , Miocárdio/metabolismo , Plantas Medicinais/química , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Anal Methods ; 16(18): 2878-2887, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38639924

RESUMO

Shikimic acid (SA) is one of the most effective drugs against the A (H1N1) virus and has high medicinal value. Additionally, it has the ability to generate non-toxic herbicides and antimicrobial medications. The extraction from plants has proven to be the main route of production of SA with economic benefits and environmental efficiency. Therefore, it is necessary to perform purification of SA from these herbal medicines before quantifying it. In this study, researchers employed a boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) as highly effective solid phase extraction (SPE) adsorbents for the isolation and purification of SA. 3-Fluoro-4-formylphenylboronic acid functionalized silica nanoparticles were used as supporting materials for immobilizing SA. Poly(2-anilinoethanol) with a higher hydrophilic domain can be used as an effective imprinting coating. The prepared SA-imprinted silica nanoparticles exhibited several significant results, such as good specificity, high binding capacity (39.06 ± 2.24 mg g-1), moderate binding constant (6.61 × 10-4 M-1), fast kinetics (8 min) and low binding pH (pH 5.0) toward SA. The replication of SA-imprinted silica nanoparticles was deemed satisfactory. The SA-imprinted silica nanoparticles could be still reused after seven adsorption-desorption cycles, which indicated high chemical stability. In addition, the recoveries of the proposed method for SA at three spiked level analysis in star aniseed and meadow cranesbill were 96.2% to 109.0% and 91.6% to 103.5%, respectively. The SA-imprinted silica nanoparticles that have been prepared are capable of identifying the target SA in real herbal medicines. Our approach makes sample pre-preparation simple, fast, selective and efficient.


Assuntos
Ácidos Borônicos , Impressão Molecular , Nanopartículas , Ácido Chiquímico , Dióxido de Silício , Extração em Fase Sólida , Dióxido de Silício/química , Nanopartículas/química , Impressão Molecular/métodos , Ácido Chiquímico/química , Ácido Chiquímico/isolamento & purificação , Ácidos Borônicos/química , Extração em Fase Sólida/métodos , Polímeros Molecularmente Impressos/química , Adsorção , Medicina Herbária/métodos
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