RESUMO
Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), may result from immune system dysfunction, leading to the sustained overproduction of reactive oxygen species (ROS) and subsequent cellular oxidative stress damage. Recent studies have identified both peroxisome proliferator-activated receptor-γ (PPARγ) and endoplasmic reticulum (ER) stress as critical targets for the treatment of IBD. Oroxyloside (C22H20O11), derived from the root of Scutellariabaicalensis Georgi, has traditionally been used in treating inflammatory diseases. In this study, we investigated the molecular mechanisms by which oroxyloside mitigates dextran sulfate sodium (DSS)-induced colitis. We examined the effects of oroxyloside on ROS-mediated ER stress in colitis, including the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, and CHOP, which are associated with ER stress. The beneficial impact of oroxyloside was reversed by the PPARγ antagonist GW9662 (1 mg·kg-1, i.v.) in vivo. Furthermore, oroxyloside decreased pro-inflammatory cytokines and ROS production in both bone marrow-derived macrophages (BMDM) and the mouse macrophage cell line RAW 264.7. However, PPARγ siRNA transfection blocked the anti-inflammatory effect of oroxyloside and even abolished ROS generation and ER stress activation inhibited by oroxyloside in vitro. In conclusion, our study demonstrates that oroxyloside ameliorates DSS-induced colitis by inhibiting ER stress via PPARγ activation, suggesting that oroxyloside might be a promising effective agent for IBD.
Assuntos
Colite , Sulfato de Dextrana , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL , PPAR gama , Espécies Reativas de Oxigênio , Animais , PPAR gama/metabolismo , PPAR gama/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Masculino , Humanos , Substâncias Protetoras/farmacologiaRESUMO
Aralia elata (Miq.) Seem is a medicinal plant that shares a common pathway for the biosynthesis of triterpenoid saponins with Panax ginseng. Here, we transferred the dammarenediol-II synthase gene from P. ginseng (PgDDS; GenBank: AB122080.1) to A. elata. The growth of 2-year-old transgenic plants (L27; 9.63 cm) was significantly decreased compared with wild-type plants (WT; 74.97 cm), and the leaflet shapes and sizes of the transgenic plants differed from those of the WT plants. Based on a terpene metabolome analysis of leaf extracts from WT, L13, and L27 plants, a new structural skeleton for ursane-type triterpenoid saponins was identified. Six upregulated differentially accumulated metabolites (DAMs) were detected, and the average levels of Rg3 and Re in the leaves of the L27 plants were 42.64 and 386.81 µg/g, respectively, increased significantly compared with the WT plants (15.48 and 316.96 µg/g, respectively). Thus, the expression of PgDDS in A. elata improved its medicinal value.
Assuntos
Aralia , Plantas Medicinais , Saponinas , Triterpenos , Aralia/genética , Aralia/química , Saponinas/química , Triterpenos/química , Plantas Medicinais/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Folhas de Planta/metabolismoRESUMO
As a key rate-limiting enzyme in the de novo synthesis of pyrimidine nucleotides, human dihydroorotate dehydrogenase (hDHODH) is considered a known target for the treatment of autoimmune diseases, including inflammatory bowel disease (IBD). Herein, BAY 41-2272 with a 1H-pyrazolo[3,4-b]pyridine scaffold was identified as an hDHODH inhibitor by screening an active compound library containing 5091 molecules. Further optimization led to 2-(1-(2-chloro-6-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-cyclopropylpyrimidin-4-amine (w2), which was found to be the most promising and drug-like compound with potent inhibitory activity against hDHODH (IC50 = 173.4 nM). Compound w2 demonstrated acceptable pharmacokinetic characteristics and alleviated the severity of acute ulcerative colitis induced by dextran sulfate sodium in a dose-dependent manner. Notably, w2 exerted better therapeutic effects on ulcerative colitis than hDHODH inhibitor vidofludimus and Janus kinase (JAK) inhibitor tofacitinib. Taken together, w2 is a promising hDHODH inhibitor for the treatment of IBD and deserves to be developed as a preclinical candidate.
Assuntos
Colite Ulcerativa , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Humanos , Estrutura Molecular , Colite Ulcerativa/tratamento farmacológico , Desenho de Fármacos , Di-Hidro-Orotato Desidrogenase , Inibidores Enzimáticos/farmacologiaRESUMO
Hafnium oxide-based ferroelectric materials are promising candidates for next-generation nanoscale devices because of their ability to integrate into silicon electronics. However, the intrinsic high coercive field of the fluorite-structure oxide ferroelectric devices leads to incompatible operating voltage and limited endurance performance. We discovered a complementary metal-oxide semiconductor (CMOS)-compatible rhombohedral ferroelectric Hf(Zr)1+xO2 material rich in hafnium-zirconium [Hf(Zr)]. X-ray diffraction combined with scanning transmission electron microscopy reveals that the excess Hf(Zr) atoms intercalate within the hollow sites. We found that the intercalated atoms expand the lattice and increase the in-plane and out-of-plane stresses, which stabilize both the rhombohedral phase (r-phase) and its ferroelectric properties. Our ferroelectric devices, which are based on the r-phase Hf(Zr)1+xO2, exhibit an ultralow coercive field (~0.65 megavolts per centimeter). Moreover, we achieved a high endurance of more than 1012 cycles at saturation polarization. This material discovery may help to realize low-cost and long-life memory chips.
RESUMO
Blocking the de novo biosynthesis of pyrimidine by inhibiting human dihydroorotate dehydrogenase (hDHODH) is an effective way to suppress the proliferation of cancer cells and activated lymphocytes. Herein, eighteen teriflunomide derivatives and four ASLAN003 derivatives were designed and synthesized as novel hDHODH inhibitors based on a benzophenone scaffold. The optimal compound 7d showed a potent hDHODH inhibitory activity with an IC50 value of 10.9 nM, and displayed promising antiproliferative activities against multiple human cancer cells with IC50 values of 0.1-0.8 µM. Supplementation of exogenous uridine rescued the cell viability of 7d-treated Raji and HCT116 cells. Meanwhile, 7d significantly induced cell cycle S-phase arrest in Raji and HCT116 cells. Furthermore, 7d exhibited favorable safety profiles in mice and displayed effective antitumor activities with tumor growth inhibition (TGI) rates of 58.3% and 42.1% at an oral dosage of 30 mg/kg in Raji and HCT116 cells xenograft models, respectively. Taken together, these findings provide a promising hDHODH inhibitor 7d with potential activities against some tumors.
Assuntos
Antineoplásicos , Neoplasias , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Humanos , Camundongos , Animais , Di-Hidro-Orotato Desidrogenase , Relação Estrutura-Atividade , Inibidores Enzimáticos , Benzofenonas/farmacologia , Proliferação de Células , Antineoplásicos/farmacologia , Linhagem Celular TumoralRESUMO
The rainwater and rainfall runoff of roofs in the central district of Beijing from June to September in 2019 were sampled and analyzed to study the characteristics of the water quality, the first flush effect, and the main influential factors and sources of pollutants. The results showed that the roof runoff was seriously polluted by total nitrogen, ammonia nitrogen, chemical oxygen demand, and total suspended solids whose event mean concentration (EMC) exceeded the fifth level of environmental quality standards for surface water (GB 3838-2002) (the EMC of suspended solids exceeded the second level of discharge standard of pollutants for municipal wastewater treatment plants (GB 18918-2002)). The rainwater was relatively less polluted than the rainfall runoff, but the EMC of ammonia nitrogen and total nitrogen of the rainwater also exceeded the standard in some rainfall events. The first flush intensity of the rainfall runoffs was between weak and medium. The sequence of strength of the first flush of different pollutants was ammonia nitrogen>total suspended solids>chemical oxygen demand>total nitrogen>mercury>zinc>total phosphorus>lead. The concentration of total suspended solids, chemical oxygen demand, and total phosphorus in roof runoff were significantly positively correlated with the length of rainfall and the dry period and negatively correlated with the rainfall intensity. According to the results of principal component analysis, the main pollutant in rainwater was nitrogen emitted by vehicles, and the main pollutants in roof runoffs were suspended solids, organic matters, and phosphorus pollutants released from the aging of roofing materials and the corrosion of metal down pipes.
Assuntos
Poluentes Ambientais , Movimentos da Água , Amônia/análise , Pequim , Monitoramento Ambiental , Poluentes Ambientais/análise , Nitrogênio/análise , Fósforo/análise , Chuva , Qualidade da ÁguaRESUMO
Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 µM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
Assuntos
Inibidores Enzimáticos/síntese química , Fosfoglicerato Desidrogenase/antagonistas & inibidores , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Combinatória , Dano ao DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Fosfoglicerato Desidrogenase/metabolismo , Relação Estrutura-AtividadeRESUMO
Enhancement of the transesterification efficiency of triglyceride has come under heated study in biodiesel-making industry. In this research, the NiMo/La-Al2O3 nanopowders have been prepared for producing biodiesel efficiently. The screening test showed that the NiMo/La-Al2O3 catalyst has the best catalytic activity for triglyceride transesterification. Besides, the process parameters including reaction temperature, time, oil-to-alcohol ratio and catalyst loading etc., also have been investigated for optimization of the transesterification process. The results showed that with 5â wt% of catalyst loading, and oil to methanol molar ratio of 1:9, the conversion yield of triglyceride could be up to 95.2% within 120â min at 160°C. The NiMo/La-Al2O3 catalyst has the outstanding recycle property, which proved that the prepared NiMo/La-Al2O3 powders can be suitable for biodiesels' production.
Assuntos
Biocombustíveis , Óleos de Plantas , Catálise , Esterificação , Pós , TriglicerídeosRESUMO
PURPOSE: To effectively predict lateral neck lymph nodes (LLN) metastasis in papillary thyroid carcinoma (PTC) patients with central lymph nodes (CLN) invasion, and devise targeted treatment strategies. METHODS: Four hundred and thirty-four PTC patients with CLN metastasis from two medical centers were retrospectively analyzed. A new statistical model was established for predicting LLN involvement in these patients to guide lymph nodes management strategies. RESULTS: Patients with more than five positive CLN metastasis appeared to have extremely high risk (83.0%) of LLN involvement. For patients with five or less positive CLN invasion, multivariate logistic analyses were applied. Independent risk factors for LLN involvement were determined to be: age over 40, maximum tumor diameter of no less than 1.0 cm, existence of thyroid capsular invasion, and tumor with ipsilateral nodular goiter (iNG). These factors were used to construct a predictive nomogram. The accuracy and validity of our newly built model were verified by C-index 0.761 (95% CI, 0.707-0.815) in development cohort and 0.759 (95% CI, 0.745-0.773) in validation cohort and calibration curve. The patients were stratified into three groups based on their nomogram risk scores. Possible LLN involvement rates for low-risk, moderate-risk, and relatively high-risk subgroups were 8.9%, 22.8%, and 48.2%, respectively. CONCLUSIONS: Our newly established model can effectively predict possible LLN metastasis in PTC patients, and a new strategy selection flow chart was created for patients with positive CLN invasion. For patients in high-risk group, prophylactic LLN dissection is recommended, if not, adjuvant radioactive iodine or a closer follow-up scheme should at least be conducted. For those in low-risk group, surgical intervention is unnecessary and regular follow-up is recommended.
Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/cirurgia , Humanos , Radioisótopos do Iodo , Linfonodos , Metástase Linfática , Esvaziamento Cervical , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.
Assuntos
Antineoplásicos/química , Neoplasias da Mama/terapia , Campos Magnéticos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Hipertermia Induzida , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia , Polietilenoglicóis/química , Solução Salina/química , Transplante HeterólogoRESUMO
The powder X-ray diffraction(PXRD) technique was used to investigate fourteen kinds of Ranunculaceae herbal decoction pieces(RHDP) recorded in Chinese Pharmacopoeia and to explore a novel PXRD quality control method for RHDP. The results indicated that only three RHDP-Paeoniae Radix Alba, Paeoniae Radix Rubra, and Moutan Cortex, contained calcium oxalate monodydrate(COM), whereas no COM existed in other eleven kinds of RHDP. The difference in PXRD for Paeoniae Radix Alba and Paeoniae Radix Rubra from different growing areas were investigated. The quantitative analysis method for COM was discussed by considering the water-boiling manufacturing process of herbal decoction pieces. The water-boiling experiments revealed that the PXRD peaks from COM crystals in RHDP were enhanced significantly after boiling. Paeoniae Radix Alba, Paeoniae Radix Rubra, Moutan Cortex, Aconiti Lateralis Radix Praeparata, Aconiti Radix, Aconiti Kusnezoffii Radix, and Anemone Raddeanae Rhizoma exhibited a similar series of broader peaks in the 2θ region of 15° to 35°, whose origins were discussed on the basis of chemical constituents RHDP reported by other researchers. These diffraction broader peaks most likely originated from periodic orientation of benzene ring in organic molecular crystals of aconitine-and paeonolum-based alkaloids and glycosides chemical constituents, subsequently, possibly from some other organic constituents. The PXRD technique can be used to rapidly identify Cimicifuga heracleifolia with an amorphous dispersion peak and C. dahurica with a sharp-peak feature. Climatidis Radix et Rhizoma exhibited a series of sharp PXRD peaks. The PXRD method can provide a valuable quality control method for RHDP.
Assuntos
Aconitum , Química , Medicamentos de Ervas Chinesas , Química , Paeonia , Química , Compostos Fitoquímicos , Ranunculaceae , Química , Rizoma , Química , Difração de Raios XRESUMO
Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe3O4 nanoparticles into chitosan/polyethylene glycol (PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field (AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells (MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.
Assuntos
Diferenciação Celular/fisiologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Campos Magnéticos , Células-Tronco Mesenquimais/citologia , Nanocompostos/química , Proliferação de Células , Sobrevivência Celular , Quitosana/química , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Osteogênese/fisiologia , TemperaturaRESUMO
Angiogenesis is associated with the progression of multiple myeloma (MM). Wogonin is an active mono-flavonoid with remarkable antitumor activity. However, its impact on MM-stimulated angiogenesis remains largely unknown. Here, we demonstrated that wogonin decreased expression and secretion of pro-angiogenic factors in MM cells via c-Myc/HIF-1α signaling axis, reducing MM-stimulated angiogenesis and MM cell proliferation in vivo. Overexpression of c-Myc in MM cells disrupted the balance between VHL SUMOylation and ubiquitination, and thus inhibited proteasome-mediated HIF-1α degradation. Impaired function of VHL ubiquitination complex in c-Myc-overexpressing cells was fully reversed by wogonin treatment via increasing HIF-1α-VHL interaction and promoting HIF-1α degradation. Collectively, our in vitro and in vivo studies reveal for the first time that wogonin represses MM-stimulated angiogenesis and tumor progression via c-Myc/VHL/HIF-1α signaling axis.
Assuntos
Inibidores da Angiogênese/farmacologia , Flavanonas/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mieloma Múltiplo/irrigação sanguínea , Neovascularização Patológica/prevenção & controle , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Adulto , Idoso , Indutores da Angiogênese/farmacologia , Animais , Western Blotting , Adesão Celular , Movimento Celular , Proliferação de Células , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas Imunoenzimáticas , Imunoprecipitação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
AIM: Aconiti Lateralis Radix Preparata is a traditional Chinese medicine used to treat chronic arthritis and is highly effective against rheumatoid arthritis. However, the effects of aconine, a derivative of aconitum alkaloids, on osteoclasts, which can absorb bone, remain unknown. Here, we investigated the effects of aconine on osteoclast differentiation and bone resorption in vitro. METHODS: The viability of mouse leukemic monocyte/macrophage cell line RAW264.7 was measured using CCK-8 assays. Osteoclast differentiation was induced by incubation of RAW264.7 cells in the presence of RANKL, and assessed with TRAP staining assay. Bone resorption was examined with bone resorption pits assay. The expression of relevant genes and proteins was analyzed using RT-PCR and Western blots. The activation of NF-κB and nuclear factor of activated T-cells (NFAT) was examined using stable NF-κB and NFATc1 luciferase reporter gene systems, RT-PCR and Western blot analysis. RESULTS: Aconine (0.125, 0.25 µmol/L) did not affect the viability of RAW264.7 cells, but dose-dependently inhibited RANKL-induced osteoclast formation and bone resorptive activity. Furthermore, aconine dose-dependently inhibited the RANKL-induced activation of NF-κB and NFATc1 in RAW264.7 cells, and subsequently reduced the expression of osteoclast-specific genes (c-Src, ß3-Integrin, cathepsin K and MMP-9) and the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which played an important role in cell-cell fusion. CONCLUSION: These findings suggest that aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing the activation of NF-κB and NFATc1 and the expression of the cell-cell fusion molecule DC-STAMP.
Assuntos
Aconitina/análogos & derivados , Adjuvantes Imunológicos/farmacologia , Proteínas de Membrana/genética , NF-kappa B/imunologia , Fatores de Transcrição NFATC/imunologia , Proteínas do Tecido Nervoso/genética , Osteoclastos/efeitos dos fármacos , Ligante RANK/imunologia , Aconitina/farmacologia , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Reabsorção Óssea/imunologia , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Camundongos , Osteoclastos/citologia , Osteoclastos/imunologia , Osteoclastos/metabolismo , Células RAW 264.7RESUMO
Somatic embryogenesis (SE) has been studied as a model system to understand molecular events in physiology, biochemistry, and cytology during plant embryo development. In particular, it is exceedingly difficult to access the morphological and early regulatory events in zygotic embryos. To understand the molecular mechanisms regulating early SE in Eleutherococcus senticosus Maxim., we used high-throughput RNA-Seq technology to investigate its transcriptome. We obtained 58,327,688 reads, which were assembled into 75,803 unique unigenes. To better understand their functions, the unigenes were annotated using the Clusters of Orthologous Groups, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases. Digital gene expression libraries revealed differences in gene expression profiles at different developmental stages (embryogenic callus, yellow embryogenic callus, global embryo). We obtained a sequencing depth of >5.6 million tags per sample and identified many differentially expressed genes at various stages of SE. The initiation of SE affected gene expression in many KEGG pathways, but predominantly that in metabolic pathways, biosynthesis of secondary metabolites, and plant hormone signal transduction. This information on the changes in the multiple pathways related to SE induction in E. senticosus Maxim. embryogenic tissue will contribute to a more comprehensive understanding of the mechanisms involved in early SE. Additionally, the differentially expressed genes may act as molecular markers and could play very important roles in the early stage of SE. The results are a comprehensive molecular biology resource for investigating SE of E. senticosus Maxim.
Assuntos
Eleutherococcus/embriologia , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Plantas/genética , Análise de Sequência de RNA/métodos , Eleutherococcus/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Redes e Vias Metabólicas , Anotação de Sequência Molecular , Técnicas de Embriogênese Somática de Plantas , Plantas Medicinais/embriologia , Plantas Medicinais/genéticaRESUMO
A novel multifunctional poly(γ-glutamic acid)/silk sericin (γ-PGA/SS) hydrogel has been developed and used as wound dressing. The physical and chemical properties of the γ-PGA/SS gels were systemically investigated. Furthermore, these γ-PGA/SS gels have been found to promote the L929 fibroblast cells proliferate, and in the in vivo study, significant stimulatory effects were also observed on granulation and capillary formation on day 9 in H-2-treated wounds, indicating that this new complex hydrogel could maintain a moist healing environment, protect the wound from bacterial infection, absorb excess exudates, and promote cell proliferation to reconstruct damaged tissue. Considering the simple preparation process and excellent biological property, this γ-PGA/SS hydrogel might have a wide range of applications in biomedical and clinical areas.
Assuntos
Curativos Biológicos , Fibroblastos/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato , Ácido Poliglutâmico , Sericinas , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/prevenção & controle , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/patologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Camundongos , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologia , Ratos , Ratos Sprague-Dawley , Sericinas/química , Sericinas/farmacologiaRESUMO
Here, we report a bio-inspired chitosan (CS)-based mesh with high separation efficiency, oil-fouling repellency, and stability in a complex liquid environment. The surface of the CS coating maintains underwater superoleophobicity and low oil adhesion (<1 µN) in pure water and hyper-saline solutions, and it can keep stable special wettability in broad pH range environments after the CS mesh is fully cross-linked with glutaraldehyde and then reduced by sodium borohydride to form a stable carbon-nitrogen single bond. The separation process is solely gravity-driven, and the mesh can separate a range of different oil/water mixtures with >99% separation efficiency in hyper-saline and broad pH range conditions. We envision that such a separation method will be useful in oil spill cleanup and industrial oily wastewater treatment in extreme environments.
Assuntos
Quitosana/química , Poluição por Petróleo , Petróleo , Água do Mar/química , Águas Residuárias/química , Purificação da Água/métodos , Concentração de Íons de HidrogênioRESUMO
Breviscapine is a flavonoid constituent isolated from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz. To investigate the apoptosis-inducing effect of breviscapine on human hepatocellular carcinoma cell line HepG2 and explore the relative molecular mechanisms. HepG2 cells were treated with breviscapine at different concentrations and the inhibitory rate was analyzed by MTT assay. The morphological changes in cells were observed under an inverted light microscope and a fluorescence microscope and the apoptosis rate were detected by flow cytometry. Western blot was used to evaluate the protein expression. The viability of HepG2 cells was markedly inhibited in a concentration-dependent manner and obvious morphological changes were confirmed, including condensed chromatin and reduction in volume. The increased percentage of apoptotic cells was displayed by flow cytometry and the altered expression level of several apoptosis-associated proteins, Bcl-2, Bax and caspase-3, was detected by western blot. It is first discovered that breviscapine exhibited potential antitumor activity, induces remarkable apoptosis in HepG2 cells and promises to be a new candidate in future cancer therapy.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Caspase 3/metabolismo , Citometria de Fluxo , Células Hep G2 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/análise , Proteína X Associada a bcl-2/metabolismoRESUMO
PURPOSE: In this study, we investigated the correlation between p53 and bcl-2 in gambogic acid (GA)-induced apoptosis. METHOD: MTT assay was employed to evaluate MCF-7 cell viability after GA treatment. Cell morphological changes were observed follow-up under the inverted microscope after GA withdrawal. To observe the cell apoptosis, DAPI staining was used. Meanwhile, p53 small interfering RNA (si-RNA) was adopted to knock p53 down. All expressions of p53 and bcl-2 were evaluated by Western blot analysis. RESULTS: MTT assay showed that GA inhibited MCF-7 cell growth effectively in a time-dependent manner. With 0.5 h GA treatment, p53 was significantly increased, whereas bcl-2 was reduced potently with 6 h GA treatment. After GA withdrawal, p53 expressions were maintained in high levels. Furthermore, bcl-2 decreasing was attenuated after co-treatment with PFT alpha, a p53 transcription blocker. Same result was observed after p53 knock-down by p53 si-RNA. CONCLUSIONS: Gambogic acid induced human breast cancer cells MCF-7 apoptosis by reducing bcl-2 expression via p53.
Assuntos
Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/fisiologia , Xantonas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Modelos Biológicos , RNA Interferente Pequeno/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidoresRESUMO
<p><b>OBJECTIVE</b>To observe the effect of multi-glycosides of tripterygii (MT) on latent autoimmune diabetes of adults (LADA) in early stage.</p><p><b>METHODS</b>The diabetic patients were divided randomly into the control group treated with insulin alone and the treated group treated with insulin and MT. Levels of insulin, C-peptide, glutamic acid decarboxylase antibody (GADAb) and islet cell antibody (ICA) were detected and clinical features of the disease were observed.</p><p><b>RESULTS</b>There was no difference between the control group and the treated group in body mass index (BMI), the occurrence of diabetic keto-acidosis and the function of liver and kidney (P >0.05). After 6 months' treatment, the positive rate of GADAb and ICA decreased, plasma levels of fasting and 2 hrs post-prandial C-peptide and also 2 hrs post-prandial true insulin in the treated group increased (P <0.01), while all the above indexes improved more significantly after 1 year's treatment (P <0.01).</p><p><b>CONCLUSION</b>Compared treatment of insulin with multi-glycosides of tripterygii in early stage of LADA has better effects in relieving autoimmune injury and recovering function of pancreatic island than insulin alone.</p>