Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
1.
Nat Mater ; 22(6): 786-792, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37217702

RESUMO

Seeded growth of crystallizable block copolymers and π-stacking molecular amphiphiles in solution using living crystallization-driven self-assembly is an emerging route to fabricate uniform one-dimensional and two-dimensional core-shell micellar nanoparticles of controlled size with a range of potential applications. Although experimental evidence indicates that the crystalline core of these nanomaterials is highly ordered, a direct observation of their crystal lattice has not been successful. Here we report the high-resolution cryo-transmission electron microscopy studies of vitrified solutions of nanofibres made from a crystalline core of poly(ferrocenyldimethylsilane) (PFS) and a corona of polysiloxane grafted with 4-vinylpyridine groups. These studies show that poly(ferrocenyldimethylsilane) chains pack in an 8-nm-diameter core lattice with two-dimensional pseudo-hexagonal symmetry that is coated by a 27 nm 4-vinylpyridine corona with a 3.5 nm distance between each 4-vinylpyridine strand. We combine this structural information with a molecular modelling analysis to propose a detailed molecular model for solvated poly(ferrocenyldimethylsilane)-b-4-vinylpyridine nanofibres.

2.
Org Biomol Chem ; 22(13): 2677, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477554

RESUMO

Expression of Concern for 'Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway' by Zhi-Yong Tian et al., Org. Biomol. Chem., 2009, 7, 4651-4660, https://doi.org/10.1039/B912685F.

3.
Mol Divers ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935305

RESUMO

The urokinase-type plasminogen activator receptor (uPAR) emerges as a key target for anti-metastasis owing to its pivotal role in facilitating the invasive and migratory processes of cancer cells. Recently, we identified the uPAR-targeting anti-metastatic ability of diltiazem (22), a commonly used antihypertensive agent. Fine-tuning the chemical structures of known hits represents a vital branch of drug development. To develop novel anti-metastatic drugs, we performed an interface-driven structural evolution strategy on 22. The uPAR-targeting and anti-cancer abilities of this antihypertensive drug wereidentified by us recently. Based on in silico strategy, including extensive molecular dynamics (MD) simulations, hierarchical binding free energy predictions, and ADMET profilings, we designed, synthesized, and identified three new diltiazem derivatives (221-8, 221-57, and 221-68) as uPAR inhibitors. Indeed, all of these three derivatives exhibited uPAR-depending inhibitory activity against PC-3 cell line invasion at micromolar level. Particularly, derivatives 221-68 and 221-8 showed enhanced uPAR-dependent inhibitory activity against the tumor cell invasion compared to the original compound. Microsecond timesclae MD simulations demonstrated the optimized moiety of 221-68 and 221-8 forming more comprehensive interactions with the uPAR, highlighting the reasonability of our strategy. This work introduces three novel uPAR inhibitors, which not only pave the way for the development of effective anti-metastatic therapeutics, but also emphasize the efficacy and robustness of an in silico-based lead compound optimization strategy in drug design.

4.
Angew Chem Int Ed Engl ; 63(8): e202315599, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38169100

RESUMO

Polypeptides, as natural polyelectrolytes, are assembled into tailored proteins to integrate chromophores and catalytic sites for photosynthesis. Mimicking nature to create the water-soluble nanoassemblies from synthetic polyelectrolytes and photocatalytic molecular species for artificial photosynthesis is still rare. Here, we report the enhancement of the full-spectrum solar-light-driven H2 production within a supramolecular system built by the co-assembly of anionic metalloporphyrins with cationic polyelectrolytes in water. This supramolecular photocatalytic system achieves a H2 production rate of 793 and 685 µmol h-1 g-1 over 24 h with a combination of Mg or Zn porphyrin as photosensitizers and Cu porphyrin as a catalyst, which is more than 23 times higher than that of free molecular controls. With a photosensitizer to catalyst ratio of 10000 : 1, the highest H2 production rate of >51,700 µmol h-1 g-1 with a turnover number (TON) of >1,290 per molecular catalyst was achieved over 24 h irradiation. The hierarchical self-assembly not only enhances photostability through forming ordered stackings of the metalloporphyrins but also facilitates both energy and electron transfer from antenna molecules to catalysts, and therefore promotes the photocatalysis. This study provides structural and mechanistic insights into the self-assembly enhanced photostability and catalytic performance of supramolecular photocatalytic systems.

5.
Amino Acids ; 55(5): 563-578, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37067568

RESUMO

Diabetes mellitus (DM) is a severe chronic diseases with a global prevalence of 9%, leading to poor health and high health care costs, and is a direct cause of millions of deaths each year. The rising epidemic of diabetes and its complications, such as retinal and peripheral nerve disease, is a huge burden globally. A better understanding of the molecular pathways involved in the development and progression of diabetes and its complications can facilitate individualized prevention and treatment. High diabetes mellitus incidence rate is caused mainly by lack of non-invasive and reliable methods for early diagnosis, such as plasma biomarkers. The incidence of diabetes and its complications in the world still grows so it is crucial to develop a new, faster, high specificity and more sensitive diagnostic technologies. With the advancement of analytical techniques, metabolomics can identify and quantify multiple biomarkers simultaneously in a high-throughput manner, and effective biomarkers can greatly improve the efficiency of diabetes and its complications. By providing information on potential metabolic pathways, metabolomics can further define the mechanisms underlying the progression of diabetes and its complications, help identify potential therapeutic targets, and improve the prevention and management of T2D and its complications. The application of amino acid metabolomics in epidemiological studies has identified new biomarkers of diabetes mellitus (DM) and its complications, such as branched-chain amino acids, phenylalanine and arginine metabolites. This study focused on the analysis of metabolic amino acid profiling as a method for identifying biomarkers for the detection and screening of diabetes and its complications. The results presented are all from recent studies, and in all cases analyzed, there were significant changes in the amino acid profile of patients in the experimental group compared to the control group. This study demonstrates the potential of amino acid profiles as a detection method for diabetes and its complications.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Humanos , Aminoácidos/metabolismo , Diabetes Mellitus/metabolismo , Biomarcadores , Metabolômica/métodos , Aminoácidos de Cadeia Ramificada , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico
6.
J Org Chem ; 88(17): 12445-12450, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37594367

RESUMO

An efficient and convenient strategy has been successfully developed for the preparation of novel furantetrahydroquinoline derivatives using d/l-ribose with a 2,3-O-isopropylidene group through the aza-Diels-Alder mechanism. This method has high atom and step economy, high stereoselectivity, and gram-scale synthesis (yield 67%).

7.
Support Care Cancer ; 31(12): 640, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37851143

RESUMO

PURPOSE: There are no well-recognized guidelines for antiemesis during concurrent chemoradiotherapy (CCRT) for cervical cancer (CC) and nasopharyngeal cancer (NPC) until now. The study was designed to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low-dose cisplatin chemotherapy in patients with CC or NPC. METHODS: Patients with CC or NPC were scheduled to receive fractionated radiotherapy and weekly cisplatin (25-40 mg/m2) chemotherapy for at least 5 weeks. Patients stratified by tumor type and induction chemotherapy were 1:1 randomly assigned to receive fosaprepitant, tropisetron, and dexamethasone or tropisetron plus dexamethasone as an antiemetic regimen. Efficacy was assessed primarily by the cumulative incidence of emesis after 5 weeks of treatment, and safety by adverse events (AEs). RESULTS: Between July 2020 and July 2022, 116 patients consented to the study of whom 103 were included in this interim analysis (fosaprepitant group [N = 52] vs control group [N = 51]). The cumulative incidence of emesis at 5 weeks (competing risk analysis) was 25% (95% CI 14.2-37.4) for the fosaprepitant group compared with 59% (95% CI 43.9-71.0) for the control group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group (HR 0.35 [95% CI 0.19-0.64]; p < 0.001). Fosaprepitant was well tolerated as the incidences of adverse events in the two groups were comparable. CONCLUSION: The addition of fosaprepitant to tropisetron plus dexamethasone significantly reduced the risk of nausea and vomiting during 5 weeks of CCRT in patients with CC or NPC, and fosaprepitant was well tolerated. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on October 3, 2022, number NCT05564286.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias Nasofaríngeas , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino , Tropizetrona/uso terapêutico , Dexametasona , Antineoplásicos/efeitos adversos , Vômito/induzido quimicamente , Vômito/prevenção & controle , Estudos Prospectivos , Náusea/etiologia , Náusea/prevenção & controle , Náusea/tratamento farmacológico , Antieméticos/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Fracionamento da Dose de Radiação , Quimioterapia Combinada
8.
Mol Pain ; 18: 17448069221097760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35430901

RESUMO

Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. However, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystal-induced gout model, we performed genome-wide transcriptome analysis of the inflamed ankle joint, dorsal root ganglion (DRG), and spinal cord of gouty mice. Our results revealed important transcriptional changes, including highly elevated inflammation and broad activation of immune pathways in both the joint and the nervous system, in gouty mice. Integrated analysis showed that there was a remarkable overlap between our RNAseq and human genome-wide association study (GWAS) of gout; for example, the risk gene, stanniocalcin-1 (STC1) showed significant upregulation in all three tissues. Interestingly, when compared to the transcriptomes of human osteoarthritis (OA) and rheumatoid arthritis (RA) joint tissues, we identified significant upregulation of cAMP/cyclic nucleotide-mediated signaling shared between gouty mice and human OA with high knee pain, which may provide excellent drug targets to relieve gout pain. Furthermore, we investigated the common and distinct transcriptomic features of gouty, inflammatory pain, and neuropathic pain mouse models in their DRG and spinal cord tissues. Moreover, we discovered distinct sets of genes with significant differential alternative splicing or differential transcript usage in each tissue, which were largely not detected by conventional differential gene expression analysis approaches. Based on these results, our study provided a more accurate and comprehensive depiction of transcriptomic alterations related to gout inflammation and pain.


Assuntos
Gota , Ácido Úrico , Animais , Modelos Animais de Doenças , Estudo de Associação Genômica Ampla , Gota/induzido quimicamente , Gota/complicações , Gota/genética , Inflamação/complicações , Inflamação/genética , Camundongos , Dor/genética
9.
Cell Commun Signal ; 20(1): 175, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348350

RESUMO

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/patologia , Antígeno B7-H1/metabolismo , beta Catenina , Neoplasias Hepáticas/patologia , Espermina/farmacologia , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Microambiente Tumoral
10.
Cancer Sci ; 112(2): 679-690, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33164305

RESUMO

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma (HCC) cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in HCC cells remains largely unclear. Here, we showed that the expression HMGA2 was upregulated in HCC, and that elevated HMGA2 could promote tumor metastasis. Incubation of HCC cells with epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through the PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, whereas a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified that p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteína HMGA2/biossíntese , Histonas/metabolismo , Neoplasias Hepáticas/patologia , Acetilação , Animais , Carcinoma Hepatocelular/metabolismo , Receptores ErbB/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Ratos Sprague-Dawley , Transcrição Gênica , Fatores de Transcrição de p300-CBP/metabolismo
11.
Cancer Cell Int ; 19: 168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285694

RESUMO

BACKGROUND: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. METHODS: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. RESULTS: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. CONCLUSIONS: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

12.
Cell Biol Int ; 43(8): 931-939, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124219

RESUMO

Phosphoinositide 3-kinase (PI3K) signaling is frequently deregulated in breast cancer and plays a critical role in tumor progression. However, resistance to PI3K inhibitors in breast cancer has emerged, which is due to the enhanced ß-catenin nuclear accumulation. Until now, the mechanisms underlying PI3K inhibition-induced ß-catenin nuclear accumulation remains largely unknown. In the present study, we found inhibition of PI3K with LY294002 promoted ß-catenin nuclear accumulation in MCF-7 and MDA-MB-231 breast cancer cells. Combining PI3K inhibitor LY294002 with XAV-939, an inhibitor against ß-catenin nuclear accumulation, produced an additive anti-proliferation effect against breast cancer cells. Subsequent experiments suggested ß-catenin nuclear accumulation induced by PI3K inhibition depended on the feedback activation of epidermal growth factor receptor (EGFR) signaling pathway in breast cancer cells. Inhibition of EGFR phosphorylation with Gefitinib enhanced anti-proliferation effect of PI3K inhibitor LY294002 in MCF-7 and MDA-MB-231 cells. Taken together, our findings may elucidate a possible mechanism explaining the poor outcome of PI3K inhibitors in breast cancer treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Gefitinibe/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Morfolinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Células MCF-7 , Inibidores de Fosfoinositídeo-3 Quinase , beta Catenina/antagonistas & inibidores
13.
Fish Shellfish Immunol ; 95: 635-643, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678183

RESUMO

Small heat shock proteins (sHSPs) are ATP-independent chaperones and involved into various physiological and stress processes. In the present study, a 28.6-kD sHSP coding gene, MnHSP28.6, was cloned and characterized from the oriental river prawn Macrobrachium nipponense. Tissue distribution analysis via qPCR and western blot revealed that MnHSP28.6 predominantly expressed in muscle. The temporal transcription of MnHSP28.6 in muscle after bacterial challenge, heavy metal exposure and doxorubicin (DOX) injection was investigated by qPCR. The results showed that the expression of MnHSP28.6 were strongly enhanced by both Cd2+ and Cu2+ exposure, as well as DOX injection, but not by bacterial infection. Aggregation assays showed that recombinant MnHSP28.6 could effectively prevent temperature-induced aggregation of citrate synthase, and reduction-induced aggregation of insulin in vitro. MnHSP28.6 also could protect muscle extracts from heat-induced protein denaturation and superoxide dismutase (SOD) inactivation. Expressing MnHSP28.6 in E. coli conferred host cell impressive protection against H2O2 compared to control. These results suggest a protective role of MnHSP28.6 in maintaining protein homeostasis, preventing aggregation, promoting resistance to heavy metal and keeping redox balance.


Assuntos
Proteínas de Artrópodes/metabolismo , Proteínas de Choque Térmico Pequenas/metabolismo , Intoxicação por Metais Pesados/veterinária , Estresse Oxidativo , Palaemonidae/genética , Animais , Proteínas de Artrópodes/genética , Proteínas de Choque Térmico Pequenas/genética , Intoxicação por Metais Pesados/prevenção & controle , Temperatura Alta , Chaperonas Moleculares/genética , Músculos/metabolismo , Oxirredução , Substâncias Protetoras , Proteostase
14.
Fish Shellfish Immunol ; 89: 701-709, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004801

RESUMO

Based on the transcriptome database, we screened out four ferritin subunit genes (MnFer2-5) from the oriental river prawn Macrobrachium nipponense, which encode two non-secretory and two secretory peptides. MnFer2 and 4 possess a strictly conserved ferroxidase site, and MnFer3 has a non-typical ferroxidase site. MnFer5 seems to be a number of ferritin families, which has a distinct dinuclear metal binding motif, but lacks an iron ion channel, a ferroxidase site and a nucleation site. Diverse tissue-specific transcriptions of the four genes indicate their functional diversity in the prawn. Among them, MnFer2 is mainly expressed in hepatopancreas and intestines, MnFer3 and 4 are predominantly expressed in gills, and MnFer5 is widely expressed in various tissues with high presence in intestines, hepatopancreas and haemocytes. The transcription of all the four MnFer genes can be strongly induced by doxorubicin, indicating the involvement of these ferritin subunits in protection from oxidative stress. Upon Aeromonas hydrophila infection, only MnFer5 is persistently up-regulated, while other subunits including MnFer2-4 are down-regulated during the early stage, followed by recovery and even a slight increase at 48 h post bacterial challenge. Moreover, the iron binding capacity of recombinant MnFer2 is also demonstrated in vitro. The E. coli expressing MnFer2 displays increased resistance to hydrogen peroxidase cytotoxicity. These results suggest a protective role of ferritins from M. nipponense in iron homeostasis, redox biology and antibacterial immunity and shed light on the molecule evolution of crustacean ferritin subunits.


Assuntos
Ferritinas/genética , Ferritinas/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Estresse Oxidativo/imunologia , Penaeidae/genética , Penaeidae/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Ferritinas/química , Perfilação da Expressão Gênica , Homeostase/imunologia , Oxirredução , Palaemonidae , Filogenia , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Distribuição Aleatória , Alinhamento de Sequência
15.
Cell Commun Signal ; 16(1): 82, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445978

RESUMO

BACKGROUND: Knockdown of Akt1 promotes Epithelial-to-Mesenchymal Transition in breast cancer cells. However, the mechanisms are not completely understood. METHODS: Western blotting, immunofluorescence, luciferase assay, real time PCR, ELISA and Matrigel invasion assay were used to investigate how Akt1 inhibition promotes breast cancer cell invasion in vitro. Mouse model of lung metastasis was used to measure in vivo efficacy of Akt inhibitor MK2206 and its combination with Gefitinib. RESULTS: Knockdown of Akt1 stimulated ß-catenin nuclear accumulation, resulting in breast cancer cell invasion. ß-catenin nuclear accumulation induced by Akt1 inhibition depended on the prolonged activation of EGFR signaling pathway in breast cancer cells. Mechanistic experiments documented that knockdown of Akt1 inactivates PIKfyve via dephosphorylating of PIKfyve at Ser318 site, resulting in a decreased degradation of EGFR signaling pathway. Inhibition of Akt1 using MK2206 could induce an increase in the expression of EGFR and ß-catenin in breast cancer cells. In addition, MK2206 at a low dosage enhance breast cancer metastasis in a mouse model of lung metastasis, while an inhibitor of EGFR tyrosine kinase Gefitinib could potentially suppress breast cancer metastasis induced by Akt1 inhibition. CONCLUSION: EGFR-mediated ß-catenin nuclear accumulation is critical for Akt1 inhibition-induced breast cancer metastasis.


Assuntos
Neoplasias da Mama/patologia , Núcleo Celular/metabolismo , Receptores ErbB/metabolismo , Técnicas de Silenciamento de Genes , Proteínas Proto-Oncogênicas c-akt/deficiência , Proteínas Proto-Oncogênicas c-akt/genética , beta Catenina/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Núcleo Celular/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Gefitinibe/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Células MCF-7 , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo
16.
J Sep Sci ; 41(9): 2085-2091, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29370473

RESUMO

Isoelectric focusing plays a critical role in the analysis of complex protein samples. Conventionally, isoelectric focusing is implemented with carrier ampholytes in capillary or immobilized pH gradient gel. In this study, we successfully exhibited a carrier ampholyte-free isoelectric focusing on paper-based analytical device. Proof of the concept was visually demonstrated with color model proteins. Experimental results showed that not only a pH gradient was well established along the open paper fluidic channel as confirmed by pH indicator strip, the pH gradient range could also be tuned by the catholyte or anolyte. Furthermore, the isoelectric focusing fractions from the paper channel can be directly cut and recovered into solutions for post analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. This paper-based isoelectric focusing method is fast, cheap, simple and easy to operate, and could potentially be used as a cost-effective protein sample clean-up method for target protein analysis with mass spectrometry.


Assuntos
Misturas Anfolíticas/química , Focalização Isoelétrica , Papel , Proteínas/análise , Misturas Anfolíticas/análise , Soluções Tampão , Fracionamento Químico , Análise Custo-Benefício , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Espectrometria de Massas , Dodecilsulfato de Sódio
17.
Sensors (Basel) ; 18(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441781

RESUMO

A low Earth orbiter (LEO)-based navigation signal augmentation system is considered as a complementary of current global navigation satellite systems (GNSS), which can accelerate precise positioning convergence, strengthen the signal power, and improve signal quality. Wuhan University is dedicated to LEO-based navigation signal augmentation research and launched one scientific experimental satellite named Luojia-1A. The satellite is capable of broadcasting dual-frequency band ranging signals over China. The initial performance of the Luojia-1A satellite navigation augmentation system is assessed in this study. The ground tests indicate that the phase noise of the oscillator is sufficiently low to support the intended applications. The field ranging tests achieve 2.6 m and 0.013 m ranging precision for the pseudorange and carrier phase measurements, respectively. The in-orbit test shows that the internal precision of the ephemeris is approximate 0.1 m and the clock stability is 3 × 10-10. The pseudorange and carrier phase measurement noise evaluated from the geometry-free combination is about 3.3 m and 1.8 cm. Overall, the Luojia-1A navigation augmentation system is capable of providing useable LEO navigation augmentation signals with the empirical user equivalent ranging error (UERE) no worse than 3.6 m, which can be integrated with existing GNSS to improve the real-time navigation performance.

18.
Aesthetic Plast Surg ; 42(5): 1364-1369, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30019241

RESUMO

BACKGROUND: Linear hypertrophic scar is a common surgical problem that can be difficult to manage, especially for the median sternotomy scar. Botulinum toxin type A (BTA) is widely used in cosmetic surgery and has been shown to improve scar quality recently. The aim of this study was to evaluate the efficacy of BTA injected in the early postoperative of median sternotomy on preventing scar formation. METHODS: In this prospective randomized controlled trial, 19 consecutive patients who underwent median sternotomy were enrolled. The median sternotomy wound in each patient was divided into the upper half and the lower half. Both halves of the wound were randomized to receive the treatment with either BTA or normal saline. At 6-month follow-up, scars were assessed using the Vancouver Scar Scale, scar widths were measured, and patients were asked to evaluate their overall satisfaction. RESULTS: Seventeen patients with median sternotomy wounds completed the entire study. At 6-month follow-up, the mean Vancouver Scar Scale score for the BTA-treated group was 3.44 ± 1.68 and for the normal saline control group was 6.29 ± 2.39, and there was a statistically significant difference between the two groups (P < 0.05). There were also significant improvements in scar width and patient satisfaction for the BTA-treated halves of the wounds (P < 0.05). CONCLUSIONS: The study demonstrates that early postoperative BTA injection can decrease scar formation and reduce scar width in median sternotomy wounds, and the overall appearance is more satisfactory. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Cicatriz/prevenção & controle , Esternotomia/métodos , Cicatrização/efeitos dos fármacos , Adulto , China , Método Duplo-Cego , Estética , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Medição de Risco , Esternotomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
19.
Fish Shellfish Immunol ; 70: 327-334, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28882803

RESUMO

In Macrobrachium nipponense, the rhodanese homologue 2 (MnRDH2) gene codes for a single rhodanese domain protein. Considering the lack of information on the biological role of the ubiquitous rhodaneses in invertebrate, we examined the functions of MnRDH2 using both in silico and in vitro approaches. Quantitative PCR analysis of different tissues indicated that expression of MnRDH2 was enriched in hepatopancreas, in which bacterial challenge by Aeromonas hydrophila induced MnRDH2 expression. Knocking down MnRDH2 by RNA interference caused significant accumulations of reactive oxygen species and malondialdehyde (MDA). Using Escherichia coli (DE3), we expressed MnRDH2 and the mutant MnRDH2C78A, in which the predicted catalytic cysteine was mutated to alanine, and found significant rodanese activity of the recombinant MnRDH2 in vitro, but not for the mutant rMnRDH2C78A. We observed that rMnRDH2 was able to significantly increase tolerance of the host bacteria to oxidative stressor phenazine methosulfate. These results suggest that MnRDH2 might have the potential to buffer general levels of oxidants via regulation of redox reactions. In conclusion, our study begins to hint a possible biological functionality of MnRDH2 as a redox switch to activate defensive activities against oxidative damage, which helps host in maintaining the cellular redox balance. These characteristics will facilitate future investigations into the physiological functions for invertebrate rhodanese family genes.


Assuntos
Antioxidantes/metabolismo , Imunidade Inata , Palaemonidae/genética , Palaemonidae/imunologia , Tiossulfato Sulfurtransferase/genética , Tiossulfato Sulfurtransferase/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Escherichia coli/fisiologia , Especificidade de Órgãos , Alinhamento de Sequência
20.
Angew Chem Int Ed Engl ; 56(39): 11764-11768, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28727219

RESUMO

Screw dislocation structures in crystals are an origin of symmetry breaking in a wide range of dense-phase crystals. Preparation of such analogous structures in framework-phase crystals is of great importance in zeolites but is still a challenge. On the basis of crystal-structure solving and model building, it was found that the two specific intergrowths in MTW zeolite produce this complex fractal and spiral structure. With the structurally determined parameters (spiral pitch h, screw angle θ, and spatial angle ψ) of Burgers circuit, the screw dislocation structure can be constructed by two different dimensional intergrowth sections. Thus the reported complexity of various dimensions in diverse crystals can be unified.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA