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1.
J Transl Med ; 22(1): 220, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429732

RESUMO

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. RESULTS: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. CONCLUSION: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.


Assuntos
Antígeno CD47 , Neoplasias , Animais , Humanos , Neoplasias/patologia , Fagocitose , Macrófagos/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Modelos Animais de Doenças , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/farmacologia , Antígenos de Diferenciação/uso terapêutico
2.
J Org Chem ; 89(7): 4979-4989, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38536713

RESUMO

Two efficient and convenient methods for the synthesis of 3-alkylideneoxindoles are described in this paper. The InCl3/TfOH-mediated tandem Knoevenagel condensation-deacylation sequence of various 2-oxindoles with 1,3-diones or acetoacetate furnished 3-alkylideneoxindoles in satisfactory to excellent yields (up to >99% yield). Employing the reaction system, the condensation of 2-oxindoles with ketones or aldehydes also proceeded smoothly to produce 3-alkylideneoxindoles. This protocol can be amenable to scale up. The effect of acids on this condensation reaction and intermolecular competition experiments were investigated to understand the aspect of the reaction.

3.
Org Biomol Chem ; 21(48): 9542-9546, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38018160

RESUMO

An efficient and convenient method for the synthesis of 2-trifluoromethyl benzimidazoles is described in this paper. The cyclization reaction of various o-phenylenediamines with hexafluoroacetylacetone proceeded smoothly in the presence of Cu2O as the catalyst to produce 2-trifluoromethyl benzimidazoles in satisfactory to excellent yields (up to >99% yield). The CF3 source, hexafluoroacetylacetone, acted not only as cyclization partner, but also acted as a ligand for the Cu catalyst. Various synthetically useful functional groups, such as halogen atoms, cyano, and methoxycarbonyl groups, remained intact during the cyclization reactions. The reaction mechanism was thoroughly investigated and was determined to involve a seven-membered cyclic diimine intermediate.

4.
Bull Environ Contam Toxicol ; 111(5): 63, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904061

RESUMO

The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.


Assuntos
Metais Pesados , Poluentes do Solo , Criança , Humanos , Esgotos , Ecossistema , Monitoramento Ambiental , Rios , Cádmio , Poluentes do Solo/análise , Medição de Risco , Metais Pesados/análise , China
5.
Chemistry ; 24(9): 2109-2116, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29071782

RESUMO

Phosphopeptide enrichment is essential for the phosphoprotein profiling, due to the low abundance in complex biological samples. Moreover, selective binding of multi-phosphopeptides over mono-phosphopeptides is rarely established, but strongly needed in real sample analysis, especially for the investigation of cell behaviors with the multisite phosphorylation cascades. Here two-dimensional (2D) nanosheets were synthesized of Egyptian blue (CaCuSi4 O10 ), the well-known ancient pigment, and its analogues (SrCuSi4 O10 and BaCuSi4 O10 ), which were employed in the enrichment of phosphopeptides for the first time. Surprisingly, the 2D CaCuSi4 O10 nanosheet was highly selective towards multi-phosphopeptides without enriching the mono-phosphorylated peptides in a wide range of acidic conditions or buffer compositions. Meanwhile, the SrCuSi4 O10 and BaCuSi4 O10 nanosheet analogues do not exhibit this unique selectivity. Moreover, the ultrathin and well-defined 2D morphology, with abundant CaII , of Egyptian blue nanosheet was applied in cortical samples of forebrain specific PDK1 conditional knockout mice and their age-matched littermate controls, that are associated with Alzheimer's disease. The as-prepared 2D CaCuSi4 O10 nanosheet not only showed specific selectivity, but also exhibited high sensitivity (detection limit of 4×10-7 m).


Assuntos
Cobre/química , Nanoestruturas/química , Fosfopeptídeos/análise , Silicatos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Cobre/metabolismo , Nanopartículas Metálicas/química , Camundongos , Camundongos Knockout , Leite/química , Leite/metabolismo , Fosfopeptídeos/química , Fosfopeptídeos/metabolismo , Ligação Proteica , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , Silicatos/metabolismo , Titânio/química , Proteínas tau/química , Proteínas tau/metabolismo
6.
Ecotoxicol Environ Saf ; 147: 1065-1072, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28867554

RESUMO

Atrazine is widely used in agriculture. In this study, dissolved organic matter (DOM) from soils under four types of land use (forest (F), meadow (M), cropland (C) and wetland (W)) was used to investigate the binding characteristics of atrazine. Fluorescence excitation-emission matrix-parallel factor (EEM-PARAFAC) analysis, two-dimensional correlation spectroscopy (2D-COS) and Stern-Volmer model were combined to explore the complexation between DOM and atrazine. The EEM-PARAFAC indicated that DOM from different sources had different structures, and humic-like components had more obvious quenching effects than protein-like components. The Stern-Volmer model combined with correlation analysis showed that log K values of PARAFAC components had a significant correlation with the humification of DOM, especially for C3 component, and they were all in the same order as follows: meadow soil (5.68)>wetland soil (5.44)>cropland soil (5.35)>forest soil (5.04). The 2D-COS further confirmed that humic-like components firstly combined with atrazine followed by protein-like components. These findings suggest that DOM components can significantly influence the bioavailability, mobility and migration of atrazine in different land uses.


Assuntos
Atrazina/análise , Substâncias Húmicas/análise , Modelos Químicos , Poluentes do Solo/análise , Solo/química , Agricultura , Atrazina/química , Florestas , Poluentes do Solo/química , Espectrometria de Fluorescência/métodos , Áreas Alagadas
7.
Yi Chuan ; 40(7): 561-571, 2018 Jul 20.
Artigo em Zh | MEDLINE | ID: mdl-30021719

RESUMO

CRISPR/Cas technology enables efficient and specific editing the genome. Since different bacterial sources or artificially modified Cas9, as well as Cpf1 and other nucleases, recognize different PAMs (protospacer adjacent motifs), different gene editing nucleases may use different types of sgRNAs (small guide RNA). MicroRNAs (miRNAs) are a class of regulatory small non-coding RNAs. To determine whether specific targets for sgRNAs in miRNA precursor exit, the abundance and specificity of 11 different types of sgRNA targeting 28 645 miRNA precursors were analyzed in the present study using the CRISPR-offinder, a bioinformatics software developed in our own laboratory. The CRISPR/Cas9 lentivirus technology was used to target the miR-302/367 cluster in a porcine cell line, and its knockout efficiency for the miRNA target was evaluated. The results show that there are about 8 different types of sgRNAs that can target individual miRNA precursors. By assessing the off-target effect, only 18.2% of the sgRNAs showed high specificity for targeting the porcine miRNA precursors. Lastly, using the miR-302/367 cluster target as an example, we showed that the CRISPR/Cas9 lentivirus technology was 40% efficient in successfully establishing correct knockout of the target miRNA in the porcine cell line. This present study provides an important resource for the use of CRISPR/Cas technology to target miRNAs for knockout studies.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , MicroRNAs/genética , RNA Guia de Cinetoplastídeos/genética , Animais , Técnicas de Inativação de Genes , Suínos
8.
Med Sci Monit ; 23: 2065-2071, 2017 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-28456815

RESUMO

BACKGROUND Although many attempts have been made to advance the treatment of complex anal fistula, it continues to be a difficult surgical problem. This study aimed to describe the novel technique of video-assisted anal fistula treatment (VAAFT) and our preliminary experiences using VAAFT with patients with complex anal fistula. MATERIAL AND METHODS From May 2015 to May 2016, 52 patients with complex anal fistula were treated with VAAFT at Yangpu Hospital of Tongji University School of Medicine, and the clinical data of these patients were reviewed. RESULTS VAAFT was performed successfully in all 52 patients. The median operation time was 55 minutes. Internal openings were identified in all cases. 50 cases were closed with sutures, and 2 were closed with staplers. Complications included perianal sepsis in 3 cases and bleeding in another 3 cases. Complete healing without recurrence was achieved in 44 patients (84.6%) after 9 months of follow-up. No fecal incontinence was observed. Furthermore, a significant improvement in Gastrointestinal Quality of Life Index (GIQLI) score was observed from preoperative baseline (mean, 85.5) to 3-month follow-up (mean, 105.4; p<0.001), and this increase was maintained at 9-months follow-up (mean, 109.6; p<0.001). CONCLUSIONS VAAFT is a safe and minimally invasive technique for treating complex anal fistula with preservation of anal sphincter function.


Assuntos
Fístula Retal/cirurgia , Cirurgia Vídeoassistida/métodos , Adulto , Idoso , Canal Anal/cirurgia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Qualidade de Vida , Fístula Retal/terapia , Recidiva , Resultado do Tratamento , Cicatrização
9.
Asian-Australas J Anim Sci ; 29(7): 1037-43, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26954143

RESUMO

Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade. DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Up to now, the importance of epigenetic marks in the regulation of Pax7 and myogenic regulatory factors (MRFs) expression is far less explored. In the present study, semi-quantitative the real-time polymerase chain reaction (RT-PCR) analyses showed MyoD and Myf5 were expressed in activated and quiescent C2C12 cells. MyoG was expressed in a later stage of myogenesis. Pax7 was weakly expressed in differentiated C2C12 cells. To further understand the regulation of expression of these genes, the DNA methylation status of Pax7, MyoD, and Myf5 was determined by bisulfite sequencing PCR. During the C2C12 myoblasts fusion process, the changes of promoter and exon 1 methylation of Pax7, MyoD, and Myf5 genes were observed. In addition, an inverse relationship of low methylation and high expression was found. These results suggest that DNA methylation may be an important mechanism regulating Pax7 and MRFs transcription in cell myogenic differentiation.

10.
J Mater Sci Mater Med ; 26(3): 126, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25690620

RESUMO

Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P < 0.05). These findings indicate that the SF microspheres containing a very low dose of rhBMP-2 improve fusion in sheep using BCP constructs.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Fibroínas/administração & dosagem , Vértebras Lombares/cirurgia , Modelos Animais , Fusão Vertebral , Animais , Microesferas , Proteínas Recombinantes/administração & dosagem , Ovinos , Seda/química
11.
J Fluoresc ; 24(1): 143-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23900848

RESUMO

The complex characteristics of p-sulfonated calix[n]arene (SCnA) and two tryptophans N-[(tert-butoxy) carbonyl]-tryptophan (trp-A) and N-carbobenzoxy-tryptophane (trp-B) were examined through various techniques. Spectrofluorimetry was performed at different temperatures to determine the stability constants and evaluate the thermodynamic parameters of the two complexes. The effect of pH on complex formation was estimated. According to the fluorescence data, the assumption about the steric hindrance of the tert-butyl group of trp-A and the phenyl group of trp-B was put forward. (1)H NMR was also performed to determine the binding interaction mechanism. Results showed that the indole benzene rings of the two tryptophans partly penetrated into the cavity of p-sulfonated calix[n]arene. The shift in Ha, Hb and Hc, Hd positions became more significant as the number of phenolic units of the calixarene ring increased. Molecular modeling of the complexes elucidated the assumption about the steric hindrance of the tert-butyl group of trp-A and the phenyl group of trp-B. These observations of molecular modeling computation are consistent with previous fluorescence data and (1)H NMR results.


Assuntos
Calixarenos/química , Ácidos Sulfônicos/química , Triptofano/química , Substâncias Macromoleculares/química , Modelos Moleculares , Estrutura Molecular , Espectrometria de Fluorescência
12.
J Mater Sci Mater Med ; 25(7): 1709-19, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24659100

RESUMO

To prepare a bioactive bone substitute, which integrates biphasic calcium phosphate (BCP) and rhBMP-2/silk fibroin (SF) microsphere, and to evaluate its characteristics. Hydroxyapatite and ß-tricalcium phosphate were integrated with a ratio of 60­40%. RhBMP-2/SF (0.5 µg/1 mg) microsphere was prepared, and its rhBMP-2-release kinetics was assed. After joining pore-forming agent (Sodium chloride, NaCl), porous BCP/rhBMP-2/SF were manufactured, and its characteristics and bioactivity in vitro were evaluated. Mean diameter of rhBMP-2/SF microsphere was 398.7 ± 99.86 nm, with a loading rate of 4.53 ± 0.08%. RhBMP-2 was released in a dual-phase pattern, of which fast-release (nearly half of protein released) focused on the initial 3 days, and slow-release sustained more than 28 days. With the increase in concentration of NaCl, greater was porosity and pore size, but smaller mechanical strength of BCP/rhBMP-2/SF. Material with 150% (w/v) NaCl had an optimal performance, with a porosity of 78.83%, pore size of 293.25 ± 42.77µm and mechanical strength of 31.03 MPa. Proliferation of human placenta-derived mesenchymal stem cells (hPMSCs) on leaching extract medium was similar to the normal medium (P = 0.89), which was better than that on control group (P = 0.03). Activity of alkaline phosphatase on BCP/rhBMP-2/SF surface was higher than on pure BCP at each time point except at 1 day (P < 0.05). RhBMP-2 has a burst release on early times and a sustaining release on later times. BCP/rhBMP-2/SF with 150% (w/v) pore-forming agent has excellent porosity, pore size and mechanical strength. The biomaterial induces proliferation and differentiation hPMSCs effectively.


Assuntos
Proteína Morfogenética Óssea 2/química , Fosfatos de Cálcio/química , Fibroínas/química , Microesferas , Fator de Crescimento Transformador beta/química , Animais , Materiais Biocompatíveis/química , Bombyx , Osso e Ossos/metabolismo , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Durapatita/química , Feminino , Humanos , Cinética , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Placenta/metabolismo , Porosidade , Gravidez , Proteínas Recombinantes/química , Cloreto de Sódio/química , Estresse Mecânico , Fatores de Tempo
13.
Yao Xue Xue Bao ; 49(1): 1-15, 2014 Jan.
Artigo em Zh | MEDLINE | ID: mdl-24783499

RESUMO

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.


Assuntos
Desenho de Fármacos , Descoberta de Drogas/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Sítios de Ligação , Sistema Enzimático do Citocromo P-450/metabolismo , Recall de Medicamento , Humanos , Relação Estrutura-Atividade
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(8): 2137-42, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25474950

RESUMO

The fluorescence spectra of 22 samples of 8 kinds of edible vegetable oils (soybean oil, maize oil, olive oil, rice oil, peanut oil, walnut oil, sunflower oil and sesame oil) were measured with FS920 fluorescence spectrometer and the fluorescence matrixs (EEMs) were analyzed with parallel factor (PARAFAC) analysis model. To synthesize the capabilities of material characterization and component identification, fluorescence spectra combined with PARAFAC fulfill the classification of vegetable oils. The map feature (peak position, peak value and peak number) was obtained by analyzing three dimensional spectra and con tour maps in the range of emission wavelength from 260 to 750 nm, and excitation wavelengths from 250 to 550 nm. The fluorescent substances (unsaturated fatty acids, vitamin E and its derivatives, chlorophyll and carotenoid) corresponding to spectrum peaks were determined. The factor-number was selected and the components (vitamin E and its derivatives, linoleic acid and linolenic acid, fatty acid oxidation products, vegetable oil oxidation products) corresponding to each factor were ascertained. The four-factor excitation and emission profiles and projection score plots of PARAFAC model were plotted. Different vegetable oils can be characterized and distinguished with the map features of fluorescence spectra and sample projection plots of PARAFAC model. The results demonstrate the capability of the combination of fluorescence spectra technology and four-factor PARAFAC model for differentiating and characterizing vegetable oils.


Assuntos
Análise Fatorial , Óleos de Plantas/análise , Espectrometria de Fluorescência , Carotenoides/análise , Clorofila/análise , Óleo de Milho , Ácidos Graxos/análise , Fluorescência , Azeite de Oliva , Oxirredução , Óleo de Amendoim , Óleos de Plantas/classificação , Óleo de Gergelim , Óleo de Soja , Óleo de Girassol , Verduras , Vitamina E/análise
15.
World J Gastroenterol ; 30(19): 2564-2574, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38817663

RESUMO

BACKGROUND: Cell division cyclin 25C (CDC25C) is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that CDC25C could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood. AIM: To explore the impact of CDC25C on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development. METHODS: Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV-CDC25C shRNA) to knock down CDC25C. Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo. Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting. RESULTS: CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction. A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice. CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells. CONCLUSION: The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.


Assuntos
Apoptose , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Estresse do Retículo Endoplasmático , Técnicas de Silenciamento de Genes , Neoplasias Hepáticas , Camundongos Endogâmicos C57BL , Fosfatases cdc25 , Animais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Fosfatases cdc25/metabolismo , Fosfatases cdc25/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Camundongos , Humanos , RNA Interferente Pequeno/metabolismo , Masculino , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinogênese/genética
16.
Waste Manag Res ; 31(3): 273-82, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23381972

RESUMO

The quantitative effects of three operational factors, that is initial compaction, decomposition condition and leachate level, on municipal solid waste (MSW) landfill settlement and storage capacity are investigated in this article via consideration of a hypothetical case. The implemented model for calculating landfill compression displacement is able to consider decreases in compressibility induced by biological decomposition and load dependence of decomposition compression for the MSW. According to the investigation, a significant increase in storage capacity can be achieved by intensive initial compaction, adjustment of decomposition condition and lowering of leachate levels. The quantitative investigation presented aims to encourage landfill operators to improve management to enhance storage capacity. Furthermore, improving initial compaction and creating a preferential decomposition condition can also significantly reduce operational and post-closure settlements, respectively, which helps protect leachate and gas management infrastructure and monitoring equipment in modern landfills.


Assuntos
Eliminação de Resíduos/métodos , Resíduos Sólidos , Poluentes Químicos da Água/análise , Biodegradação Ambiental , Modelos Teóricos
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(1): 151-4, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23586245

RESUMO

The Er3+ and Yb3+ doped Y2O3 Nano powder was prepared by sol-gel method. Based on 2H11/2 --> 4I15/2 and 4S3/2 --> 4I15/2 green conversion luminescence intensity rate of Er3+, the sample surface temperature changes caused by the increase in 980 nm diode laser pump power were studied. The results show that with pump power increasing, the sample surface temperature substantially rises. And the surface temperature reached to 820 K when the pump power was 1 000 mW. The phenomenon plays an important role in the analysis of upconversion process, especially with saturation power. And this feature has a potential application prospect in the biomedicine, soft tissue hole burning as well as the field of temperature sensing materials.


Assuntos
Tecnologia Biomédica , Érbio/química , Nanoestruturas/química , Itérbio/química , Temperatura Alta , Lasers
18.
World J Gastrointest Surg ; 15(7): 1465-1473, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37555102

RESUMO

BACKGROUND: Total mesorectal excision along the "holy plane" is the only radical surgery for rectal cancer, regardless of tumor size, localization or even tumor stage. However, according to the concept of membrane anatomy, multiple fascial spaces around the rectum could be used as the surgical plane to achieve radical resection. AIM: To propose a new membrane anatomical and staging-oriented classification system for tailoring the radicality during rectal cancer surgery. METHODS: A three-dimensional template of the member anatomy of the pelvis was established, and the existing anatomical nomenclatures were clarified by cadaveric dissection study and laparoscopic surgical observation. Then, we suggested a new and simple classification system for rectal cancer surgery. For simplification, the classification was based only on the lateral extent of resection. RESULTS: The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side around the rectum and form three spaces (medial, middle and lateral), and blood vessels and nerves are precisely positioned in the fascia or space. Three types of radical surgery for rectal cancer are described, as are a few subtypes that consider nerve preservation. The surgical planes of the proposed radical surgeries (types A, B and C) correspond exactly to the medial, middle, and lateral spaces, respectively. CONCLUSION: Three types of radical surgery can be precisely defined based on membrane anatomy, including nerve-sparing procedures. Our classification system may offer an optimal tool for tailoring rectal cancer surgery.

19.
Mol Biol Rep ; 39(5): 6329-35, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22290286

RESUMO

PCR-RFLP was used to analyze the polymorphisms of MC4R, LEP, H-FABP genes in a swine breed composite (DIV2) and 4 swine breeds (Yorkshire, Landrace, Meishan, Bamei). The association study of these polymorphisms with several economic traits was carried out on a DIV2 population. The results obtained showed that MC4R/TaqI genotype had an effect for average backfat thickness (P < 0.05) and lean meat percentage (P < 0.05). At locus LEP/HinfI animals of AA genotype had lower test daily gain than that of BB (P < 0.01) or AB genotype (P < 0.05). At the H-FABP/HaeIII locus lean meat percentage of the individuals with genotype DD were higher than that with genotype dd (P < 0.05). Linkage disequilibrium analysis among MC4R, LEP and H-FABP revealed that these genes were independent. This represented two or more genes that could be combined together within one genotype in order to facilitate breeding for objective traits. In addition, a method allowing simultaneous detection of fragments of MC4R and LEP gene was developed.


Assuntos
Proteínas de Ligação a Ácido Graxo/genética , Leptina/genética , Desequilíbrio de Ligação/genética , Carne/economia , Polimorfismo Genético , Receptor Tipo 4 de Melanocortina/genética , Sus scrofa/genética , Animais , Cruzamento , Frequência do Gene/genética , Estudos de Associação Genética , Loci Gênicos/genética , Genótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , Característica Quantitativa Herdável
20.
Exp Ther Med ; 24(2): 525, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35837035

RESUMO

The present study investigated the characteristics, diagnosis, treatment and prognosis of hepatic portal venous gas (HPVG) using the data of 20 patients from the Tongji University School of Medicine Affiliated with Yangpu Hospital (Shanghai, China). The aim of the present study was to optimize the management method and improve the prognosis of patients with HPVG. A total of 20 patients were selected using a CT scan to confirm HPVG. All patients were enrolled and identified via a search engine, which examined all CT radiology reports containing the words pneumatosis and/or portal venous gas/air. Data were collected and analyzed, including sex, age, laboratory evidence, etiologies at admission, therapeutic method and in-hospital mortality. The patients consisted of 14 women (mean age, 79.1 years) and six men (mean age, 67.8 years). The results demonstrated that HPVG indicated a higher inflammatory index. The etiologies of HPVG included abdominal infection, pulmonary infection and hemorrhage, whereas the comorbidities included hypertension, diabetes, coronary disease, cerebrovascular disease and renal insufficiency. The present study determined that intestinal obstruction, acute enteritis and pulmonary infection were the main causes of HPVG. Of the 20 patients enrolled in the present study, four patients received surgery and 16 patients received conservative treatment. The overall in-hospital mortality was 25%. The present study indicated that the causes of HPVG may be closely related to inflammation and blood vessel injury. It was also determined that hemodynamic disorders of the intestinal tract and the combination of different types of infection were important contributors towards patient mortality.

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