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The present study optimized the extraction characterization and antioxidant activities of water-soluble compound polysaccharides (CPs) from hawthorn, lotus leaf, Fagopyrum tataricum, semen cassiae, Lycium barbarum, and Poria cocos Chinese herbal medicines that have mass ratios of 4 : 2 : 2 : 1.5 : 1 : 1. The CPs yield equation was predicted using quantitative theory, to which a maximum CPs yield of 7.18±0.24 % under the following optimal extraction conditions: a water-to-raw material ratio of 30â mL/g, an extraction temperature of 65 °C, an extraction time of 45â min, and extraction mode ultrasonic-assistant extraction. CPs were consisted of Ara, Gal, Glc, Xyl, Man, GalA and GlcA in a molar ratio of 3.1 : 2.6 : 50.6 : 1.7 : 20.4 : 17.2 : 4.2. The HPGPC profiles and FT-IR spectra implied that CPs were heterogeneous acidic polysaccharides and possessed the ß-d-pyranose configuration. Congo red test, CD spectrum and SEM revealed that CPs with three helix conformation showed a flocculent, granulous or sheet-like appearance. Furthermore, the relationships between antioxidant activity and concentration of CPs displayed significant positive correlation, and the scavenging abilities for DPPH, hydroxyl radical, ABTS, superoxide-anion radical and reducing power of CPs were 93.56±2.51 %, 84.03±1.69 %, 83.29±1.93 %, 37.49±1.93 % and 0.467±0.006 at a concentration of 4.0â mg/mL. Therefore, CPs could be applied as a potential natural antioxidant in pharmaceutical or functional food fields.
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Antioxidantes/química , Medicamentos de Ervas Chinesas/química , Polissacarídeos/química , Radical Hidroxila/química , Peso Molecular , Monossacarídeos/análise , Polissacarídeos/isolamento & purificação , Solubilidade , Sonicação , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
Degeneration of immune organs like thymus and spleen has been discovered in tumor-bearing mice; which increases the difficulties on oncotherapy. More effective drugs which target the protection of immune organs are expected to be researched. In this study; we aim to analyze the antitumor and immunoregulatory activities of seleno-ß-lactoglobulin (Se-ß-lg) on S180 tumor-bearing mice. Results indicated that Se-ß-lg exhibited a remarkable inhibitory effect on S180 solid tumors with the inhibition rate of 48.38%; and protected the thymuses and spleens of S180-bearing mice. In addition, Se-ß-lg could also balance the proportions of CD4⺠and CD8⺠T cells in spleens; thymuses and peripheral bloods; and improve Levels of IL-2; IFN-γ; TNF-α in mice serums. ß-lg showed weaker bioactivities while SeO2 showed stronger toxicity on mice. Therefore our results demonstrated that Se-ß-lg possessed stronger antitumor and immunoregulatory activities with lower side effects and had the potential to be a novel immunopotentiator and antitumor agent.
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Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactoglobulinas/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Sarcoma 180/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Interleucina-2/metabolismo , Camundongos , Sarcoma 180/imunologia , Sarcoma 180/metabolismo , Baço/metabolismo , Linfócitos T/metabolismo , Timo/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The MYB gene family comprises one of the richest groups of transcription factors in plants. The full length of two MYB genes were isolated through heterologous screening of Aquilaria sinensis calli transcriptome data, and the reverse transcription PCR was performed to obstain the corrected MYB clones, named AsMYB1, AsMYB2. The MYB transmembrane domain and phylogenetic analysis were predicted by different software to analyze the bioinformatics of MYB proteins. The transcript level of AsMYB1, AsMYB2 was performed by real-time quantitative RT-PCR in different tissues and in responds to abiotic stresses including salt, cold, metal and drought stress, and hormone treatments including abscisic acid (ABA), salicylic acid (SA), gibberellins (GA3) and methyl jasmonate (MeJA) treatment. The AsMYB1 cDNA sequence had an ORF of 1 063 nucleotides, encoding a protein of 353 amino acids. The largest AsMYB2 ORF was 1 081 nucleotides, and its predicted translation products consisted of 359 amino acids. Two MYB genes had a tissues-specific pattern in A. sinensis. Moreover, the expression level of AsMYB1 and AsMYB2 was regulated by different abiotic stresses and hormone treatments, suggesting the transcription factors AsMYB1 and AsMYB2 play an important role in plant defense and hormone signal transduction in A. sinensis.
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Proteínas de Plantas/genética , Estresse Fisiológico , Thymelaeaceae/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Fases de Leitura Aberta , FilogeniaRESUMO
Objective To observe the effect of Wenhua Juanbi Recipe (WJR) on the expres- sions of DNA methyltransferases (DNMTs) in peripheral blood mononuclear cells (PBMCs) of collagen- inducing arthritis (CIA) , and to study its mechanism for treating CIA. Methods Totally 90 Wistar rats were randomly divided into the model group (n =80) and the normal control group (n = 10). Rats of the model group were injected with type II collagen of bovine (BC II) emulsion from the tail to establish CIA model. Successfully modeled 50 CIA rats were randomly divided into five groups, i.e., the model group, the methotrexate (MTX) group, the low dose WJR group, the middle dose WJR group, the high dose WJR group, 10 in each group. Rats in the model group were administered with normal saline by gastrogavage, once per day. Rats in low, middle, and high dose WJR groups were administered with WJR by gas- trogavage at the daily dose of 22. 9, 45. 8, 68. 7 g/kg, respectively (once per day). Rats in the MTX group were administered with MTX suspension (0.78 mg/kg) by gastrogavage, once per week for 30 successive days. The paw swelling was evaluated using volume method (draining volume). PBMCs were extrac- ted from each group after intervention. mRNA expression levels of DNMTs (DNMT1 , DNMT3a, DNMT3b) were detected by real-time quantitative PCR. Results Compared with the normal group, the paws were obviously swollen in the model group (P <0. 01). Compared with the model group, swollen paws were obviously alleviated in low, middle, and high dose WJR groups, and the MTX group (P <0.01). Compared with before treatment in the same group, swollen paws were obviously alleviated in low, middle, and high dose WJR groups, and the MTX group (P <0. 01 ). Compared with the normal group, expression levels of DNMT1, DNMT3a, and DNMT3b in PBMCs were obviously lowered in the model group (P <0.01). Compared with the model group, expression levels of DNMT1 , DNMT3a, DNMT3b in PBMCs were obviously elevated in low, middle, and high dose WJR groups, and the MTX group (all P <0. 01). There was no sig- nificant difference in expression levels of DNMT1, DNMT3a, or DNMT3b in PBMCs among low, middle, and high dose WJR groups (P>0.05). Conclusions Expression levels of DNMTs in PBMCs of CIA rats decreased. WJR up-regulated the expression level of DNMTs in PBMCs of CIA rats in no obvious dose de- pendent way. One of WJR's mechanisms for treating CIA might be up-regulating expression levels of DN- MTs, and adjusting the state of DNA methylation.
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Artrite , Metilação de DNA , Metilases de Modificação do DNA , Leucócitos Mononucleares , Animais , Artrite/tratamento farmacológico , Artrite/metabolismo , Bovinos , Colágeno , DNA , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/efeitos dos fármacos , Metilases de Modificação do DNA/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Ratos WistarRESUMO
The ectonucleotidase CD39 is pivotal in the conversion of immunostimulatory adenosine triphosphate (ATP) into immunosuppressive adenosine which potently inhibits host immune responses against cancer. This study investigated the expression level and prognostic significance of CD39 in human rectal adenocarcinoma. Our data demonstrated that CD39 staining strongly marked malignant epithelial cells where the protein and messenger RNA (mRNA) expression levels of CD39 were significantly increased compared with paracancerous controls. In addition to primary tumors, CD39 was also abundantly expressed in liver metastases and tumor-draining lymph nodes from metastatic rectal adenocarcinoma. Although patients with higher CD39 density in tumor cells were more likely to have favorable characteristics (early TNM and N stages) and overall survival, the singular parameter cannot be used as an independent factor for predicting patients' prognosis. Intriguingly, combined analysis of CD39 and CD73 expression was more efficient to foretell patient's outcome where patients with increased CD73 but decreased CD39 levels displayed a worst prognosis. Taken together, the current study revealed that malignant epithelial cells of human rectal adenocarcinoma strongly express CD39 that may play a potential role in the tumor invasion and metastasis. Although high expression of CD39 in tumor cells is correlated with favorable clinical outcome, the combination of CD39 and CD73 expression may have a better prognostic value.
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Adenocarcinoma/genética , Antígenos CD/biossíntese , Apirase/biossíntese , Prognóstico , Neoplasias Retais/genética , 5'-Nucleotidase/biossíntese , 5'-Nucleotidase/genética , Adenocarcinoma/patologia , Adulto , Idoso , Antígenos CD/genética , Apirase/genética , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias Retais/patologiaRESUMO
Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.
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Cricetulus , Biossíntese de Proteínas , Proteínas de Ligação a RNA , Proteínas Recombinantes , Animais , Células CHO , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Biossíntese de Proteínas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , CricetinaeRESUMO
Chinese hamster ovary (CHO) cells are expected to acquire the ability to produce higher recombinant therapeutic protein levels using various strategies. Genetic engineering targeting the cell cycle and autophagy pathways in the regulation of cell death in CHO cell cultures has received attention for enhancing the production of therapeutic proteins. In this study, we examined the small-molecule compound apilimod, which was found to have a positive influence on recombinant protein expression in CHO cells. This was confirmed by selective blocking of the cell cycle at the G0/G1 phase. Apilimod treatment resulted in decreased expression of cyclin-dependent kinase 3 (CDK3) and Cyclin C and increased expression of cyclin-dependent kinase suppressor p27Kip1, which are critical regulators of G1 cell cycle progression and important targets controlling cell proliferation. Furthermore, total transcription factor EB (TFEB) was lower in apilimod-treated CHO cells than in control cells, resulting in decreased lysosome biogenesis and autophagy with apilimod treatment. These multiple effects demonstrate the potential of apilimod for development as a novel enhancer for the production of recombinant proteins in CHO cell engineering.
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Autofagia , Cricetinae , Animais , Cricetulus , Células CHO , Pontos de Checagem do Ciclo Celular , Ciclo Celular/genética , Proteínas Recombinantes/genéticaRESUMO
A new water-soluble polysaccharide, CMP90, with a molecular weight of 23.9 kDa was isolated from Castanea mollissima Blume and the preliminary structural characteristics and antitumor effects of CMP90 in vitro and in vivo were investigated in the research. CMP90 consists of arabinose, galactose, glucose, xylose and mannose (molar ratio: 0.08:0.11:5.14:0.12:0.08) with α- and ß-anomeric units. The results of in vitro experiments indicated that CMP90 exhibited a significant inhibitory effect on the proliferation of HL-60 cells with typical apoptotic characteristics by inducing cell cycle arrested at G1/M phase. Additionally, the results in vivo suggested CMP90 was able to inhibit the growth of S180 solid tumors via protecting immune organs, improving the levels of serum cytokines (TNF-α, IL-2 and IFN-γ), enhancing the activities of immune cells (macrophages, lymphocytes and NK cells) and inducing cell apoptosis or death. Taken together, these combined data clearly indicated that CMP90 may be used as a potential candidate agent for cancer therapy.
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Antineoplásicos Fitogênicos/farmacologia , Fagaceae/química , Polissacarídeos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HL-60 , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
This study investigated the effects of heat treatment on structural characteristics and in vitro antitumor activity of polysaccharides from Grifola frondosa. GFP-4 (extracted at 4 °C), GFP-4-80 (80 °C treatment on GFP-4) and GFP-80 (extracted at 80 °C) were prepared, and the chemical composition analysis showed that their total sugar contents were all higher than 90%, high-performance gel-permeation chromatography (HPGPC), ion chromatography (IC) and Fourier-transform infrared spectroscopy (FTIR) results demonstrated that GFP-4 were degraded and denatured after 80 °C heat treatment, MTT and JC-1 results showed that GFP-4 exhibited higher inhibitory effects on HepG2 cells in vitro than GFP-4-80 and GFP-80. Our study suggested that heat treatment at 80 °C on polysaccharides from Grifola frondosa would destroy their structure and attenuate their antitumor effects.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Grifola/química , Antineoplásicos/isolamento & purificação , Biotecnologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Polissacarídeos Fúngicos/isolamento & purificação , Células Hep G2 , Temperatura Alta , Humanos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Grifola frondosa is a widely eaten and medicinal fungus. In this study, we extracted a cold-water-soluble polysaccharide from Grifola frondosa (cGFP) and investigated its effects on the proliferation and apoptosis of human hepatoma HepG2 cells. MTT assay showed that cGFP induced apoptosis of HepG2 cells in a dose-dependent manner. Flow cytometry analysis showed that cGFP induced apoptosis in HepG2 cells through S phase arrest. The distribution of cells at different apoptotic stages was determined by Annexin V-FITC and Propidium Iodide (PI) staining. Scanning electron microscopy (SEM) results indicated that cGFP induced typical apoptotic morphological features in HepG2. Mitochondrial membrane potential was reduced according to the screening of JC-1 staining. And western blot analysis of Bax, Bcl-2, cytochrome C (Cyto-c), caspase-3, and caspase-9 further demonstrated that the cGFP-induced apoptosis effect functioned through the mitochondrial pathway. Further analysis by qRT-PCR showed that Bax expression increased and Bcl-2 expression decreased. These findings suggested that cGFP could inhibit the proliferation of HepG2 cells and induce apoptosis mainly through the intrinsic activation mitochondrial pathway.
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Apoptose/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Grifola/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Expressão Gênica , Genes Reporter , Células Hep G2/ultraestrutura , Humanos , Potencial da Membrana Mitocondrial , Monossacarídeos/química , Análise EspectralRESUMO
Polysaccharide of Atractylodes macrocephala Koidz (PAMK) was extracted by alcohol sedimenting ranging from 60% to 90% and purified by ultrafiltration membrane. The high-performance gel permeation chromatography (HPGPC), Fourier-transform infrared spectroscopy (FT-IR), gas chromatography (GC) and Nuclear magnetic resonance (NMR) revealed that PAMK was a 4.1KDa neutral heteropolysaccharide composed of galactose, arabinose and glucose with α-configuration (molar ratio, 1: 1.5: 5). Results of determination of chemical components suggested that PAMK contained 96.47% of polysaccharide and little protein, nucleic acid and uronic acid. Antitumor experiments in vivo could be concluded that PAMK had a significantly cytotoxic and anti-tumor effect by blocking tumor cells in S phase. And not only that, PAMK could protect immune organ efficiently, comparing with cyclophosphamide. The research provided a potential antineoplastic drug component for tumor treatment.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Atractylodes/química , Polissacarídeos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Camundongos , Polissacarídeos/química , Polissacarídeos/isolamento & purificaçãoRESUMO
In this study, polysaccharides from Atractylodes macrocephala Koidz (APA) which were soluble in alcohol were prepared, purified, analyzed the structure and investigated the antitumor activity in vitro cell experiment. Results of high-performance gel permeation chromatography (HPGPC), fourier-transform infrared spectroscopy (FT-IR), and gas chromatography (GC) showed that APA was a 2.1KDa neutral hetero polysaccharide composed of arabinose and glucose (molar ratio, 1.00:4.57) with pyranose rings and α-type and ß-type glycosidic linkages. Results by MTT experiments showed that the proliferation inhibition was 74.63% in Eca109 cells treated with 2â¯mg/mL dose of APA. Annexin V/PI assay, Hoechst 33,258 staining, cell cycle distribution, rhodamine 123 dye assay and western blot assay clarified that APA could accelerate the apoptosis of Eca109 cells by mitochondrial pathway and stocked cells at S phase. These data indicated that APA is a promising potential candidate for therapeutic treatment of esophageal cancer.
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Apoptose/efeitos dos fármacos , Atractylodes/metabolismo , Polissacarídeos/química , Polissacarídeos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Etanol , Humanos , Mitocôndrias/efeitos dos fármacos , SolubilidadeRESUMO
Seleno-short-chain chitosan (SSCC) is a derivative of chitosan. In the present study, we sought to investigate the underlying antitumor mechanism of SSCC on human gastric cancer BGC-823 cells in vitro. MTT assay suggested that SSCC exhibited a dose-dependent inhibitory effect on the proliferation of BGC-823 cells. We found the SSCC-treated cells showed typical morphological characteristics of apoptosis in a dose dependent manner by observing on microscope. Annexin V-FITC/PI double staining and cell cycle assay identified that SSCC could induce BGC-823 cells apoptosis by triggering G2/M phase arrest. Our research provided the first evidence that SSCC could effectively induce the apoptosis of BGC-823 cells via an intrinsic mitochondrial pathway, as indicated by inducing the disruption of mitochondrial membrane potential (MMP), the excessive accumulation of reactive oxidative species (ROS), the increase of Bax/Bcl-2 ratio and the activation of caspase 3, caspase 9 and cytochrome C (Cyt-C) in BGC-823 cells. These combined results clearly indicated that SSCC could induce BGC-823 cells apoptosis by the involvement of mitochondrial signaling pathway, which provided precise experimental evidence for SSCC as a potential agent in the prevention and treatment of human gastric cancer.
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In this study, a 304/20MnSi stainless-steel clad rebar was prepared by single-pass compression process using the MMS-200 Thermal Mechanical Simulator. The impact of different degrees of deformation and deformation temperature on microstructure evolution and the mechanical properties of stainless steel clad rebars were investigated. The study indicated that with the increase of the degree of deformation, the content of pearlite in a carbon steel matrix was increased, and the grains refined. The metallurgical bonding of the bonded interface was formed under high temperature and high extrusion force. With the increase of the deformation temperature, more bainite was obtained on the side of carbon steel, and the grain size increased. The obvious diffusion of Fe, Cr and Ni elements near the bonding interface resulted in higher microhardness of the stainless steel side and smaller microhardness of the carbon steel side. Moreover, the engineering stress-strain curves obtained by the tensile test showed that the plastic deformation of stainless steel and carbon steel was more coordinated. With the increase of deformation temperature and the degree of deformation, the tensile strength of the stainless steel clad rebar was as high as 690 MPa and the elongation was 26%, which was superior to the properties of the clad rebar prepared by other process parameters.
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In this study, the impact of different surface treatment and degree of vacuum on the interface and mechanical properties of 304/Q345 stainless steel clad plate was investigated. The study indicated that more continuous or aggregated Al2O3 and Si-Mn composite oxides were formed at the interface after brush grinding. However, less inclusions such as Al2O3, MnS and Ca-Mg-Al-Si composite oxides were formed at the interface after pickling treatment. For the vacuum degrees of 10-2 Pa, 1 Pa and 105 Pa, the oxidation reaction became more intense with the decrease in vacuum degree. The interface inclusions were gradually changed from Al2O3 and Si-Mn complex oxides to oxide scale and MnCr2O4 spinel oxide. The interfacial bonding strength of stainless steel clad plate was improved with the increase in degree of vacuum. The bonding strength was 55 MPa at vacuum of 105 Pa, but it was 484 MPa at vacuum of 10-2 Pa, which is far greater than that of the national standard, and an excellent performance was obtained.
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OBJECTIVES: To study the effect of Wenhua Juanbi Recipe (, WJR) on expression of receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor receptor superfamily member 14 (TNFRSF14, also known as LIGHT) in rats with collagen-induced arthritis (CIA). METHODS: CIA rats were generated by subcutaneous injection of bovine collagen type-II at the tail base. Sixty CIA rats were randomly assigned (10 animals/group) to: model, methotrexate (MTX)-treated (0.78 mg/kg body weight), and WJR-treated (22.9 g/kg) groups. Healthy normal rats (n=10) were used as the normal control. Treatments or saline were administered once daily by oral gavage. Rats were sacrifificed at day 28 post-treatment and knee synovium and peripheral blood serum were collected. Toe swelling degree and expression of RANKL, OPG, and LIGHT were determined by Western blot and immunohistochemistry. RESULTS: Compared with the normal group, toe swelling degree was signifificantly increased in the model group (P<0.01). After treatment, toe swelling degree decreased signifificantly in the WJR and MTX groups compared with the model group (P<0.01). Compared with the normal group, expression of RANKL and LIGHT were signifificantly increased and OPG signifificantly decreased in peripheral blood and synovium of the model group (P<0.01). Conversely, RANKL and LIGHT expression were signifificantly reduced and OPG increased in the WJR and MTX groups compared with the model group (P<0.01). No statistically significant difference existed between WJR and MTX groups. CONCLUSION: WJR likely acts by reducing RANKL expression and increasing OPG expression, thus inhibiting RANKL/RANK interaction and reducing LIGHT expression, thereby inhibiting osteoclast formation/activation to block bone erosion.
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Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Western Blotting , Bovinos , Medicamentos de Ervas Chinesas/farmacologia , Imuno-Histoquímica , Masculino , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologiaRESUMO
The overexpression of programmed cell death-ligand 1(PD-L1) has been observed in gastric cancer (GC). However, whether the expression of PD-L1 in tumor cells or blood serum is associated with the prognosis of patients with GC remains unclear. Therefore, we performed a meta-analysis to evaluate the prognostic significance of PD-L1 expression in GC. Electronic databases were searched systematically. Studies that met the inclusion criteria were included in the meta-analysis. Data concerning the hazard ratio (HR) for overall survival and disease-free survival with a 95% confidence interval (CI) according to the expression status of PD-L1 evaluated by immunohistochemistry or enzyme-linked immunosorbent assay were extracted. The data were analyzed using a random effects model. Subgroup analyses were proposed. Our results showed that eight studies with 950 patients met the inclusion criteria and were included in the meta-analysis. The pooled HR for overall survival indicated that patients with PD-L1-positive expression had significantly shorter survival time compared with the PD-L1-negative group (HR 1.60, 95% CI 1.09-2.36, P=0.012). The pooled HR for disease-free survival demonstrated that the difference between the two groups was not statistically significant (HR 1.02, 95% CI 0.32-3.20, P=0.98). In conclusion, our results indicate that the evaluation of PD-L1 overexpression in GC tissue or blood serum may be useful in the future as a novel prognostic factor.
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PURPOSE: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor-positive tumors. METHODS: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 µg; vehicle-rhG-CSF group, normal saline 0.25 µg; and high-rhG-CSF group, rhG-CSF 0.25 µg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction. RESULTS: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%. CONCLUSION: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.
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AIM: To assess midterm results of stapled transanal rectal resection (STARR) for obstructed defecation syndrome (ODS) and predictive factors for outcome. METHODS: From May 2007 to May 2009, 75 female patients underwent STARR and were included in the present study. Preoperative and postoperative workup consisted of standardized interview and physical examination including proctoscopy, colonoscopy, anorectal manometry, and defecography. Clinical and functional results were assessed by standardized questionnaires for the assessment of constipation constipation scoring system (CSS), Longo's ODS score, and symptom severity score (SSS), incontinence Wexner incontinence score (WS), quality of life Patient Assessment of Constipation-Quality of Life Questionnaire (PAC-QOL), and patient satisfaction visual analog scale (VAS). Data were collected prospectively at baseline, 12 and 30 mo. RESULTS: The median follow-up was 30 mo (range, 30-46 mo). Late postoperative complications occurred in 11 (14.7%) patients. Three of these patients required procedure-related reintervention (one diverticulectomy and two excision of staple granuloma). Although the recurrence rate was 10.7%, constipation scores (CSS, ODS score and SSS) significantly improved after STARR (P < 0.0001). Significant reduction in ODS symptoms was matched by an improvement in the PAC-QOL and VAS (P < 0.0001), and the satisfaction index was excellent in 25 (33.3%) patients, good in 23 (30.7%), fairly good in 14 (18.7%), and poor in 13 (17.3%). Nevertheless, the WS increased after STARR (P = 0.0169). Incontinence was present or deteriorated in 8 (10.7%) patients; 6 (8%) of whom were new onsets. Univariate analysis revealed that the occurrence of fecal incontinence (preoperative, postoperative or new-onset incontinence; P = 0.028, 0.000, and 0.007, respectively) was associated with the success of the operation. CONCLUSION: STARR is an acceptable procedure for the surgical correction of ODS. However, its impact on symptomatic recurrence and postoperative incontinence may be problematic.
Assuntos
Defecação , Reto/cirurgia , Grampeamento Cirúrgico , Adulto , Idoso , Distribuição de Qui-Quadrado , China , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Constipação Intestinal/psicologia , Constipação Intestinal/cirurgia , Incontinência Fecal/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Reto/fisiopatologia , Reoperação , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the safety of stapled transanal rectal resection (STARR) for the treatment of obstructed defecation syndrome(ODS). METHODS: A retrospective study was performed in 112 female patients with ODS eligible for STARR. The short-lerm and long-term postoperative complications were recorded and assessed. RESULTS: Short-term postoperative complications and adverse events were reported in 18 patients (16.1%) including fecal incontinence (4.5%), anastomotic bleeding (2.7%), staple line partial dehiscence (0.9%), anal fissure (2.7%), acute urinary retention (1.8%), thrombosed external hemorrhoid (1.8%), hematoma of the rectovaginal septum (0.9%) and fecal impaction (0.9%). Reoperation was required in 2 patients (1.8%) due to the short-term postoperative complications. The median length of follow-up was 24 months. There were 6 patients with long-term postoperative complications (5.4%) including fecal incontinence (1.8%), defecatory urgency (0.9%), chronic pain due to anastomotic inflammation (1.8%), and chronic pain due to anal rectal diverticulum (0.9%). Three patients (2.7%) were reoperated. CONCLUSION: STARR appears to be a safe technique for patients with obstructed defecation.