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The prevalence of selenium-cadmium ï¼Se-Cdï¼ symbiosis in soils of geologically high background areas directly affects the safe utilization of Se-rich land resources. To investigate the migration and accumulation characteristics and bio-effectiveness of Se-Cd in the soil-crop system in typical geological high background areas of Southwest China and to realize the safe use of natural Se-rich land resources in geological high background areas, we collected 84 samples of agricultural crops ï¼maizeï¼ and their supporting root systems and analyzed the Se-Cd content and physicochemical properties. Se-Cd accumulation characteristics, influencing factors, and bio-effectiveness of the soil-crop system were evaluated using geostatistics, bioenrichment factors, and geographic detectors. The results showed that the Se-Cd content in the study area was significantly higher than the background value of the soil in the whole country and in Yunnan Province. Influenced by the geological background, secondary enrichment in the process of soil formation, and agricultural activities, the accumulation and enrichment characteristics of Se in the root soil varied from no enrichment to slightly enriched, and the occurrence form was dominated by the residue state. The accumulation index of soil Cd was mainly in the medium pollution level, and the occurrence form was mainly in the residual state and the combined state of iron and manganese. The Se-enrichment rate of crop seeds reached 98.8% ï¼DB 50/T 524-2013 standardï¼, and the average value of bioconcentration factor was 5.8%. The exceeding rate of Cd content in crop seeds was only 1.19% ï¼GB 2762-2022 standardï¼, and the average value of Cd bioconcentration factor was 2.11%, so the ecological risk of heavy metal Cd in crop seeds was relatively low. In the Se-Cd symbiosis area under geological background, the weak alkaline environment of the soil could effectively reduce the bioavailability of Cd in crop seeds, and the Se-rich soil could inhibit the uptake of Cd by the crops to a certain extent. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system were affected by the elemental accumulation pattern and the physical and chemical properties ï¼pHï¼ of the soil, and at the same time, there was a certain synergistic-antagonistic effect between Se and Cd in the soil-crop system. Correlation analysis showed that the migration and accumulation of Se and Cd from soil to crop seeds in the soil-crop system was influenced by the occurrence of elements, soil physicochemical properties ï¼pHï¼, and other factors, and there was also a certain synergistic-antagonistic interaction between Se and Cd in the soil-crop system.
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Wasps play important roles as predators and pollinators in the ecosystem. The Jingpo minority residing in Yunnan Province, China, has a traditional practice of using wine infused with mature wasps as a customary remedy for managing rheumatoid arthritis. The larva of the wasp is also a tasteful folk dish that has created a tremendous market. There is a paucity of survival knowledge, which has greatly restricted their potential applications in food and healthcare. Recent research has highlighted the importance of gut microbiota in insect growth. Nevertheless, there is still a lack of understanding regarding the composition, changes, and functions of the gut microbiota in Vespa mandarinia during development. In this research, the gut microbiota were investigated across three growth stages of Vespa mandarinia using a metagenomic technology. The result revealed that there are significant variations in the proportion of main gut microbes during the metamorphosis of Vespa mandarinia. Tenericutes were found to dominate during the larval stage, while Proteobacteria emerged as the dominant group post-pupation. Through a comprehensive analysis of the gut microbiota metagenome, this study revealed functional differences in the wasp gut microbiota at various growth stages. During the larval stage, the gut microbiota plays a central role in promoting metabolism. Following pupation, the gut microbiota exhibited diversified functions, likely due to the complex environments and diverse food sources encountered after metamorphosis. These functions included amino acid metabolism, compound degradation, and defense mechanisms. This research provides an extensive dataset on the gut microbiota during the metamorphosis of Vespa mandarinia, contributing to a deeper understanding of the influence of gut microbiota on wasp growth. Furthermore, this study uncovers a unique microbial treasure within insect guts, which is important for advancing the application of wasps in the fields of food and medicine.
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ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.
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Artrite Reumatoide , Ferroptose , Sinoviócitos , Vespas , Animais , Humanos , Venenos de Vespas/farmacologia , Venenos de Vespas/metabolismo , Venenos de Vespas/uso terapêutico , Interleucina-6/metabolismo , Vespas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proliferação de Células , Antioxidantes/farmacologia , Oxirredução , Fibroblastos , Luciferases , Lipídeos/farmacologia , Células CultivadasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. AIM OF THE STUDY: Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. MATERIALS AND METHODS: The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF-α, IL-1ß and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. RESULTS: Among crude extracts from C. chinensis, ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N-[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p-N,N-dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. CONCLUSIONS: Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis.
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Anti-Inflamatórios/farmacologia , Besouros , Inflamação/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Anti-Inflamatórios/química , Medicina Tradicional Chinesa , Camundongos , Células RAW 264.7 , Transdução de SinaisRESUMO
In order to evaluate the potential ecological risk of heavy metals in the soil-crop system in the Xiong'an New District, the heavy metal contents and forms in wheat seed and root soil samples are analyzed, and the comprehensive pollution index (IPIN), potential ecological risk index (RI), bio-enrichment coefficient (BFC), risk assessment code (RAC), principal component analysis, and correlation analysis are used to assess the potential ecological risk of heavy metals and analyze their sources. The results indicate that the average content of Cd, Cu, Pb, and Zn in the root soil is significantly higher than the soil background value in Hebei province. The IPIN ranges from 0.2 to 5.18, 94.83% of the soil samples are in the safe and pollution-free grade, and the potential ecological risks of heavy metal are slight and moderate, accounting for 64.66% and 30.17%, respectively. Cd has the greatest potential ecological harm, followed by Hg, Cr, Ni, and Zn. All the heavy metal elements besides Cd in the root soil are dominated by the residual form, which accounts for 60%, and the bioactive form (ion-exchange and water-soluble state) of Cd accounts for 33.43%, indicating relatively high bio-availability. The risk assessment code can be ranked as Cd > Ni > Hg > As > Cu > Cr > Zn > Pb, and the risk of Cd is moderate, while other elements are of low or no risk. The leading potential source of heavy metals is human activity combined with the geological background. The migration and enrichment capability of the wheat seeds is in order from strong to weak of Zn > Cu > Cd > Hg > As > Ni > Pb > Cr, and the biological effective components of As, Cd, Pb, and Zn plays an substantial role in promoting the absorption of heavy metals. The content of heavy metals in the wheat seeds has a negative correlation with the soil pH, and the physical and chemical indices, such as OM and CEC, has bi-directional influence on the biological effective state of the heavy metals.
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Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análiseRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease. Wasp venom (WV), which is considered as a traditional folk medicine in Jingpo nationality in Yunnan, China, relieves rheumatoid arthritis. The current study aimed to investigate the effect of wasp venom ameliorating rheumatoid arthritis symptoms in experimental rats. We established a model of type II collagen- (CII-) induced arthritis (CIA) in SD rats and examined the inhibition of inflammation and autoimmune response. The antiarthritic effects of WV were evaluated through the paw swelling, and histopathological score and histopathology changes of the affected paw were assessed. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1ß, and the number of inflammatory cells in peripheral blood. The alteration of the T cell subset ratio in the spleen of rats was detected by flow cytometry, and at the same time, the viscera index and immune serum globulin levels were evaluated. The results suggested that various doses of WV (0.125, 0.25, and 0.5 mg/kg) significantly alleviated paw swelling and arthritis score in CIA rats with the untreated control (P < 0.05). WV (0.25 and 0.5 mg/kg) relieved synovial tissue lesions of ankle joints and histopathology scores of synoviocyte hyperplasia and inflammatory cell infiltration with vehicle group (P < 0.05). Regarding immunological regulation, 0.5 mg/kg WV lowered the immune serum globulin levels (P < 0.05), and we further found that WV (0.5 mg/kg) suppressed the immune response of Th cells, while enhancing the functions of Tc cells and Treg cells in spleen cells markedly (P < 0.05). The immunosuppressive action of WV displayed was analogous to its inhibitory effect on IL-1ß, TNF-α, IL-8, IL-6, COX-2, and PGE2 levels in rat serum. In conclusion, these findings demonstrated that WV exhibited antiarthritic activity, which might be associated with their inhibitory effects on immunoregulation and anti-inflammatory action.
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A new heterodimer, rynchopeterine F (1), a new natural product, rynchopeterine G (2), and eleven known phenolics were isolated from Blap rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi and Bai Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS) along with calculated electronic circular dichroism method. Rynchopeterine F was a unusual heterodimer of a 3,4-dihudroxy phenylethanol unit fused to a 3,4-dihudroxy phenylacetyl group through two ester bonds with lactic acid, and rynchopeterine G was a 3,4-dihudroxy phenylethanyl monoester succinate. Attributed to the adjacent dihydroxyl grops, compounds 1 and 2 exhibited significant anti-radical activity with an IC50 value of 3.52 and 7.83⯵g/mL for DPPH radical-scavenging, similar with that of the positive controls, vitamin C, 6.92⯵g/mL and rutin, 8.28⯵g/mL.
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Besouros/química , Sequestradores de Radicais Livres/farmacologia , Fenóis/farmacologia , Animais , China , Sequestradores de Radicais Livres/isolamento & purificação , Ácido Láctico/química , Estrutura Molecular , Fenóis/isolamento & purificação , Álcool Feniletílico/químicaRESUMO
This paper concerns four species of the spider genus Uroctea Dufour, 1820 (Oecobiidae) from China. Two species, U. compactilis L. Koch, 1878 and U. lesserti Schenkel, 1936 are redescribed. Two new species are described here under the names U. multiprocessa Yang Zhang sp. nov. (male only, from Batang County of Sichuan Prov.) and U. yunlingensis Yang Zhao sp. nov. (both sexes from Yunling Mountains area of Yunnan Prov.). Color images of habitus and genitalia, SEM images of the male palps, and illustrations of epigynes of all species are provided. Specimens examined are deposited in the Institute of Entomoceutics Research, Dali University, China (DUIER) and School of Life Sciences, Southwest University, China (SWUC).
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Aranhas , Animais , China , Cor , Feminino , MasculinoRESUMO
As a folk medicine of the Jingpo minority in Yunnan province, the venom of Vespa magnifica has been commonly used for the treatment of rheumatoid arthritis. Quality standardization of the wasp venom is a necessary step for its pharmaceutical research and development. To control the quality of the wasp venom, a method based on high-performance liquid chromatography (HPLC) was developed for chemical fingerprint analysis. In the chromatographic fingerprinting, chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), and principal component analysis (PCA), were applied to classify 134 batches (S1-S134) of wasp venom from different origins. The HPLC fingerprint method displayed good precision (Relative standard deviation, RSD < 0.27%), stability (in 16 h, RSD < 0.34%), and repeatability (RSD < 1.00%). Simultaneously, four compounds (VMS1, VMS2, VMS3, and VMS4) in the wasp venom were purified and identified. VMS1 was 5-hydroxytryptamine, and the other compounds were three peptides that were sequenced as follows: Gly-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg-Ile-Asp-NH2 (VMS2), Ile-Asn-Leu-Lys-Ala-Ile-Ala-Ala-Leu-Ala-Lys-Lys-Leu-Leu-NH2 (VMS3), and Phe-Leu-Pro-Ile-Ile-Gly-Lys-Leu-Leu-Ser-Gly-Leu-Leu-NH2 (VMS4). The quantifications for these components were 110.2 mg/g, 26.9 mg/g, 216.3 mg/g, and 58.0 mg/g, respectively. The results of this work indicated that the combination of the chemical fingerprint and quantitative analysis offers a reasonable way to evaluate the quality of wasp venom.
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Anti-Inflamatórios/isolamento & purificação , Peptídeos/isolamento & purificação , Serotonina/isolamento & purificação , Venenos de Vespas/química , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/química , Artrite Reumatoide/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/normas , Humanos , Medicina Tradicional Chinesa , Medicina Tradicional/métodos , Mapeamento de Peptídeos/métodos , Peptídeos/química , Análise de Componente Principal , Controle de Qualidade , Serotonina/química , VespasRESUMO
The effects of walnut oil on wound healing and skin injury repair was observed in Sprague-Dawley (SD) rats, and mechanism of action was investigated. Normal SD rats were divided into an experimental group and a control group. Each group was observed at4 time points (day [D]3, D7, D14, and D21). In both groups, a skin wound was created on the back of the rats, with the spine as the central axis. In the experimental group, the wound was covered with walnut oil, and then bandaged and fixed with sterile gauze. In the control group, the wound was bandaged with vaseline gauze. At each corresponding time point, the wound area and wound healing time of each rat were examined. Epithelial cells of the wound tissues were observed using haematoxylin and eosin staining and immunohistochemical analysis,and the numbers of inflammatory cells and capillaries were counted. A western blot method was used to detect the expression of nuclear factor (NF)-κB and epidermal growth factor (EGF) in the wound tissues of both groups. Meanwhile, enzyme-linked immunosorbent analysis (ELISA) was used to detect the expression of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-1 in rat sera. A total of 48 SD rats completed the experiment. Healing time of residual wounds in the experimental group was 10.0±3.5 days, which was significantly shorter than that in the control group (18.0±6.0 days) (p<0.05). The wound healing rates in the experimental group were 54.14 % (D3) and 91.2 3% (D7), whereas those in the control group were 22.12% (D3) and 54.84% (D7 (p<0.05).Histological examinations revealed no epithelial cells on D3, D7, D14, and D21 in both the experimental and control groups. However, the number of inflammatory cells decreased significantly and the number of capillaries increased significantly in the experimental group compared to control (p<0.05). NF-κB expression was significantly lower, EGF expression significantly higher in the in the experimental group. Conversely, ELISA showed a significant increase in the expression of TGF-ß1 and MMP-1 in rat sera in the experimental group. So we conclude that walnut oil has significant effects in promoting the healing of skin defect wounds in SD rats.
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Juglans/química , NF-kappa B/metabolismo , Óleos de Plantas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento Epidérmico/genética , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Masculino , Metaloproteinase 1 da Matriz/genética , Óleos de Plantas/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Tempo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Toxoplasma gondii has been suggested as an important opportunistic pathogen in immunocompromised patients. We conducted a global meta-analysis to assess the prevalence and odds ratios (ORs) of T. gondii infection in immunocompromised individuals. Electronic databases were reviewed for T. gondii infection in HIV/AIDS patients, cancer patients, and transplant recipients, and meta-analyses were conducted to calculate overall estimated prevalence and ORs using random or fixed-effects models. Totally, 72 eligible studies were included. The estimated pooled prevalence of T. gondii infection in immunocompromised patients and the control was 35.9 and 24.7% (p < 0.001), with an OR of 2.24, i.e., 42.1 and 32.0% for HIV/AIDS patients and the control (p < 0.05), 26.0 and 12.1% for cancer patients and the control (p < 0.001), and 42.1 and 34.5% for transplant recipients and the control (p > 0.05), whose estimated pooled ORs were 1.92 (95% CI, 1.44-2.55), 2.89 (95% CI, 2.36-3.55), and 1.51 (95% CI, 1.16-1.95), respectively. This study is the first to demonstrate that the immunocompromised patients are associated with higher odds of T. gondii infection, and appropriate prevention and control measures are highly recommended for these susceptible populations.
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Anoikis is a form of apoptosis which occurs when anchorage-dependent cells either show loss of adhesion or inappropriate adhesion. Only a few cancer cells that detach from the primary site of the tumor acquire the ability to resist anoikis and form metastasis. The mechanism underlying the resistance of colorectal cancer (CRC) cells to anoikis remains unclear. Interleukin-8 (alternatively known as CXCL8) is associated with CRC angiogenesis and progression. Here, we found that a high abundance of CXCL8 or TOPK strongly correlated with poor overall and disease-free survival of 186 patients with CRC. A combination of high CXCL8 and high TOPK expressions had the worst prognosis. We showed that CXCL8 expression was negatively correlated with anoikis in CRC cells. CXCL8 treatment enhanced the resistance of CRC cells to apoptosis, which was accompanied by the increase of TOPK, and the activation of AKT and ERK. Moreover, we demonstrated that the inhibition of either ERK or AKT by specific chemical inhibitors attenuated the CXCL8-mediated resistance to anoikis. Treatment with AKT inhibitor abolished the effects of CXCL8 on TOPK expression, suggesting that TOPK was downstream of AKT in the process of anoikis. Taken together, we demonstrated that CXCL8 is strongly implicated in the resistance of CRC cells to anoikis, and that the AKT, TOPK and ERK pathway may be a potential therapeutic target for CRC.
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Anoikis , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Imunofluorescência , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Adulto JovemRESUMO
Liver metastases represent the major cause of death in patients with colorectal cancer (CRC). Recent studies have suggested that the chemotactic responses of tumor cells are necessary for metastatic spread to the liver, and CCL20 and CXCL8 have a strong association with CRC metastasis. The aim of our study was to identify the mechanisms by which CCL20 and CXCL8 synergize to promote metastatic progression and evaluated their potential as prognostic markers for CRC patients. The abilities of CCL20 and CXCL8 to promote CRC cell progression and epithelial-mesenchymal transition(EMT)phenotype were analyzed in vitro. Possible signaling pathways were investigated with specific pathway inhibitors and small interfering RNA (siRNA). 213 Patients with CRC who underwent surgery were enrolled for analysis of CCL20, CXCL8 and E-cadherin expressions in tumor tissues. Prognostic factors were then identified. CCL20 or CXCL8 alone was not sufficient to induce complete EMT in CRC cells, but both of them could coordinately induce EMT-like phenotype that was required to maintain CRC cell proliferation, migration and invasion. PI3K/AKT-ERK1/2 pathway crosstalk was demonstrated to be responsible for this process. Coexpression of CCL20 and CXCL8 was negatively correlated with E-cadherin expression in human CRC tissues. CRC patients with coexpression of CCL20 and CXCL8 were more likely to develop liver metastases and both coexpression was an independent high-risk factor for a most poor prognosis. CCL20 and CXCL8 synergize to promote CRC metastatic progression by coordinated induction of EMT via PI3K/AKT-ERK1/2 signaling axis. Detection of both coexpressions can be used to predict clinical outcomes in CRC patients.
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Adenocarcinoma/metabolismo , Quimiocina CCL20/metabolismo , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Interleucina-8/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Antígenos CD , Células CACO-2 , Caderinas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Adulto JovemRESUMO
Orthodenticle homeobox 1 (OTX1), a transcription factor containing a bicoid-like homeodomain, plays a role in brain and sensory organ development. In this study, we report that OTX1 is overexpressed in human colorectal cancer (CRC) and OTX1 overexpression is associated with higher stage. Functional analyses reveal that overexpression of OTX1 results in accumulation of CRC cell proliferation and invasion in vitro and tumor growth in vivo, whereas ablation of OTX1 expression significantly inhibits the proliferative and invasive capability of CRC cells in vitro. Together, our results indicate that OTX1 is involved in human colon carcinogenesis and may serve as a potential therapeutic target for human colorectal cancer.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Fatores de Transcrição Otx/genética , Fatores de Transcrição Otx/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Progressão da Doença , Células HCT116 , Humanos , Oncogenes , Fatores de Transcrição Otx/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , RNA Interferente Pequeno/genética , Regulação para CimaRESUMO
BACKGROUND AND OBJECTIVE: Thrombospondin-1(TSP1) is an inhibitor of angiogenesis and its promoter hypermethylation has been found resulting in gene silencing in some primary human carcinomas. This study was to investigate the promoter methylation of TSP1 and its correlation with TGF-beta1 level and T cell immunity in gastric cardia adenocarcinoma (GCA). METHODS: Methylation specific polymerase chain reaction (MSP) approach and immunohistochemistry method were used to examine the methylation status of the 5' CpG island and expression of TSP1 protein, respectively. The level of TGF-beta1 was measured by ELISA and T cell immunity of GCA by flow cytometry analysis. RESULTS: TSP1 methylation frequency was significantly higher in tumor specimens than in corresponding normal tissues (35.4% vs. 3.1%, P<0.001) and significantly higher in Stages III and IV tumor tissues than in Stages I and II tumor tissues (P<0.05). TSP1 protein expression was significantly lower in the tumor tissues than in corresponding normal tissues (P<0.05) and statistically correlated with its methylation status (P<0.01). The total level of TGF-beta1 was significantly higher in the GCA patients than in healthy controls(P<0.05) and significantly higher in Stages III and IV GCA patients than in Stages I and II GCA patients (P<0.05). The level of active TGF-beta1 was significantly higher in the GCA patients with hypermethylation of TSP1 than in the GCA patients without methylation of TSP1(P<0.05), but there was no statistical difference(P>0.05). The function of T cell immunity was significantly different between the GCA patients with hypermethylation of TSP1 and those without methylation of TSP1 (P<0.05). CONCLUSION: Promoter hypermethylation of TSP1 may play an important role in the development of GCA and reflect the biological behaviours of GCA.
Assuntos
Adenocarcinoma , Cárdia , Neoplasias Gástricas , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta1/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/metabolismo , Adulto , Idoso , Complexo CD3/metabolismo , Relação CD4-CD8 , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismoRESUMO
BACKGROUND: The mda-7/IL-24 receptor belongs to the type II cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy. METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were amplified by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed. RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1; BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL-20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor. CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.
Assuntos
Interleucinas/metabolismo , Neoplasias Hepáticas/genética , Receptores de Interleucina/genética , Northern Blotting , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Multimerização Proteica , Receptores de Interleucina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To study the influence of preoperative chemoradiotherapy, preoperative chemotherapy, and operation alone on the cellular immunity in patients with middle or lower rectal cancer. METHODS: Ninety middle or lower rectal cancer patients were non-randomly divided into 3 equal groups: preoperative radiotherapy group, receiving conventional radiotherapy with a total dose of 30 Gy in 10 fractions completed within 2 weeks; preoperative chemoradiotherapy group, receiving 2 cycles of single-oral drug regimen (capecitabine 1000 mg/m(2) for 2 weeks as a cycle with an interval of 1 week) and then, i.e., 2 days later, receiving conventional radiotherapy as prescribed for the patients in the preoperative radiotherapy group; and operation alone group. Operation was performed on the patients of the former 2 groups 3 weeks after the completion of the relevant treatment. Blood samples were collected on the admission day, 1 day before operation, and 7 day and 1 month after operation. Flow cytometry was used to detect the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells. RESULTS: There were no significant differences in the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells before and after radiotherapy between the preoperative chemoradiotherapy group and preoperative chemotherapy group (all P > 0.05). 7 days after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were degraded and the CD(8)(+) level was increased significantly (all P < 0.05) in all 3 groups. One month after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were all significantly higher and the CD(8)(+) level was significantly lower than those before operation and 7 days after operation (all P < 0.05)in all 3 groups. There were no significant differences in the T cell number and the proportions of different categories of cells at different time points in these 3 group (all P < 0.05). CONCLUSION: Preoperative chemoradiotherapy and preoperative chemotherapy have no significant impact on the cellular immune function in the patients with rectal cancer.
Assuntos
Neoplasias Retais/imunologia , Neoplasias Retais/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Imunidade Celular , Células Matadoras Naturais , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Neoplasias Retais/cirurgiaRESUMO
Field experiments were conducted in Anyang and Nanjing, the typical representatives of ecological regions in the Yellow River Valley and the lower reaches of Yangtze River Valley in China, to quantitatively analyze the spatiotemporal variability of biomass accumulation of the fruiting branch of cotton variety Nucotn 33B at its flower and boll stage under effects of 0, 120, 240, 360, and 480 kg N x hm(-2) (marked as N0, N1, N2, N3, and N4, respectively). The results indicated that both in Nanjing and in Anyang, the temporal variability of biomass accumulation of vegetative and reproductive organs at different positions of fruiting branch could be described by Logistic equation, but the spatial variability was obviously different. Under the nitrogen application rate of 360 kg x hm(-2) in Anyang and of 240 kg x hm(-2) in Nanjing, the biomass accumulation had the characteristics of earlier starting date, shorter duration, and maximal speed of rapid increase. These nitrogen application rates could accelerate the biomass accumulation to benefit the high lint yield and fiber quality, while excess or deficient nitrogen supply was disadvantageous to the biomass accumulation of fruiting branch. Therefore, it could be possible to apply appropriate amount of nitrogen to regulate the growth eigenvalues of different positions fruiting branch at its speed growth stage to obtain high lint yield and fiber quality.