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Tracking and detection have brought great challenges to network security. Therefore, this paper proposes a monitoring method of stealthy complex network attacks considering security situation awareness. By constructing a tracking model of invisible complex network attacks, public monitoring nodes are selected for monitoring. The cost of a single monitoring node is calculated by the algorithm, and the monitoring node is determined by the monitoring node algorithm, so as to reduce the resource occupancy rate of the monitoring node and improve the monitoring accuracy. The simulation results show that this method is stable in the range of 1000 to 4000 nodes, and can effectively monitor the complex network attacks of stealing secrets.
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Conscientização , Roubo , Segurança Computacional , Simulação por Computador , AlgoritmosRESUMO
The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner of ATP/P2Y2 dependence. Incubation of human bronchial epithelia with RBD induced IL-6 and IL-8 release, which could be inhibited by antibody. The incubation of RBD also up-regulated the expression of inflammatory indicators such as ho-1 and mkp-1. Furthermore, ATP secretion was observed after RBD treatment, P2Y2 receptor knock down by siRNA significantly suppressed the IL-6 and IL-8 release evoked by RBD. Additionally, S-RBD elevated the phosphorylation level of ERK1/2, and the effect that PD98059 can inhibit the pro-inflammatory cytokine release suggested the participation of ERK1/2. These novel findings provide new evidence of SARS-CoV-2 on airway inflammation and introduce purinergic signaling as promising treatment target.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Sistema de Sinalização das MAP Quinases , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células Endoteliais/metabolismo , SARS-CoV-2/metabolismo , COVID-19/metabolismo , Transdução de Sinais , Mucosa Respiratória/metabolismo , Inflamação/metabolismo , Trifosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Ligação ProteicaRESUMO
BACKGROUND: Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PURPOSE: We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. METHODS: First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. RESULTS: Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. CONCLUSION: This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
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Microbioma Gastrointestinal , Probióticos , Reishi , Animais , Camundongos , Fermentação , Probióticos/farmacologia , Probióticos/uso terapêutico , Ciclofosfamida/efeitos adversos , Imunidade , Terapia de Imunossupressão , SementesRESUMO
The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely associated with the pathogenesis of several human diseases. Innate lymphoid cells (ILCs), which include NK cells, ILC1s, ILC2s, ILC3s and LTi cells, are a type of innate immune cells. They are enriched in the mucosal tissues of the body, and have recently received extensive attention. The gut microbiota and its metabolites play important roles in various intestinal mucosal diseases, such as inflammatory bowel disease (IBD), allergic disease, and cancer. Therefore, studies on ILCs and their interaction with the gut microbiota have great clinical significance owing to their potential for identifying pharmacotherapy targets for multiple related diseases. This review expounds on the progress in research on ILCs differentiation and development, the biological functions of the intestinal microbiota, and its interaction with ILCs in disease conditions in order to provide novel ideas for disease treatment in the future.
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Microbioma Gastrointestinal , Humanos , Imunidade Inata , Imunidade nas Mucosas , Mucosa Intestinal , Células Matadoras NaturaisRESUMO
Melophagus ovinus is a hematophagous insect that is distributed worldwide and plays a crucial role in transmitting disease-causing pathogens. From June 2021 to March 2022, a total of 370 M. ovinus were collected from 11 sampling points in southern Xinjiang, China. The specimens were identified using morphological and molecular analyses. Rickettsia spp. and Anaplasma ovis were detected from all the samples using seven Rickettsia-specific genetic markers and the msp-4 gene of A. ovis. Approximately 11% of the M. ovinus specimens were positive for Rickettsia spp., and Candidatus Rickettsia barbariae was the most predominant species (35/41; 85.4%), while R. massiliae was least prevalent (6/41; 14.6%). Approximately 10.5% (39/370) of the M. ovinus specimens were positive for A. ovis of genotype III, which was co-detected with Candidatus R. barbariae in M. ovinus (3/370; 0.8%). To the best of our knowledge, this is the first report of the detection of R. massiliae and Candidatus R. barbariae in M. ovinus globally. The detection and control of insect-borne diseases originating from M. ovinus should be strengthened in southern Xinjiang, an area important to animal husbandry and production.
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Anaplasma ovis , Dípteros , Rickettsia , Animais , Ovinos , Rickettsia/genética , Filogenia , Dípteros/microbiologia , China , AnaplasmaRESUMO
Background: Anaplasma ovis are obligate intracellular bacteria that can endanger human and animal health, and they can be transmitted by arthropod vectors, such as Melophagus ovinus and ticks. Materials and Methods: In this study, 433 specimens, including 370 M. ovinus and 63 sheep blood samples, were collected from nine districts of South Xinjiang to investigate the distribution and molecular epidemiology of A. ovis in M. ovinus and small ruminant. Results: DNA of A. ovis was detected in 109 (25.2%, 109/433) of the 433 samples using PCR and sequencing. The analysis of A. ovis msp4 sequences revealed four different genotypes, including genotype III (47.7%; 52/109), GB3 (34.0%; 37/109), AoGOv3 (15.6%; 17/109), and XJ9 (2.8%; 3/109). Conclusions: To the best of our knowledge, A. ovis genotypes GB3, AoGOv3, and XJ9 detected in this study are the first to be reported in M. ovinus, and our data indicate that XJ9 is a novel A. ovis genotype presented herein for the first time. These findings provide important references for the new understanding and prevention of A. ovis in border counties in China.
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Anaplasma ovis , Anaplasmose , Dípteros , Doenças dos Ovinos , Carrapatos , Humanos , Ovinos , Animais , Anaplasma ovis/genética , Epidemiologia Molecular , Carrapatos/microbiologia , China/epidemiologia , Dípteros/microbiologia , Ruminantes , Anaplasma/genética , Filogenia , Anaplasmose/epidemiologia , Anaplasmose/microbiologia , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologiaRESUMO
Background: The existing health resources and services are difficult to meet the needs of rapid economic development and the aging population in China. This paper evaluates the regional differences of individual and allocation efficiencies of health resources in China to explore ways to change the current situation. Methods: The models of single-input single-output efficiency (SISOE), single-input multi-output efficiency (SIMOE), multi-input single-output efficiency (MISOE), and multi-input multi-output efficiency (MIMOE) were developed to calculate the individual and allocation efficiencies of health resources of China in this study. Results: It was found that the efficiencies of the number of health institutions (NHI) in the eastern and western regions of China were relatively close, with values of 0.61 and 0.59, respectively, significantly higher than 0.49 in the middle region. The efficiencies of the number of health personnel (NHP) in the eastern, middle, and western regions were closer, with values of 0.77, 0.75, and 0.79, respectively. The efficiencies of the number of health institution beds (NHIB) in the eastern and western regions were very close, with values of 0.79 and 0.78, respectively, while that in the middle region was 0.72. The efficiencies of the total health expenditure (THE) were 0.72, 0.76, and 0.79 in the east, middle, and western regions, respectively. The efficiencies of the number of diagnosis and treatment persons (NDTP) were 0.81, 0.70, and 0.71 in the eastern, middle, and western regions, respectively, while the efficiencies of the number of inpatients (NI) were 0.75, 0.79, and 0.81, respectively. The efficiencies of the utilization rate of beds (URB) and the average days of hospitalization (ADH) in the three regions were below 0.51. The health resources allocation efficiencies (HRAEs) were 0.86, 0.83, and 0.87 in the eastern, middle, and western regions, respectively. Conclusion: There were obvious regional differences in HRAE in China with the situation of "Middle Collapse." The main direct reason for the low HRAE in the middle region was the lower efficiencies of NHI, NHIB, URB, and ADH. It revealed that there was relatively blind expansion of health institutions and beds with lower health service quality in the middle region. Governments should make strategic adjustments to public health resources and increase the investment in medical technology and manpower in the middle region. Hospitals in the eastern region should strengthen inter-regional medical and health technical cooperation with partners in the middle region by establishing a tele-medical network. The models of SISOE, SIMOE, MISOE, and MIMOE put forward in this study are simple, reasonable, and useful for resource efficiency analysis, which makes it convenient to adopt targeted measures to upgrade the efficiency of resource allocation. This study provides a new perspective and method to understand the mechanism of regional differences in China's health resource allocation efficiency.
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Recursos em Saúde , Alocação de Recursos , Eficiência , Serviços de Saúde , ChinaRESUMO
BACKGROUND: Preeclampsia (PE) is a syndrome commonly occurring among the pregnant. Shallow trophoblast invasion is considered to be closely related to PE. Therefore, in trophoblast cells, we explored the potential mechanisms of lncRNA XIST in the modulation of trophoblast invasion and proliferation. METHODS: GEO online analyzer was used to screen the abnormally expressed RNAs in placenta tissues from patients with severe PE and healthy controls. The prediction of target bindings was performed on TargetScan and starBase. Transfection was conducted to regulate the RNA expression levels in trophoblast cells, HTR-8/SVneo. RT-qPCR measured expression of lncRNA XIST, miR-340-5p and KCNJ16. The CCK-8 assay examined cell viability. Flow cytometer analyzed apoptosis and luciferase assay determined the luciferase activity. Transwell assays detected the invasion and western blot verified the changes in protein expression of MMP2, MMP9 and KCNJ16 in trophoblast cells. RESULTS: lncRNA XIST expression was enhanced in PE patients. Upregulation of lncRNA XIST in HTR-8/SVneo cells inhibited the cell proliferation and invasion, and induced apoptosis. XIST upregulation inhibited MMP2 and MMP9 protein expression. lncRNA XIST/ KCNJ16 interplayed as ceRNAs of miR-340-5p. Specifically,miR-340-5p overexpression reversed the effect of XIST upregulation on the cell apoptosis, proliferation and invasive ability and the knockdown of KCNJ16 could add to the effect of miR-340-5p overexpression in HTR-8/SVneo. CONCLUSION: lncRNA XIST was upregulated in PE. Upregulation of lncRNA XIST exerted the inhibitory effects on the proliferation and invasion of trophoblast cells through the interactions with miR-340-5p/KCNJ16, which suggests that the lncRNA XIST/miR-340-5p/KCNJ16 axis might play a role in PE.
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MicroRNAs , Pré-Eclâmpsia , RNA Longo não Codificante , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Canais de Potássio Corretores do Fluxo de Internalização , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Trofoblastos/metabolismoRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease, in addition, gut microbiota plays an important role in the etiology of RA. However, our understanding of alterations to the gut fungal microbiota in Chinese population with RA is still limited. METHODS: Serum samples were obtained from 62 patients with RA, and 39 age- and gender-matched healthy controls (HCs). Fecal samples were obtained from 42 RA patients and 39 HCs. Fecal fungal microbiota targeting internal transcribed spacer region 2 (ITS2) rRNA genes was investigated using MiSeq sequencing, as well as their associations with some diagnostic biomarkers for RA. RESULTS: Our results showed that the fungal diversity did not alter in RA patients but taxonomic composition of the fecal fungal microbiota did. The gut mycobiota of RA patients was characterized by decreased abundance of Pholiota, Scedosporium, and Trichosporon. The linear discriminant analysis (LDA) effect size analysis (LEfSe) analysis identified several RA-enriched fungal genera, which were positively correlated with most RA biomarkers. Furthermore, since RA is an age- and gende-related disease, we classified RA patients into subgroups with age and gender and analyzed the sequencing results. Our data demonstrated that Wallemia and Irpex were the most discriminatory against RA patients over 60 years old, while Pseudeurotiaceae was the most discriminatory against female RA patients. CONCLUSIONS: The case-control study presented here confirmed the alterations of gut fungal microbiota in Chinese patients with RA, and we speculated that the fungal dysbiosis may contribute to RA development.
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Artrite Reumatoide , Microbioma Gastrointestinal , Micobioma , Humanos , Feminino , Pessoa de Meia-Idade , Microbioma Gastrointestinal/genética , Estudos de Casos e Controles , Artrite Reumatoide/diagnóstico , BiomarcadoresRESUMO
Unlike olfaction, taste, touch, vision, and proprioception, which are widespread across animal phyla, hearing is found only in vertebrates and some arthropods. The vast majority of invertebrate species are thus considered insensitive to sound. Here, we challenge this conventional view by showing that the earless nematode C. elegans senses airborne sound at frequencies reaching the kHz range. Sound vibrates C. elegans skin, which acts as a pressure-to-displacement transducer similar to vertebrate eardrum, activates sound-sensitive FLP/PVD neurons attached to the skin, and evokes phonotaxis behavior. We identified two nAChRs that transduce sound signals independently of ACh, revealing an unexpected function of nAChRs in mechanosensation. Thus, the ability to sense airborne sound is not restricted to vertebrates and arthropods as previously thought, and might have evolved multiple times independently in the animal kingdom, suggesting convergent evolution. Our studies also demonstrate that animals without ears may not be presumed to be sound insensitive.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Mecanotransdução Celular/fisiologia , Propriocepção , Tato/fisiologiaRESUMO
AIM: Recently, microRNA-149 (miR-149) has been indicated to act as an oncogene or a tumor suppressor in various malignant tumors, while its inner mechanisms in recurrent miscarriage (RM) are still in infancy. Therein, this study intends to decode the mechanism of miR-149 in RM. METHODS: miR-149 and RUNX2 expression in the chorionic tissues of normal pregnant women and RM patients were first examined, and the correlation between miR-149 and RUNX2 was analyzed. Subsequently, miR-149 was upregulated in HTR-8 cells or downregulated in BEWO cells, and then the changes in biological functions of trophoblasts in RM were detected. Furthermore, the expression of PTEN/Akt signaling pathway-related factors in trophoblasts was detected by western blot analysis. RESULTS: miR-149 expression was increased while RUNX2 expression was suppressed in RM patients, and miR-149 was negatively correlated with RUNX2. Overexpressed miR-149 induced cell apoptosis and inhibited cell activity, while reduced miR-149 in trophoblasts contributed to opposite experimental results. Moreover, miR-149 promoted the expression of PTEN and inhibited Akt phosphorylation by targeting RUNX2, thereby inhibiting trophoblast activity and promoting their apoptosis. CONCLUSION: Our study demonstrates that miR-149 knockdown halted the RM development through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.
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Carcinoma Hepatocelular/genética , MicroRNAs/genética , Transativadores/genética , Adulto , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , RNA Antissenso/genética , RNA Longo não Codificante/genética , Transativadores/metabolismoRESUMO
BACKGROUND The expression of TSPAN8 (tetraspanin 8) is upregulated in colorectal cancer; however, its roles in colorectal cancer progression are never been revealed. This work aimed to investigate TSPAN8 effects and the molecular basis in regulating colorectal cancer stemness. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and western blot analysis were used to detect the expression of TSPAN8 expression in clinical samples and the expression of stemness genes in colorectal cancer cells. Sphere forming analysis was performed to detect TSPAN8 effects on sphere forming ability of colorectal cancer cells. Co-IP and ChIP analysis were performed to confirm the molecular basis contributing to TSPAN8-mediated effects on colorectal cancer stemness. RESULTS TSPAN8 expression is increased in colorectal cancer tissues. Knockdown of TSPAN8 reduced the expression of stemness genes and sphere forming capacity in colorectal cancer cells. Mechanistically, TSPAN8 directly interacted ß-catenin and enhanced its protein expression, which is necessary for TSPAN8-mediated effects on colorectal cancer stemness. Conversely, ß-catenin directly bound to TSPAN8 promoter and enhanced TSPAN8 transcription. CONCLUSIONS TSPAN8 promotes colorectal cancer stemness through a positive TSPAN8/ß-catenin regulatory loop.
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Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Tetraspaninas/metabolismo , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Humanos , Cultura Primária de Células , Tetraspaninas/biossíntese , Tetraspaninas/genética , Transcriptoma , Via de Sinalização WntRESUMO
We demonstrate highly efficient energy harvesting devices for dim-light application under 200 lux irradiation using dye-sensitized solar cells (DSCs) and perovskite solar cells (PSCs). The high-efficiency DSCs are composed of cobalt-based redox mediators in 3-methoxypropionitrile (MPN) solvent with MK-2 sensitizer. With the introduction of under layer treatment and fine-tuning of compositions in cobalt-based electrolyte, the power conversion efficiency of cobalt-based DSCs achieves 16.0% under 200 lux illumination. That outperforms the best device using the conventional iodine-based electrolyte illuminated with the same light intensity. Especially, cobalt-based electrolyte system exhibits a higher open circuit voltage than iodine-based electrolyte counterpart. We also investigate perovskite solar cells under dim-light condition. PSCs show higher open circuit voltage and short circuit current density than DSCs with efficiency up to 23.4%. In this work, our results demonstrate the promising potential of DSCs and PSCs in the dim-light applications.
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Drought stress negatively affects wheat growth and yield. Application of drought agent is an effective way to improve crop drought tolerance, therefore increasing crop yield. Based on the structure of abscisic acid (ABA), Pyrabactin and coronatine (COR), we designed the target compound B2. To investigate the function of B2 in alleviating drought stress on wheat, the drought-resistant variety ND212 and drought-sensitive variety LX99 were used under hydroponic conditions. The results showed that B2 had a similar function with ABA, especially 0.01 µmol·L-1 B2. Under drought stress conditions, 0.01 µmol·L-1 B2 increased the water content of wheat, enhanced the osmotic adjustment ability of leaves, and reduced the toxicity of reactive oxygen species on cells. What's more, 0.01 µmol·L-1 B2 improved the expression level of ABA-responsive genes TaSnRK2.4 and TaMYB3R1. It also improved the expression level of drought-responsive genes TaSRHP and TaERF3. Taken together, B2 enhanced drought tolerance in wheat by activating ABA signaling pathway.
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Ácido Abscísico/análogos & derivados , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Ácido Abscísico/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Triticum/efeitos dos fármacos , Triticum/metabolismoRESUMO
Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential carcinogenic biomarker in certain types of cancer, such as melanoma. However, its function and clinical significance in non-small cell lung cancer (NSCLC) has not been well studied. Therefore, the present study aimed to analyze the association between ATF2/phosphorylated (p)-ATF2 expression and NSCLC malignant behavior, and discuss its clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression of ATF2 in NSCLC cell lines and fresh NSCLC tissue samples. In addition, immunohistochemistry (IHC) was performed to identify the location and expression of ATF2 and p-ATF2 (threonine 71) in paraffin-embedded sections of NSCLC and adjacent normal tissue. The results demonstrated that ATF2 was markedly overexpressed in the NSCLC cells and significantly overexpressed in the fresh NSCLC tissues compared with the control cells and samples (86 paraffin-embedded tissue sections), respectively (P<0.01). Further data demonstrated that ATF2 expression levels were significantly increased in tumor tissues compared to normal tissues and ATF2 was located in the cytoplasm and nucleus. ATF2 expression was closely associated with adverse clinical characteristics such as TNM stage (P=0.002), tumor size (P=0.018) and metastasis (P=0.027). In addition, nuclear p-ATF2 staining was positive in 65/86 samples of NSCLC. Furthermore, the Kaplan-Meier analysis indicated that patients with high levels of ATF2 and p-ATF2 expression had a significantly shorter overall survival compared with patients exhibiting a low expression (P<0.01 and P<0.05, respectively). Subsequent in vitro experiments revealed that cell growth decreased following knockdown of ATF2 expression using RNA interference, indicating that ATF2 may suppress cell proliferation. Taken together, the results of the present study demonstrated that ATF2 and p-ATF2 were significantly overexpressed in NSCLC tissues, and ATF2 and p-ATF2 overexpression predicted significantly worse outcomes for patients with NSCLC.
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AIM: The aim of this study was to explore the genes and pathways involved in the aggressive breast cancer cells. METHODS: The gene expression profiles of GSE40057, including four aggressive breast cell lines and six less aggressive cell lines, were downloaded from the Gene Expression Omnibus (GEO) database. The gene differential expression analysis was carried out with limma software with the method of Bayes for multiple tests. The gene ontology (GO) term enrichment and pathway cross-talk analysis were performed with the online tool of DAVID and Cytoscape software. RESULTS: A total of 401 differentially expressed genes (DEG), such as pentraxin 3 (PTX3), snail family zinc finger 2 (SNAI2), interleukin-8/6 (IL-8/6), osteonectin (SPARC), matrix metallopeptidase-1 (MMP-1) and Ras-related protein Rab-25 (Rab 25), were identified between aggressive and less aggressive cell lines. They were mainly enriched in the GO terms of response to wounding, negative regulation of cell proliferation and calcium binding. Pathways in cancer dysfunctionally interacted with glyoxylate and dicarboxylate metabolism (P < 0.0001), basal transcription factors (P < 0.0001), tyrosine metabolism (P < 0.0001), calcium signaling pathway (P = 0.0021), FcγR-mediated phagocytosis (P = 0.0022), metabolism of xenobiotics by cytochrome P450 (P = 0.0097) and phagosome (P = 0.0102). CONCLUSION: The screened aggressive cancer-associated DEG (PTX3, SNAI2, IL-8/6, SPARC, MMP-1 and Rab25) and significant pathways (calcium signaling pathway, tyrosine metabolism, alanine, aspartate and glutamate metabolism) give us new insights into the mechanism of aggressive breast cancer cells, and these DEG may become promising target genes in the treatment of metastatic breast cancer.
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Neoplasias da Mama/metabolismo , Receptor Cross-Talk , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Ontologia Genética , HumanosRESUMO
A novel magnetic Fe3O4 nanoparticles (MNPs) coupled with agarose (AMNPs) was synthesized using co-precipitation via alkaline condition and span-80 surfactants in organic solvent. Iminodiacetate was first attached to the MNPs through epichlorohydrin agent and then chelated with metal ions. The morphology and chemical properties of these prepared supports were characterized by scanning electron microscopy (SEM), X-ray power diffraction (XRD), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FT-IR). Among them, the Co(2+)-chelated AMNPs (AMNPs-ECH-IDA-Co(2+)) showed the second highest enzyme adsorption capacity of 1.81 mg/g particles, and achieved the largest activity recovery of 117% per protein gram in immobilization of ß-glucosidase (BGL). The Michaelis constant (Km) and Vmax of the immobilized BGL were 0.904 mM and 0.057 µmol/min, respectively, and its activation energy was much lower than the free form. Moreover, the immobilized enzyme exhibited enhanced thermostability and operational stability. It still retained more than 90% of its initial activity after being operated for 15 successive batches. This study demonstrates that the immobilized ß-glucosidase has a good prospect in industrial applications.
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Enzimas Imobilizadas/metabolismo , Nanopartículas de Magnetita/química , Proteínas de Plantas/metabolismo , beta-Glucosidase/metabolismo , Adsorção , Catálise , Cátions Bivalentes/química , Cobalto/química , Ativação Enzimática , Concentração de Íons de Hidrogênio , Microbiologia Industrial/métodos , Quelantes de Ferro , Cinética , Microscopia Eletrônica de Varredura , Modelos Moleculares , Tamanho da Partícula , Conformação Proteica , Estabilidade Proteica , Prunus/enzimologia , Sefarose/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios XRESUMO
Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.