scholarly journals Identification of an at-risk subpopulation with high immune infiltration based on the peroxisome pathway and TIM3 in colorectal cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Jinwen Yin ◽  
Hao Wang ◽  
Yuntian Hong ◽  
Anli Ren ◽  
Haizhou Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Subtype ◽  
Immune Infiltration ◽  
Tumor Mutational Burden ◽  
Domain 3 ◽  
High Level ◽  
Almost All ◽  
Checkpoint Genes ◽  
Cell Death Protein

Abstract Background Peroxisomes are pivotal metabolic organelles that exist in almost all eukaryote cells. A reduction in numbers and enzymatic activities of peroxisomes was found in colon adenocarcinomas. However, the role of peroxisomes or the peroxisome pathway in colorectal cancer (CRC) is not defined. Methods In the current study, a peroxisome score was calculated to indicate the activity of the peroxisome pathway using gene set variant analysis based on transcriptomic datasets. CIBERSORTx was chosen to infer enriched immune cells for tumors among subgroups. The SubMap algorithm was applied to predict its sensitivity to immunotherapy. Results The patients with a relatively low peroxisome score and high level of T-cell immunoglobulin and mucin domain 3 (TIM-3) presented the worse overall survival than others. Moreover, low peroxisome scores were associated with high infiltration of lymphocytes and poor prognosis in those CRC patients. Thus, a PERLowTIM3High CRC risk subpopulation was identified and characterized by high immune infiltration. The results also showed that CD8 T cells and macrophages highly infiltrated tumors of the PERLowTIM3High group, regardless of consortium molecular subtype and microsatellite instability status. This subgroup had the highest tumor mutational burden and overexpression of immune checkpoint genes. Further, the PERLowTIM3High group showed a higher probability of responding to programmed cell death protein-1-based immunotherapy. In addition, genes involved in peroxisomal metabolic processes in CRC were also investigated since peroxisome is a rather pleiotropic and highly metabolic organelle in cell. The results indicated that only those genes involved in fatty acid alpha oxidation could be used to stratify CRC patients as similar as peroxisome pathway genes. Conclusions We revealed the favorable prognostic value of the peroxisome pathway in CRC and provided a new CRC stratification based on peroxisomes and TIM3, which might be helpful for CRC diagnostics and personalized treatment.

Methyl mercury in the dutch rhine delta

1994 ◽  
Vol 30 (10) ◽  
pp. 213-219 ◽  
Author(s):  
Hendrik Pieters ◽  
Victor Geuke
Keyword(s):  
Suspended Matter ◽  
Methyl Mercury ◽  
Mercury Contamination ◽  
Benthic Organisms ◽  
Considerable Decrease ◽  
Continuous Sedimentation ◽  
Highly Correlated ◽  
High Level ◽  
Almost All

Samples of yellow eel from various locations in the Dutch Rhine area have been analyzed for trend monitoring of mercury since 1977. In the western Rhine delta mercury levels in eels have hardly changed since the seventies, whereas in the eastern part of the Dutch Rhine area a considerable decrease of mercury concentrations in eel has occurred. Because of continuous sedimentation of contaminated suspended matter transported from upstream regions, accumulation rates and concentrations of mercury in eel in the western Rhine delta remained at a relatively high level. Analyses of methyl mercury in biota have been performed to elucidate the role of methyl mercury in the mercury contamination of the Dutch Rhine ecosystem. Low percentages of methyl mercury were observed in zooplankton (3 to 35%). In benthic organisms (mussels) percentages of methyl mercury ranged from 30 to 57%, while in fish species and liver of aquatic top predator birds almost all the mercury was present in the form of methyl mercury (> 80%). During the period 1970-1990 mercury concentrations of suspended matter in the eastern Rhine delta have drastically decreased. These concentrations seemed to be highly correlated with mercury concentrations of eel (R = 0.84). The consequences of this relation are discussed.

scholarly journals Percepción de los entrenadores de alto rendimiento de atletismo: caracterización de su perfil polifacético (Perception of high performance track and field coaches: characterization of their multifaceted profile)

Retos ◽  
2015 ◽  
pp. 42-47
Author(s):  
Angeles Filgueira Perez
Keyword(s):  
High Performance ◽  
Target Population ◽  
Track And Field ◽  
Personal Qualities ◽  
High Level ◽  
Almost All ◽  
Methodological Aspects ◽  
The Ideal

En el presente estudio se ha tratado de obtener una aproximación al perfil ideal del entrenador de alto rendimiento en atletismo. En el mundo del deporte de alta competición, el entrenador debe desarrollar funciones de maestro, técnico y líder, lo cual hace difícil delimitar sus competencias (conocimientos, habilidades y cualidades personales). Por tanto, la principal motivación de este trabajo es establecer el papel que debe desempeñar el entrenador para la preparación física, técnica, táctica, psicológica y moral del deportista de alto nivel. Para ello, se ha considerado como población objeto de estudio al conjunto de entrenadores de alto rendimiento que en el momento de la investigación estuviesen activo, ya que interesaba realizar este estudio desde su propia perspectiva. Los datos recogidos forman parte de una investigación más amplia, llevada a cabo mediante encuesta, para la que se diseñó un cuestionario de 78 preguntas en el que se abarcaban tres temas: el perfil del entrenador y del deportista, así como la figura del formador de entrenadores en el Practicum. En este trabajo nos centramos en el primer tema y el análisis de la información obtenida nos permite concluir que la que práctica totalidad de los entrenadores de atletismo consideran necesario dominar con precisión los aspectos técnico-metodológicos. Además, consideran que su ética profesional debe estar regida por los principios de autonomía y beneficencia, de modo que valores como la honestidad y la justicia deben primar en el desarrollo de sus funciones.Abstract: In the current study, we have tried to get an approximation of the ideal profile of high performance coaches in athletics. In the high-level sports world, the coach must develop the role of teacher, technician and leader,  which makes it difficult to delimit  his/her competencies (knowledge, skills and personal qualities). Therefore, the main motivation of this work is to define the role that the coach plays in relation  to the physical, technical, tactical, psychological and moral preparation of elite athletes. Keeping this aim as an objective, we have considered as the target population the high performance coaches who are active at the time of the investigation, since we were interested  in knowing their own perspective. The data that was collected is a part of a wider investigation, conducted by a survey, for which we designed a questionnaire of 78 questions divided on three topics: the profile of the coach and the athlete, as well as the figure of the coach educator in the Practicum. In this work, we focus on the first topic and the analysis of the information that we obtained allows us to conclude that almost all the track and field coaches find it necessary to dominate the technical and methodological aspects. They also consider that professional ethics must be governed by the principles of autonomy and care that values   like honesty and justice must prevail in the performance of their work.

scholarly journals Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Morvarid Siri ◽  
Hamid Behrouj ◽  
Sanaz Dastghaib ◽  
Mozhdeh Zamani ◽  
Wirginia Likus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chemotherapy Resistance ◽  
Casein Kinase ◽  
Autophagy Flux ◽  
Casein Kinase 1 ◽  
Colorectal Cancer Cells ◽  
High Level ◽  
Casein Kinase 1 Alpha ◽  
Hct116 Cells

AbstractAdjuvant chemotherapy with 5-fluorouracil (5-FU) does not improve survival of patients suffering from a form of colorectal cancer (CRC) characterized by high level of microsatellite instability (MSI-H). Given the importance of autophagy and multi-drug-resistant (MDR) proteins in chemotherapy resistance, as well as the role of casein kinase 1-alpha (CK1α) in the regulation of autophagy, we tested the combined effect of 5-FU and CK1α inhibitor (D4476) on HCT116 cells as a model of MSI-H colorectal cancer. To achieve this goal, the gene expression of Beclin1 and MDR genes, ABCG2 and ABCC3 were analyzed using quantitative real-time polymerase chain reaction. We used immunoblotting to measure autophagy flux (LC3, p62) and flow cytometry to detect apoptosis. Our findings showed that combination treatment with 5-FU and D4476 inhibited autophagy flux. Moreover, 5-FU and D4476 combination therapy induced G2, S and G1 phase arrests and it depleted mRNA of both cell proliferation-related genes and MDR-related genes (ABCG2, cyclin D1 and c-myc). Hence, our data indicates that targeting of CK1α may increase the sensitivity of HCT116 cells to 5-FU. To our knowledge, this is the first description of sensitization of CRC cells to 5-FU chemotherapy by CK1α inhibitor. Graphic abstract

scholarly journals The Association of Aberrant Expression of FGF1 and mTOR-S6K1 in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Tinghui Duan ◽  
Diyuan Zhou ◽  
Yizhou Yao ◽  
Xinyu Shao
Keyword(s):  
Colorectal Cancer ◽  
Malignant Neoplasms ◽  
Aberrant Expression ◽  
Protein Levels ◽  
And Migration ◽  
High Level ◽  
Proliferation And Migration

Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide, and the effect of treatments is limited. Fibroblast growth factor 1 (FGF1) has been involved in a wide variety of several malignant diseases and takes part in the tumorigenesis of CRC. However, the function and mechanism of FGF1 in CRC remains elusive. In this study, the results indicated that FGF1 is elevated in CRC tissues and linked with poor prognosis (P < 0.001). In subgroup analysis of FGF1 in CRC, regardless of any clinic-factors except gender, high level FGF1 expression was associated with markedly shorter survival (P < 0.05). In addition, the expression of p-S6K1 and FGF1 was not associated in normal tissue (P = 0.781), but their expression was closely related in tumor tissue (P = 0.010). The oncogenic role of FGF1 was determined using in vitro and in vivo functional assays. FGF1 depletion inhibited the proliferation and migration of CRC cells in vitro and vivo. FGF1 was also significantly correlated with mTOR-S6K1 pathway on the gene and protein levels (P < 0.05). In conclusion, FGF1 acts as a tumor activator in CRC, and against FGF1 may provide a new visual field on treating CRC, especially for mTORC1-targeted resistant patients.

scholarly journals Host–MicroRNA–Microbiota Interactions in Colorectal Cancer

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 270 ◽  
Author(s):  
Ce Yuan ◽  
Clifford J. Steer ◽  
Subbaya Subramanian
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Tumor Cells ◽  
Immune Cell ◽  
Review Article ◽  
Microbiota Composition ◽  
Cell Fractions ◽  
High Level ◽  
Gut Microbiota Composition

Changes in gut microbiota composition have consistently been observed in patients with colorectal cancer (CRC). Yet, it is not entirely clear how the gut microbiota interacts with tumor cells. We know that tumor cells undergo a drastic change in energy metabolism, mediated by microRNAs (miRNAs), and that tumor-derived miRNAs affect the stromal and immune cell fractions of the tumor microenvironment. Recent studies suggest that host intestinal miRNAs can also affect the growth and composition of the gut microbiota. Our previous CRC studies showed a high-level of interconnectedness between host miRNAs and their microbiota. Considering all the evidence to date, we postulate that the altered nutrient composition and miRNA expression in the CRC microenvironment selectively exerts pressure on the surrounding microbiota, leading to alterations in its composition. In this review article, we present our current understanding of the role of miRNAs in mediating host–microbiota interactions in CRC.

scholarly journals Prognostic and Immunological Role of THBS2 in Colorectal cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bin Deng ◽  
Xiu-Ping Liu ◽  
Xiong Wang
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Histological Subtype ◽  
Free Survival ◽  
Immune Infiltration ◽  
Prognostic Analysis ◽  
Functional Mechanisms ◽  
Disease Free

Objective. Thrombospondin 2 (THBS2) acts as oncogenic or tumor suppressive gene in diverse cancers. Here we studied the prognostic and immunological role of THBS2 in colorectal cancer (CRC) using bioinformatic analysis. Methods. The genetic and protein expression of THBS2 in CRC were explored across several databases, including ONCOMINE, GEPIA2, TIMER 2.0, UALCAN and HPA databases. Correlation between THBS2 expression and clinical features in CRC was assessed using UALCAN tool. Prognostic analysis was performed using GEPIA2 and PrognoScan. Immune infiltration correlation with THBS2 in CRC was investigated with TIMER 2.0 and TISIDB. THBS2 binding and correlated genes were analyzed using String, GEPIA2, and TIMER 2.0. Results. THBS2 was significantly higher in CRC across multiple databases. Age and histological subtype were correlated with THBS2 level. High THBS2 expression correlated with short overall and disease-free survival. THBS2 expression was positively correlated with immune infiltrates in CRC. Moreover, extracellular matrix structural constituent and organization, PI3K-Akt pathway, were involved in the functional mechanisms of THBS2. Conclusions. THBS2 correlates with poor prognosis and immune infiltration in CRC. THBS2 may act as a prognostic and immunological biomarker for CRC.

scholarly journals Features of competitive activity of qualified football players at the stage of preparation for higher achievements taking into account the game role

2020 ◽  
pp. 16-20
Author(s):  
В. Balan
Keyword(s):  
Motor Activity ◽  
Individual Characteristics ◽  
Football Players ◽  
Competitive Activity ◽  
Intense Training ◽  
High Level ◽  
Almost All ◽  
Number Of Passes ◽  
Competitive Activities

At present, a significant amount of research has been performed to study the motor activity of football players in the conditions of competitions, as a result of which data on the nature and scope of players' actions both with and without the ball have been obtained. The article considers the structure of technical and tactical actions of qualified football players in competitive activities at the stage of preparation for higher achievements, taking into account the role of the game. The technical and tactical actions of football players in competitive activities are analyzed, taking into account the game role. The results of the study of the structure of technical and tactical actions of qualified football players at the stage of preparation for higher achievements in competitive activities, taking into account the role of the game allowed to establish a high level of performance of almost all techniques, largely due to team functions. It is determined that the maximum possible indicators at the stage of preparation for higher achievements are largely due to the course of natural age development. In the process of attacking actions, players use from 2 to 14 passes. Tactical combinations in 2-4 passes more often lead to taking the goal. As the number of passes increases, the effectiveness of the attacks decreases. Work on improving the relevant physical qualities can be effective only if the time coincides with purposeful intense training with the peak of age development of a certain quality. It is proved that at this stage it is necessary to gradually increase the level of general and special physical training of football players aged 19-20, taking into account individual characteristics and game role.

scholarly journals MiR-208a-3p functions as an oncogene in colorectal cancer by targeting PDCD4

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Henglan Wu ◽  
Lele Xu ◽  
Yaou Chen ◽  
Chunfang Xu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Biological Function ◽  
Invasion And Migration ◽  
Functional Assays ◽  
Direct Target ◽  
And Migration ◽  
Cell Death Protein

AbstractAccumulating evidences have shown microRNAs (miRNAs) play important roles in the progression of human cancers including colorectal cancer (CRC). However, the biological function and molecular mechanism of miRNAs in CRC still remains to be further investigated. Using microarray, we found and confirmed that miR-208a-3p was up-regulated in CRC tissues. Its high expression was statistically associated with distant metastasis and TNM stage. Functional assays revealed inhibition of miR-208a-3p suppressed proliferation, invasion and migration, and induced cell apoptosis of CRC cells. Moreover, we identified programmed cell death protein 4 (PDCD4), a well-known tumor suppressor, is a direct target of miR-208a-3p. We also found that overexpression of PDCD4 suppressed cell proliferation, invasion, and migration. Importantly, silencing of PDCD4 efficiently abrogated the promoting effects on CRC cells proliferation, invasion, and migration caused by inhibition of miR-208a-3p. Our findings confirmed the oncogenic role of miR-208a-3p via targeting PDCD4 in CRC, identifying miR-208a-3p as a potential diagnosis and therapeutic biomarker for CRC.

scholarly journals Features of cash audit in the conditions of ensuring the enterprise’s cybersecurity

2021 ◽  
pp. 16-22
Author(s):  
Hanna BULKOT ◽  
Iryna MIRKO
Keyword(s):  
Information Security ◽  
Business Environment ◽  
General Strategy ◽  
Economic Activities ◽  
Box Office ◽  
Demand Deposits ◽  
High Level ◽  
Almost All ◽  
Significant Attention

Introduction. Today, cash accounting transactions are important in the organization and activities of any enterprise, because they cover almost all areas of its financial and economic activities and require significant attention from the auditor, as during their implementation may occur various violations and overuses by officials of the enterprise. Since cash is the most mobile asset and in today’s business environment, basically, all cash payments are non-cash (electronically), there is a high probability of overuse by third parties. Therefore, performing an audit of cash operations and implementation cybersecurity of data about their calculations is an extremely important issue to increase the efficiency of accounting and management them in enterprises. The purpose of the paper is to determine the role of cash audit for the company and ways to increase efficiency of its implementation in terms of cybersecurity of the enterprise. Results. The article acquaints with the work of various economists on the interpretation of the concept of “cash”, so we can say that cash – are the most liquid assets of the company, which are in the form of cash at the box office, cash in the bank accounts and demand deposits. The general strategy and the plan of cash audit in terms of cybersecurity of the enterprise are considered. The main reasons occurrence of problem ensuring of cybersecurity of operations with cash of the enterprise are indicated. An appropriate level of information security for cash transactions has been proposed in order to prevent threats in the enterprise. Ways to damage information security in the process of conducting an audit of cash of the enterprise are improved. Conclusions. Cash audit must be conducted in conjunction with the implementation of the necessary cybersecurity measures in the enterprise in order to reduce the level of disclosure, leakage and unauthorized access to confidential information about cash and to ensure a high level of protection of the company’s own information sources.

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