Search results for: constitutive expression

Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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Authors: Andrey Angorsky

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In the article an issue about the possible number of fundamental physical interactions is studied. The theory of similarity on the dimensionless quantity as the damping ratio serves as the instrument of analysis. The structure with the features of Higgs field comes out from non-commutative expression for this ratio. The experimentally checked up supposition about the nature of dark energy is spoken out.

Keywords: damping ratio, dark energy, dimensionless quantity, fundamental physical interactions, Higgs field, non-commutative expression

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Authors: Hanan Alsaeid Alshenawy

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Background: Cervical dysplasia, which is potentially precancerous, has increased in young women. Detection of cervical is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki67 in cervical intraepithelial lesions and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Methods: 75 specimens were analyzed including 15 cases CIN 1, 28 CIN 2, 20 CIN 3, and 12 cervical squamous carcinoma, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. Results: p16 expression increased during the progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappear in carcinoma. Strong Ki-67 expression was observed with high grades CIN and carcinoma. p16, HPV L1 and Ki67 were sensitive but with variable specificity in detecting CIN lesions. Conclusions: p16, HPV L1 and Ki67 are useful set of markers in establishing the risk of high-grade CIN. They complete each other to reach accurate diagnosis and prognosis.

Keywords: p16, HPV L1, Ki67, CIN, cervical carcinoma

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Authors: Marek Pawlikowski, Krzysztof Jankowski, Konstanty Skalski, Anna Makuch

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Nanoindentation or depth-sensing indentation (DSI) technique has proven to be very useful to measure mechanical properties of various tissues at a micro-scale. Bone tissue, both trabecular and cortical one, is one of the most commonly tested tissues by means of DSI. Most often such tests on bone samples are carried out to compare the mechanical properties of lamellar and interlamellar bone, osteonal bone as well as compact and cancellous bone. In the paper, a relation between stress and strain for human trabecular bone is presented. The relation is based on the results of nanoindentation tests. The formulation of a constitutive model for human trabecular bone is based on nanoindentation tests. In the study, the approach proposed by Olivier-Pharr is adapted. The tests were carried out on samples of trabecular tissue extracted from human femoral heads. The heads were harvested during surgeries of artificial hip joint implantation. Before samples preparation, the heads were kept in 95% alcohol in temperature 4 Celsius degrees. The cubic samples cut out of the heads were stored in the same conditions. The dimensions of the specimens were 25 mm x 25 mm x 20 mm. The number of 20 samples have been tested. The age range of donors was between 56 and 83 years old. The tests were conducted with the indenter spherical tip of the diameter 0.200 mm. The maximum load was P = 500 mN and the loading rate 500 mN/min. The data obtained from the DSI tests allows one only to determine bone behoviour in terms of nanoindentation force vs. nanoindentation depth. However, it is more interesting and useful to know the characteristics of trabecular bone in the stress-strain domain. This allows one to simulate trabecular bone behaviour in a more realistic way. The stress-strain curves obtained in the study show relation between the age and the mechanical behaviour of trabecular bone. It was also observed that the bone matrix of trabecular tissue indicates an ability of energy absorption.

Keywords: constitutive model, mechanical behaviour, nanoindentation, trabecular bone

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Authors: Ikenna Michael Onuorah

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The relentless march of globalization in architecture has led to a homogenization of built environments, often characterized by an overreliance on imported, resource-intensive materials and a disregard for local cultural contexts. This research posits that such practices pose significant environmental and cultural perils, trapping communities in "caged concrete jungles" devoid of both ecological sustainability and a meaningful connection to their heritage. Through a mixed-method approach encompassing quantitative and qualitative data analysis, the study investigated the impacts of neglecting local materials and cultural expression in architectural design. The research is anticipated to yield significant insights into the multifaceted consequences of neglecting locally available materials and cultural expression in architecture. It creates a compelling case for reasserting local materials and cultural expression in architectural design. Based on the anticipated research findings, the study proposed series of actionable recommendations for architects, policymakers, and communities to promote sustainable and culturally sensitive built environments. This will serve as a wake-up call, urging architects, policymakers, and communities to break free from the confines of "caged concrete jungles" and embrace a more sustainable and culturally sensitive approach to design.

Keywords: sustainability, cultural identity, building materials, sustainable dsigns

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Authors: Farshid Hajati, Soheila Gheisari, Ali Cheraghian, Yongsheng Gao

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This paper presents a new Surface Geodesic Derivative Pattern (SGDP) for matching textured deformable 3D surfaces. SGDP encodes micro-pattern features based on local surface higher-order derivative variation. It extracts local information by encoding various distinctive textural relationships contained in a geodesic neighborhood, hence fusing texture and range information of a surface at the data level. Geodesic texture rings are encoded into local patterns for similarity measurement between non-rigid 3D surfaces. The performance of the proposed method is evaluated extensively on the Bosphorus and FRGC v2 face databases. Compared to existing benchmarks, experimental results show the effectiveness and superiority of combining the texture and 3D shape data at the earliest level in recognizing typical deformable faces under expression, illumination, and pose variations.

Keywords: 3D face recognition, pose, expression, surface matching, texture

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Authors: Behailu Bezabih Ayele

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Illustrative expressions in art education and in overall learning are being given increasing attention in the transmission of knowledge. The objective of this paper, therefore, is to present an analysis of graffiti on school desks-a way of smuggling knowledge on the edge of classroom education and learning. The methodological approach focuses on the systematic collection and selection of desk graffiti. Four schools are chosen to reflect socioeconomic status and gender composition. The analysis focused on the categorization of graffiti by genre. This was followed by an analysis of the style, intensity as well as content of the messages in terms of overall social impacts. The paper grounds the analysis by reviewing the literature on modern education and art education in the Ethiopian context, as well as the place of desk graffiti. The findings generally show that the school desks and the school environment, by and large, have managed to serve as vessels through which formal and informal knowledge is acquired, transmitted, engrained into the students and transformed into messages by the students. The desks have also apparently served as a springboard to maximize the interfaces between several ideas and disciplines and communications. However, the very fact that the desks serve as massive channels of expression and knowledge transmission also points to a lack of breadth availability of channels of expression, perhaps confounding the ability of classrooms as means of outlet of expression and documentation for the students. This points to the need for efforts in education policy and funding of artistic endeavors for young students.

Keywords: artistic expression, desk graffiti, education, school children, Ethiopia

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Salman Naveed, Nitant Gandhi, Grant Billings, Zachary Jones, B. Todd Campbell, Michael Jones, Sachin Rustgi

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Cotton (Gossypium spp.) is the primary source of natural fiber in the U.S. and a major crop in the Southeastern U.S. Despite constant efforts to increase the cotton fiber yield, the yield gain has stagnated. Therefore, we undertook a novel approach to improve the cotton fiber yield by altering its growth habit from perennial to annual. In this effort, we identified genotypes with high-expression alleles of five floral induction and meristem identity genes (FT, SOC1, FUL, LFY, and AP1) from an upland cotton mini-core collection and crossed them in various combinations to develop cotton lines with annual growth habit, optimal flowering time and enhanced productivity. To facilitate the characterization of genotypes with the desired combinations of stacked alleles, we identified markers associated with the gene expression traits via genome-wide association analysis using a 63K SNP Array (Hulse-Kemp et al. 2015 G3 5:1187). Over 14,500 SNPs showed polymorphism and were used for association analysis. A total of 396 markers showed association with expression traits. Out of these 396 markers, 159 mapped to genes, 50 to untranslated regions, and 187 to random genomic regions. Biased genomic distribution of associated markers was observed where more trait-associated markers mapped to the cotton D sub-genome. Many quantitative trait loci coincided at specific genomic regions. This observation has implications as these traits could be bred together. The analysis also allowed the identification of candidate regulators of the expression patterns of these floral induction and meristem identity genes whose functions will be validated via virus-induced gene silencing.

Keywords: cotton, GWAS, QTL, expression traits

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Authors: Mohammed Abdelsabour-Khalaf, F. Yusuf , B Brand-Saberi

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Purpose: Applications of nanotechnology nowadays extended to include a wide range of scientific areas such electron micrscopy and gene expression. The aim of the current study was to investigate the developmental expression pattern of genes involved in human glomerulo-nephropathies associated with massive proteinuria and podocyte differentiation using the chicken mesonephros as a model system. Method: We performed in situ hybridization using chicken specific mRNA probes for genes expressed in the early nephron and slit diaphragm genes. The probes used were cNeph1, cNeph2, cSim1, cLmx1b, and cAtoh8. Chicken embryos from Hamburger Hamilton developmental stage HH19 (E3) to HH 34 (E9) were used for the in situ hybridization (ISH). ISH was performed on whole mount embryos which were sectioned by vibratome. Results: Our result show that Neph1, Neph2, Sim1. Lmx1b and Atoh8 genes are dynamically expressed during nephron morphogenesis and Neph1 and Atoh8 are also specifically expressed in the podocytes during late stages of differentiation. Conclusion: We conclude from our results that the genes implicated in congenital and acquired glomerulo-nephropathies like Neph1 and Neph2 are dynamically expressed during mesonephros development pointing towards a role in the formation of the filtration barrier and the differentiation of the mesonephric podocytes. Thus the avian mesonephros could serve as a model to study human kidney diseases.

Keywords: mesonephros, chicken embryo, gene expression, immunohistochemistry

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Yan Zeng, Li Tao, Liujun Han, Tianye Zhang, Yongan Yu, Kaijun Ma, Long Chen

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Mechanical asphyxia is one of the main cause of death; however, death by mechanical asphyxia may be difficult to prove in court, particularly in cases in which corpses exhibit no obvious signs of asphyxia. To identify a credible biomarker of asphyxia, we first examined the expression levels of all the mRNAs in human cardiac tissue specimens subjected to mechanical asphyxia and compared these expression levels with those of the corresponding mRNAs in specimens subjected to craniocerebral injury. A total of 119 differentially expressed mRNAs were selected and the expression levels of these mRNAs were examined in 44 human cardiac tissue specimens subjected to mechanical asphyxia, craniocerebral injury, hemorrhagic shock and other causes of death. We found that DUSP1 and KCNJ2 were up-regulated in tissue specimens of mechanical asphyxia compared with control tissues, with no significant correlation between age, environmental temperature and PMI, indicating that DUSP1 and KCNJ2 may associate with mechanical asphyxia-induced death and can thus serve as useful biomarkers of death by mechanical asphyxia.

Keywords: mechanical asphyxia, biomarkers, DUSP1, KCNJ2, cardiac tissue

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Authors: AliAkbar Hafezi, Jahanbakhsh Asadi, Majid Shahbazi, Alijan Tabarraei, Nader Mansour Samaei, Hamed Sheibak, Roghaye Gharaei

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Background: Breast cancer is the most common cancer in women. In most cancer cells, apoptosis is blocked. As for the importance of apoptosis in cancer cell death and the role of different genes in its induction or inhibition, the search for compounds that can begin the process of apoptosis in tumor cells is discussed as a new strategy in anticancer drug discovery. The aim of this study was to investigate the effect of Naringenin (NGEN) on the apoptosis in the T47D cell line of breast cancer. Materials and Methods: In this experimental study in vitro, the T47D cell line of breast cancer was selected as a sample. The cells at 24, 48, and 72 hours were treated with doses of 20, 200, and 1000 µm of Naringenin. Then, the transcription levels of the genes involved in apoptosis, including Bcl-2, Bax, Caspase 3, Caspase 8, Caspase 9, P53, PARP-1, and FAS, were assessed using Real Time-PCR. The collected data were analyzed using IBM SPSS Statistics 24.0. Results: The results showed that Naringenin at doses of 20, 200, and 1000 µm in all three times of 24, 48, and 72 hours increased the expression of Caspase 3, P53, PARP-1 and FAS and reduced the expression of Bcl-2 and increased the Bax/Bcl-2 ratio, nevertheless in none of the studied doses and times, had not a significant effect on the expression of Bax, Caspase 8 and Caspase 9. Conclusion: This study indicates that Naringenin can reduce the growth of some cancer cells and cause their deaths through increased apoptosis and decreased anti-apoptotic Bcl-2 gene expression and, resulting in the induction of apoptosis via both internal and external pathways.

Keywords: apoptosis, breast cancer, naringenin, T47D cell line

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Ovidiu Anemtoaicei

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This paper offers a possible answer to the question of what it means to think about men and masculinities through the philosophy of sexual difference as developed by Luce Irigaray, employing Gilles Deleuze’s concept of 'critique' and arguing, at the same time, for a concept of 'becoming-man' as an expression of this answer. First, while examining the nature of the role of male bodies underlying the theorizing of men and masculinities in the field of the Critical Studies of Men and Masculinities, the paper argues for a turn to sexual difference theory as an answer to the 'gap' between the representations on male bodies and their participation in thought and masculine subjective production. Secondly, sharing Luce Irigaray’s critique of Western thought, the paper explores alternative morphological bodily 'locations' for rethinking male imaginary in relation to male embodiments, on the one hand, and in relation to the maternal and the feminine, on the other hand. Thirdly, the paper develops the idea that a phenomenologically-influenced approach towards male bodies might be productive, especially when thought through Irigaray’s sexual difference as a relational and experiential ontology. Finally, while showing that Irigaray and Deleuze share a similar critique of Western philosophical thought and of the masculine historical subject, it proposes a rethinking of the concept of 'becoming-man' as an assemblage meeting between Irigaray’s theory of sexual difference and Deleuze and Guattari’s nomadologic project, as a possibility of thinking change in men’s masculine subjective constitution in relation to both women and other men. As far as the ethical implications of such rethinking are concerned, the paper urges for the cultivation of a masculine culture of stepping back and its constitutive political, social and cultural practices so as to make possible the construction of new spaces that would allow for the becoming of at least two subjects based on the respect for their differences.

Keywords: feminist philosophy, male bodies, masculinities, phenomenology, sexual difference

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Authors: Yungeng Xie, Cong Liu, Yi Liu, Xuanao Wan

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The study aims to explore microblog users’ emotion expression and sharing behaviors on the Chinese microblog (Weibo). The first theme of study analyzed whether microblog emotions impact readers’ message sharing behaviors, specifically, how the strength of emotion (positive and negative) in microblog messages facilitate/inhibit readers’ sharing behaviors. The second theme compared the differences among the three types of microblog users (i.e., verified enterprise users, verified individual users and unverified users) in terms of their profiles and microblog behaviors. A total of 7114 microblog messages about 24 hot public events in China were sampled from Sina Weibo. The first study results show that strength of negative emotions that microblog messages carry significantly increase the possibility of the message being shared. The second study results indicate that there are significant differences across the three types of users in terms of their emotion expression and its influence on microblog behaviors.

Keywords: emotion expression, information diffusion, microblog, sharing

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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Authors: Harika Atmaca, Emir Bozkurt, Latife Merve Oktay, Selim Uzunoglu, Ruchan Uslu, Burçak Karaca

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Microarrays have been developed for highly parallel enzyme-linked immunosorbent assay (ELISA) applications. The most common protein arrays are produced by using multiple monoclonal antibodies, since they are robust molecules which can be easily handled and immobilized by standard procedures without loss of activity. Protein expression profiling with protein array technology allows simultaneous analysis of the protein expression pattern of a large number of proteins. Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate, Ecteinascidia turbinata, has been shown to have antitumor effects. Here, we used a novel proteomic approach to explore the mechanism of action of trabectedin in prostate cancer cell line PC-3 by apoptosis antibody microarray. XTT cell proliferation kit and Cell Death Detection Elisa Plus Kit (Roche) was used for measuring cytotoxicity and apoptosis. Human Apoptosis Protein Array (R&D Systems) which consists of 35 apoptosis related proteins was used to assess the omic protein expression pattern. Trabectedin induced cytotoxicity and apoptosis in prostate cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL R2/DR5, TNF R1/TNFRSF1A, FADD were significantly increased by 4.0-, 21.0-, 4.20- and 11.5-fold by trabectedin treatment in PC-3 cells. Moreover, mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, and Cleaved Caspase-3 expressions were induced by 2.68-, 2.07-, 2.8-, and 4.5-fold and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 3.5- and 5.2-fold in PC-3 cells. Proteomic (antibody microarray) analysis suggests that the mechanism of action of trabectedin may be exerted via the induction of both intrinsic and extrinsic apoptotic pathways. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

Keywords: trabectedin, prostate cancer, omic protein expression profile, apoptosis

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Authors: Paula Buldres, Jorge Toledo

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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

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Authors: Narimen Hamdini

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The mastery of a foreign language often implies adequate speaking competency and communication. However, it has been marked that the Algerian students’ oral performance is affected by the lack of language practice opportunities. The present study aims at investigating the impact of cooperative learning strategies on the learners’ oral performance through integrating some learning strategies in oral expression classes. Thus, a quasi-experimental study with one group pretest-posttest design was conducted. A convenience sample of 27 second-year students from the University of Jijel, Algeria, was taught during three consecutive weeks through cooperative learning activities in conjunction with regular language instruction in oral expression classes. Regarding data collection, the study makes use of students’ questionnaire, a semi-structured interview with the teachers of oral expression, and orally scored pre-posttest. While the students’ questionnaire aims at exploring the learners ‘speaking difficulties and attitudes towards the implementation of the strategy, the semi-structured interview aims at revealing the teachers’ instructional practices and attitudes toward the integration of CL activities. Finally, the oral tests were conducted before and after the intervention to measure the effect of the strategy on the learners’ oral production. The findings showed that the experimental group scored higher in the posttest. Cooperative learning promotes not only the learner’s oral performances, but also motivation and social skills. Consequently, its implementation in the oral expression classes is validated and recommended.

Keywords: cooperative learning, learning, oral performance, teaching

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Authors: Mukesh N. Kher, Anju P. Kunjadia, Dev S. Nauriyal, Chaitanya G. Joshi, Navin R. Sheth, Vaibhav D. Bhatt

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In-vivo immunotherapeutic potential on cytokines production and antibacterial activity of a topical herbal gel was evaluated in two breeds of cattle in bovine subclinical mastitis. The response to treatment was evaluated by enumerating somatic cell count (SCC), determining total bacterial count and studying the expression of different cytokines like (interleukin 6, 8, 12, GMCSF, interferon–γ and TNF‑α). The pre‑ and post‑treatment SCC in mastitic quarters did not differ statistically-significantly. However, total bacterial count declined significantly from day 0 onwards in both the breeds. Significant differences (P < 0.01) were observed in all types of cytokines production on day 0, 5, and 21 post last treatments in both the breeds. The comparison of cytokine expression profiles between crossbred and Gir cattle affirmed a significant difference in expression of IL-6 and TNF-α. The topical herbal gel showed immunomodulatory and antimicrobial activities in subclinical mastitis, and therefore the work supports its use as substitute herbal therapy against subclinical mastitis in bovines.

Keywords: antibacterial activity, immunomodulation, herbal gel, subclinical mastitis

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Authors: J. Vinay , Kusumbati Besra, Niharika Pattnaik, Shivaram Prasad Singh, Manjusha Dixit

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Gallbladder cancer (GBC) is rare but highly malignant cancer; its prevalence is more in certain geographical regions and ethnic groups, which include the Northern and Eastern states of India. Previous studies in India have reported genetic predisposition as one of the risk factors in GBC pathogenesis. Although the matrix metalloproteinase-14 (MMP14) is a well-known modulator of the tumor microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in the genetic predisposition for GBC is completely unknown. We elucidated the role of MMP14 promoter variants as genetic risk factors and their implications in expression modulation. We screened MMP14 promoter variants association with GBC using Sanger’s sequencing in approximately 300 GBC and 300 control subjects and 26 GBC tissue samples of Indian ethnicity. The immunohistochemistry was used to check the MMP14 protein expression in GBC tissue samples. The role of promoter variants on expression levels was elucidated using a luciferase reporter assay. The variants rs1004030 (p-value = 0.0001) and rs1003349 (p-value = 0.0008) were significantly associated with gallbladder cancer. The luciferase assay in two different cell lines, HEK-293 (p = 0.0006) and TGBC1TKB (p = 0.0036) showed a significant increase in relative luciferase activity in the presence of risk alleles for both the single nucleotide polymorphisms (SNPs). Similarly, genotype-phenotype correlation in patients samples confirmed that the presence of risk alleles at rs1004030 and rs1003349 increased MMP14 expression. Overall, this study unravels the genetic association of MMP14 promoter variants with gallbladder cancer, which may contribute to pathogenesis by increasing its expression.

Keywords: gallbladder cancer, matrix metalloproteinase-14, single nucleotide polymorphism, case control study, genetic association study

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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Deer antler, traditionally used as a tonic and valuable drug in oriental medicine, has been considered to possess bone-strengthening activity. The upper section, mid section, and base of the antler has been known to exhibit different biological properties. Present study was performed to examine the effects of different parts of deer antler extract (DH) on osteogenic gene expressions in MG-63 cells and longitudinal bone growth in adolescent male rats. The expressions of osteogenic genes, collagen, alkaline phosphatase, osteocalcin, and osteopontin, were measured by quantitative real-time PCR. Longitudinal bone growth was measured in 3-week-old male Sprague-Dawley rats using fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and bone morphogenetic protein-2 (BMP-2) were measured. Collagen and osteocalcin mRNA expressions were increased by all three parts of the DH treatment while osteopontin gene expression was not affected by any of the DH treatment. Alkaline phosphatase gene expression was increased by upper and mid part of DH while base part of DH fails to affect alkaline phosphatase gene expression. The upper and mid parts of the DH treatment enhanced longitudinal bone growth and total height of growth plate. The induction of BMP-2 protein expression in growth plate assessed by immunostaining was also promoted by upper and mid parts of the DH treatment. These results suggest that DH, especially upper and mid parts, stimulate osteogenic gene expressions and have the effect on bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

Keywords: bone morphogenetic protein-2, deer antler, longitudinal bone growth, osteogenic genes

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Authors: Hala Alshamlan, Ghada Badr, Yousef Alohali

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Cancer is one of the dreadful diseases, which causes considerable death rate in humans. DNA microarray-based gene expression profiling has been emerged as an efficient technique for cancer classification, as well as for diagnosis, prognosis, and treatment purposes. In recent years, a DNA microarray technique has gained more attraction in both scientific and in industrial fields. It is important to determine the informative genes that cause cancer to improve early cancer diagnosis and to give effective chemotherapy treatment. In order to gain deep insight into the cancer classification problem, it is necessary to take a closer look at the proposed gene selection methods. We believe that they should be an integral preprocessing step for cancer classification. Furthermore, finding an accurate gene selection method is a very significant issue in a cancer classification area because it reduces the dimensionality of microarray dataset and selects informative genes. In this paper, we classify and review the state-of-art gene selection methods. We proceed by evaluating the performance of each gene selection approach based on their classification accuracy and number of informative genes. In our evaluation, we will use four benchmark microarray datasets for the cancer diagnosis (leukemia, colon, lung, and prostate). In addition, we compare the performance of gene selection method to investigate the effective gene selection method that has the ability to identify a small set of marker genes, and ensure high cancer classification accuracy. To the best of our knowledge, this is the first attempt to compare gene selection approaches for cancer classification using microarray gene expression profile.

Keywords: gene selection, feature selection, cancer classification, microarray, gene expression profile

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Authors: Hannah R. Devens, Phillip L. Davidson, Dione Deaker, Kathryn E. Smith, Gregory A. Wray, Maria Byrne

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Marine invertebrate species with calcifying larvae are especially vulnerable to ocean acidification (OA) caused by rising atmospheric CO₂ levels. Acidic conditions can delay development, suppress metabolism, and decrease the availability of carbonate ions in the ocean environment for skeletogenesis. These stresses often result in increased larval mortality, which may lead to significant ecological consequences including alterations to the larval settlement, population distribution, and genetic connectivity. Importantly, many of these physiological and developmental effects are caused by genetic and molecular level changes. Although many studies have examined the effect of near-future oceanic pH levels on gene expression in marine invertebrates, little is known about the impact of OA on gene expression in a developmental context. Here, we performed mRNA-sequencing to investigate the impact of environmental acidity on gene expression across three developmental stages in the sea urchin Heliocidaris erythrogramma. We collected RNA from gastrula, early larva, and 1-day post-metamorphic juvenile sea urchins cultured at present-day and predicted future oceanic pH levels (pH 8.1 and 7.7, respectively). We assembled an annotated reference transcriptome encompassing development from egg to ten days post-metamorphosis by combining these data with datasets from two previous developmental transcriptomic studies of H. erythrogramma. Differential gene expression and time course analyses between pH conditions revealed significant alterations to developmental transcription that are potentially associated with pH stress. Consistent with previous investigations, genes involved in biomineralization and ion transport were significantly upregulated under acidic conditions. Differences in gene expression between the two pH conditions became more pronounced post-metamorphosis, suggesting a development-dependent effect of OA on gene expression. Furthermore, many differences in gene expression later in development appeared to be a result of broad downregulation at pH 7.7: of 539 genes differentially expressed at the juvenile stage, 519 of these were lower in the acidic condition. Time course comparisons between pH 8.1 and 7.7 samples also demonstrated over 500 genes were more lowly expressed in pH 7.7 samples throughout development. Of the genes exhibiting stage-dependent expression level changes, over 15% of these diverged from the expected temporal pattern of expression in the acidic condition. Through these analyses, we identify novel candidate genes involved in development, metabolism, and transcriptional regulation that are possibly affected by pH stress. Our results demonstrate that pH stress significantly alters gene expression dynamics throughout development. A large number of genes differentially expressed between pH conditions in juveniles relative to earlier stages may be attributed to the effects of acidity on transcriptional regulation, as a greater proportion of mRNA at this later stage has been nascent transcribed rather than maternally loaded. Also, the overall downregulation of many genes in the acidic condition suggests that OA-induced developmental delay manifests as suppressed mRNA expression, possibly from lower transcription rates or increased mRNA degradation in the acidic environment. Further studies will be necessary to determine in greater detail the extent of OA effects on early developing marine invertebrates.

Keywords: development, gene expression, ocean acidification, RNA-sequencing, sea urchins

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Authors: S. Shujan, A. T. Rupasinghe, N. L. Gunawardena

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Numerous studies have determined that there is a direct correlation between the successful interviewee and the nonverbal behavioral patterns of that person during the interview. In this study, we focus on formations of interview questions in such a way that, it gets an opportunity for assessing interviewee through the answers using the nonverbal behavioral cues. From all the nonverbal behavioral factors we have identified, in this study priority is given to the ‘facial expression variations’ with the assistance of facial expression analytics tool; this research proposes a novel approach in question formation for the assessment of interviewees in ‘Software Industry’.

Keywords: assessments, hirability, interviews, non-verbal behaviour patterns, question formation

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

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Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

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Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

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