Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is... more Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is an important therapeutic target in melanoma due to its association with cancer progression. However, developing effective Src-targeting drugs remains challenging and personalized medicine relies on biomarkers and targeted therapies for precise and effective treatment. This study focuses on Si162, a newly synthesized c-Src inhibitor, to identify reliable biomarkers for predicting Si162 sensitivity and explore associated biological characteristics and pathways in melanoma cells. Materials and methods: Primary melanoma cells (M1, M21, M24, M84, M133, M307, and M2025) were obtained from patients diagnosed with melanoma. Si162 cytotoxicity tests were performed using luminescent adenosine triphosphate detection and the halfmaximal inhibitory concentration (IC 50) values were calculated. Gene expression profiles were analyzed using microarray-based gene expression data. Differentially expressed genes between the resistant and sensitive groups were identified using Pearson correlation analysis. Gene coexpression, interactions, and pathways were investigated through clustering, network, and pathway analyses. Biological functions were examined using the Database for Annotation, Visualization, and Integrated Discovery. Molecular pathways associated with different responses to Si162 were identified using gene set enrichment analysis. The gene expressions were validated using reverse transcription-quantitative polymerase chain reaction. Results: The cells revealed significant differences in response to Si162 based on the IC 50 values (p < 0.05). A total of 36 differentially expressed genes associated with Si162 susceptibility were identified. Distinct expression patterns between the sensitive and resistant groups were observed in 9 genes (LRBA, MGMT, CAND1, ADD1, SETD2, CNTN6, FGF18, C18orf25, and RPL13). Coexpression among the differentially expressed genes was highlighted, and 9 genes associated with molecular pathways, including EMT, transforming growth factor-beta (TGF-β) signaling, and ribosomal protein synthesis, between groups. Genes involved in dysregulated immune response were observed in the resistant group. The involvement of 5 genes (ADD1, CNTN6, FGF18, C18orf25, and RPL13) in Si162 resistance was confirmed through qRT-PCR validation. Conclusion: These findings contribute to our understanding of the underlying biological differences among melanoma cells and suggest potential biomarkers and pathways associated with Si162 response and resistance.
DOAJ (DOAJ: Directory of Open Access Journals), Aug 1, 2020
OBJECTIVE COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection... more OBJECTIVE COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.
Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been appro... more Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of disease symptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinibinduced JAK/STAT pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. However, the biological basis and significance of this pharmacobiological adverse event is unknown. The aim of this bioinformatics study is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders. Materials and methods: The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silico analysis. Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines. Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcription factors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptions protective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, and proliferation of malignant neoplastic B cells.
Melanoma is a highly aggressive cancer with poor prognosis. Although more than 80% of melanomas h... more Melanoma is a highly aggressive cancer with poor prognosis. Although more than 80% of melanomas harbor an activating mutation in genes within the MAPK pathway, which are mutually exclusive, usefulness of therapies targeting MAPK pathway are impeded by innate and/or acquired resistance in most patients. In this study, using melanoma cells, we report the efficacy of a recently developed pyrazolo[3,4-d]pyrimidine derived c-Src inhibitor 10a and identify a molecular signature which is predictive of 10a chemosensitivity. We show that the expression of TMED7, PLOD2, XRCC5, and NSUN5 are candidate biomarkers for 10a sensitivity. Although an undifferentiated/mesenchymal/ invasive status of melanoma cells is associated with resistance to 10a, we show here for the first time that melanoma cells can be sensitized to 10a via treatment with valproic acid, a histone deacetylase inhibitor.
Journal of the Renin-Angiotensin-Aldosterone System, Apr 1, 2020
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identifi... more Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. Methods: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. Results: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. Conclusion: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.
On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announce... more On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announced that these cases were of viral origin and the cause was a new coronavirus (CoV). Initially, the virus was called "novel CoV " and then defined as "severe acute respiratory syndrome CoV 2 (SARS-CoV-2)" after more detailed investigations. The disease caused by SARS-CoV-2 was named CoV disease 2019 (COVID-19) by the World Health Organization. The rapid spread of the disease in a few months has resulted in a global pandemic and it continues. However, there are no specific effective anti-viral drugs for SARS-CoV-2 infection, some antiviral drugs are using in the therapy of COVID-19 with limited success. Currently, for the prevention of the pandemic, global vaccination seems to be important. Antiviral protection of vaccines is provided by the development of antibodies that can neutralize the virus. Antibody response develops against spike protein and nucleocapsid protein but neutralizing antibodies are formed against the receptor-binding domain of the spike protein. It has also been shown that most viral proteins are recognized in T-cell responses. Vaccine discovery trials for COVID-19 have begun all over the world since the outbreak began. More than 100 vaccine studies against COVID-19 have been published in the last year. Some of them were urgently approved and used worldwide. The current study aimed to review the progression and current use of COVID-19 vaccines.
Interferon (IFN) family has a significant impact on both SARS-CoV and SARS-CoV-2. The aim of this... more Interferon (IFN) family has a significant impact on both SARS-CoV and SARS-CoV-2. The aim of this current bioinformatics study is to assess IFN-gene family alterations following the SARS-CoV infection in association with the iron metabolism and lymphoid biology.Gene expression data of human bronchial epithelial cells treated with SARS-CoV for 12, 24, 48 hours were obtained from Array Express (GSE17400). In order to use the obtained data in other targeted analyses,the raw data were normalized by robust multisequence analysis in accordance with the procedure in the Affy package in R. These data consist of 23344 genes (54675 probe sets). In addition, each gene has three repeated expression data values for 12, 24, 48 hours, respectively. For the 48 hours group,positive regulations of the natural killer (NK) cell activation and NK cell-mediated cytotoxicity, as well as hematopoietic stem cells proliferation,were found to be more significant regard to their nominal p-value, family-wise error rate, and false discovery rate (q-value) calculated by gen set enrichment analysis. The gene sets with nominal (NOM) p-value < 0.01, false discovery rate (FDR) q-value ≤ 1, and familywise error rate (FWER) < 1 considered as significantly correlate between compared groups. Our study exhibited that important IFN genes (IFNAR2, IFNA10, IFNA1, IFNLR1, IFNA21, IFNA4, IFNL2, IFNL1, IFNA16, IFNA17) behave like immune genes that show low expression in 12 hours virus exposure, unlike demonstrate high gene expression at 48 hours virus exposure. Likewise, three IFN genes (IF-NAR1, IFNGR1, IFNG) have high expression levels at the 12 hours exposure and low expressions at the 48 hours virus expression. All of these interferon genes expression were highly correlated and statistically significant (p< 0.05, pearson r-value > 0.8) with exposure time to the virus. These results suggest that hematopoietic stem cell proliferation pathway is affected by the viral SARS-CoV infection.
Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells nee... more Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin–angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were a...
On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announce... more On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announced that these cases were of viral origin and the cause was a new coronavirus (CoV). Initially, the virus was called "novel CoV" and then defined as "severe acute respiratory syndrome CoV 2 (SARS-CoV-2)" after more detailed investigations. The disease caused by SARS-CoV-2 was named CoV disease 2019 (COVID-19) by the World Health Organization. The rapid spread of the disease in a few months has resulted in a global pandemic and it continues. However, there are no specific effective anti-viral drugs for SARS-CoV-2 infection, some antiviral drugs are using in the therapy of COVID-19 with limited success. Currently, for the prevention of the pandemic, global vaccination seems to be important. Antiviral protection of vaccines is provided by the development of antibodies that can neutralize the virus. Antibody response develops against spike protein and nucleocapsid protein b...
Supplemental material, Suppelementary_File for In vitro analysis of the renin–angiotensin system ... more Supplemental material, Suppelementary_File for In vitro analysis of the renin–angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus by Can Turk, Seyhan Turk, Elif Sena Temirci, Umit Yavuz Malkan and İbrahim C. Haznedaroglu in Journal of the Renin-Angiotensin-Aldosterone System
Background and Objectives: Toxoplasmosis is a life-threatening zoonotic infection in immunosuppre... more Background and Objectives: Toxoplasmosis is a life-threatening zoonotic infection in immunosuppressive individuals. Determining the prevalence and seropositivity rates of toxoplasmosis in asymptomatic blood donors is crucial in terms of the risk status of the transmission of this infection to the blood recipients. Materials and Methods: In this study, the presence and level of the specific Toxoplasma IgG and IgM antibodies in blood donors was investigated by electrochemiluminescence immunoassay (ECLIA). The statistical significance levels between Toxoplasma seropositivity and demographic characteristics of the donors such as age, educational status, raw meat consumption, drinking water supply were examined. Results: Toxoplasma IgG seropositivity was found among the 225 (25.6%) of the donors present in the study group, while IgM seropositivity was detected in 20 donors (2.3%). The number of donors with only IgM (+) was 8 (0.9%). Both IgG and IgM seropositivities were found in 12 dono...
Purpose Enterococcus faecalis ( E. faecalis ) is an important commensal microbiota member of the ... more Purpose Enterococcus faecalis ( E. faecalis ) is an important commensal microbiota member of the human gastrointestinal tract. It has been shown in many studies that infection rates with E. faecalis in gastric cancer significantly increase. It has been scientifically proven that some infections develop during the progression of cancer, but it is still unclear whether this infection factor is beneficial (reduction in metastasis) or harmful (increase in proliferation, invasion, stem cell-like phenotype) of the host. These opposed data can significantly contribute to the understanding of cancer progress when analyzed in detail. Methods The gene expression data were retrieved from Array Express (E-MEXP-3496). Variance, t test and linear regression analysis, hierarchical clustering, network, and pathway analysis were performed. Results In this study, we identified altered genes involved in E. faecalis infection in the gastric cell line MKN74 and the relevant pathways to understand whethe...
Medicine Science | International Medical Journal, 2021
While chemotherapeutics without any selective properties were used in cancer treatment in the pas... more While chemotherapeutics without any selective properties were used in cancer treatment in the past, they are now replaced by targeted drugs. Imatinib has common use in the treatment of acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML) but not Acute myeloid leukemia (AML). It is a highly effective oral drug treatment and provides stable remission in many people treated. Treatment of imatinib mesylate can cause various side effects such as swelling around the eyes, nausea, and vomiting. However, it is likely to act on normal cells, and this effect causes side effects. To create a better design with increased bioactivity with decreased possible side effects of imatinib we calculated the molecular pharmaceutical properties and biological activity and investigated its analogs. Also, we figured out which genetically subclasses of AML can benefit from therapy with imatinib analog, imatinib B. The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project d...
Medicine Science | International Medical Journal, 2021
Pinostrobin as a famous member of flavonoid family has been investigated in terms of its therapeu... more Pinostrobin as a famous member of flavonoid family has been investigated in terms of its therapeutic effect on a variety of diseases, and positive effect has been reported in many in vitro and in vivo studies. As one of the essential elements of blood plasma in human body, serum albumin functions a carrier protein for fatty acids, hormones, and drugs because of its abundance and strength in blood. For that, serum albumin plays an important role on the understanding of pharmacological effect of the promising therapeutic agent, pinostrobin. For providing insight into the preclinical studies of albumin targeted therapeutics, we, in this study, investigated the binding characteristics of human serum albumin – pinostrobin complex in terms of binding energy, bounded residues, and association constants, and compared them with various mammalian albumins such as goat, bovine, porcine, rabbit, sheep, and dog albumins. We used molecular modeling and molecular docking methods with the softwares PyRX and PyMol. We found that pinostrobin-human serum albumin had an association constant in between (10.26-20.16)105 M-1 with the interaction energy in a range of (-8.2(-8.6)) kcal/mol. Among animal proteins, porcine (5IIU) and sheep (4LUF) showing the interaction energy of -8.4 kcal/mol and -8.1 kcal/mol, respectively, were found to be the most appropriate animal models to be used in albumin based preclinical investigations.
Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of coronavi... more Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of coronavirus family which leads to a respiratory disease like severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are from the same virus family origin and their features of structure, genetics, and pathobiology are similar to each other. Our research group had recently published that coronaviruses may affect pulmonary tissues and some critical immune genes play essential roles after their interaction with renin-angiotensin system (RAS) elements [1]. Local tissue-based RASs, for instance bone marrow (BM) RAS [2,3], serve for the dissemination of the SARS-CoV-2 infection for the genesis of COVID-19 syndrome associated with macrophage activation [4]. We have demonstrated that the RAS genes play a significant role at the initiation of the infections caused by coronaviruses and may have a strong association with the exchange of immune genes during the clinical course following the infection. On the other hand, there are ongoing discussions regarding the clinical course of COVID-19. Our team had proposed three critical prominent phases regarding the clinic-genomic course of the COVID-19 immune syndrome [5]. We have previously disclosed that the COVID-19 clinical course follows three consequent periods which are 'asymptomatic/presymptomatic phase' , Background/aim: COVID-19 syndrome due to the SARS-CoV-2 virus is a currently challenging situation ongoing worldwide. Since the current pandemic of the SARS-CoV-2 virus is a great concern for everybody in the World, the frequently asked question is how and when the COVID-19 process will be concluded. The aim of this paper is to propose hypotheses in order to answer this essential question. As recently demonstrated, SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome. Our main hypothesis is that the ultimate aim of the SARS-CoV-2 virus is the incorporation to human genome and being an element of the intestinal virobiota. Materials and methods: We propose that the SARS-CoV-2 genomic incorporation to be a part of human virobiota is essentially based on three pathobiological phases which are called as the 'induction' , 'consolidation' , and 'maintenance phases'. The phase of 'recurrence' complicates any of these three disease phases based on the viral load, exposure time, and more contagious strains and/or mutants. We have performed the 'random walk model' in order to predict the community transmission kinetics of the virus. Results: Chimerism-mediated immunotherapy at the individual and community level with the help of vaccination seems to be the only option for ending the COVID-19 process. After the integration of SARS-CoV-2 virus into the human genome via the induction, consolidation, and maintenance phases as an element of intestinal virobiota, the chimerism would be concluded. The 'viral load' , the 'genomic strain of the SARS-CoV-2' , and 'host immune reaction against the SARS-CoV-2' are the hallmarks of this long journey. Conclusion: Elucidation of the functional viral dynamics will be helpful for disease management at the individual-and communitybased long-term management strategies.
Despite the availability of various treatment protocols, response to therapy in patients with Acu... more Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin...
Journal of the Renin-Angiotensin-Aldosterone System, 2020
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identifi... more Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin–angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. Methods: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. Results: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours w...
Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is... more Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is an important therapeutic target in melanoma due to its association with cancer progression. However, developing effective Src-targeting drugs remains challenging and personalized medicine relies on biomarkers and targeted therapies for precise and effective treatment. This study focuses on Si162, a newly synthesized c-Src inhibitor, to identify reliable biomarkers for predicting Si162 sensitivity and explore associated biological characteristics and pathways in melanoma cells. Materials and methods: Primary melanoma cells (M1, M21, M24, M84, M133, M307, and M2025) were obtained from patients diagnosed with melanoma. Si162 cytotoxicity tests were performed using luminescent adenosine triphosphate detection and the halfmaximal inhibitory concentration (IC 50) values were calculated. Gene expression profiles were analyzed using microarray-based gene expression data. Differentially expressed genes between the resistant and sensitive groups were identified using Pearson correlation analysis. Gene coexpression, interactions, and pathways were investigated through clustering, network, and pathway analyses. Biological functions were examined using the Database for Annotation, Visualization, and Integrated Discovery. Molecular pathways associated with different responses to Si162 were identified using gene set enrichment analysis. The gene expressions were validated using reverse transcription-quantitative polymerase chain reaction. Results: The cells revealed significant differences in response to Si162 based on the IC 50 values (p < 0.05). A total of 36 differentially expressed genes associated with Si162 susceptibility were identified. Distinct expression patterns between the sensitive and resistant groups were observed in 9 genes (LRBA, MGMT, CAND1, ADD1, SETD2, CNTN6, FGF18, C18orf25, and RPL13). Coexpression among the differentially expressed genes was highlighted, and 9 genes associated with molecular pathways, including EMT, transforming growth factor-beta (TGF-β) signaling, and ribosomal protein synthesis, between groups. Genes involved in dysregulated immune response were observed in the resistant group. The involvement of 5 genes (ADD1, CNTN6, FGF18, C18orf25, and RPL13) in Si162 resistance was confirmed through qRT-PCR validation. Conclusion: These findings contribute to our understanding of the underlying biological differences among melanoma cells and suggest potential biomarkers and pathways associated with Si162 response and resistance.
DOAJ (DOAJ: Directory of Open Access Journals), Aug 1, 2020
OBJECTIVE COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection... more OBJECTIVE COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.
Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been appro... more Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of disease symptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinibinduced JAK/STAT pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. However, the biological basis and significance of this pharmacobiological adverse event is unknown. The aim of this bioinformatics study is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders. Materials and methods: The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silico analysis. Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines. Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcription factors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptions protective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, and proliferation of malignant neoplastic B cells.
Melanoma is a highly aggressive cancer with poor prognosis. Although more than 80% of melanomas h... more Melanoma is a highly aggressive cancer with poor prognosis. Although more than 80% of melanomas harbor an activating mutation in genes within the MAPK pathway, which are mutually exclusive, usefulness of therapies targeting MAPK pathway are impeded by innate and/or acquired resistance in most patients. In this study, using melanoma cells, we report the efficacy of a recently developed pyrazolo[3,4-d]pyrimidine derived c-Src inhibitor 10a and identify a molecular signature which is predictive of 10a chemosensitivity. We show that the expression of TMED7, PLOD2, XRCC5, and NSUN5 are candidate biomarkers for 10a sensitivity. Although an undifferentiated/mesenchymal/ invasive status of melanoma cells is associated with resistance to 10a, we show here for the first time that melanoma cells can be sensitized to 10a via treatment with valproic acid, a histone deacetylase inhibitor.
Journal of the Renin-Angiotensin-Aldosterone System, Apr 1, 2020
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identifi... more Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. Methods: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. Results: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. Conclusion: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.
On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announce... more On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announced that these cases were of viral origin and the cause was a new coronavirus (CoV). Initially, the virus was called "novel CoV " and then defined as "severe acute respiratory syndrome CoV 2 (SARS-CoV-2)" after more detailed investigations. The disease caused by SARS-CoV-2 was named CoV disease 2019 (COVID-19) by the World Health Organization. The rapid spread of the disease in a few months has resulted in a global pandemic and it continues. However, there are no specific effective anti-viral drugs for SARS-CoV-2 infection, some antiviral drugs are using in the therapy of COVID-19 with limited success. Currently, for the prevention of the pandemic, global vaccination seems to be important. Antiviral protection of vaccines is provided by the development of antibodies that can neutralize the virus. Antibody response develops against spike protein and nucleocapsid protein but neutralizing antibodies are formed against the receptor-binding domain of the spike protein. It has also been shown that most viral proteins are recognized in T-cell responses. Vaccine discovery trials for COVID-19 have begun all over the world since the outbreak began. More than 100 vaccine studies against COVID-19 have been published in the last year. Some of them were urgently approved and used worldwide. The current study aimed to review the progression and current use of COVID-19 vaccines.
Interferon (IFN) family has a significant impact on both SARS-CoV and SARS-CoV-2. The aim of this... more Interferon (IFN) family has a significant impact on both SARS-CoV and SARS-CoV-2. The aim of this current bioinformatics study is to assess IFN-gene family alterations following the SARS-CoV infection in association with the iron metabolism and lymphoid biology.Gene expression data of human bronchial epithelial cells treated with SARS-CoV for 12, 24, 48 hours were obtained from Array Express (GSE17400). In order to use the obtained data in other targeted analyses,the raw data were normalized by robust multisequence analysis in accordance with the procedure in the Affy package in R. These data consist of 23344 genes (54675 probe sets). In addition, each gene has three repeated expression data values for 12, 24, 48 hours, respectively. For the 48 hours group,positive regulations of the natural killer (NK) cell activation and NK cell-mediated cytotoxicity, as well as hematopoietic stem cells proliferation,were found to be more significant regard to their nominal p-value, family-wise error rate, and false discovery rate (q-value) calculated by gen set enrichment analysis. The gene sets with nominal (NOM) p-value < 0.01, false discovery rate (FDR) q-value ≤ 1, and familywise error rate (FWER) < 1 considered as significantly correlate between compared groups. Our study exhibited that important IFN genes (IFNAR2, IFNA10, IFNA1, IFNLR1, IFNA21, IFNA4, IFNL2, IFNL1, IFNA16, IFNA17) behave like immune genes that show low expression in 12 hours virus exposure, unlike demonstrate high gene expression at 48 hours virus exposure. Likewise, three IFN genes (IF-NAR1, IFNGR1, IFNG) have high expression levels at the 12 hours exposure and low expressions at the 48 hours virus expression. All of these interferon genes expression were highly correlated and statistically significant (p< 0.05, pearson r-value > 0.8) with exposure time to the virus. These results suggest that hematopoietic stem cell proliferation pathway is affected by the viral SARS-CoV infection.
Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells nee... more Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin–angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were a...
On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announce... more On December 31, 2019; unidentified pneumonia cases were reported from China. It was soon announced that these cases were of viral origin and the cause was a new coronavirus (CoV). Initially, the virus was called "novel CoV" and then defined as "severe acute respiratory syndrome CoV 2 (SARS-CoV-2)" after more detailed investigations. The disease caused by SARS-CoV-2 was named CoV disease 2019 (COVID-19) by the World Health Organization. The rapid spread of the disease in a few months has resulted in a global pandemic and it continues. However, there are no specific effective anti-viral drugs for SARS-CoV-2 infection, some antiviral drugs are using in the therapy of COVID-19 with limited success. Currently, for the prevention of the pandemic, global vaccination seems to be important. Antiviral protection of vaccines is provided by the development of antibodies that can neutralize the virus. Antibody response develops against spike protein and nucleocapsid protein b...
Supplemental material, Suppelementary_File for In vitro analysis of the renin–angiotensin system ... more Supplemental material, Suppelementary_File for In vitro analysis of the renin–angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus by Can Turk, Seyhan Turk, Elif Sena Temirci, Umit Yavuz Malkan and İbrahim C. Haznedaroglu in Journal of the Renin-Angiotensin-Aldosterone System
Background and Objectives: Toxoplasmosis is a life-threatening zoonotic infection in immunosuppre... more Background and Objectives: Toxoplasmosis is a life-threatening zoonotic infection in immunosuppressive individuals. Determining the prevalence and seropositivity rates of toxoplasmosis in asymptomatic blood donors is crucial in terms of the risk status of the transmission of this infection to the blood recipients. Materials and Methods: In this study, the presence and level of the specific Toxoplasma IgG and IgM antibodies in blood donors was investigated by electrochemiluminescence immunoassay (ECLIA). The statistical significance levels between Toxoplasma seropositivity and demographic characteristics of the donors such as age, educational status, raw meat consumption, drinking water supply were examined. Results: Toxoplasma IgG seropositivity was found among the 225 (25.6%) of the donors present in the study group, while IgM seropositivity was detected in 20 donors (2.3%). The number of donors with only IgM (+) was 8 (0.9%). Both IgG and IgM seropositivities were found in 12 dono...
Purpose Enterococcus faecalis ( E. faecalis ) is an important commensal microbiota member of the ... more Purpose Enterococcus faecalis ( E. faecalis ) is an important commensal microbiota member of the human gastrointestinal tract. It has been shown in many studies that infection rates with E. faecalis in gastric cancer significantly increase. It has been scientifically proven that some infections develop during the progression of cancer, but it is still unclear whether this infection factor is beneficial (reduction in metastasis) or harmful (increase in proliferation, invasion, stem cell-like phenotype) of the host. These opposed data can significantly contribute to the understanding of cancer progress when analyzed in detail. Methods The gene expression data were retrieved from Array Express (E-MEXP-3496). Variance, t test and linear regression analysis, hierarchical clustering, network, and pathway analysis were performed. Results In this study, we identified altered genes involved in E. faecalis infection in the gastric cell line MKN74 and the relevant pathways to understand whethe...
Medicine Science | International Medical Journal, 2021
While chemotherapeutics without any selective properties were used in cancer treatment in the pas... more While chemotherapeutics without any selective properties were used in cancer treatment in the past, they are now replaced by targeted drugs. Imatinib has common use in the treatment of acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML) but not Acute myeloid leukemia (AML). It is a highly effective oral drug treatment and provides stable remission in many people treated. Treatment of imatinib mesylate can cause various side effects such as swelling around the eyes, nausea, and vomiting. However, it is likely to act on normal cells, and this effect causes side effects. To create a better design with increased bioactivity with decreased possible side effects of imatinib we calculated the molecular pharmaceutical properties and biological activity and investigated its analogs. Also, we figured out which genetically subclasses of AML can benefit from therapy with imatinib analog, imatinib B. The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project d...
Medicine Science | International Medical Journal, 2021
Pinostrobin as a famous member of flavonoid family has been investigated in terms of its therapeu... more Pinostrobin as a famous member of flavonoid family has been investigated in terms of its therapeutic effect on a variety of diseases, and positive effect has been reported in many in vitro and in vivo studies. As one of the essential elements of blood plasma in human body, serum albumin functions a carrier protein for fatty acids, hormones, and drugs because of its abundance and strength in blood. For that, serum albumin plays an important role on the understanding of pharmacological effect of the promising therapeutic agent, pinostrobin. For providing insight into the preclinical studies of albumin targeted therapeutics, we, in this study, investigated the binding characteristics of human serum albumin – pinostrobin complex in terms of binding energy, bounded residues, and association constants, and compared them with various mammalian albumins such as goat, bovine, porcine, rabbit, sheep, and dog albumins. We used molecular modeling and molecular docking methods with the softwares PyRX and PyMol. We found that pinostrobin-human serum albumin had an association constant in between (10.26-20.16)105 M-1 with the interaction energy in a range of (-8.2(-8.6)) kcal/mol. Among animal proteins, porcine (5IIU) and sheep (4LUF) showing the interaction energy of -8.4 kcal/mol and -8.1 kcal/mol, respectively, were found to be the most appropriate animal models to be used in albumin based preclinical investigations.
Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of coronavi... more Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of coronavirus family which leads to a respiratory disease like severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are from the same virus family origin and their features of structure, genetics, and pathobiology are similar to each other. Our research group had recently published that coronaviruses may affect pulmonary tissues and some critical immune genes play essential roles after their interaction with renin-angiotensin system (RAS) elements [1]. Local tissue-based RASs, for instance bone marrow (BM) RAS [2,3], serve for the dissemination of the SARS-CoV-2 infection for the genesis of COVID-19 syndrome associated with macrophage activation [4]. We have demonstrated that the RAS genes play a significant role at the initiation of the infections caused by coronaviruses and may have a strong association with the exchange of immune genes during the clinical course following the infection. On the other hand, there are ongoing discussions regarding the clinical course of COVID-19. Our team had proposed three critical prominent phases regarding the clinic-genomic course of the COVID-19 immune syndrome [5]. We have previously disclosed that the COVID-19 clinical course follows three consequent periods which are 'asymptomatic/presymptomatic phase' , Background/aim: COVID-19 syndrome due to the SARS-CoV-2 virus is a currently challenging situation ongoing worldwide. Since the current pandemic of the SARS-CoV-2 virus is a great concern for everybody in the World, the frequently asked question is how and when the COVID-19 process will be concluded. The aim of this paper is to propose hypotheses in order to answer this essential question. As recently demonstrated, SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome. Our main hypothesis is that the ultimate aim of the SARS-CoV-2 virus is the incorporation to human genome and being an element of the intestinal virobiota. Materials and methods: We propose that the SARS-CoV-2 genomic incorporation to be a part of human virobiota is essentially based on three pathobiological phases which are called as the 'induction' , 'consolidation' , and 'maintenance phases'. The phase of 'recurrence' complicates any of these three disease phases based on the viral load, exposure time, and more contagious strains and/or mutants. We have performed the 'random walk model' in order to predict the community transmission kinetics of the virus. Results: Chimerism-mediated immunotherapy at the individual and community level with the help of vaccination seems to be the only option for ending the COVID-19 process. After the integration of SARS-CoV-2 virus into the human genome via the induction, consolidation, and maintenance phases as an element of intestinal virobiota, the chimerism would be concluded. The 'viral load' , the 'genomic strain of the SARS-CoV-2' , and 'host immune reaction against the SARS-CoV-2' are the hallmarks of this long journey. Conclusion: Elucidation of the functional viral dynamics will be helpful for disease management at the individual-and communitybased long-term management strategies.
Despite the availability of various treatment protocols, response to therapy in patients with Acu... more Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin...
Journal of the Renin-Angiotensin-Aldosterone System, 2020
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identifi... more Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin–angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. Methods: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. Results: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours w...
Uploads
Papers by CAN TURK