Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D rece... more Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells that are key players in the fight against breast cancer (BC). Shedding of MICA during BC progression acts as a formidable barrier against NK cells' immune-surveillance. Recently, miR-20a was found to mediate immune escape through repressing MICA levels on BC cells. However, targeting miR-20a/MICA using natural compounds has seldomly been investigated. Vitexin, a flavone Cglycoside, showed potent anticancer properties. It was reported that acetylation of glycosides increases their cytotoxic activity, with an unknown impact on immunogenicity. Our group has successfully isolated 3'-O-acetylvitexin from Ocimum basilicum which showed potent cytotoxic effects against colon cancer cells but has never been investigated in BC. Our aim is to unravel the role of the immunogenic miR-20a/MICA axis in BC patients and its regulation by vitexin and 3'-O-acetylvitexin. Methods: Breast tissues were collected from 26 BC patients. ER, PR and HER2 expression was quantified using immunohistochemistry. MDA-MB-231 TNBC cells and MCF-7 HRþ BC cells were treated with serial dilutions of vitexin and 3'-O-acetylvitexin. Their cytotoxic activities were assessed using MTT, colony forming and migration assays. Total RNA was extracted, reverse transcribed, then MICA and miR-20a were quantified using qRT-PCR. Results: miR-20a is upregulated in BC patients, while MICA was downregulated in MDA-MB-231 compared to MCF7 cells. Vitexin decreased MDA-MB-231 cellular viability and migration capacity. 3'-O-acetylvitexin resulted in a more pronounced dosedependent repression of TNBC cellular viability, colonogenicity and migration capacity. Treatment with vitexin didn't show any alteration in miR-20a but showed only 2 folds increase in MICA. However, 3'-O-acetylvitexin markedly decreased miR-20a with a concomitant increase in MICA by 12 folds. Conclusions: 3'-O-acetylvitexin displays more pronounced anticancer properties against TNBC through halting their progression and immune suppressive nature by modulating miR-20a/MICA axis. This highlights miR-20a/MICA axis as a potential therapeutic target in BC.
Overview of the covered topics: action mechanisms for ephedrine stimulation of α and β adrenocept... more Overview of the covered topics: action mechanisms for ephedrine stimulation of α and β adrenoceptor, impact of processing and combination on the pharmacokinetics of its ephedrine content, and key players in pharmacokinetics.
Cardiovascular disease (CVD) remains the leading cause of death worldwide. Despite huge efforts a... more Cardiovascular disease (CVD) remains the leading cause of death worldwide. Despite huge efforts and great advances in studying the genetic component of CVD, there is still a great need for exploring the genetic and environmental factors contributing to the development of this disease. Among these factors evolve modulation of nitric oxide (NO) homeostasis and oxidative stress as central players according to recent reports. A wide range of biochemical disturbances, including reduced bioavailability of NO and oxidative stress, has been shown to be associated with endothelial dysfunction (ED). Many studies described the contribution of ED in the predisposition of CVD, particularly coronary artery disease (CAD). Recent evidence indicates that ED may be genetically determined. This chapter points out to the key players that influence vascular NO levels and their role in the protection against and/or predisposition to CAD.
Vitamin D deficiency has become a globally acknowledged problem whose impact on societies has pro... more Vitamin D deficiency has become a globally acknowledged problem whose impact on societies has proven to surpass all medical expectations. Vitamin D is no longer peerlessly associated with bone diseases. In fact, collaborations of M.A. Abu el Maaty (*) Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universitat Heidelberg, Heidelberg, Germany e-mail: [email protected]; [email protected] S.I. Hassanein Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt e-mail: [email protected]; [email protected] M.Z. Gad Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt Division of Pharmacy and Biotechnology, Biochemistry Department, German University in Cairo (GUC), Cairo Governorate, Egypt e-mail: [email protected] # Springer Science+Business Media Dordrecht 2015 V.B. Patel, V.R. Preedy (eds.), Biomarkers in Cardiovascular Disease, DOI 10.1007/978-94-007-7741-5_23-1 1 clinicians and researchers have yielded the undeniable truth, that is, the affiliation of this unconventional vitamin with diseases that are currently grasping the media’s attention like autoimmune diseases and cancers. Having established the importance of this phenomenon, assuming complete understanding of the association of vitamin D with one of the leading causes of death in the world, cardiovascular disease, is only mildly precise. Observational studies tend to highlight the association of low vitamin D levels with various forms of cardiovascular disease as well as with the risk factors associated, whereas interventional studies have been conflicting. Nonetheless, in vitro studies have identified the presence of nuclear vitamin D receptors in the cardiovascular system in cells such as cardiomyocytes and endothelial cells, thereby warranting cardiovascular actions. Moreover, recent studies have demonstrated the ability of vitamin D to beneficially modulate effectors of the cardiovascular system such as the reninangiotensin-aldosterone system and the nitric oxide system. While there appears to be abundance in the number of publications on the epidemiological and mechanistic association of the vitamin with the disease, studies aiming to investigate the genetic component of the relationship are sparse. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in the vitamin D pathway, whether synthesis, metabolism, or elimination, that are associated with circulating levels of 25-hydroxyvitamin D [25(OH)D], the biomarker of vitamin D status, and thus it is conceptualized that such SNPs may act as novel genetic markers for cardiovascular disease since the disease has been associated with low levels of 25(OH)D. Several studies have investigated this hypothesis, yielding both positive and negative associations, highlighting the need for further investigations into the proposed triangular relationships between the SNPs, 25(OH)D levels, and the disease, which would spawn sound evidence prompting or discouraging professionals to extrapolate the findings to clinical genetic testing.
Background Triple Negative Breast cancer (TNBC) is a complex challenging disease that is not amen... more Background Triple Negative Breast cancer (TNBC) is a complex challenging disease that is not amenable to conventional treatment. Our research group has recently portrayed hydrogen sulphide (H2S) and its synthesizing enzymes, cystathionine β-synthase (CBS) and cystathionine-γ-lyase (CSE), as potent oncogenic mediators for TNBC progression. Recently, H2S has been casted as a potential modulator of cancer immune surveillance as well. Yet, the impact of H2S on the immunological profile of TNBC cells has never been investigated. Natural Killer (NK) cells are the native sentinels of the immune system that plays an indisputable role in TNBC-immune surveillance. TNBC immune suppressive tumour microenvironment is also rate-limiting step when immunotherapeutic approaches are tackled in case of TNBC patients. Thus the main aim of this study is to identify the role of endogenous H2S on NK cells' activating ligands present on TNBC cells, immune suppressive tumour microenvironment and net effect on NK cells cytotoxicity. Methods Breast tissues were collected from 80 BC patients. ER, PR, HER-2 and Ki-67 levels were quantified using immunohistochemistry. MDA-MB-231 and MCF7 cells were cultured and transfected with different oligonucleotides. Total RNA was extracted and quantified by qRT-PCR. IFN-γ and TNF-α in cellular supernatant was measured using representative ELISA kits. NK cells were isolated from 30 healthy controls. The cytotoxicity of NK cells was measured using LDH Cytotoxicity Assay. Results MICA, MICB and ULBP2 were significantly down-regulated in TNBC tissues and cell lines. Knocking down of CBS and CSE using siRNAs resulted in a marked increase in MICA/B and ULBP2 expression in MDA-MB-231 cells. Nonetheless, knocking down of CBS and CSE resulted in a marked induction in IFN-γ production and attenuation of TNF-α levels. Upon co-culturing with healthy NK cells, Knocking down of endogenous H2S resulted in a marked increase in NK cells cytotoxicity. Conclusion This study showed that knocking down of CBS and CSE resulted in a improving NK cells cytotoxicity and alleviating tumor-induced immune suppressive microenvironment in TNBC patients. Legal entity responsible for the study German University in Cairo. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
Background: Myocardial microRNAs (Myo-miR) like MiR-1, miR-133 and miR-208 are speci c to cardiac... more Background: Myocardial microRNAs (Myo-miR) like MiR-1, miR-133 and miR-208 are speci c to cardiac muscles development and function. Diagnostic potential of MiR-1, miR-133 and miR-208 in acute episodes of myocardial infarction is unknown. Methods: Patient of newly onset of acute myocardial infarction with elevated ST-segment admitted to Ain-Shams university hospital Cairo from May 2013 to December 2022 were enrolled. Written consent was obtained. Circulating MiRNAs were measured at 04, 08, 12, 24, 48 hours from onset of angina by RT-PCR and compare with conventional creatin-kinases for diagnostic potential. Results were analyzed by student t-test, ROC curve calculations and ANOVA were performed using GraphPad-Prism-9Version. Results: 746 patients admitted with STEMI and 10(1.34%) cases were presented with new-onset episodes of STEMI with mean±SD age 54.2±8.49 year. miR-133a peaks at 8 hours, miR-208b peaks at 12 hours from onset of AMI compared to cTnI and CK-MB peak at 12hrs(P<0.001). ROC-curve for miR-133a AUC was 0.583,0.8,1,0.78 and 0.58 at 4,8,12,24 & 48 hours respectively. AUC for miR-208b was 0.87,0.888,0.888,0.627 compared to AUC of cTnI concentrations 0.59,1,1,0.75,0 and (ROC) curve for CK-MB was 0.59,1,1,0.8&0.73 respectively. Positive correlation was present between miR-133a and cTnI (R=0.926-R 2 = 0.858 P=0.47), miR-208b and cTnI (R=0.8-R 2 =0.64 P=0.1) , miR-208b and CK-MB was (R=0.888-R 2 =0.789 P=0.044) and CK-MB-cTnI (R=0.72) respectively. Conclusion: We showed miR-133a and miR-208b diagnostic speci city superior over conventional blood biomarkers for acute onset of STEMI. (NCT05692752)
Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D rece... more Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells that are key players in the fight against breast cancer (BC). Shedding of MICA during BC progression acts as a formidable barrier against NK cells' immune-surveillance. Recently, miR-20a was found to mediate immune escape through repressing MICA levels on BC cells. However, targeting miR-20a/MICA using natural compounds has seldomly been investigated. Vitexin, a flavone Cglycoside, showed potent anticancer properties. It was reported that acetylation of glycosides increases their cytotoxic activity, with an unknown impact on immunogenicity. Our group has successfully isolated 3'-O-acetylvitexin from Ocimum basilicum which showed potent cytotoxic effects against colon cancer cells but has never been investigated in BC. Our aim is to unravel the role of the immunogenic miR-20a/MICA axis in BC patients and its regulation by vitexin and 3'-O-acetylvitexin. Methods: Breast tissues were collected from 26 BC patients.
reduced growth of the AR dependent cell line and miR-1271-5 p mimic had the opposite effect. AR m... more reduced growth of the AR dependent cell line and miR-1271-5 p mimic had the opposite effect. AR mRNA levels were altered, as well as levels of miR specific target genes, after manipulation of PCa cell lines with miR-1271-5 p inhibitor and mimic. Similar effects were noticed with the use of an antisense oligonucleotide for miR-27a-3p, which has been previously demonstrated to be an AR regulated oncomiR in PCa. Conclusion From a panel of different miRs, we have demonstrated the androgenic potential and oncogenic capacity of miR-1271-5 p in PCa. Also, the use of antisense oligonucleotides for inhibition of miR-27a-3p has therapeutic potential for castrate resistant disease. Predicted targets of both miR-27a-3p and miR-1271-5 p include genes with roles in growth arrest, apoptosis and DNA repair. Further studies are ongoing, to elucidate the molecular and biological role of these miRs in PCa, providing a better understanding of disease development, as well as a foundation for advances in diagnosis and in treatment.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background: Acute myocardial infarction (AMI) is one of the leading causes of death among Egyptia... more Background: Acute myocardial infarction (AMI) is one of the leading causes of death among Egyptians. Monocyte chemoattractant protein-1 (MCP-1), regulation on activation normal T cell expressed and secreted (RANTES) and fractalkine (FKN) are chemokines that act as components of inflammatory response while methylenetetrahydrofolate reductase (MTHFR) is important enzyme in folate metabolism essential for homocysteine metabolism. Hyperhomocysteinemia has been linked to AMI. MCP-1 A-2518G, RANTES G-403A, CX3CR1 V249I and MTHFR C677T are important polymorphisms identified in MCP-1, RANTES, CX3CR1 and MTHFR genes respectively. There are conflicting data in the literature about their association with AMI. Therefore, the aim of the current study was to investigate the contribution of these gene variants to risk of AMI among Egyptians. Subjects and methods: The study comprised 200 subjects; 100 AMI patients and 100 age-matched healthy controls. The MCP-1, RANTES, CX3CR1 and MTHFR genotypes were determined by restriction fragment length polymorphism (PCR-RFLP). Results: Genotypes distributions for RANTES, fractalkine and MTHFR genes were significantly different between AMI patients and controls (p = 0.0221, 0.0498 and 0.0083) while those results in MCP-1 were not significantly different. A significant risk for AMI with concurrent presence of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) genotypes was observed. Conclusions: 1-Each of MTHFR 677T, RANTES-403A and CX3CR1 249V alleles is considered an independent risk factor for AMI. 2-Concurrent presence of high risk genotypes of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) increases risk of AMI more than their individual risks. 3-MCP-1 polymorphism is not associated with AMI among Egyptians.
Introduction: Breast cancer, being the most prevalent of its sort among women, is the second lead... more Introduction: Breast cancer, being the most prevalent of its sort among women, is the second leading causing of death in females after lung cancer. Most treatments are based upon breast receptors, of which HER2 receptors are found to be particularly important due to their aberrant overexpression In addition to enhancing the proliferation of cancer cells, HER2 functions as an intermediate receptor, facilitating communication between them. Of note, over 90% of breast tumors overexpress MUC1 receptor which, according to literature, the expression of MUC1 affects the growth of HER2 expression. In fact, after stress signals reach a cell's surface, MUC1 spreads over the cell surface, thereby activating HER2. Moreover, MUC1 oncogenesis increases tamoxifen resistance via the ER receptor. Therefore, targeting MUC1 can be effective in developing drugs that are tamoxifen responsive. In this study, by modulating the MUC1 receptor with an antibody previously made by our group, the expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 receptors in breast cancer cells were measured. Materials and Methods: MCF7 (ER/PR breast cancer cells and SKBR3 (HER2) positive were cultured in DMEM with 10% FBS. Cells were then treated with anti-MUC1 antibody for 24 and 48 hours. RNAs were extracted and cDNAs were synthetized. Primers were designed and synthesized and the expression alterations were compared to control using RT-PCR. Results: ER/PR gene expression in MCF7 cells treated with anti-MUC1 antibody, increased up to 70% and 60% for ER and PR respectively in
Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D rece... more Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells that are key players in the fight against breast cancer (BC). Shedding of MICA during BC progression acts as a formidable barrier against NK cells' immune-surveillance. Recently, miR-20a was found to mediate immune escape through repressing MICA levels on BC cells. However, targeting miR-20a/MICA using natural compounds has seldomly been investigated. Vitexin, a flavone Cglycoside, showed potent anticancer properties. It was reported that acetylation of glycosides increases their cytotoxic activity, with an unknown impact on immunogenicity. Our group has successfully isolated 3'-O-acetylvitexin from Ocimum basilicum which showed potent cytotoxic effects against colon cancer cells but has never been investigated in BC. Our aim is to unravel the role of the immunogenic miR-20a/MICA axis in BC patients and its regulation by vitexin and 3'-O-acetylvitexin. Methods: Breast tissues were collected from 26 BC patients. ER, PR and HER2 expression was quantified using immunohistochemistry. MDA-MB-231 TNBC cells and MCF-7 HRþ BC cells were treated with serial dilutions of vitexin and 3'-O-acetylvitexin. Their cytotoxic activities were assessed using MTT, colony forming and migration assays. Total RNA was extracted, reverse transcribed, then MICA and miR-20a were quantified using qRT-PCR. Results: miR-20a is upregulated in BC patients, while MICA was downregulated in MDA-MB-231 compared to MCF7 cells. Vitexin decreased MDA-MB-231 cellular viability and migration capacity. 3'-O-acetylvitexin resulted in a more pronounced dosedependent repression of TNBC cellular viability, colonogenicity and migration capacity. Treatment with vitexin didn't show any alteration in miR-20a but showed only 2 folds increase in MICA. However, 3'-O-acetylvitexin markedly decreased miR-20a with a concomitant increase in MICA by 12 folds. Conclusions: 3'-O-acetylvitexin displays more pronounced anticancer properties against TNBC through halting their progression and immune suppressive nature by modulating miR-20a/MICA axis. This highlights miR-20a/MICA axis as a potential therapeutic target in BC.
Overview of the covered topics: action mechanisms for ephedrine stimulation of α and β adrenocept... more Overview of the covered topics: action mechanisms for ephedrine stimulation of α and β adrenoceptor, impact of processing and combination on the pharmacokinetics of its ephedrine content, and key players in pharmacokinetics.
Cardiovascular disease (CVD) remains the leading cause of death worldwide. Despite huge efforts a... more Cardiovascular disease (CVD) remains the leading cause of death worldwide. Despite huge efforts and great advances in studying the genetic component of CVD, there is still a great need for exploring the genetic and environmental factors contributing to the development of this disease. Among these factors evolve modulation of nitric oxide (NO) homeostasis and oxidative stress as central players according to recent reports. A wide range of biochemical disturbances, including reduced bioavailability of NO and oxidative stress, has been shown to be associated with endothelial dysfunction (ED). Many studies described the contribution of ED in the predisposition of CVD, particularly coronary artery disease (CAD). Recent evidence indicates that ED may be genetically determined. This chapter points out to the key players that influence vascular NO levels and their role in the protection against and/or predisposition to CAD.
Vitamin D deficiency has become a globally acknowledged problem whose impact on societies has pro... more Vitamin D deficiency has become a globally acknowledged problem whose impact on societies has proven to surpass all medical expectations. Vitamin D is no longer peerlessly associated with bone diseases. In fact, collaborations of M.A. Abu el Maaty (*) Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universitat Heidelberg, Heidelberg, Germany e-mail: [email protected]; [email protected] S.I. Hassanein Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt e-mail: [email protected]; [email protected] M.Z. Gad Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt Division of Pharmacy and Biotechnology, Biochemistry Department, German University in Cairo (GUC), Cairo Governorate, Egypt e-mail: [email protected] # Springer Science+Business Media Dordrecht 2015 V.B. Patel, V.R. Preedy (eds.), Biomarkers in Cardiovascular Disease, DOI 10.1007/978-94-007-7741-5_23-1 1 clinicians and researchers have yielded the undeniable truth, that is, the affiliation of this unconventional vitamin with diseases that are currently grasping the media’s attention like autoimmune diseases and cancers. Having established the importance of this phenomenon, assuming complete understanding of the association of vitamin D with one of the leading causes of death in the world, cardiovascular disease, is only mildly precise. Observational studies tend to highlight the association of low vitamin D levels with various forms of cardiovascular disease as well as with the risk factors associated, whereas interventional studies have been conflicting. Nonetheless, in vitro studies have identified the presence of nuclear vitamin D receptors in the cardiovascular system in cells such as cardiomyocytes and endothelial cells, thereby warranting cardiovascular actions. Moreover, recent studies have demonstrated the ability of vitamin D to beneficially modulate effectors of the cardiovascular system such as the reninangiotensin-aldosterone system and the nitric oxide system. While there appears to be abundance in the number of publications on the epidemiological and mechanistic association of the vitamin with the disease, studies aiming to investigate the genetic component of the relationship are sparse. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in the vitamin D pathway, whether synthesis, metabolism, or elimination, that are associated with circulating levels of 25-hydroxyvitamin D [25(OH)D], the biomarker of vitamin D status, and thus it is conceptualized that such SNPs may act as novel genetic markers for cardiovascular disease since the disease has been associated with low levels of 25(OH)D. Several studies have investigated this hypothesis, yielding both positive and negative associations, highlighting the need for further investigations into the proposed triangular relationships between the SNPs, 25(OH)D levels, and the disease, which would spawn sound evidence prompting or discouraging professionals to extrapolate the findings to clinical genetic testing.
Background Triple Negative Breast cancer (TNBC) is a complex challenging disease that is not amen... more Background Triple Negative Breast cancer (TNBC) is a complex challenging disease that is not amenable to conventional treatment. Our research group has recently portrayed hydrogen sulphide (H2S) and its synthesizing enzymes, cystathionine β-synthase (CBS) and cystathionine-γ-lyase (CSE), as potent oncogenic mediators for TNBC progression. Recently, H2S has been casted as a potential modulator of cancer immune surveillance as well. Yet, the impact of H2S on the immunological profile of TNBC cells has never been investigated. Natural Killer (NK) cells are the native sentinels of the immune system that plays an indisputable role in TNBC-immune surveillance. TNBC immune suppressive tumour microenvironment is also rate-limiting step when immunotherapeutic approaches are tackled in case of TNBC patients. Thus the main aim of this study is to identify the role of endogenous H2S on NK cells&amp;amp;amp;amp;amp;amp;#39; activating ligands present on TNBC cells, immune suppressive tumour microenvironment and net effect on NK cells cytotoxicity. Methods Breast tissues were collected from 80 BC patients. ER, PR, HER-2 and Ki-67 levels were quantified using immunohistochemistry. MDA-MB-231 and MCF7 cells were cultured and transfected with different oligonucleotides. Total RNA was extracted and quantified by qRT-PCR. IFN-γ and TNF-α in cellular supernatant was measured using representative ELISA kits. NK cells were isolated from 30 healthy controls. The cytotoxicity of NK cells was measured using LDH Cytotoxicity Assay. Results MICA, MICB and ULBP2 were significantly down-regulated in TNBC tissues and cell lines. Knocking down of CBS and CSE using siRNAs resulted in a marked increase in MICA/B and ULBP2 expression in MDA-MB-231 cells. Nonetheless, knocking down of CBS and CSE resulted in a marked induction in IFN-γ production and attenuation of TNF-α levels. Upon co-culturing with healthy NK cells, Knocking down of endogenous H2S resulted in a marked increase in NK cells cytotoxicity. Conclusion This study showed that knocking down of CBS and CSE resulted in a improving NK cells cytotoxicity and alleviating tumor-induced immune suppressive microenvironment in TNBC patients. Legal entity responsible for the study German University in Cairo. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
Background: Myocardial microRNAs (Myo-miR) like MiR-1, miR-133 and miR-208 are speci c to cardiac... more Background: Myocardial microRNAs (Myo-miR) like MiR-1, miR-133 and miR-208 are speci c to cardiac muscles development and function. Diagnostic potential of MiR-1, miR-133 and miR-208 in acute episodes of myocardial infarction is unknown. Methods: Patient of newly onset of acute myocardial infarction with elevated ST-segment admitted to Ain-Shams university hospital Cairo from May 2013 to December 2022 were enrolled. Written consent was obtained. Circulating MiRNAs were measured at 04, 08, 12, 24, 48 hours from onset of angina by RT-PCR and compare with conventional creatin-kinases for diagnostic potential. Results were analyzed by student t-test, ROC curve calculations and ANOVA were performed using GraphPad-Prism-9Version. Results: 746 patients admitted with STEMI and 10(1.34%) cases were presented with new-onset episodes of STEMI with mean±SD age 54.2±8.49 year. miR-133a peaks at 8 hours, miR-208b peaks at 12 hours from onset of AMI compared to cTnI and CK-MB peak at 12hrs(P<0.001). ROC-curve for miR-133a AUC was 0.583,0.8,1,0.78 and 0.58 at 4,8,12,24 & 48 hours respectively. AUC for miR-208b was 0.87,0.888,0.888,0.627 compared to AUC of cTnI concentrations 0.59,1,1,0.75,0 and (ROC) curve for CK-MB was 0.59,1,1,0.8&0.73 respectively. Positive correlation was present between miR-133a and cTnI (R=0.926-R 2 = 0.858 P=0.47), miR-208b and cTnI (R=0.8-R 2 =0.64 P=0.1) , miR-208b and CK-MB was (R=0.888-R 2 =0.789 P=0.044) and CK-MB-cTnI (R=0.72) respectively. Conclusion: We showed miR-133a and miR-208b diagnostic speci city superior over conventional blood biomarkers for acute onset of STEMI. (NCT05692752)
Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D rece... more Background: The activating immune ligand, MICA, acts as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells that are key players in the fight against breast cancer (BC). Shedding of MICA during BC progression acts as a formidable barrier against NK cells' immune-surveillance. Recently, miR-20a was found to mediate immune escape through repressing MICA levels on BC cells. However, targeting miR-20a/MICA using natural compounds has seldomly been investigated. Vitexin, a flavone Cglycoside, showed potent anticancer properties. It was reported that acetylation of glycosides increases their cytotoxic activity, with an unknown impact on immunogenicity. Our group has successfully isolated 3'-O-acetylvitexin from Ocimum basilicum which showed potent cytotoxic effects against colon cancer cells but has never been investigated in BC. Our aim is to unravel the role of the immunogenic miR-20a/MICA axis in BC patients and its regulation by vitexin and 3'-O-acetylvitexin. Methods: Breast tissues were collected from 26 BC patients.
reduced growth of the AR dependent cell line and miR-1271-5 p mimic had the opposite effect. AR m... more reduced growth of the AR dependent cell line and miR-1271-5 p mimic had the opposite effect. AR mRNA levels were altered, as well as levels of miR specific target genes, after manipulation of PCa cell lines with miR-1271-5 p inhibitor and mimic. Similar effects were noticed with the use of an antisense oligonucleotide for miR-27a-3p, which has been previously demonstrated to be an AR regulated oncomiR in PCa. Conclusion From a panel of different miRs, we have demonstrated the androgenic potential and oncogenic capacity of miR-1271-5 p in PCa. Also, the use of antisense oligonucleotides for inhibition of miR-27a-3p has therapeutic potential for castrate resistant disease. Predicted targets of both miR-27a-3p and miR-1271-5 p include genes with roles in growth arrest, apoptosis and DNA repair. Further studies are ongoing, to elucidate the molecular and biological role of these miRs in PCa, providing a better understanding of disease development, as well as a foundation for advances in diagnosis and in treatment.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background: Acute myocardial infarction (AMI) is one of the leading causes of death among Egyptia... more Background: Acute myocardial infarction (AMI) is one of the leading causes of death among Egyptians. Monocyte chemoattractant protein-1 (MCP-1), regulation on activation normal T cell expressed and secreted (RANTES) and fractalkine (FKN) are chemokines that act as components of inflammatory response while methylenetetrahydrofolate reductase (MTHFR) is important enzyme in folate metabolism essential for homocysteine metabolism. Hyperhomocysteinemia has been linked to AMI. MCP-1 A-2518G, RANTES G-403A, CX3CR1 V249I and MTHFR C677T are important polymorphisms identified in MCP-1, RANTES, CX3CR1 and MTHFR genes respectively. There are conflicting data in the literature about their association with AMI. Therefore, the aim of the current study was to investigate the contribution of these gene variants to risk of AMI among Egyptians. Subjects and methods: The study comprised 200 subjects; 100 AMI patients and 100 age-matched healthy controls. The MCP-1, RANTES, CX3CR1 and MTHFR genotypes were determined by restriction fragment length polymorphism (PCR-RFLP). Results: Genotypes distributions for RANTES, fractalkine and MTHFR genes were significantly different between AMI patients and controls (p = 0.0221, 0.0498 and 0.0083) while those results in MCP-1 were not significantly different. A significant risk for AMI with concurrent presence of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) genotypes was observed. Conclusions: 1-Each of MTHFR 677T, RANTES-403A and CX3CR1 249V alleles is considered an independent risk factor for AMI. 2-Concurrent presence of high risk genotypes of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) increases risk of AMI more than their individual risks. 3-MCP-1 polymorphism is not associated with AMI among Egyptians.
Introduction: Breast cancer, being the most prevalent of its sort among women, is the second lead... more Introduction: Breast cancer, being the most prevalent of its sort among women, is the second leading causing of death in females after lung cancer. Most treatments are based upon breast receptors, of which HER2 receptors are found to be particularly important due to their aberrant overexpression In addition to enhancing the proliferation of cancer cells, HER2 functions as an intermediate receptor, facilitating communication between them. Of note, over 90% of breast tumors overexpress MUC1 receptor which, according to literature, the expression of MUC1 affects the growth of HER2 expression. In fact, after stress signals reach a cell's surface, MUC1 spreads over the cell surface, thereby activating HER2. Moreover, MUC1 oncogenesis increases tamoxifen resistance via the ER receptor. Therefore, targeting MUC1 can be effective in developing drugs that are tamoxifen responsive. In this study, by modulating the MUC1 receptor with an antibody previously made by our group, the expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 receptors in breast cancer cells were measured. Materials and Methods: MCF7 (ER/PR breast cancer cells and SKBR3 (HER2) positive were cultured in DMEM with 10% FBS. Cells were then treated with anti-MUC1 antibody for 24 and 48 hours. RNAs were extracted and cDNAs were synthetized. Primers were designed and synthesized and the expression alterations were compared to control using RT-PCR. Results: ER/PR gene expression in MCF7 cells treated with anti-MUC1 antibody, increased up to 70% and 60% for ER and PR respectively in
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