Differential expression of 16 genes coding for cell cycle – and apoptosis-related proteins in vitamin D-induced differentiation of HL-60 cells

Objective: The aim of the study was to analyze expression of several genes related to cell cycle regulation and apoptosis in realization of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced differentiation of HL-60 cells. Methods: The cultured HL-60 cells were treated with 1,25(OH)2D3. Quantitative real-time PCR was used for analyzing the changes in expression of 16 genes (Bcl-2, Bcl-xL, Mcl-1, Bik, caspase 6, caspase 7, cytochrome c, TNFR1, Myc, TGF-beta, JNK1, p38MAPK, p21, p27, Cdk2, cyclin E) at early phases of cell differentiation of HL-60 cells induced by 1,25(OH)2D3. Results: Among investigated genes, Bik and Myc gene expression was down-regulated at 48 h time points. JNK1 gene was markedly up-regulated and caspase-6 and cyclin E genes were down-regulated at 18 h time point. Conclusion: These findings suggest that there are no distinct apoptotic signals at early phases of cell differentiation. It is speculated that changes in the expression of the genes involved in vitamin D-induced apoptosis of HL-60 cells could be better visualized after the terminal stages of cell differentiation.Цель: проанализировать экспрессию ряда генов, участвующих в регуляции клеточного цикла и апоптоза в дифференцировке клеток HL-60 промиелоцитарного лейкоза человека, индуцированной 1альфа,25-дигидроксивитамином 3(1,25(OH 2 3). Методы: культивируемые клетки HL-60 инкуировали с 1,25(OH 2 D3. Количественную ПЦР в режиме реального времени использовали для анализа изменений экспрессии 16 генов (Bcl-2, Bc l-xL , l 1, k, каспаза 6, каспаза 7, цитохром с, TNFR1, Myc, TGF- beta, K 1, p38 MAPK, p21, p , Cdk2, иклин Е ) при индукции апоптоза и дифференцировки в клетках HL-60 под дествием 1,25(OH 2 D3. Результаты: среди исследованных генов отмечено снижение экспресси Bik и Myc через 48 ч. Экспрессия гена JNK1 повышена, а генов каспазы-6 и циклина Е снижена в точке 18 ч. Выводы: эти данные свидетельствуют об отсутствии четких сигналов экспрессии апоптоз-ассоциированных генов на ранних фазах клеточной дифференцировки. Предполагается, что изменения в экспрессии генов, участвующих в реализации апоптоза клеток HL-60, индуцированного витаминомD, могут быть выражены лишь на терминальных стадиях дифференцировки этих клеток

Serum uric acid level is associated with type 2 diabetes mellitus and diabetic regulation

Aim: Serum uric acid is a risk factor for cardiovascular and renal diseases. The role of uric acid as a renal and cardiac risk factor is more prominent in subjects with diabetes mellitus and hypertension. In present retrospective analyze, we aimed to compare serum uric acid levels of subjects with well and poorly controlled type 2 diabetes mellitus (T2DM) and healthy population. Methods: Patients with T2DM, who admitted to outpatient clinics of our institution between April 2017 and January 2018 were retrospectively analyzed. Diabetic subjects grouped into well or poorly regulated T2DM groups according to the HbA1c level (patients with an HbA1c lower than 7% were grouped as well regulated while others grouped as poorly regulated T2DM). Control subjects were healthy individuals whom asked for a routine check-up in our institution. Clinical and laboratory parameters of the study groups compared. Results: Serum uric acid levels of well-controlled T2DM, poorly controlled T2DM and control groups were 5.9±1, 6.7±1.8 and 4.3±1 mg/dL, respectively (p<0.001). Post Hoc analysis revealed that uric acid levels of well controlled diabetics were significantly lower than the uric acid levels of poorly controlled diabetics (p=0.04) and significantly higher than that of the control subjects (p<0.001). Conclusion: We suggest that elevated uric acid indicates a cellular level of damage and can be used as a prognostic indicator of pre-diabetes and T2DM. &nbsp

Takayasu Arteritis Initially Mimicking Infective Endocarditis

Takayasu’s arteritis (TA) is a chronic inflammatory disease that affects large vessels, predominantly the aorta and its main branches, leading to vessel wall thickening, fibrosis and stenosis. Cardiac and vascular symptoms are also commonly present at disease onset. In TA with thoracic or abdominal involvement, although murmur can be present at physical examination, the pulse difference may be absent. Here, we report a case of TA who initially resembled infective endocarditis and had widespread thoracic murmur

Quantitative real time PCR analysis of apoptosis-related gene expression in leukemias in ukrainian patients

Background: The complete medical consequences of the long-term exposure of population to ionizing radiation in post-Chernobyl period are still a controversial issue. The molecular biological analysis of malignant diseases of hematopoietic and lymphoid tissues in contaminated territories requires the precise diagnosis based on criteria of novel classifications. Aim: To analyze the relative gene expression of six apoptosis-related genes in different types of tumors of hematopoietic and lymphoid tissues in patients living in areas of Ukraine contaminated with radionuclides in post-Chernobyl period. Material and methods: The samples of the peripheral blood and bone marrow of 189 Ukrainian leukemia patients and 16 patients with reactive lymphocytosis were analyzed morphologically and immunocytochemically for precise delineation of the main forms and cytological variants of hematological malignancies according to new WHO classification. Expression of six apoptosis-related genes was analyzed in the individual samples of 9 different groups of malignant diseases of hematopoietic and lymphoid tissues and one group of patients with reactive lymphocytosis by quantitative RT-PCR. Expression of genes was assessed relative to that in control group of healthy donors. Results: Up-regulation of six analyzed apoptosis-related genes is observed in all groups of leukemia. In most groups of leukemia being analyzed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up-regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin’s lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1 and P38MAPK is evident. Practically all the groups of leukemia are characterized by stable high ratios of P53 up-regulation. Conclusion: In Ukrainian patients, up-regulation of six analyzed apoptosis-related genes is observed practically in all types of malignant diseases of hematopoietic and lymphoid tissues under study. Microarray-based analysis of these samples would be of great importance in terms of elucidating genomic interactions in leukemias and their possible association with ionizing radiation

SREDNJI VOLUMEN TROMBOCITA: PREVIDJELI GLASNIK ZLOĆUDNIH ČVOROVA ŠTITNJAČE

Physicians and surgeons pay much attention to evaluating thyroid nodules due to the malignant potential of these growths. Inflammation has a crucial role in the development of cancer. Increase in the mean platelet volume (MPV) has been described in various inflammatory conditions. Since some of thyroid nodules are malignant, we aimed to compare MPV values between patients with malignant and benign thyroid nodules after precise pathologic diagnosis. We retrospectively analyzed hemograms of patients having undergone thyroid surgery for thyroid nodule between January 2013 and January 2015, and compared them to those recorded in healthy subjects. MPV was higher in the malignant thyroid nodule group than in the benign nodule group (9.1±1 fL vs. 7.8±0.8 fL). The difference was statistically significant (p<0.001). Increased MPV should be considered as an assistive diagnostic tool in differentiating malignant and benign thyroid nodules. However, further prospective studies are required to confirm its usefulness in this population.Liječnici i kirurzi pridaju veliku pozornost procjeni čvorova štitne žlijezde zbog malignog potencijala ovih novotvorina. Upala ima ključnu ulogu u razvoju raka. Povećani srednji volumen trombocita (mean platelet volume, MPV) opisuje se u raznim upalnim stanjima. Kako su neki od čvorova štitne žlijezde zloćudni cilj nam je bio usporediti vrijednosti MPV između bolesnika sa zloćudnim i dobroćudnim čvorovima štitnjače nakon precizne patološke dijagnoze. Retrospektivno su analizirani hemogrami bolesnika podvrgnutih operaciji štitne žlijezde zbog čvorova od siječnja 2013. do siječnja 2015. godine te uspoređeni s vrijednostima dobivenim u zdravih osoba. MPV je bio viši u skupini zloćudnih tireoidnih čvorova nego u skupini dobroćudnih čvorova (9,1±1 fL prema 7,8±0,8 fL), a razlika je bila statistički značajna (p<0,001). Povišeni MPV može se smatrati pomoćnim dijagnostičkim alatom u razlikovanju zloćudnih i dobroćudnih čvorova štitnjače. Međutim, potrebna su daljnja istraživanja kako bi se potvrdila njegova korist kod ove populacije

Gene expression profiling of B-CLL in Ukrainian patients in post-Chernobyl period

Background: Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity. Material and methods: The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors. Results: We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes. Conclusion: In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 — as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination

Superior Vena Cava Syndrome and Multiple Venous Thrombosis in a Patient with B Cell Lymphoma

Background: Superior vena cava syndrome (SVCS) develops due to external mechanical pressure of superior vena cava (SVC) by a mass lesion or by an enlarged lymph node, tumor invasion of the vessel wall, or venous thrombosis resulting in intraluminal obstruction. Approximately 3,9% of lymphomas are complicated with SVCS. This rate reaches to 7% in diffuse large B cell lymphoma. The objective of this article was to describe a case report of  a young woman with a diffuse large B cell lymphoma, complicated with pericardial-pleural effusion and SVCS. Methods: A 25 year old woman referred to the Internal Medicine Clinic of Abant Izzet Baysal University Hospital with complaints of bloating in the neck and both arms. She had chest pain, dyspnea, cough, and epigastric discomfort for 10 days. A thoracic magnetic resonance imaging (MRI) test and pathological assessment were carried out. Results: A mediastinal mass 64x112x82 mm in size, displaced the heart and main mediastinal structures to posterior, was detected by thoracic magnetic resonance imaging (MRI) test. The result of the pathological assessment of the biopsy specimen revealed large B cell lymphoma, stained strongly and diffusely with CD20 and bcl-2. She was referred to the hematology unit and doing well after a chemotherapy. Conclusions: Diagnosis of SVCS requires high level of clinical suspicion, detailed and complete physical examination. Moreover,  SVCS should be kept in mind in the differential diagnosis of patients  presented with edema in the neck and upper extremities

Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus

Background: Type 2 diabetes mellitus is associated with chronic low grade inflammation. One of the novel inflammatory markers is hemogram derived neutrophil to lymphocyte ratio (NLR). Objective: We aimed to compare NLR levels of diabetic subjects and healthy controls and to observe possible correlation between NLR and HbA1c. Methods: Medical data of type 2 diabetic subjects admitted to out-patient clinics of our institution between April to July in 2017 were obtained from database and retrospectively analyzed. Control group was chosen from healthy subjects who visited our institution for a routine check-up. Anthropometric measures, laboratory data, including, HbA1c, NLR were recorded. Results: Median NLR of the type 2 DM group 2.44 (1.9) was significantly elevated when compared to healthy controls (1.5 (0.9), (p&lt;0.001). In addition, a Pearson\u2019s correlation test revealed that NLR was strongly correlated with age (r=0.26, p=0.008), fasting plasma glucose (r=0.38, p&lt;0.001), and HbA1c (r=0.49, p&lt;0.001). Conclusion: Elevated NLR in otherwise healthy subjects may be indicative of underlying impaired glucose metabolism and moreover, NLR should be used as a marker of diabetic control level in addition to HbA1c in type 2 diabetic subjects. DOI: https://dx.doi.org/10.4314/ahs.v19i1.35 Cite as: Duman TT, Aktas G, Atak BM, Kocak MZ, Erkus E, H S. Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus. Afri Health Sci. 2019;19(1). 1602-1606. https://dx.doi.org/10.4314/ahs.v19i1.3

Transcriptome analysis of Pseudomonas aeruginosa PAO1 grown at both body and elevated temperatures

YesFunctional genomics research can give us valuable insights into bacterial gene function. RNA Sequencing (RNA-seq) can generate information on transcript abundance in bacteria following abiotic stress treatments. In this study, we used the RNA-seq technique to study the transcriptomes of the opportunistic nosocomial pathogen Pseudomonas aeruginosa PAO1 following heat shock. Samples were grown at both the human body temperature (37 C) and an arbitrarily-selected temperature of 46 C. In this work using RNA-seq, we identified 133 genes that are differentially expressed at 46 C compared to the human body temperature. Our work identifies some key P. aeruginosa PAO1 genes whose products have importance in both environmental adaptation as well as in vivo infection in febrile hosts. More importantly, our transcriptomic results show that many genes are only expressed when subjected to heat shock. Because the RNA-seq can generate high throughput gene expression profiles, our work reveals many unanticipated genes with further work to be done exploring such genes products.University of Malaya High Impact Research (HIR) UM-MOHE HIR Grants (UM.C/625/1/HIR/MOHE/CHAN/14/1, No. H-50001-A000027; UM.C/625/1/HIR/MOHE/CHAN/01, No. A000001-50001); PPP Grant (PG081-2015B