Comparison of Early Warning Scores in Determining the Prognosis of COVID-19 Patients.

OBJECTIVE:  To compare the effectiveness of early warning score systems in predicting 30-day poor outcomes in Coronavirus Disease (COVID-19) patients admitted to the emergency department. STUDY DESIGN: Descriptive study. Place and and Duration of the Study: Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkiye, from March 2020 to March 2021. METHODOLOGY: The patients who presented to the emergency department, diagnosed with COVID-19 and tested positive for polymerase chain reaction were analysed. The study included the calculation of the rapid emergency medicine score, risk stratification in the emergency department in acutely ill older patients score, 4C mortality score, and modified early warning score for the patients. These scores were then compared in terms of their ability to predict adverse outcomes, defined as intensive care admission and/or mortality. RESULTS: During the study period, 10,281 COVID-19 patients were admitted to the emergency department. Out of them, 1,826 patients were included in the study. There were 159 (8.7%) cases with poor outcomes. The risk stratification in the emergency department in acutely ill older patients Score was the most successful in poor prognosis. CONCLUSION: Based on the findings of this study, the risk stratification in the emergency department in acutely ill older patients score demonstrated greater efficacy compared to other early warning scores in identifying patients diagnosed with COVID-19 who had an early indication of a poor prognosis. KEY WORDS: Early warning score, 4C mortality score, REMS, Rise-up score, MEWS, Emergency department, COVID-19.

TERT Promoter Methylation Is Oxygen-Sensitive and Regulates Telomerase Activity.

Telomere repeats protect linear chromosomes from degradation, and telomerase has a prominent role in their maintenance. Telomerase has telomere-independent effects on cell proliferation, DNA replication, differentiation, and tumorigenesis. TERT (telomerase reverse transcriptase enzyme), the catalytic subunit of telomerase, is required for enzyme activity. TERT promoter mutation and methylation are strongly associated with increased telomerase activation in cancer cells. TERT levels and telomerase activity are downregulated in stem cells during differentiation. The link between differentiation and telomerase can provide a valuable tool for the study of the epigenetic regulation of TERT. Oxygen levels can affect cellular behaviors including proliferation, metabolic activity, stemness, and differentiation. The role of oxygen in driving TERT promoter modifications in embryonic stem cells (ESCs) is poorly understood. We adopted a monolayer ESC differentiation model to explore the role of physiological oxygen (physoxia) in the epigenetic regulation of telomerase and TERT. We further hypothesized that DNMTs played a role in physoxia-driven epigenetic modification. ESCs were cultured in either air or a 2% O2 environment. Physoxia culture increased the proliferation rate and stemness of the ESCs and induced a slower onset of differentiation than in ambient air. As anticipated, downregulated TERT expression correlated with reduced telomerase activity during differentiation. Consistent with the slower onset of differentiation in physoxia, the TERT expression and telomerase activity were elevated in comparison to the air-oxygen-cultured ESCs. The TERT promoter methylation levels increased during differentiation in ambient air to a greater extent than in physoxia. The chemical inhibition of DNMT3B reduced TERT promoter methylation and was associated with increased TERT gene and telomerase activity during differentiation. DNMT3B ChIP (Chromatin immunoprecipitation) demonstrated that downregulated TERT expression and increased proximal promoter methylation were associated with DNMT3B promoter binding. In conclusion, we have demonstrated that DNMT3B directly associates with TERT promoter, is associated with differentiation-linked TERT downregulation, and displays oxygen sensitivity. Taken together, these findings help identify novel aspects of telomerase regulation that may play a role in better understanding developmental regulation and potential targets for therapeutic intervention.

Combinatorial islet protective therapeutic approaches in ß-cell transplantation: Rationally designed solutions using a target product profile.

While progress has been made in the development of islet cell transplantation (ICT) as a viable alternative to the use of exogenous insulin therapy in the treatment of type 1 diabetes, it has not yet achieved its full potential in clinical studies. Ideally, ICT would enable lifelong maintenance of euglycemia without the need for exogenous insulin, blood glucose monitoring or systemic immune suppression. To achieve such an optimal result, therapeutic approaches should simultaneously promote long-term islet viability, functionality, and localized immune protection. In practice, however, these factors are typically tackled individually. Furthermore, while the requirements of optimal ICT are implicitly acknowledged across numerous publications, the literature contains few comprehensive articulations of the target product profile (TPP) for an optimal ICT product, including key characteristics of safety and efficacy. This review aims to provide a novel TPP for ICT and presents promising tried and untried combinatorial approaches that could be used to achieve the target product profile. We also highlight regulatory barriers to the development and adoption of ICT, particularly in the United States, where ICT is only approved for use in academic clinical trials and is not reimbursed by insurance carriers. Overall, this review argues that the clear definition of a TPP in addition to the use of combinatorial approaches could help to overcome the clinical barriers to the widespread adoption of ICT for the treatment of type 1 diabetes.

The effect of the COVID-19 pandemic on forensic cases admitted to an emergency department.

INTRODUCTION: The COVID-19 disease has given rise to various negative effects on human life in terms of health and economic and social well-being. We believe that these negative effects may have led to increased forensic incidents such as violence and suicide. Therefore, in this study, we sought to examine the effects of COVID-19 in forensic cases admitted to an emergency department. Methods: This is a retrospective observational study, performed at the emergency department of Fatih Sultan Mehmet Education and Research Hospital. Forensic cases admitted between March and June 2020 (pandemic period) and forensic cases admitted between March and June 2019 (pre-pandemic period) were compared in the study. Results: A total of 4296 patients were included in the study, of which 3011 were admitted during the pre-pandemic period and 1285 during the time of the COVID-19 pandemic. While the percentages of suicide attempts (3.6%), motorcycle traffic accidents (7.4%), and violent incidents (29.4%) were higher during the pandemic period, the percentages of in-vehicle traffic accidents (5.4%) and pedestrian traffic accidents (2.2%) were lower (respectively, p = 0.035, p = 0.005, p < 0.001, p = 0.015, p = 0.008). At the time of the pandemic, the percentages of incidents of violence against women (44.2%) and traffic accidents with a motorcycle involving men (9.3%) were higher than during the time before the pandemic (p < 0.001 and p < 0.001, respectively). Conclusions: The effects of the pandemic on our lifestyle are indisputable. This study reveals that the pandemic also affected patients who were admitted to the emergency department for forensic reasons. In addition, the increase in the percentages of suicide and violent events indicates that pandemics probably increase feelings of fear, loss, and hopelessness, and special precautions should be taken to maintain order in the society.

How physicians approach hereditary angioedema: a single center study.

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by C1-inhibitor deficiency. It is characterized by recurrent attacks of cutaneous and upper respiratory tract swelling, and abdominal pain due to mucosal edema. Early detection and treatment prevent unnecessary interventions, improves quality of life, and prevents potentially fatal attacks. Objective: The present study aims to investigate physicians level of knowledge and awareness regarding HAE. Methods: A questionnaire about HAE was applied to 393 physicians from a university hospital. Participants were requested to choose one or several answers to multiple-choice questions. Results: Seven and three tenths percent of study participants stated to have never heard of HAE. Twenty-seven physicians (7.4%) chose the exact correct answers regarding diagnostic tests, and 2 (0.8%) chose the exact correct answers regarding emergency management. A composite of internists, pediatrists and emergency medicine specialists had a significantly higher mean score than other physicians (p = 0.047). Physicians from internal medical sciences scored significantly higher than physicians from surgical medical sciences (p = 0.022). Conclusion: The present study reveals that physician awareness about HAE is low, and physicians misdiagnose HAE attacks as histaminergic angioedema attacks, and therefore provide ineffective treatment. Although HAE is a rare disease, physician awareness must be increased, because early diagnosis and effective treatment are vital for the patients.

Physoxia Influences Global and Gene-Specific Methylation in Pluripotent Stem Cells.

Pluripotent stem cells (PSC) possess unlimited proliferation, self-renewal, and a differentiation capacity spanning all germ layers. Appropriate culture conditions are important for the maintenance of self-renewal, pluripotency, proliferation, differentiation, and epigenetic states. Oxygen concentrations vary across different human tissues depending on precise cell location and proximity to vascularisation. The bulk of PSC culture-based research is performed in a physiologically hyperoxic, air oxygen (21% O2) environment, with numerous reports now detailing the impact of a physiologic normoxia (physoxia), low oxygen culture in the maintenance of stemness, survival, morphology, proliferation, differentiation potential, and epigenetic profiles. Epigenetic mechanisms affect multiple cellular characteristics including gene expression during development and cell-fate determination in differentiated cells. We hypothesized that epigenetic marks are responsive to a reduced oxygen microenvironment in PSCs and their differentiation progeny. Here, we evaluated the role of physoxia in PSC culture, the regulation of DNA methylation (5mC (5-methylcytosine) and 5hmC (5-hydroxymethylcytosine)), and the expression of regulatory enzyme DNMTs and TETs. Physoxia enhanced the functional profile of PSC including proliferation, metabolic activity, and stemness attributes. PSCs cultured in physoxia revealed the significant downregulation of DNMT3B, DNMT3L, TET1, and TET3 vs. air oxygen, accompanied by significantly reduced 5mC and 5hmC levels. The downregulation of DNMT3B was associated with an increase in its promoter methylation. Coupled with the above, we also noted decreased HIF1A but increased HIF2A expression in physoxia-cultured PSCs versus air oxygen. In conclusion, PSCs display oxygen-sensitive methylation patterns that correlate with the transcriptional and translational regulation of the de novo methylase DNMT3B.

Epigenetic features in regulation of telomeres and telomerase in stem cells.

The epigenetic nature of telomeres is still controversial and different human cell lines might show diverse histone marks at telomeres. Epigenetic modifications regulate telomere length and telomerase activity that influence telomere structure and maintenance. Telomerase is responsible for telomere elongation and maintenance and is minimally composed of the catalytic protein component, telomerase reverse transcriptase (TERT) and template forming RNA component, telomerase RNA (TERC). TERT promoter mutations may underpin some telomerase activation but regulation of the gene is not completely understood due to the complex interplay of epigenetic, transcriptional, and posttranscriptional modifications. Pluripotent stem cells (PSCs) can maintain an indefinite, immortal, proliferation potential through their endogenous telomerase activity, maintenance of telomere length, and a bypass of replicative senescence in vitro. Differentiation of PSCs results in silencing of the TERT gene and an overall reversion to a mortal, somatic cell phenotype. The precise mechanisms for this controlled transcriptional silencing are complex. Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which presents an important prospect for understanding cancer and stem cell biology. Control of down-regulation of telomerase during differentiation of PSCs provides a convenient model for the study of its endogenous regulation. Telomerase reactivation has the potential to reverse tissue degeneration, drive repair, and form a component of future tissue engineering strategies. Taken together it becomes clear that PSCs provide a unique system to understand telomerase regulation fully and drive this knowledge forward into aging and therapeutic application.

DNMT3B Is an Oxygen-Sensitive De Novo Methylase in Human Mesenchymal Stem Cells.

The application of physiological oxygen (physoxia) concentrations is becoming increasingly commonplace within a mammalian stem cell culture. Human mesenchymal stem cells (hMSCs) attract widespread interest for clinical application due to their unique immunomodulatory, multi-lineage potential, and regenerative capacities. Descriptions of the impact of physoxia on global DNA methylation patterns in hMSCs and the activity of enzymatic machinery responsible for its regulation remain limited. Human bone marrow-derived mesenchymal stem cells (BM-hMSCs, passage 1) isolated in reduced oxygen conditions displayed an upregulation of SOX2 in reduced oxygen conditions vs. air oxygen (21% O2, AO), while no change was noted for either OCT-4 or NANOG. DNA methylation marks 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) showed decreases in 2% O2 environment (workstation) (2% WKS). DNMT3B (DNA methyltransferase 3B) and TET1 (Ten-eleven translocation enzyme 1) displayed reduced transcription in physoxia. Consistent with transcriptional downregulation, we noted increased promoter methylation levels of DNMT3B in 2% WKS accompanied by reduced DNMT3B and TET1 protein expression. Finally, a decrease in HIF1A (Hypoxia-inducible factor 1A) gene expression in 2% WKS environment correlated with protein levels, while HIF2A was significantly higher in physoxia correlated with protein expression levels vs. AO. Together, these data have demonstrated, for the first time, that global 5mC, 5hmC, and DNMT3B are oxygen-sensitive in hMSCs. Further insights into the appropriate epigenetic regulation within hMSCs may enable increased safety and efficacy development within the therapeutic ambitions.

Telomerase Regulation: A Role for Epigenetics.

Telomerase was first described by Greider and Blackburn in 1984, a discovery ultimately recognized by the Nobel Prize committee in 2009. The three decades following on from its discovery have been accompanied by an increased understanding of the fundamental mechanisms of telomerase activity, and its role in telomere biology. Telomerase has a clearly defined role in telomere length maintenance and an established influence on DNA replication, differentiation, survival, development, apoptosis, tumorigenesis, and a further role in therapeutic resistance in human stem and cancer cells including those of breast and cervical origin. TERT encodes the catalytic subunit and rate-limiting factor for telomerase enzyme activity. The mechanisms of activation or silencing of TERT remain open to debate across somatic, cancer, and stem cells. Promoter mutations upstream of TERT may promote dysregulated telomerase activation in tumour cells but additional factors including epigenetic, transcriptional and posttranscriptional modifications also have a role to play. Previous systematic analysis indicated methylation and mutation of the TERT promoter in 53% and 31%, respectively, of TERT expressing cancer cell lines supporting the concept of a key role for epigenetic alteration associated with TERT dysregulation and cellular transformation. Epigenetic regulators including DNA methylation, histone modification, and non-coding RNAs are now emerging as drivers in the regulation of telomeres and telomerase activity. Epigenetic regulation may be responsible for reversible silencing of TERT in several biological processes including development and differentiation, and increased TERT expression in cancers. Understanding the epigenetic mechanisms behind telomerase regulation holds important prospects for cancer treatment, diagnosis and prognosis. This review will focus on the role of epigenetics in telomerase regulation.

Drug-induced anaphylaxis in the emergency department: A prospective observational study.

Objective: Anaphylaxis is an acute, life-threatening, systemic hypersensitivity reaction. It is usually triggered by drugs, foods, and insect stings. The primary objective of our study is to determine the factors affecting drug-induced anaphylaxis to contribute to early diagnosis and treatment in these patients. Methods: Patients over 18 years old who were diagnosed drug-induced anaphylaxis in the Goztepe Hospital within a period of 1 year were evaluated prospectively. Patients demographical data, etiological factors, clinical findings, and treatment information were recorded. Results: Forty-four patients were enrolled in the study of which 25 (56.8%) were female. The median age of women and men was 54 (min: 22, max 82) and 44 (min 18, max 82), respectively. Twenty-three (52%) of them had a history of anaphylaxis. The most common causes of drug-induced anaphylaxis were antibiotics (36%) and nonsteroidal anti-inflammatory drugs (18%), respectively. Adrenaline was applied to 17 (38%) of the patients in the treatment. Conclusion: Antibiotics were the most common drugs causing drug-induced anaphylaxis and adrenaline was underused which is the first-line treatment in the anaphylaxis. Some clinicians refrain from administering adrenaline. The reasons underlying this approach should be investigated.

Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin-Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers.

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.

[Investigation of Anti-leishmanial Effects of Bee Products (Honey, Propolis) on Leishmania tropica Promastigotes]. / Ari Ürünlerinin (Bal, Propolis) Leishmania tropica Promastigotlari Üzerine Antileysmanyal Etkilerinin Arastirilmasi.

This study was aimed to investigate the anti-leishmanial effects of bee products (honey and propolis) by using the causative agent of cutaneous leishmaniasis Leishmania tropica promastigotes, in in vitro culture. In vitro anti-leishmanial efficacy of honey (pine, flower and chestnut) and propolis used in the study were evaluated using the microdilution method. Honey, which is a bee product, was dissolved with RPMI medium containing fetal calf serum (FCS) and diluted in the same medium, and serial dilutions were prepared in concentrations between 62.5-1000 mg/ml. Propolis, on the other hand, was dissolved with ethyl alcohol and only 2.5 µl was used from all these concentrations since the alcohol content was more than 50% in these concentrations prepared and we thought that this rate would negatively effect the parasite development. Then, RPMI containing FCS was diluted in the medium and serial dilutions were prepared at concentrations between 50-800 µg/ml. To the dilutions prepared, the promastigot suspension was added so that their final concentrations in the wells were 1 x 106 promastigot/ml and then the medium was incubated for 24 and 48 hours in 26°C. After the incubation, promastigotes were determined microscopically for morphology, mobility and live parasite density, and cell viability was determined by MTS method and 50% inhibitor concentrations (IC50) were compared with control groups. Anti-leishmanial activity of propolis (50, 100, 200, 400 and 800 µg/ml) and honey (62.5, 125, 250, 500 and 1000 mg/ml) on promastigotes was evaluated in vitro. In microscopic examinations, pine honey showed anti-leishmanial activity starting from 62.5 mg/ml, flower honey 250 mg/ml, and chestnut honey 125 mg/ml, and pine honey was more effective on promastigotes (p< 0.05), and propolis was effective from 100 µg/ml concentration. It has been determined that very low concentrations of propolis caused changes in the morphological structure of the parasites and were more effective than the other bee products. The prevention of cell proliferation and decreasing of the IC50 values according with the time of pine honey (IC50= 109.28 mg/ml), flower honey (IC50= 248.07 mg/ml), chestnut honey (IC50= 147.65 mg/ml) and propolis (IC50= 82.98 µg/ml) applied on L.tropica promastigot cell culture was determined by MTS method. In this study, it was found that various concentrations of pine, flower, chestnut honey and propolis showed anti-leishmanial activity on L. tropica promastigotes. It has been observed that pine honey is more effective on promastigotes after 48 hours of incubation period, and propolis is more effective in both morphology and cell inhibition of the parasites even at very low concentrations. It is believed that these data can be used as an alternative treatment method against cutaneous leishmaniasis infections and further studies are required.

Revision arthroplasty with rotating hinge systems for total knee arthroplasty instability.

OBJECTIVE: Restoring stability after total knee arthroplasty (TKA) and improving joint function using a cemented rotating hinge system. INDICATIONS: Ligament instability and/or osseous defects (including Anderson Orthopaedic Research Institute [AORI] classification type II defects) after primary TKA or TKA revision surgery. CONTRAINDICATIONS: Distal femoral or proximal tibial bowing requiring implant systems that provide femoral or tibial offset stems. Persistent periprosthetic infection. Poor therapeutic compliance. AORI type III defects. SURGICAL TECHNIQUE: Medial arthrotomy. Femoral and tibial component removal with small saw blades and chisels. Intramedullary alignment for the tibial and femoral cuts. Debridement and removal of membranes and cement remnants. Reconstruction of joint line and correct TKA alignment. Trial reduction. Cement fixation. POSTOPERATIVE MANAGEMENT: Unrestricted range of motion, partial weight bearing for 4 weeks. RESULTS: Between 2012 and 2013, 18 patients suffering from ligament insufficiency after TKA were revised using the described system and included in a prospective study protocol. The mean follow-up was 37 months (range 30-46 months). There was a significant improvement of the Oxford Knee Score (OKS) from 19 (range 7-29) preoperatively to 29 (range 10-45) postoperatively (p = 0.004). The Knee Society Score (KSS) knee assessment subscore improved from 35 (range 9-70) to 67 (range 35-97) (p = 0.002) and the pain score from 7 (range 0-50) to 24 (range 0-50) (p = 0.008).

Demographic characteristics and delayed neurological sequelae risk factors in carbon monoxide poisoning.

AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240 days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43 ±â€¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.

The effect of ICRT-3 on Wnt signaling pathway in head and neck cancer.

The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of ß-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to ß-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water-soluble tetrazolium salt-1 method. The effect of ICRT-3 on apoptosis was detected by using Annexin V and caspase-3, caspase-9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT-3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT-3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.

Investigation of the effect of telomerase inhibitor BIBR1532 on breast cancer and breast cancer stem cells.

It is emphasized that cancer stem cells (CSCs) forming the subpopulation of tumour cells are responsible for tumour growth, metastasis, and cancer drug resistance. Inadequate response to conventional therapy in breast cancer leads researchers to find new treatment methods and literature surveys that support CSC studies. A selective anticancer agent BIBR1532 inhibits the telomerase enzyme. Many of the chemotherapeutic drugs used in clinical trials have harmful effects, but the advantage of telomerase-based inhibitors is that they are less toxic to healthy tissues. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway is common in breast cancer, and the interaction between the mTOR pathway and human telomerase reverse transcriptase (hTERT) is essential for the survival of cancer cells. In our study, we treated MCF-7, breast cancer stem cell (BCSC) and normal breast epithelial cell MCF10A with the BIBR1532 inhibitor. The IC 50 doses for the 48th hour of BIBR1532 treatment were detected as 34.59 µM in MCF-7, 29.91 µM in BCSCs, and 29.07 µM in MCF10A. It has been observed that this agent induces apoptosis in the BCSC and MCF-7 cell lines. According to the results of cell cycle analysis, G 2 /M phase accumulation was observed in BCSC and MCF-7 cell lines. It has also been shown that BIBR1532 suppresses telomerase activity in BCSC and MCF-7. The effect of BIBR1532 on the mTOR signalling pathway has been investigated for the first time in this study. It is thought that the telomerase inhibitor may bring a new approach to the treatment and it may be useful in the treatment of CSCs.

Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies.

Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2-[(E)-3-Naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K-562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST-1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K-562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41-fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K-562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.

Correlation between telomerase and mTOR pathway in cancer stem cells.

Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able to self-renew, proliferate, differentiate similar to normal stem cells. Therefore, targeting CSCs has been considered as a new approach in cancer therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase which plays an important role in regulating cell proliferation, differentiation, cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation provides replicative feature and immortality to CSCs, so the stemness and replicative properties of CSCs depend on telomerase activity. Therefore hTERT/telomerase activity may become a universal biomarker for anticancer therapy and it is an attractive therapeutic target for CSCs. It is known that mTOR regulates telomerase activity at the translational and post-translational level. Researchers show that mTOR inhibitor rapamycin reduces telomerase activity without changing hTERT mRNA activity. Correlation between mTOR and hTERT is important for survival and immortality of cancer cells. In addition, the PI3K/AKT/mTOR signaling pathway and hTERT up-regulation are related with cancer stemness features and drug resistance. mTOR inhibitor and TERT inhibitor combination may construct a novel strategy in cancer stem cells and it can make a double effect on telomerase enzyme. Consequently, inhibition of PI3K/AKT/mTOR signaling pathway components and hTERT activation may prohibit CSC self-renewal and surpass CSC-mediated resistance in order to develop new cancer therapeutics.

Serum Preptin and Amylin Values in Psoriasis Vulgaris and Behçet's Patients.

BACKGROUND: Insulin resistance is found in both psoriasis and Behçet's disease. No study has yet explored whether preptin and amylin, two hormones associated with insulin resistance, are involved in the insulin resistance observed in patients with psoriasis and Behçet's disease. OBJECTIVES: We aimed to explore how the amounts of preptin and amylin change in psoriasis and Behçet's disease and whether they are involved in the etiopathology of these two diseases, by comparing hormone levels in patients and healthy controls. METHODS: The study registered 30 patients with psoriasis, 30 patients with Behçet's disease, and 30 healthy volunteers (as a control group). Fasting blood sugar, triglyceride, LDL, VLDL, HDL, total cholesterol, HbA1c, C-peptide, insulin, and serum preptin and amylin levels were measured in all subjects. RESULTS: Serum preptin and amylin levels were significantly lower in the patients with psoriasis and Behçet's disease than in the control group (P < 0.001, P = 0.004, and P = 0.008, respectively). A comparison of the serum preptin and amylin levels between the patients with psoriasis and Behçet's disease did not reveal a statistically significant difference. Serum insulin level and The homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly lower in the psoriasis patient group relative to the control group (P = 0.02 and P = 0.03, respectively), while the values for the Behçet's disease group did not differ significantly from those for the control group CONCLUSIONS: Serum levels of preptin and amylin were significantly lower in patients with psoriasis and Behçet's disease, indicating that these hormones may be a factor for development of metabolic syndrome in these two diseases.

A case of acute hepatitis following mad honey ingestion.

Acute hepatitis is characterized by liver inflammation and liver cell necrosis. The most frequently observed underlying cause thereof is viruses, but various other causes, such as alcohol, medication, or toxins may also lead thereto. In this paper, a case of acute hepatitis presenting with bradycardia, hypotension, and a prominent increase in liver enzymes following mad honey ingestion is discussed. Since there are only few cases of acute hepatitis following mad honey ingestion in the literature, we want to present this subject matter.