Kolorektal Kanser Riski ile Hipoksiyle İndüklenen Faktör-1 Alfa (HIF-1?) ve von Hippel-Lindau (VHL)

Colorectal cancers (CRC) are among the four most frequently seen cancers in humans and are the second leading cause of can-cer-related deaths. Hypoxia up regulates multiple genes involved in different steps of metastatic process, including angiogenesis, proliferation, migration, invasion, motility, adhesion and survival. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator protein of cellular hypoxia-response and triggers the expression of above-mentioned metastatic-process genes. Von Hippel Lindau (VHL) is a protein that plays critical role in the response to hypoxia and product of a tumor suppressor gene. We studied three single nu-cleotide polymorphisms, rs11549465 (1772C T), rs11549467 (1790G A) in HIF-1? and rs779805 (5’UTR A G) in VHL, and assessed their associations with CRC risk, clinicopathologic and demographic features and lifestyle, and tumor stage and grade of CRC patients and/or healthy controls. ARMS-PCR technique for genotyping of rs11549465 C T and rs11549467 GA and PCR-RFLP technique for genotyping of rs779805 AG were used. CT/TT genotypes of HIF-1? 1772C T polymorphism were found to increase the risk of colorectal cancer in patients (OR 1.96, 95% CI 1.02-3.77, p 0.05). Additionally, it was demon-strated via statistical analyses that higher age, male gender, cancer history in family, co-existing diseases, and exposure to white soil stands to be risk factors of colorectal cancer (p 0.05). No significant relation was found between patient’s TNM stages and distributions of genotype (p 0.05). The findings from our study demonstrates that, in addition to risk factors for colorectal can-cer, scanning CT/TT genotypes of HIF-1? C1772T polymorphism can be advantageous in early-diagnosis of colorectal cancer.Kolorektal kanser insanda sık görülen dört kanser türü arasında yer alır ve ölüme götüren kanserler içerisinde ikinci sıradadır. Hipoksi, anjiogenez, proliferasyon, migrasyon, invazyon, adhezyon ve sağkalımı içeren metastatik süreçte rol alan pek çok geni kontrol eder. Birçok kanser türünün gelişmesinde etkili olduğu düşünülen HIF-1? gen proteini hücrenin hipoksiye cevabının anahtar regülatörüdür. VHL proteini tümör baskılayıcı bir genin ürünü olup, hipoksiye cevap yolağında önemli rol alır. Biz bu çalışmada, HIF-1? geninin rs11549465 (1772C T), rs11549467 (1790G A) polimorfizmleri ile VHL geninin rs779805 (5’UTR A G) polimorfizmini ve ayrıca yaş, cinsiyet, ailede kanser öyküsü, sistemik hastalıklar, beyaz toprak maruziyeti, sigara ve alkol tüketimi ile CRC riski arasındaki ilişkiyi araştırdık. Çalışmaya, histolojik olarak teyit edilen CRC tanısı almış 92 hasta ile kontrol grubu olarak 101 birey katıldı. DNA izolasyonu için periferal kan kullanıldı. HIF-1? genindeki rs11549465 C T ve rs11549467 GA polimorfizm değişimlerini genotiplemek için ARMS-PZR; VHL rs779805 A G polimorfizm değişimini genotiplemek için PZR-RFLP moleküler tanı yöntemleri kullanıldı. Hasta grubunda, HIF-1?1772C T polimorfizminin CT/TT genotipleri CRC riski ile istatistiksel anlamda ilişkili bulundu (OR 1.96, 95% CI 1.02-3.77, p 0.05). Ayrıca kanser öyküsü, ileri yaş, erkek cinsiyet, eşlik eden hastalıklar ve beyaz toprak maruziyetinin kolorektal kanser için birer risk faktörü olduğu istatistiksel analizlerle belirlendi (p 0.05). Hastaların TNM evreleri ile genotip dağılımları arasında belirgin bir ilişkiye rastlanmadı (p 0.05). Sonuç olarak, HIF-1? C1772T polimorfizminin CT/TT genotipleri, ailede kanser öyküsü ve beyaz toprak maruziyeti CRC için birer risk faktörüdür ve CT/TT genotipi kolorektal kanserin erken tanısında avantaj sağlayabilir bir risk belirteci olarak kullanılabilecekti

Synthesis, structure, electrochemical and antimicrobial properties of N,N '-bis(ferrocenylmethyl)imidazolinium salts

WOS: 000345115900057The N, N'-bis(ferrocenylmethyl)imidazolinium chloride (3) and bromide (4) were prepared by reaction of N,N'-bis(ferrocenylmethyl)ethylenediamine (2) with NH4X (X = Cl, Br). The N,N'-bis(ferrocenylmethyl)imidazolinium tetrafluoroborate (6) was obtained in two steps from compound (2). The first step involves the synthesis of N,N'-bis(ferrocenylmethyl)imidazolidine (5) by condensation of (2) with aqueous formaldehyde. Compound (5) was successfully converted to the N,N'-bis(ferrocenylmethyl)imidazolinium tetrafluoroborate (6) by treatment with tritylium tetrafluoroborate. The new compounds were characterized by H-1 and C-13 NMR, IR and elemental analysis techniques which support the proposed structures. The X-ray crystal structure of the N,N'-bis(ferrocenylmethyl)imidazolidine (5) shows two ferrocenyl moieties bridged by an imidazolidine ring. The electrochemical properties were determined by cyclic voltammetry for all compounds. The compounds were screened for their in vitro antimicrobial activities against the Gram-positive, Gram-negative bacteria and antifungal activity against a Candida albicans. (3), (4), (6) show significant antimicrobial activity and theirs MIC values ranged from 169 to 520 mu g/mL. (C) 2014 Elsevier B.V. All rights reserved.Celal Bayar UniversityCelal Bayar University [BAP 2011-033, BAP 2012-078]This work was financially supported by Celal Bayar University (BAP 2011-033, BAP 2012-078). We thank Prof. Stephen T. Astley of Ege University for assistance in checking the English language of the manuscript and Asst. Prof. Dr. Suleyman Kocak for helpful discussion on CV studies

COVID-19: vaccination vs. hospitalization

Objective Vaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols. Setting Inoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose. Methods We collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status. Results We identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac. Conclusion Effective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort

Background and objectivesAlthough several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. MethodsPatients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. ResultsWe retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 +/- 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (beta [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (beta [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (beta [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). ConclusionOur findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment

The predictors of long-COVID in the cohort of Turkish Thoracic Society- TURCOVID multicenter registry: One year follow-up results

Objective: To evaluate long-term effects of COVID-19, and to determine the risk factors in long-COVID in a cohort of the Turkish Thoracic Society (TTS)-TURCOVID multicenter registry.Methods: Thirteen centers participated with 831 patients; 504 patients were enrolled after exclusions. The study was designed in three-steps: (1) Phone questionnaire; (2) retrospective evaluation of the medical records; (3) face-to-face visit. Results: In the first step, 93.5% of the patients were hospitalized; 61.7% had a history of pneumonia at the time of diagnosis. A total of 27.1% reported clinical symptoms at the end of the first year. Dyspnea (17.00%), fatigue (6.30%), and weakness (5.00%) were the most prevalent long-term symptoms. The incidence of long-term symptoms was increased by 2.91 fold (95% CI 1.04-8.13, P=0.041) in the presence of chronic obstructive pulmonary disease and by 1.84 fold (95% CI 1.10-3.10, P=0.021) in the presence of pneumonia at initial diagnosis, 3.92 fold (95% Cl 2.29-6.72, P=0.001) of dyspnea and 1.69 fold (95% Cl 1.02-2.80, P=0.040) fatigue persists in the early-post-treatment period and 2.88 fold (95% Cl 1.52- 5.46, P=0.001) in the presence of emergency service admission in the post COVID period. In step 2, retrospective analysis of 231 patients revealed that 1.4% of the chest X-rays had not significantly improved at the end of the first year, while computed tomography (CT) scan detected fibrosis in 3.4%. In step 3, 138 (27.4%) patients admitted to face-to-face visit at the end of first year; at least one symptom persisted in 49.27% patients. The most common symptoms were dyspnea (27.60%), psychiatric symptoms (18.10%), and fatigue (17.40%). Thorax CT revealed fibrosis in 2.4% patients. Conclusions: COVID-19 symptoms can last for extended lengths of time, and severity of the disease as well as the presence of comorbidities might contribute to increased risk. Long-term clinical issues should be regularly evaluated after COVID-19

The Importance of Pleural Fluid and Serum NT-proBNP Levels in Differentiating Pleural Effusion due to Heart Failure from Other Causes of Effusion (Retracted article. See vol. 48, pg. 1783, 2009)

Background and Objective Pleural effusion due to congestive heart failure (CHF) typically are transudates. Light's criteria may be insufficient in determining if the pleural effusion is transudative or exudative in patients with CHF. The aim of our study was to assess the diagnostic performance of the amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in pleural fluid and serum for the identification of pleural effusion owing to heart failure

Dermal Fibroblast Transcriptome Indicates Contribution Of Wnt Signaling Pathways In The Pathogenesis Of Apert Syndrome

Cranial sutures are unossified connective tissue structures between the cranial bones, which allow expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert syndrome is a well-defined genetic syndrome, which is characterized by craniosynostosis and arises as a result of two missense mutations in Fibroblast Growth Factor Receptor, type 2 gene (FGFR2). In this study, differentially expressed genes in dermal fibroblasts from individuals with Apert syndrome and controls were investigated to identify important pathways in the pathogenesis of Apert syndrome. For this purpose, primary skin fibroblast cultures obtained from 3 individuals with Apert syndrome and 3 controls without craniosynostosis were compared by transcriptome microarray, GeneChip Human Genome U133 Plus 2.0. As a result, 181 genes were shown to be differentially expressed between experimental groups. Among these, 10 genes, which significantly differ in Apert syndrome fibroblasts compared to controls, were shown to be involved in a common interaction network and have common Gene ontology (GO) biological processes terms. COLI 1A1, COMP, CPXM2, ITGA8, MGF and INC are differentially expressed genes that have GO terms associated with extracellular matrix (ECM) organization, while FRZB, SFRP2 and WNT2 are involved in WNT signaling pathway. Reorganization of ECM and changes in WNT signaling pathway show that Apert syndrome primary fibroblast cultures may have an increased potential for bone differentiation. The results of this study support craniosynostosis in Apert syndrome may be the result of fast and early differentiation of connective tissue along the sutures.Wo

Detection of Axitinib Using Multiwalled Carbon Nanotube-Fe₂O₃/Chitosan Nanocomposite-Based Electrochemical Sensor and Modeling with Density Functional Theory

In this study, axitinib (AXI), a potent and selective inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase and used as a second-generation targeted drug, was investigated electrochemically under optimized conditions using multiwalled carbon nanotubes/iron(III) oxide nanoparticle–chitosan nanocomposite (MWCNT/Fe2O3@chitosan NC) modified on the glassy carbon electrode (GCE) surface. Characterization of the modified electrode was performed using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The adsorptive stripping differential pulse voltammetric (AdSDPV) technique was used for the sensitive, rapid, and precise detection of AXI. The current peak obtained with the MWCNT/Fe2O3@chitosan NC modified electrode was 23 times higher compared to the bare electrode. The developed modified electrode showed excellent electrocatalytic activity in AXI oxidation. Under optimized conditions, the effect of supporting electrolyte and pH was investigated, and 0.1 M H2SO4 was chosen as the electrolyte with the highest peak current for the target analyte. In the concentration range of MWCNT/Fe2O3@chitosan NC/GCE, 6 × 10–9 and 1 × 10–6 M, the limit of detection (LOD) and limit of quantification (LOQ) values were calculated to be 0.904 and 0.0301 pM, respectively. Tablet and serum samples were used for the applicability of the developed sensor, relative standard deviation (RSD) values for all samples were below 2%, and the recovery results were 99.23 and 101.84%, respectively. The MWCNT/Fe2O3@chitosan NC/GCE designed to determine AXI demonstrated the applicability, selectivity, precision, and accuracy of the sensor. The mechanism of electron transfer from the modified GCE surface to the analyte solution is studied via modeling the modified GCE surface by the density functional theory (DFT) method at B3LYP/6-311+g(d,p) and M062X/6-31g(d,p) levels. We observed that the iron oxide nanoparticles play an important role in channeling electron flow from the analyte solution to the MWCNT-coated GCE electrode surface. Adsorption of the nanocomposite material onto the GCE surface occurs via strong electrostatic interactions, including ionic and hydrogen bond formations. During the adsorption-controlled oxidation process of the axitinib, the electrons are transferred via the highest occupied molecular orbital (HOMO) localized on the iron oxide moiety to the lowest unoccupied molecular orbital (LUMO) of the MWCNT/GCE surface