For many years, ionophores have been used to control coccidiosis in poultry. However, misuse of ionophores can cause toxicity with significant clinical symptoms. The most critical factors influencing ionophores’ toxicity are administration dose, species, and animal age. Although clinical signs of ionophore intoxication are well studied, the toxicity mechanisms of the ionophores at the molecular level still are not fully elucidated. This review summarizes the studies focused on polyether ionophores toxicity mechanisms in animals at the clinical and molecular levels. Studies show that ionophore toxicity mainly affects myocardial and skeletal muscle cells. The molecular mechanism of the toxication could be explained by the inhibition of oxidative phosphorylation via dysregulation of ion concentration. Tiamulin-ionophore interaction and the synergetic effect of tiamulin in ionophore biotransformation are discussed. Furthermore, in recent years ionophores were candidates for reprofiling as antibacterial and anti-cancer drugs. Identifying ionophores’ toxicity mechanisms at the cellular level will likely help develop novel therapies in veterinary and human medicine.
Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR gene mutations. Despite having the same mutation, CF patients may demonstrate clinical variability in severity and prognosis of the disease. In this study, we aimed to determine differentially expressed genes between mild and severe siblings with same genotype. We performed targeted real‐time polymerase chain reaction based transcriptomic analysis of nasal epithelial cells obtained from two families with two siblings with Class II mutations (F508del/F508del) and (F508del/G85E), one family with three siblings with Class IV mutation (I1234V/I1234V). In severe siblings with Class II mutations, TNFRSF11A, KCNE1, STX1A, SLC9A3R2 were found to be up regulated. CXCL1, CFTR, CXCL2 were found to be down regulated. In the severe sibling with Class IV mutation; mainly genes responsible from complement and coagulation system were identified. Comparison of CF patients to non‐CF control; showed that ICAM1 was up regulated whereas EZR, TNFRSF1A, HSPA1A were down regulated in patients. As a result of this study, differentially expressed genes responsible for clinical severity among affected siblings carrying the same mutation were identified. The results will provide an opportunity for the development of novel target molecules for treatment of disease.
Gen ifade kontrolünde önemli rollere sahip olan mikroRNA'lar (miRNA), 20-25 nükleotid uzunluğunda kodlamayan RNA molekülleridir (1). Bugüne kadar insanlarda 2500'den fazla miRNA tanımlanmıştır ve bu miRNA'lar insan hücrelerinde protein kodlayan genlerin %60'ını düzenlemektedir (2,3). mRNA'ların 3' ucunda bulunan ve proteine çevrilmeyen (3'UTR) bölgesine komplementerlik esasına dayanarak bağlanan miRNA'lar, mRNA yıkımı veya protein sentezinin engellemesiyle sonuçlanan mekanizmalar ile gen ifadesini baskılarlar (1). ÖZ Kodlanmayan RNA grubunda yer alan mikroRNA'lar (miRNA) son yıllarda otoimmün hastalıklar, kanser, kardiyovasküler hastalıklar ve bazı solunum yolu hastalıklarında klinik ciddiyet ile ilişkilendirilmiştir ve tedavi hedefi olarak kullanılmalarına ilişkin birçok araştırma gerçekleştirilmiştir. CFTR genindeki mutasyonlar sonucu oluşan ve otozomal resesif kalıtılan solunum sistemi hastalıklarından birisi olan kistik fibroziste günümüze kadar hastalık patogenezi ile ilişkilendirilen çok sayıda miRNA tanımlanmıştır. Bu derlemede, kistik fibrozis hastalığında miRNA'ların rolü, hastalık ciddiyeti ile ilişkisi, miRNA temelli tedavi yaklaşımları ve ileride prognostik ve terapötik biyobelirteç olarak kullanılmalarına yönelik gerçekleştirilen araştırmalar özetlenmiştir. Anahtar Kelimeler: kistik fibrozis, CFTR geni, mikroRNA, biyobelirteç ABSTRACT MicroRNAs (miRNA), which belong to non-coding RNA group, have been associated with clinical severity in autoimmune diseases, cancer, cardiovascular diseases and some respiratory diseases. Many studies have been carried out on their use as therapeutic targets in recent years. In cystic fibrosis, an autosomal recessive inherited respiratory system disease caused by mutations in the CFTR gene, many miRNAs associated with the pathogenesis have been identified. This review, summarizes the research about the role of miRNAs in cystic fibrosis, their relationship with the severity of the disease, miRNA based treatment approaches and their use as prognostic and therapeutic biomarkers.
The coronavirus disease-2019 (COVID-19) pneumonia which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) virus is the current urgent issue world over. According to the Health Ministry of Turkey, the first COVID-19 patient was diagnosed on March 11, 2020. Since then, approximately 5.5 million patients have been confirmed to be positive SARS CoV-2 virus. In this retrospective study, we aimed at analyzing the epidemiological and radiological findings of COVID-19 cases at the Hospital of Grand National Assembly of Turkey from April 1, 2020 to December 31, 2020. A total of 130 patients (84 male, 25–87 years) were diagnosed as positive with High Resolution Computed Tomography (HRCT) scans and 71 of them confirmed with positive Real Time Polymerase Chain Reaction using the patients’ nasopharyngeal and throat samples. HRCT scans were classified into 4 stages. Stage I (39.2%) patients’ group; the HRCT results were found to be mosaic perfusion, whereas Stage II (39.2%) were found to be Ground Glass Opacity. Also, consolidation was detected in Stage III (20%). Finally, Stage IV, considered the most severe lung findings, and named as a crazy paving pattern was determined in 2 patients (1.53%). Furthermore, 20% of patients were found to be positive using IgG antibody against to SARS CoV-2 virus. Our findings showed that HRCT could be most prominent technique compared to real time polymerase chain reaction for the diagnosis of COVID-19 pneumonia. The novel classification of HRCT findings will be helpful to early diagnosis of the disease, time saving and eventually cost-effective.
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