Türkan Yiğitbaşı’s research while affiliated with Istanbul Medipol University and other places

Introduction: Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor β3 (TGF-β3) family and plays a crucial role in decidualization and implantation. Myomas can adversely affect endometrial receptivity and embryo implantation. Recent studies have highlighted the importance of understanding the molecular mechanisms underlying endometrial receptivity. The aim of this study is to determine BMP-2 secretion capacity of intramural, subserous, submucous myomas and their effects on endometrial tissue BMP-2 levels. Material- methods: Ninety-seven women who underwent hysterectomy or myomectomy because of symptomatic myomas were divided into three groups as submucous (SMM, n=26), intramural (IMM, n=34), and subserous (SSM, n=37). Myoma, myometrium and endometrial tissue samples were isolated and homogenized. BMP-2 concentrations of myoma, myometrium and endometrium tissue samples were evaluated with ELISA kits. Results: BMP-2 levels showed no significant difference between myoma samples of SMM, IMM, SSM (p>0,05). Within the groups, endometrium of SMM have the lowest BMP-2 levels (2417±720 pg/ml, p value

This study aimed to examine the effects of low-level laser therapy (LLLT) combined with levothyroxine replacement therapy on thyroid function, oxidative stress (OS), and quality of life in patients with Hashimoto's thyroiditis (HT). Forty-six patients diagnosed with HT were randomized to receive active LLLT (n = 23) and sham LLLT (n = 23) twice a week for three weeks. Clinical and laboratory evaluations of the participants were performed before treatment and three months after treatment. Biochemical parameters were taken from the patient file requested by the physician as a routine examination. Malondialdehyde and nitricoxide indicating oxidant stress and superoxide dismutase, catalase, and glutathione, which indicate antioxidant capacity, were used in OS evaluation. The Oxidative Stress Index was calculated by measuring the Total Antioxidant Status and the Total Oxidant Status. At the end of our study, a significant improvement in oxidant and antioxidant biomarker levels showing OS and quality of life was observed in the treatment groups (p < 0.05). There was no change in thyroid function and autoimmunity at the end of the treatment between the two groups (p > 0.05). Improvements in glutathione levels and quality of life were significantly higher in the active treatment group than in the sham-controlled group. LLLT was found to be more effective on OS and quality of life in patients with HT than in patients in the sham-controlled group. It was concluded that LLLT is a safe and effective method that can be used in the treatment of patients with HT.

This study aimed to investigate the effects of the calpain inhibitor N-Acetyl-Leu-Leu-norleucinal (ALLN) on neuroapoptotic cell damage caused by Copper Oxide Nanoparticles (CuO-NP) and exacerbation of damage through brain ischemia/reperfusion (I/R) in a rat model. Male Wistar Albino rats (n=80) were divided into eight groups: Control, I/R, CuO-NP, CuO-NP+I/R, I/R+ALLN, CuO NP+ALLN, CuO-NP+I/R+ALLN, and DMSO. Biochemical markers (MBP, S100B, NEFL, NSE, BCL-2, Cyt-C, Calpain, TNF-α, Caspase 3, MDA, and CAT) were measured in serum and brain tissue samples. Histological examinations (H&E staining), DNA fragmentation analysis (TUNEL) were performed, along with Caspase-3 assessment. The ALLN-treated groups exhibited significant improvements in biochemical markers and a remarkable reduction in apoptosis compared to the damaged groups (CuO-NP and I/R). H&E and Caspase-3 staining revealed damage-related morphological changes and reduced apoptosis in the ALLN treated group. However, no differences were observed among the groups with TUNEL staining. The findings suggest that ALLN, as a calpain inhibitor, has potential implications for anti-apoptotic treatment, specifically in mitigating neuroapoptotic cell damage caused by CuO-NP and I/R.

Introduction Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. Methods One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Results Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. Discussion The results showed that “liquid biopsy” is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.

Although many genetic etiologies, such as Fanconi anemia, Shwachman–Diamond syndrome, dyskeratosis congenita, and Diamond–Blackfan anemia, from hereditary bone marrow failure are known today, the responsible gene remains unknown in a significant part of these patients. A 6-year-old girl, whose parents were first-cousin consanguineous, was referred to the pediatric hematology department due to growth retardation, thrombocytopenia, neutropenia, and anemia. The patient had low-set ears, pectus excavatum inferiorly, and cafe-au-lait spots. In whole-exome analysis, p.K385T (c.1154A > C) variant in the RASA3 gene was detected as homozygous. The amino acid position of the alteration is located in the conserved and ordered region, corresponding to the Ras GTPase activation domain (Ras-GAP) in the center of the protein. Importantly, most of in silico prediction tools of pathogenicity predicts the variant as damaging. RASopathies, which are characterized by many common clinical findings, such as atypical facial features, growth delays, and heart defects, are a group of rare genetic diseases caused by mutations in the genes involved in the Ras-MAPK pathway. The findings in this patient were consistent with the RASopathy-like phenotype and bone marrow failure. Interestingly, enrichment of RASopathy genes was observed in the RASA3 protein–protein interaction network. Furthermore, the subsequent topological clustering revealed a putative function module, which further implicates RASA3 in this disease as a novel potential causative gene. In this context, the detected RASA3 mutation could be manifesting itself clinically as the observed phenotype by disrupting the functional cooperation between the RASA3 protein and its interaction partners. Relatedly, current literature also supports the obtained findings. Overall, this study provides new insights into RASopathy and put forward the RASA3 gene as a novel candidate gene for this disease group.

Background Alopecia areata (AA) is a chronic immune-mediated disease characterized by sudden-onset, sharply circumscribed alopecic patches that can occur in any part of the body, mostly on the scalp. Its etiology has not yet been fully clarified. Recently, increasing data regarding the relationship between oxidative stress and AA are available in the literature. Objectives To evaluate the effect of oxidative stress with ischemia-associated albumin (IMA) and conventional methods together with total oxidant state (TOS), total antioxidant state (TAS) and oxidative stress index (OSI) in patients with new-onset mild AA. Methods The study was conducted as a single-center, prospective, case-control study and included 36 patients with AA and 34 healthy volunteers. Serum TAS, TOS, OSI and IMA levels were compared between the two groups. Results The TOS and OSI levels were found to be significantly higher and the TAS level was significantly lower in the AA group. Although the IMA level was higher in the AA group, it did not significantly differ from the control group. Conclusions This study supports the presence of a relationship between oxidative stress and AA. Antioxidant defense mechanisms may be delayed to compensate for the high oxidant levels in mild acute AA. Oxidative damage can also be caused by non-ischemic pathways, and IMA levels may become more pronounced in more chronic and severe cases. We consider that there is a need to investigate individual oxidative causes in larger and different subgroup populations of AA and re-evaluate related markers after antioxidant treatment.

Objective: The study aims to determine what proportion of Turkey’s preoperative patient population has tested positive for COVID-19 and to ascertain whether the increasing or decreasing trend in the numbers of positive preoperative patients resembles the general population of Turkey during the same period. Methods: The study cohort is comprised of the 14,776 patients who had a preoperative COVID-19 real-time polymerase chain reaction (RT-PCR) test request as a result of various services between January 1-December 31, 2021. Isolated SARS-CoV-2 RNAs were detected with Bio-Speedy® SARS-CoV-2 Double Gene RT-qPCR and Bio-Speedy® SARS-CoV-2 Triple Gene RT-qPCR kits (Bioeksen R&D Technologies Ltd., Istanbul, Turkey) and Bio-Rad CFX96 and Bio-Rad DX Real-Time PCR system (Hercules, CA, USA). Results: SARS-CoV-2 RT-PCR positivity was detected in 422 (2.86%) patients, of which 59.72% (n = 252) were female and 40.28% (n = 170) were male; their mean age was 40.2 years. Of the 422 positive cases, 84.12% were young adults (18-65 years), and 9% were middle-aged (66-79 years). Positive cases involving those under the age of 18 were found to account for 5.22% (n = 22) of the total. The highest positivity rate was observed in April 2021 at 8.28% of all test requests, while the lowest positivity rate was observed in June 2021, at 0.36% of all test requests. The highest positivity rate of April was followed by March (5.07%), October (4.74%), and August (3.13%). Conclusion: In conclusion, the COVID-19 RT-PCR positivity rate in the series was detected as 2.85% in preoperative patients over the one- year period. Monthly positivity rates in screening results are consistent with the number of cases seen in the general population.

Objective: Of the existing variants, alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and omicron (B.1.1.529) were defined as variants of concern (VOCs) by World Health Organization. We aimed to retrospectively assess the distribution of VOCs in patients with positive COVID-19 real-time polymerase chain reaction (RT-PCR) test. Methods: Between April 2021 and December 31, 2021, 4260 patients whose clinical samples were sent with a COVID- 19 PCR test request were included in the study. Of the patients whose samples were evaluated, 2173 (51%) were male, and 2087 (49%) were female. Viral nucleic acid isolation was performed by treating nasopharyngeal swabs, bronchoal- veolar lavage, and tracheal aspirate samples with viral nucleic acid buffer (vNAT). SARS-CoV-2 variants were detected by Bio-Speedy® SARS-CoV-2 Variant Plus kit (Bioeksen AR-GE Technologies, Turkey), which targets variant-specific genome regions only found in B.1.1.7, B.1.351, and P.1 as well as ORF1ab and N gene regions. We used Bio-Speedy® SARS-CoV-2 Emerging Plus kit and CFX96 DX real-time PCR system to detect SARS-Cov-2 variants; N D3L mutation was targeted to detect the alpha variant, SL452R mutation to detect the delta variant, and S E484K mutation, which is widespread, to detect the gamma and the mu variants. Results: SARS-CoV-2 RT-PCR was positive in 773 (18.14%) of 4260 samples, and different SARS-CoV-2 variants were detected in 316 (40.88%) of positive samples. 407 (52.65%) of the patients with real-time polymerase chain reac- tion (RT-PCR) positive test were women, and the mean age was 41.7 years. While no variant type was detected in 457 (59.12%) of the patients, the alpha variant was detected in 156 (20.18%) and the delta variants in 137 (17.72%) patients. Conclusion: In our study, we found that the alpha variant was the dominant type in April, May, and June, and the delta variant became dominant as of July until the end of the year. Decreased rates of delta variants towards the end of 2021 and an increase in the other variants suggest the omicron variant, widely spread globally. Therefore, we believe that the omicron variant has been our country’s dominant type since November 2021. In conclusion, molecular surveillance studies that are planned in the light of epidemiological data and assessment of the frequency and genomic analyzes of regional and global variants are required.