Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to the development of resistance to standard chemotherapeutic agents such as cisplatin. Recent evidence has highlighted the regulatory role of long non-coding RNAs (lncRNAs) in mediating drug resistance mechanisms. In this study, we aimed to reveal the role of MCM3AP-AS1 in cisplatin-induced cell death in lung cancer cells. As a result, we found that MCM3AP-AS1, a lncRNA previously associated with poor prognosis in various cancers, was significantly upregulated in A549 lung cancer cells following cisplatin treatment. Using RNA interference-mediated silencing of MCM3AP-AS1, we observed a marked increase in cell viability and a decrease in apoptosis, as determined by MTT assay, annexin V/PI flow cytometry, and acridine orange/ethidium bromide staining. These findings suggest that MCM3AP-AS1 may be a crucial modulator of cisplatin-induced apoptosis in lung cancer cells.

Breast cancer is the leading cause of death among women. Natural compounds play an important role in the prevention of breast cancer. In this study, the anticancer properties of Lobaria pulmonariawere investigated. Cell viability and proliferation were assessed using MTT test, apoptotic cell percentages were determined by AnnexinV/PI assay, protein levels of BCL2, CASP3 and P53 were measured by western blot. Additionally, F-actin levels were analyzed using Immunofluorescence staining. It was determined that L. pulmonariareduced the viability of MCF7 cells. While the percentage of apoptotic cells did not change, the percentage of non-apoptotic cell death increased. Moreover, there were no significant changes in BCL2, CASP3, and P53 protein levels, nor in the amount of F-actin. In conclusion, L. pulmonariadid not induce apoptosis in MCF7 breast cancer cells but appeared to trigger a non-apoptotic cell death pathway, such as necrosis.

Colon cancer is a significant cause of cancer death and morbidity worldwide. Despite significant advancements in anti-tumor therapies over recent years, enhancing the overall prognosis still presents a substantial challenge. A prevalent characteristic of many solid tumors, including colon cancer, is tumor necrosis. Recent studies have indicated that under specific conditions, cell death through necrosis can be orchestrated rather than occurring randomly. Receptor-interacting protein (RIP) kinases have been identified to be key regulators of this controlled form of necrosis. In addition, the deregulation of necroptosis has been identified to be a key driving factor during malignant progression of human tumors, including colon cancer. Accordingly, to extend our understanding of the modulatory effects of miR-421 on the necroptosis pathway, herein we performed gain-of-function studies of miR-421 in colon cancer cell lines and analyzed differential expression of receptor integrating serine-threonine kinase-1 (RIPK1), a key regulator of necroptosis in cells. Remarkably, overexpression of miR-421 significantly suppressed the expression of RIPK1 in colon cancer cells, indicating that miR-421 is a key regulatory miRNA targeting RIPK1 activity in colon cancer. Collectively, the findings obtained here strongly suggest that miR-421 can be a druggable target for the modulation of RIK1-mediated necroptotic signaling.

Objective:We aimed to assess the frequency of Y-chromosome microdeletions (YCMs) in a non-multiethnic urban population in our region, define predictive factors, and determine a new clinical threshold for YCMs in infertile men. Materials and Methods:A total of 281 patients with a sperm concentration ≤5 million/mL were retrospectively evaluated. Oligozoospermic and/or azoospermic patients with a sperm concentration of ≤5 million/mL were screened for the YCM analysis. Results:Y-chromosome microdeletion was detected in 9 (3.2%) of the 281 patients. All patients with YCM were azoospermic. The presence of azoospermia, a high folliclestimulating hormone level, and a high luteinizing hormone level were found to be important determinants for the identification of a microdeletion (P = .002, P = .002, and P=.021, respectively). If the presence of azoospermia and a sperm concentration threshold of <1 million/mL had been applied for the YCM test, the number of tests performed would have been reduced by 54.4% (153 tests) and 42.7% (120 tests), respectively, resulting in cost saving of approximately $11 474 and $9000, respectively. Conclusion:We recommend that the threshold for sperm concentration for YCM analysis be set at <1 million in individuals in developed countries and only in patients with azoospermia in developing countries, in order to reduce costs and save labor by excluding unnecessary tests. These proposed thresholds (azoospermia and sperm counts less than <1 million/mL) provide cost-effectiveness by significantly reducing the number of genetic tests ordered without affecting the diagnosis rate.

Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

Amaç: Quercetin kolon kanseri dahil birçok kanser çeşidinde anti-kanser aktivite gösteren bir bileşiktir. Ancak, quercetinin nekroptoz yolağı üzerine etkilerini gösteren çalışmalar kısıtlıdır ve bu nedenle bu çalışmada quercetinin nekroptoz yolağına etkisinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: HT-29 ve HCT-116 kolon kanseri hücreleri kültür edilip farklı konsantrasyondaki quercetinin hücre canlılığına etkisi MTT yöntemi ile belirlendi. Sonrasında quercetinin nekroptoza etkisinin belirlenmesi için RIPK1, RIPK3 ve MLKL genlerinin ekspresyon seviyesi analiz edildi. Bulgular: HT-29 hücrelerinde quercetinin aktif dozu 50 µM (p=0,0286) olarak bulunurken HCT-116 hücrelerinde 100 µM (p=0,009) bulundu. 50 ve 100 µM quercetin ile maruz bırakılan HT-29 hücrelerinde nekroptoz belirteçlerinin ekspresyon seviyesinde ciddi bir artış tespit edildi. Sonuç: Bu çalışmanın sonuçları quercetinin nekroptoz yolağının aktif bir düzenleyicisi olabileceğini göstermiştir.

Colon cancer is the one of the most common types of cancer in humans. A sedentary lifestyle, increasing obesity and the consumption of food additives favor the development and occurrence of colon cancer. It is emphasized that curcumin, a yellow compound isolated from the turmeric plant, is important in preventing cancer. Studies have shown that curcumin has an anticancer effect by driving cancer cells into apoptosis, but studies showing its effect on necroptosis are inconclusive. Necroptosis is a form of programmed cell death mediated by RIP proteins and has been shown to play an important role in cancer. This study aims to determine the effect of curcumin on the necroptosis signaling pathway. For this purpose, HT-29 and HCT-116 colon cancer cells were cultured and exposed to different concentrations of curcumin and MTT experiments were performed to determine the effect on cell viability. The expression levels of RIPK1, RIPK3, and MLKL genes, which are markers of necroptosis, were analyzed by real-time PCR. It was found that the expression level of RIPK1, RIPK3, and MLKL genes significantly increased after exposure of HT -29 cells to 50 µM curcumin. Moreover, the expression of RIPK1 and MLKL genes increased in HCT-116 cells after curcumin administration. Consequently, the current data clearly suggest that curcumin is a prominent driver of necroptotic signaling-mediated colon cancer cell death.

Spinal muscular atrophy, X-linked 2 (SMAX2) is a rare type of spinal muscular atrophy characterized by muscle weakness, hypotonia, areflexia, myopathic face, tongue fibrillations, contractures, bone fractures, and cryptorchidism. Variants of the UBA1 gene lead to SMAX2. The UBA1 gene encodes a protein that activates the ubiquitin pathway which is responsible for protein degradation. Here, we describe a family presenting with hypotonia, muscle weakness, areflexia, contractures, weak cry, in association with other anomalies including myopathic face, scoliosis, tongue fibrillations, and cryptorchidism. Molecular analysis in 2 patients revealed a hemizygous pathogenic variant in the UBA1 gene (NM_153280.3, NP_695012.1: c.1731C>T [p.Asn577Asn]) inherited from their carrier mothers. Our study presents the first patients from Turkey, widening the phenotypic spectrum of SMAX2 by pectus carinatum, medullary sponge kidney, and frontal cyst.

Kleefstra syndrome (KS), previously referred to as 9q subtelomeric deletion syndrome (9qSTDS), is characterised by moderate to severe developmental delay/mental retardation, childhood hypotonia, and brachy-microcephaly (main clinical phenotype), midface hypoplasia, prognathism, lip and eyebrow shape anomalies. The true prevalence of KS is unknown, but it is estimated that it occurs with a frequency of 1/200.000 in cases with mental retardation. On literature search, approximately 110 patients have been reported so far. Genetic analysis should be planned and interdisciplinary monitoring should be provided in cases suspected to have KS.   Key Words: Child, Genetic disorder, Kleefstra Syndrome, Dysmorphism.

The Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL , SMC1A , SMC3 , RAD21 , and HDAC8 . On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

A pregnant woman with no previous routine pregnancy follow-up referred to our obstetrics clinic. Ultrasonography revealed the presence of a fetal heartbeat 26 weeks and 4 days old. Polyhydramnios, omphalocele, a diaphragmatic hernia, left ventricular hypoplasia, an occipital bone defect, a fetal head in severe retroflexion, and exaggerated cervicothoracic lordosis were detected in the fetus. After obtaining parental consent, the board decided to terminate the pregnancy. An examination performed after the termination revealed that the fetus was female and weighed 780 g. The first phalanx of the left thumb was hypoplastic. An X-ray examination showed coat hanger–shaped costal fusions and cranial structures consistent with iniencephaly. Fetus karyotyping revealed a normal 46, XX female karyotype. We speculate that this case represents a variant of Gershoni-Baruch syndrome.

Purpose: This study aimed to determine the role of vitamin D receptor in the pathogenesis of pterygium. The vitamin D receptor eexpression levels in pterygium tissue, blood vitamin D levels, and frequency of selected vitamin D receptor gene polymorphisms (BsmI, FokI, and TaqI) were compared between patients with pterygium and healthy participants. Methods: The study included patients with pterygiumeee (n=50) and healthy volunteers (n=50). The serum vitamin D levels were measured for both groups. Immunohistochemical staining for vitamin D receptor ewas performed on sections obtained from the pterygium and adjacent healthy conjunctival tissues of the same individuals. The genomic existence of vitamin D receptor epolymorphisms (BsmI, FokI, and TaqI) were analyzed in DNA obtained from venous blood of participants using polymerase chain reaction and restriction fragment length polymorphism methods. Results: There was no difference found between the serum vitamin D levels of patients with pterygium and healthy controls. However, tissue expression of vitamin D receptor was higher in the pterygium endothelial cells of micro-vessels (p=0.002), subepithelial stromal (p=0.04), and intravascular inflammatory cells (p=0.0001), in comparison with the adjacent healthy conjunctival tissue. Moreover, while the BBtt haplotype was 2-fold higher, the bbTt haplotype was 2.5-fold lower, and the BbTT haplotype was 2.25-fold lower in the control group than in the pterygium group (p<0.001). Conclusions: Vitamin D serum levels did not differ between the healthy and pterygium groups. Vitamin D receptor expression was increased in the pterygium tissue versus the adjacent healthy tissue. However, vitamin D receptor polymorphism analysis in patients with pterygium did not reveal any significant difference in BsmI, FokI, or TaqI polymorphisms in comparison with the healthy volunteers.

Long noncoding RNAs (lncRNAs) constitute the largest class of noncoding RNAs and play significant roles in the development of cardiovascular pathologies. In the present study, we aimed to evaluate whether 4 candidate lncRNAs - MIAT, MEG3, MALAT1, and MCM3AP-AS1 - have distinct expression levels in patients with obstructive coronary artery disease (CAD) and reveal the diagnostic and therapeutic potentials of these lncRNAs for CAD. A total of 90 patients who subjected to coronary angiography were enrolled. Relative expression of lncRNAs were assayed using qRT-PCR methodology. As a result, MIAT was downregulated, while MEG3 was upregulated in CAD patients. Receiver operating characteristic curves demonstrated that these lncRNAs have a high potential to provide sensitive and specific diagnosis of CAD. The calculated area under curve levels indicated that MIAT and MEG3 have high diagnostic value for detecting the presence of significant CAD. However, MALAT1 and MCM3AP-AS1 levels were not sufficiently reliable for CAD development in our cases. Here, we demonstrate that MIAT and MEG3 were differentially expressed in our patients and might be promising biomarkers and therapeutic targets for CAD. These results indicate that MIAT and MEG3 could play chief roles in CAD development.

Background Prostate cancer antigen 3 (PCA3) is the most promising diagnostic biomarker for the differential diagnosis of prostate cancer identified to date. As a dominant-negative oncogene, PCA3 negatively regulates the expression of tumor suppressor PRUNE2 (a human homolog of the Drosophila prune gene) gene. Although interaction between PCA3-PRUNE2 was clearly reported, the precise mechanism how PCA3 is upregulated in prostate cancer remained highly elusive. Accordingly, here we aimed demonstrate the role of microRNAs in PCA3 upregulation and interplay between these miRNAs and PCA3-PRUNE2 axis. Methods and results We evaluated expression of PCA3, PRUNE2 and miRNAs by quantitative reverse transcription polymerase chain reaction. Overexpression and silencing of miRNAs were achieved by synthetic miRNA mimics and inhibitors, respectively. Colony formation, migration, apoptosis, and cell cycle assays were performed to reveal the effects of miRNA modulation. We identified that PCA3 expression was significantly downregulated in both prostate cancer tissues and cells and inversely correlated with the expressions of miR-19a and miR-421. Restoring the functions of miR-19a and miR-421 by miRNA mimics significantly downregulated the expression of PCA3 and promoted apoptosis and cell cycle blockade and interfered with the proliferation and migration in prostate cancer cells. Conversely, silencing the expressions of these miRNAs yielded the opposite effect. Conclusions Collectively, our results uncover a previously unrecognized novel mechanism on PCA3 upregulation in prostate cancer and proved that miR-19a and miR-421 might be responsible for the increased expression of PCA3, indicating that both miRNAs might be novel candidates for prostate cancer diagnosis and therapy.

Ellis‐van Creveld syndrome 10‐year‐old Turkish girl and her parents were first degree cousins. A novel pathogenic variant (p.Glu1178Glyfs*82) was detected in the EVC2 gene in patient. She had no peg‐shaped teeth, multiple frenula, and limb shortness.

Copy number variation in loss of 7q21 is a genetic disorder characterized by split hand/foot malformation, hearing loss, developmental delay, myoclonus, dystonia, joint laxity, and psychiatric disorders. Osteogenesis imperfecta caused by whole gene deletions of COL1A2 is a very rare condition. We report a Turkish girl with ectrodactyly, joint laxity, multiple bone fractures, blue sclera, early teeth decay, mild learning disability, and depression. A copy number variant in loss of 4.8Mb at chromosome 7 ( q21.2q21.3) included the 58 genes including DLX5, DLX6, DYNC1I1, SLC25A13, SGCE, and COL1A2. They were identified by chromosomal microarray analysis. We compared the findings in our patients with those previously reported. This case report highlights the importance of using microarray to identify the genetic etiology in patients with ectrodactyly and osteogenesis imperfecta.

Amaç: Fragile-X sendromunda değişen derecelerde zihinsel gerilik, uzun ve dar yüz, öne çıkan alın ve çene yapısı, büyük kulaklar temel bulgulardır. Bu çalışmada Fragile X sendromu tanısı konulan olguların özgeçmiş-soygeçmiş, klinik özellikleri, laboratuvar bulguları ve yakın klinik izlemlerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Fragile X sendromu tanısı koyulan olguların klinik ve fizik muayene özellikleri, laboratuvar sonuçları retrospektif olarak değerlendirildi. Bulgular : Yaşları 5-14 yaş arasında değişen 5 erkek olgu çalışmaya dahil edildi. Olguların tamamında değişen derecelerde mental retardasyon ve kaba yüz görünümü mevcuttu. Hastalarımızın polikliniğe en sık başvuru yakınması zihinsel gerilikti. İki hastada hiperaktivite, bir hastada kendine zarar verme, bir hastada unutkanlık ve enürezis mevcuttu. Çalışmaya dahil edilen olguların tamamında nöromotor retardasyon olduğu ve bu nedenle özel eğitim aldığı, bir olgunun atipik otizm tanısı olduğu, bir hastanın ise DEHAB nedeni ile ilaç kulanım öyküsü olduğu belirlendi. Metabolik, hemogram ve biokimyasal parametreler normal aralıktaydı. İki hastanın kranial görüntülemesi normaldi, diğer hastaların kranial görüntülemesinde; Olgu 1’de bilateral hipokampal alanda subraknoid mesafede ılımlı artış, Olgu 3’te korpus kallosum gövde 1/3 arka kısım ve spleniumda hipoplazi, Olgu 4’te periventrikuler posterior alanda T2A/FLAIR’de hiperintensite izlendi. Olguların 6-9 aylık izleminde herhangi bir sorunla karşılaşılmadı. Ailelere verilen genetik danışmanlık sonrasında bir olgunun iki erkek kardeşinde de Fragile X sendromu tanısı konularak özel eğitime yönlendirildi. Sonuçlar : Genel pediatri polikliniği ve çocuk yan dal polikliniklerine her gün çok sayıda tanısı konulamayan mental retarde hasta başvurmaktadır. Uzun/dar yüz, öne çıkan alın/çene yapısı, büyük kulaklar, makroorşidizm ve zihinsel geriliği olan hastalarda ilk düşünmemiz gereken Fragile X sendromudur