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Background: The occurrence of indirect inguinal hernias (IIH) is 5 times more prevalent than that of direct inguinal hernias (IH) and it is 7 times more common in males, owing to the attendance of the processus vaginalis (PV) throughout testicular descent. Summary: In children, the immense mainstream of IH is indirect. The progress of IIH development in children is instigated with a patent PV, which is mostly treated by simple herniorrhaphy. Syndromes of the collagen, microfibril, elastin, and glycosaminoglycan constituents of the extracellular matrix may attend to the development of IH. Our recent research showed that the lack of epithelial-mesenchymal transition (EMT) in children contributes to the development of IIH, while the scenario is defined as the opposite in adults. However, there is still a lack of knowledge on all of the genetic and molecular causes of the disease. Key Messages: Here we aimed to review the published genetic background of IH, the deficiencies of connective tissue causing the disease, recently defined molecular pathways involved including EMT, and possible recurrence reasons. This comprehensive study can deliver an analytic outline aiding to define patients with IH combined with fundamental genetic diseases.

Objective: glioblastoma is the most malicious type of glioma presenting a genetic background via diverse mutations and exhibits differential sensitivity to treatment. Meanwhile, schizophrenia is a heterogeneous disease with a complex etiology. Studies report an elevation in pro-inflammatory cytokines in patients with schizophrenia and changes in biochemical metabolism. In the present study, the tumor spheroid technology is applied to two different glioblastoma lines which resemble schizophrenia manifestation along with the investigation of the potential anti-tumor effect of an atypical antipsychotic drug, risperidone. Our hypothesis built on case reports showing patients with schizophrenia being treated with risperidone that turned out to have glioblastoma in post-mortem evaluation. Risperidone has been suggested to carry therapeutic effects for glioblastoma and elongated lifespan after the diagnosis of cancer. Materials and methods: in this current study, 3D models using C6 and U87 glioblastoma cells and monocytes for representing the disease grown as multicellular spheroids were established. Spheroids were treated with the anti-schizophrenic agent risperidone and indicated almost similar results to the clinics suggesting that glioblastoma and schizophrenia share mutual physiological characteristics. Results: U87 and C6 spheroid systems were analyzed molecularly after the treatment of risperidone where U87 spheroid models were found highly resembling the overall behavior of schizophrenia. This present work correlated the stated two diseases in molecular level to encourage the efforts for personalized medicine. Conclusion: The anti-tumor effects of risperidone on glioblastoma is not very well established yet. It should not be missed that a picture of schizophrenia in clinics may be the result of an underlying lesion in a specific brain area. Thus, especially schizophrenia patients who may be at risk for developing brain tumors should be further investigated and treated accordingly., NA

Sedef hastalığı; genetik, bağışıklık sistemi ve çevrenin karşılıklı etkileşiminden kaynaklanan, çok faktörlü kronik inflamatuar bir hastalıktır. Epitel hücrelerinin hiperproliferasyonu ile karakterizedir ve hastaların yaşamında büyük olumsuz etkileri olan kırmızı, pullu psoriatik plaklar oluşturur. Kortikosteroidler veya D vitamini analogları iyileşmeye bir dereceye kadar yardımcı olabilse de hastalığın henüz tam bir tedavisi yoktur. Bu çalışmada, β2-adrenerjik reseptör agonisti salbutamol'ün potansiyel etkinliğinin taranması için üç boyutlu (3D) stresle ilişkili psoriatik deri sferoidleri oluşturulması amaçlanmıştır. İnsan dermal fibroblast (HDF), İnsan epidermal keratinosit (HEK) ve İnsan monosit hücreleri (THP-1) ile 3D kültür modelleri oluşturulmuş ve buna göre stres kökenli psoriatik model protokolü uygulanmıştır. İlacın etkinliği, gen ve protein ekspresyon seviyelerindeki değişiklikler ve çeşitli metabolik deneylerle değerlendirilmiştir. Sedef hastalığının sferoid modellerini in vitro olarak büyütebilmek için optimize bir yöntem geliştirilmiştir. Salbutamol'ün sedef sferoidleri üzerindeki potansiyel terapatik etkileri test edilmiştir. Salbutamol ile tedavi edilen sferoidler, tedavinin etkinliğini kanıtlayan literatürle paralel sonuçlar göstermiştir. 3D sferoroid sistemimiz, in vitro olarak sedef hastalığının fizyolojik özelliklerini taklit etmede kısmen etkili bulunmuştur. Çalışmamız, stresle ilişkili bir psoriatik model oluşturduğu ve potansiyel bir tedavi seçeneği olarak bir β2 agonistini deneyen ilk çalışma olduğu için bir başlangıç noktası olabilir. Salbutamol'ün etkileri ve uygunluğu göz önünde bulundurulduğunda etkinliği küçümsenmemeli ve gelecekte klinikte kullanım potansiyeli göz önünde bulundurulmalıdır., Psoriasis is a multifactorial chronic inflammatory disorder resulting by the interplay of genetics, the immune system and the environment. It is characterized by the hyperproliferation of epithelial cells, generating red, itchy psoriatic plaques which have no cure but have great negative impact in patients’ life. Although corticosteroids or vitamin D analogs might help recovery to some extent, there is yet no total cure for the disease. In this study, we sought to generate three-dimensional (3D) stress-related psoriatic skin spheroids with the screening of the potential efficacy of a β2-adrenergic receptor agonist, salbutamol. 3D Culture spheroids with human dermal fibroblasts (HDF), human epithelial keratinocytes (HEK) and human monocytic cell line (THP-1) were generated as a representative model of skin and the protocol of stress-related modelling was conducted. The efficacy of the drug salbutamol was evaluated by the changes in mRNA and protein expression levels of selected genes, as well as by several metabolic assays. We developed a method for culturing spherical organoid models of psoriasis in vitro. We tested the potential theurapetic effects of salbutamol on psoriasis spheroids. Spheroids treated with salbutamol indicated the effictiveness of the treatment. 3D spheroid system was found partially efficient for mimicking the physiological features of psoriasis in vitro. This present work may be a starting point for future investigation as it is the first to generate a stress-related psoriatic model and first to try a β2 agonist as a potential treatment option. Considering the effects and suitability of topical application of salbutamol, its efficacy should not be underestimated and should be investigated further for translating this knowledge into clinics.

Introduction Epithelial–mesenchymal transition (EMT) describes rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell–cell adhesion, alter polarity, reorganize cytoskeleton, become isolated, motile, and resistant to anoikis. Epithelial breakdown and epithelial cell migration are the key processes involved in the obliteration of processus vaginalis. The great majority of abnormalities are because of nonobliteration or incomplete fusion of PV. We aimed to analyze the quantitative changes of epithelial genes in adult/child patients and their controls to examine differences of the genesis of these hernias. We also aimed to investigate the potential epigenetic causes of indirect inguinal hernia in adult patients. Methods Ten adult, ten child indirect inguinal hernia sacs and ten adult, ten child parietal peritonea were used. Hernial sac samples were obtained from indirect inguinal hernia surgeries. Peritonea of adult patients who underwent open cholecystectomy for cholelithiasis via subcostal incision were included in the study as the healthy control groups. Ages of the children were selected to be between 0 and 5 whereas the age of adults was chosen as 35–55, respectively. Total RNA isolation and cDNA synthesis were made from hernia sacs and peritoneum samples. Relative Keratin 1, Keratin 15, Filaggrin2 and STAT3 expressions were analyzed via qPCR. Indirect inguinal hernia sac cells were seeded and grown in vitro. Child diseased cells were employed in immunocytochemistry (ICC) analysis for Cytokeratin 15, Filaggrin2 and Bcl-2. Adult indirect inguinal hernia cells were examined for H3 modifications through ICC. Results In child indirect inguinal hernia, Keratin expressions were found higher than their controls. They were meaningfully lower than the healthy group in adult indirect inguinal hernia. Keratin 15, Keratin 1 and Filaggrin2 expressions were all correlating since they are members of related pathways. STAT3 expressions were opposite to Keratin and Filaggrin expressions suggesting that adult cells might have a switch to the mesenchymal state from the epithelial state. Adult indirect inguinal hernia samples have switched to the mesenchymal state whereas child indirect inguinal hernia samples have shown lack of transition. Conclusion Irregular changes of EMT associated genes act in the progression of indirect inguinal hernia. Hence, the information on the epigenetic regulation of EMT in patients with primary inguinal hernia can aid to comprehend the pathogenesis in adults and infers new therapeutic approaches for this disease. Type of study Prognosis study. Level of evidence Level 2.

Background Meningomyelocele (MMC) is a condition that is originated by the fusion defect of the neural tube. It is a congenital anomaly and can be characterized by spinal cord defects and impaired skin integrity. It is very important to close the skin openings via three-dimensional artificial skin like construction for preventing infection and maintaining the healthy skin structure. Therefore, we aim to generate artificial skin like structures formed by the own cells of donor for treating the MMC-related skin disorder. Methods In this study, waste placental tissues were collected and decellularization process was applied. Decellularized and normal placental tissues were compared by immunohistochemistry (IHC). Donor’s own placental stem cells were seeded onto biological scaffold and were differentiated into skin related cell types. Finally, gene expressions were evaluated, and the structural integrity were analyzed with IHC. Tube formation assay was also performed for examining the angiogenesis formation of the tissue in order to evaluate the possibility of a healthy organ development. Results Characterization experiments proved that the decellularized skin preserved a normal skin 3D construction and vasculature along with significant ECM arrangements. The well-kept placental ECM scaffold was cytocompatible, supportive of mesenchymal cell types. Native organ related scaffold is expected to carry a huge influence in skin tissue engineering via delivering a niche for skin-based cells and even for stem/progenitor cells. Regarding to the data obtained from this study, in vivo investigation the skin-like structure in animal models is thought to be the next step as a future prospect. Conclusion This study is a reference investigation for skin engineering based on placental stem cells and biological scaffolds.

A previous study performed by the authors of the current study revealed the characterization and differentiation of newly defined stem cells known as human newborn foreskin stem cells (hnFSSCs). According to their stem cell properties, this study aimed at investigating myogenic differentiation and related tissue engineering. Human newborn foreskin stem cells were characterized by flow cytometry. The results showed that hnFSSCs carries a noble prospective for myogenic differentiation and can be used as a beneficial method for muscle related diseases, including muscular dystrophy, neuromuscular disorders, muscle damages, muscle weakness, lesion formations, and other problems associated with tissue obtainability and multi-potency; these cells may be accepted as effortlessly accessible and functional, and even superior to other stem cell origins. Furthermore, hnFFSCs were also seeded onto 3D micro-wells and Polycaprolactone (PCL) scaffolds in order to examine tissue development. Human newborn foreskin stem cells on PCL scaffolds showed good cell-cell integration, so that they may be thought as a stem cell basis for tissue engineering.