NOVEL APPROACH TO THE HEDGEHOG SIGNALING PATHWAY: COMBINED TREATMENT OF SMO AND PTCH INHIBITORS

Purpose: Abnormal Sonic Hedgehog signaling Pathway (Shh) activation is crucial for the development of cancer stem cells, neoplastic growth, and epithelial-mesenchymal transition processes in adulthood. Activation of the Hedgehog signaling pathway may induce the changes in cilia found in the cell membrane, initiates the Gli1 transcription factor that is translocated to the cell nucleus and finally, the target genes are transcribed. In this study, investigation of the antiproliferative, anti-invasive, and antimigrative effect of the combined use of robotnikinin (Ptch1 antagonist) and vismodegib (Smo inhibitor) on the hedgehog signaling pathway was aimed. Material and Methods: After demonstrating the presence of the hedgehog signaling pathway in the glioblastoma cell line U87-MG, the effect of the combined use of the robotnikinin and the vismodegib on the hedgehog signaling pathway was investigated. In-vitro cell proliferation, migration, and invasion analysis of the combination of antagonist and inhibitor and in silico drug-likeness analysis were performed. Results: Two different combinations of robotnikinin and vismodegib were tested. In vitro studies show that the combined use of agents in combined treatments of Smo and Ptch1 is more effective than their individual usage. Conclusion: Inhibition of the hedgehog signaling pathway with specific inhibitors and antagonists is considered an innovative strategy for cancer therapy

Warburg and pasteur phenotypes modulate cancer behavior and therapy.

Energetic pathways combine in the heart of metabolism. These essential routes supply energy for biochemical processes through glycolysis and oxidative phosphorylation. Moreover, they support the synthesis of various biomolecules employed in growth and survival over branching pathways. Yet, cellular energetics are often misguided in cancers as a result of the mutations and altered signaling. As nontransformed and Pasteur-like cells metabolize glucose through oxidative respiration when only oxygen is sufficient, some cancer cells bypass this metabolic switch and run glycolysis at higher rates even in the presence of oxygen. The phenomenon is called aerobic glycolysis or the Warburg effect. An increasing number of studies indicate that both Warburg and Pasteur phenotypes are recognized in the cancer microenvironment and take vital roles in the regulation of drug resistance mechanisms such as redox homeostasis, apoptosis and autophagy. Therefore, the different phenotypes call for different therapeutic approaches. Combined therapies targeting energy metabolism grant new opportunities to overcome the challenges. Nevertheless, new biomarkers emerge to classify the energetic subtypes, thereby the cancer therapy, as our knowledge in coupling energy metabolism with cancer behavior grows.</p

Role of mesenchymal stem cell-derived soluble factors and folic acid in wound healing

Background/aim: Mesenchymal stem cells (MSCs) are a type of adult stem cell consisting of a heterogeneous subset of stromal stem cells that can be isolated from adult tissues. Folic acid is another important contributor to tissue regeneration and repair, which affects the synthesis of some building block molecules used for wound healing. In this study, we examine the effect of folic acid and MSC-derived soluble factors in the wound healing model

Determination of Cell Stiffness Using Polymer Microbeads as Reference

Knowing the mechanical properties of cells is very important in cell detection, analysis of cell activities, diagnosis and drug treatment. The determination of cell stiffness, which used effectively in cell analysis, is carried out with different measurement techniques. In this study, the stiffness of cells is determined by comparison to the displacement of polystyrene microparticles induced by vibration generated by piezoelectric transducers. The difference of stiffness of the cells and polystyrene microparticles is measured using a digital holographic imaging technique

Enteric Duplication Cysts in Children: A Single-Institution Series with Forty Patients in Twenty-Six Years

The purpose of the study was to evaluate our experience with enteric duplication cysts in 40 children during the past 26 years, while assessing the variability of their presentations and to propose an algorithm for surgical management

A prospective long-term evaluation of the ocular findings of children followed with the diagnosis of multisystem inflammatory syndrome (long-term evaluation of ocular findings following MIS-C)

Background/Objectives: The most frequently reported ocular finding in the acute phase of the multisystem inflammatory syndrome in children (MIS-C), is conjunctivitis. More rarely, punctuate epitheliopathy, anterior uveitis and optic disc oedema can be seen. We aimed to investigate the acute and long-term ocular effects of MIS-C. Subjects/Methods: Cases aged 1 month to 18 years who were diagnosed with MIS-C between January 2022 and June 2022 in the Department of Pediatric Infectious Diseases in our hospital were included in the study. Ophthalmological examinations were performed immediately after diagnosis, at one month, three months, and six months. Results: Males consisted of 64.7% of the 34 cases included in the study and the mean age was 8.68 ± 4.32 years (min-max:2–17). In the first examination, conjunctivitis was observed in 6 (17.6%), punctuate epitheliopathy in 4 (11.7%), and subconjunctival haemorrhage in 3 (8.8%) patients. Two patients (5.8%) had optic disc oedema. No pathological anterior or posterior segment findings were observed in the sixth-month examination. The relationship between subconjunctival haemorrhage and intensive care hospitalisation was statistically significant (p = 0.014). Also, all patients with subconjunctival haemorrhage were clinically classified as severe MIS-C (p = 0.002). Conclusion: Although pathological ocular findings were observed in the acute phase of the disease, all of them were found to be improved at the sixth-month follow-up. The most striking finding of our study is that cases with subconjunctival haemorrhage were clinically more severe, and all patients needed intensive care. This study may be informative in establishing ocular follow-up protocols that are expected to be carried out in the acute period and in the follow-up of these patients

Optimization of Different Surface Modifications for Binding of Tumor Cells in a Microfluidic Systems

Objectives:Microfluidic technology is a fast-growing area and provide high-efficient MEMS (Micro-Electro-Mechanical-Systems) sensor integration platform that helps to advance healthcare systems. Due to proper the chemical and mechanical properties of polymers, PDMS (Polydimethylsiloxane) (6) and PMMA (Poly-methyl-methacrylate), they became on the best candidate for health care studies in microfluidic studies (7). Besides, they perform great optical properties for observation of living cell experiments. To increase their performance, surface interactions works with cells, modification techniques are widely used in microfluidic chips. In this paper, our primary purpose is to modify such polymers and glass with matrigel, PDA and APTES so as to increase cell-surface interaction

Parental Attitudes About Lumbar Puncture in Children With Suspected Central Nervous System Infection

Objectives This study aimed to evaluate parents' attitudes toward lumbar puncture (LP) for their children with suspected central nervous system infection to determine the reasons for rejection and related factors. Methods The survey was provided to parents of children (1 month to 18 years old) for whom LP was recommended because of a concern for central nervous system infection. Sociodemographic characteristics and other related factors of parents who did and did not approve of LP were compared statistically. The reasons for the disapproval of parents who refused LP were revealed. Results A total of 100 parents were included in the study. Eighty-two percent of the participating parents were mothers, and the median age of the mothers was 31 years (min: 17 years; max: 70 years). The median age of the fathers was 37 years (min: 22 years; max: 60 years). Among the parents, 34% did not give consent for LP. The most common reason for the participants to refuse LP was fear of paralysis of their children due to the procedure (82.3%). There was a statistical difference between the approval of the LP procedure and the person who informed the parents about the LP procedure and read the informed consent form (P = 0.004 and P = 0.038, respectively). As a result of the binary logistic regression analysis, it was seen that the rate of acceptance of the LP procedure by the parents informed by the specialist doctors was 7.1-fold (P = 0.02; 95% confidence interval, 1.3-37.6) higher than the parents informed by the resident physicians. Conclusion The informed consent process mainly influenced parents' attitudes toward LP. To increase the acceptance rates of LP, we should standardize the informed consent process so that it is not affected by factors such as seniority of the physician