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Objective: Osteoarthritis (OA) is the most common joint disease. In this study it was aimed to compare the general features of OA such as location, placement, severity and shape of the lesions in terms of radiological and morphological aspects and to determine their relationship with each other. Methods: In our study, the antero-posterior and lateral radiographies of knee talocrural and transverse tarsal joints of 20 cadavers by age between 30 and 50 years were taken. The results obtained from the radiological examination were graded according to the Kellgren and Lawrence scale. For each of the identified regions, the presence of degenerative changes was noted. Then samples were taken from these regions were examined by microscopic methods. The cartilage degeneration changes, presence of fibrillations, density, depth, chondrocyte aggregation, and necrotic changes were evaluated. Results: In the radiological examination OA was found in 35% in knee joint, 25% in the talocrural joint, 15% in the transverse tarsal joint. In the morphological examination OA was found in 31.5% knee joint, 25% ankle joint and 5% transverse tarsal joint. In the microscopic examination OA was found in 94.7% knee joint, in 94.7% ankle joint and in 100% transverse tarsal joint. Conclusion: Although radiological and macroscopic OA was detected in approximately 1/3 of cadavers aged between 30 and 50 years, degeneration of varying degrees was detected in all joints examined in microscopic examination. This shows that an advanced age disease OA, starts at a very early age. Key words: Osteoarthritis, Knee joint, Talocrural joint, Transverse tarsal joint

Baglama is the most common folk string instrument in Turkey. It has a bowl-shaped resonator box called a chest which amplifies the sound. The chest can be constructed in various forms by the luthiers. This study aims to determine the sound characteristics of the baglama associated with different chest forms. First, a prototypical baglama was modeled and analyzed numerically with the SolidWorks, HyperMesh and Actran software programs. Operational Deflection Shape (ODS) measurements of the baglama were also carried out experimentally. The numerical results were compared with the experimental ones and had an excellent agreement. Using this experimentally validated numerical model, the natural frequencies, mode shapes and sound propagation properties of the baglama were investigated for chests of different geometries.

Introduction This study aims to investigate the effects of preoperative serum transthyretin (TTR) levels on surgical success, pain scores, and postoperative morbidity. Methods Note that, in our clinic, 188 patients who were operated for spinal pathologies between June 2010 and January 2011 were included in this study. Blood samples were drawn from all patients on the morning of surgery and then serum TTR measurements were made. Demographic data of all patients were collected, and then their preoperative and postoperative neurological examinations, Karnofsky scores, visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, postoperative infection and wound healing status, hospital stay, and morbidity levels were recorded and TTR levels were compared. Results When preoperative TTR level of patients were low, their Karnofsky scores decreased, ODI scores increased, the early postoperative VAS and late postoperative VAS values increased, and the length of hospital stay was increased. Moreover, in patients with low TTR levels, postoperative Karnofsky scores were lower, postoperative ODI levels were higher, postoperative early and late VAS scores were higher, hospital stays were longer, peroperative complication rates were higher, wound infection rates were higher, the delay in wound site healing was higher, and the morbidity rate was higher. Conclusion Consequently, preoperative low TTR levels have been reported to be an effective parameter that can be used to predict surgical results, wound infection and wound site healing status, perioperative complications, and morbidity in spinal surgery.

Redox homeostasis and redox signaling are constituents of preservation of a normal physiological state. Whereas the equilibrium between oxidants and nucleophiles is conserved in redox homeostasis, oxidative stress promotes the formation of a radically altered redox state. It is known that modification of circadian clock may lead to severe alteration in redox balance. Melatonin [N-acetyl-5-methoxytryptamine, (MLT)] regulates numerous physiological functions including circadian rhythm, sleep-wake cycle, gonadal activity, redox homeostasis, neuroprotection, immune-modulation, and anticancer activity in organisms. Insufficient MLT production is closely related to development of aging process, tumorigenesis, visceral adiposity, neurodegenerative disorders, etc. Reactive oxygen species (ROS) are not intrinsically harmful or beneficial in cellular redox metabolism. Redox homeostasis is an integrative status for both of the hormetic response to ROS overproduction and subsequent redox signaling. MLT and its derivatives are traditionally classified as hormone-like substances. Their redox sensitive regulatory activity and direct interaction with intracellular ROS serve as second messenger in cell signaling. This review involves the role of redox homeostasis in the pathogenesis of age-related disorders and its relationship with MLT, therefore, targeting the circadian rhythm may propose new therapeutic approach for these disorders.

Introduction: Ovarian cancer is the deadliest gynecological malignancy, usually not detected until the late stages. In vitro cell culture is a method used to study the behavior of cells in a controlled environment. Turmeric has attracted the attention of scientists due to its anticancer potential. Method: OVCAR-3 cells were cultured in RPMI medium with 100 units/mL-100 μg/mL of penicillin-streptomycin and 10% foetal bovine serum in a CO2 incubator. Turmeric extract was diluted in DMSO. Different concentrations of turmeric extract were prepared. Annexin-V staining was performed to test the translocation of phosphatidylserine to the outer side of the cell membrane as a clear indicator of apoptosis. Results: Turmeric extract significantly reduced the viability of OVCAR-3 cells both within 24 and 48 hours of exposure. OVCAR-3 cells were treated with IC50 concentration of turmeric extract for 24 hours. 82.60% of cells were viable. The percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.80%, 9.70%, and 6.90%, respectively. Untreated OVCAR-3 cells had migration ability. OVCAR-3 cells exposed to an IC50 concentration of turmeric extract for 24 hours did not close the scratch area. Conclusion: In this research, anticancer effects of turmeric have been demonstrated by different analysis methods.

Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice.

Background MicroRNAs (miRNAs) have important function in cancer development and progression.Aims This study aims to determine the expression levels of miR-639, miR-641, miR-1915-3p, and miR-3613-3p in tissues of colorectal cancer (CRC) patients and the role of these miRNAs in the CRC pathogenesis.Methods Tumor and non-tumor tissues were collected from a total of 59 CRC patients. qRT-PCR was used to identify the expressions of miR-639, miR-641, miR-1915-3p and miR-3613-3p. Through bioinformatics analysis, the target genes of miRNAs were identified by using DIANA mirPath v.3. Signaling pathways were generated using KEGG pathway database. Biological pathway, cellular component analysis, and analysis of Protein–Protein Interactions (PPI) Networks were performed using FunRich and STRING database.Results Our findings revealed that miR-639, miR-641 and miR-3613-3p were significantly downregulated, and miR-1915-3p was significantly upregulated in tumor tissues compared to non-tumor tissues (p˂0.05). Furthermore, MAPK signaling pathway was the most enriched KEGG pathway regulated by miR-639, miR-641, miR-1915-3p and miR-3613-p. According to the FunRich, it was demonstrated that the targeted genes by miRNAs related to the cellular component and biological pathways such as beta-catenin-TCF7L2, axin-APC-beta-catenin-GSK3B complexes, Arf6 signaling, Class I PI3K signaling, EGF receptor signaling, etc. And, by the PPI analysis, it was established that the target genes were clustered on CTNNB1 and KRAS.Conclusions These outcomes imply that miR-639, miR-641 and miR-3613-3p have tumor suppressor roles, while miR-1915-3p has an oncogenic role in the pathogenesis of CRC. According to the results of the current study, dysregulated miR-639, miR-641, miR-1915-3p, and miR-3613-3p might contribute to the development of CRC.

Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.

Supplementary Data from Immuno-PET Monitoring of Lymphocytes Using the CD8-Specific Antibody REGN5054

This paper uses bibliometric analysis to evaluate the literature on immigration, crime, and violence to find out how these concepts are studied across disciplines. The paper gave specific attention to the field of Criminology to demonstrate the variation of the use of these concepts in the literature and how much it differs from other disciplines. To meet these expectations, we examined how journals are categorized based on covering how immigration and crime interact in social science disciplines. Moreover, the analysis maps how research articles interact in different journals and what types of topics receive the most attention among researchers by looking at cross-citation data and keyword selection. The findings show that, overall, the number of publications used at least one of the studied items (immigration, crime, and violence) as a keyword increased tremendously in the last two decades. The most studied concept amongst all disciplines is violence, followed by gender and crime with the combination of migration, immigration, immigrants. The topic has been mostly studied from the ‘receiving country’ perspective and funding leads to an increase in publications. The findings suggest Criminology is the top field producing most of the studies in the field followed by public health-related research. These findings suggest that migration, when it is connected to crime and violence, is considered an individual- and social-level challenge requiring the attention of experts in understanding criminal and deviant behavior as well as experts from public health.

Background: Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently prescribed and used safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in endocrine-related adverse effects. background: Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals that are frequently prescribed and used safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in endocrine related adverse effects. Objective: In this research, we aimed to determine the endocrine disrupting potential of paracetamol, indomethacin, alpha-methyldopa and pantoprazole which are frequently prescribed pharmaceuticals during pregnancy. objective: The objective of the present research is to assess potential endocrine related adverse effect of paracetamol, indomethacin, alpha-methyldopa and pantoprazole. Methods: In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay. method: In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay. Results: None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-7/BUS cell viability at 100µM and 300µM. Among the tested pharmaceuticals, only paracetamol and indomethacin showed aromatase inhibitory activity with IC 50 values of 14.7 x 10 -5 M and 57.6 x 10 -5 M, respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa increased E2 at all tested concentrations and T at 1.48 and 4.4µM. Contrarily other tested pharmaceuticals did not affect steroidogenesis. result: None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-7/BUS cell viability at 100µM and 300µM. Among the tested pharmaceuticals, only paracetamol and indomethacin showed aromatase inhibitory activity with IC50 values of 14.7 x 10-5M and 57.6 x 10-5M respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa increased E2 at all tested concentrations and T at 1.48 and 4.4µM. Contrarily other tested pharmaceuticals did not affect steroidogenesis. Conclusion: Present data suggest that all tested pharmaceuticals may have potential endocrine disrupting effect, which should be considered when used in pregnancy. conclusion: As a conclusion, present data suggest that all tested pharmaceuticals may have potential endocrine disrupting effect which should be considered when using in pregnancy.

An “endocrine disruptor” has been broadly defined as an exogenous chemical that interferes with the production, release, transportation, metabolism, binding, action, or the elimination of endogenous hormones, which are responsible for homeostasis, reproduction, development or behaviour. Diverse groups of chemicals such as pharmaceuticals, phytoestrogens, natural hormones, and synthetic chemicals such as pesticides, plasticizers, phthalates, parabens, polychlorinated/polybrominated biphenyls, bisphenols are shown to interfere with the endocrine system, and they have been defined as EDs in the last three decades. As for all chemicals, the biotransformation of EDs has a decisive role in their potential toxic effects. Humans are exposed to vast amounts of diverse chemicals throughout their lives. Fortunately, most of the chemicals are converted via biotransformation reactions catalyzed by the enzymes, into more hydrophilic metabolites, which are readily excreted in urine or bile. Biotransformation reactions resulting in less toxic metabolites are known as detoxification. However, some biotransformation reactions are called bioactivation, in which more toxic metabolites are formed. In the case of EDs, metabolites formed via bioactivation usually have a higher affinity for a hormone receptor or induce/inhibit an enzyme involved in the synthesis or catabolism of an endogenous hormone more dramatically compared to their parent compound. In the present review, the role of bioactivation in endocrine modulating effects of chemicals from all groups of EDs, namely endogenous estrogens, phytoestrogens, synthetic/industrial chemicals, and pharmaceuticals it can be were discussed.

Introduction: Ovarian cancer is the deadliest gynecological malignancy, usually not detected until the late stages. In vitro cell culture used for studies such as the study of interactions of drugs. Dihydromyricetin is a key ingredient in many healthy foods or beverages. It has an excellent safety profile for human. Material-Method: SKOV-3 cells were cultured in RPMI medium with 100 units/mL-100 μg/mL of penicillin-streptomycin and 10% fetal bovine serum in a CO2 incubator. After incubation for 3 h at 37°C with 5% CO2, the media was removed and 0.1 mL of DMSO was added. The plates were read at 570 nm in the spectrophotometer. The MTT assay was repeated at least three times independently. Following this procedure, RT-PCR was performed. Results: SKOV-3 cells were treated with different concentrations of DHM. DHM was found to be cytotoxic to the SKOV-3 cell line in a time- and concentration-dependent manner. SKOV-3 cells were treated with different concentrations of BEV. Cell viability was decreased at the different concentrations. To evaluate the cytotoxic effects of DHM and BEV together on the SKOV-3 cell line, cells were treated with a combination of IC50 concentrations of DHM and BEV. According to combination results, DHM + BEV treatment was found to be more cytotoxic to SKOV-3 cells than treatment with DHM or BEV alone. Conclusion: In our study, the combined effects of two anti-cancer agents on ovarian cancer cell lines were investigated. It has been determined that the effect of the agents in the combined treatment is greater than that of the agents alone

Background: The term premature ovarian failure is defined as a persistent decrease in ovarian function in women. Platelet-rich plasma contains growth factors. In our study, the aim was to test the effectiveness of platelet-rich plasma that was tried in patients who did not benefit from routine infertility treatments on experimental animals. Material and Methods: In the study, 40 female rats were used, and to obtain platelet-rich plasma eight male rats were used. The animals used in the study were randomly divided into four groups, with 10 animals in each group, prospectively. At the end of the 21st day, rats in all groups were euthanized by taking intracardiac blood. Following anti-mullerian hormone measurement, histological analysis, follicle count and real time-polymerize chain reaction analyzes were made Results: In our study, the highest anti-mullerian hormone concentration was measured only in the group given platelet-rich plasma and the lowest value was measured in the group with ovarian damage. The results of Bcl-2 m-RNA expression analysis by real time-polymerize chain reaction also showed that the lowest expression occurred in the group with ovarian damage. The results of the correlation analysis showed that there was a statistically significant, negative moderate correlation between the ovarian damage group and the ovarian damage + Platelet-rich plasma group. Conclusions: As a result, it is evaluated that platelet-rich plasma can be used as a preventative in women who are treated with cyclophosphamide and similar agents and subsequently develop ovarian side effects that are very difficult to treat

Amac: Pediatrik yas donemi nevogevez icin dinamik bir yapiya sahip olup nevus gelisimi icin onemli ip uclarini bunyesinde barindirmaktadir. Bu calismada pediatrik yas grubunda kazanilmis melanositik nevuslerin dermoskopik patern ve pigment ag yapilari incelenerek banal ve atipik yapili nevuslarin taninmasina katki saglanmasi amaclanmistir. Hastalar ve Yontem: Calismaya nevogenez icin yatkinligi bulunmayan 150 pediatrik gonullu dahil edilmistir. Cocuklar 7 yas ve alti ve 8 yas ve ustu olarak iki gruba ayrilmistir. Muayene edilen nevuslerden govde ve ekstremite yerlesimli nevuslerin sayi, boyut, patern ve pigment yapilari incelenmistir. Bulgular: Nevus sayi ortalamasi buyuk yas grubunda (9,72) kucuk yas grubundan (3,44) daha fazla oldugu izlendi. Her iki grupta da predominant patern yapisinin globuler patern oldugu, 8 yas ve ustu grubunda retikuler paterne sahip nevuslarin 7 yas ve alti grubundan daha fazla oldugu izlendi (p=0,03). Her iki grupta da globuler paterne sahip nevuslarin govdede, retikuler paterne sahip nevuslarin ekstremite de daha yogun oldugu izlendi (p=0,001). Nevuslerin Pigment ag yapilari incelendiginde en sik izlenen pigment ag yapisi uniform olmakla birlikte 8 yas ve ustu grupta santral pigmentasyon degisikligi bulunan nevuslarin daha fazla izlendigi goruldu (p=0,001). Sonuc: Pediatrik yas grubunda kazanilmis melanositik nevusler siklikla globuler patern ve uniform pigment ag yapisina sahip olsa da artan yas ile birlikte retikuler paterne ve santral pigmentasyon degisikligine sahip nevus sayisi artmaktadir.

Abstract: The conventional central dogma of molecular biology dictates that the genetic information contained within deoxyribonucleic acid (DNA) is passed onto messenger ribonucleic acids (mRNAs), which are then used as templates to synthesize proteins. Although these types of proteincoding genes have been historically prioritized in typical phenotype-genotype studies with a parallel disregard to the rest of the genome, the completion of genome projects has unveiled a surprising layer of genetic information that can play critical roles in cellular processes without coding for proteins. These types of genes are called noncoding genes as they do not code for proteins. Noncoding genes come in different sizes and shapes, and they are just as versatile in carrying out cellular biochemical processes as proteins. In this review, we cover a comprehensive review of housekeeping and regulatory noncoding genes and their mode of action.

Introduction: Cervical cancer is the deadliest gynecological malignancy. This study aims to examine the anticancer effects of L-citrulline on HeLa cell culture. Materials-Methods: HeLa cells were cultured in complete Eagle's minimum essential medium. HeLa cells were seeded in 96-well plates and incubated with L-citrulline. After incubation, MTT dye was added and incubated. Annexin- V technique was used to test the apoptosis. The activated caspases of HeLa cells by L-citrulline exposure were measured with the Caspase 3/7 technique. One-way variance analysis was conducted for statistical analysis by using GraphPad Prism 6.0 for Windows. Results: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner in application times of 24 and 48 hours. The IC50 dose of L-citrulline was 0.19 and 0.16 mg/mL at 24 and 48 hours, respectively. When HeLa cells were exposed to an IC50 dose of L-citrulline for 24 hours, the percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.75%, 23.05%, and 12.75%, respectively. The differences in the wideness of the scratch area were observed at the initial stage and after 24 hours of applying L-citrulline. Conclusion: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner. Based on Annexin and Caspase findings, it can be concluded that L-citrulline exerted a pro-apoptotic effect on HeLa cells in only a short exposure time. L-citrulline also showed a migration inhibitory effect. The findings of this study indicate L-citrulline to be worthy of investigation for its anticancer activities in vitro and in vivo, and as a candidate for cancer therapy.

Despite the enormous promise of T cell therapies, the isolation and study of human T cell receptors (TCRs) of dedicated specificity remains a major challenge. To overcome this limitation, we generated mice with a genetically humanized system of T cell immunity. We used VelociGene technology to replace the murine TCRαβ variable regions, along with regions encoding the extracellular domains of co-receptors CD4 and CD8, and major histocompatibility complex (MHC) class I and II, with corresponding human sequences. The resulting “VelociT” mice have normal myeloid and lymphoid immune cell populations, including thymic and peripheral αβ T cell subsets comparable with wild-type mice. VelociT mice expressed a diverse TCR repertoire, mounted functional T cell responses to lymphocytic choriomeningitis virus infection, and could develop experimental autoimmune encephalomyelitis. Immunization of VelociT mice with human tumor-associated peptide antigens generated robust, antigen-specific responses and led to identification of a TCR against tumor antigen New York esophageal squamous cell carcinoma-1 with potent antitumor activity. These studies demonstrate that VelociT mice mount clinically relevant T cell responses to both MHC-I– and MHC-II–restricted antigens, providing a powerful new model for analyzing T cell function in human disease. Moreover, VelociT mice are a new platform for de novo discovery of therapeutic human TCRs.

We develop a multi-cell smart city simulator called LEAN that is targeted at the development and testing of Medium Access Control (MAC) layer protocols for massive Internet of Things (mIoT). Our simulator supports any number of cells, each of which is centered around an IoT gateway, over any geographic area, which is displayed on a Graphical User Interface (GUI). In addition to all of the static IoT devices that appear on the GUI, our simulator keeps track of the associations of all mobile IoT devices across time and furnishes these associations to any back-end MAC protocol that is developed in the simulation environment. In contrast with general-purpose smart city simulators, LEAN has relatively low time and space complexity in the number of IoT devices and is well-suited for quick testing of novel MAC protocols for massive IoT.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have major functions in the development and progression of colorectal cancer (CRC) as tumor suppressors or oncogenes. The aim of the current research was to assess the role of miR-485-3p and miR-4728-5p in the pathogenesis of CRC. In this study, fresh tumor and adjacent non-tumor tissue samples were obtained from a total of 59 CRC patients, 37 from colon and 22 from rectum. The expression profiles of miR-485-3p and miR-4728-5p were determined using qRT-PCR. miRNA-related transcription factor (TF) regulatory networks were constructed using the TransmiR v2.0, TF-regulated target genes were determined using the Human.mirFFL.DB and TRRUST v2.0, functional annotation and pathway enrichment analyses were performed using DIANA-mir-Path v3.0 and -Tarbase v7.0. The results demonstrated that the expression levels of both miR-485-3p and miR-4728-5p were very significantly downregulated in CRC tissues (fold changes = 0.42 ± 0.70 and 0.59 ± 1.06, respectively; both p = 0.000). On the other hand, lower expression levels of miR-485-3p were detected in the both rectum and colon. Moreover, the decrease in the expression levels of miR-4728-5p was correlated with increasing age. However, these differences were not statistically significant according to the FDR-related p-values (0.126 and 0.168, respectively). By bioinformatics analyses, miR-485-3p and miR-4728-5p-related TFs were identified. Some of these TFs, namely, AR, CREB1, CEBPB, FOXA1, GTF2I, MAZ, NCOR2, NFIC, NRF1, SIN3A, SREBF1, SREBF2, p53 and YY1, appeared to be associated with CRC and were, therefore, selected to construct miRNA-TF-gene networks of potential targets for the early diagnosis and treatment of CRC. Pathway enrichment analysis indicated Hippo signaling pathway as heavily regulated by miR-485-3p. It seems that the decrease in expression levels of miR-485-3p and miR-4728-5p might be associated with development of colorectal cancer.

The study aimed to determine the expressions of SP1 and SP3 and the clinic pathological characteristics of patients, and the correlation between the expressions of SP1 and SP3 in colorectal cancer (CRC). In this study, tumour and adjacent non-tumour tissue samples were obtained from 41 individuals with CRC. SP1 and SP3 expressions were performed using Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). According to the results of our study, there was no statistically significant difference in SP1 and SP3 expression levels between tumour tissues and non-tumour tissues (p>0.05), as well as no association with clinic pathological features of patients. In addition, a high positive correlation was found between the expressions of SP1 and SP3 genes in CRC (p=0.01). Consequently, it can be said that there is a correlation between SP1 and SP3 expressions, but SP1 and SP3 expressions are not related to CRC carcinogenesis.

This study aimed to develop fluconazole loaded buccal mucoadhesive oral strip for local treatment of oral candidiasis. Oral strip was prepared by solvent casting method with different polymer combinations and evaluated for weight, thickness, drug content, tensile strength, swelling behavior, in vitro disintegration time and drug release, ex vivo mucoadhesive performance, stability study, ex vivo drug diffusion and in vitro antifungal activity. Oral strips were smooth and elegant in appearance; were uniform in thickness, weight and drug content. The disintegration time was within the range of 23–28 s. The release rates of fluconazole from oral strips reached ?96%. The optimum formulation was stable for 6 months. The in vitro antifungal activity studies showed the efficacy of the oral strip against Candida albicans for an extended period. Cytotoxicity was also studied, and no cytotoxic effect was observed at the tested concentration. The developed oral strip can be a promising delivery system in oral candidiasis. © 2018 12/ECZ/010 This study was supported by a research grant from Ege University ( 12/ECZ/010 ). We would like to acknowledge Ege University Pharmaceutical Sciences Research Center (FABAL) for enabling us to use its laboratory instruments (Nüve Stability Cabin).

Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.

To analyze the effects of various obstetric and perinatal factors on the severity of retinopathy of prematurity (ROP).Infants born at ≤ 32 weeks of gestation, with less than 1500 g gestational weight and having at least stage 1 ROP, were reviewed. Group1A included treatment-requiring ROP (TR-ROP), and group 2A included the remaining patients not requiring treatment. Group 1B included stage 3 ROP cases, and group 2B included the remaining stage 2 or 1 ROP cases. Group 1C included cases with zone III disease, and group 2C the remaining. The control group (group C) was composed of premature infants without ROP. The multiple comparisons were made among groups 1A, 2A, and C; 1B, 2B, and C; 1C, 2C, and C.A total of 311 infants were included. Group 1A included 34 cases, group 1B 60, group 1C 51, and group C 98. Antenatal steroid administration, gestational diabetes mellitus (GDM), gestational weight (GW), gestational age (GA), sepsis, continuous positive airway pressure (CPAP) time, and invasive mechanical ventilation (MV) time were associated with TR-ROP, stage 3 ROP, and zone I, and II disease (p 0.05). Pregestational diabetes mellitus (DM) was only associated with stage 3 ROP (p = 0.031). Gestational hypertension was only associated with zone I and II disease (p = 0.034). The use of low-molecular-weight heparin may be protective against stage 3 disease (p = 0.031).Antenatal steroid administration, GDM, GW, GA, sepsis, CPAP time, and invasive MV time were risk factors for TR-ROP and stage 3 ROP, while pregestational DM was only associated with stage 3 ROP.

The aim of this study was to investigate the effect of subacromial decompression on the results of full thickness rotator cuff repair applied arthroscopically. Examination was also made of the effect of acromion type on the subacromial decompression procedure in patients applied with arthroscopic rotator cuff repair.The study included a total of 150 patients, comprising 102 (68%) females and 48 (32%) males with a full thickness rotator cuff tear repaired arthroscopically. The patients were separated into three groups of 50. Group A comprised those with acromioplasty and bursectomy applied additional to the repair. In Group B, only bursectomy was performed additional to the repair and in Group C, only rotator cuff repair was applied. Evaluation was made of the post-operative long-term pain and functional results.The mean age of the cases was 65.63±9.22 years (range, 46-86 years). The affected side was right side in 95 (63.3%) cases and left side in 55 (36.7%). No statistically significant difference was determined between the groups according to the post-operative Constant Murley and ASES scores (p0.05). In the paired comparisons, the post-operative VAS scores of Group C were higher than those of Groups A and B (p=0.018, p=0.029, p0.05). No statistically significant difference was determined between Group A and Group B in respect of the post-operative VAS scores (p0.05).In the arthroscopic repair of full thickness rotator cuff tears, neither acromioplasty, coracoacromial ligament loosening nor bursectomy were determined to have any positive effect on the results. Whatever the acromion type, there is no need for an additional subacromial decompression procedure after rotator cuff repair, in respect of pain and functional outcomes. Only acromial spurs should be gently removed paying attention to the coraco-acromial ligament.

This work reports the production of activated carbons (AC) from bitter orange peel by using ZnCl2 or H3PO4 as activating agent at two different carbonization temperatures (450 °C and 550 °C). Surface morphology analyses of produced bitter orange activated carbons (BOACs) were done by SEM. The surface areas of the produced BOACs, functional groups on the AC surfaces and compositions, were determined by using BET, FT-IR, and TGA analyses. Furthermore, their application for the removal of methylene blue (MB) was studied. The parameters affecting adsorption, such as pH and temperature, were evaluated. BOAC produced with ZnCl2 at 550 °C, exhibits the highest surface area (1450.6 m2 g−1), whereas BOAC produced with ZnCl2 at 450 °C yielded with the highest adsorption capacity (108.9 m2 g−1). Langmuir isotherm shows a good fit for the BOACs. Adsorption kinetics were studied and follows pseudo-second-kinetic model. The thermodynamic parameter studies indicate that the adsorption process is endothermic and spontaneous.

Cisplatin is a chemotherapeutic drug with pleiotropic effects known to modulate the expression of long non-coding RNAs (lncRNAs). With the annotation of many novel lncRNAs, it is imperative to employ a more comprehensive approach to identify cisplatin-mediated changes in the expression of lncRNAs. Next generation sequencing (NGS)-based profiling of total RNAs from cisplatin-treated HeLa cells identified 3489 expressed lncRNAs, of which 1930 and 1051 were up- and downregulated upon cisplatin treatment, respectively. For functional analyses, we selected one of the cisplatin inducible lncRNAs situated antisense to the death receptor 5 and thus named death receptor 5 antisense lncRNA (DR5-AS). Knock-down of DR5-AS lncRNA caused a morphological change in cell shape without inducing any cell death. A second round of NGS-based profiling of total RNAs from DR5-AS-silenced cells revealed differential expression of genes associated with the immune system and cell cycle. Further analyses showed that DR5-AS reduces cell proliferation and causes a cell cycle arrest at S and G2/M phases. These results suggest that cisplatin-mediated reduction in cell proliferation and cell cycle may be mediated by long non-coding RNAs.SignificanceCisplatin is known to induce DNA-damage-induced cell death, which is used in combination chemotherapies in various cancer types. However, many patients develop resistance to cisplatin, which involves both protein-coding and noncoding genes. Although a number of long noncoding RNAs are linked to cisplatin resistance, a more comprehensive study is required. In this study, we took advantage of next-generation-sequencing based lncRNA profiling to unveil the extent of cisplatin inducible lncRNAs in HeLa cells. Additionally, we functionally characterized one of the cisplatin-inducible lncRNA, death receptor 5 antisense. Interestingly, this spesific lncRNA modulates cell morphology, proliferation and cell cycle without affecting cell death.

AIM demonstrate the changes in Grade II and III glial tumors after a new classification. MATERIAL AND METHODS The previous diagnoses and postoperative treatment of the 83 patients were recorded. We used real-time PCR (mutation assay) for the analysis of IDH1 and IDH2, while we used FISH test to determine 1p/19q codeletion. The integrated diagnosis was compared with classical histopathological diagnoses. RESULTS We studied 13 oligodendendrogliomas, 41 astrocytomas and 29 oligoastrocytomas patients with classical histopathological diagnosis group. IDH mutation was detected in 51 of the patients after genetic analysis, whereas 1p/19q codeletion was detected in 20 patients. We found that grade II IDH-mut astrocytoma patients had significantly better survival outcomes compared to grade III IDH-mut astrocytoma patients. CONCLUSION Grade II and III gliomas are separated into more homogeneous diagnostic groups for survival after molecular marker analyses. Compared to histopathological diagnosis, the WHO 2016 glioma classification with molecular markers provides new perspectives in patient prognosis and treatment. However, due to the costs of using molecular markers, the extent to which it can be used remains questionable.

Over the last decade, there has been substantial interest in the use of melatonin (MLT) and MLT-like compounds in the treatment of several diseases. MLT can scavenge different reactive oxygen species and can also stimulate the synthesis of antioxidant enzymes. Our ongoing study relies on changing the groups in the different modifiable sites of the indole ring to increase the antioxidant activity. In this study a new approach for substitution of indole ring as indole based MLT analogue was proposed. We report the synthesis and characterization of a series of new indole-7-aldehyde hydrazide/hydrazone derivatives as indole-based MLT analogues. Anticancer potential of the compounds were evaluated both by their antioxidant and CYP1 inhibitory activities. In vitro antioxidant capacity of the compounds was investigated both in a cell-based (DCFH assay) and a cell-free (DPPH assay) assay. Potential inhibitory effects of the compounds on CYP1 catalytic activity were investigated via EROD assay. Cytotoxic activity of the compounds was further evaluated by the MTT assay in CHO-K1 cells. MLT analogues having an o-halogenated aromatic moiety exhibited effective antioxidant properties without having any cytotoxic effect. In conclusion, MLT derivatives represent promising scaffolds for discovery of effective antioxidant agents. © 2020 Elsevier Inc., 109S099 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, This work was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) Research and Development Grant 109S099. All spectral analyses were performed at Ankara University, Faculty of Pharmacy, Central Laboratory. All biological activity measurements were performed at Ege University, Faulty of Pharmacy, Pharmaceutical Sciences Research Center (FABAL).

Modifications in the crystal properties, chemical compositions and bond contents as a result of irradiation of Yb2O3/Si structures annealed at different temperatures in the dose range of 1-50 kGy were investigated. Beside, comprehensive results on the effect of the structural changes on radiation response of the MOS capacitors produced with these structures was presented in this study. 122 nm-thick Yb2O3 films were grown on p-type Si by RF magnetron sputtering, and the Yb2O3/Si structures were annealed at 200 degrees C, 400 degrees C, 600 degrees C, 800 degrees C under nitrogen ambient. The radiation exposure disrupts the crystalline properties of the film. Yb 4 d and O 1s spectra were taken from different depths in the Yb2O3/Si structures with X-ray photoelectron spectroscopy. Reasons of the right-side shift in the capacitance voltage (C-V) curves of the as-deposited and 200 degrees C-Yb2O3 MOS capacitors with radiation exposure were determined as increasing 2+ oxidation state occurring with the trapping of the electrons in the Yb3+ defect centers, decreasing Si-Si bond contents causing the positive charge trapping at Yb2O3/Si interface, existence of the hydrogen defect precursors. Events causing the left-side shift of the C-V with radiation exposure may be the silicate layer developing at the interface, increase in the trapping of the positive charges in the Si-Si defect centers, and decreasing Yb-Yb and 2+ contents. The radiation responses of the 400 degrees C, 600 degrees C, 800 degrees C-Yb2O3 MOS capacitors could not be measured at the frequencies lower than 2 MHz due to high charge trapping, high binding energies of the Yb-O and Yb3+ peaks, increasing 2+ oxidation content. The C-V curve shifted to the left-side at the relatively lower dose of 1 kGy for only device composed of 200 degrees C-Yb2O3 film. The sensitivities of the 200 degrees C-Yb2O3 MOS capacitor were found to be 16.3 mV/Gy for 70 Gy.

Taking reduced relative clauses as the basis of comparison, this study investigates Karachay-Balkar non-subject relative clauses with two different patterns. The subject in the modifier clause can bear the genitive case in the presence of agreement morphology on the head noun, or the nominative case in the absence of agreement morphology. Based on binding and adverbial placement tests, the current study suggests that (i) Karachay-Balkar relative clause patterns with genitive or nominative subjects are deficient in the absence of CP and TP; (ii) in the absence of TP, temporal interpretation is a secondary effect of AspP; (iii) the genitive subject moves into the DP domain to check the definiteness feature; (iv) the genitive pattern is preferred when the referents of the genitive construction and the head noun are shared by the speaker and the hearer; and (v) in the absence of the definiteness feature and CP/TP, the nominative case is licensed as the default case. This study shows that Karachay-Balkar relative clauses are reduced with respect to the absence of CP/TP. However, the size of the structure does not differ in genitive and nominative patterns, and the patterns are not in free variation as a syntax-semantic interface is at play. (C) 2020 Elsevier B.V. All rights reserved.

International and regional conflicts have been the most significant source of forced displacement and mass migration for decades. In a globalized world, human displacement reached its highest numbers and conflict became the number one reason for people to leave their home countries. This chapter analyzes the relationship between conflict and human displacement in a globalized context and demonstrates different stages of displacement. Each stage is connected with relevant levels of analysis (international, state, society, and individual) and the chapter argues that refugees become subjects of different risks at international, state, and societal levels during and after the displacement process. At each level, the nature of vulnerability changes and refugees are mostly affected by several external conditions, of which they have very limited control. By looking at the human (forced) displacement as a phenomenon from global to regional than local will help us to understand how the displacement process itself increases the vulnerability of displaced groups and individuals.

In the presented work, the parameters of a new MAPD-3NM-II photodiode with buried pixel structure manufactured in cooperation with Zecotek Company are investigated. The photon detection efficiency, gain, capacitance and gamma-ray detection performance of photodiodes are studied. The SPECTRIG MAPD is used to measure the parameters of the MAPD-3NM-II and scintillation detector based on it. The obtained results show that the newly developed MAPD-3NM-II photodiode outperforms its counterparts in most parameters and it can be successfully applied in space application, medicine, high-energy physics and security.