Search

Turkey is a rich country in historical monuments. In the district of Harran, Şanlıurfa province, the work was done, an ancient city and many other ruins beside the world's first university can be found. Considering the climate and sensitive structure of the studied region 3D modeling is a suitable technique. By means of such works reconstruction, that can show us the former state of the region will be enabled at a later point of time. In case the historical site would be destroyed in any way, it will be useful for recording the work as a visual and digital resource. Then, when the work has to be restored, the data can be used as a base and realistic restoration projects could be carried out.

A structural or functional cervix problem prevents a woman from carrying a full-term pregnancy, which leads to the disease known as cervical insufficiency. Cervical insufficiency is partially inherited, and in certain situations, variations in genes related to connective tissue metabolism may be involved. The main objective of this investigation was to describe the collagen type I alpha 1 chain (COL1A1) gene rs1800012 polymorphism and the transforming growth factor beta 1 (TGFB1) gene rs1800471 polymorphism in a cohort of patients suffering from cervical insufficiency. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays have been used to analyze the DNAs of 93 patients with cervical insufficiency and 103 healthy controls. The chi-square test was used for statistical analysis. There were significant differences in the genotype frequencies of the COL1A1 gene rs1800012 (G > T) and TGFB1 gene rs1800471 (G > C) polymorphisms between the patient and the control groups (p = 0.049 and p = 0.049, respectively). Also, the C allele of the TGFB1 rs1800471 polymorphism was significantly higher in the patient group than the control group (p = 0.016). Following clinical assessment, the COL1A1 rs1800012 polymorphism was found to be connected to the history of cerclage (p = 0.010). Additionally, the frequency of the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms was significantly lower in the patient group than the control group (p = 0.049). The TT genotype of COL1A1 rs1800012 polymorphism was found to be protective against cervical insufficiency, while the C allele of TGFB1 rs1800471 polymorphism was found to predispose to the disease. It appears that the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms protects against cervical insufficiency., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Autophagy is a recycling pathway in which damaged or dysfunctional proteins, protein aggregates, and organelles are delivered to lysosomes for degradation. Insufficiency of autophagy is thought to contribute to several age-related diseases including osteoporosis. Consistent with this, elimination of autophagy from the osteoblast lineage reduces bone formation and causes low bone mass. However, whether increasing autophagy would benefit bone health is unknown. Here, we increased expression of the endogenous Transcription Factor EB gene ( Tfeb ) in osteoblast lineage cells in vivo via CRISPR activation. Tfeb overexpression stimulated autophagy and lysosomal biogenesis in osteoblasts. Tfeb overexpressing male mice displayed a robust increase in femoral and vertebral cortical thickness at 4.5 months of age. Histomorphometric analysis revealed that the increase in femoral cortical thickness was due to increased bone formation at the periosteal surface. Tfeb overexpression also increased femoral trabecular bone volume. Consistent with these results, bone strength was increased in Tfeb overexpressing mice. Female Tfeb overexpressing mice also displayed a progressive increase in bone mass over time and at 12 months of age had high cortical thickness and trabecular bone volume. This increase in vertebral trabecular bone volume was due to elevated bone formation. Osteoblastic cultures showed that Tfeb overexpression increased proliferation and osteoblast formation. Overall, these results demonstrate that stimulation of autophagy in osteoblast lineage cells promotes bone formation and strength and may represent an effective approach to combat osteoporosis.

We aimed to investigate the promoter methylation status of RASSF1A and RASSF2A tumor suppressor genes in endometrial endometrioid carcinomas with p53 wild type and mismatch repair proficient. Genomic DNAs were isolated from 50 specimens (15 formalin-fixed paraffin embedded tumor tissues, 15 paired blood samples and 20 normal endometrial tissues). Bisulfide modification and methylation-specific polymerase chain reaction were performed. As a result of the study, while no significance was found for RASSF1A gene ( p  = 0.08), a statistically significance was found for RASSF2A gene ( p  < 0.001), RASSF2A gene methylation status was also found higher in high grade tumors, advanced age (≥50) and nonsmokers groups. Our results indicate that RASSF2A gene may play a role in the carcinogenesis of endometrioid and it could be potential biomarker for early detection for endometrioid carcinoma. Further and larger investigations are needed to confirm our results.

Purpose: We aimed to determine the tongue edema that may develop due to the pressure exerted by the endotracheal intubation (ETI) tube on the tongue during the follow-up period of mechanical ventilation in patients intubated in the intensive care unit (ICU) by submental ultrasonography (USG). Also, we aimed to investigate the effect of tongue edema on the oxygen saturation values (SpO 2 ) measured two h after extubation., Methods: One hundred patients aged 18-65 years, who were followed up with mechanical ventilation in the ICU from the 0th day of intubation, were included. Patients (n = 57) who were followed up on mechanical ventilation for four days or longer after ETI were included in the study group. Those who were followed up on mechanical ventilation for three days or less after endotracheal intubation and were extubated during this period were included in the control group (n = 43). The tongue cross-sectional areas (TSAs) of patients in both groups were measured twice with submental USG. The first measurement (TSA 1 ) was performed on the 0th day of ETI in all patients in both groups. The second measurement (TSA 2 ) was performed on the 4th day of ETI in the study group and just before extubation in the control group. The difference between TSA 2 and TSA 1 was defined as tongue edema. Also, the effect of tongue edema on the oxygen saturation levels measured at the 2nd h after extubation of the patients in the control group was investigated., Results: The tongue edema was more prevalent in the study group (p < 0.01). A significant negative correlation was found between the SpO 2 levels two hours after extubation and the increase in the mean TSA values indicating tongue edema (p < 0.01). The oxygen saturations of the patients with tongue edema were 4% lower than those without tongue edema., Conclusions: Tongue edema may develop due to the long-term application of pressure of the ETI tube on the tongue and may impair oxygenation after extubation., Gov Identifier: NCT05249738., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Adenoid tissue is a first-line host defense secondary lymphoid organ, especially in childhood. The endoplasmic reticulum (ER) is required to maintain balanced cellular activity. With impaired ER functions, protein accumulation occurs, resulting in ER stress, which plays a role in the etiopathogenesis of many diseases., Objective: We aimed to investigate the relationship between ER stress and adenoid tissue disorders, thereby elucidating the mechanisms of immunity-related diseases., Methods: Fifty-four pediatric patients (>3 years old) who underwent adenoidectomy for chronic adenoiditis (CA) or adenoid hypertrophy (AH) were enrolled in this prospective, parallel-group clinical study. Adenoids were divided into two groups (CA or AH) based on their size and evaluated for ER stress pathway and apoptosis pathway markers by Real-time PCR and Western blot analysis., Results: ER stress pathway markers significantly differed between the CA and AH groups. Children with CA had higher ER stress marker levels than the AH group ( p  < .001 for ATF-4, ATF-6, and GRP78, and p  < .05 for EDEM1, CHOP, EIF2AK3, ERNI, and GRP94). Apoptosis pathway marker levels (BAX and BCL-2) were not different between groups., Conclusions: ER stress contributes to the etiopathogenesis of adenoid tissue diseases and the pathogenesis of adenoid tissue disorders, which are part of the immune response. These results may guide the development of new and alternative treatments for immune system disorders., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Single-cell RNA-seq has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single-cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types associated with murine bone. We created an atlas of murine bone-associated cells by harmonizing published datasets with in-house data from cells targeted by Osx1-Cre and Dmp1-Cre driver strains. Cells from periosteal bone were analyzed separately from those isolated from the endosteum and trabecular bone. Over 100,000 mesenchymal cells were mapped to reveal 11 major clusters designated fibro-1, fibro-2, chondrocytes, articular chondrocytes, tenocytes, adipo-Cxcl12 abundant reticular (CAR), osteo-CAR, preosteoblasts, osteoblasts, osteocytes, and osteo-X, the latter defined in part by periostin expression. Osteo-X, osteo-CAR, and preosteoblasts were closely associated with osteoblasts at the trabecular bone surface. Wnt16 was expressed in multiple cell types from the periosteum but not in cells from endocortical or cancellous bone. Fibro-2 cells, which express markers of stem cells, localized to the periosteum but not trabecular bone in adult mice. Suppressing bone remodeling eliminated osteoblasts and altered gene expression in preosteoblasts but did not change the abundance or location of osteo-X or osteo-CAR cells. These results provide a framework for identifying bone cell types in murine single-cell RNA-seq datasets and suggest that osteoblast progenitors reside near the surface of remodeling bone., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Published by Elsevier Inc.)

Chaperone-mediated autophagy (CMA) is a lysosome-dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age-associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age-associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS-32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age-related bone loss, we hypothesized that declining CMA contributes to the age-associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA-deficient mice and controls up to 24 months of age and examined age-associated changes in bone mass and architecture. We showed that lack of CMA did not alter age-associated decline in bone mineral density as measured by dual x-ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA-deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age-related bone loss., (©2024 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

Objective: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population., Methods: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied., Results: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively)., Conclusion: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

Cre-mediated recombination is frequently used for cell type-specific loss of function (LOF) studies. A major limitation of this system is recombination in unwanted cell types. CRISPR interference (CRISPRi) has been used effectively for global LOF in mice. However, cell type-specific CRISPRi, independent of recombination-based systems, has not been reported. To test the feasibility of cell type-specific CRISPRi, we produced two novel knock-in mouse models that achieve gene suppression when used together: one expressing dCas9::KRAB under the control of a cell type-specific promoter and the other expressing a single guide RNA from a safe harbor locus. We then compared the phenotypes of mice in which the same gene was targeted by either CRISPRi or the Cre-loxP system, with cell specificity conferred by Dmp1 regulatory elements in both cases. We demonstrate that CRISPRi is effective for cell type-specific LOF and that it provides improved cell type-specificity compared to the Cre-loxP system., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objective: Classification of polycystic ovary syndrome (PCOS) according to their phenotypes is important in terms of understanding which parameter has clinical and laboratory implications. This study was designed to measure the follicular fluid total oxidant capacity (TOC) and total antioxidant capacity (TAC) and DNA degradation products of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with different PCOS phenotypes undergoing In-Vitro Fertilization/Intra-Cytoplasmic Sperm Injection (IVF/ICSI)., Patients and Methods: Thirty women who were diagnosed with PCOS and twenty infertile patients who did not have the clinical and laboratory findings of PCOS were included. Women carrying at least two of the three parameters below were considered to have PCOS. (1) Biochemical or clinical manifestations of hyperandrogenism (HA); (2) Ovulatory dysfunction (OD); (3) Polycystic ovarian morphology (PCOM). Patients were then classified into four different PCOS phenotypes: (1) Phenotype A is also known as classical PCOS and meets all three criteria (HA/OD/PCOM). (2) Phenotype B has two criteria, HA and OD. (3) Phenotype C consists of HA and PCOM criteria. (4) Phenotype D is the non-hyperandrogenic form and consists of OD and PCOM criteria. Antagonist protocol was used in both PCOS and control groups. During oocyte pick-up, follicular fluid of the dominant follicle was collected. TAC and TOC levels, which are redox balance markers, and 8-OHdG levels, which are DNA degradation products, were measured in follicular fluid samples (FF)., Results: Follicular fluid 8-OHdG levels of all four types of phenotypes were significantly higher than the control group. When the phenotype groups were evaluated among themselves, FF-8-OHdG levels of each group were found to be similar. Serum TOC levels of each phenotype group were found to be significantly higher than the control group. TAC levels of the patients in the control group were significantly higher than the other four phenotype groups. Oxidative stress index (OSI) values were significantly higher in all four phenotype groups compared to the control group. OSI values of phenotype B and D groups were significantly higher than phenotypes A and C., Conclusions: In each phenotype of PCOS, TOC and OSI increased while TAC decreased. Increased OSI leads to DNA degradation and an increase in the level of 8-OHdG. The cumulative effect of oxidative stress and DNA degradation may be the main mechanism of PCOS-related subfertility.

Genetically modified mouse models have shaped our understanding of biological systems in both physiological and pathological conditions. For decades, mouse genome engineering has relied on transgenesis and spontaneous gene replacement in embryonic stem (ES) cells. While these technologies provided a wealth of knowledge, they remain imprecise and expensive to use. Recent advances in genome editing technologies such as the development of targetable nucleases, the improvement of delivery systems, and the simplification of targeting strategies now allow for the rapid, precise manipulation of the mouse genome. In this review article, we discuss novel methods and targeting strategies for the generation of mouse models for the study of bone and skeletal muscle biology., (Copyright © 2022 Elsevier Inc. All rights reserved.)