Turkish Journal of Medical Sciences最新文献

Background/aim: Circadian rhythm proteins (CRPs) play critical roles in both physiological and pathophysiological conditions, including neurodegenerative disorders. As members of CRPs, the nuclear receptors Rev-Erbα/β regulate circadian rhythm particularly by inhibiting Bmal1 protein and are involved in the neuroinflammation and cell death processes. However, their roles in the development of neuronal injury after traumatic brain injury (TBI) were largely unexplored, and so were investigated in the present study.

Materials and methods: For the induction of TBI, animals were subjected to the cryogenic model of TBI, which is a commonly used animal model and shares essential similarities with cerebral ischemia in terms of pathophysiological cascades. To assess the impact of Rev-Erb proteins on TBI, both Rev-Erbα and Rev-Erbβ proteins were activated or deactivated, and their expression profiles were determined by western blot analyses. Infarct volume and brain swelling were analyzed by cresyl violet staining. Blood-brain barrier (BBB) permeability was analyzed by immunoglobulin G extravasation. Neuronal survival was analyzed by NeuN immunohistochemistry.

Results: Our observations indicate that Rev-Erbβ significantly reduced brain injury after TBI, which was reversed by inhibiting this protein. Not activation but the inhibition of both Rev-Erb proteins increased brain swelling significantly. In addition, both Rev-Erbα and Rev-Erbβ improved BBB permeability and neuronal survival significantly, which were reversed by their inhibitions.

Conclusion: Our results show that Rev-Erbα and particularly Rev-Erbβ play significant roles in the development of neuronal injury after TBI. Our findings suggest that Rev-Erb proteins would be a potential therapeutic target for the treatment of neurodegenerative diseases.

Background/aim: Doxorubicin (Dox) is a potent anticancer medication. However, due to nephrotoxicity, its clinical application is restricted. Achillea millefolium (AM) is a plant used in traditional medicine to treat several conditions, including kidney disorders. The aim of this work was to investigate the preventative properties of AM extract (AME) and their mechanisms against nephrotoxicity caused by Dox in rats.

Materials and methods: The rats were assigned randomly to six groups, including a control group, Dox group (5 mg/kg/week via i.p. for 4 weeks), two groups receiving AME (100 or 200 mg/kg, orally for 28 days), and the last two groups receiving Dox + AME (100 or 200 mg/kg, orally for 4 weeks). After the treatment period concluded, samples of blood and renal tissue were collected for analysis. Serum creatinine, urea, and uric acid levels were used to determine nephrotoxicity biochemically. In renal tissue samples, superoxide dismutase (SOD), catalase, glutathione (GSH), glutathione peroxidase (GPx), total antioxidant capacity (TAC), nitric oxide (NOx), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor kappa B (NF-κB) were measured. Histopathological analysis of the kidneys was also performed.

Results: Dox caused a considerable increase in kidney function parameters and the occurrence of histological changes, which were significantly reversed by AME treatment. Mechanistically, Dox caused renal oxidative stress by raising malondialdehyde and NOx levels while lowering SOD, GSH, GPx, and TAC. It also caused inflammation via the stimulation of proinflammatory cytokines in renal tissues. Conversely, the treatment of AME mitigated Dox-evoked abnormalities in the above-mentioned tests.

Conclusion: AME could protect against nephrotoxicity caused by Dox by reducing oxidative stress, stimulating antioxidant mechanisms, and suppressing proinflammatory cytokines, suggesting that AME may be useful as an adjuvant therapy for Dox-induced nephrotoxicity.

Background/aim: Breast cancers are one of the most common cancers in women and are responsible for many deaths worldwide. Mast cells are inflammatory cells. Their role in cancers is controversial, and there is limited data on systemic mast cell activation in cancer cases. This study aimed to evaluate systemic mast cell activation in an experimentally induced rat model of breast cancer.

Materials and methods: Sprague Dawley female rats were divided into control (n = 6) and mammary tumor (n = 12) groups. In the tumor group, 20 mg 7,12-dimethylbenz[a]anthracene (DMBA) dissolved in 1 mL cottonseed oil was administered intragastrically by gavage, and the rats were followed daily until their mammary tumors reached 3 cm in diameter. The control group received only cottonseed oil. Paraffin sections obtained from the mammary tumor tissue were subjected to hematoxylin-eosin, toluidine blue staining, and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Mesenteric tissues from each subject were also stained with toluidine blue. The number and activation status of mast cells in mammary tumors and mesenteric tissues were evaluated.

Results: Toluidine blue staining showed that activated mast cells were commonly found in tumor tissues. Based on the mesenteric tissue analysis, severe degranulation of the mesenteric mast cells was found in the tumor-induced groups compared to the control group.

Conclusion: This study demonstrated for the first time that systemic mast cell activation develops in both tumoral and mesenteric tissues in an experimental cancer model. However, it is not known at which stage of tumor development it occurs.

Background/aim: Y₂O₃-Al₂O₃-SiO₂ (YAS) glass microspheres are currently used in radioembolization treatment. However, abscess formation can occur following this treatment. This study aims to endow YAS glass microspheres with antibacterial properties to address the abscesses forming in patients after radioembolization treatment.

Materials and methods: In this study, undoped YAS glass microspheres and those doped with antibacterial agents zinc (Zn) and/or copper (Cu) were successfully fabricated using a sol-gel derived method.

Results: After heat treatment, the microspheres exhibited an amorphous structure. Additionally, the incorporation of Zn and/or Cu dopants did not alter the patterns observed in the X-ray diffraction analysis. Fourier transform infrared spectroscopy analysis detected Si-O-Si, Al-O-Al, and Y-O band vibrations within the structure. The presence of Zn and Cu dopants was confirmed through X-ray photoelectron spectroscopy analysis. Scanning electron microscopy revealed that all samples possessed a regular microsphere morphology, with average particle sizes ranging from 6 to 50 μm. These average particle sizes were further confirmed using a mastersizer.

Conclusion: The antibacterial agent-doped YAS glass microspheres show promise in combating infections that occur following radioembolization treatment.

Background/aim: This study aimed to scrutinize nationwide utilization trends of shoulder arthroplasty for proximal humerus fractures (PHFs) using a comprehensive national surgical database.

Materials and methods: A retrospective study was conducted with 4181 patients who underwent shoulder arthroplasty due to PHF between 2016 and 2022 using national health records. They are grouped as hemiarthroplasty (HA), anatomical total shoulder arthroplasty (TSA), and reverse shoulder arthroplasty (RSA). The patients' demographic data, length of hospital stay, revision histories, transfusion rates, mortality data, trends in arthroplasty methods over the years, the distribution of cases by hospital characteristics and geographical regions were analyzed.

Results: Treatment with HA was administered to 22.1% of patients, TSA to 30.2%, and RSA to 47.7%. The lowest revision rate was observed after HA (4.3%), while higher rates were recorded after TSA (7.9%) and RSA (7.4%) (p = 0.019). It was observed that there was a significant increasing trend in RSA rates and a decreasing trend in HA and TSA rates over time (p < 0.001).

Conclusion: From 2016 to 2022, there appears to have been a significant increase in the utilization of RSA for the arthroplasty treatment of proximal humeral fractures in Türkiye, and it is used more frequently than HA. However, revision rates after RSA are still higher than those after HA.

Level of evidence: Level III, retrospective cohort study.

Background/aim: This study aims to compare the success rates of rigid registration (RR) and elastic registration (ER) systems in diagnosing all cancers and clinically significant prostate cancer (csPC) in software-based targeted prostate biopsies (TPBs) by performing matching analysis.

Materials and methods: The data of 2061 patients from six centers where software-based TPB is performed were used. All cancer and csPC detection rates of the RR and ER systems were compared following Mahalanobis distance matching with the propensity score caliper method. Logistic regression analysis was applied to identify factors predicting clinically insignificant prostate cancer (ciPC) and csPC diagnoses. Additionally, the International Society of Urological Pathology Grade Group (ISUP GG) upgrade rates of RR and ER systems were compared between biopsy and radical prostatectomy pathologies.

Results: The matched sample included 157 RR and 157 ER patients. No statistically significant difference was found between ER and RR in terms of csPC detection rate (28.0% vs. 22.3% respectively, p = 0.242). The detection rate of all cancers by ER compared to RR was found to be significantly higher (54.8% vs. 35.7% respectively p < 0.001,). No statistically significant difference was found between the ER and RR groups regarding pathological upgrade (39.7% vs. 24.2% respectively, p = 0.130). In the logistic regression analysis performed to determine the factors predicting ciPC, decreased prostate volume and ER system use were found to be independent predictive factors.

Conclusion: While the detection rate of csPC was similar for the RR and ER systems, the detection rate of all cancers and ciPC was significantly higher with the ER systems.

Background/aim: Lung cancer, a predominant contributor to cancer mortality, is characterized by diverse etiological factors, including tobacco smoking and genetic susceptibilities. Despite advancements, particularly in nonsmall-cell lung cancer (NSCLC), therapeutic options for lung squamous cell carcinoma (LUSC) are limited. Transposable elements (TEs) and their regulatory proteins, such as tigger transposable element derived (TIGD) family proteins, have been implicated in cancer development. TIGD1, upregulated in various cancers, including LUSC, lacks a defined function. The aim of our study was to elucidate the biological functions, associated pathways, and interacting proteins of TIGD1.

Materials and methods: The GSE229260 microarray dataset was investigated using the GEO2R tool to identify the differentially expressed genes (DEGs) in TIGD1 silenced in A549 lung cancer cells in contrast to controls. Enrichment analyses and protein-protein interaction (PPI) network construction were performed to uncover key pathways using KEGG and STRING analyses. Hub genes were determined through the intersection of DEGs with lung cancer-related genes via Cytoscape software and the cytoHubba plug-in, and their functions were analyzed. Immune and stromal scores of hub genes were also evaluated using the ESTIMATE algorithm.

Results: Analyzing microarray data from TIGD1-silenced A549 NSCLC cells, a total of 13 upregulated DEGs and 1 downregulated DEGs were identified. The TIGD1-associated DEGs revealed significant involvement in crucial molecular pathways, including the PI3K/AKT, FOXO, and p53 signaling pathways. The hub genes AKT1, BRAF, SRC, GAPDH, CCND1, CDKN2A, CTNNB1, KRAS, MYC, and TP53 emerged as central regulators of cell proliferation, apoptosis, and protein metabolism. The hub genes exhibited negative correlations with immune and stromal components in the tumor microenvironment, suggesting their potential as biomarkers for lung cancer therapy.

Conclusion: This study elucidates the potential functions of TIGD1 in lung cancer and identifies promising biomarker candidates associated with TIGD1 gene expression, presenting potential therapeutic targets for lung cancer therapies.

Background/aim: There is currently no data from Türkiye on whether, following a diagnosis of asthma, patients are given an asthma action plan to implement. There is also no data on whether patients can manage their treatment based on the provided asthma action plans. The present study aimed to determine the use of asthma action plans in Türkiye and the awareness levels of patients about these plans.

Materials and methods: A multicenter, cross-sectional descriptive study was conducted in the outpatient immunology, allergy, and pulmonology clinics of secondary and tertiary healthcare centers. Adult asthmatics filled out a case registration form regarding age, sex, educational status, duration of asthma, and smoking history. Subjects answered the Global Initiative for Asthma (GINA) assessment of control questions, indicated whether they had previously been offered an asthma action plan, and if they had received one, whether they benefited from it.

Results: Data from 265 asthmatic adults (mean age: 48.4 years, standard deviation: 13.4 years), including 194 (73.2%) females were analyzed. The asthma of 212 (80.0%) patients was controlled, and was uncontrolled in 53 (20.0%) patients. An asthma action plan had been mentioned to 91 (34.3%) of the 265 patients. Among these 91 patients, 85 (93.4%) had been given a written asthma action plan, and 85 (93.4%) stated that they had benefited from the plan. The rate of being given an asthma action plan was significantly lower for illiterate patients than for patients with any education (p < 0.001).

Conclusion: The rate of mentioning an asthma action plan to asthmatic patients is low. However, almost all patients who received an asthma action plan benefitted significantly from the plan. Thus, it is important to give asthmatic patients an action plan, ideally in written form.

Background/aim: Melanoma is one of the most aggressive cancers and treatment methods commonly used for patients with skin cancer include checkpoint and BRAF/MEK inhibitors, traditional chemotherapy drugs, radiation, and adjuvant treatment methods. Due to the resistance and toxic effects that patients develop against the drugs, an effective treatment method has not been developed for melanoma yet. In this study we evaluated the anticancer effect of usnic acid (UA) on A-375 melanoma cells and human epidermal melanocytes using the xCELLigence real-time cell analysis system.

Materials and methods: To determine the cell death pathway through which UA exerts its antiproliferative effect, its potential for apoptotic effects was investigated. Caspase-3 and caspase-9 enzyme assays and the expression analysis of 84 genes from the apoptosis pathway were carried out in UA-treated and nontreated A-375 cells.

Results: UA was found to have an antiproliferative effect on A-375 cells while it did not have a cytotoxic effect on human epidermal melanocytes. UA treatment led to statistically significant increases in both caspase-3 and caspase-9 enzyme activities. Moreover, the expression levels of 61 genes (mainly proapoptotic genes) were increased and the expression levels of 23 genes (mainly antiapoptotic genes) were decreased in response to UA treatment. This effect might have developed through both the extrinsic and intrinsic apoptosis pathways; however, the extrinsic pathway was more pronounced.

Conclusion: As a result of the obtained findings, it could be concluded that UA might be a promising candidate drug molecule for melanoma treatment in the future through topical application or encapsulation with nanocarriers.

Background/aim: Microbiota awareness, nutritional literacy, and health literacy levels in adolescents have a significant impact on their health and well-being. This research was conducted to examine the relationship between microbiota awareness, nutrition literacy, and health literacy in adolescents.

Material and methods: This research was structured with a descriptive-correlational design. The study population comprised adolescents aged 10-19 years, living in Türkiye (n = 739), between June 2022 and February 2024. Data were analyzed using SPSS 22.0, G*Power 3.1, and R programming language 4.1.3.

Results: The total effect of the health literacy variable on nutritional literacy was 0.2311, and this was statistically significant at a 95% confidence interval (CI) (p < 0.05). In terms of the health literacy variable, the direct effect of the nutrition literacy variable on the microbiota awareness variable was 0.2888, and this was statistically significant at the 95% CI (p < 0.05). In terms of the nutritional literacy variable, the direct effect of the health literacy variable on the microbiota awareness variable was 0.1707, and this was statistically significant at the 95% CI (p < 0.05). Nutrition literacy had a partial mediating role in the effect of health literacy on microbiota awareness (lower limit CI: 0.045; upper limit CI: 0.0894). The most accurate prediction of machine learning approaches to predict microbiota awareness was made with random forest with shapley additive explanations values, and the most important variable that should be in the model to predict the microbiota awareness variable was the nutrition literacy variable.

Conclusion: Microbiota awareness increased as health literacy and nutrition literacy increased. In the machine learning approach prediction, the most important variables affecting microbiota awareness were health literacy and nutritional literacy. Longitudinal studies on microbiota awareness are recommended.