👤 Yoldas Yildiz

Studies have shown that essential oils not only increase cell viability but also affect lipid metabolism in mammals. However, the extent to which these effects are realized in goose liver has not yet been fully elucidated. The object of research is to investigate the effects of four essential oil mixtures (juniper oil, mint oil, thyme oil, rosemary oil) on lipid metabolic gene expressions in goose. We measured mRNA levels of metabolic genes (ACSBG2, ELOVL1, ELOVL2, CYP2Cl9, CYP2K1), antioxidative gene (SOD1) and very low-density lipoprotein triglyceride (VLDL) synthesis genes (APOB, FOXO1, MTTP), in goose (Anser anser) liver. Search groups were formed as C (control; no additives), EK1 (0.4 mL/L essential oil mixture supplemented) and EK2 (0.8 mL/L essential oil mixture supplemented). The relative expression levels of genes in the liver were measured using RT-qPCR. β-Actin was used as reference gene control for normalization of qPCR data. As a result, essential oil supplementation downregulated metabolic genes compared to the control group. APOB gene among VLDL genes was significantly downregulated. Antioxidative effect gene was downregulated in parallel with the others. This indicates that essential oil intake with drinking water downregulates the genes involved in lipid metabolism in goose liver. Our data show that essential oils have a significant effect on the regulation of genes and pathways involved in hepatic lipid metabolism. Show less

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer. Multiomics analysis of CTC-derived organoids along with preclinical modeling with xenografts identified neuregulin 1 (NRG1)-ERBB2 receptor tyrosine kinase 3 (ERBB3/HER3) signaling as a key pathway required for CTC survival, growth and dissemination. Genome-wide CRISPR activation screens revealed that fibroblast growth factor receptor 1 (FGFR1) signaling serves a compensatory function to the NRG1-HER3 axis and rescues NRG1 deficiency in CTCs. Conversely, NRG1-HER3 activation induced resistance to FGFR1 inhibition, whereas combinatorial blockade impaired CTC growth. The dynamic interplay between NRG1-HER3 and FGFR1 signaling reveals the molecular basis of cancer cell plasticity and clinically relevant strategies to target it. Our CTC organoid platform enables the identification and validation of patient-specific vulnerabilities and represents an innovative tool for precision medicine. Show less

This study was conducted to examine the effect of hope and psychological well-being on quality of life in elderly cancer patients using latent profile analysis (LPA). The study was conducted with 398 elderly cancer patients in Ataturk University Research in Turkey between September 2024 and January 2025. R programming language 4.1.3, G*Power 3.1 and SPSS-22 program were used in the analysis of the study. In our study, in the first stage of LPA analysis, BIC values were obtained by iterating each model and each class for 4 models and 9 classes. Since the lowest BIC value was found in the EEE model, the EEE model was considered as the appropriate model in the study and the class analysis was performed over this model. It is concluded that the best fitting class is the 2-class solution. As a result of LPA, class 1 has the lowest arithmetic mean in all indicators. According to the latent classes of the individuals in our study; it was found that the quality of life of individuals with Low Psychological Status was significantly lower than individuals with High Psychological Status (p < 0.05). In our study, two classes were found as a result of LPA. According to the classes, it was found that the quality of life of individuals with low psychological status was lower than individuals with high psychological status. Increased hope and psychological well-being were found to improve quality of life in elderly cancer patients. Longitudinal studies on quality of life in elderly cancer patients are recommended. Show less

SARS-CoV-2 infection is marked by an excessive inflammatory response, leading to elevated production of pro-inflammatory cytokines through activation of intracellular pathways like mitogen-activated protein kinase (MAPK). Viruses can use the MAPK signaling pathway to their advantage, but the relationship of this pathway to the severe SARS-CoV-2 period has not been fully elucidated. MAP2K4 is involved in the MAPK signaling pathway and affects cellular processes such as cell-cell junction, cell proliferation, differentiation and apoptosis. In this study, we sought to determine the associated biomarkers that are involved in the MAP2K4 pathway and elucidate its possible roles in terms of some clinical features associated with COVID-19. We evaluated the expressions of MAP2K4, SNAI1, SLUG, ZEB1 and E-Cadherin. For this purpose, we prospectively recruited 66 individuals, 39 of whom were women and had a mean age of 65 years. The results revealed that MAP2K4 upregulation increased SNAI1 gene expression level whereas E- Cadherin level was decreased in SARS-CoV-2 positive participants. In addition, negative correlations were determined with PLT, Lymphocyte and CKMB and E- Cadherin levels in positive participants. We also observed a negative correlation between the MAP2K4 and AST, and a positive correlation between SLUG and BUN, ZEB1 and CK. We conclude that SARS-CoV-2 infection triggers fibrosis by increasing MAP2K4 regulation. Additionally, this is the first study to demonstrate the possible contribution of MAP2K4 in influencing COVID-19 clinical features, which may be relevant for identifying COVID-19 positive participants with severe complications. Show less

Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated macrophages (TAMs). High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. However, there is a lack of understanding of whether IMP2 affects the cargo of cancer cell-derived EVs, thereby modulating macrophage polarization. EVs were isolated from IMP2-expressing HCT116 parental cells (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells. EVs were characterized according to MISEV guidelines, microRNA cargo was assessed by microRNA-Seq, and the protein cargo was analyzed by proteomics. Primary human monocyte-derived macrophages (HMDMs) were polarized by EVs, and the expression of genes and surface markers was assessed using qPCR and flow cytometry, respectively. Morphological changes of macrophages, as well as the migratory potential of cancer cells, were assessed by the Incucyte EVs from WT and KO cells had a similar size and concentration and were positive for 25 vesicle markers. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs than KO EVs, while the expression of TNF and IL6 was reduced. A similar pattern was observed in macrophages from zebrafish larvae treated in vivo. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. MicroRNA-Seq revealed a significant difference in the microRNA composition of WT and KO EVs, particularly a high abundance of miR-181a-5p in WT EVs, which was absent in KO EVs. Inhibitors of macropinocytosis and phagocytosis antagonized the delivery of miR-181a-5p into macrophages and the downregulation of the miR-181a-5p target DUSP6. Proteomics data showed differences in protein cargo in KO vs. WT EVs, with the differentially abundant proteins mainly involved in metabolic pathways. WT EV-treated macrophages exhibited a higher basal oxygen consumption rate and a lower extracellular acidification rate than KO EV-treated cells. Our results show that IMP2 determines the cargo of EVs released by cancer cells, thereby modulating the EVs' actions on macrophages. Expression of IMP2 is linked to the secretion of EVs that polarize macrophages towards a tumor-promoting phenotype. Show less

Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4. Show less

Hepatocellular carcinoma (HCC) represents a major form of primary liver cancer in adults. Chronic infections with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse are the major factors leading to HCC. This deadly cancer affects more than 500,000 people worldwide and it is quite resistant to conventional chemo- and radiotherapy. Genetic and epigenetic studies on HCC may help to understand better its mechanisms and provide new tools for early diagnosis and therapy. Recent literature on whole genome analysis of HCC indicated a high number of mutated genes in addition to well-known genes such as TP53, CTNNB1, AXIN1 and CDKN2A, but their frequencies are much lower. Apart from CTNNB1 mutations, most of the other mutations appear to result in loss-of-function. Thus, HCC-associated mutations cannot be easily targeted for therapy. Epigenetic aberrations that appear to occur quite frequently may serve as new targets. Global DNA hypomethylation, promoter methylation, aberrant expression of non-coding RNAs and dysregulated expression of other epigenetic regulatory genes such as EZH2 are the best-known epigenetic abnormalities. Future research in this direction may help to identify novel biomarkers and therapeutic targets for HCC. Show less

The purpose of this study was to compare the effects of the Traditional acupuncture point ST.36 and 'Omura's ST.36 Point' ("True ST.36") needling on the isokinetic knee extension & flexion strength of young soccer players. The Bi-Digital O-Ring Test (B.D.O.R.T.) of Yoshiaki Omura, M.D.,Sc.D. was used to determine the "True ST.36". Young soccer players (N = 24) between 16-18 years of age (Mean = 16.92 +/- 0.65) were involved in the study. The extension & flexion strengths of dominant legs were measured with Cybex 350 Extremity System isokinetically. The testing velocity was 60 degrees/sec. The peak torque value in Newton meters (Nm) was evaluated. Subjects were tested 3 times. Extension & Flexion 1 (EXT1, FLEX1) without acupuncture application, EXT2 & FLEX2 after application on the traditional acupuncture point, ST.36 and EXT3 & FLEX3 after application onto the 'Omura's New Foot-point' ("True ST.36"). Before each test, subjects warmed up for 10 minutes by cycling on an isokinetic ergometer at 50 RPM, 75 Watts load followed by stretching exercises of lower extremity. Mean EXT1, EXT2, EXT3 values were 196.92 +/- 28.70: 210.00 +/- 23.00; 224.42 +/- 21.70 respectively, where FLEX1, FLEX2, FLEX3 were 140.88 +/- 22.45; 151.13 +/- 21.27; 161.00 +/- 22.23. Comparisons of EXT1-EXT2, EXT1-EXT3, EXT2-EXT3, FLEX1-FLEX2, FLEX1-FLEX3, FLEX2-FLEX3 strength values showed all very high significance (P < 0.001) in favor of 1) Needling on relevant points and 2) Omura's ST.36 Point ("True ST.36"). We conclude that B.D.O.R.T. can help to determine new (True) Acupuncture points and, both points were effective for increasing the isokinetic knee extension & flexion strength of young soccer players very significantly where as Omura's ST.36 Point ("True ST.36") was more effective than Traditional Acupuncture point, ST.36. Show less