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Biology subjects

Kaya, M.

Publications and source records attributed to Kaya, M..

7 recordsLinked to original sources

Transcriptomic FOLFIRINOX sensitivity signatures stratify overall survival and reveal directional reclassification after neoadjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer

Background: Transcriptomic FOLFIRINOX-component sensitivity signatures have been clinically evaluated in resected and advanced PDAC, but their relevance and longitudinal stability in the neoadjuvant BR/LA setting are unknown. Patients and methods: We retrospectively studied 77 patients with borderline resectable or locally advanced PDAC treated with neoadjuvant FOLFIRINOX followed by resection. Pretreatment sensitivity to 5-fluorouracil, oxaliplatin and irinotecan was determined using previously developed locked transcriptomic classifiers and integrated into a regimen-level FOLFIRINOX classification. The primary molecular cohort comprised 53 patients whose pretreatment biopsies had [≥]10% tumour cellularity. Cox models assessed associations with survival. Longitudinal changes were assessed in 35 paired tumours. Results: Thirty-one pretreatment tumours were classified as FOLFIRINOX-sensitive (FFX-Sens), and 22 were not classified as FOLFIRINOX-sensitive (FFX-Res). FFX-Sens status was associated with longer overall survival (OS; hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25-0.93; p=0.029). In the complete-case model adjusted for baseline carbohydrate antigen 19-9 (CA19-9) and tumour size (n=50), the association with OS persisted (adjusted HR 0.47, 95% CI 0.23-0.96; p=0.037), whereas the adjusted association with disease-free survival was not statistically significant (adjusted HR 0.55, 95% CI 0.28-1.10; p=0.090). Among paired tumours, 15 changed from FFX-Sens to FFX-Res and four in the opposite direction (exact McNemar p=0.019). The OS association also persisted after adjustment for postoperative pathological factors (adjusted HR 0.40; p=0.015). Conclusions: Pretreatment FOLFIRINOX sensitivity was associated with OS under neoadjuvant FOLFIRINOX, while matched pretreatment and residual-tumour analyses revealed significant directional reclassification after treatment. These findings extend the clinical evaluation of validated drug-specific FOLFIRINOX sensitivity classifiers to the neoadjuvant setting and provide a longitudinal assessment of their stability during treatment. They support prospective evaluation of both pretreatment stratification and molecular reassessment of residual disease.

cancer biology↗

Current Situation of Breeding Bird Species in the Gediz Delta, Turkey

Gediz Delta, one of the most important wetland ecosystems in the Mediterranean Basin, also is one of the most important areas for birds in Turkey. Breeding bird atlas studies were carried out in 2002, and 2006 and extensive breeding species were revealed. In 2021, we conducted an atlas of breeding birds using the same method as previous studies and observed the change over the last 15 years. Bird species seen and heard between May 3 and June 15 in 294 1x1 square kilometres were recorded and classified with internationally accepted breeding codes. Breeding codes were given to 113 species belonging to 48 families throughout the study. Of these, 32 species are classified as possible breeding, 34 species as probable breeding and 47 species as confirmed breeding. Threat factors of species and habitats are grouped under five main topics. According to previous studies, we observed that the number of breeding bird species increased. It is thought that the number of breeding bird species will increase with the elimination of threats and carrying out the necessary restoration works.

zoology↗

Bioinformatics Analysis of the Potentially Functional circRNA-miRNA-mRNA Network in Breast Cancer

ObjectiveBreast cancer (BC) is a heterogeneous type of cancer that occurs as a result of distinct molecular alterations in breast tissue. Although there are many new developments in treatment and targeted therapy for BC in recent years, this cancer type is still the most common one among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection. MethodsGSE101124 and GSE182471 datasets were obtained from Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray (PAM50) classification. The circRNA-miRNA-gene relationship was investigated using the Cancer Specific CircRNA (v2.0) (CSCD), miRDB, miRWalk and miRTarBase databases. The circRNA-miRNA-mRNA regulatory network was constructed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation. The protein-protein interaction network was constructed by the STRING 2021 database and visualized by the Cytoscape tool (v3.9.0). Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The overall survival (OS) and disease-free survival (DFS) analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study. ResultsWe identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype. ConclusionsWe conclude that hsa_circ_0000515/ miR-486-5p/ SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC group, especially according to the PAM50 classification of BC.

bioinformatics↗

Protein scaffold-based multimerization of soluble ACE2 efficiently blocks SARS-CoV-2 infection in vitro

Soluble ACE2 (sACE2) decoy receptors are promising agents to inhibit SARS-CoV-2, as their efficiency is less likely to be affected by common escape mutations in viral proteins. However, their success may be limited by their relatively poor potency. To address this challenge, we developed a large decoy library of sACE2 fusion proteins, generated with several protease inhibitors or multimerization tags. Among these decoys, multimeric sACE2 consisting of SunTag or MoonTag systems, which were originally utilized for signal amplification or gene activation systems, were extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates. These novel sACE2 fusion proteins exhibited greater than 100-fold SARS-CoV-2 neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag in combination with a more potent version of sACE2, which has multiple point mutations for greater binding (v1), achieved near complete neutralization at a sub-nanomolar range, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutant versions of Spike, alpha, beta, gamma or delta variants, were also neutralized efficiently with SunTag or MoonTag fused sACE2(v1). Finally, therapeutic treatment of sACE2(v1)-MoonTag provided protection against SARS-CoV-2 infection in an in vivo mouse model. Overall, we suggest that the superior activity of the sACE2-SunTag or sACE2-MoonTag fusions is due to the greater occupancy of the multimeric sACE2 receptors on Spike protein as compared to monomeric sACE2. Therefore, these highly potent multimeric sACE2 decoy receptors may offer a promising treatment approach against SARS-CoV-2 infections. One Sentence SummaryMultimerization of sACE2 markedly enhanced the neutralization of SARS-CoV-2 by blocking multiple viral spike proteins simultaneously.

molecular biology↗

Newly isolated sporopollenin microcages from Cedrus libani and Pinus nigra for controlled delivery of Oxaliplatin

Sporopollenin-mediated controlled drug delivery has been studied extensively owing to its physicochemical and biological charachteristics. In the present study, sporopollenin was successfully extracted from pollen grains of C. libani and P. nigra followed by the loading of a commonly known anticancer drug Oxaliplatin. Both the drug loading and physicochemical features were confirmed by using light microscopy, FT-IR, SEM and TGA. For the first time, real-time cell analyzer system, xCELLigence, was employed to record the Oxaliplatin-loaded and sporopollenin-mediated cell death (CaCo-2 and Vero cells) in real time. Both the assays confirmed the slow release of Oxaliplatin from sporopollenin for around 40-45 h. The expression of MYC and FOXO-3 genes significantly increased in CaCo2 cell and decreased non-cancerous Vero cell confirming that sporopollenin-mediated controlled release of Oxaliplatin was promoting apoptosis cell death preventing the spread of its negative effects to nearby healthy cells. All the results suggested that C. libani and P. nigra could be suitable candidates for slow delivery of drugs.

pharmacology and toxicology↗

Chitin is present within the Ampullae of Lorenzini of chondrichthyan fishes

ABSTRACTChitin is synthesized by a variety of organisms using enzymes called chitin synthases and was recently discovered in a number of aquatic vertebrates. In our ongoing investigations into the presence of vertebrate chitin, we unexpectedly found evidence of the polysaccharide within the electrosensory organs, known as Ampullae of Lorenzini, of diverse chondrichthyan fishes. Experiments with histochemical reagents, chemical analyses, and enzymatic digestions suggested that chitin is a component of the hydrogel filling the structures. Further, in situ hybridization with a sequence from the little skate (Leucoraja erinacea) revealed that chitin synthase expression is localized to cells inside the organs. Collectively, these findings suggest that chondrichthyan fishes endogenously synthesize chitin and beg further investigation into the function of chitin in the electrosensory system.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

Developing a 3- to 6-state EEG-based brain-computer interface for a robotic manipulator control

Recent developments in BCI techniques have demonstrated high-performance control of robotic prosthetic systems primarily via invasive methods. In this work we develop an electroencephalography (EEG) based noninvasive BCI system that can be used for a similar, albeit lower-speed robotic control, and a signal processing system for detecting users mental intent from EEG data based on up to 6-state motor-imagery BCI communication paradigm. We examine the performance of that system on experimental data collected from 12 healthy participants and analyzed offline. We show that our EEG BCI system can correctly identify different motor imageries in EEG data with high accuracy: 3 out of 12 participants achieved accuracy of 6-state communication in 80-90% range, while 2 participants could not achieve a satisfactory accuracy. We further implement an online BCI system for control of a virtual 3 degree-of-freedom prosthetic manipulator and test it with our 3 best participants. The participants ability to control the BCI is quantified by using the percentage of successfully completed BCI tasks, the time required to complete a task, and the error rate. 2 participants were able to successfully complete 100% of the test tasks, demonstrating on average the error rate of 80% and requiring 5-10 seconds to execute a manipulator move. 1 participant failed to demonstrate a satisfactory performance in online trials. Our results lay a foundation for further development of EEG BCI-based robotic assistive systems and demonstrate that EEG-based BCI may be feasible for robotic control by paralyzed and immobilized individuals.

bioinformatics↗