Turkish journal of biology = Turk biyoloji dergisi最新文献

{"title":"Combinatorial effect of epirubicin and 5-fluorouracil in the treatment of temozolomide-resistant glioblastoma cells.","authors":"Mehrsa Bayat, Muhlis Akman, Türker Kiliç, Timuçin Avşar","doi":"10.55730/1300-0152.2799","DOIUrl":"10.55730/1300-0152.2799","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a highly aggressive form of brain tumor characterized by rapid proliferation and invasiveness. It is associated with a poor prognosis due to acquired resistance to temozolomide (TMZ). In this study, we investigated whether a combination of epirubicin, 5-fluorouracil (5-FU), and TMZ could improve TMZ sensitivity in resistant GBM cells and help overcome resistance.</p><p><strong>Materials and methods: </strong>TMZ resistance was established in the U87MG cell line. The MTT assay was used to measure cell viability. Reactive oxygen species (ROS) and apoptosis were measured using flow cytometry. RNA-seq was used to evaluate genomic changes based on treatment with drugs alone or in combination.</p><p><strong>Results: </strong>We demonstrated that the triple-drug combination significantly reduced cell viability. The biochemical pathways involved revealed that this combination therapy significantly increased the generation of ROS. The RNA-seq analysis indicated that combination therapy effectively suppressed cell cycle regulatory pathways, enhancing cell cycle arrest and promoting apoptosis in TMZ-resistant cells.</p><p><strong>Conclusion: </strong>These findings underscore the potential viability of integrating epirubicin and 5-FU with TMZ to improve therapeutic outcomes in patients suffering from chemoresistant GBM. These combination therapies could represent an important advance in the treatment of this challenging malignancy.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"170-184"},"PeriodicalIF":0.9,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-assisted enzymatic extraction improves the antiinflammatory activity of red dragon fruit peel pectin.","authors":"Bao LE, Seung Hwan Yang, Hoang Dang Khoa Ta","doi":"10.55730/1300-0152.2797","DOIUrl":"10.55730/1300-0152.2797","url":null,"abstract":"<p><strong>Background/aim: </strong>Inflammatory bowel disease is a chronic inflammatory disorder characterized by excessive immune activation, primarily mediated by nitric oxide and proinflammatory cytokines. This condition encompasses ulcerative colitis and Crohn's disease, both of which significantly impair patients' quality of life and pose persistent challenges in clinical management. Pectin, a complex carbohydrate found in plant cell walls, has shown promise in reducing inflammation.</p><p><strong>Materials and methods: </strong>In this study, pectin was extracted from red dragon fruit peel using two methods: ultrasound-assisted extraction and ultrasound-assisted enzymatic extraction. The structural characteristics and antiinflammatory effects of the extracted pectin were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages.</p><p><strong>Results: </strong>Ultrasound-assisted enzymatic extraction produced pectin with a higher yield (19.38%), a lower degree of esterification (46.51%), a reduced molecular weight (94.67 kDa), and a greater galacturonic acid content (67.51%) compared with ultrasound extraction alone. Both pectin preparations were noncytotoxic to RAW 264.7 macrophages and significantly reduced nitric oxide production and the expression of key inflammatory mediators. Structural analysis confirmed the integrity of the pectin molecules.</p><p><strong>Conclusion: </strong>These findings suggest that ultrasound-assisted enzymatic extraction enhances the physicochemical properties and antiinflammatory activity of pectin, thereby supporting its potential application in future studies targeting inflammatory bowel disease.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"146-157"},"PeriodicalIF":0.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of pinocembrin on zearalenone-induced hepatotoxicity via PI3K/AKT and NRF2 signaling in albino mice.","authors":"Sujatha Tejavat","doi":"10.55730/1300-0152.2795","DOIUrl":"10.55730/1300-0152.2795","url":null,"abstract":"<p><strong>Background/aim: </strong>Zearalenone (ZEA) is a Fusarium-derived mycotoxin that frequently contaminates food and feed and induces hepatotoxicity in humans and animals through oxidative stress and inflammation. Pinocembrin (PCM), a naturally occurring flavonoid, has potent antioxidant and antiinflammatory properties. This study investigated the hepatoprotective effects of PCM against ZEA-induced liver injury in albino mice, with a focus on the nuclear factor erythroid 2-related factor 2 (NRF2) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathways.</p><p><strong>Materials and methods: </strong>Twenty-four albino male mice were allocated into four groups: (1) control (vehicle 0.05% dimethyl sulfoxide), (2) ZEA-treated (40 mg/kg body weight), (3) PCM-treated (50 mg/kg body weight), and (4) ZEA + PCM. After 42 days of oral treatment, serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were determined. Hepatic oxidative stress markers were assessed. Liver histopathology was evaluated using standard staining techniques. Western blot analysis was performed to determine the expression of several proinflammatory cytokines signaling proteins: interleukin-6, interleukin-1β, tumor necrosis factor-α, NRF2 pathway components, apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2], cleaved caspase-3), and PI3K/Akt.</p><p><strong>Results: </strong>ZEA administration caused significantly elevated serum liver enzyme and hepatic malondialdehyde levels while causing a reduction in other oxidative stress markers. Histopathological examination revealed marked hepatic architectural disruption and cellular degeneration in the ZEA-treated group. Additionally, ZEA caused downregulation of antiapoptotic signaling proteins (such as Bcl-2) and upregulation of proinflammatory cytokines and cleaved caspase-3 expression. The coadministration of PCM facilitated markedly attenuated ZEA-induced biochemical, oxidative, inflammatory, apoptotic, and histopathological alterations. PCM treatment restored antioxidant enzyme activities and produced significant enhancement of NRF2/HO-1/NQO1 and PI3K/Akt signaling.</p><p><strong>Conclusion: </strong>PCM effectively protects against ZEA-induced hepatotoxicity in albino mice by mitigating oxidative stress, inflammation, and apoptosis. These protective effects are partially mediated through activation of the NRF2 signaling pathway and modulation of the PI3K/Akt pathway.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"122-131"},"PeriodicalIF":0.9,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA sequencing identifies tsRNA-05020 as a potential regulator of cervical cancer progression.","authors":"Cheng Peng, Cong Liang, Jie Liu, Yunlu Liu, Ping Liu","doi":"10.55730/1300-0152.2802","DOIUrl":"10.55730/1300-0152.2802","url":null,"abstract":"<p><strong>Background/aim: </strong>Cervical cancer (CC) is a malignant gynecologic tumor. Small RNAs derived from tRNAs (tsRNAs) have been reported to play regulatory roles in tumor progression and suppression. However, the functional role of tsRNAs in CC remains largely unclear.</p><p><strong>Materials and methods: </strong>Small RNA sequencing was performed on normal, cervical intraepithelial neoplasia (CIN), and CC clinical samples to identify differentially expressed tsRNAs (DEtsRNAs). qRT-PCR was used to validate the selected DEtsRNAs. The effects of tsRNA-05020 on HeLa cell proliferation, apoptosis, and epithelial-to-mesenchymal transition were assessed.</p><p><strong>Results: </strong>Compared with the normal group, 215 tsRNAs were significantly differentially expressed in CIN tissues, of which 196 were upregulated and 19 were downregulated. A total of 184 DEtsRNAs were identified between CC and CIN tissues, including 81 upregulated and 103 downregulated in CC. In total, three candidate DEtsRNAs were validated, among which tsRNA-05020 exhibited the largest fold change and was significantly downregulated in CC compared with CIN. Target gene network analysis identified 278 putative target mRNAs of tsRNA-05020 in CC. Overexpression of tsRNA-05020 significantly inhibited HeLa cell proliferation and promoted apoptosis. Moreover, overexpression of tsRNA-05020 significantly reduced vimentin expression and increased ZO-1 expression.</p><p><strong>Conclusion: </strong>This study identifies a previously uncharacterized role of tsRNA-05020 in CC progression, expands the current understanding of tsRNA-associated regulatory networks, and suggests that tsRNA-05020 may serve as a potential molecular regulator in CC.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 3","pages":"197-208"},"PeriodicalIF":0.9,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual RNA polymerase II patterns in meiotic prophase I in <i>Nannospalax xanthodon</i>: insights into chromatin, telomeres, and sex chromosomes.","authors":"Sergey N Matveevsky, Ferhat Matur, Faruk Çolak, Andrei Kandaurov, Mustafa Sözen, Svetlana V Pavlova, Oxana Kolomiets","doi":"10.55730/1300-0152.2794","DOIUrl":"10.55730/1300-0152.2794","url":null,"abstract":"<p><strong>Background: </strong>Meiotic transcription is a highly regulated process involving stage-specific chromatin remodeling and dynamic RNA polymerase II (RNAPII) activity. Nevertheless, our current understanding is largely based on classical model organisms, while many nonmodel mammals remain unexplored. This study investigates the transcriptional dynamics and chromatin features during meiotic prophase I in <i>Nannospalax xanthodon</i>, a subterranean blind mole rat species with extensive intraspecific karyotype variation.</p><p><strong>Materials and methods: </strong>Using immunofluorescence, we analyzed synapsis and transcriptional activity in spermatocyte nuclei of two geographically distant <i>N. xanthodon</i> males, detecting SYCP3, CREST, γH2AFX, and phosphorylated RNAPII (Ser5, Ser2). Telomere-associated proteins RAP1 and TERT were also examined to assess transcriptional activity at chromosomal ends.</p><p><strong>Results: </strong>Transcriptional activity was detected at all substages of prophase I. Unlike classical models, <i>N. xanthodon</i> exhibited no sharp pachytene-specific transcriptional reactivation; instead, RNAPII-Ser2 and Ser5 signals increased gradually from leptotene to pachytene. Notably, RNAPII-Ser5, but not Ser2, was consistently localized at telomeric regions of autosomes and sex chromosomes. These RNAPII-Ser5 foci coincided with RAP1-positive telomeres, suggesting a poised but transcriptionally inactive polymerase state at chromosome ends. The variability of RNAPII signals around the XY bivalent may also suggest a dynamic regulation of sex chromosome silencing. This is the first analysis of meiotic transcription in mole rats. The gradual transcriptional enhancement in the chromatin of prophase I nuclei and the RNAPII-Ser5 enrichment at telomeres reflect species-specific regulatory features.</p><p><strong>Conclusions: </strong>These findings highlight the importance of investigating nonmodel organisms to uncover novel mechanisms of meiotic regulation and suggest that transcriptional control during meiosis may be more evolutionarily diverse than previously recognized.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"109-121"},"PeriodicalIF":0.9,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating microtubule stability via α-tubulin acetylation partially restores Golgi fragmentation in spinal muscular atrophy.","authors":"Pelin Zobaroğlu Özer, Memet Gözüböyük, Özge Çetin, Niko Hensel, Güzin Emecen, Adam Malik, Melissa Bowerman, Peter Claus, Hayat Erdem Yurter, Gamze Bora Akoğlu","doi":"10.55730/1300-0152.2798","DOIUrl":"10.55730/1300-0152.2798","url":null,"abstract":"<p><strong>Background/aim: </strong>Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of survival of motor neuron (SMN) protein. SMN deficiency leads to perturbations of the cytoskeleton, including microtubules, which are mainly involved in motility-related cellular processes. However, the molecular mechanisms of microtubule dysregulation in SMA remain elusive. Alpha (α)-tubulin is a structural component of microtubules, and its posttranslational modifications affect microtubule dynamics. Here, we aimed to investigate α-tubulin acetylation and related molecular mechanisms in SMA.</p><p><strong>Materials and methods: </strong>Two different SMA mouse models, the <i>Drosophila melanogaster</i> model and patient-derived fibroblasts, were used in the study. Western blot and quantitative microscopic analysis were performed to analyze α-tubulin acetylation and related mechanisms.</p><p><strong>Results: </strong>The acetylation level of α-tubulin was decreased in the <i>Drosophila</i> model and in SMA patient fibroblast cells but not in mouse models. This decrease in acetylation is associated with upregulation of the major tubulin deacetylase, HDAC6, in patient cells compared with healthy controls. Microtubules play a role in the organization of the Golgi apparatus, and we demonstrated that increasing α-tubulin acetylation by pharmacological inhibition of HDAC6 partially restored the fragmented morphology of the Golgi apparatus in SMA.</p><p><strong>Conclusion: </strong>Our findings provide new insight into the molecular basis of SMA, indicating that cellular pathologies, including abnormal Golgi morphology, are associated with microtubule dysregulations caused by altered α-tubulin posttranslational modifications and regulatory proteins. Our findings support that microtubule perturbations are part of SMA pathology.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"158-169"},"PeriodicalIF":0.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-walled carbon nanotube-mediated plasmid DNA delivery in the model monocot <i>Brachypodium distachyon</i>.","authors":"Kaya Işleyen Bilge, Bahar Soğutmaz Özdemir","doi":"10.55730/1300-0152.2796","DOIUrl":"10.55730/1300-0152.2796","url":null,"abstract":"<p><strong>Background/aim: </strong>Plant genetic engineering is a valuable approach for improving stress tolerance, crop productivity, and quality traits. However, its progress is limited by the drawbacks of traditional transformation methods. Commonly used techniques, such as <i>Agrobacterium</i>-mediated transformation and biolistics, are restricted by genotype dependency, lengthy tissue culture steps, and low efficiency, particularly in monocot species. Therefore, the development of alternative gene delivery strategies remains an ongoing research focus in plant biotechnology. Nanoparticle-based delivery systems have recently gained attention due to their physiochemical properties, biocompatibility, and potential for alternative gene delivery approaches in plant systems.</p><p><strong>Materials and methods: </strong>We investigated the use of single-walled carbon nanotubes (SWCNTs) as nanocarriers for plasmid DNA delivery in the model monocot plant <i>Brachypodium distachyon</i>. SWCNTs were functionalized with polyethyleneimine (PEI) and plasmid DNA (pCAMBIA1301) was loaded via electrografting. Successful complex formation was confirmed with transmission electron microscopy (TEM), atomic force microscopy (AFM), and zeta potential measurements.</p><p><strong>Results: </strong>The TEM and AFM analyses revealed that the SWCNTs retained a thin, elongated needle-like structure, consistent with their ability to pass through the plant cell wall. Zeta potential measurements showed a negative surface charge of -43 mV for COOH-SWCNTs that shifted to +56 mV after PEI functionalization, enabling electrostatic binding of plasmid DNA. pDNA-SWCNT complexes at different mass ratios were applied to both callus and seed explants to evaluate their delivery potential. Successful delivery was confirmed by <i>b-glucuronidase</i> (GUS) reporter gene expression in both callus tissues and seeds, with ImageJ-based quantification showing that the 3:1 SWCNT:pDNA ratio yielded the highest mean signal intensity.</p><p><strong>Conclusion: </strong>Our findings show that the SWCNT-based system enabled the delivery of a large plasmid (~12 kb), supporting transient reporter gene expression in monocot tissues. Overall, the data suggest that SWCNT-mediated delivery represents a promising technique for DNA delivery in monocots, and further optimization is expected to improve its efficiency.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"132-145"},"PeriodicalIF":0.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ankrd2 may alleviate denervation-induced skeletal muscle atrophy by inhibiting inflammation.","authors":"Yalin Zhang, Lin Zhang, Li Li, Liqin Zhang, Li Zeng, Jiaying Qiu, Zhengrong Xi, Wenwen Wang","doi":"10.55730/1300-0152.2793","DOIUrl":"10.55730/1300-0152.2793","url":null,"abstract":"<p><strong>Background/aim: </strong>Sciatic nerve injury causes a loss of skeletal muscle innervation, reduced motor function, and eventual muscle atrophy. Inflammation and increased protein degradation are key factors contributing to muscle atrophy. Inflammation is activated early during muscle atrophy and can be modulated by various factors. However, the precise role of inflammation in denervation-induced muscle atrophy remains unclear.</p><p><strong>Materials and methods: </strong>Transcriptome sequencing was used to determine that the inflammatory response occurs early during denervation-induced muscle atrophy. RT-qPCR validation of several inflammatory factors showed rapid upregulation at early stages, followed by gradual downregulation. Weighted gene coexpression network analysis of differentially expressed genes identified gene modules whose expression patterns were correlated with or inversely correlated to the inflammatory phenotype, thereby identifying key regulatory factors. A total of 14 coexpression modules were identified, and expression patterns opposite to those of inflammatory factors were examined to investigate potential regulatory molecules that could inhibit inflammation and protect skeletal muscle.</p><p><strong>Results: </strong>Ankrd2 was identified in the darkorange module, showing no significant change at 36 h postdenervation, followed by gradual upregulation, which was opposite to the expression of inflammatory factors. An Ankrd2-overexpressing lentivirus was injected into the tibialis anterior muscle, and Ankrd2 overexpression was found to significantly alleviate muscle atrophy. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that Ankrd2 overexpression was associated with downregulation of inflammation-related pathways, particularly the NF-κB signaling pathway. Proatrophy genes in both the ubiquitin-proteasome and autophagic-lysosomal systems were also suppressed.</p><p><strong>Conclusion: </strong>The present study suggests that denervation-induced muscle atrophy is alleviated by Ankrd2, potentially through inhibition of inflammation, highlighting its potential as a therapeutic target.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 2","pages":"94-108"},"PeriodicalIF":0.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic identification and developmental mapping of <i>nrg3b</i> expression in zebrafish.","authors":"Elham Tarahomi, Nuray Söğünmez Erdoğan","doi":"10.55730/1300-0152.2791","DOIUrl":"10.55730/1300-0152.2791","url":null,"abstract":"<p><strong>Background/aim: </strong>Neuregulin 3 (NRG3) is an epidermal growth factor-like ligand that is involved in neuronal circuit formation in mammals. However, the expression profile of its zebrafish ortholog, <i>nrg3b</i>, remains poorly defined. The transcriptomic analyses of zebrafish <i>sco-spondin</i> mutants, which display alterations in their neurodevelopmental pathways, have indicated potential dysregulation of Nrg3b. Guided by these insights, this study aimed to characterize the temporal and spatial expression patterns of <i>nrg3b</i> in vivo in embryonic and adult zebrafish.</p><p><strong>Materials and methods: </strong>Publicly available RNA-seq data from heterozygous and maternal-zygotic zebrafish <i>sco-spondin</i> mutants at 5, 15, and 30 days postfertilization (dpf) were analyzed to evaluate differential expression, coexpression network positioning, and functional enrichment. Temporal expression of <i>nrg3b</i> was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in embryos at 1, 3, and 5 dpf. Spatial <i>nrg3b</i> localization at 5 dpf was validated by whole-mount in situ hybridization (WISH), alongside neuronal subtype specificity using GABAergic and glutamatergic markers. Adult brain expression was further evaluated via ISH on telencephalon sections.</p><p><strong>Results: </strong>Developmental stage was the main driver of early transcriptomic variation, with minor genotype-specific differences detected at 5 dpf. Network analysis positioned <i>nrg3b</i> as a hub gene within a neuronal function associated module. RT-qPCR showed a significant increase in <i>nrg3b</i> expression on days 3 and 5 compared to day 1. WISH revealed strong <i>nrg3b</i> expression in anterior brain regions and the spinal cord at 5 dpf, with greater overlap observed with the glutamatergic marker compared to the GABAergic one. In adults, ISH suggested the expression of <i>nrg3b</i> in telencephalic nuclei, particularly in dorsomedial and ventral regions.</p><p><strong>Conclusion: </strong><i>nrg3b</i> exhibits stage-dependent upregulation and preferential enrichment in excitatory neuronal regions during development, with sustained expression in adult telencephalon. These findings suggest a potential role for Nrg3b in synaptic organization and provide a foundation for future studies on the Nrg3b-ErbB4 signaling axis in zebrafish neurodevelopment.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 1","pages":"81-93"},"PeriodicalIF":0.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity modeling and hybrid machine learning-based prediction of bioactivity in pyrazole derivatives for drug discovery applications.","authors":"Kader Şahin, Serhat Kiliçarslan, Serdar Durdaği, Emin Saripinar","doi":"10.55730/1300-0152.2789","DOIUrl":"10.55730/1300-0152.2789","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background/aim: &lt;/strong&gt;Pyrazole derivatives are of growing interest due to their diverse pharmacological activities. However, their biological activity is often highly sensitive to subtle structural modifications. Existing quantitative structure-activity relationships (QSAR) approaches frequently fail to capture the conformational flexibility and nonlinear structure-activity relationships (SAR) of such heterocyclic scaffolds, creating a gap in the accurate prediction of their biological profiles. Therefore, there is a strong need for more robust and predictive computational frameworks. This study addresses this gap by integrating four-dimensional (4D)-QSAR descriptors with hybrid machine learning (ML) techniques to improve predictive accuracy and provide a more reliable tool for structure-based drug design. In this work, it was aimed to investigate the SAR of a series of pyrazole-based compounds using this advanced integrative computational strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The dataset consisted of 54 pyrazole derivatives, of which 50 compounds were used for model construction and 4 compounds were reserved as a test set for validation. Although the test set was limited in size, the selected compounds were structurally representative of the training set, sharing the same core scaffold while covering different substitution patterns and biological activity values. The 4D-QSAR approach included multiple conformations of each compound and utilized matrix-based representations of geometric and electronic properties to capture dynamic molecular behavior. A pharmacophore model was generated using EMRE software based on the spatial and electronic features of used compounds. EMRE is an in-house software developed by our research group. It has been employed in several previously published 4D-QSAR studies for electron-conformational matrix of contiguity construction, pharmacophore modeling, descriptor matrix generation, and activity prediction. EMRE operates on standard geometric and electronic descriptors derived from quantum-chemical calculations, ensuring methodological transparency and reproducibility despite its proprietary implementation. Comparable performance trends obtained with EMRE-based 4D-QSAR models have been reported in previous studies, supporting the validity of the software for pharmacophore-driven QSAR analysis (Şahin et al., 2011; Sahin and Saripinar, 2020; Sahin et al., 2021).Using this framework, a total of 204 molecular descriptors were computed using Spartan 07. To reduce redundancy and prevent overfitting, descriptor selection was optimized through a genetic algorithm (GA)-based procedure (Fernandez et al., 2011), and only statistically significant descriptors with low intercorrelation were retained for model construction. Subsequently, multiple ML algorithms, including artificial neural network, decision tree, and hybrid models, were evaluated to enhance prediction accuracy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: ","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"50 1","pages":"37-61"},"PeriodicalIF":0.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}