Biology-Basel最新文献

{"title":"Update in the Molecular Pathogenesis of Sebaceous Carcinoma.","authors":"Francisco Mano, João Teixeira, José Carlos Cardoso","doi":"10.3390/biology15191771","DOIUrl":"10.3390/biology15191771","url":null,"abstract":"<p><p>Sebaceous carcinoma is an uncommon but potentially aggressive adnexal malignancy whose molecular pathogenesis has been substantially clarified in recent years. Rather than representing a single molecular entity, sebaceous carcinoma is now understood as a biologically heterogeneous group of tumors arising through distinct yet sometimes overlapping oncogenic pathways. Recent genomic and multi-omics studies have identified several major molecular subsets, including mismatch repair-deficient (dMMR)/microsatellite instability (MSI)-associated tumors, ultraviolet (UV) radiation-driven tumors, and pauci-mutational tumors characterized predominantly by alterations in cell-cycle and epithelial differentiation regulators such as <i>TP53</i>, <i>RB1</i>, and <i>ZNF750</i>. These findings have also reinforced biologically relevant differences between ocular and extraocular sebaceous carcinoma, with periocular tumors more often enriched for <i>TP53</i>/<i>RB1</i>/<i>ZNF750</i>-driven mechanisms and extraocular tumors more frequently showing UV-related and dMMR signatures. In addition to these core pathways, recent evidence has highlighted the contribution of NOTCH signaling, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway alterations, copy-number changes including <i>MYC</i> amplification, rare human papillomavirus (HPV)-associated cases, and emerging transcriptomic abnormalities involving cholesterol metabolism and sebaceous differentiation programs. These advances not only deepen current understanding of sebaceous carcinoma biology but also have important diagnostic, prognostic, and therapeutic implications, particularly in relation to Lynch/Muir-Torre syndrome screening, molecular subclassification, and the potential use of immune checkpoint inhibitors and other targeted strategies in selected patients. This review provides an updated overview of the molecular pathogenesis of sebaceous carcinoma, focusing on the main genomic, transcriptomic, and biologically actionable alterations described to date, and discusses their implications for tumor classification, pathogenesis, and future translational research.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Influencing Cannibalistic Behavior of Tiger Puffer, <i>Takifugu rubripes</i>: Insights into Teeth and Stocking Density Aspects.","authors":"Haotian Ren, Zhijun Zhang, Yang Liu, Jiahao Liu, Chenchen Bian, Qiang Ma, Mengqing Liang, Houguo Xu, Yuliang Wei","doi":"10.3390/biology15191766","DOIUrl":"10.3390/biology15191766","url":null,"abstract":"<p><p>The current study explored the factors influencing the cannibalistic behavior of tiger puffer (<i>Takifugu rubripes</i>) based on different stocking densities and tooth clipping. Two separate experiments were carried out in this study. In the experiment testing different stocking densities, fish were reared in 300 L circular tanks with different initial stocking densities of 20, 40, and 80 fish per tank. In the experiment testing tooth clipping, some fish underwent tooth clipping treatment, while the other fish without tooth clipping served as the control. The growth results showed that high initial stocking density reduced growth, while tooth clipping numerically increased final body weight by 12.63% from 71.76 ± 2.54 g to 80.82 ± 3.33 g. The Kaplan-Meier survival curve showed that during the first 20 days of the feeding trial, the number of dead fish increased rapidly in both experiments. Cannibalism-related parameters (survival rate, caudal fin damage, and bite marks on the body surface) revealed that both intact teeth and high initial stocking density increased cannibalistic behavior. Fish with intact teeth or reared at high initial stocking density had increased serum glucose and/or lactate concentrations. Increased stocking density elevated the ratio of 5-HIAA/5-HT in the brain and altered the expression of <i>tph2</i> and <i>ddc</i> related to 5-HT metabolism. In addition, tooth clipping increased the level of brain dopamine. In conclusion, increasing the initial stocking density is a factor contributing to the increase in the cannibalism of tiger puffer. Tooth clipping alleviated cannibalism and tended to improve growth. Furthermore, tiger puffer may need about 20 days to re-establish their social hierarchy order when being relocated to a new rearing environment.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of <i>Rhinella marina</i> Extracts on the Effector Functions of Human Neutrophils.","authors":"Lucinéia Reuse Albiero, Valfran da Silva Lima, Cleni Mara Marzocchi-Machado, Luiz Fernando Fortunato Tucci, Antônio Carlos Alves De Sousa, Domingos de Jesus Rodrigues, Lucas Castro Fernandes Pimenta, Marcos Penhacek, Marcilei Juvenal da Conceição Horn, Jessyca Hathenher Gomes, Valéria Dornelles Gindri Sinhorin, Adilson Paulo Sinhorin","doi":"10.3390/biology15191770","DOIUrl":"10.3390/biology15191770","url":null,"abstract":"<p><p>Neutrophils play a central role in the innate immune response. However, in inflammatory and autoimmune diseases, the exacerbated activation of these cells can result in excessive release of reactive oxygen species (ROS), proteases, and inflammatory mediators, contributing to tissue damage. In this context, natural compounds derived from amphibian venoms have attracted interest due to their pharmacological and immunomodulatory potential. This study aimed to evaluate in vitro the effects of the crude methanolic extract (CME) of <i>Rhinella marina</i> on the effector functions of human neutrophils. For this purpose, peripheral blood neutrophils from healthy individuals were treated with CME (0.5, 5, and 50 µg/mL) or untreated controls. Cytotoxicity, total ROS production, superoxide anion production, myeloperoxidase (MPO) activity, elastase degranulation, NET (Neutrophil Extracellular Trap) formation, and parameters related to cellular redox status, including antioxidant enzymes and markers of oxidative damage, were evaluated. CME showed concentration-dependent cytotoxicity. There were no changes in ROS production by luminol-dependent chemiluminescence after stimulation with myristoylphorbol acetate (PMA). However, it reduced superoxide anion production in neutrophils in both stimuli in the NBT assay. CME did not significantly modulate MPO activity or NET formation, but it reduced elastase release, suggesting modulation of neutrophil degranulation. Additionally, it increased glutathione-S-transferase (GST) activity and reduced glutathione (GSH) levels. It can be concluded that CME partially modulated neutrophil effector functions, such as superoxide anion production and degranulation, in addition to exhibiting partial protective effects on cellular redox state parameters. These findings suggest the extract's immunomodulatory potential and reinforce the need for further studies to clarify its mechanisms of action and possible applicability in neutrophil-mediated inflammatory conditions.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fish 3D Clustering App (F3DCA): A Non-Supervised Clustering Method with a Machine Learning Autoencoder for Analyzing 3D Trajectories of Three Fish Species.","authors":"Ali Farhan, Gilbert Audira, Cao Thang Luong, Chih-Hsin Hung, Tzong-Rong Ger, Chung-Der Hsiao","doi":"10.3390/biology15191768","DOIUrl":"10.3390/biology15191768","url":null,"abstract":"<p><p>Fish behaviors are widely studied in various research fields due to their relevance to many aspects, including neurodegenerative processes, since they can impair motor control, complex behavior, habituation, and response to environmental stimuli. 3D locomotion trajectory analysis is one of the assays to analyze complex behaviors in fish. However, while existing 3D tracking software can capture the 3D trajectories of fish, they still rely heavily on manual or semi-automated analysis. Moreover, traditional analysis methods are inadequate for handling the high complexity of raw 3D data (X, Y, Z coordinates), and manual/semi-automated procedures introduce subjective human bias and are highly time-consuming, highlighting the need for a fully automated, unsupervised machine learning method. Here, we aimed to develop an unsupervised clustering method with machine learning to automatically analyze fish behaviors by using fish 3D coordinates. To evaluate the performance of this method, five different datasets, including (1) interspecies fish that consisted of three fish species, which were <i>Danio rerio</i>, <i>Oryzias woworae</i>, and <i>Kryptopterus vitreolus</i>, (2) shoal sex composition, (3) caudal fin amputation effect, (4) habituation time effect, and (5) acute ethanol exposure effect on zebrafish behaviors, were analyzed. The current method utilizes multiple clustering algorithms, including K-Means, BIRCH, Gaussian Mixture Model, and Spectral Clustering, which were then applied to the 3D trajectory data in every dataset. Afterward, the clustering performance was evaluated using the Silhouette Score and Davies-Bouldin Index, followed by the use of deep-learning autoencoders to improve latent feature representation and enhance cluster separation. The clustering outcomes were further compared with predefined experimental groups using ARI and NMI and were qualitatively interpreted alongside conventional behavioral endpoints. External agreement varied among datasets and clustering algorithms. The proposed method can characterize differences in zebrafish 3D locomotor trajectory patterns across experimental conditions, while its separation power may decrease when behavioral differences are subtle or highly overlapping. Furthermore, the present study evaluated the method using multiple behavioral datasets; a similar framework can be extended to zebrafish models of neurodegenerative disease to identify disease-associated alterations in movement patterns and neurobehavioral organization. Finally, a user-friendly software package with easy installation and readable trajectory-analysis outputs was also developed that can be useful in biomedical research.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethylene Biosynthesis Dynamics and Genome-Wide Characterization of the ACS and ACO Gene Families During Fruit Development in 'Kuerle Xiangli' (<i>Pyrus sinkiangensis</i> Yu).","authors":"Tingting Fan, Deen Zhang, Wenjie Li, Zhihua Guo, Xiaoyan Lu","doi":"10.3390/biology15191769","DOIUrl":"10.3390/biology15191769","url":null,"abstract":"<p><p><b>Background:</b> Fruit ripening in 'Kuerle Xiangli' (<i>Pyrus sinkiangensis</i> Yu) is a complex physiological process orchestrated by ethylene; however, the molecular mechanisms governing ethylene biosynthesis during fruit development to ripening remain incompletely understood. <b>Methods:</b> In this study, we systematically characterized ethylene production, fruit quality parameters, and the ACS (1-aminocyclopropane-1-carboxylic acid synthase) and ACO (ACC oxidase) gene families in 'Kuerle Xiangli' across nine developmental stages from 30 to 150 days after full bloom (DAFB). <b>Results:</b> Ethylene production remained suppressed during fruit growth and expansion but exhibited a massive climacteric burst at the ripening stage (150 DAFB). Soluble solids content peaked at 120 DAFB (16.2%), whereas fruit firmness declined significantly from 135 to 150 DAFB, indicating a temporal asynchrony between sugar accumulation and cell wall disassembly. A total of 12 <i>PsinACS</i> and 5 <i>PsinACO</i> genes were identified from the genome (<i>Pyrus sinkiangensis</i> Yu). Phylogenetic analysis classified the PsinACS proteins into four groups (I-IV) and the PsinACO proteins into two groups (B and C), with Group I ACS members clustering with well-characterized ripening-associated orthologs. Conserved motif and gene structure analyses revealed high conservation within each phylogenetic group. Gene duplication analysis indicated that most <i>PsinACS</i> and <i>PsinACO</i> genes originated from whole-genome duplication or segmental duplication events, with only a few arising from proximal or tandem duplications. Synteny analysis demonstrated strong evolutionary conservation across Rosaceae species, and Ka/Ks ratios (<1) indicated that both gene families have undergone strong purifying selection. Expression profiling by qRT-PCR revealed distinct patterns: <i>PsinACS2</i>, <i>PsinACS3</i> and <i>PsinACS4</i> were highly expressed in early fruitlets (30 DAFB), and eight <i>ACS</i> genes (<i>PsinACS1, PsinACS5-9</i>, <i>PsinACS11-12</i>) and <i>PsinACO1</i> showed maximal expression at 150 DAFB, coinciding with the ethylene climacteric burst. <b>Conclusions:</b> Taken together, combined with phylogenetic tree analysis, indicates that <i>PsinACS1</i> and <i>PsinACO1</i> are crucial genes in ethylene biosynthesis that positively regulate fruit ripening. These results provide a comprehensive characterization of the <i>ACS</i> and <i>ACO</i> gene families in <i>P. sinkiangensis</i> and reveal a coordinated transcriptional network that governs ethylene biosynthesis during pear fruit ripening.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Function-Based Assessment of Small Airway Dysfunction in Chronic Respiratory Diseases.","authors":"Chalerm Liwsrisakun, Athavudh Deesomchok, Chaicharn Pothirat, Warawut Chaiwong","doi":"10.3390/biology15191765","DOIUrl":"10.3390/biology15191765","url":null,"abstract":"<p><p>Small airway dysfunction (SAD) is increasingly recognized as an early and clinically important component of chronic respiratory diseases. Because pathological changes in the peripheral airways may remain clinically silent until disease is advanced, sensitive methods to detect and characterize SAD are required to improve phenotyping and support mechanism-based therapeutic development. This narrative review summarized key SAD mechanisms, including epithelial injury and dysregulated repair, mucus retention, inflammation-driven mucosal edema, smooth muscle dysfunction, and matrix remodeling, that contribute to small-airway narrowing and ventilation heterogeneity. We synthesized lung function approaches used to quantify SAD and relate measurement outputs to functional abnormalities, including ventilation heterogeneity, small-airway narrowing, airway closure, and gas trapping. We reviewed commonly used clinical and research assessments, including spirometry, forced oscillation techniques (FOTs), impulse oscillometry (IOS), multiple-breath washout (MBW), fractional exhaled nitric oxide (FeNO), and static lung volume measurements. We also highlighted the practical advantages, key limitations, and interpretive pitfalls of each modality and proposed a pragmatic framework for integrating these physiological tests into clinical evaluation and phenotypic identification of SAD. Finally, we identified priorities for standardization and future studies to determine how lung function-based SAD endpoints can guide treatment decisions and serve as outcome measures in clinical trials.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Chronic Paroxetine Exposure and Irisin Treatment on Sexual Motivation, Reproductive Endocrine Profile, and Vaginal Histological and Immune-Inflammatory Outcomes in Adult Female Rats.","authors":"Ahmet Yardimci, Tugrul Ertugrul, Nazife Ulker Ertugrul, Sinan Canpolat","doi":"10.3390/biology15191767","DOIUrl":"10.3390/biology15191767","url":null,"abstract":"<p><p>Selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, are frequently associated with sexual dysfunction, yet their effects on female reproductive endocrine regulation and the local vaginal tissue environment remain incompletely characterized. Irisin is an exercise-responsive adipomyokine with reported reproductive and immunomodulatory actions, but its influence during chronic paroxetine exposure is unknown. This study evaluated the behavioral, endocrine, histological, and immune-related effects of chronic paroxetine treatment and examined whether irisin changed responses. Forty regularly cycling female Sprague-Dawley rats were allocated to sham control, paroxetine, irisin, or paroxetine + irisin groups (<i>n</i> = 10/group). Paroxetine was administered orally at 20 mg/kg/day for 8 weeks, while irisin was delivered continuously by subcutaneous mini-osmotic pumps at 100 ng/kg/day during the final 4 weeks. Sexual incentive motivation and active investigation behaviors, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and anti-Müllerian hormone (AMH), vaginal fibroblast and plasma cell numbers, Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) immunoreactivity, and periodic acid-Schiff (PAS) reactivity were evaluated. Paroxetine did not significantly affect sexual incentive motivation parameters or circulating reproductive hormone concentrations (<i>p</i> > 0.05), but both paroxetine-treated groups showed a lower duration of investigation directed toward the female and a higher male investigation preference ratio than the sham control (<i>p</i> < 0.05). Irisin alone reduced locomotor activity (<i>p</i> < 0.01). Paroxetine increased vaginal fibroblast counts (<i>p</i> = 0.0001) and NF-κB immunoreactivity (<i>p</i> = 0.003) compared with the sham control, whereas TLR4 immunoreactivity remained unchanged. Plasma cell counts were elevated in all treatment groups compared with the sham control (<i>p</i> < 0.0001). Irisin co-treatment reduced fibroblast counts relative to paroxetine group and reduced plasma cell counts relative to both single-treatment groups (all <i>p</i> < 0.001). Vaginal epithelial PAS reactivity was severe (+++) in sham control, weak (+) after paroxetine, and moderate (++) in both irisin-treated groups. Overall, chronic paroxetine exposure produced selective behavioral and local vaginal stromal, immune-inflammatory, and epithelial alterations without significant changes in the measured reproductive hormonal profile. Irisin influenced several vaginal tissue responses but did not change the paroxetine-associated alterations in active investigation behavior.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Structure, Evolution, and Comparative Genomics of the <i>Dendrobium officinale</i> Mitochondrial Genome.","authors":"Zemei Zhu, Jiamei Zheng, Yue Zhang, Chunfan Xiang, Shiqing Xie, Feiya Zhao, Aien Tao","doi":"10.3390/biology15191763","DOIUrl":"10.3390/biology15191763","url":null,"abstract":"<p><p><i>Dendrobium officinale</i> is an important medicinal Orchidaceae species with considerable ecological and economic value. While its chloroplast genome has been well characterized, the structure features of its mitochondrial genome remain largely unexplored, which further hinders our understanding of its evolutionary dynamics and adaptive mechanisms. This study presents a comprehensive characterization of the mitochondrial genome of <i>D. officinale</i>, revealing a complex multibranched structure of 22 chromosomes totaling 639,931 bp, encoding 35 PCGs, 3 rRNA genes, and 24 tRNA genes. Codon usage analysis revealed a distinct codon bias, while the genome harbors abundant repetitive elements and 522 RNA editing sites. Comparative genomic analysis identified 125 MTPT fragments totaling 108,012 bp (16.88% of the mitogenome), indicating frequent inter-organellar DNA transfer. <i>Dendrobium nobile</i> exhibited the highest genomic homology with <i>D. officinale</i>. Ka/Ks analysis indicated that most mitochondrial genes are under strong purifying selection. In addition, we conducted a comparative analysis between the newly assembled mitochondrial genome of <i>D. officinale</i> and seven Orchidaceae species. Phylogenetic analysis based on the maximum likelihood, maximum parsimony and bayesian inference approaches resolved the phylogenetic position of <i>D. officinale</i> within Orchidaceae. Collectively, these findings provide a valuable reference for future studies on Orchidaceae phylogenomics and mitochondrial evolution.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triokinase/FMN Cyclase: A Bifunctional Enzyme Linking Metabolism, Stress Responses and Disease.","authors":"João Meireles Ribeiro, Fernando Martín-Ruiz, José Carlos Cameselle","doi":"10.3390/biology15191764","DOIUrl":"10.3390/biology15191764","url":null,"abstract":"<p><p>Triokinase/FMN cyclase (TKFC) is a bifunctional enzyme that catalyzes both ATP-dependent triose phosphorylation and the formation of riboflavin 4',5'-cyclic phosphate (cFMN) from FAD, thereby linking fructose and flavin metabolism through a single protein. Structural modeling supports a model of TKFC as a conformationally dynamic homodimer in which interacting K and L domains cooperate through composite intersubunit active sites to support both kinase and cyclase reactions. Beyond its classical role in fructose metabolism, TKFC has emerged as a determinant of fructose-derived carbon partitioning and has been implicated in nutrient sensing, oxidative stress adaptation, innate immunity, ferroptosis and several inherited human disorders. Recent biochemical and analytical studies have renewed interest in cFMN as a bona fide metabolite and provide evidence consistent with cFMN synthesis and degradation, while its physiological turnover remains to be established. Here, we review the historical development, structural organization, catalytic mechanisms and expanding biological functions of TKFC, highlighting its links with intermediary metabolism, cellular stress adaptation and human disease.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT6 Deficiency Accelerates DMBA/TPA-Induced Skin Papilloma Development and Is Associated with Regulatory T-Cell Accumulation and Reduced CD8+IFN-γ+ Responses.","authors":"Aranza Mejía-Muñoz, Tania Galindo-Santamaría, Valeria Moreno-Tovar, Citlaltepetl Salinas-Lara, Carlos Sánchez-Garibay, Rubén D Arroyo Olarte, Sonia Leon-Cabrera","doi":"10.3390/biology15191747","DOIUrl":"10.3390/biology15191747","url":null,"abstract":"<p><p>Inflammation and the balance between antitumor surveillance and immunoregulatory mechanisms influence chemically induced skin tumor development. STAT6 is a central mediator of IL-4/IL-13 signaling, but its contribution to early skin papilloma development remains unclear. Here, we examined papilloma onset and burden, histopathological alterations, Treg accumulation, and CD8+ T-cell-associated responses in WT and STAT6-deficient mice subjected to a two-stage DMBA/TPA protocol. STAT6-/- mice developed papillomas significantly earlier and exhibited a markedly greater lesion burden than WT mice. This phenotype was associated with more prominent keratinization-related histopathological features, increased Foxp3+ Treg frequency and PD-1 expression in skin-draining lymph nodes, and a broader distribution of Foxp3+ cells within papillomas. STAT6 deficiency was also accompanied by attenuated CD8+IFN-γ+ responses in draining lymph nodes and reduced CD8+ cell infiltration within lesions. Collectively, these findings reveal a distinct immune profile associated with enhanced susceptibility to chemically induced skin papillomas and underscore the context-dependent role of STAT6 in cutaneous tumor immunity.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}