Frontiers in bioscience (Landmark edition)最新文献

{"title":"The Protective Effect of Venetoclax on the Calcium-Induced Mitochondrial Pore and ROS Production as a New Possible Factor Contributing to Drug Resistance.","authors":"Alexey G Kruglov, Tatiana A Fedotcheva, Nadezhda I Fedotcheva","doi":"10.31083/FBL55451","DOIUrl":"https://doi.org/10.31083/FBL55451","url":null,"abstract":"<p><strong>Objective: </strong>Recent data show that there are direct relationships between mitochondrial activity, cancer progression, and chemoresistance. Venetoclax (Ven) is a mitochondria-targeted chemotherapeutic drug, which facilitates apoptosis by selectively inhibiting the antiapoptotic protein Bcl-2. Ven exhibits a dual effect, affecting not only mitochondria but also the cell drug resistance system. There is also evidence indicating that cancer cells develop resistance to Ven, which is mediated by the upregulation of antiapoptotic proteins, simultaneous activation of multiple signaling pathways, an alteration in the cellular and mitochondrial metabolism, and other defensive mechanisms. The influence of Ven on the opening of the mitochondrial permeability transition pore (mPTP), a key event in the induction of mitochondria-dependent cell death, has not been previously studied.</p><p><strong>Methods: </strong>The effect of Ven on calcium-induced mPTP opening, respiration, and reactive oxygen species (ROS) production was examined in isolated rat liver mitochondria, using cation-selective electrodes, as well as fluorescent and chemiluminescent methods.</p><p><strong>Results: </strong>Ven was found to have a protective effect against the Ca²⁺-induced mPTP opening, increasing the threshold calcium concentrations and the calcium load that activate pore opening. A comparison with the known mPTP inhibitors ADP, bongkrekic acid (BA), cyclosporine A (Cs), oligomycin, used separately and in combination with Ven, showed a similarity of the effect of Ven (at a concentration of 50 µM) to the effect of BA (20 µM). The effects of both were prevented by carboxyatractyloside (CATR). Also, the protective effect of Ven, as well as that of BA, was completely eliminated by 2-thenoyltrifluoroacetone (TTFA), an inhibitor of the ubiquinone-binding site of succinate dehydrogenase complex at low concentrations (5 µM and 50 µM under the oxidation of succinate and NAD-dependent substrates, respectively). Simultaneously, Ven decreased the ROS production induced by TTFA under the same conditions.</p><p><strong>Conclusions: </strong>Ven shows two protective activities, namely, the inhibition of mPTP opening and the suppression of ROS production in mitochondria, which may be additional causes of the development of drug resistance. The results of the TTFA test are consistent with the data on the dependence of Ven resistance on the state of the respiratory chain.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"55451"},"PeriodicalIF":3.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Commiphora africana</i> Ethanol Extract Attenuates Inflammatory Responses With Reduced NF-κB/AP-1 Activation and Src/TAK1-Related Signaling Changes.","authors":"Canglang Mou, Yuhao Wang, Lei Huang, Jinghan Su, Long You, Ziliang He, Yeye Hu, Weizhaole Wei, Wooram Choi, Byoung-Hee Lee, Woo Young Bang, Hye-Woo Byun, Jongsung Lee, Ji Hye Kim, Jae Youl Cho","doi":"10.31083/FBL55796","DOIUrl":"https://doi.org/10.31083/FBL55796","url":null,"abstract":"<p><strong>Background: </strong>The bark, resin, and roots of <i>Commiphora africana</i> (A. Rich.) Engl. have traditionally been used in African medicine to treat fever, stomach disorders, colic, and swelling. However, despite this traditional use, its anti-inflammatory activity and the underlying molecular mechanisms remain poorly characterized.</p><p><strong>Methods: </strong>We evaluated the anti-inflammatory activity of <i>C. africana</i> ethanol extract (Caf-EE) in lipopolysaccharide (LPS)-stimulated macrophages and in murine models of HCl/EtOH-induced acute gastric mucosal injury and LPS-induced acute lung injury. Reporter assays, gene expression analysis, immunoblotting, cellular thermal shift assay (CETSA), gas chromatography-mass spectrometry (GC-MS)-guided compound annotation, network pharmacology, and molecular docking were used to investigate the anti-inflammatory mechanisms of Caf-EE.</p><p><strong>Results: </strong>Caf-EE inhibited nitrite production without cytotoxicity in LPS-stimulated RAW264.7 macrophages. GC-MS-guided feature annotation identified representative candidate constituents of Caf-EE, and network pharmacology indicated their association with inflammation-related pathways. Mechanistically, Caf-EE suppressed MyD88- and TRIF-mediated NF-κB/Activator protein 1 (AP-1) transcriptional activity and reduced the expression of inflammatory genes. Caf-EE also inhibited phosphorylation of Src/IκB kinase (IKK)/IκB- and Transforming growth factor-β-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK)/c-Jun-associated signaling proteins and increased the thermal stability of Src and TAK1. <i>In vivo</i>, Caf-EE attenuated HCl/EtOH-induced acute gastric mucosal injury and LPS-induced acute lung injury, accompanied by reduced phosphorylation of Src and TAK1 in both tissues. Among the representative GC-MS-annotated compounds, 9,19-cyclolanost-24-en-3-ol exhibited the highest predicted binding affinity for Src and TAK1 in molecular docking analysis.</p><p><strong>Conclusions: </strong>Collectively, this study provides mechanistic evidence for the anti-inflammatory effects of Caf-EE through modulation of Src/TAK1-associated signaling. Furthermore, the protective effects observed in acute inflammatory disease models support the further development of Caf-EE as a therapeutic candidate for inflammatory disorders.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"55796"},"PeriodicalIF":3.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Signatures of Cardiac Mitochondrial Remodelling During Acute Diabetes Reflect Metabolic and Redox Adaptations.","authors":"Natália Andelová, Dávid Janko, Milan Zvarík, Iveta Waczulíková, Simona Papežíková, Veronika Farkašová, Táňa Ravingerová, Miroslav Ferko","doi":"10.31083/FBL55463","DOIUrl":"https://doi.org/10.31083/FBL55463","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria play a central role in cardiac energy metabolism and dynamically adapt to changes in metabolic demand. However, the early mitochondrial adaptations accompanying the acute phase of diabetes mellitus remain insufficiently understood. This study aimed to characterise diabetes-induced mitochondrial remodelling in the rat heart.</p><p><strong>Methods: </strong>Diabetes was induced using an established streptozotocin-induced rat model. Cardiac mitochondrial proteomes were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in control and diabetic animals. Differential protein abundance was assessed by statistical comparison between groups using the <i>limma</i> package in R, and machine learning classification was used to identify proteins with the strongest discriminatory power between control and diabetic states.</p><p><strong>Results: </strong>Diabetes was associated with distinct mitochondrial proteomic remodelling. In the diabetic group, monoamine oxidase A (AOFA, <i>p_adjust</i> = 0.003) was markedly upregulated, fatty acid β-oxidation-related enzymes including dienoyl-CoA isomerase (ECH1, <i>p_adjust</i> < 0.001) and dienoyl-CoA reductase (DECR, <i>p_adjust</i> = 0.003) showed increased abundance, and respiratory chain complex I components, particularly NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUS1, <i>p_adjust</i> = 0.016) and NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUS2, <i>p_adjust</i> = 0.016), were elevated. Machine learning analysis consistently identified AOFA and key metabolic proteins as the strongest discriminators between diabetic and control animals (<i>n</i> = 6 per group). These changes indicate a coordinated shift towards enhanced lipid utilisation, altered mitochondrial respiratory function, and involvement of redox-associated processes.</p><p><strong>Conclusions: </strong>The observed proteomic changes may reflect early adaptive and compensatory mechanisms supporting mitochondrial function under increased energetic and oxidative load and highlight pathways that may represent promising candidates for targeted therapeutic modulation in diabetic cardiac dysfunction.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"55463"},"PeriodicalIF":3.1,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DADOS Spectroscopy of Organotypic Brain Slices to Determine Hydrogen Peroxide-Induced Oxidative Stress.","authors":"Christian Humpel","doi":"10.31083/FBL54348","DOIUrl":"https://doi.org/10.31083/FBL54348","url":null,"abstract":"<p><strong>Background: </strong>Organotypic brain slices are state-of-the-art <i>ex vivo</i> preparations that allow the study of all types of brain cells for several weeks to months. The brain slices are cultured on semi-permeable membranes, and as the slices flatten and become transparent, remain viable for several weeks. However, without cellular staining, assessing slice health remains challenging. Thus, this study aimed to determine whether assessing spectroscopy of the living brain slices can detect oxidative stress.</p><p><strong>Methods: </strong>Brain slices (300 µm) were prepared from postnatal day 8-10 mouse brains and cultured as quarter-brain slices at the hippocampal level. Spectrography was performed using an adapted DADOS spectrograph. Fresh, living slices were tested with exposure to three laser wavelengths: red-green-blue, ultraviolet (UV), and infrared (IR) light, and a neon and mercury lamp. To induce oxidative stress, some slices were treated with 9.7 mM hydrogen peroxide for 2 days, and others were then stained with the red fluorescent nuclear cell death dye propidium iodide.</p><p><strong>Results: </strong>Our data showed that the DADOS spectrograph can detect spectra in living brain slices using all seven light sources. PI treatment alone decreased the detected wavelength signal when exposed to mercury, but increased it when exposed to neon. Hydrogen peroxide reduced the wavelength after exposure to IR and the red laser, while the area (intensity) was enhanced after exposure to UV, mercury, neon, and IR.</p><p><strong>Conclusion: </strong>Our data show that oxidative stress-mediated processes can be measured with a DADOS spectrograph in living organotypic brain slices. The slices showed a differential spectral pattern when stimulated with seven different light sources. This study pioneers a novel, low-cost, easy-to-use DADOS spectroscopy tool for living brain slices.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54348"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracorporeal Shock Wave Alleviates Knee Contracture in Rats by Inhibiting Hypoxia-Mediated Pyroptosis in Joint Capsular Fibroblasts.","authors":"Quan-Bing Zhang, Xue-Ming Li, Xiu-Li Kan, Feng Wang, Lei Huo, A-Ying Liu, Mian Li, Qian-Qian Bao, Run Zhang, De-Ting Zhu, Zun-Yu Du, Jing Mao, Yun Zhou","doi":"10.31083/FBL52155","DOIUrl":"https://doi.org/10.31083/FBL52155","url":null,"abstract":"<p><strong>Background: </strong>Joint immobilization frequently causes joint contracture, which may significantly impact an individual's quality of life. Consequently, extracorporeal shock wave (ESW) has been increasingly adopted to manage various bone and joint diseases. Our study investigated whether ESW therapy relieves knee contracture and if it mitigates the underlying hypoxia-induced pyroptosis of joint-capsule fibroblasts.</p><p><strong>Methods: </strong>A rat model of knee contracture was established through prolonged unilateral knee joint immobilization. Following the application of ESW, the levels of joint capsule fibrosis and cell pyroptosis were evaluated. During the immobilization phase, the NOD-like receptor protein 3 (NLRP3) specific inhibitor MCC950 was administered to assess its impact on pyroptosis levels. <i>In vitro</i>, hypoxia-induced rat knee joint synovial fibroblasts were exposed to hypoxia to induce myofibroblast differentiation. Hypoxia-inducible factor 1 alpha (HIF-1α) small interfering RNA was then used to inhibit HIF-1α expression, followed by the measurement of cell pyroptosis and fibrosis levels.</p><p><strong>Results: </strong>ESW intervention successfully mitigated knee contracture while decreasing pyroptosis and fibrosis in the joint capsule. Similarly, MCC950 treatment effectively inhibited both pyroptotic cell death and fibrotic tissue development within the capsule. Hypoxia induced the differentiation of synovial fibroblasts into myofibroblasts and increased pyroptosis. However, inhibiting HIF-1α expression mitigates these effects, leading to reduced pyroptosis and fibrosis in rat knee synovial fibroblasts.</p><p><strong>Conclusions: </strong>Hypoxic conditions promote pyroptosis in rat knee synovial fibroblasts and drive their differentiation into myofibroblasts, contributing to joint contracture. ESW therapy may alleviate joint contractures by partially inhibiting structural and cellular changes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"52155"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclical Iron Homeostasis: The Role of Sex Hormones in Female Iron Regulation.","authors":"Darsiha Balakirishnan, Fanija Dukovski, Heather Bytheway, Cory Dugan","doi":"10.31083/FBL54404","DOIUrl":"https://doi.org/10.31083/FBL54404","url":null,"abstract":"<p><p>Iron homeostasis in premenopausal women is governed by a dual regulatory architecture that has been incompletely characterized in the clinical literature. The hepcidin-ferroportin axis, established as the master regulator of systemic iron flux, operates within a second-order hormonal framework in females of reproductive age: 17β-estradiol (E2) and progesterone (P4) directly modulate hepatic hepcidin transcription, superimposing a predictable, cycle-dependent oscillation on baseline iron availability. This review summarizes the molecular mechanisms underlying this cyclical regulation. E2 suppresses hepcidin expression through estrogen receptor-dependent regulation of the <i>HAMP</i> gene, mapped in hepatocyte models to an estrogen-responsive element (ERE) half-site. Preclinical evidence also implicates a competing pathway, mediated by the G protein-coupled estrogen receptor 1 (GPR30, also designated <i>GPER1</i>) and bone morphogenetic protein 6 (BMP6), with opposing upregulatory effects on hepcidin. Progesterone has an opposing effect, raising hepcidin in women when administered exogenously, an effect attributed in preclinical models to the progesterone receptor membrane component-1 (PGRMC1). When mapped onto the menstrual cycle, these hormonal actions predict a follicular phase of enhanced iron acquisition and a luteal phase of iron restriction. We distinguish that prediction from the evidence: the predicted late luteal hepcidin maximum is not evident in cohorts sampled serially across the cycle, and circulating interleukin-6 does not rise in the luteal phase, so the cycle-level consequence of the hormonal mechanism remains the central open question. The clinical implications extend to diagnostics and therapeutics: standard iron status biomarkers fluctuate predictably with cycle phase, confounding single-time-point assessments; and the clinical significance of these fluctuations differs mechanistically depending on whether the underlying deficit reflects absolute storage depletion, impaired functional delivery, or erythropoietic cellular restriction. This review proposes a mechanism-oriented biomarker subtyping framework to address this diagnostic gap and discusses cycle-synchronized iron supplementation as a biologically plausible hypothesis that warrants rigorous evaluation in future clinical trials.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54404"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine Residues Are Required for the Sliding Clamp-Dependent Endonuclease Activity of <i>Neisseria gonorrhoeae</i> MutL.","authors":"Viktoriia Yu Savitskaya, Mayya V Monakhova, Daniil R Bazanov, Anastasiia V Litvinova, Viktoriia G Snyga, Tatiana S Oretskaya, Elena A Kubareva","doi":"10.31083/FBL55117","DOIUrl":"https://doi.org/10.31083/FBL55117","url":null,"abstract":"<p><strong>Background: </strong><i>Neisseria gonorrhoeae</i> is a human pathogen that causes gonorrhea and employs a methylation-independent mismatch repair (MMR) pathway to regulate genomic stability and pilin antigenic variation. A key effector of this pathway, MutL, possesses ATPase, DNA-binding, and endonuclease activities, yet the molecular determinants governing its catalytic activity remain poorly understood. In particular, the functional relevance of conserved cysteine (Cys) residues located in the vicinity of the active site is unclear.</p><p><strong>Methods: </strong>We characterized a Cys free-variant of <i>Neisseria gonorrhoeae</i> MutL, in which all Cys residues were replaced with evolutionarily conserved substitutes, in comparison with the wild-type enzyme. ATPase activity, DNA-binding capacity, and endonuclease activity on supercoiled plasmid and linear DNA duplex substrates were assessed, and molecular dynamics simulations were performed to examine the conformational behavior of the C-terminal domain (CTD).</p><p><strong>Results: </strong>Cys substitutions do not markedly affect ATPase activity, DNA-binding capacity, or endonuclease activity on supercoiled plasmid substrates. However, the same amino acid substitutions led to an almost complete loss of sliding clamp-dependent endonuclease activity on linear DNA duplexes. Molecular dynamics simulations revealed that the cysteine substitutions alter the conformational dynamics of the CTD, displacing the catalytically active monomer from its productive orientation relative to the sliding clamp and thereby impairing sliding clamp-dependent endonuclease activity.</p><p><strong>Conclusions: </strong>These results indicate that Cys residues are not directly involved in catalysis but provide the conformational rigidity of the C-terminal domain required for productive engagement with the sliding clamp.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"55117"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-Printed DOX-LF-Loaded PLGA Biphasic Composite Scaffold Modulates Macrophage Polarization and Enhances Osteogenic-Angiogenic Regenerative Potential for Periodontitis.","authors":"Chunfeng Wang, Caijuan Wu, Chan Xiao, Yepo Hou","doi":"10.31083/FBL54017","DOIUrl":"https://doi.org/10.31083/FBL54017","url":null,"abstract":"<p><strong>Background: </strong>To develop an immunomodulatory scaffold integrating antibacterial activity with osteogenic-angiogenic coupling for inflammatory periodontal repair.</p><p><strong>Methods: </strong>A biphasic poly(lactic-co-glycolic acid) (PLGA) scaffold incorporating doxycycline-lactoferrin (DOX-LF)-loaded calcium alginate microspheres and fibroblast growth factor 2/bone morphogenetic protein 9 (FGF2/BMP9)-loaded chitosan nanospheres was fabricated by low-temperature three-dimensional (3D) printing, porogen leaching, and freeze-drying. Material properties, antibacterial activity, macrophage polarization, periodontal ligament stem cell (PDLSC) osteogenesis, and human umbilical vein endothelial cell (HUVEC) angiogenesis were evaluated. Small interfering RNA (siRNA)-mediated milk fat globule-epidermal growth factor 8 (MFGE8) knockdown was used to investigate the underlying mechanism.</p><p><strong>Results: </strong>The scaffold formed an interconnected porous network and released approximately 88.4% of DOX and 60% of LF over 240 h. PLGA/DOX-LF reduced Porphyromonas gingivalis viability to approximately 20% (<i>p</i> < 0.001). In lipopolysaccharide (LPS)-stimulated macrophages, it produced the greatest suppression of M1-associated markers and induction of M2-associated markers, while MFGE8 knockdown significantly reduced MFGE8 expression (<i>p</i> < 0.001) and attenuated these effects. Conditioned medium restored PDLSC migration, ALP activity, and mineralization to approximately 70%, 70-75%, and 80% of control levels, respectively, and increased HUVEC tube length (<i>p</i> < 0.01) and angiogenic gene expression (all <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>A 3D-printed biphasic PLGA scaffold incorporating DOX-LF-loaded calcium alginate microspheres and FGF2/BMP9-loaded chitosan nanospheres was successfully constructed. These <i>in vitro</i> findings support PLGA/DOX-LF as a proof-of-concept platform for antibacterial immunomodulation and osteogenic-angiogenic coupling, pending <i>in vivo</i> validation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54017"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Organ Metatranscriptomics Establishes Organ-Specific Functional Baselines in the Crested Ibis (<i>Nipponia nippon</i>).","authors":"Guoqiang Qiu, Jinshi Ran, Jian Shi, Liying Yuan, Wenwen Dai, Jichen Jin, Pengqi Zhang, Xiaojun Wang, Xinyue Chen, Chen Li, Yongmei Xi","doi":"10.31083/FBL53784","DOIUrl":"https://doi.org/10.31083/FBL53784","url":null,"abstract":"<p><strong>Background: </strong>The crested ibis (<i>Nipponia nippon</i>) is an iconic East Asian species on the International Union for Conservation of Nature's (IUCN) Red List, with recurrent stress-related sudden death reported in captivity and in the wild. However, the mechanisms underlying stress responses remain poorly characterized.</p><p><strong>Methods: </strong>Using opportunistic post-mortem samples, we generated, to our knowledge, the first organ-resolved metatranscriptomic reference dataset for this species in a stress-associated context. Matched libraries from small intestine, liver, spleen, and lung were sequenced and processed using a unified pipeline; microbial transcriptional activity was quantified following host and rRNA removal and stringent detection criteria, enabling concurrent readouts of community composition and functional gene expression.</p><p><strong>Results: </strong>Transcriptional activity was intestine-centric, whereas liver, spleen, and lung harbored low-load communities with limited taxon sharing. The small intestine was dominated by the aquatic-associated <i>Cetobacterium somerae</i> (~54.8%), consistent with fish-based feeding, while <i>Romboutsia</i> was scarce, suggesting a weak butyrate-producing guild. Functionally, transcripts were enriched for small-molecule metabolism, nucleotide/cofactor turnover, central carbon conversion, and membrane/envelope-associated precursor pathways. Stratified pathway analysis further resolved uneven classified contributions: <i>Paraclostridium bifermentans</i> spanned the broadest classified pathway repertoire, <i>Cetobacterium somerae</i> contributed more strongly to nucleotide-linked functions, and <i>Clostridium perfringens</i> retained a more distinctive inositol-related branch. Antimicrobial resistance (AMR)-linked transcripts in the intestine were dominated by target-site mechanisms (elongation factor Tu (EF-Tu), RNA polymerase β' subunit (rpoC) and DNA gyrase subunit A (gyrA)) with a low-level ErmQ-associated macrolide-lincosamide-streptogramin (MLS) resistance signature, consistent with background expression of core targets.</p><p><strong>Conclusions: </strong>This organ-resolved dataset provides a practical baseline for microbiome, pathogen, and resistance surveillance in captive crested ibis, and a reference for future comparisons among captive, wild, and reintroduced populations. AMR signals are best read as contextual markers rather than phenotypic resistance and can serve as auxiliary sentinels alongside composition and function. Overall, the dataset provides a reusable framework for health assessment and conservation planning.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"53784"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Chronic Myeloid Leukaemia (CML): Emerging Molecular and Immunotherapeutic Targets.","authors":"Jingyi Dai, Panpan Zheng, Jian Liu, Linyan Cheng, Xiao Zheng, Lujun Chen, Jingting Jiang, Zhuojun Zheng","doi":"10.31083/FBL48912","DOIUrl":"https://doi.org/10.31083/FBL48912","url":null,"abstract":"<p><p>Chronic myeloid leukaemia (CML), a distinct myeloproliferative neoplasm, results from the malignant reprogramming of haematopoietic stem cells (HSCs) into leukaemia stem cells (LSCs), primarily driven by breakpoint cluster region and Abelson (<i>BCR-ABL1</i>) fusion oncogene. Although the advent of tyrosine kinase inhibitors (TKIs) has significantly transformed clinical management, leading to improved patient survival and quality of life, sustained treatment-free remission (TFR) remains achievable in only a minority of patients. This limitation is largely attributable to the persistence of LSCs and the development of resistance mechanisms. Emerging evidence indicates that LSCs evade TKI-induced apoptosis through aberrant expression of specific cell-surface markers, dysregulated intracellular signalling pathways, and extensive epigenetic alterations. This review examines recent advancements in CML therapy, with a focus on these novel therapeutic targets. It highlights the pivotal role of LSCs in disease progression and relapse, evaluates potential molecular and epigenetic regulators as new targets for intervention, and supports the development of combination treatment strategies to improve TFR rates and move towards curative outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"48912"},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}