PLoS Comput Biol. 2025 Apr 15;21(4):e1012298. doi: 10.1371/journal.pcbi.1012298. Online ahead of print.

ABSTRACT

Cellular senescence is known to drive age-related pathology through the senescence-associated secretory phenotype (SASP). However, it also plays important physiological roles such as cancer suppression, embryogenesis and wound healing. Wound healing is a tightly regulated process which when disrupted results in conditions such as fibrosis and chronic wounds. Senescent cells appear during the proliferation phase of the healing process where the SASP is involved in maintaining tissue homeostasis after damage. Interestingly, SASP composition and functionality was recently found to be temporally regulated, with distinct SASP profiles involved: a fibrogenic, followed by a fibrolytic SASP, which could have important implications for the role of senescent cells in wound healing. Given the number of factors at play a full understanding requires addressing the multiple levels of complexity, pertaining to the various cell behaviours, individually followed by investigating the interactions and influence each of these elements have on each other and the system as a whole. Here, a systems biology approach was adopted whereby a multi-scale model of wound healing that includes the dynamics of senescent cell behaviour and corresponding SASP composition within the wound microenvironment was developed. The model was built using the software CompuCell3D, which is based on a Cellular Potts modelling framework. We used an existing body of data on healthy wound healing to calibrate the model and validation was done on known disease conditions. The model clearly shows how differences in the spatiotemporal dynamics of different senescent cell phenotypes lead to several distinct repair outcomes. These differences in senescent cell dynamics can be attributed to variable SASP composition, duration of senescence and temporal induction of senescence relative to the healing stage. The range of outcomes demonstrated strongly highlight the dynamic and heterogenous role of senescent cells in wound healing, fibrosis and chronic wounds, and their fine-tuned control. Further specific data to increase model confidence could be used to explore senolytic treatments in wound disorders.

PMID:40233102 | DOI:10.1371/journal.pcbi.1012298

FASEB J. 2025 Apr 30;39(8):e70541. doi: 10.1096/fj.202403146RR.

ABSTRACT

Injured liver cells undergoing chronic wound healing produce excessive amounts of extracellular matrix (ECM) components, such as collagen and fibronectin, leading to fibrosis. This process is largely mediated by transforming growth factor-β (TGFβ) signaling, which intersects with the tumor suppressor p53 pathway. However, the roles of specific p53 isoforms in this interaction remain unclear. In this study, we report the involvement of the Δ40p53α isoform, an N-terminal truncated variant of p53, in regulating ECM gene expression in TGFβ1-activated LX-2 human hepatic stellate cells. RT-PCR analysis of cirrhotic liver tissues revealed clinically relevant increases in Δ40p53 expression. Knockdown of Δ40p53 using antisense oligonucleotides in LX-2 cells attenuated TGFβ1-induced activation and significantly reduced collagen production and deposition, particularly fibrillar collagen III. Conversely, overexpression of Δ40p53α upregulated collagen III expression in concert with full-length p53 (FLp53). Co-immunoprecipitation analysis demonstrated that Δ40p53α forms a complex with FLp53, which associates with phosphorylated Smad3 following TGFβ1 stimulation. These findings suggest that Δ40p53 enhances collagen III expression by interacting with FLp53 and Smads, highlighting its role in profibrogenic ECM expression.

PMID:40232888 | DOI:10.1096/fj.202403146RR

Physiol Plant. 2025 Mar-Apr;177(2):e70210. doi: 10.1111/ppl.70210.

ABSTRACT

Plant root systems play a crucial role in taking up water and nutrients, as well as in facilitating symbiotic partnerships with microorganisms like rhizobia and mycorrhizae that enhance nutrient fixation and assimilation. Extensive research in seed plants has demonstrated the dominant role of the phytohormone auxin during root development in this group of vascular plants. Non-seed vascular plants (lycophytes, horsetails and ferns) occupy a key phylogenetic position as the sister group to seed plants, making them essential for understanding the evolution of roots. These lineages exhibit distinct root development and branching patterns, in which the hormone auxin might play a pivotal role. However, the molecular basis underlying its function during root development in these plant groups remains poorly understood. In this review, we summarize the current progress in our understanding of auxin-mediated root initiation, patterning, and branching in vascular non-seed plants while highlighting outstanding key questions. Despite limited research, the available evidence suggests that both conserved and lineage-specific auxin-dependent genetic circuits regulate root development in these species. While remaining relatively limited in lycophytes and ferns, seed plants have evolved extensive environmentally sensitive regulatory networks facilitating the adaptation of their branching strategies to perceived external cues. These networks likely emerged through the duplication and neofunctionalization of gene families involved in auxin transport and signalling, as well as their downstream factors, such as LBD and PLT genes.

PMID:40231754 | DOI:10.1111/ppl.70210

Proteins. 2025 Apr 15. doi: 10.1002/prot.26826. Online ahead of print.

ABSTRACT

The high lethality and infectiousness of coronaviruses, particularly SARS-Cov-2, pose a significant threat to human society. Understanding coronaviruses, especially the interactions between these viruses and humans, is crucial for mitigating the coronavirus pandemic. In this study, we conducted a comprehensive comparison and evaluation of five prevalent computational methods: interolog mapping, domain-domain interaction methodology, domain-motif interaction methodology, structure-based approaches, and machine learning techniques. These methods were assessed using unbiased datasets that include C1, C2h, C2v, and C3 test sets. Ultimately, we integrated these five methodologies into a unified model for predicting protein-protein interactions (PPIs) between coronaviruses and human proteins. Our final model demonstrates relatively better performance, particularly with the C2v and C3 test sets, which are frequently used datasets in practical applications. Based on this model, we further established a high-confidence PPI network between coronaviruses and humans, consisting of 18,012 interactions between 3843 human proteins and 129 coronavirus proteins. The reliability of our predictions was further validated through the current knowledge framework and network analysis. This study is anticipated to enhance mechanistic understanding of the coronavirus-human relationship a while facilitating the rediscovery of antiviral drug targets. The source codes and datasets are accessible at https://github.com/covhppilab/CoVHPPI.

PMID:40231383 | DOI:10.1002/prot.26826

Am Heart J Plus. 2025 Mar 1;53:100520. doi: 10.1016/j.ahjo.2025.100520. eCollection 2025 May.

ABSTRACT

The development of vascularized organoids as novel modelling tools of the human cardio-cerebrovascular system for preclinical research has become an essential platform for studying human vascularized tissues/organs for development of personalized therapeutics during recent decades. Organ-on-chip technology is promising for investigating physiological in vitro responses in drug screening development and advanced disease models. Vascularized tissue/organ-on-a-chip benefits every step of drug discovery pipeline as a screening tool with close human genome relevance to investigate human systems biology. Simultaneously, cardio-cerebrovascular-on-chip-integrated microfluidic system serves as an alternative to preclinical animal research for studying (patho-)physiological processes of human blood vessels during embryonic development and cardio-cerebrovascular disease. Integrated with next-generation techniques, such as three-dimensional bioprinting of both cells and matrix, may enable vascularized organoid-on-chip-based novel drug development as personalized therapeutics.

PMID:40230658 | PMC:PMC11995107 | DOI:10.1016/j.ahjo.2025.100520

Exp Ther Med. 2025 Mar 27;29(5):106. doi: 10.3892/etm.2025.12856. eCollection 2025 May.

ABSTRACT

Influenza infections damage the airway and induce the innate immune response that contributes to hyper-inflammation. Eucommiae Cortex (EC) enhances immune function and suppresses inflammation. To determine potential compounds and targets of EC associated with influenza, bioinformatics analyses and experimental verification were employed. The active compounds of EC were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersecting targets of EC and influenza were determined and examined using network pharmacology to analyze the relationship between the compounds and disease targets. The network identified three main compounds (quercetin, genistein and kaempferol) and four main targets (IL6, BCL2, IL1B and TNF). The ligand-target binding affinity was calculated by molecular docking, a computational method used in drug design to predict the interaction between the compound and protein target. The docking results revealed that kaempferol and TNF showed the strongest binding affinity. In vitro experiments confirmed the therapeutic effect of EC in influenza virus-infected Madin-Darby canine kidney cells. Collectively, the present study identified the active compounds and potential targets of EC in influenza and suggested EC as a future influenza treatment.

PMID:40230620 | PMC:PMC11995446 | DOI:10.3892/etm.2025.12856

iScience. 2025 Mar 15;28(4):112120. doi: 10.1016/j.isci.2025.112120. eCollection 2025 Apr 18.

ABSTRACT

Alisertib is a potent aurora A kinase inhibitor in clinical trials for cancer treatment, but its efficacy on cancer vaccines remains unclear. Here, we developed a DNA vaccine targeting glypican-3 (pGPC3) and evaluated its efficacy with alisertib in hepatocellular carcinoma (HCC) models. The combination therapy of pGPC3 vaccine and alisertib significantly inhibited subcutaneous tumor growth, enhanced the induction and maturation of CD11c+ and CD8+CD11c+ dendritic cells (DCs), and expanded tumor-specific CD8+ T cell responses. CD8+ T cell depletion abolished the anti-tumor effects, underscoring the essential role of functional CD8+ T cell responses. Moreover, the combined treatment promoted memory CD8+ T cell induction, providing long-term protection. In liver orthotopic tumor models, the combination of pGPC3 vaccine and alisertib demonstrated potent therapeutic efficacy through CD8+ T cell responses. These results indicate that alisertib enhances the pGPC3 vaccine's therapeutic effect, offering a promising strategy for HCC treatment.

PMID:40230537 | PMC:PMC11995041 | DOI:10.1016/j.isci.2025.112120

iScience. 2025 Mar 13;28(4):112221. doi: 10.1016/j.isci.2025.112221. eCollection 2025 Apr 18.

ABSTRACT

Here, we aim to improve our understanding of various colorectal cancer (CRC) risk factors (obesity, unhealthy diet, and gut microbiota/metabolome alteration), analyzing 120 patients with colon polyps, divided in normal-weight (NW) or overweight/obese (OB). Dietary habits data (validated EPIC questionnaires) revealed a higher consumption of processed meat among OB vs. NW patients. Both mucosa-associated microbiota (MAM) on polyps and lumen-associated microbiota (LAM) analyses uncovered distinct bacterial signatures in the two groups. Importantly, we found an enrichment of the pathogenic species Finegoldia magna in MAM of OB patients, regardless of their polyp stage. We observed distinct mucosal-associated metabolome signatures, with OB patients showing increased pyroglutamic acid and reduced niacin levels, and performed microbiota-metabolome integrated analysis. These findings support a model where different risk factors may contribute to tumorigenesis in OB vs. NW patients, highlighting the potential impact of processed meat consumption and F. magna on CRC development among OB patients.

PMID:40230532 | PMC:PMC11995084 | DOI:10.1016/j.isci.2025.112221

ACS Synth Biol. 2025 Apr 15. doi: 10.1021/acssynbio.4c00780. Online ahead of print.

ABSTRACT

The subunit dissociation of oligomeric enzymes is a major challenge that limits their practical applications. In this study, yeast-surface-displayed tetrameric β-glucuronidase with a C-terminal anchor protein fusion was found partially dissociated into dimers. The coexpression of free and anchored subunits significantly improved the display efficiency and catalytic activity. Given that oligomeric enzymes may adopt a non-native conformation on the cell surface, the subunit interfaces of surface-displayed β-glucuronidase were in situ characterized using a Förster resonance energy transfer (FRET) strategy, and the tetrameric structure was well maintained in the coexpressed β-glucuronidases. Finally, the coexpression strategy was applied to yeast-surface-displayed oligomeric cellulases, significantly enhancing the activities of tetrameric endoglucanase and dimeric β-glucosidase and the concentration of cellulosic ethanol for the two-enzyme codisplaying strain. This work provides insights into the structure-activity relationship and the efficient utilization of surface-displayed oligomeric enzymes.

PMID:40230192 | DOI:10.1021/acssynbio.4c00780

Mol Syst Biol. 2025 Apr 14. doi: 10.1038/s44320-025-00101-9. Online ahead of print.

NO ABSTRACT

PMID:40229558 | DOI:10.1038/s44320-025-00101-9

Commun Biol. 2025 Apr 15;8(1):609. doi: 10.1038/s42003-025-07810-9.

ABSTRACT

Early life gut microbiota is being increasingly recognized as a major contributor to short and/or long-term human health and diseases. However, little is known about these early-life events in the human microbiome of the lower respiratory tract. This study aims to investigate fungal and bacterial colonization in the lower airways over the first year of life by analyzing lung tissue from autopsied infants. The fungal and bacterial communities of lung tissue samples from 53 autopsied infants were characterized by Next-Generation Sequencing (NGS), based on universal PCR amplification of the ITS region and the 16S rRNA gene, respectively. Our study highlights a high degree of inter-individual variability in both fungal and bacterial communities inhabiting the infant lung. The lower respiratory tract microbiota is mainly composed of transient microorganisms that likely travel from the upper respiratory tract and do not establish permanent residence. However, it could also contain some genera identified as long-term inhabitants of the lung, which could potentially play a role in lung physiology or disease. At 3-4 months of age, important dynamic changes to the microbial community were observed, which might correspond to a transitional time period in the maturation of the lung microbiome. This timeframe represents a susceptibility period for the colonization of pathogens such as Pneumocystis. The asymptomatic colonization of Pneumocystis was associated with changes in the fungal and bacterial communities. These findings suggest that the period of 2-4 months of age is a "critical window" early in life. Pneumocystis jirovecii could be a potential pivotal ecological driver contributing to shifts in microbial equilibrium during the early-life lower airway microbiome assembly, and to the future health of children.

PMID:40229539 | DOI:10.1038/s42003-025-07810-9

NPJ Vaccines. 2025 Apr 14;10(1):69. doi: 10.1038/s41541-025-01103-2.

ABSTRACT

Correlates of protection (CoPs) for SARS-CoV-2 have yet to be sufficiently defined. This study uses the machine learning platform, SIMON, to accurately predict the immunological parameters that reduced clinical pathology or viral load following SARS-CoV-2 challenge in a cohort of 90 non-human primates. We found that anti-SARS-CoV-2 spike antibody and neutralising antibody titres were the best predictors of clinical protection and low viral load in the lung. Since antibodies to SARS-CoV-2 spike showed the greatest association with clinical protection and reduced viral load, we next used SIMON to investigate the immunological features that predict high antibody titres. It was found that a pre-immunisation response to seasonal beta-HCoVs and a high frequency of peripheral intermediate and non-classical monocytes predicted low SARS-CoV-2 spike IgG titres. In contrast, an elevated T cell response as measured by IFNγ ELISpot predicted high IgG titres. Additional predictors of clinical protection and low SARS-CoV-2 burden included a high abundance of peripheral T cells. In contrast, increased numbers of intermediate monocytes predicted clinical pathology and high viral burden in the throat. We also conclude that an immunisation strategy that minimises pathology post-challenge did not necessarily mediate viral control. This would be an important finding to take forward into the development of future vaccines aimed at limiting the transmission of SARS-CoV-2. These results contribute to SARS-CoV-2 CoP definition and shed light on the factors influencing the success of SARS-CoV-2 vaccination.

PMID:40229322 | DOI:10.1038/s41541-025-01103-2

Life Sci Alliance. 2025 Apr 14;8(7):e202503222. doi: 10.26508/lsa.202503222. Print 2025 Jul.

ABSTRACT

STAT5B is a vital transcription factor for lymphocytes. Here, the function of two STAT5B mutations from human T-cell leukemias: one substituting tyrosine 665 with phenylalanine (STAT5BY665F) and the other with histidine (STAT5BY665H), was interrogated. In silico modeling predicted divergent energetic effects on homodimerization with a range of pathogenicity. In primary T cells in vitro, STAT5BY665F showed gain-of-function, whereas STAT5BY665H demonstrated loss-of-function. Introducing the mutation into the mouse genome illustrated that the gain-of-function Stat5b Y665F mutation resulted in accumulation of CD8+ effector and memory and CD4+ regulatory T cells, altering CD8+/CD4+ ratios. In contrast, STAT5BY665H "knock-in" mice showed diminished CD8+ effector and memory and CD4+ regulatory T cells. In contrast to WT STAT5B, the STAT5BY665F variant displayed greater STAT5 phosphorylation, DNA binding, and transcriptional activity after cytokine activation, whereas the STAT5BY665H variant resembled a null. The work exemplifies how joining in silico and in vivo studies of single nucleotides deepens our understanding of disease-associated variants, revealing structural determinants of altered function, defining mechanistic roles, and, specifically here, identifying a gain-of-function variant that does not directly induce hematopoietic malignancy.

PMID:40228864 | DOI:10.26508/lsa.202503222

BMJ Open. 2025 Apr 14;15(4):e102029. doi: 10.1136/bmjopen-2025-102029.

ABSTRACT

INTRODUCTION: Myocardial protection against ischaemia-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, myocardial injury still occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. del Nido cardioplegia was designed to protect the immature myocardium and is widely used in the USA but has not previously been available in the UK, where St. Thomas' blood cardioplegia is most common. The del Nido versus St. Thomas' blood cardioplegia in the young (DESTINY) trial will evaluate whether one solution is better than the other at improving myocardial protection by reducing myocardial injury, shortening ischaemic time and improving clinical outcomes.

METHODS AND ANALYSIS: The DESTINY trial is a multicentre, patient-blinded and assessor-blinded, parallel-group, individually randomised controlled trial recruiting up to 220 children undergoing surgery for congenital heart disease. Participants will be randomised in a 1:1 ratio to either del Nido cardioplegia or St. Thomas' blood cardioplegia, with follow-up until 30 days following surgery. The primary outcome is area under the time-concentration curve for plasma high-sensitivity troponin I in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include the incidence of low cardiac output syndrome and Vasoactive-Inotropic Score in the first 48 hours, total aortic cross-clamp time, duration of mechanical ventilation and lengths of stay in the paediatric intensive care unit and the hospital.

ETHICS AND DISSEMINATION: The trial was approved by the West Midlands-Coventry and Warwickshire National Health Service Research Ethics Committee (21/WM/0149) on 30 June 2021. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a national charity.

TRIAL REGISTRATION NUMBER: ISRCTN13638147; Pre-results.

PMID:40228861 | DOI:10.1136/bmjopen-2025-102029

J Biotechnol. 2025 Apr 12:S0168-1656(25)00093-8. doi: 10.1016/j.jbiotec.2025.04.008. Online ahead of print.

ABSTRACT

Beta-ketoadipate (βKA) is an intermediate of the βKA pathway involved in the degradation of aromatic compounds in several bacteria and fungi. Beta-ketoadipate also represents a promising chemical for the manufacturing of performance-advantaged nylons. We established a strategy for the in planta synthesis of βKA via manipulation of the shikimate pathway and the expression of bacterial enzymes from the βKA pathway. Using Nicotiana benthamiana as a transient expression system, we demonstrated the efficient conversion of protocatechuate (PCA) to βKA when plastid-targeted bacterial-derived PCA 3,4-dioxygenase (PcaHG) and 3-carboxy-cis,cis-muconate cycloisomerase (PcaB) were co-expressed with 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (AroG) and 3-dehydroshikimate dehydratase (QsuB). This metabolic pathway was reconstituted in Arabidopsis by introducing a construct (pAtβKA) with stacked pcaG, pcaH, and pcaB genes into a PCA-overproducing genetic background that expresses AroG and QsuB (referred as QsuB-2). The resulting QsuB-2 x pAtβKA stable lines displayed βKA titers as high as 0.25% on a dry weight basis in stems, along with a drastic reduction in lignin content and improvement of biomass saccharification efficiency compared to wild-type controls, and without any significant reduction in biomass yields. Using biomass sorghum as a potential crop for large-scale βKA production, techno-economic analysis indicated that βKA accumulated at titers of 0.25% and 4% on a dry weight basis could be competitively priced in the range of $2.04-34.49/kg and $0.47-2.12/kg, respectively, depending on the selling price of the residual biomass recovered after βKA extraction. This study lays the foundation for a more environmentally-friendly synthesis of βKA using plants as production hosts.

PMID:40228630 | DOI:10.1016/j.jbiotec.2025.04.008

J Phys Chem B. 2025 Apr 14. doi: 10.1021/acs.jpcb.4c08792. Online ahead of print.

ABSTRACT

A classical problem in colloidal physics is the behavior of a spherical particle when it randomly walks close to the interface between a fluid and a rigid wall. Solutions to the two complementary aspects of this problem have been provided by Faxén and Brenner, respectively, based on continuum mechanics. Their results predict that the closer the particle is to the interface the slower it moves, but the pace of the slow-down depends on whether the particle steps parallel with or perpendicular to the interface; that is, the particle's diffusivity divaricates in a distance- and direction-dependent manner. While the theoretical predictions enjoy unequivocal experimental supports for μm-sized particles, their applicability on the smaller length scales remains unclear, however. Here we present the first direct experimental test for the complete Faxén-Brenner solutions on the nanoscale. Our experiment was enabled by a new multiresolution instrument which concurrently and synchronously recorded both the high-resolution lifetime-gated μs 3D tracking of a single diffusing nanoparticle for nanoscale diffusivity and the lower-resolution two-photon laser-scanning microscopy images for the nanoparticle's location relative to the wall interface. The directional diffusivity divarication predicted by Faxén and Brenner was reproduced on the single-nanoparticle level with no adjustable parameters. Our results thus provided experimental supports for the underlying fluid-dynamics physical picture down to ∼ 65 nm, the radius of the nanoparticle sample used in this work, and pointed to next experimental challenges being in the sub-100 nm regime where finite-temperature fluctuations and the molecularity of the fluid are expected to become increasingly noticeable for smaller nanoparticles.

PMID:40228157 | DOI:10.1021/acs.jpcb.4c08792

Biomacromolecules. 2025 Apr 14. doi: 10.1021/acs.biomac.4c01505. Online ahead of print.

ABSTRACT

Trehalose has sparked considerable interest in a variety of pharmaceutical applications as well as in cryopreservation. Recently, there have been growing efforts in the development of trehalose delivery nanocarriers to address the issue of the poor bioavailability of trehalose. The majority of the strategies comprise physical entrapment of trehalose, since its covalent, yet biolabile, conjugation is challenging. Here, we present research on trehalose-releasing nanogels, in which covalent, yet biolabile, conjugation of trehalose was achieved through the co-incorporation of trehalose (meth)acrylate(s) together with hydrophilic primary/secondary acrylamides in one polymeric network. In this case, the primary and secondary amide groups participated in ester hydrolysis in the (meth)acrylate units, making the hydrolysis feasible under physiologically relevant conditions. A set of nanogels with precisely selected compositions were synthesized, characterized, and then studied to evaluate the influence of various structural and environmental factors on the release rate of trehalose. The study also provides insights into some other aspects that are important in view of potential biomedical applications, including specific interactions of nanogels through their terminal α-d-glucopyranosyl moieties from pendant trehalose, protein corona formation, and cellular uptake.

PMID:40228144 | DOI:10.1021/acs.biomac.4c01505

Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2504470122. doi: 10.1073/pnas.2504470122. Epub 2025 Apr 14.

NO ABSTRACT

PMID:40228138 | DOI:10.1073/pnas.2504470122

Proc Natl Acad Sci U S A. 2025 Apr 22;122(16):e2426385122. doi: 10.1073/pnas.2426385122. Epub 2025 Apr 14.

ABSTRACT

Insights into the molecular processes that drive early development of the human placenta is crucial for our understanding of pregnancy complications such as preeclampsia and fetal growth restriction, since defects in maturation of its epithelial cell, the trophoblast, have been detected in the severe forms of these diseases. However, key regulators specifying the differentiated trophoblast subtypes of the placenta are only slowly emerging. By using diverse trophoblast cell models, we herein show that the transcriptional coactivator of HIPPO signaling, TAZ, plays a pivotal role in the development of invasive extravillous trophoblasts (EVTs), cells that are essential for decidual vessel remodeling and adaption of maternal blood flow to the placenta. Ribonucleic acid sequencing (RNA-seq) or protein analyses upon TAZ gene silencing or CRISPR-Cas9-mediated knockout in differentiating trophoblast stem cells, organoids, primary EVTs, choriocarcinoma cells, or villous explant cultures unraveled that the coactivator promoted expression of genes associated with EVT identity, motility, and survival. Accordingly, depletion or chemical inhibition of TAZ, interacting with TEA domain family member 1 (TEAD1), impaired EVT differentiation, invasion, and migration and triggered apoptosis in the different trophoblast models. Notably, the coactivator also suppressed cell cycle genes and regulators of trophoblast self-renewal and prevented EVTs from cell fusion in organoids and primary cultures. Moreover, TAZ promoted human leukocyte antigen G (HLA-G) surface expression and increased NUAK1 kinase in EVTs thereby maintaining its own expression. In summary, the transcriptional coactivator TAZ plays a multifaceted role in the development of the EVT cell lineage by controlling different biological processes that initiate and preserve differentiation.

PMID:40228123 | DOI:10.1073/pnas.2426385122

J Mol Neurosci. 2025 Apr 14;75(2):49. doi: 10.1007/s12031-025-02331-w.

ABSTRACT

Multiple sclerosis (MS), an autoimmune condition of the central nervous system (CNS), can lead to demyelination and axonal degeneration in the brain and spinal cord, which can cause progressive neurologic disability. MS symptoms include dysautonomia and progressive decline in motor abilities. In this investigation, we performed an integrated bioinformatics and experimental approach to find the expression level and interaction of a novel long non-coding RNA (lncRNA), PAN3-AS1, in MS samples. Microarray analysis was performed by R Studio using GEOquery and limma packages. lncRNA-mRNA RNA interaction analysis was performed using the lncRRIsearch database. Pathway enrichment analysis was performed by KEGG and Reactome online software through the Enrichr database. Protein-protein interaction analysis was performed by STRING online software. Gene ontology (GO) analysis was performed by Enrichr database. Based on microarray analysis, lncRNA PAN3-AS1 has a significantly low expression in MS samples compared to the control (logFC - 1.2, adj. P. Val 0.03). qRT-PCR results approved bioinformatics analyses. ROC analysis revealed that PAN3-AS1 could be considered a potential diagnostic biomarker of MS. Based on lncRNA-mRNA interaction analysis, lncRNA PAN3-AS1 regulates the expression level of RPGR. RPGR and its protein interactome regulate the cilium assembly, chaperon-mediated autophagy, and microarray biogenesis. lncRNA PAN3-AS1, as a significant low-expressed lncRNA in MS samples, could be a potential diagnostic MS biomarker. PAN3-AS1 might regulate the expression level of cilium assembly and chaperon-mediated autophagy. Dysregulation of PAN3-AS1 might affect the expression of RPGR and its protein interactome.

PMID:40227518 | DOI:10.1007/s12031-025-02331-w