Chronic psychological stress is a major cause of various psychiatric disorders, such as depression and anxiety; however, the pathophysiological features of these disorders remain largely unknown. Polysialic acid (PSA), a linear homopolymer of α2-8-linked sialic acid residues, binds to the neural cell adhesion molecule (NCAM) and is involved in cell-to-cell interactions during neural cell migration and neurite outgrowth. Decreased PSA and PSA-NCAM expression have been observed in the brains of patients with psychiatric disorders. Nevertheless, the relationship between psychological stress and PSA has not been clarified. Thus, we examined whether chronic social defeat stress (cSDS), a well-established psychosocial stress model in rodents, affects PSA levels in the male mouse brain. Male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days, after which their whole brains were collected. PSA and NCAM protein levels in the hippocampus and prefrontal cortex were analyzed by western blotting. In addition, we measured the expression of genes involved in PSA metabolism by real-time quantitative PCR analysis. Exposure to cSDS decreased PSA and NCAM protein levels in the hippocampus, but not in the prefrontal cortex. We also found that the expression of genes involved in removing sialic acid from NCAM, such as neuraminidase 3 and 4, was significantly elevated in the hippocampus of mice exposed to cSDS. We provide evidence showing that psychosocial stress disrupts PSA metabolism in adult mice brains. These findings advance our understanding of the mechanisms underlying the onset of stress-related psychiatric disorders.

Severe traumatic brain injury includes neurovascular unit (NVU) damage that is linked to the later development of neurodegenerative diseases. Cell-type-specific contributions and crosstalk between cells of the neurovascular unit following brain injury remain poorly defined in human cells. Here, we developed a three-dimensional (3D) human NVU model using silk–collagen scaffolds to examine cellular responses to controlled cortical impact (CCI). Using this platform, we show that CCI induced acute cell death in astrocytes, microglia, and endothelial cells but spared pericytes, which occurred independently of classical apoptotic or necroptotic pathways. Astrocytes and microglia were the primary sources of early bioactive IL-1β release, while endothelial junctional integrity was differentially regulated by support cells: astrocytes destabilized VE-cadherin, pericytes preserved barrier proteins, and microglia contributed to Claudin-5 loss in multicellular settings. Conditioned media experiments demonstrated that soluble factors from injured support cells alone were sufficient to disrupt endothelial junctional proteins (ZO-1 and Occludin) and induce inflammatory adhesion molecules (ICAM-1 and VCAM-1). Together, these findings define cell-type-specific injury responses and reveal how NVU interactions regulate vascular dysfunction after trauma, providing a human-based framework for understanding blood–brain barrier (BBB) disruption following traumatic brain injury (TBI).

Monocyte exhaustion is a dysfunctional state characterized by prolonged pathogenic inflammation and immune suppression, commonly observed in chronic infections and sepsis. However, the mechanisms underlying the generation and propagation of exhausted monocytes remain poorly understood. In this study, we investigate the impacts of exhausted monocytes on neighboring naïve monocytes, endothelial cells, and T cell function. Using an in vitro co-culture system, we demonstrate that exhausted monocytes induced by prolonged LPS stimulation propagate the exhaustion phenotype to neighboring naïve monocytes. Meanwhile these exhausted monocytes can promote endothelial apoptosis, upregulate adhesion molecules ICAM-1 and VCAM-1, and enhance monocyte transmigration, contributing to endothelial dysfunction. Pharmacological inhibition of CD38, a key marker of monocyte exhaustion, significantly mitigates these effects, highlighting its critical role in monocyte-driven endothelial alterations. Furthermore, we show that exhausted monocytes suppress T cell proliferation and activation, a process reversed by CD38 inhibition. We also identify mTOR signaling as a key regulator of monocyte exhaustion and its propagation, with mTOR inhibition partially restoring monocyte functionality by downregulating exhaustion markers and STAT1/STAT3/S6K signaling. Collectively, our findings highlight the CD38-mTOR axis as a central driver of monocyte exhaustion and its pathological consequences, offering potential therapeutic targets for reversing immune dysfunction in inflammatory diseases.

BRCA1 (breast cancer 1, early onset) is originally identified as a tumor suppressor in hereditary breast and ovarian cancer. Recent studies have suggested that BRCA1 contributes to the cell fate decisions in mammary epithelium. Although BRCA1 has been shown to be expressed in the thymus, its physiologic role(s) in the thymus remain unclear. In this study, we found that BRCA1 was expressed in a subset of thymic medullary epithelial cells: epithelial cell adhesion molecule (EpCAM, CD326) positive, UEA-1 ligand positive, and Aire negative. To clarify its functional significance, we analyzed the differentiation of thymic epithelial cells in mice in which BRCA1 was specifically deleted in K14-expressing cells. Interestingly, conditional BRCA1-deficient mice displayed enhanced development of Hassall’s corpuscles. Notably, thymoproteasome catalytic subunit β5t (proteasome subunit beta 11), a marker of cortical thymic epithelial cells (cTECs), was frequently detected adjacent to Hassall’s corpuscles in BRCA1 knockout mice. In addition, medullary β5t+ cells appeared to differentiate into cTECs. In addition, BRCA1 deficiency led to increased generation of regulatory T cells. Thus, BRCA1 was also found to regulate epithelial differentiation in the thymus. Our observations in BRCA1-deficient mice may be relevant to understanding the immune system in human with BRCA1 germline mutations.

ObjectiveA cardiovascular safety issue has been associated with JAK inhibitors (JAKi). This study compares the effects of distinct approved JAKi on endothelial cell (EC) dysfunction and apoptosis during inflammation.MethodsMassive inflammation was induced in human vascular ECs by tumor necrosis factor (TNF) with interleukin‐17A (IL‐17A) treated or not treated with tofacitinib, baricitinib, upadacitinib, peficitinib, ruxolitinib, and fedratinib at 1 or 10 μM. Levels of IL‐6 and IL‐8 were measured by enzyme‐linked immunosorbent assay. Variations in gene expression of adhesion molecules and factors of blood coagulation and fibrinolysis pathways were quantified by quantitative reverse transcriptase–polymerase chain reaction. Endothelial apoptosis was measured by Annexin V staining.ResultsAll JAKi decreased IL‐6 release of ECs stimulated with TNF+IL‐17A. In contrast, only baricitinib and fedratinib decreased IL‐8 overproduction, from 1 μM. Fedratinib decreased the up‐regulation of vascular adhesion molecule 1 (VCAM‐1) and E‐selectin expression at 1 and 10 μM. Tofacitinib reduced intercellular adhesion molecule 1 (ICAM‐1) and E‐selectin induction at 1 μM. However, at 10 μM, tofacitinib, baricitinib, upadacitinib, peficitinib, and ruxolitinib enhanced induction of VCAM‐1 and ICAM‐1 triggered by TNF+IL‐17A. Peficitinib and fedratinib at 1 and 10 μM decreased tissue factor up‐regulation induced by TNF+IL‐17A, whereas ruxolitinib was effective only at 1 μM. None of the JAKi could prevent the down‐regulation of the anticoagulant molecule thrombomodulin. Fedratinib and peficitinib were both proapoptotic and cytotoxic for ECs.ConclusionAll JAKi reduced EC inflammation but most JAKi could not prevent the up‐regulation of adhesion molecules or the increase in procoagulant and the decrease in anticoagulant factors triggered by proinflammatory cytokines. Peficitinib and fedratinib exhibited cytotoxic effects causing EC apoptosis.

SOX (SRY-related HMG-box) transcription factors are key regulators of embryogenesis and vascular development, with emerging roles in cancer biology. In non-small-cell lung cancer (NSCLC), the contributions of SOX18 and SOX30 remain insufficiently understood, particularly regarding their epigenetic regulation and network interactions with angiogenic and immune-modulatory pathways. We examined 800 NSCLC specimens (400 lung adenocarcinomas, 400 squamous cell carcinomas) using immunohistochemistry, RT-qPCR, Western blotting, and spatial transcriptomics to profile SOX18, SOX30, and related signaling partners (SOX7, SOX17, MEF2C—Myocyte Enhancer Factor 2C, VCAM1—Vascular Cell Adhesion Molecule 1, p-STAT3—Signal Transducer and Activator of Transcription 3). Epigenetic regulation was assessed via droplet digital methylation-specific PCR of promoter CpG islands, while functional validation employed adenoviral delivery of hsa-miR-24-3p in NSCLC cell lines and 3D spheroid cultures. SOX18 protein was markedly overexpressed in both NSCLC subtypes, despite reduced transcript levels and consistent promoter hypermethylation, suggesting post-transcriptional regulation. In contrast, SOX30 expression was uniformly downregulated at both mRNA and protein levels, frequently linked to promoter hypermethylation, especially in squamous carcinoma. Spatial transcriptomics revealed SOX18 enrichment at tumor cores and invasive borders, co-localizing with MEF2C, VCAM1, and p-STAT3 in vascular and stromal niches, while SOX30 expression remained low across all tumor regions. Functional assays demonstrated that hsa-miR-24-3p suppressed SOX18 expression and partially modulated SOX30 and MEF2C, reinforcing a miRNA-driven regulatory axis. In summary, SOX18 and SOX30 play divergent roles in NSCLC progression: SOX18 functions as a pro-oncogenic factor driving angiogenesis and tumor–stroma interactions, while SOX30 acts as an epigenetically silenced tumor suppressor. Regulation of SOX18 by miR-24-3p highlights a potential therapeutic vulnerability. These findings underscore the significance of SOX transcription factors as biomarkers and potential targets for novel treatment strategies in NSCLC.

Epicardial adipose tissue (EAT) regulates lipid metabolism and immune cell recruitment in coronary arteries. Increased EAT contributes to coronary artery disease (CAD), but exercise prevents CAD. We hypothesized that exercise, irrespective of CAD presence, would produce EAT with increased M2 macrophages and upregulation of anti-inflammatory cytokine transcripts. Female Yucatan pigs (n = 7) were sedentary or exercised, and the left circumflex coronary artery was occluded or remained nonoccluded (2 × 2 design). Bulk and single-nuclei transcriptomic sequencing performed on EAT identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs predominant. Nonoccluded (N) sedentary (Sed) EAT had the most M1 macrophages and CD8+ T cells. Sed EAT had the most cells expressing tumor necrosis factor (TNF) superfamily genes. Exercise (Ex) upregulated peroxisome proliferator-activated receptor (PPAR) γ (G) expression and enriched PPAR signaling, which suppresses activation, in macrophages and T cells, particularly in occluded (O) Ex EAT. By contrast, N_Ex EAT had few CD8+ T cells with low PPARG expression. Adipocytes and immune cells in O_Sed EAT had the most communication via growth factors and adhesion molecules. Exercise mitigates EAT inflammation via modulation of immune cell subpopulations, decreased TNF superfamily, and increased PPARG gene expression, and decreased communication between adipocytes and immune cells. However, the effect of exercise on the EAT immune environment is modulated by coronary artery occlusion status. Future studies of the impact of exercise and coronary artery occlusion on EAT would benefit from using a progressive nutritionally induced model of CAD.NEW & NOTEWORTHY A sedentary lifestyle increases the number of inflammatory M1 macrophages and CD8+ T cells, their expression of tumor necrosis factor genes, and the number of communications between these immune cells and adipocytes in epicardial adipose tissue (EAT). The expression of peroxisome proliferator receptor and genes in control of cell activation in macrophages and T cells in nonoccluded and occluded EAT increases in response to exercise.

Endothelial CD40L serves as a pro-atherogenic adhesion receptor in the inflamed vasculature.

Reproductive tissue toxicity of deoxynivalenol and α-zearalenol alone or in combination: Insights from a porcine explant model.

Boosted breast cancer treatment with cell membrane-coated PLGA nanocarriers: Investigating the interactions with various cell types.

Mitsugumin 53 improves myocardial ischemia-reperfusion injury by promoting iPSCs survival through regulating AnxA6 axis.

Microplastic exposure induces structural hyperplasia in the gill tissue of grass carp (Ctenopharyngodon idellus) through immunosuppression, metabolic disruption, and structural damage.

Targeting cadherins with colicins: Molecular docking and dynamics reveal disruptive potential in cancer metastasis.

Colorectal cancer (CRC) is a common gastrointestinal tumor with a high incidence worldwide. L1 cell adhesion molecule (L1CAM) is highly expressed in CRC tissues and can promote tumor growth and metastasis. Autophagy regulates oncogenesis and tumor progression through context-dependent mechanisms and is regulated by multiple signaling pathways, including the p38 MAPK signaling pathway. However, the relationship between L1CAM and autophagy is not known yet. In this study, we are trying to dissect the role of L1CAM-autophagy interaction in the development and progression of CRC and its underlying mechanism. Stable L1CAM knockdown was achieved in SW480 and HT29 cells via lentiviral transduction of specific shRNAs. Autophagic flux was detected using western blotting and Tandem mRFP-GFP-LC3 assay. The protein levels were measured via western blotting. Cell proliferation was tested via CCK-8 proliferation assay and Edu staining. Apoptosis was evaluated using flow cytometry. We found that upon L1CAM knockdown, the phosphorylation of p38 was enhanced, and autophagy was weakened. When p38 phosphorylation was inhibited, the inhibitory effect of L1CAM knockdown on autophagy was restored. And L1CAM can promote cell proliferation and inhibit cell apoptosis. Taken together, these findings indicate that L1CAM promotes autophagy by inhibiting the phosphorylation of p38, and that it also promotes cell proliferation and inhibits cell apoptosis in colon cancer cells. L1CAM might be as a new target in CRC therapy.

Cannabinoid effective targeting of atherosclerotic plaquesin vivoby optimized-PLGA nanoparticles.

Clinicopathological implications of EpCAM immunoexpression in canine gastric carcinoma and its association with other immunomarkers.

For neurons to establish the correct connections in animal nervous systems, interactions between cell adhesion molecules (CAMs), expressed presynaptically and postsynaptically, are thought to guide neurons to their targets. Here, we assess the role that affinity between two cognate CAMs-DIP-α and Dpr10-plays in establishing the leg neuromuscular system in Drosophila If affinity decreases or, surprisingly, increases past certain thresholds, motor neuron (MN) terminal branches fail to be maintained. Live imaging during development shows that when affinities are aberrant, MN filopodia are unable to productively engage their muscle targets. Thus, CAM affinities are tuned to achieve proper neuronal morphology.

Constructing an in situ biomimetic basement membrane within tumor tissue to disrupt intercellular adhesion molecule communication and prevent metastasis in TNBC

Single-nucleotide polymorphisms (SNPs) in sperm adhesion molecule 1 (SPAM1) gene are associated with egg production in Yangzhou geese

Long COVID is associated with female sex; Anti-NCAM1 autoantibodies are absent in patients with long COVID.