Search Results (2,319)

Background: This narrative review summarizes recent progress in artificial intelligence (AI), especially radiomics and deep learning, for non-invasive diagnosis and molecular profiling of gliomas. Methodology: A thorough literature search was conducted on PubMed, Scopus, and Embase for studies published from January 2020 to July 2025, focusing on clinical and technical research. In key areas, these studies examine AI models’ predictive capabilities with multi-parametric Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Results: The domains identified in the literature include the advancement of radiomic models for tumor grading and biomarker prediction, such as Isocitrate Dehydrogenase (IDH) mutation, O6-methylguanine-dna methyltransferase (MGMT) promoter methylation, and 1p/19q codeletion. The growing use of convolutional neural networks (CNNs) and generative adversarial networks (GANs) in tumor segmentation, classification, and prognosis was also a significant topic discussed in the literature. Deep learning (DL) methods are evaluated against traditional radiomics regarding feature extraction, scalability, and robustness to imaging protocol differences across institutions. Conclusions: This review analyzes emerging efforts to combine clinical, imaging, and histology data within hybrid or transformer-based AI systems to enhance diagnostic accuracy. Significant findings include the application of DL to predict cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion and chemokine CCL2 expression. These highlight the expanding capabilities of imaging-based genomic inference and the importance of clinical data in multimodal fusion. Challenges such as data harmonization, model interpretability, and external validation still need to be addressed. Full article

Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with subtypes ranging from patchy alopecia (AAP) to alopecia totalis and universalis (AT/AU). The aim of this research is to investigate molecular features across AA severity by performing an integrated analysis of scalp transcriptomic datasets (GSE148346, GSE68801, GSE45512, GSE111061) and matched serum proteomic data from GSE148346. Differential expression analysis indicated that, relative to normal scalp, non-lesional AA tissue shows early immune activation—including Type 1 (C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CD8a molecule (CD8A), C-C motif chemokine ligand 5 (CCL5)) and Type 2 (CCL13, CCL18) signatures—together with reduced expression of hair-follicle structural genes (keratin 32(KRT32)–35, homeobox C13 (HOXC13)) (FDR < 0.05, |fold change| > 1.5). Lesional AAP and AT/AU scalp showed stronger pro-inflammatory upregulation and greater loss of keratins and keratin-associated proteins (KRT81, KRT83, desmoglein 4 (DSG4), KRTAP12/15) compared with non-lesional scalp (FDR < 0.05, |fold change| > 1.5). Ferroptosis-associated genes (cAMP responsive element binding protein 5 (CREB5), solute carrier family 40 member 1 (SLC40A1), (lipocalin 2) LCN2, SLC7A11) and IRS (inner root sheath) differentiation genes (KRT25, KRT27, KRT28, KRT71–KRT75, KRT81, KRT83, KRT85–86, trichohyalin (TCHH)) were consistently repressed across subtypes, with the strongest reductions in AT/AU lesions versus AAP lesions, suggesting that oxidative-stress pathways and follicular structural integrity may contribute to subtype-specific pathology. Pathway analysis of lesional versus non-lesional scalp highlighted enrichment of IFN-α/γ, cytotoxic, and IL-15 signaling. Serum proteomic profiling, contrasting AA vs. healthy controls, corroborated scalp findings, revealing parallel alterations in immune-related proteins (CXCL9–CXCL10, CD163, interleukin-16 (IL16)) and structural markers (angiopoietin 1 (ANGPT1), decorin (DCN), chitinase-3-like protein 1 (CHI3L1)) across AA subtypes. Together, these data offer an integrated view of immune, oxidative, and structural changes in AA and found ferroptosis-related and IRS genes, along with immune signatures, as potential molecular indicators to support future studies on disease subtypes and therapeutic strategies. Full article

Therapy with chimeric antigen receptor (CAR)-T cells has revolutionized the treatment of hematological malignancies. However, their application in solid tumors remains a formidable challenge due to obstacles such as the immunosuppressive tumor microenvironment, tumor heterogeneity, and limited T cell persistence. Although second- and third-generation CAR-T cells have shown restricted efficacy in clinical trials, next-generation strategies—including cytokine-armored CAR-T cells (e.g., IL-15, IL-7/CCL19), logic-gated systems, and localized delivery approaches—demonstrate promising potential to overcome these limitations. This review examines the major barriers impeding CAR-T cell efficacy in solid tumors, evaluates clinical outcomes from conventional CAR constructs, and highlights innovative strategies being tested in recent clinical trials. Key advances discussed include the use of dominant-negative receptors (e.g., TGFβRII) to combat immunosuppression and the co-expression of bispecific T cell engagers (BiTEs) to address antigen escape. Full article

The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, particularly at the level of specific ovarian cell types, remain poorly understood in equids. Here, we constructed a single-cell transcriptomic atlas to investigate ovarian changes in Kazakh horses. Using single-cell RNA sequencing (scRNA-seq), we profiled 112,861 cells from follicle-containing and follicle-absent ovaries, identifying nine distinct ovarian cell types and their subtypes, each with distinct gene expression signatures. Functional enrichment analyses revealed cell type-specific engagement in biological pathways, including ECM–receptor interaction, PI3K-Akt signaling, and oxytocin signaling. Gene expression patterns indicated tightly regulated processes of ovarian activation and cell differentiation. Notably, stromal cells exhibited high expression of ROBO2, LOC111770199, and TMTC2, while smooth muscle cells (SMCs) were marked by elevated levels of CCL5, KLRD1, and NKG7. Moreover, cell–cell interaction analyses revealed robust signaling interactions among SMCs, endothelial cells, neurons, and proliferating (cycling) cells. Together, these findings provide a comprehensive single-cell transcriptomic map of normal and abnormal ovarian states during estrus in Kazakh horses, offering novel insights into the cellular mechanisms of follicular development and identifying potential diagnostic biomarkers and therapeutic targets for ovarian quiescence in equids. Full article

Mesenchymal stem cells (MSCs) are known to assist liver regeneration. In this study, we show a dose-dependent mode of recovery from liver fibrosis after intravenous injections of MSCs. Male Wistar rats experienced a 42-day-long modeling of liver fibrosis via CCl₄ poisoning and received either a single injection of 2.5 × 10⁶ MSCs on Day 3 after the last CCl₄ dose or two MSC injections on Days 3 and 10. We dynamically monitored levels of liver cytolysis markers and cytokines in the venous blood and performed a histological study of Mallory-stained liver sections. All experimental groups experienced a nearly complete recovery of biochemical markers up to 4 weeks after the end of CCl₄ administration, although we observed anti-inflammatory changes in the cytokine levels only in animals treated by two MSC injections. Histological study revealed minor signs of liver damage up to Day 90 in animals receiving two MSC doses with worse pathology in those who received a single MSC dose. Morphometric values stayed consistent with visual data, demonstrating a significantly larger number of binuclear hepatocytes, a smaller number of false lobules, and a lesser area of connective tissue proper in animals treated by two MSC injections. Our results reflect MSC grafting in applied doses to affect liver fibrosis in a dose-dependent mode. These findings provide a deeper understanding of MSC action in liver fibrosis, and the doses applied may serve as a milestone for further studies in humans. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that poses an increasing burden on society. It is characterized by the presence of neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques. AD is a multifactorial disease, with one of the strongest genetic risk factors being the APOE4 allele. In this study, we investigated the impact of APOE4 on NF-κB signaling in induced pluripotent stem (iPS) cells. Our results indicate that APOE4 may influence the subcellular localization of the pluripotency marker OCT4, showing a predominantly nuclear localization in APOE4 cells, whereas it appears cytoplasmic in APOE3 cells. Additionally, NF-κB activation via its canonical subunits is blunted in APOE4 cells. Interestingly, APOE4 cells still exhibit increased transcription of key hyperinflammatory markers CCL2, CXCL10 and COX2, which are known NF-κB target genes, and exhibit a significantly higher rate of apoptosis compared to APOE3 cells—independent of TNF-α stimulation. Moreover, an elevated incidence of DNA double-strand breaks was observed in APOE4 cells. However, the precise molecular mechanisms by which APOE4 suppresses NF-κB activation while simultaneously promoting inflammation and apoptosis remain unclear. Further research is required to elucidate these underlying pathways. Full article

Smartphone-based strain monitoring of structural components is an emerging approach to structural health monitoring. However, the existing techniques suffer from limited accuracy and poor cross-device adaptability. This study aims to optimize the smartphone-based Micro Image Strain Sensing (MISS) method by replacing the traditional Connected Component Labeling (CCL) algorithm with the arc-support line segments (ASLS) algorithm, thereby significantly enhancing the stability and adaptability of circle detection in micro-images captured by diverse smartphones. Additionally, this study evaluates the impact of lighting conditions and lens distortion on the optimized MISS method. The experimental results demonstrate that the ASLS algorithm outperforms CCL in terms of recognition accuracy (maximum error of 0.94%) and cross-device adaptability, exhibiting greater robustness against color temperature and focal length variations. Under fluctuating lighting conditions, the strain measurement noise remains within ±0.5 με and with a maximum error of 7.0 με compared to LVDT measurements, indicating the strong adaptability of the optimized MISS method to external light changes. Barrel distortion in microscopic images induces a maximum pixel error of 5.66%, yet the final optimized MISS method achieves highly accurate strain measurements. The optimized MISS method significantly improves measurement stability and engineering applicability, enabling effective large-scale implementation for strain monitoring of civil infrastructure. Full article

Rheumatoid arthritis synovial fibroblasts (RASFs) play a pivotal role in joint destruction in RA. Myostatin (MSTN), a myokine, is highly expressed in the RA synovium; however, its role in the function of RASFs is unclear. We hypothesized that MSTN amplifies inflammatory cytokines/chemokines, promotes RASF invasion, and facilitates CD4⁺ Th cell transmigration. Immortalized MH7A cells (RASFs) and healthy synovial fibroblasts (HSFs) were treated with MSTN (0, 10, 20 ng/mL) for 0, 24, and 48 h. Cytokines (IL-8, IL-17, TNF-α, IL-6, IL-23, IFN-γ, IFN-β) and chemokines (CCL2, CCL20, CXCL13, CXCL1) were quantified by ELISA, RT-qPCR, and Western blotting. To evaluate MSTN regulation, cells were treated with pro-inflammatory mediators (TNF-α, IL-17, IFN-γ, IFN-β, CCL2, CXCL1). MSTN’s effects on Thy-1(CD90)⁺ RASF/HSF proliferation, RASF invasion, and CD4⁺ T-cell transmigration were assessed. Compared with HSFs, RASFs exhibited greater proliferative activity. MSTN significantly upregulated cytokines/chemokines, with CXCL1 showing the strongest induction in RASFs. IFN-γ and IL-17 robustly increased MSTN expression, indicating a feed-forward loop. MSTN did not alter Thy-1(CD90)⁺ fibroblast proliferation but significantly enhanced RASF invasion and CD4⁺ T-cell transmigration. Neutralizing CXCL1 or IL-17 reduced transmigration, with stronger inhibition via CXCL1. These findings offer new insights into the role of MSTN in RA pathogenesis and highlight its potential as a therapeutic target. Full article

Glioblastoma (GBM) is an aggressive brain tumor with a highly immunosuppressive microenvironment that promotes tumor progression and therapy resistance. Tumor-associated macrophages (TAMs), comprising up to 50% of the tumor mass, are recruited via chemokine axes such as CCL2/CCR2, CX3CL1/CX3CR1, and CXCL12/CXCR4 and adopt an M2-like immunosuppressive phenotype, facilitating immune escape and angiogenesis. Key signaling pathways, including CSF1R, STAT3, NF-κB, PI3K/Akt, and HIF-1α, regulate TAM function, making them promising therapeutic targets. Strategies such as TAM depletion, reprogramming, and immune checkpoint blockade (PD-1/PD-L1, and CD47-SIRPα) have shown potential in preclinical models. Emerging approaches, including CAR-macrophage (CAR-M) therapy, nanotechnology-based drug delivery, and exosome-mediated modulation, offer new avenues for intervention. However, clinical translation remains challenging due to GBM’s heterogeneity and adaptive resistance mechanisms. Future research should integrate multi-omics profiling and AI-driven drug discovery to refine TAM-targeted therapies and improve patient outcomes. This review provides a comprehensive analysis of TAM-mediated immune regulation in GBM and explores evolving therapeutic strategies aimed at overcoming its treatment barriers. Full article

Electroacupuncture (EA) has shown analgesic potential for neuropathic pain, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether EA relieves neuropathic pain by modulating CCL2/CCR2 signaling and microglial activation in the spinal cord. Neuropathic pain was induced in rats by L5 spinal nerve ligation. EA was administered at acupoints ST36 and GB34 (1 mA, 2 Hz, 30 min) daily from postoperative days 3 to 7. Rats were assigned to anesthetized control (ANE), non-acupoint stimulation (NAP), and acupoint stimulation (ACU) groups. Pain behavior was evaluated using paw withdrawal threshold and latency. Western blot and immunofluorescence were used to assess CCL2, CCR2, Iba1, IL-1β, and TNF-α expression in the L4–L6 spinal cord. EA significantly attenuated mechanical allodynia and thermal hyperalgesia in the ACU group, accompanied by reductions in CCL2, CCR2, microglial marker Iba1, and pro-inflammatory cytokines. Most importantly, intrathecal administration of recombinant CCL2 completely abolished EA’s analgesic effects, establishing the causal necessity of CCL2/CCR2 signaling in EA-mediated analgesia. These findings suggest that EA exerts its analgesic effects through downregulation of the CCL2/CCR2 pathway and inhibition of microglial activation. The reversal of EA’s effects by exogenous CCL2 supports the critical role of spinal chemokine signaling in EA-mediated analgesia. Full article

HIV-associated neurocognitive impairment (HIV-NCI), a comorbidity of human immunodeficiency virus (HIV) infection, affects up to 50% of people with HIV (PWH). HIV-infected monocytes that transmigrate across the blood–brain barrier and mature into macrophages establish a central nervous system (CNS) viral reservoir that activates and infects parenchymal cells, contributing to neuronal damage that characterizes HIV-NCI. Methamphetamine (meth) use is prevalent in PWH and further impairs cognitive functioning. To examine whether meth-mediated dysregulation of macrophage functions may contribute to increased HIV-NCI, we characterized differential gene expression in primary human HIV-infected macrophages treated daily with meth for five days by RNA-sequencing. We identified increases in multiple gene isoforms of metallothionein 1 (MT1), a heavy metal binding protein involved in protective mechanisms against metal toxicity and oxidative stress. Nuclear localization of MT1 protein was previously shown to either positively or negatively affect nuclear factor κB (NF-κB) activity in a cell type specific manner, with nuclear MT1 contributing to LPS-induced TNF-α and IL-6 in macrophages. We found that daily meth treatment for one to five days increased nuclear localization of MT1 in macrophages acutely infected with HIV which was associated with increased LPS-induced CXCL8 and CCL8, and a trend towards increased basal and/or LPS-induced expression of other cytokines/chemokines, including TNF-α and IL-6, that was donor specific. Reactive oxygen species (ROS) levels were not changed with meth treatment although there was a donor specific trend towards increased ROS with multiple days of meth treatment. These data indicate that repeated exposure of macrophages to meth in the context of HIV increases nuclear MT1 localization, which is associated with increased inflammatory mediator production, and therefore may be a mechanism that contributes to meth-mediated exacerbation of HIV-NCI. Full article

Sjögren’s disease (SjD) targets the salivary and lacrimal glands and is characterized by autoantibody production and glandular lymphocytic infiltrate with ectopic germinal centers (EGCs). The chemokine CCL25 recruits CCR9⁺ CD4⁺ T cells to the salivary glands to promote B cell activation. However, the therapeutic potential of targeting the CCL25–CCR9 axis to limit glandular inflammation and lymphoid neogenesis remains largely unexplored. Evaluate whether blocking the CCL25–CCR9⁺ T cell axis with a monoclonal antibody could reduce immune infiltration, ectopic germinal center (EGC) formation, and local autoantibody production in the NOD.H2(h4) mouse model of SjD. Female NOD.H2(h4) mice were administered anti-CCL25 antibody, isotype control, or PBS intraperitoneally for 12 weeks. Sera and saliva were collected to evaluate anti-Ro52 antibodies via ELISA across treatment groups. Salivary glands were harvested and processed for H&E staining to assess lymphocytic infiltration and focus scores. Treatment with α-CCL25 was well tolerated, with no significant differences in body weight or stimulated salivary flow between treatment groups. Histopathological evaluation revealed no reduction in lymphocytic infiltration, focus scores, or percentage of inflamed tissue in α-CCL25-treated mice compared to controls. Anti-Ro52 antibodies were undetectable in plasma or saliva across all groups and timepoints. Systemic CCL25 blockade did not significantly alter salivary gland inflammation, function, or autoantibody production in NOD.H2(h4) mice. These findings suggest that monotherapy targeting the CCL25–CCR9 axis may be insufficient to resolve glandular autoimmunity in this model and that additional or combinatorial strategies may be necessary for effective intervention. Full article

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health concern. Soy protein isolate (SPI) is a plant-derived protein with high nutritional value and has shown promising effects in regulating lipid metabolism and inflammation. Objectives: This study aimed to investigate the effects of an α-subunit-deficient SPI (α-lack-SPI) on MASLD and the underlying molecular mechanisms. Methods: Rats were fed with a high-fat, high-cholesterol diet (HFD) to induce MASLD. Results: The results showed that α-lack-SPI significantly reduced the levels of hepatic TG and TC, serum ALT, AST, TC, and LDL-C, and increased serum HDL-C in rats with HFD-induced MASLD. α-lack-SPI significantly attenuated hepatic steatosis and hepatocyte ballooning revealed by histopathological analysis. Meanwhile, α-lack-SPI markedly downregulated the mRNA expressions of Srebf1, Acaca, Fasn, Pcsk9, and Hmgcr, while significantly upregulating Pparα. Additionally, α-lack-SPI treatment significantly reduced the mRNA expressions of hepatic pro-inflammatory cytokines (Tnf-α, Il-1β, Il6), chemokine (Ccl2), and inflammasome component (Nlrp3), as well as the protein expression of COX-2. Conclusions: In conclusion, α-lack-SPI alleviated MASLD in HFD-fed rats probably via improving hepatic lipid metabolism and mitigating hepatic inflammation. These findings indicate that α-lack-SPI may serve as a promising nutritional intervention for MASLD management. Full article

Inflammatory cytokines, particularly interferon-γ (IFN-γ), are markedly elevated in the peripheral blood of patients with immune checkpoint inhibitor-induced myocarditis (ICI-M). Endomyocardial biopsies from these patients also show GBP-associated inflammasome overexpression. While both factors are implicated in ICI-M pathophysiology, their interplay and cellular targets remain poorly characterized. Our aim was to elucidate how ICI-M-associated cytokines affect the viability and inflammatory responses of endothelial cells (ECs) and cardiomyocytes (CMs) using human induced pluripotent stem cell (hiPSC)-derived models. ECs and CMs were differentiated from the same hiPSC line derived from a healthy donor. Cells were exposed either to IFN-γ alone or to an inflammatory cytokine cocktail (CCL5, GZMB, IL-1β, IL-2, IL-6, IFN-γ, TNF-α). We assessed large-scale transcriptomic changes via microarray and evaluated inflammatory, apoptotic, and cell death pathways at cellular and molecular levels. hiPSC-ECs were highly sensitive to cytokine exposure, displaying significant mortality and marked transcriptomic changes in immunity- and inflammation-related pathways. In contrast, hiPSC-CM showed limited transcriptional changes and reduced susceptibility to cytokine-induced death. In both cell types, cytokine treatment upregulated key components of the inflammasome pathway, including regulators (GBP5, GBP6, P2X7, NLRC5), a core component (AIM2), and the effector GSDMD. Increased GBP5 expression and CASP-1 cleavage mirrored the findings found elsewhere in endomyocardial biopsies from ICI-M patients. This hiPSC-based model reveals a distinct cellular sensitivity to ICI-M-related inflammation, with endothelial cells showing heightened vulnerability. These results reposition endothelial dysfunction, rather than cardiomyocyte injury alone, as a central mechanism in ICI-induced myocarditis. Modulating endothelial inflammasome activation, particularly via AIM2 inhibition, could offer a novel strategy to mitigate cardiac toxicity while preserving antitumor efficacy. Full article