Search Results (149)

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life. Full article

Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. They represent a promising but still investigational therapeutic approach for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD), as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Recent phase II/III trials in steroid-refractory (SR)-aGVHD have demonstrated overall response rates ranging from 48 to 71%. Efficacy appears particularly enhanced in pediatric patients and with early MSC administration. Across studies, MSC therapy shows a favorable safety profile; however, heterogeneity in response and inconsistent survival outcomes remain notable limitations. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials. Full article

Background/Objectives: The cardiac hypoxia- and inflammation-associated processes in patients with chronic coronary artery disease remain unknown. The coronary sinus (CS) can be used to explore changes in cardiac microenvironment. This study sought to evaluate acute changes in the CS concentration of hypoxia and inflammation-associated biomarkers after the percutaneous revascularization of chronic total occlusions (CTO-PCI). Additionally, we explored changes in systemic inflammation and the potential of CS biomarkers to predict left ventricular ejection fraction (LVEF) improvement on follow-up. Methods: Thirty-three patients undergoing CTO-PCI were included. Samples from CS were collected before and after the revascularization. Twenty-six protein biomarkers associated with hypoxia and inflammation were measured using proximity extension assay technology. Systemic inflammation markers and LVEF on cardiac magnetic resonance imaging were assessed at baseline and 6-month follow-up. Results: CTO-PCI yielded a significant decrease in the concentration of CS pro-angiogenic biomarkers (angiopoietin-1, vascular endothelial growth factors). In addition, there was a significant increase in the anti-inflammatory biomarker interleukin-10 and a decrease in several pro-inflammatory biomarkers like interleukin-1β. The acute response in cardiac microenvironment was followed by a mid-term reduction in systemic inflammatory markers, particularly high-sensitivity C-reactive protein. Notably, interleukin-10 showed good performance to identify patients achieving LVEF improvement on follow-up in our cohort. Conclusions: Our results suggest that CTO-PCI might attenuate cardiac hypoxic and inflammatory stress. These exploratory findings warrant confirmation in larger, controlled studies. Full article

Background/Objectives: Ankylosing Spondylitis (AS) is associated with increased cardiovascular disease risk due to chronic systemic inflammation. The Atherogenic Index of Plasma (AIP) and Systematic Coronary Risk Evaluation (SCORE) are valuable tools for cardiovascular risk assessment, while Klotho, an anti-aging protein with cardioprotective properties, may serve as a potential biomarker for cardiovascular health. Recent studies have shown that soluble α-Klotho contributes to vascular protection by increasing endothelial cell proliferation, reducing apoptosis, and enhancing angiogenic capacity, thereby helping to maintain microvascular integrity. We aimed to assess cardiovascular event risk in AS patients using AIP and SCORE and investigate the relationship between serum Klotho levels and these factors. Methods: A case–control study was conducted between August and September 2019. The study included 24 AS patients and 24 healthy controls aged 18 and above, with 13 females and 11 males. Results: No significant difference was found in serum Klotho levels between the AS and control groups in terms of SCORE and AI classifications. In the high-risk SCORE classification group, AI was found to be elevated at 0.42. In the AS group, Klotho levels were observed as 0.73 in the low-risk group, 0.60 in the moderate-risk group, and 0.61 in the high-risk group (p = 0.974). When evaluating HDL levels, Klotho was determined to be 7.29 ± 6.81 for HDL < 35 and 0.60 [0.33] for HDL ≥ 35 (p = 0.036). Conclusions: An AI exceeding 0.40 in the high-risk SCORE group and in patients with active disease according to the BASDAI score indicated an increased cardiovascular event risk in the AS group. Further studies are warranted regarding serum Klotho levels, HDL, and LDL subclasses in AS patients. Full article

Diffuse pleural mesothelioma (PM) is a rare thoracic malignancy with historically limited treatment options and poor outcomes. Despite the recent breakthrough of dual immune checkpoint blockade (ICB)—notably the combination of anti-PD-1 and anti-CTLA-4 therapies—clinical responses remain variable and overall survival gains modest. Consequently, there is an urgent need for multidimensional biomarkers and adaptive trial designs to unravel the complexity of PM immune biology. This review provides a comprehensive overview of current evidence on how histological subtypes (epithelioid vs. non-epithelioid) influence ICB efficacy, highlighting distinct genetic landscapes (e.g., BAP1, CDKN2A, NF2 mutations) and tumor microenvironment (TME) features, including immune infiltration patterns and PD-L1 or VISTA expression, that underlie differential responses. We further examine intrinsic tumor factors—such as mutational burden and checkpoint ligand expression—and extrinsic determinants, including immune cell composition, stromal architecture, patient immune status, and microbiota, as modulators of immunotherapy outcomes. We also discuss the rationale behind emerging strategies designed to enhance ICB efficacy, currently under clinical evaluation. These include combination regimens with chemotherapy, radiotherapy, surgery, epigenetic modulators, anti-angiogenic agents, and novel immunotherapies such as next-generation checkpoint inhibitors (LAG-3, VISTA), immune-suppressive cell–targeting agents, vaccines, cell-based therapies, and oncolytic viruses. Collectively, these advancements underscore the importance of integrating histological classification with molecular and microenvironmental profiling to refine patient selection and guide the development of combination strategies aimed at transforming “cold” mesotheliomas into “hot,” immune-responsive tumors, thereby enhancing the efficacy of ICB. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predictive performance was validated by means of nested cross-validation, Firth logistic regression, and safe stratified 0.632+ bootstrap ridge regression. The profiling revealed distinct gene expression patterns between the groups: the upregulation of ribosomal and translational pathways, as well as the suppression of neutrophil degranulation and antimicrobial defense mechanisms, and identified key candidate genes, including PDE4B, JAK1, ETS1, EIF4A2, FCMR, IGKV4-1, and XPO7. These genes demonstrated substantial discriminatory capability, with an area under the curve ranging from 0.95 to 0.99, and were found to be functionally linked to immune system dysfunction, cytokine signaling, NF-κB activation, and a maladaptive stress response. These findings link MRONJ to systemic immune-inflammatory imbalance and translational stress disruption, offering novel insights and potential biomarkers for diagnosis and risk evaluation. Full article

The premetastatic niche (PMN) represents a specialized microenvironment established in distant organs before the arrival of metastatic cells. This concept has fundamentally altered our understanding of cancer progression, shifting it from a random event-driven process to an orchestrated one. This review examines the critical role of extracellular proteases in PMN formation, focusing on matrix metalloproteinases (MMPs), serine proteases, and cysteine cathepsins that collectively orchestrate extracellular matrix remodeling, immune modulation, and vascular permeability changes essential for metastatic colonization. Key findings demonstrate that MMP9 and MMP2 facilitate basement membrane degradation and the recruitment of bone marrow-derived cells. At the same time, tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes organ-specific hepatic PMN recruitment through neutrophil recruitment mechanisms. The plasminogen–plasmin system emerges as a master regulator through its broad-spectrum proteolytic activity and ability to activate downstream proteases, with S100A10-mediated plasmin generation providing mechanistic pathways for remote PMN conditioning. Neutrophil elastase and cathepsin G contribute to the degradation of anti-angiogenic proteins, thereby creating pro-metastatic microenvironments. These protease-mediated mechanisms represent the earliest interventional window in metastatic progression, offering therapeutic potential to prevent niche formation rather than treat established metastases. However, significant methodological challenges remain, including the need for organ-specific biomarkers, improved in vivo methods for measuring protease activity, and a better understanding of temporal PMN dynamics across different target organs. Full article

Advanced hepatocellular carcinoma (HCC) exhibits a poor prognosis. Immunotherapy has emerged as a major player for both the upfront treatment of advanced HCC and disease progression on prior systemic therapies. In the first-line treatment of advanced HCC, immunotherapy demonstrated superior efficacy outcomes compared to tyrosine kinase inhibitors and a favourable safety profile. Initial treatment strategies of single-agent immune checkpoint inhibitors (ICIs) yielded only limited clinical activity. A deeper understanding of the hepatic tumour microenvironment and immunotolerance has driven the development of biologically relevant immunotherapy combinations. These combinations, which include antiangiogenic agents or dual ICIs targeting both PD-1/PD-L1 and CTLA-4, are the focus of current research. Recently published clinical trials involving ICI-based combination therapies achieved improved treatment outcomes, continuing to reshape the treatment paradigm for advanced HCC. While different immunotherapy combinations have shown variable efficacy in augmenting anti-tumour immunity, they inevitably increase toxicity and costs. Furthermore, the search for predictive biomarkers remains an unmet challenge in advanced HCC. In this review, we will summarise the notable advances in immunotherapy for the treatment of advanced HCC, discuss the underlying immune microenvironment and rationale for combinations, and explore opportunities for novel therapeutic targets beyond conventional immune checkpoints to overcome immunotherapy resistance. Full article

Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H₂O₂) or by subjecting retinal neuronal cells to 8 h of oxygen–glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties. Full article

Thymic carcinoma (TC) is a rare, aggressive cancer that originates from thymus’s epithelial cells. It distinguishes itself from other thymic epithelial tumors with its unique pathological structure, clinical behavior, and immune characteristics. Immune checkpoint inhibitors (ICIs) targeting the Programmed cell death protein 1/Programmed cell death protein ligand 1 (PD-1/PD-L1) pathway have shown promise in advanced TC, potentially benefiting from frequent PD-L1 overexpression and abundant CD8⁺ tumor-infiltrating lymphocytes (TILs), despite typically low tumor mutational burden (TMB). While ICI monotherapy can achieve disease control in some patients, its overall efficacy is limited and it is associated with a distinct profile of immune-related adverse events (irAEs) which occur less often than in thymomas. The predictive value of biomarkers—particularly PD-L1 expression—remains uncertain, underscoring the importance of consistent assessment criteria. In this review, we summarize evidence on ICI monotherapy as well as combination approaches that incorporate anti-angiogenic agents, chemotherapy, or dual checkpoint blockade. Emerging therapeutic targets—such as CD70, TIM-3, and B7-H4—are also considered in the context of their potential clinical relevance. Finally, we discuss future directions aimed at improving efficacy, extending response durability, and reducing treatment-related toxicity through biomarker-based patient selection and tailored therapeutic strategies. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across gastrointestinal malignancies. Methods: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science up to August 2025 to evaluate the role of omentin in gastrointestinal cancers. Both preclinical and clinical studies evaluating omentin, its analogues and omentin-enhancing agents in gastric, colorectal, hepatic, pancreatic, and esophageal cancers were included. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and anti-angiogenic effects within the tumor microenvironment in several GI malignancies. However, evidence also indicates a dual role. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers; in contrast, elevated circulating levels–particularly in colorectal and pancreatic cancers–have been paradoxically associated with increased cancer risk and poor outcomes. Mechanistically, omentin modulates PI3K/Akt, NF-κB, AMPK, and oxidative stress pathways, and interacts with TMEM207. However, most available studies are small-scale and heterogeneous, with methodological inconsistencies and limited multi-omics integration, leaving major knowledge gaps. Conclusions: This review highlights omentin’s distinct systemic and local roles across GI cancers, underscoring its translational implications. Omentin emerges as a promising but context-dependent biomarker and therapeutic target, with future research needed to address heterogeneity, standardize assays, and validate its clinical utility in large-scale prospective studies. Full article

Preeclampsia affects 2–8% of pregnancies globally and remains a leading cause of maternal and perinatal morbidity, with limited preventive options beyond low-dose aspirin. Low-molecular-weight heparin (LMWH) has emerged as a promising therapeutic candidate due to its pleiotropic effects extending beyond anticoagulation, including anti-inflammatory, pro-angiogenic, and placental-protective properties. This comprehensive narrative review examines LMWH’s effects on preeclampsia-associated biomarkers and evaluates clinical evidence for its preventive efficacy. LMWH exerts multifaceted effects on disease pathophysiology, including restoration of angiogenic balance through sFlt-1 reduction and PlGF preservation, attenuation of inflammatory responses via decreased TNF-α and IL-6 production, normalization of coagulation parameters, and enhancement of trophoblast invasion and placental vascularization. Clinical trials reveal heterogeneous results, with meta-analyses suggesting significant benefit primarily in high-risk subgroups. Women with previous severe placenta-mediated complications demonstrate relative risk reductions of 40–60% for recurrent preeclampsia with LMWH prophylaxis, particularly when initiated before 16 weeks’ gestation. Combination therapy with low-dose aspirin appears to enhance protective effects. However, larger trials in unselected populations have failed to demonstrate significant benefit, highlighting the importance of appropriate patient selection. Current international guidelines reflect this evidence heterogeneity, with most recommending against routine LMWH use while acknowledging potential benefit in selected high-risk populations, particularly those with antiphospholipid syndrome or previous severe early-onset disease. Future research should focus on biomarker-guided patient selection, optimal dosing regimens, and integration with multimodal preventive strategies to maximize therapeutic benefit while minimizing unnecessary interventions. Full article

Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article

UDP-Gal-β-1,4 galactosyltransferase-V (GalT-V) is a member of a large family of galactosyltransferases whose function is to transfer galactose from the nucleotide sugar UDP-galactose to a glycosphingolipid glucosylceramide, to generate lactosylceramide (LacCer). It also causes the N and O glycosylation of proteins in the Trans Golgi area. LacCer is a bioactive lipid second messenger that activates an “oxidative stress pathway”, leading to critical phenotypes, e.g., cell proliferation, migration angiogenesis, autophagy, and apoptosis. It also activates an “inflammatory pathway” that contributes to the progression of disease pathology. β-1,4-GalT-V gene expression is regulated by the binding of the transcription factor Sp-1, one of the most O-GlcNAcylated nuclear factors. This review elaborates the role of the Sp-1/GalT-V axis in disease phenotypes and therapeutic approaches targeting not only Sp-1 but also Notch-1, Wnt-1 frizzled, hedgehog, and β-catenin. Recent evidence suggests that β-1,4GalT-V may glycosylate Notch-1 and, thus, regulate a VEGF-independent angiogenic pathway, promoting glioma-like stem cell differentiation into endothelial cells, thus contributing to angiogenesis. These findings have significant implications for cancer and cardiovascular disease, as tumor vascularization often resumes aggressively following anti-VEGF therapy. Moreover, LacCer can induce angiogenesis independent of VEGF and its level are reported to be high in tumor tissues. Thus, targeting both VEGF-dependent and VEGF-independent pathways may offer novel therapeutic strategies. This review also presents an up-to-date therapeutic approach targeting the β-1,4-GalT-V interactome. In summary, the β-1,4-GalT-V interactome orchestrates a broad network of signaling pathways essential for maintaining cellular homeostasis. Conversely, its dysregulation can promote unchecked proliferation, angiogenesis, and inflammation, contributing to the initiation and progression of multiple diseases. Environmental factors and smoking can influence β-1,4-GalT-V expression and its interactome, whereas elevated β-1,4-GalT-V expression may serve as a diagnostic biomarker of colorectal cancer, inflammation—exacerbated by factors that may worsen pre-existing cancer malignancies, such as smoking and a Western diet—and atherosclerosis, amplifying disease progression. Increased β-1,4-GalT-V expression is frequently associated with tumor aggressiveness and chronic inflammation, underscoring its potential as both a biomarker and therapeutic target in colorectal and other β-1,4-GalT-V-driven cancers, as well as in cardiovascular and inflammatory diseases. Full article