UNASSIGNED: Changes in blood transcript abundance levels have been associated with pathogenesis in a wide range of diseases. While next generation sequencing technology can measure transcript abundance on a genome-wide scale, downstream clinical applications often require small sets of genes to be selected for inclusion in targeted panels. Here we set out to gather information from the literature and transcriptome datasets that would help researchers determine whether to include the gene CEACAM6 in such panels.
UNASSIGNED: We employed a workflow to systematically retrieve, structure, and aggregate information derived from both the literature and public transcriptome datasets. It consisted of profiling the CEACAM6 literature to identify major diseases associated with this candidate gene and establish its relevance as a biomarker. Accessing blood transcriptome datasets identified additional instances where CEACAM6 transcript levels differ in cases vs controls. Finally, the information retrieved throughout this process was captured in a structured format and aggregated in interactive circle packing plots.
UNASSIGNED: Although it is not routinely used clinically, the relevance of CEACAM6 as a biomarker has already been well established in the cancer field, where it has invariably been found to be associated with poor prognosis. Focusing on the blood transcriptome literature, we found studies reporting elevated levels of CEACAM6 abundance across a wide range of pathologies, especially diseases where inflammation plays a dominant role, such as asthma, psoriasis, or Parkinson\'s disease. The screening of public blood transcriptome datasets completed this picture, showing higher abundance levels in patients with infectious diseases caused by viral and bacterial pathogens.
UNASSIGNED: Targeted assays measuring CEACAM6 transcript abundance in blood may be of potential utility for the management of patients with diseases presenting with systemic inflammation and for the management of patients with cancer, where the assay could potentially be run both on blood and tumor tissues.

UNASSIGNED: Patients with systemic sclerosis (SSc) have an increased risk of endothelial dysfunction, atherosclerosis, and cardiovascular events compared to the general population. Therefore, the availability of robust circulating biomarkers of endothelial dysfunction and atherogenesis may facilitate early recognition and management of cardiovascular risk in SSc. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating various types of circulating cell adhesion molecules involved in endothelial dysfunction and atherogenesis (i.e., immunoglobulin-like vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, Down syndrome cell, DSCAM, and endothelial cell-selective, ESAM, adhesion molecules, E-, L-, and P-selectin, integrins, and cadherins) in SSc patients and healthy controls.
UNASSIGNED: We searched PubMed, Scopus, and Web of Science from inception to 1 May 2024. Risk of bias and certainty of evidence were assessed using validated tools.
UNASSIGNED: In 43 eligible studies, compared to controls, patients with SSc had significantly higher plasma or serum concentrations of ICAM-1 (standard mean difference, SMD=1.16, 95% CI 0.88 to 1.44, p<0.001; moderate certainty), VCAM-1 (SMD=1.09, 95% CI 0.72 to 1.46, p<0.001; moderate certainty), PECAM-1 (SMD=1.65, 95% CI 0.33 to 2.98, p=0.014; very low certainty), E-selectin (SMD=1.17, 95% CI 0.72 to 1.62, p<0.001; moderate certainty), and P-selectin (SMD=1.10, 95% CI 0.31 to 1.90, p=0.007; low certainty). There were no significant between-group differences in L-selectin concentrations (SMD=-0.35, 95% CI -1.03 to 0.32, p=0.31; very low certainty), whereas minimal/no evidence was available for cadherins, NCAM, DSCAM, ESAM, or integrins. Overall, no significant associations were observed between the effect size and various patient and study characteristics in meta-regression and subgroup analyses.
UNASSIGNED: The results of this systematic review and meta-analysis suggest that specific circulating cell adhesion molecules, i.e., ICAM-1, VCAM-1, PECAM-1, E-selectin, and P-selectin, can be helpful as biomarkers of endothelial dysfunction and atherogenesis in the assessment of cardiovascular risk in SSc patients.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42024549710.

BACKGROUND: Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by glioblastoma stem cells (GSCs). The interplay between GSCs and immunosuppressive microglia plays crucial roles in promoting the malignant growth of GBM; however, the molecular mechanisms underlying this crosstalk are unclear. This study aimed to investigate the role of POSTN in maintaining GSCs and the immunosuppressive phenotype of microglia.
METHODS: The expression of POSTN in GBM was identified via immunohistochemistry, quantitative real-time PCR, and immunoblotting. Tumorsphere formation assay, Cell Counting Kit-8 assay and immunofluorescence were used to determine the key role of POSTN in GSC maintenance. ChIP-seq and ChIP-PCR were conducted to confirm the binding sequences of β-catenin in the promoter region of FOSL1. Transwell migration assays, developmental and functional analyses of CD4+ T cells, CFSE staining and analysis, enzyme-linked immunosorbent assays and apoptosis detection tests were used to determine the key role of POSTN in maintaining the immunosuppressive phenotype of microglia and thereby promoting the immunosuppressive tumor microenvironment. Furthermore, the effects of POSTN on GSC maintenance and the immunosuppressive phenotype of microglia were investigated in a patient-derived xenograft model and orthotopic glioma mouse model, respectively.
RESULTS: Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway. In addition to its intrinsic effects on GSCs, POSTN can recruit microglia and upregulate CD70 expression in microglia through the αVβ3/PI3K/AKT/NFκB pathway, which in turn promotes Treg development and functionality and supports the formation of an immunosuppressive tumor microenvironment. In both in vitro models and orthotopic mouse models of GBM, POSTN depletion disrupted GSC maintenance, decreased the recruitment of immunosuppressive microglia and suppressed GBM growth.
CONCLUSIONS: Our findings reveal that POSTN plays critical roles in maintaining GSCs and the immunosuppressive phenotype of microglia and provide a new therapeutic target for treating GBM.

BACKGROUND: MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines.
METHODS: The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen-related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells.
RESULTS: The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-β), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor.
CONCLUSIONS: Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target.

Acute myeloid leukemia (AML) is a predominant form of leukemia. Central nervous system (CNS) involvement complicates its diagnosis due to limited diagnostic tools, as well as its treatment due to inadequate therapeutic methodologies and poor prognosis. Furthermore, its incidence rate is unclear. The mechanisms of AML cell mobilization from the bone marrow (BM) to the CNS are not fully elucidated, and the molecular factors contributing to CNS infiltration are insufficiently recognized. The present review aimed to enhance the understanding of CNS involvement of AML and its impact on CNS. The latest research on the pathways and mechanisms facilitating AML cells to escape the BM and infiltrate the CNS was reviewed. Additionally, novel therapeutic strategies targeting specific molecules and genes for treating CNS involvement in AML were examined.

Triple-negative breast cancer (TNBC) represents a major therapeutic challenge due to its heterogeneous and aggressive phenotype, and limited target-specific treatment options. The trophoblast cell surface antigen (Trop-2), a transmembrane glycoprotein overexpressed in various cancers, has emerged as a promising target for TNBC. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop-2, has recently entered treatment algorithms for advanced and metastatic TNBC, independently from Trop-2 expression status, with manageable toxicity. Despite the impressive results, questions remain unsolved regarding its efficacy, safety profile, and Trop-2 biological role in cancer. Currently, Trop-2 cannot be designated as a predictive biomarker in SG treatment, albeit its expression correlates with disease outcome, yet its levels are not uniform across all TNBCs. Additionally, data regarding Trop-2 expression variations in primary and metastatic sites, and its interplay with other biomarkers are still ambiguous but mandatory in light of future applications of SG in other indications and settings. This poses the questions of a careful evaluation of the efficacy and toxicity profile of SG in such early stages of disease, and in personalized and combinatorial strategies. Research and clinical data are mandatory to address SG drawbacks and minimize its benefits, to realize its full potential as therapeutic agent in different epithelial tumors.

Laminins are essential components of the basement membranes, expressed in a tissue- and cell-specific manner under physiological conditions. During inflammatory circumstances, such as atherosclerosis, alterations in laminin composition within vessels have been observed. Our study aimed to assess the influence of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine abundantly found in atherosclerotic lesions, on endothelial laminin gene expression and the effects of laminin-332 (LN332) on endothelial cells\' behavior. We also evaluated the expression of LN332-encoding genes in human carotid atherosclerotic plaques. Our findings demonstrate that TNF induces upregulation of LAMB3 and LAMC2, which, along with LAMA3, encode the LN332 isoform. Endothelial cells cultured on recombinant LN332 exhibit decreased claudin-5 expression and display a loosely connected phenotype, with an elevated expression of chemokines and leukocyte adhesion molecules, enhancing their attractiveness and adhesion to leukocytes in vitro. Furthermore, LAMB3 and LAMC2 are upregulated in human carotid plaques and show a positive correlation with TNF expression. In summary, TNF stimulates the expression of LN332-encoding genes in human endothelial cells and LN332 promotes an endothelial phenotype characterized by compromised junctional integrity and increased leukocyte interaction. These findings highlight the importance of basement membrane proteins for endothelial integrity and the potential role of LN332 in atherosclerosis.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human PN2 was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of PN1-2 mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP\'s inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance.
METHODS: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes.
RESULTS: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC.
CONCLUSIONS: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.