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Microplastics (MPs) are an emerging environmental issue due to their accumulation in ecosystems and living organisms. Increasing evidence shows that MPs impact vascular function, with recent studies finding MPs in atheromas linked to cardiovascular events. Since vascular smooth muscle cells (VSMCs) are crucial to maintaining vascular function, this study examined how MPs activate VSMCs, leading to cardiovascular diseases like atherosclerosis and vascular calcification. The study used polyethylene (PE) and polystyrene (PS), common in food packaging, as "virgin" or photo-degraded to simulate environmental conditions. VSMC viability, apoptosis, cytotoxicity, inflammation, and activation markers were evaluated. PE and PS affected VSMC viability, induced apoptosis, and triggered pathological changes such as altered migration and proliferation. Key markers like RUNX-2 and galectin-3, which regulate cardiovascular pathology, were activated, alongside the inflammasome complex. In conclusion, MPs can induce harmful activation of VSMCs, posing potential health risks through inflammation, cell damage, and phenotypic changes. Understanding these toxic mechanisms may reveal critical pathways for intervention and prevention. [ABSTRACT FROM AUTHOR]

Background: Vascular calcification (VC) is a dynamic, tightly regulated process driven by cellular activity and resembling the mechanisms of bone formation, with specific molecules playing pivotal roles in its progression. We aimed to investigate the involvement of the bone morphogenic proteins (BMP-2, BMP-4, BMPR-1a/1b, and BMPR-2) system in this process. Our study used an advanced in vitro model that simulates the biological environment of the vascular wall, assessing the ability of a phosphate mixture to induce the osteoblastic switch in human coronary artery smooth muscle cells (HCASMCs). Methods: HCASMCs were grown in mono- and co-culture with human coronary artery endothelial cells (HCAECs) in a double-flow bioreactor (LiveBox2 and IVTech), allowing static and dynamic conditions through a peristaltic pump. The VC was stimulated by incubation in a calcifying medium for 7 days. A BMP system Real-Time PCR was performed at the end of each experiment. Results: In monocultures, BMP-2 expression increased in calcified HCASMCs in static (p = 0.01) and dynamic conditions. BMP-4 and the biological receptors were expressed in all the experimental settings, increasing mainly in dynamic flow conditions. In co-cultures, we observed a marked increase in BMP-2 and BMP-4, BMPR-1a (p = 0.04 and p = 0.01, respectively), and BMPR-2 (p = 0.001) in the calcifying setting mostly in dynamic conditions. Conclusions: The increase in BMP-2/4 in co-culture suggests that these genes might promote the switch towards an osteogenic-like phenotype, data also supported by the rise of both BMPR-1a and BMPR-2. Thus, our findings provide insights into the mechanisms by which dynamic co-culture modulates the BMP system activation in an environment mimicking in vivo VC's cellular and mechanical characteristics. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) and Primary biliary cholangitis (PBC) are chronic inflammatory biliary diseases characterized by progressive damage of the bile ducts, resulting in hepatobiliary fibrosis and cirrhosis. Currently, specific biomarkers that allow to distinguish between PSC and PBC do not exist. In this study, we examined the salivary proteome by carrying out a comprehensive and non-invasive screening aimed at highlighting possible quali-quantitative protein deregulations that could be the starting point for the identification of effective biomarkers in future. Saliva samples collected from 6 PBC patients were analyzed using a liquid chromatography–tandem mass spectrometry technique, and the results were compared with those previously obtained in the PSC group. We identified 40 proteins as significantly deregulated in PSC patients compared to the PBC group. The Gene Ontology and pathway analyses highlighted that several proteins (e.g., small integral membrane protein 22, cofilin-1, macrophage-capping protein, plastin-2, and biliverdin reductase A) were linked to innate immune responses and actin cytoskeleton remodeling, which is a critical event in liver fibrosis and cancer progression. These findings provide new foundations for a deeper understanding of the pathophysiology of PSC and demonstrate that saliva is a suitable biological sample for obtaining proteomic fingerprints useful in the search for biomarkers capable of discriminating between the two cholestatic diseases. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an inflammatory disease wherein neutrophils play a key role in plaque evolution. We observed that neutrophil CD11b was associated with a higher necrotic core volume in coronary plaques. Since platelets modulate neutrophil function, we explored the influence of neutrophil–platelet conjugates on the cytokine-modulated neutrophil complex CD11b/CD18 and CCR5 receptor expression. In 55 patients [68.53 ± 7.95 years old (mean ± SD); 71% male], neutrophil positivity for CD11b, CD18 and CCR5 was expressed as Relative Fluorescence Intensity (RFI) and taken as a dependent variable. Cytokines and chemokines were assessed by ELISA. Following log-10-based logarithmic transformation, they were used as independent variables in Model 1 of multiple regression together with Body Mass Index and albumin. Model 1 was expanded with the RFI of neutrophil CD41a+ (model 2). The RFI of neutrophil CD41a+ correlated positively and significantly with CD11b, CD18, and CCR5. In Model 2, CCR5 correlated positively only with the RFI of neutrophil CD41a+. Albumin maintained its positive effect on CD11b in both models. These observations indicate the complexity of neutrophil phenotypic modulation in stable CAD. Despite limitations, these findings suggest there is a role played by neutrophil–platelet interaction on the neutrophil cytokine-modulated expression of adhesive and chemotactic receptors. [ABSTRACT FROM AUTHOR]

Vascular calcification (VC) is a cardiovascular disease characterized by calcium salt deposition in vascular smooth muscle cells (VSMCs). Standard in vitro models used in VC investigations are based on VSMC monocultures under static conditions. Although these platforms are easy to use, the absence of interactions between different cell types and dynamic conditions makes these models insufficient to study key aspects of vascular pathophysiology. The present study aimed to develop a dynamic endothelial cell–VSMC co-culture that better mimics the in vivo vascular microenvironment. A double-flow bioreactor supported cellular interactions and reproduced the blood flow dynamic. VSMC calcification was stimulated with a DMEM high glucose calcification medium supplemented with 1.9 mM NaH2PO4/Na2HPO4 (1:1) for 7 days. Calcification, cell viability, inflammatory mediators, and molecular markers (SIRT-1, TGFβ1) related to VSMC differentiation were evaluated. Our dynamic model was able to reproduce VSMC calcification and inflammation and evidenced differences in the modulation of effectors involved in the VSMC calcified phenotype compared with standard monocultures, highlighting the importance of the microenvironment in controlling cell behavior. Hence, our platform represents an advanced system to investigate the pathophysiologic mechanisms underlying VC, providing information not available with the standard cell monoculture. [ABSTRACT FROM AUTHOR]

pRb2/p130 is a key tumor suppressor, whose oncosuppressive activity has mainly been attributed to its ability to negatively regulate cell cycle by interacting with the E2F4 and E2F5 transcription factors. Indeed, pRb2/p130 has been found altered in various cancer types in which it functions as a valuable prognostic marker. Here, we analyzed pRb2/p130 expression in gastric cancer tissue samples of diffuse histotype, in comparison with their normal counterparts. We found a cytoplasmic localization of pRb2/p130 in cancer tissue samples, whereas, in normal counterparts, we observed the expected nuclear localization. pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation, but considering the emerging involvement of pRb2/p130 in other key cellular processes, it could contribute to gastric tumorigenesis also through other mechanisms. Our data support the necessity of further investigations to verify the possibility of using pRb2/p130 as a biomarker or potential therapeutic target for diffuse gastric cancer. J. Cell. Physiol. 230: 802-805, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Optimal medical treatment in patients with stable coronary artery disease (CAD) reduced morbidity and mortality but left a substantial residual risk (RR) of disease progression and events. According to recent evidence, insulin resistance or pre-diabetes together with elevated levels of triglycerides, low levels, and functionality of HDL-cholesterol, often associated with a chronic inflammatory state, are deemed to be relevant components of cardiometabolic and vascular RR. In the present project, we aim at discovering specific individual genetic/molecular profiles subtending emerging cardiometabolic and vascular risk patterns and associated with more severe stable CAD phenotypes. To this end, we will analyse clinical data, blood samples, and imaging data already gathered in a retrospective population of 561 patients with suspected stable coronary disease and will develop integrated predictive models of severity and extent of disease defined by qualitative and quantitative analysis of coronary plaques by cardiac computed tomography. The new predictive models, which will incorporate relevant clinical and genetic/molecular variables associated with more severe coronary atherosclerosis, will be validated in a similar prospective population of patients and extended to the prediction of progression (at 1 year follow-up) of coronary disease phenotypes, occurring despite optimal medical treatment. Registration  ClinicalTrials.gov ID: NCT06601153., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. Overall, our findings suggest that SFK inhibition, besides reducing RMS cell growth and invasive potential, could also represent a differentiation therapeutic strategy for RMS.