Search Results (23,795)

Objective: While Sanzi Sijun Formula (SSF) has exhibited preliminary efficacy against metabolic dysfunction-associated steatotic liver disease (MASLD), its mode of action remains undefined. This study therefore aimed to unravel its core therapeutic mechanisms. Methods: UPLC-MS was employed to characterize the major components of SSF. Male C57BL/6J mice were fed a high-fat diet combined with high-fructose/glucose drinking water (HFD-HF/G) for 10 weeks to establish a MASLD model, followed by SSF intervention. After 8-week treatment, body and liver weight, hepatic histopathological alterations, serum levels of lipids, transaminase, and inflammatory cytokines were detected, and transcriptomic sequencing was performed on mouse liver tissues for mechanistic exploration. AML12 hepatocytes stimulated with palmitic acid (PA) were treated with SSF alone or in combination with AMPK or SIRT1 specific inhibitors. RT-qPCR and Western blotting were used to detect the expression or activation levels of AMPK, SIRT1, and key lipid metabolism-related molecules. Results: A total of 77 active components were identified in SSF by UPLC-MS analysis. In MASLD model mice, SSF significantly reduced body and liver weight, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and alanine aminotransferase (ALT), suppressed the pro-inflammatory cytokines including TNF-α and IL-6, and elevated adiponectin levels. Histopathological staining demonstrated that SSF effectively alleviated hepatic steatosis, ballooning, and inflammatory cell infiltration. Transcriptomic profiling analysis verified the major regulatory effect of SSF on lipid metabolism and identified the AMPK/SIRT1 signaling pathway as a potential mechanism. Further experiments confirmed that SSF restored the levels of AMPK/ACC phosphorylation and SIRT1 expression, thereby modulating downstream lipid metabolism-related genes in liver tissues. In PA-induced AML12 cells, SSF significantly reduced intracellular accumulation of lipid and reactive oxygen species (ROS), which were partially abrogated by the inhibitors of AMPK or SIRT1. Conclusions: SSF exerts prominent effects against MASLD in both in vivo and in vitro models. Modulation of the AMPK/SIRT1 signaling pathway primarily contributes to its therapeutic mechanism against lipid metabolism disorder and lipotoxic liver injury. These findings provide experimental evidence to support the clinical application of SSF for MASLD treatment. Full article

This study combines ligand- and structure-based in silico strategies to predict the inhibitory activity of natural flavonoids on the Polo-Like Kinase-1 (PLK-1) enzyme as candidate anticancer agents. This enzyme participates in mitosis and is overexpressed in cancer cells. Furthermore, it has been shown to have important implications for tumor metastasis, and its inhibitors are attractive starting points for drug development. First, classification models are developed using linear discriminant analysis and a multilayer perceptron neural network. Models with accuracy greater than 80%, validated using standard statistical performance metrics and applicability domain, are used for virtual screening identifying four compounds as potential antitumor drugs. Subsequently, the identified compounds are evaluated using a molecular docking methodology to verify their binding mode and interactions with the catalytic domain of PLK-1. Finally, the integration of molecular dynamics simulations, at 300 ns, with Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) thermodynamic calculations demonstrates that the hydroxylation pattern of ring B in the flavonol scaffold is the fundamental chemical-structural determinant of electrostatic interactions and the architecture of water-mediated networks. Among the evaluated flavonoids, myricetin showed the most favorable overall computational profile, including the highest virtual-screening score and the most favorable mean MM/GBSA estimate, supporting its prioritization for experimental evaluation as a potential PLK-1 inhibitor. The integration of these approaches offers a robust methodological framework for proposing candidates with a higher probability of success, in subsequent stages of experimental validation, reducing time and costs in the early stages of drug development. Full article

Acute liver failure (ALF) is a fulminant hepatic syndrome characterized by rapid hepatocellular destruction, severe impairment of liver function, and high mortality. Effective pharmacological interventions capable of limiting early hepatic injury remain lacking. Upadacitinib (UPA), a selective inhibitor for Janus kinase 1 (JAK1) with established anti-inflammatory activity, has not previously been investigated in experimental ALF. Consequently, the current study examined the hepatoprotective potential and underlying mechanisms of UPA in a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF murine model. Mice were pretreated with UPA (10 or 20 mg/kg) prior to LPS/D-GalN challenge. UPA significantly attenuated liver injury, as demonstrated by marked reductions in serum ALT, AST, ALP, and γ-GT levels, together with substantial improvement in hepatic histopathology, attenuation of necroinflammation, and reduction in neutrophil accumulation. UPA also restored hepatic redox balance through reduction in lipid peroxidation and nitrosative stress, alongside enhancement of antioxidant capacity. Mechanistically, UPA suppressed IFN-γ/JAK1/STAT1 signaling and downregulated NF-κB p65 and inducible nitric oxide synthase (iNOS) expression, with subsequent reduction in hepatic TNF-α production. In parallel, UPA inhibited MAPK pathway activation, including ERK1/2, JNK, and p38 signaling. Moreover, UPA attenuated hepatocellular apoptosis through suppression of active caspase-3 and Bax expression with restoration of Bcl-2 levels. The 20 mg/kg dose consistently produced greater biochemical, molecular, and histopathological protection than the lower dose. In conclusion, UPA confers significant protection against LPS/D-GalN-induced ALF through coordinated suppression of oxidative stress, inflammatory signaling, and apoptosis, primarily associated with inhibition of the IFN-γ/JAK1/STAT1 and TNF-α/NF-κB/MAPK pathways and modulation of the Bax/Bcl-2 ratio, underscoring its viability as a promising therapeutic candidate for ALF. Full article

Extracellular stimuli, including hormones, growth factors and nutrients in the milieu of cells often initiate intracellular changes via signaling pathways, of which the cyclic 5′, 3′-adnosine monophosphate (cAMP)-dependent protein kinase (PKA) signaling pathway is prototypical. Research in the past decades has demonstrated that PKA plays versatile roles during cell proliferation and differentiation, mainly through phosphorylating a plethora of protein substrates by its protein kinase activity. Studies using model systems including yeast, neurons and mammalian germ cells indicate that PKA functionality is regulated by not only the cell-type-specific expression of its regulatory and catalytic subunits, but also the spatiotemporal distribution of its binding proteins and secondary messengers. How PKA elicits its functional specificity in a spatiotemporal manner constitutes fundamental mechanisms that regulate development, aging and regeneration. In this review, we first summarize basic aspects that drive the functional diversity of PKA and then focus on the less studied regulatory roles of PKA during synthesis of cellular proteins, the functional units of the cell. Direct links between PKA signaling and protein synthesis machinery are yet to be fully characterized. We anticipate that research in this area, combining model systems and newly developed methodologies, will continue to deepen our understanding of animal development and the etiology of human diseases. Full article

The ABA signaling pathway plays a central role in the regulation of plant responses to stress, with ABI5 serving as an important transcription factor within this pathway and exerting a key regulatory function. However, upstream kinases that regulate ABI5 have not been fully elucidated, especially the specific relationship between ABI5 and SnRK2 members in rice. Rice contains ten OsSAPK family members, which are classified into three conserved phylogenetic groups, including Group I (OsSAPK1/2/3), Group II (OsSAPK4/5/6/7), and Group III (OsSAPK8/9/10). This study aims to identify potential OsABI5-interacting kinases involved in ABA-mediated salt stress responses in rice. Phylogenetic analysis confirmed that the ten OsSAPKs were distributed into three conserved groups. Phenotypic analysis showed that ABA pretreatment alleviated salt-induced growth inhibition in rice seedlings, while RT-qPCR analysis revealed increased transcript levels of several OsSAPKs following ABA pretreatment under salt stress. Promoter analysis identified multiple hormone-responsive cis-elements in OsSAPK promoters, consistent with their transcriptional responses to ABA treatment. Integrated protein–protein interaction analyses revealed that OsSAPK1/3/4/9 physically bind to OsABI5, as demonstrated by complementary in vitro and in vivo assays. These findings identify four candidate OsABI5-interacting kinases and reveal potential SnRK2–ABI5 regulatory mechanisms in ABA-mediated salt stress responses. Full article

Vascular smooth muscle cells (VSMCs), the contractile cells in the tunica media of blood vessels, maintain vascular tone. The proliferation of VSMCs is an important feature of vascular remodeling that contributes to the regulation of blood pressure. Autophagy, an intracellular self-degrading process that delivers cytoplasmic constituents to lysosomes, plays a vital role in VSMC proliferation. This is regulated by the dopaminergic and renin–angiotensin systems but their interplay in their regulation of autophagy in VSMCs is not well-understood. In rat VSMCs, fenoldopam (Fen), a dopamine D1-like receptor agonist, increased autophagy, as determined by the increase in the protein expressions of microtubule-associated protein 1 light chain (LC)3-II and beclin-1 (BECN1), in a time- and concentration-dependent manner. Conversely, angiotensin II (Ang II), the endogenous Ang II type 1 receptor (AT₁R) agonist, decreased the protein expression of LC3-II and BECN1, also in a time- and concentration-dependent manner. The production of cyclic adenosine monophosphate (cAMP) and autophagic LC3-II puncta in VSMCs were increased by Fen and decreased by Ang II. Pre-treatment of VSMCs with Rp-cAMPS, a protein kinase A inhibitor, prevented the Fen-mediated increase and the Ang II-mediated decrease in LC3-II protein expression. Fen decreased, whereas Ang II increased the phosphorylation of P70S6K, a direct downstream mammalian target of rapamycin (mTOR). The inhibitory effect of Fen and stimulatory effect of Ang II on P70S6K phosphorylation were prevented by Rp-cAMPS. Ang II also decreased the Fen-mediated increase in cAMP production, while Fen attenuated the Ang II-mediated increase in cell proliferation, a response that occurs downstream of autophagy. Moreover, Ang II prevented the Fen-mediated inhibition of cell proliferation, an effect that was blocked by losartan, an AT₁R antagonist. These results demonstrate that Fen and Ang II counter-regulate autophagy and proliferation of VSMCs via the mTOR pathway, which is cAMP-dependent. Full article

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches. Full article

Peptides as signaling molecules play an important role in intercellular communication. Exogenous peptides AlaGluAspLeu (AEDL) and AlaGluAsp(OMe)Leu (AED(OMe)L) at a concentration of 10⁻⁷ M stimulate the growth and development of Nicotiana tabacum. A detailed study of Nicotiana tabacum root cells grown in the presence of exogenous peptides AEDL and AED(OMe)L using transmission electron microscopy revealed characteristic differences in the ultrastructure of some cytoplasmic organelles compared to control cells. Importantly, vacuoles and autophagosomes differing in size and content, as well as amyloplasts and proteinoplasts never previously described in the literature, were found in the cells of the outer and inner root cortex. Only lytic vacuoles were detected in the cytoplasm of control cells, whereas in the presence of peptides, predominantly protein-storing vacuoles were found in root cells. In the presence of the exogenous short peptide AEDL, tobacco root cells contained amyloplasts with numerous large starch granules in the stroma, which were not detected in control cells. In the presence of the modified short peptide AED(OMe)L, leukoplasts contained protein bodies. Moreover, in contrast to control cells and cells grown in the presence of the AEDL peptide, a megaphagic (pexophagic) variant of autophagosomes with peroxisomes was detected for the first time in tobacco cells treated with AED(OMe)L. Characteristic types of phagophores were identified, forming numerous small autophagosomes with cytoplasmic regions, multivesicular bodies or concentric membranes, and cytoskeletal elements. Data on the expression of the ATG, TOR, and FREE1 genes confirmed the pattern of the existence of a large number of small autophagosomes. Based on the obtained data, a scheme for the regulation of the formation of root architecture of Nicotiana tabacum in the presence of AEDL and AED(OMe)L was proposed. Full article

Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) remains a major challenge in the treatment of EGFR-mutant lung adenocarcinoma. Identifying biomarkers associated with resistance may improve understanding of the underlying molecular mechanisms. Objective: This study aimed to identify candidate biomarkers associated with EGFR-TKI resistance using integrated bioinformatics analysis and RT-qPCR validation. Methods: Two Gene Expression Omnibus (GEO) datasets (GSE123066 and GSE178755) were analysed to identify differentially expressed genes (DEGs). Overlapping DEGs were subjected to protein–protein interaction (PPI) network construction, Gene Ontology (GO), KEGG pathway enrichment, and Kaplan–Meier survival analyses. Selected candidate genes were subsequently validated by RT-qPCR in an independent clinical cohort. Results: A total of 76 overlapping DEGs were identified, including 52 upregulated genes enriched in cell proliferation, hypoxia response, EGFR signalling, and metabolic processes. KEGG analysis identified the PI3K–Akt signalling pathway as significantly enriched. Kaplan–Meier analysis showed that higher expression of TGFA, DDIT4, and SOX9 was associated with shorter progression-free survival. RT-qPCR validation demonstrated significantly increased SOX9 expression in the resistant group, whereas TGFA and DDIT4 showed no statistically significant differences. Conclusions: Integrated bioinformatics analysis identified TGFA, DDIT4, and SOX9 as candidate genes associated with EGFR-TKI resistance in EGFR-mutant lung adenocarcinoma. These findings provide a basis for further investigation of resistance-associated biomarkers, although larger independent cohorts and functional studies are required before clinical application. Full article

Background and Objectives: Conversion therapy has expanded treatment options for patients with initially unresectable hepatocellular carcinoma (HCC), but the surgical literature remains focused more often on radiologic response than on the pathological, perioperative, and postoperative outcomes of patients who actually proceed to hepatectomy. This focused systematic review aimed to synthesize the available evidence on conversion hepatectomy after contemporary combination downstaging for initially unresectable HCC. Materials and Methods: A structured PubMed/MEDLINE search with backward reference-list screening was performed and last updated on 3 February 2026. The full Boolean strategy, field tags, and eligibility framework are now reported explicitly. Because the literature was observational and clinically heterogeneous, findings were synthesized narratively and complemented by structured assessments of reporting completeness, potential cohort overlap, and study-level bias. Results: Fourteen studies were included, nearly all retrospective and predominantly from East Asia. Treatment platforms clustered into systemic doublets, systemic plus HAIC strategies, and broader locoregional–systemic triplet or multimodal approaches. Across studies reporting pathological response, pathological complete response ranged from 28.0% to 50.0%, while R0 resection ranged from 85.7% to 100%, where stated. Postoperative morbidity ranged from 14.3% to 71.4%, and major complication rates from 9.5% to 16.9%; however, extent of resection, liver reserve, post-hepatectomy liver failure, transfusion, and perioperative mortality were not uniformly reported. Most studies carried moderate-to-high overall concerns for bias because of response-based surgical selection, heterogeneous denominators, incomplete perioperative reporting, and possible partial overlap among some cohorts. Conclusions: The available literature suggests that conversion hepatectomy can be feasible and oncologically meaningful in carefully selected patients treated in experienced centers, but current evidence remains hypothesis-generating rather than practice-standardizing because it is observational, heterogeneous, and incompletely reported. Full article

Colorectal cancer (CRC) remains a major cause of cancer mortality worldwide, highlighting the need for novel molecular targets and alternative therapeutic strategies. TYRO3, a member of the TAM receptor tyrosine kinase family, has been associated with tumor progression and poor prognosis in CRC. In this study, the effects of the natural compounds Meleagrin and Cucurbitacin B on TYRO3 expression and CRC cell behavior were investigated in HCT-116 and HT-29 cells. Cell proliferation, apoptosis, migration, and TYRO3 expression were evaluated using functional and expression-based analyses. Both compounds modulated TYRO3 expression and suppressed proliferation and wound closure dynamics in CRC cells. Cucurbitacin B exerted more pronounced antiproliferative and pro-apoptotic effects, whereas Meleagrin demonstrated antiproliferative activity with comparatively lower effects on normal colon epithelial cells (CCD 841 CoN), suggesting a potentially more favorable selectivity profile. Collectively, these findings support further mechanistic investigation of TYRO3-modulating natural compounds as potential therapeutic candidates for CRC. Full article

Many kinases are known to homo- or hetero-merize and phosphorylate themselves or each other. Phosphorylation by itself (autophosphorylation) is mechanistically perceived as either cis- or trans-interactions. Identification of autophosphorylation sites in kinases provides an opportunity to assess the activity of the kinome in phosphoproteome datasets as an efficient indicator of kinase activity. In order to predict kinase activity-associated autophosphorylation sites, we first encompassed the currently reported homodimeric interactions between kinases from various sources. Subsequently, we accounted for the autophosphorylation sites in kinases that are predicted by phosphomotif screening approaches, in vitro kinase assays, and those perceived based on phosphomotif mutant analysis. Together, we identified 4184 autophosphorylation sites in 386 kinases, and among them, 315 kinases were reported with homodimeric protein–protein interactions. Furthermore, we analysed 361 kinases that harbor multiple autophosphorylation sites and 25 kinases with a single autophosphosite based on contemporary kinase–substrate interactions. Among the 386 kinases, autophosphosites for 17 kinases were derived through high-throughput or low-throughput approaches, and for 80 kinases, they were predicted based on their phosphomotif analysis. The remaining 289 were based on predictions by multiple tools or were reported in more than one dataset. There were many instances in which, although one auto-phosphorylation site was reported, multiple other sites were also predicted. In this regard, we analysed the instances of phosphosites in kinases that are already associated with the induction or inhibition of kinase activity and identified 223 kinases with one or more sites with functional association. To evaluate their potential as auto-phosphorylation sites, we systematically assembled 1572 profiles and 978 differential cellular phosphoproteome datasets. Subsequently, we accounted for the frequency of co-detection or co-differential regulation of these autophosphosites with multiple kinase activity-associated sites within each kinase and further accounted for their known/predicted substrate phosphorylation sites. Together, we provide a reference compendium of autophosphorylation sites secluded in the human kinome and their co-regulation with substrates based on global phosphoproteome datasets, AutoPhosDb. As indicators of kinase activity, these phosphosites in kinases would serve as a surrogate to enrich the active kinases and their potential substrate-specificity in phosphoproteome datasets. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid malignancies, with poor survival driven by late presentation, aggressive tumor biology, and limited responsiveness to conventional systemic therapy. Advances in molecular profiling have expanded opportunities for biomarker-guided and targeted therapeutic approaches. Methods: A literature review was conducted using PubMed and the Cochrane Library through July 2026, supplemented by abstracts and proceedings from major international oncology conferences. Results: Pancreatic cancer is driven mainly by somatic changes in KRAS, TP53, CDKN2A, and SMAD4. Established precision approaches include maintenance olaparib for selected platinum-sensitive tumors with germline BRCA1 or BRCA2 pathogenic variants, immune checkpoint inhibition for mismatch repair-deficient or microsatellite instability-high tumors, and tropomyosin receptor kinase inhibition for cancers with neurotrophic tyrosine receptor kinase gene fusions. Direct inhibition of KRAS and RAS represents a major therapeutic breakthrough. KRAS G12C inhibitors established proof of concept, while agents targeting the more common KRAS G12D mutation are showing encouraging early activity. In the randomized phase III RASolute 302 trial, the multiselective RAS inhibitor daraxonrasib improved survival compared with chemotherapy in previously treated metastatic disease with oncogenic RAS mutations. Early studies of zoldonrasib combinations have extended this progress to KRAS G12D-mutant disease, although confirmation is required. Molecular profiling, next-generation sequencing, patient-derived organoids, and circulating tumor DNA may further improve treatment selection and monitoring. Conclusions: Precision oncology is becoming clinically relevant in pancreatic ductal adenocarcinoma. KRAS- and RAS-directed therapies are central advances, but resistance, toxicity, limited durability, and access to comprehensive testing remain important challenges. Full article

Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article

Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using β-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD. Full article