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Platelet-derived growth factor receptor beta (PDGFRβ) belongs to the receptor tyrosine kinase (RTK) protein family and is implicated in several disorders such as hematopoietic, glial, and soft-tissue cancer, non-cancerous disorders, including skeletal defects, brain calcification, and vascular anomalies. The research on small molecule inhibitors targeting PDGFRβ in cancer treatment has seen promising developments, but significant gaps remain. PDGFRβ, receptor tyrosine kinase, is overexpressed in various cancers and plays an important role in tumor progression, making it a potential therapeutic target. However, despite advances in identifying and characterizing PDGFRβ inhibitors, few have progressed to clinical trials, and the mechanistic details of PDGFRβ′s interactions with small molecule inhibitors are still not fully understood. Moreover, the specificity and selectivity of these inhibitors remain challenging, as off-target effects can lead to unwanted toxicity. In this investigation, two compounds, Genostrychnine and Chelidonine, were discovered that help inhibit the kinase activity of PDGFRβ. These small molecules were identified by employing various parameters involved in the drug discovery process, such as Lipinski’s rule of five (RO5), 2D similarity search and 3D pharmacophore-based virtual screening followed by MD simulation studies. The identified molecules were found to be effective and significantly bound with the PDGFRβ kinase domain. Overall, our findings demonstrate that these small drug-like compounds can be beneficial tools in studying the properties of PDGFRβ and can play a crucial role in the therapeutic development of cancers and other associated diseases.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration.Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed.Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006).Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

ObjectiveTo analyze the correlation between the changes of learning and memory and the progressive degeneration of white matter nerve fibers and pericytes in the corpus callosum and hippocampus of rats with chronic cerebral ischemia, then to explore the mechanism of learning and memory impairment caused by chronic cerebral ischemia, and provide a possible predictive target for vascular cognitive impairment.MethodsA total of 24 SPF male SD rats were divided randomly into sham operation group, 28 days after operation group and 56 days after operation group, with eight rats in each group. The sham operation group were treated with bilateral common carotid arteries separation without ligation, and chronic cerebral ischemia models were established by ligation of bilateral common carotid arteries in the 28 days after operation group and the 56 days after operation group. At 28 d and 56 d after operation, morris water maze was used to detect spatial learning and memory ability; diffusion tensor imaging was used to observe the fractional anisotropy (FA) and mean diffusivity (MD) rate of white matter nerve fibers in corpus callosum and hippocampus; luxol fast blue (LFB) staining was used to observe demyelination in corpus callosum; Western blot was used to detect the expression of myelin basic protein (MBP) and pericyte marker platelet-derived growth factor receptor β (PDGFR-β) in corpus callosum and hippocampus.Results(1) Learning and memory ability: compared with the sham operation group, the escape latency prolonged significantly from day 2 to day 4 after operation in the 28 days after operation group and on the 3rd day in the 56 days after operation group (PPPr=0.832, Pr=0.777, PPPP

Pericytes, as the mural cells surrounding the microvasculature, play a critical role in the regulation of microcirculation; however, how these cells respond to ischemic stroke remains unclear. To determine the temporal alterations in pericytes after ischemia/reperfusion, we used the 1-hour middle cerebral artery occlusion model, which was examined at 2, 12, and 24 hours after reperfusion. Our results showed that in the reperfused regions, the cerebral blood flow decreased and the infarct volume increased with time. Furthermore, the pericytes in the infarct regions contracted and acted on the vascular endothelial cells within 24 hours after reperfusion. These effects may result in incomplete microcirculation reperfusion and a gradual worsening trend with time in the acute phase. These findings provide strong evidence for explaining the “no-reflow” phenomenon that occurs after recanalization in clinical practice.

Abstract Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location‐specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all‐cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet‐derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p

Objective: Microvascular angina (MVA) is a coronary microcirculation disease. Research on microcirculatory dysfunction has revealed several biomarkers involved in the etiopathogenesis of MVA. Platelet-derived growth factor receptor β (PDGFR-β) and brain-derived neurotrophic factor (BDNF) are 2 biomarkers associated with microcirculation, particularly pericytes function. The aim of this study was to investigate the role of PDGFR-β and BDNF in MVA. Methods: Ninety-one patients (median age, 56 y; age range, 40–79 y; 36 men) with MVA and 61 control group subjects (median age, 52 y; age range, 38–76 y; 29 men) were included in the study. Serum concentrations of PDGFR-β and BDNF were measured with commercially available enzyme-linked immunosorbent assay kits. Results: PDGFR-β [2.82 ng/ml; interquartile range (IQR), 0.57–7.79 ng/ml vs. 2.27 ng/ml; IQR, 0.41–7.16 ng/ml; p