Search Results (97)

This study evaluated the bone regeneration effect and mechanical properties of “Sticky bone”, a mixture of platelet-rich fibrin (PRF) and synthetic bone grafts (SBGs), in the repair of large femoral bone defects in rabbits. Eighteen New Zealand white rabbits were included and randomly divided into a Sticky bone group and an SBG alone group. Bone graft samples were collected and analyzed at 4, 8, and 12 weeks after surgery. Micro- computed tomography (CT) analysis showed that the amount of the Sticky bone group in the grayscale ranges of 255–140 (highly mineralized tissue or unabsorbed bone powder) and 140–90 (representing new cancellous bone) was higher than that of the SBG group at each time point and decreased with the number of weeks. The compression strength test showed that the average compression strength of the Sticky bone group reached 5.17 MPa at the 12th week, which was 1.62 times that of the intact bone (3.19 MPa) and was significantly better than that of the SBG group (about 4.12 MPa). This study also confirmed for the first time that the use of a new polyethylene terephthalate (PET) blood collection tube to prepare PRF can stably release key growth factors such as platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF), which are conducive to early bone vascularization and cell proliferation. In summary, Sticky bone has the potential to promote bone formation, enhance tissue integration and mechanical stability, and can be used as an effective alternative material for repairing large-scale bone defects in clinical practice in the future. Full article

The abnormal growth of smooth muscle cells (SMCs) contributes to the vascular remodeling associated with coronary artery disease, a leading cause of death in women. Estradiol (E2) mediates cardiovascular protective actions, in part, by inhibiting the abnormal growth (proliferation and migration) of SMCs through various mechanism. Since microRNAs (miRNAs) play a major role in regulating cell growth and vascular remodeling, we hypothesize that miRNAs may mediate the protective actions of E2. Following preliminary leads from E2-regulated miRNAs, we found that platelet-derived growth factor (PDGF)-BB-induced miR-193a in SMCs is downregulated by E2 via estrogen receptor (ER)α, but not the ERβ or G-protein-coupled estrogen receptor (GPER). Importantly, miR-193a is actively involved in regulating SMC functions. The ectopic expression of miR-193a induced vascular SMC proliferation and migration, while its suppression with antimir abrogated PDGF-BB-induced growth, effects that were similar to E2. Importantly, the restoration of miR-193a abrogated the anti-mitogenic actions of E2 on PDGF-BB-induced growth, suggesting a key role of miR-193a in mediating the growth inhibitory actions of E2 in vascular SMCs. E2-abrogated PDGF-BB, but not miR-193a, induced SMC growth, suggesting that E2 blocks the PDGF-BB-induced miR-193a formation to mediate its anti-mitogenic actions. Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism. Furthermore, we found that miR-193a induces SMC growth by activating the phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway and promoting the G1 to S phase progression of the cell cycle, by inducing Cyclin D1, Cyclin Dependent Kinase 4 (CDK4), Cyclin E, and proliferating-cell-nuclear-antigen (PCNA) expression and Retinoblastoma-protein (RB) phosphorylation. Importantly, in mice, treatment with miR-193a antimir, but not its control, prevented cuff-induced vascular remodeling and significantly reducing the vessel-wall-to-lumen ratio in animal models. Taken together, our findings provide the first evidence that miR-193a promotes SMC proliferation and migration and may play a key role in PDGF-BB-induced vascular remodeling/occlusion. Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease. Full article

Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article

Lafora progressive myoclonus epilepsy (LD, OMIM#254780, ORPHA:501) is an ultra-rare and severe autosomal recessive neurological disorder that typically manifests in early adolescence. It is characterized by the accumulation of insoluble forms of aberrant glycogen in the brain and peripheral tissues. Given the urgent need for reliable tools to monitor disease progression, we aimed to identify reliable biomarkers in minimally invasive fluids, which could also provide valuable insights into the natural history of the disease. Plasma-EDTA samples from eleven LD patients and healthy controls were analyzed to identify potential biomarkers of LD using a high-throughput assay. The findings were subsequently validated using specific enzyme-linked immunosorbent assays (ELISAs). Eleven cytokines and growth factors were identified to be significantly reduced in LD patient samples compared to healthy controls. Among these, four mediators [platelet-derived growth factor subunit B (PDGF-BB), epidermal growth factor (EGF), brain derived growth factor (BDNF), and macrophage migration inhibitory factor (MIF)] exhibited the greatest fold change between the groups and were further validated. Given the minimally invasive nature of plasma sampling and the straightforward quantification via ELISA assays, these biomarkers hold strong promise for rapid translation to the clinic, potentially enhancing early diagnosis and longitudinal disease monitoring in LD patients. Full article

Prostate cancer with bone metastasis exhibits significant heterogeneity, complicating prognosis, and treatment. This study explores the potential of plasma, serum, and urine biomarkers to stratify patients and evaluate their prognostic value. Using two-step clustering, we analyzed baseline levels of Platelet-derived growth factor-BB (PDGF-BB), Insulin-like growth factor-binding protein 1 (IGFBP-1), Bone Morphogenetic Protein 2 (BMP-2), Vascular endothelial growth factor (VEGF) (plasma and urine), prostate-specific antigen (PSA), neuron-specific enolase (NSE), chromogranin A (CgA) and bone-specific alkaline phosphatase (BAP) (serum) and creatinine (Cr), and type I collagen-cross-linked N telopeptide (NTx) (urine) in 29 patients with prostate cancer and bone metastasis. Longitudinal biomarker dynamics were assessed at baseline, 6 months, and 12 months. Clinical outcomes were evaluated using Kaplan–Meier and multivariate analyses. Three distinct groups (C1, C2, and C3) were identified. C1 exhibited elevated pPDGF-BB and pVEGF levels, C3 had increased pBAP and uNTx/Cr, and C2 showed lower biomarker levels. Prior treatments influenced biomarker levels, with bisphosphonates reducing bone turnover markers and radiotherapy correlating with long-term changes in growth factors. Longitudinal analysis revealed unique biomarker dynamics within each group, with a tendency for pPDGF-BB and pVEGF levels to decrease over time in C1, and distinct trends in uNTx/Cr between groups. Despite individual biomarkers failing to predict survival, C3 patients demonstrated significantly worse survival than C1 and C2. Molecular clustering of peripheral blood and urinary biomarkers identifies distinct subgroups with metastatic castration-resistant prostate cancer patients outperforming traditional models in outcome prediction and supporting its potential for personalized treatment and prognosis. Full article

Tendon ruptures are common musculoskeletal injuries associated with prolonged healing and complications such as adhesion formation and rerupture. Despite advancements in treatment strategies, full functional recovery remains a challenge. Growth factors (GFs) like insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor-BB (PDGF-BB) play key roles in tendon repair and may have synergistic effects when applied together. To support tendon healing, a bioactive electrospun polymer scaffold made of Degrapol^® (DP) was developed, incorporating IGF-1, PDGF-BB, or both. A range of in vitro and in vivo analyses were performed to assess scaffold structure, cell behavior, gene expression, metabolism, and biomechanical and adhesion outcomes three weeks post-surgery. Interestingly, the combined application of IGF-1 and PDGF-BB did not simply amplify individual effects but showed a complex interaction. Depending on the parameter and time point, the combination led to either enhanced or reduced responses compared to single-factor treatments, indicating a synergistic modulation rather than a purely additive effect. These findings suggest that the combination of IGF-1 and PDGF-BB can modulate key cellular and molecular processes in tendon regeneration, making this approach a promising strategy to improve tendon healing. Full article

People engaged in various activities in cold environments—such as those living in cold climates, polar workers, cold storage workers, and athletes engaged in winter sports—are frequently affected by cold environments. Therefore, it is of great significance to explore the modelling and remodelling of bones in cold environments. Cold environments can shorten the length of bones, thin the thickness of bones, decrease bone mineral density (BMD), change the biomechanical properties of bones, and lead to bone loss. In addition, cold directly affects the bone microenvironment. Exposure to cold causes spindle-like and fibroblast-like changes in bone marrow mesenchymal stem cells (BMSCs) and decreases their proliferation, and cold exposure promotes the osteogenic differentiation of BMSCs partly through the p38 MAPK pathway. Cold also alters the dendritic differentiation of OBs by reducing the transmembrane glycoprotein E11/podoplanin and damages endothelial cells (ECs) by elevating levels of VEGF, resulting in a reduced blood supply and thus fewer OBs. In addition, cold promotes lipolysis of marrow adipose tissue (MAT), but in combination with exercise, it can promote the differentiation of BMSCs into MAT. Cold environments interfere with angiogenesis and inhibit bone growth by affecting factors such as platelet-derived growth factor type BB (PDGF-BB), slit guidance ligand 3 (SLIT3), Notch, and VEGF. In addition, cold environments may promote bone resorption by activating sympathetic nerves to activate β-adrenergic receptors and regulating leptin secretion, and regulate bone metabolism by activating the p38 MAPK signalling pathway and increasing the synthesis of brown fat, which ultimately inhibit bone formation and enhance bone resorption. In this paper, we describe the effects of cold environments on bones in the locomotor system in terms of bone structure, bone mass, biomechanical properties, and various skeletal cells, bone blood vessels, and bone fat systems in the bone microenvironment. Full article

Aplastic anemia (AA) is characterized by bone marrow (BM) aplasia and pancytopenia. BM stromal microenvironment is closely intertwined with hematopoietic cells by reciprocal regulation. It is still unclear how hematopoietic deficiency affects the bone marrow stroma of the AA patients. Multipotent mesenchymal stromal cells (MMSCs) are the progenitors of stromal cells. In vitro, proliferation rate of MMSCs of AA patients is decreased compared to those of healthy donors. This may be explained by the influence of pathological environmental condition in the patients’ BM. The aim of the study was to compare the effect of AA patients’ sera on healthy donor MMSCs to healthy donors’ sera and to elucidate the nature of their difference. Proliferation test showed 3-fold decrease in number of MMSCs after incubation in medium supplemented with AA patients’ sera compared to donors’ serum samples. The degree of this effect correlated with the severity of thrombocytopenia in patients. The decrease in cell number was not associated with cell death, as the number of apoptotic cells defined by flow cytometry did not differ between the groups. ELISA revealed a decreased level of PDGF-BB in the patients’ sera compared to donors’ serum samples (69 ± 5 pg/mL vs. 112 ± 21 pg/mL, respectively). The addition of recombinant PDGF-BB or healthy donor’s platelet lysate to the culture medium supplemented with AA patients’ serum restored its ability to support MMSCs growth. Thus, PDGF-BB deficiency is one of the environmental factors causing MMSCs damage in AA patients. Full article

Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of 84 NEN patients and 40 healthy controls using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA. Significant alterations in cytokine levels were observed in the NEN patients compared to the controls, including elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), and reduced levels of angiogenic factors like platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor beta (TNF-β). Notably, cytokines such as growth-regulated alpha protein (GRO-α) and TNF-β demonstrated strong potential as diagnostic markers, with receiver operating characteristic (ROC) curve analyses showing high sensitivity and specificity. Additionally, a positive correlation was found between CgA levels and several inflammatory cytokines, suggesting their synergistic role in tumor progression. These findings highlight the limited reliability of CgA alone as a diagnostic marker and underscore the importance of a multi-marker approach in diagnosing and monitoring NENs. Further research on a larger cohort is necessary to validate these biomarkers and their potential clinical applications. Full article

The abnormal proliferation and differentiation of oral mucosal fibroblasts (FBs) is the key to the progression of oral submucosal fibrosis. To clarify the mechanism of platelet-derived growth factor (PDGF-BB)-induced FBs fibrosis in oral mucosa, real-time quantitative polymerase chain reaction and Western blot were used in this study to detect the expression of miR-503 and the expression of p-MEK, p-ERK, miR-503, RAF, smooth actin and type I collagen under different time and concentration stimulation of PDGF-BB. The effects of overexpression of miR-503 or RAF on the proliferation and migration of FBs were detected by cell counting kit 8 and cell scratch assay, respectively. A dual luciferase reporter gene assay was used to verify the targeting effect of miR-503 on RAF. The results showed that miR-503 was downregulated in a dose- and time-dependent manner in PDGF-BB-induced FBs. In addition, RAF is a direct target of miR-503 and can be negatively regulated. Overexpression of RAF can promote FB proliferation, migration, differentiation, collagen synthesis, and activation of downstream molecules (MEK/ERK), while overexpression of miR-503 can partially reverse the effects of RAF. Therefore, miR-503 regulates the biological behavior of PDGF-BB-induced oral mucosal FBs by influencing the activation of the RAS/RAF/MEK/ERK signaling pathway. Full article

Despite the use of screening programs, gastric cancer (GC) diagnosis may only be possible at an advanced stage. In this study, we examined the serum levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with gastric carcinoma and healthy controls to investigate the significance and usability of these potential biomarkers in the early diagnosis of GC. The study enrolled 69 GC patients and 40 healthy individuals. CCR5, CCL5, PDGF-BB, and EphA7 levels, which have been identified in the carcinogenesis of many cancers, were measured in the blood samples using the ELISA method. CCR5, CCL5, PDGF-BB, and EphA7 were all correlated with GC diagnosis (CCR5, p < 0.001, r = −0.449; CCL5, p = 0.014, r = −0.234; PDGF-BB, p < 0.001, r = −0.700; EPHA7, p < 0.001, r = −0.617). The serum CCR5, EphA7, and especially the PDGF-BB levels of the patients diagnosed with GC were discovered to be significantly higher compared to the healthy controls. PDGF-BB had the highest positive and negative predictive values when evaluated in ROC analysis to determine its diagnostic significance (cut-off value: 59.8 ng/L; AUC: 0.92 (0.87–0.97)). As far as we know, this is the first study to investigate the potential connection between GC and these four biomarkers. The fact that serum CCR5, CCL5, EphA7, and especially PDGF-BB levels in the patient group were significantly higher compared to healthy controls indicates that they can be used with high accuracy in the early diagnosis of GC. In addition, the levels of CCR5, PDGF-BB, and EphA7 can be used as important indicators to predict the biological behavior and prognosis of GC. Full article

Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir (DTG)-based ART. Data on the impact of this transition are still limited. The current study therefore investigated the metabolic profiles, cytokine inflammatory responses, and platelet activation before and after the treatment transition. Plasma samples from nine virally suppressed adults living with HIV and sixteen healthy, HIV-uninfected individuals residing in Gauteng, South Africa were compared. Metabolite and cytokine profiles, and markers associated with platelet activation, were investigated with untargeted proton magnetic resonance metabolomics, multiplex suspension bead array immunoassays, and sandwich enzyme-linked immunosorbent assays, respectively. In those individuals with normal C-reactive protein levels, the transition to a DTG-based ART regimen resulted in decreased concentrations of acetoacetic acid, creatinine, adenosine monophosphate, 1,7-dimethylxanthine, glycolic acid, 3-hydroxybutyric acid, urea, and lysine. Moreover, increased levels of formic acid, glucose, lactic acid, myo-inositol, valine, glycolic acid, and 3-hydroxybutyric acid were observed. Notably, levels of interleukin-6, platelet-derived growth factor-BB, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor–alpha, soluble cluster of differentiation 40 ligand, as well as regulated on activation, normal T-cell expressed and secreted (RANTES) reached levels close to those observed in the healthy control participants. The elevated concentration of macrophage inflammatory protein-1 alpha was the only marker indicative of elevated levels of inflammation associated with DTG-based treatment. The transition from EFV- to DTG-based regimens therefore appears to be of potential benefit with metabolic and inflammatory markers, as well as those associated with cardiovascular disease and other chronic non-AIDS-related diseases, reaching levels similar to those observed in individuals not living with HIV. Full article

(1) Background: There is a lack of knowledge about how a single dose of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) might affect the release of growth factors (GFs) and cytokines from canine platelet-rich gels (PRGs) and other hemocomponents. (2) Methods: A crossover study was conducted in six adult mongrel dogs. Animals were randomized to receive a single dose of either carprofen or firocoxib. PRG, temperature-induced platelet lysate (TIPL), chemically induced PL (CIPL), and plasma hemocomponents were obtained from each dog before (1 h) and after (6 h) the treatments. Platelet and leukocyte counts and determination of the concentrations of platelet-derived growth factor-BB, (PDGF-BB), transforming growth factor beta-1 (TGF-β₁), interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-10 concentrations were assayed by ELISA in all hemocomponents. (3) Results: Both platelet and leukocyte counts and PDGF-BB concentrations were not affected by NSAIDs and time. Total TGF-β₁ concentrations were not affected by NSAIDs; however, the release of this GF was increased in PRG supernatants (PRGS) at 6 h. IL-1β and TNF-α concentrations were significantly (p < 0.001) lower in both firocoxib PRGS and plasma at 6 h, respectively. IL-10 concentrations were significantly (p < 0.001) lower at 6 h in all hemocomponents treated with both NSAIDs. (4) Conclusions: The clinical implications of our findings could indicate that these drugs should be withdrawn from patients to allow their clearance before the clinical use of PRP/PRG. On the other hand, the prophylactic use of NSAIDs to avoid the inflammatory reactions that some patients might have after PRP/PRG treatment should be performed only in those animals with severe reactive inflammation to the treatment. Full article

Background: Tocotrienols exhibit antioxidant and anti-inflammatory activities. RhoA, a small GTPase protein, plays a crucial role in regulating contractility in airway smooth muscle (ASM). Previous studies have demonstrated that γ-tocotrienols reduce ASM proliferation and migration by inhibiting the activation of RhoA. In this present study, we investigate the effect of another vitamin E isoform, β-tocotrienols, on human ASM cell proliferation and migration stimulated by platelet-derived growth factor-BB (PDGF-BB). Methods: Human ASM cells were pre-treated with β-tocotrienol prior to being stimulated with PDGF-BB to induce ASM cell proliferation and migration. The proliferation and migration of PDGF-BB-induced human ASM cells were assessed using colorimetric and transwell migration assays. The intracellular ROS assay kit was employed to quantify reactive oxygen species (ROS) in human ASM cells. Additionally, we explored the effect of β-tocotrienols on the signaling pathways involved in PDGF-BB-induced ASM proliferation and migration. Results: β-tocotrienol inhibited PDGF-BB-induced ASM cell proliferation and migration by reducing RhoA activation and ROS production. However, in this present study, β-tocotrienol did not affect the signaling pathways associated with cyclin D1, phosphorylated Akt1, and ERK1/2. Conclusions: In conclusion, the inhibition of RhoA activation and ROS production by β-tocotrienol, resulting in the reduction in human ASM proliferation and migration, suggests its potential as a treatment for asthma airway remodeling. Full article

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC. Full article