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To evaluate the efficacy of platelet-rich fibrin (PRF) as an adjunct to scaling and root planing (ScRp) for healing shallow periodontal pockets. Twelve patients with periodontitis were enrolled in this split-mouth, randomized clinical trial. A total of 24 shallow periodontal pockets (4–6 mm) were treated by either ScRp alone (control) or PRF (test). Clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), and plaque index (PLI), as well as platelet-derived growth factor-BB (PDGF-BB) by enzyme-linked immunosorbent assay (ELISA) in gingival crevicular fluid (GCF) were measured at baseline and at 1- and 3-month follow-up visits. At 1- and 3-month follow-up visits, greater CAL gains (2.6 ± 0.25 mm and 3.26 ± 0.31 mm, respectively) and PPD reductions (2.58 ± 0.38 and 3.31 ± 0.39 mm, respectively) were observed in the test group compared to those in controls (CAL gain of 1.01 ± 0.49 mm and 1.43 ± 0.48 mm; PPD reduction of 1.1 ± 0.55 and 1.37 ± 0.49 mm, respectively). In addition, the increase in PDGF-BB in GCF in the test group (724.5 ± 186.09 pg/μl and 1957.5 ± 472.9 pg/μl) was significantly greater than that in controls (109.3 ± 24.07 and 614.64 ± 209.3 pg/μl) at 1- and 3-month follow-up visits, respectively. The noninvasive use of PRF as an adjunct to ScRp successfully improved clinical periodontal parameters and might contribute to increased PDGF-BB in GCF. [ABSTRACT FROM AUTHOR]

Abstract Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.

Multiple myeloma (MM) is an incurable B‐cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL‐18 and M‐CSF levels showed significantly shorter progression‐free survival and overall survival (OS). In contrast, patients with high PDGF‐BB levels had longer survival. Moreover, low levels of G‐CSF, IL‐7, IL‐8, and SDF‐1α were associated with shorter OS after Ld therapy. During Ld therapy, pro‐inflammatory cytokines such as IL‐2Rα, IL‐18, and TNF‐α were decreased, while IFN‐γ was increased. IL‐4 and IL‐6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, particularly those involving arterial stenosis and smooth muscle cell proliferation, pose significant health risks. This study aimed to investigate the therapeutic potential of curcumol in inhibiting platelet‐derived growth factor‐BB (PDGF‐BB)‐induced human aortic smooth muscle cell (HASMC) proliferation, migration and autophagy. Using cell viability assays, 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assays and Western Blot analyses, we observed that curcumol effectively attenuated PDGF‐BB‐induced HASMC proliferation and migration in a concentration‐dependent manner. Furthermore, curcumol mitigated PDGF‐BB‐induced autophagy, as evidenced by the downregulation of LC3‐II/LC3‐I ratio and upregulation of P62. In vivo experiments using an arteriosclerosis obliterans model demonstrated that curcumol treatment significantly ameliorated arterial morphology and reduced stenosis. Additionally, curcumol inhibited the activity of the KLF5/COX2 axis, a key pathway in vascular diseases. These findings suggest that curcumol has the potential to serve as a multi‐target therapeutic agent for vascular diseases. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.

Abstract Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the “angiogenesis and osteogenesis coupling”, and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the “angiogenesis-osteogenesis coupling” and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.

Musculoskeletal injuries and bone defects represent a significant clinical challenge, necessitating innovative approaches for effective bone tissue regeneration. In this study, we investigated the potential of harnessing periosteal stem cells (PSCs) and glycosaminoglycan (GAG)-mimicking materials for in situ bone regeneration. Our findings demonstrated that the introduction of 2-N, 6-O sulfated chitosan (26SCS), a GAG-like polysaccharide, enriched PSCs and promoted robust osteogenesis at the defect area. Mechanistically, 26SCS amplifies the biological effect of endogenous platelet-derived growth factor-BB (PDGF-BB) through enhancing the interaction between PDGF-BB and its receptor PDGFRβ abundantly expressed on PSCs, resulting in strengthened PSC proliferation and osteogenic differentiation. As a result, 26SCS effectively improved bone defect repair, even in an osteoporotic mouse model with lowered PDGF-BB level and diminished regenerative potential. Our findings suggested the significant potential of GAG-like biomaterials in regulating PSC behavior, which holds great promise for addressing osteoporotic bone defect repair in future applications.

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis. [ABSTRACT FROM AUTHOR]

Platelets are actively involved in tissue injury site regeneration by producing a wide spectrum of platelet-derived growth factors such as PDGF (platelet-derived growth factor), IGF-1 (insulin-like growth factor), TGF-β1 (transforming growth factor β), FGF (fibroblast growth factor), etc. A rotating magnetic field (RMF) can regulate biological functions, including reduction or induction regarding inflammatory processes, cell differentiation, and gene expression, to determine the effect of an RMF on the regenerative potential of platelets. The study group consisted of 30 healthy female and male volunteers (n = 15), from which plasma was collected. A portion of the plasma was extracted and treated as an internal control group. Subsequent doses of plasma were exposed to RMF at different frequencies (25 and 50 Hz) for 1 and 3 h. Then, the concentrations of growth factors (IGF-1, PDGF-BB, TGF-β1, and FGF-1) were determined in the obtained material by the ELISA method. There were statistically significant differences in the PDGF-BB, TGF-β1, IGF-1, and FGF-1 concentrations between the analyzed groups. The highest concentration of PDGF-BB was observed in the samples placed in RMF for 1 h at 25 Hz. For TGF-β1, the highest concentrations were obtained in the samples exposed to RMF for 3 h at 25 Hz and 1 h at 50 Hz. The highest concentrations of IGF-1 and FGF-1 were shown in plasma placed in RMF for 3 h at 25 Hz. An RMF may increase the regenerative potential of platelets. It was noted that female platelets may respond more strongly to RMF than male platelets. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis.Conditioned media derived from preosteoclasts pretreated with the CTSK inhibitor odanacatib (ODN), ODN supplemented small interfering RNA targeting PDGF‐BB (si‐PDGF‐BB), or PBS were prepared, to assess their proangiogenic effects on endothelial cells (HUVECs). A series of angiogenic‐related assays were conducted to evaluate HUVEC proliferation, migration, and tube formation abilities in vitro. In addition, qRT‐PCR and Western blot assays were employed to examine the expression levels of genes/proteins related to PDGF‐BB/PDGFR‐β axis components. A mouse periodontitis model was established to evaluate the effects of CTSK inhibition on type H vessel formation.CTSK inhibition promoted PDGF‐BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs in vitro. However, the conditioned medium from preosteoclasts pretreated by si‐PDGF‐BB impaired the angiogenic activities of HUVECs. This promoted angiogenesis function by CTSK inhibition may be mediated by the PDGF‐BB/PDGFR‐β axis. Functionally, in vivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis.CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF‐BB/PDGFR‐β axis. [ABSTRACT FROM AUTHOR]

Abstract Multiple myeloma (MM) is an incurable B‐cell malignancy often accompanied by profound immunodeficiency. Lenalidomide (Len) is an immunomodulatory drug that exerts promising therapeutic effects on MM through the immune system. However, predictive markers related to the effects of Len treatment are not fully understood. This study aimed to identify candidate biomarkers for predicting the clinical efficacy of Len and dexamethasone (Ld) therapy through a comprehensive analysis of serum cytokines. The levels of 48 cytokines in the serum of patients with MM just before Ld therapy (n = 77), at the time of best response (n = 56), and at disease progression (n = 49) were measured and evaluated. Patients with high IL‐18 and M‐CSF levels showed significantly shorter progression‐free survival and overall survival (OS). In contrast, patients with high PDGF‐BB levels had longer survival. Moreover, low levels of G‐CSF, IL‐7, IL‐8, and SDF‐1α were associated with shorter OS after Ld therapy. During Ld therapy, pro‐inflammatory cytokines such as IL‐2Rα, IL‐18, and TNF‐α were decreased, while IFN‐γ was increased. IL‐4 and IL‐6 levels increased during disease progression. In conclusion, this study provides a better understanding of the association between cytokines and the efficacy of Ld therapy as well as the unique changes in cytokines related to inflammatory and immune responses during Ld therapy.

Abstract The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

Abstract Background Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for the targeted delivery of bone marrow mesenchymal stem cells (MSCs) to the ischemic myocardium. However, the limited migration capacity and poor survival of MSCs remains a major therapeutic barrier. The present study was performed to investigate the synergistic effect of UTMD with platelet-derived growth factor BB (PDGF-BB) on the homing of MSCs for acute myocardial infarction (AMI). Methods MSCs from male donor rats were treated with PDGF-BB, and a novel microbubble formulation was prepared using a thin-film hydration method. In vivo, MSCs with or without PDGF-BB pretreatment were transplanted by UTMD after inducing AMI in experimental rats. The therapeutic efficacy of PDGF-BB-primed MSCs on myocardial apoptosis, angiogenesis, cardiac function and scar repair was estimated. The effects and molecular mechanisms of PDGF-BB on MSC migration and survival were explored in vitro. Results The results showed that the biological effects of UTMD increased the local levels of stromal-derived factor-1 (SDF-1), which promoted the migration of transplanted MSCs to the ischemic region. Compared with UTMD alone, UTMD combined with PDGF-BB pretreatment significantly increased the cardiac homing of MSCs, which subsequently reduced myocardial apoptosis, promoted neovascularization and tissue repair, and increased cardiac function 30 days after MI. The vitro results demonstrated that PDGF-BB enhanced MSC migration and protected these cells from H2O2-induced apoptosis. Mechanistically, PDGF-BB pretreatment promoted MSC migration and inhibited H2O2-induced MSC apoptosis via activation of the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway. Furthermore, crosstalk between PDGF-BB and stromal-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) is involved in the PI3K/AKT signaling pathway. Conclusion The present study demonstrated that UTMD combined with PDGF-BB treatment could enhance the homing ability of MSCs, thus alleviating AMI in rats. Therefore, UTMD combined with PDGF-BB pretreatment may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.

(1) Background: Current treatments for knee osteoarthritis (KOA), such as intra-articular corticosteroids or hyaluronic acid (HA) injections, are controversial due to their ineffectiveness in preventing disease progression. Platelet-rich plasma (PRP) has become a promising and possible treatment for KOA. It is thought to enhance articular cartilage regeneration and reduce OA-related impairment. PRP contains growth factors such as PDGF-BB, which stimulates growth and inhibits joint damage. Based on numerous studies, after a certain amount of time, it was found that multiple PRP treatments reduced pain more than a single injection. This study evaluates the efficacy of multiple PRP (m-PRP) injections compared to multiple HA (m-HA) injections for KOA treatment, focusing on their correlation with PDGF-BB levels. (2) Methods: In this single-center, open-label, randomized, comparative clinical trial, 30 KOA patients received m-PRP and m-HA injections. VAS and WOMAC were used to evaluate clinical outcomes and PDGF-BB concentrations. (3) Results: The study analysis revealed a statistically significant reduction in pain indices. In both the m-PRP and m-HA groups after 12 weeks, m-PRP showed superior results. PDGF-BB concentrations also increased, with a strong negative correlation and statistical significance using Spearman's rho. (4) Conclusions: Multiple PRP injections are safe and associated with elevated PDGF-BB, reduced VAS and WOMAC scores, providing the potential for articular cartilage regeneration and inhibiting knee osteoarthritis progression. [ABSTRACT FROM AUTHOR]

The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, complex, and immunologically mediated systemic disease that not only affects the skin, but also the joints and nails. It may coexist with various other disorders, such as depression, psoriatic arthritis, cardiovascular diseases, diabetes mellitus, and metabolic syndrome. In particular, the potential link between psoriasis and metabolic syndrome is an issue worthy of attention. The dysregulation of growth factors could potentially contribute to the disturbances of keratinocyte proliferation, inflammation, and itch severity. However, the pathophysiology of psoriasis and its comorbidities, such as metabolic syndrome, remains incompletely elucidated. Growth factors and their abnormal metabolism may be a potential link connecting these conditions. Overall, the objective of this review is to analyze the role of growth factor disturbances in both psoriasis and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters is important for early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understand the pathomechanism of ENL by examining IL-7 and plateletderived growth factor (PDGF)-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was an increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL. [ABSTRACT FROM AUTHOR]

Background: Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for the targeted delivery of bone marrow mesenchymal stem cells (MSCs) to the ischemic myocardium. However, the limited migration capacity and poor survival of MSCs remains a major therapeutic barrier. The present study was performed to investigate the synergistic effect of UTMD with platelet-derived growth factor BB (PDGF-BB) on the homing of MSCs for acute myocardial infarction (AMI). Methods: MSCs from male donor rats were treated with PDGF-BB, and a novel microbubble formulation was prepared using a thin-film hydration method. In vivo, MSCs with or without PDGF-BB pretreatment were transplanted by UTMD after inducing AMI in experimental rats. The therapeutic efficacy of PDGF-BB-primed MSCs on myocardial apoptosis, angiogenesis, cardiac function and scar repair was estimated. The effects and molecular mechanisms of PDGF-BB on MSC migration and survival were explored in vitro. Results: The results showed that the biological effects of UTMD increased the local levels of stromal-derived factor-1 (SDF-1), which promoted the migration of transplanted MSCs to the ischemic region. Compared with UTMD alone, UTMD combined with PDGF-BB pretreatment significantly increased the cardiac homing of MSCs, which subsequently reduced myocardial apoptosis, promoted neovascularization and tissue repair, and increased cardiac function 30 days after MI. The vitro results demonstrated that PDGF-BB enhanced MSC migration and protected these cells from H2O2-induced apoptosis. Mechanistically, PDGF-BB pretreatment promoted MSC migration and inhibited H2O2-induced MSC apoptosis via activation of the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway. Furthermore, crosstalk between PDGF-BB and stromal-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) is involved in the PI3K/AKT signaling pathway. Conclusion: The present study demonstrated that UTMD combined with PDGF-BB treatment could enhance the homing ability of MSCs, thus alleviating AMI in rats. Therefore, UTMD combined with PDGF-BB pretreatment may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases. [ABSTRACT FROM AUTHOR]

The goal of this paper is to examine the use of pig blood in the industrial mass production of platelet dry powder and to transform platelet dry powder into a low-cost and mass-produced material. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) contain multiple types of growth factors (GFs) and can be widely used in medical applications. However, neither can be mass-produced, due to the complexity of the PRP preparation process and the lack of anticoagulants in the PRF preparation process, increasing the risk of coagulation during mass production. Another obstacle is the insufficient supply of autologous PRP and autologous PRF. In this study, platelet dry powder was mass-produced from pig blood through the indirect addition of calcium chloride solution. Furthermore, the results showed that different concentrations and percentages of calcium chloride solution had significant effects on concentrations of TGF-β1 and PDGF-BB in the platelet dry powder. The platelet dry powder mass-produced from pig blood demonstrated high concentrations of GFs and long-term shelf stability, increasing the supply to industries that use it in product development. [ABSTRACT FROM AUTHOR]

Abstract Aims This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment. Main methods Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues. Key findings We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells. Significance This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment.

Simple Summary: In modern, highly industrialized countries, endometrial cancer is the most common gynecological cancer. Endometrial cancer risk has been found to be influenced by a number of variables. The pathogenesis of endometrial cancer is heavily influenced by fatty food consumption in excess, a lack of physical activity and the subsequent development of obesity or diabetes. The first symptoms of endometrial cancer may be unusual vaginal bleeding or pelvic discomfort, but they are also typical of many other diseases. It is important to search for new biomarkers that could help detect endometrial cancer, even if it shows symptoms in its early stages. PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 are growth factor proteins. We investigated whether growth factor proteins can be clinically useful diagnostic markers in endometrial cancer. The study's objective was to identify the clinical relevance of the proteins under investigation. We made a comparison between the serum protein concentrations of people with endometrial cancer and those with non-cancerous endometrial lesions. (1) Background: It is relevant to find new diagnostic biomarkers for endometrial cancer. This study aimed to investigate whether PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 could be considered new useful markers for diagnosis and survival of endometrial cancer. (2) Methods: A total of 93 women diagnosed with endometrial cancer (EC) and 66 patients with non-cancerous endometrial lesions (NCEL) were included in this study. (3) Results: Median serum levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 were significantly higher in the EC group compared to the NCEL group (for PDGF-AB, PDGF-BB, TGF-α and ANG-2, p = 0.0000; for EGF, p = 0.0186). The cut-off level of PDGF-AB was set at 127.69 pg/mL with a sensitivity of 87.1% and a specificity of 66.67% (AUC = 0.78, p < 0.000001). The cut-off level of PDGF-BB was set at 207.86 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.85, p < 0.000001). The cut-off level of TGF-α was set at 33.85 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.82, p < 0.000001). The cut-off level of EGF was set at 934.76 pg/mL with a sensitivity of 83.87% and a specificity of 28.79% (AUC = 0.61, p = 0.018472). The cut-off level of ANG-2 was set at 3120.68 pg/mL with a sensitivity of 72.04% and a specificity of 93.94% (AUC = 0.87, p < 0.000001). (4) Conlusion: It was concluded that all the proteins studied could be potential diagnostic markers in endometrial cancer. [ABSTRACT FROM AUTHOR]

Aims: This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment. Main methods: Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues. Key findings: We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells. Significance: This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as "must-check" parameters to characterize individual PRP preparations prior to clinical trials. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor-BB (PDGF-BB), a multifunctional growth factor secreted by platelets, endothelial and cancer cells, functions as an efficient and accurate biomarker. PDGF- BB has been employed in various therapeutic applications. Tuning its bioactivity via a specific binding ligand could enhance the PDGF-BB functionality. Aptamer, a single-stranded oligonucleotide that exhibits a selective binding to PDGF-BB, is the molecule of our interest. This research aims to evaluate the PDGF-BB aptamer binding by growth factor-coated particles. PDGF-BB-coated particles were confirmed by ELISA, and aptamer binding evaluation was investigated by flow cytometry. To optimize the condition for binding evaluation, the washing cycle and concentration of PDGF-BB, polystyrene particle and aptamer were studied using flow cytometer. Based on the flow cytometry results, the concentration of PDGF-BB showed an optimal level on the number of fluorescent particles. The percentage of fluorescent particles increased when the washing cycle was reduced and the particle concentration was decreased. The percentage of fluorescent particles also increased proportionally with the aptamer concentration. Using a flow cytometer to detect fluorescent signal from growth factor-coated particle is a promising strategy to study biomolecular binding. [ J Adv Biotechnol Exp Ther 2023; 6(1.000): 243-253]

Platelets are actively involved in tissue injury site regeneration by producing a wide spectrum of platelet-derived growth factors such as PDGF (platelet-derived growth factor), IGF-1 (insulin-like growth factor), TGF-β1 (transforming growth factor β), FGF (fibroblast growth factor), etc. A rotating magnetic field (RMF) can regulate biological functions, including reduction or induction regarding inflammatory processes, cell differentiation, and gene expression, to determine the effect of an RMF on the regenerative potential of platelets. The study group consisted of 30 healthy female and male volunteers (n = 15), from which plasma was collected. A portion of the plasma was extracted and treated as an internal control group. Subsequent doses of plasma were exposed to RMF at different frequencies (25 and 50 Hz) for 1 and 3 h. Then, the concentrations of growth factors (IGF-1, PDGF-BB, TGF-β1, and FGF-1) were determined in the obtained material by the ELISA method. There were statistically significant differences in the PDGF-BB, TGF-β1, IGF-1, and FGF-1 concentrations between the analyzed groups. The highest concentration of PDGF-BB was observed in the samples placed in RMF for 1 h at 25 Hz. For TGF-β1, the highest concentrations were obtained in the samples exposed to RMF for 3 h at 25 Hz and 1 h at 50 Hz. The highest concentrations of IGF-1 and FGF-1 were shown in plasma placed in RMF for 3 h at 25 Hz. An RMF may increase the regenerative potential of platelets. It was noted that female platelets may respond more strongly to RMF than male platelets.

Introduction: Erythema Nodosum Leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters are important to early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understanding the pathomechanism of ENL by examined IL-7 and PDGF-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. Materials and Methods: The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. Results: The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL.

Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive‐like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)‐dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)‐induced depression‐like behavior. Further analysis exhibits that inhibition of gamma‐aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+‐DG) increases the expression of platelet‐derived growth factor‐BB (PDGF‐BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant‐like effects. Overexpression of the PDGF‐BB or exogenous administration of PDGF‐BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult‐born hippocampal neurons, as well as on depressive‐like behaviors. Conversely, knockdown of PDGF‐BB facilitates CSDS‐induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet‐derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF‐BB. These results delineate a previously unidentified PDGF‐BB/PDGFRβ signaling in regulating depressive‐like behaviors and identify a novel mechanism by which the MSGABA+‐DG pathway regulates the expression of PDGF‐BB in SOM‐positive interneurons. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we showed that the prognostic value of serum concentrations and the tissue expressions of angiogenic growth factors VEGF, bFGF, and PDGF-bb vary according to the phenotypic subtype of the tumor. Patients were classified into phenotypic subgroups (immune, canonical, metabolic, and mesenchymal). Preoperative serum concentrations and tissue expressions of VEGF, bFGF, and PDGF-bb were determined among each phenotypic subgroup. A high tissue expression and serum concentration of angiogenic growth factors seem to indicate improved prognosis among the metabolic subgroup. Among immune patients, a high VEGF serum concentration is associated with worse prognosis. Moreover, a high serum concentration of bFGF indicated improved prognosis among canonical patients. We classified colorectal cancer (CRC) patients into four phenotypic subgroups and investigated the prognostic value of angiogenic growth factors across subgroups. Preoperative serum concentrations and tissue expressions of VEGF, bFGF, and PDGF-bb were determined among 322 CRC patients. We classified patients into phenotypic subgroups (immune, canonical, metabolic, and mesenchymal) according to a method described in our earlier work. Among the metabolic subgroup, patients with high serum concentrations of VEGF, bFGF, or PDGF-bb exhibited a significantly improved prognosis. Moreover, those with high VEGF tissue expressions exhibited a significantly improved prognosis among patients in the metabolic subgroup. Among immune patients, a high VEGF serum expression is associated with a worse prognosis. A high serum bFGF concentration is associated with a favorable prognostic factor among patients with a canonical tumor phenotype. A high PDGF-bb tissue expression is associated with non-metastasized disease and with the immune, canonical, and metabolic subtypes. To our knowledge, this is the first study to show that the prognostic value of angiogenic growth factors differs between phenotypic subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Culturing cerebrovascular smooth muscle cells (CVSMCs) in vitro can provide a model for studying many cerebrovascular diseases. This study describes a convenient and efficient method to obtain mouse CVSMCs by enzyme digestion. Methods: Mouse circle of Willis was isolated, digested, and cultured with platelet-derived growth factor-BB (PDGF-BB) to promote CVSMC growth, and CVSMCs were identified by morphology, immunofluorescence analysis, and flow cytometry. The effect of PDGF-BB on vascular smooth muscle cell (VSMC) proliferation was evaluated by cell counting kit (CCK)-8 assay, morphological observations, Western blotting, and flow cytometry. Results: CVSMCs cultured in a PDGF-BB-free culture medium had a typical peak-to-valley growth pattern after approximately 14 days. Immunofluorescence staining and flow cytometry detected strong positive expression of the cell type-specific markers alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain 11 (SMMHC), smooth muscle protein 22 (SM22), calponin, and desmin. In the CCK-8 assay and Western blotting, cells incubated with PDGF-BB had significantly enhanced proliferation compared to those without PDGF-BB. Conclusion: We obtained highly purified VSMCs from the mouse circle of Willis using simple methods, providing experimental materials for studying the pathogenesis and treatment of neurovascular diseases in vitro. Moreover, the experimental efficiency improved with PDGF-BB, shortening the cell cultivation period. [ABSTRACT FROM AUTHOR]

Introduction: Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. The malignant transformation rate of OSMF is 7.6%, with a mean transformation rate of 4.7 years. It is characterized by epithelial atrophy and progressive accumulation of collagen fibers in lamina propria and submucosa of the oral mucosa. Increased collagen synthesis and decreased collagen breakdown play a major role in OSMF pathogenesis. In such fibrotic disorders, mediators such as growth factors, hormones, cytokines, and lymphokines primarily affect the production of extracellular matrix and collagen. PDGF-BB plays a major role in stimulating the replication, survival, and migration of myofibroblasts during the pathogenesis of fibrotic diseases. Aim: The main objective of this study is to assess the correlation between clinicopathological parameters and serum expression of PDGF-BB in OSMF and healthy controls. Materials and methods: A cross-sectional study, including fifteen patients with OSMF and fifteen healthy controls, was conducted. All cases had complete clinical and histopathological investigations. The PDGF-BB serum was assessed using an enzyme-linked immunosorbent assay. Results and discussion: The mean serum PDGF-BB expression values for stages I, II, and III are 1238.3±165.3 pg/ml, 1437.7±134.6 pg/ ml, and 1739.2±143.3 pg/ml, respectively. There was a correlation between the mean difference between the OSMF and control, and the clinical staging subgroups. (p-value<0.05) The mean serum expression of PDGF-BB in subgroups of histopathological grade I, II, and III was 1654.42±187.3 pg/ml, 1873.7±276.3 pg/ml,1739.2±143.3 pg/ml, with an insignificant p-value>0.05. Conclusions: The mean serum PDGF-BB level was significantly elevated in OSMF patients. There was a positive correlation between the clinical stages, compared to the control groups. Therefore, evaluation of PDGF-BB can be used as an adjunctive serological biomarker in monitoring and predicting OSMF progression as, by inhibiting it, this protein PDGF BB could provide a unique therapeutic approach to combat fibrosis, and may also aid in an effective treatment of this precancerous condition. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidence suggests that osteoclastogenesis and angiogenesis in subchondral bone are critical destructive factors in the initiation and progression of osteoarthritis (OA). Herein, methoxypolyethylene glycol amine (mPEG-NH2) modified polydopamine nanoparticles (PDA-PEG NPs) were synthesized for treating early OA. The cytotoxicity and reactive oxygen species (ROS) scavenging ability of PDA-PEG NPs were evaluated. The effects of PDA-PEG NPs on osteoclast differentiation and vessel formation were then evaluated. Further, PDA-PEG NPs were administrated to anterior cruciate ligament transection (ACLT)-induced OA mice. Results demonstrated that PDA-PEG NPs had low toxicity both in vitro and in vivo. PDA-PEG NPs could inhibit osteoclastogenesis via regulating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDA-PEG NPs suppressed osteoclast-related angiogenesis via down-regulating platelet-derived growth factor-BB (PDGF-BB). In vivo, PDA-PEG NPs inhibited subchondral bone resorption and angiogenesis, further rescuing cartilage degradation in OA mice. In conclusion, we demonstrated that PDA-PEG NPs deployment could be a potential therapy for OA. Graphical Abstract

Cynarin, a caffeoylquinic acid compound that was mainly extracted from Cynara scolymus L., displays various activities such as antioxidant, antibacterial, choleretic, and hepatoprotective functions. However, the target of cynarin and the mechanism of its hepatoprotective effect are still unclear. To find cynarin’s target, we performed molecular docking analysis, fluorescence-based ligand-binding assay, and reporter gene system assay. Our results indicated that cynarin was a partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ). Further studies showed that cynarin significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and activation of rat CFSC-8G hepatic stellate cells (HSCs). Our results also revealed that cynarin inhibited PDGF-BB-induced extracellular regulated protein kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) phosphorylation in HSCs. In addition, this inhibition effect was PPARγ dependent since the knockdown of PPARγ significantly attenuated the effects of cynarin on PDGF-BB-induced p-ERK, p-AKT, and α-smooth muscle actin (α-SMA) expressions. Therefore, this study suggests that cynarin is a promising antifibrotic lead compound that inhibits the activation of HSCs, and it works by targeting PPARγ.

H-type blood vessel is a specialized bone marrow blood vessels that is highly coupled to osteogenic activity, characterized by high expression of EMCN and CD31. Type H vessels are formed in the cancellous bone area during long bone development to provide adequate nutritional support for cells near the growth plate and influencing the proliferation and differentiation of osteoprogenitors and osteoclasts in a paracrine manner, thus providing a suitable microenvironment to facilitate new bone formation. Because of the close relationship between H-type vessels and osteogenic activity, it has been found that H-type vessels are involved in the physiological and pathological processes of bone diseases such as fracture healing, osteoporosis, osteoarthritis, osteonecrosis, and tumor bone metastasis. Moreover, experimental treatments targeting H-type vessels can improve the outcome of these diseases. Here, we reviewed the molecular mechanisms related to H-type vessels and their coupled osteogenic activities. which are helpful to further understand the role of H-type vessels in bone metabolism and hopefully provide theoretical basis and ideas for understanding bone diseases from a vascular perspective. [ABSTRACT FROM AUTHOR]

Recent studies have shed light on the cellular and molecular mechanisms that link subchondral bone remodelling and angiogenesis in knee osteoarthritis (OA). Type H vessels are a newly identified bone blood vessel characterized by high expression of CD31 and endomucin that are coupled with osteogenesis. Factors including mechanical loading, TGF-β1, platelet-derived growth factor type BB, the osteoprotegerin–RANK ligand–RANK system, osteopontin, mechanistic target of rapamycin, VEGF, stromal cell-derived factor l and prostaglandin E2 participate in the formation of type H vessels in osteoarthritic subchondral bone. In this review, we summarize the current understanding of type H vessels in knee OA, as well as the signalling pathways involved and potential therapeutic medicines. In future, the pathogenesis of knee OA could be further clarified by connecting type H vessels and the design of new disease-modifying osteoarthritis drugs. However, further experiments are needed to determine the upstream signals regulating type H vessel formation in osteoarthritic subchondral bone. [ABSTRACT FROM AUTHOR]

Tribbles homolog 2 (TRIB2) functions as an adapter protein that regulates signal transductions involved in a variety of cellular functions, including tumorigenesis. However, the role of TRIB2 in the proliferation of vascular smooth muscle cells (VSMCs) and the underlying expression mechanisms remain unclear. The present study investigated the role of TRIB2 in VSMC proliferation and revealed that TRIB2 expression increases following vascular injury and platelet‐derived growth factor (PDGF)‐BB‐stimulated VSMCs. We found that pretreatment with diphenyleneiodonium (a nicotinamide adenine dinucleotide phosphate oxidase inhibitor), U0126 (an inhibitor of mitogen‐activated protein kinase kinase 1 [MEK1]), or siRNA targeting the gene encoding early growth response 1 (EGR‐1) significantly inhibits PDGF‐BB‐induced TRIB2 expression in VSMCs. Furthermore, TRIB2 knockdown significantly inhibits PDGF‐BB‐induced proliferation of VSMCs but does not affect the phosphorylation of AKT. However, phosphorylation of ERK1 and expression of proliferating cell nuclear antibody are significantly suppressed in VSMCs by PDGF‐BB stimulation. Thus, PDGF‐BB‐induced TRIB2 expression is mediated by ROS/ERK/EGR‐1 pathways and plays a critical role in VSMC proliferation via modulation of ERK activity. We propose TRIB2 as a promising therapeutic target for the prevention of neointima formation and vascular disease. [ABSTRACT FROM AUTHOR]

The incidence of childhood overweight and obesity has been increasing in recent years. Immune dysregulation has been demonstrated as a condition related to childhood obesity. Whether the neonatal immune status is related to infant overweight and obesity at 1 year of age is unclear. To explore the relationship between neonatal cytokines and infant overweight and obesity, we conducted a prospective study in Suzhou Municipal Hospital Affiliated to Nanjing Medical University from 2015 to 2016. 514 neonates were recruited and their dried blood spots were collected after birth. Infants were grouped into normal size groups and overweight and obesity groups based on BMI at 1 year of age. 27 neonatal cytokines levels were compared between the two groups. 370 infants were included in final analysis. Granulocyte colony stimulating factor (GCSF), interleukin-17A (IL17A) and platelet derived growth factor-BB (PDGF-BB) levels were independently associated with childhood overweight and obesity (OR =1.27, 95%CI 1.03, 1.57; OR =1.29, 95%CI: 1.06, 1.60; OR =0.69, 95%CI: 0.49, 0.96). Additionally, neonatal GCSF and IL17A levels were positively associated with increased BMI (β = 0.11, 95%CI: 0.02, 0.19; β = 0.07, 95%CI 0.01, 013) and BMI z-scores (β = 0.10, 95%CI: 0.02, 0.18; β = 0.06, 95%CI 0.01, 0.13). Neonatal PDGF-BB levels were negatively associated with BMI (β = −0.12, 95%CI: −0.23, −0.01) and BMI z-scores (β = −0.12, 95%CI: −0.23, −0.01). The inverse probability weighting (IPW) was performed to account for potential selection bias of this study, and the results were consistent with the above mentioned findings. Neonatal GCSF, IL17A and PDGF-BB levels were correlated with infant overweight and obesity at 1 year of age, suggesting that early life immune status play a significant role of late obesity. [ABSTRACT FROM AUTHOR]

Abstract Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive‐like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)‐dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)‐induced depression‐like behavior. Further analysis exhibits that inhibition of gamma‐aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+‐DG) increases the expression of platelet‐derived growth factor‐BB (PDGF‐BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant‐like effects. Overexpression of the PDGF‐BB or exogenous administration of PDGF‐BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult‐born hippocampal neurons, as well as on depressive‐like behaviors. Conversely, knockdown of PDGF‐BB facilitates CSDS‐induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet‐derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF‐BB. These results delineate a previously unidentified PDGF‐BB/PDGFRβ signaling in regulating depressive‐like behaviors and identify a novel mechanism by which the MSGABA+‐DG pathway regulates the expression of PDGF‐BB in SOM‐positive interneurons.

Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential.Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p < 0.05.Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p < 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8 weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused.Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.

The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated. The protein content of phospho-extracellular signal-regulated kinases (ERK) 1/2, total ERK 1/2, phospho-cytosolic phospholipase A2 (cPLA2), total cPLA2 and cyclooxygenase 2 (COX-2) and the release of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) from BCPs were analyzed. Finally, the protective effect of platelet-derived growth factor (PDGF-BB) on BCPs treated with cisplatin was investigated. Cisplatin reduced viability and proliferation, activated ERK 1/2, cPLA2 and COX-2 expression and increased PGE2 and VEGF release; these effects were reversed by Dexamethasone. The presence of PDGF-BB during the treatment with cisplatin significantly increased the proliferation rate. No studies on cell regeneration in ear tissue evaluated the effect of the PDGF/Dex combination. The aim of this study was to investigate the effects of cisplatin on cochlear pericytes and propose new otoprotective agents aimed at preventing the reduction of their vitality and thus maintaining the BLB structure. [ABSTRACT FROM AUTHOR]

[Display omitted] Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds. [ABSTRACT FROM AUTHOR]

The goal of this paper is to examine the use of pig blood in the industrial mass production of platelet dry powder and to transform platelet dry powder into a low-cost and mass-produced material. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) contain multiple types of growth factors (GFs) and can be widely used in medical applications. However, neither can be mass-produced, due to the complexity of the PRP preparation process and the lack of anticoagulants in the PRF preparation process, increasing the risk of coagulation during mass production. Another obstacle is the insufficient supply of autologous PRP and autologous PRF. In this study, platelet dry powder was mass-produced from pig blood through the indirect addition of calcium chloride solution. Furthermore, the results showed that different concentrations and percentages of calcium chloride solution had significant effects on concentrations of TGF-β1 and PDGF-BB in the platelet dry powder. The platelet dry powder mass-produced from pig blood demonstrated high concentrations of GFs and long-term shelf stability, increasing the supply to industries that use it in product development.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as “must-check” parameters to characterize individual PRP preparations prior to clinical trials.

The continuous increase in the prevalence of asthma poses a threat to human health. Despites numerous researches, the understanding of asthma development still remain elusive, hindering the development of effective treatment. Here, we explored the role of lncRNA RP5-857K21.7 (RP5-857K21.7) in the development of asthma and its potential molecular mechanism of regulation. Airway smooth muscle cells (ASMCs) were isolated and cultured after which some of the cells were induced with PDGF-BB to build an asthma cell model, and then, qRT-PCR analysis was used to measure the expression level of RP5-857K21.7 in the cell model. Result shows that the RP5-857K21.7 is significantly downregulated in PDGF-BB-induced ASMCs cells. Through CCK-8, transwell, and flow cytometry assay, we examined the functional impact of RP5-857K21.7 on the proliferation, migration, and apoptosis of the ASMCs, respectively, and found that the overexpression of RP5-857K21.7 markedly inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. Bioinformatics analysis predicted that the RP5-857K21.7 could sponge miR-508-3p and result was validated through a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR analysis. Mechanistically, RP5-857K21.7 regulates the PI3K/AKT/mTOR pathway by endogenously sponging miR-508-3p to inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. The current research suggests that the RP5-857K21.7 and its associated molecular pathway (miR-508-3p/PI3K/AKT/mTOR axis) might be a useful therapeutic target for the treatment of asthma disease.

IntroductionFeline leukemia virus (FeLV) is a chronic disease that leads to the weakening of a cat's immune system. Platelet-rich plasma (PRP) offers therapeutic effects for multiple diseases, the use of PRP and growth factors (GFs) determination could be an alternative treatment to improve the quality of life in these patients. The objectives of this study were to determine and compare the concentration of platelets (PLTs), red blood cells (RBCs) and white blood cells (WBCs) between samples of whole blood (WB), PRP and platelet-poor plasma (PPP) fractions, and to evaluate the concentration of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β1 (TGF-β1) in both fractions in FeLV cats using a PRGF®-Endoret® protocol previously standardized in this species.MethodsWB was collected from 11 asymptomatic FeLV-positive cats. PRP and PPP was obtained following PRGF®-Endoret® technology according to centrifugation at 265 g for 10 min. Cellular components, RBCs, WBCs, PLTs, and the PDGF-BB and TGF-β1 concentrations in PRP and PPP fractions were determined.ResultsPLT in the PRP fraction was statistically higher than WB and PPP fraction, with no statistical differences between WB and PPP. PLT concentration increased 1.4 times in PRP fraction compared to WB. Mean platelet volume (MPV) did not differ significantly between the WB, PRP, and PPP fractions. Compared to WB, the absolute numbers of RBCs and WBCs were decreased by 99% and more than 95% in the PRP and PPP fractions, respectively. TGF-ß1 concentrations increased in PRP vs. PPP, with no changes in PDGF-BB.DiscussionBased on the degree of PLT enrichment and the absence of RBCs and WBCs, this blood product could be classified as a Pure Platelet-Rich Plasma (P-PRP). The presence of GFs in PRP and PPP samples suggests that the PRGF®-Endoret® methodology is suitable for obtaining PRP in FeLV cats, despite future studies are necessary to optimize the technique, standardize the results and assess clinical efficacy.

Background: The activation of HIF-1α/CXCR4 pathway in liver sinusoidal endothelial cells (LSECs) could downregulate CXCR7, leading to the capillarization of LSECs to promote hepatic fibrosis. However, the mechanism between CXCR4 and CXCR7 is still undefined. The aim is to investigate the role of PDGF-BB in the dedifferentiation of LSECs and hepatic stellate cells (HSCs) activation. Methods: The activation of HIF-1α/CXCR4 pathway in two kinds of liver fibrosis models were observed. The effects of HIF-1α, CXCR4, PDGF-BB on the dedifferentiation of LSECs were investigated by using the inhibitors of HIF-1α, CXCR4 or PDGFR-β separately or transfecting with a CXCR4 knockdown lentiviral vector. In addition, the relationship between LSECs and HSCs was demonstrated by co-culture of LSECs and HSCs using the transwell chamber. Results: CXCR4 upregulation and CXCR7 downregulation were accompanied by LSECs capillarization and HSCs activation both in CCl4-induced and BDL-induced fibrotic liver. In vitro, downregulation of HIF-1α significantly descreased CXCR4 and CD31 expression, and enhanced the expressions of CXCR7, CD44 and LYVE1. Downregulation of CXCR4 in LSECs significantly downregulated PDGF-BB, PDGFR-β and CD31, and enhanced CXCR7, CD44 and LYVE1 expression, while the expression of HIF-1α did not change significantly. STI571, a PDGF receptor inhibitor, could significantly downregulate PDGFR-β and increase the expression of CXCR7 to inhibit the dedifferentiation of LSECs. In addition, alleviateion the dedifferentiation of LSECs could decrease the expression of PDGFR-β of HSCs, then inhibiting the activation of HSCs. Conclusions: This study revealed that HIF-1α/CXCR4/PDGF-BB/CXCR7 axis promoted the dedifferentiation of LSECs, consequently triggering HSCs activation and liver fibrosis.

Increased growth and proliferation of distal pulmonary artery vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary arterial hypertension (PAH). Transforming Growth Factor-β (TGF-β) superfamily plays a critical role in PAH, but relative impacts of self-secreted Activin A, Gremlin1, and TGF-β on PAH PAVSMC growth and proliferation are not studied. Here we report that hyper-proliferative human PAH PAVSMC have elevated secretion of TGF-β1 and, to a lesser extent, Activin A, but not Gremlin 1, and significantly reduced Ser465/467-Smad2 and Ser423/425-Smad3 phosphorylation compared to controls. Media, conditioned by PAH PAVSMC, markedly increased Ser465/467-Smad2, Ser423/425-Smad3, and Ser463/465-Smad1/5 phosphorylation, up-regulated Akt, ERK1/2, and p38 MAPK, and induced significant proliferation of non-diseased PAVSMC. Inhibitory anti-Activin A antibody reduced PAH PAVSMC growth without affecting canonical (Smads) or non-canonical (Akt, ERK1/2, p38 MAPK) effectors. Inhibitory anti-TGF-β antibody significantly reduced P-Smad3, P-ERK1/2 and proliferation of PAH PAVSMC, while anti-Gremlin 1 had no anti-proliferative effect. PDGF-BB diminished inhibitory effects of anti-Activin A and anti-TGF-β antibodies. None of the antibodies affected growth and proliferation of non-diseased PAVSMC induced by PAH PAVSMC-secreted factors. Together, these data demonstrate that human PAH PAVSMC have secretory, proliferative phenotype that could be targeted by anti-Activin A and anti-TGF-β antibodies; potential cross-talk with PDGF-BB should be considered while developing therapeutic interventions.

Accumulating evidence suggests that osteoclastogenesis and angiogenesis in subchondral bone are critical destructive factors in the initiation and progression of osteoarthritis (OA). Herein, methoxypolyethylene glycol amine (mPEG-NH2) modified polydopamine nanoparticles (PDA-PEG NPs) were synthesized for treating early OA. The cytotoxicity and reactive oxygen species (ROS) scavenging ability of PDA-PEG NPs were evaluated. The effects of PDA-PEG NPs on osteoclast differentiation and vessel formation were then evaluated. Further, PDA-PEG NPs were administrated to anterior cruciate ligament transection (ACLT)-induced OA mice. Results demonstrated that PDA-PEG NPs had low toxicity both in vitro and in vivo. PDA-PEG NPs could inhibit osteoclastogenesis via regulating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDA-PEG NPs suppressed osteoclast-related angiogenesis via down-regulating platelet-derived growth factor-BB (PDGF-BB). In vivo, PDA-PEG NPs inhibited subchondral bone resorption and angiogenesis, further rescuing cartilage degradation in OA mice. In conclusion, we demonstrated that PDA-PEG NPs deployment could be a potential therapy for OA. [ABSTRACT FROM AUTHOR]