Platelet-derived Growth factor-BB Research Articles

Nogo-B Silencing Expedites the Senescence of Platelet-Derived Growth Factor-BB-Induced Human Hepatic Stellate Cells Via Autophagy.

Liver fibrosis is a severe liver pathology in response to chronic or iterative liver injury. Senescence has emerged as a protective mechanism against liver fibrosis. Nogo-B has been well established as a significant contributor to liver fibrosis. Nonetheless, researches regarding the role of Nogo-B in cell senescence during liver fibrosis are few. In platelet-derived growth factor-BB (PDGF-BB)-treated human hepatic stellate cell line LX-2, cell proliferation was assayed by CCK-8 method. Western blotting estimated the expression of Nogo-B and fibrosis markers. After Nogo-B was silenced in LX-2 cells pretreated by an autophagy activator Rapamycin and PDGF-BB, CCK-8 method was used to assess cell proliferation. Fibrosis was measured by western blotting and immunofluorescence. Cell cycle was subjected to flow cytometry analysis and cell senescence was evaluated by SA-β-gal staining. Immunofluorescence staining assessed autophagy. Nogo-B was elevated in PDGF-BB-exposed LX-2 cells. Nogo-B silencing suppressed the proliferation, fibrosis, and autophagy while induced cell cycle arrest and senescence of LX-2 cells. Additionally, pretreatment with Rapamycin partially restored the effects of Nogo-B knockdown on the autophagy, proliferation, fibrosis, cell cycle, and senescence of LX-2 cells upon exposure to PDGF-BB. Collectively, inactivation of autophagy mediated by Nogo-B deficiency might elicit protective activities against the development of liver fibrosis.

Recombinant Platelet-Derived Growth Factor-BB (rhPDGF-BB) Augmented Collagen Grafting for Oral Mucosal Defect Reconstruction

Abstract Objective To assess the suitability of collagen grafting and compare the outcomes between rhPDGF-BB (recombinant human platelet-derived growth factor-BB) augmented collagen grafting and collagen alone grafting for oral mucosal defect reconstruction. Method A total of 30 patients, who were planned for surgical excision of various intraoral lesions, participated in the study. These participants were then randomly assigned into two groups. Group I underwent reconstruction with collagen sheet with rhPDGF-BB, while group II underwent reconstruction with collagen sheet alone. Post-operatively, haemostasis, pain, granulation, epithelialisation and healing contracture were assessed. Results The lesions that were treated included leucoplakia, erythroplakia, oral submucous fibrosis and verrucous carcinoma. Use of collagen was associated with good haemostasis, pain relief, granulation tissue formation and epithelialisation. Group I was found to develop slightly better granulation tissue, epithelisation and lesser degree of tissue contracture compared to group II, although these results were not significant statistically (p value = 0.464, 0.705 and 1.000 respectively). Conclusion This study shows that use of collagen graft augmented with rhPDGF-BB could be beneficial in oral cavity reconstruction following resection of small lesions, although further research with larger sample size is proposed to confirm the benefit.

Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-β/TXNIP pathway

ObjectiveIntervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. MethodsTo confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. ResultsMacrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes’ expression and the activation of pathways related to pyroptosis in nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-β)/ thioredoxin-interacting protein (TXNIP) pathway. ConclusionsThe absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds potential for retarding intervertebral disc degeneration in the human body.

Comparative Studies of Bone Graft and Orthobiologics for Foot Ankle Arthrodesis: A Critical Review.

Graft materials available to supplement hindfoot and ankle arthrodesis procedures include autologous (autograft) or allogeneic bone graft (allograft) but also bone graft substitutes such as demineralized bone matrix, calcium sulfate, calcium phosphate, and tricalcium phosphate/hydroxyapatite. In addition, biologic agents, such as recombinant human bone morphogenetic protein-2 or recombinant human platelet derived growth factor-BB (rhPDGF-BB), and preparations, including platelet-rich plasma or concentrated bone marrow aspirate, have been used to facilitate bone healing in ankle or hindfoot arthrodesis. The purpose of this review was to summarize the available clinical evidence surrounding the utilization and efficacy of the above materials and biological agents in ankle or hindfoot arthrodesis procedures, with emphasis on the quality of the existing evidence to facilitate clinical decision making.

The effect of calcium chloride on the release of platelet-derived growth factor-BB in the platelet-rich plasma products

The effect of calcium chloride on the release of platelet-derived growth factor-BB in the platelet-rich plasma products

Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome

BackgroundIt is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge.Main bodyPreosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells.ConclusionOur findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity.

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.

Immune analysis of urine and plasma samples from patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third most common type of urological malignancy worldwide, and it is associated with a silent progression and late manifestation. Patients with a metastatic form of ccRCC have a poor prognosis; however, when the disease is diagnosed early, it is largely curable. Currently, there are no biomarkers available in clinical practice for ccRCC. Thus, the aim of the present study was to measure 27 biologically relevant cytokines in preoperative and postoperative urine samples, and in preoperative plasma samples from 34 patients with ccRCC, and to evaluate their diagnostic significance. The concentrations of cytokines were assessed by multiplex immune assay. The results showed significantly higher levels of IL-1 receptor antagonist, IL-6, IL-15, chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, C-X-C motif ligand (CXCL)10, granulocyte-macrophage colony stimulating factor (GM-CSF) and platelet-derived growth factor-BB (PDGF-BB), and lower levels of granulocyte colony stimulating factor (G-CSF) in urine samples from patients prior to surgery compared with those in the controls. Notably, the urine levels of G-CSF, IL-5 and vascular endothelial growth factor differed following tumor removal compared with the preoperative urine levels. In addition, urinary G-CSF, GM-CSF, IL-6, CXCL10, CCL5 and PDGF-BB appeared to be potential markers of tumor grade. Plasma from patients with ccRCC contained significantly higher levels of IL-6 and lower levels of CCL2 than control plasma. In conclusion, the present findings indicated that urinary and circulating cytokines may represent a promising novel tool for the early diagnosis of ccRCC and/or prediction of tumor grade.

Endothelial HIFα-PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension.

Mechanisms underlying maintenance of pathological vascular hypermuscularization are poorly delineated. Herein, we investigated retention of smooth muscle cells (SMCs) coating normally unmuscularized distal pulmonary arterioles in pulmonary hypertension (PH) mediated by chronic hypoxia ± Sugen 5416, and reversal of this pathology. With hypoxia in mice or culture, lung endothelial cells (ECs) upregulated hypoxia-inducible factor (Hif)-1a and 2a which induce platelet-derived growth factor-B (PDGF-B), and these factors reduced to normoxic levels with re-normoxia. Re-normoxia reversed hypoxia-induced pulmonary vascular remodeling, but with EC HIFα over-expression during re-normoxia, pathological changes persisted. Conversely, after establishment of distal muscularization and PH, EC-specific deletion of Hif1a, Hif2a, or Pdgfb induced reversal. In human idiopathic pulmonary artery hypertension, HIF1A, HIF2A, PDGFB and autophagy-mediating gene products, including Beclin1, were upregulated in pulmonary artery SMCs and/or lung lysates. Furthermore, in mice, hypoxia-induced EC-derived PDGF-B upregulated Beclin1 in distal arteriole SMCs, and after distal muscularization was established, re-normoxia, EC Pdgfb deletion or treatment with STI571 (which inhibits PDGF receptors) downregulated SMC Beclin1 and other autophagy products. Finally, SMC-specific Becn1 deletion induced apoptosis, reversing distal muscularization and PH mediated by hypoxia ± Sugen 5416. Thus, chronic hypoxia induction of HIFα-to-PDGF-B axis in ECs is required for non-cell autonomous Beclin1-mediated survival of pathological distal arteriole SMCs.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis.

Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. To explore the effect of taurine on aHSC proliferation and the mechanisms involved. Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

Shenqi Yizhi prescription prevents AβO-induced memory impairment in mice by regulating the contractility of brain pericytes

BackgroundCerebral microcirculation disturbance manifested by decrease of cerebral blood flow (CBF) is one of early features of Alzheimer's disease (AD). Shenqi Yizhi prescription (SQYZ) is widely used in the treatment of AD. However, the effect of SQYZ on the early feature of AD is not clarified. PurposeTo explore the effect and mechanism of SQYZ on AD-like behavior from the perspective of early pathological features of AD. MethodsThe fingerprint of SQYZ was established by ultra-high-performance liquid chromatograph. The improvement effect of SQYZ on Aβ1–42 Oligomer (AβO)-induced AD-like behavior of mice was evaluated by behavioral test. The changes of CBF were detected by laser doppler meter and laser speckle imaging. The pathological changes of the hippocampus were observed by HE staining and transmission electron microscope. The expressions of intercellular communication molecules were detected by western blotting or immunofluorescence staining. The content of platelet-derived growth factor-BB (PDGF-BB) was detected by ELISA. Finally, the core components of SQYZ were docked with platelet-derived growth factor receptor beta (PDGFRβ) using AutoDock Vina software. ResultsThe similarity of the components in SQYZ extracted from different batches of medicinal materials was higher than 0.9. SQYZ administration could improve AβO-induced memory impairment and CBF reduction. Compared with the sham group, the number of neurons in the hippocampi of AβO group was significantly reduced, and the microvessels were shrunken and deformed. By contrary, SQYZ administration mitigated those pathological changes. Compared with the sham mice, the expressions of CD31, N-cadherin, PDGFRβ, glial fibrillary acidic protein, phosphorylation of focal adhesion kinase, integrin β1, and integrin α5 in the hippocampi of AβO mice were significantly increased. However, SQYZ administration significantly reduced AβO-induced expression of those proteins. Interestingly, the effect of PDGFRβ inhibitor, sunitinib demonstrated a consistent modulating effect as SQYZ. Finally, the brain-entering components of SQYZ, including ginsenoside Rg5, coptisine, cryptotanshinone, dihydrotanshinone IIA, stigmasterol, and tanshinone IIA had high binding force with PDGFRβ, implicating PDGFRβ as a potential target for SQYZ. ConclusionsOur data indicate that SQYZ improves CBF in AβO-triggered AD-like mice through inhibiting brain pericyte contractility, indicating the treatment potential of SQYZ for AD at the early stage.

A rhPDGF-BB/bovine type I collagen/β-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/β-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4or 8weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway.

Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated. Smooth muscle cell (SMC)-specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively. The effects of HMGB2 and its underlying mechanisms were subsequently elucidated using RNA-sequencing and cellular and molecular biology analyses. Serum HMGB2 levels were measured in the controls and patients with pulmonary arterial (PA) hypertension. HMGB2 expression was markedly increased in the PAs of patients with PA hypertension and PH rodent models and was predominantly localized in PASMCs. SMC-specific HMGB2 deficiency or silencing attenuated PH development and pulmonary vascular remodeling in hypoxia+Su5416-induced mice and monocrotaline-treated rats. SMC-specific HMGB2 overexpression aggravated hypoxia+Su5416-induced PH. HMGB2 knockdown inhibited PASMC proliferation in vitro in response to PDGF-BB (platelet-derived growth factor-BB). In contrast, HMGB2 protein stimulation caused the hyperproliferation of PASMCs. In addition, HMGB2 promoted PASMC proliferation and the development of PH by RAGE (receptor for advanced glycation end products)/FAK (focal adhesion kinase)-mediated Hippo/YAP (yes-associated protein) signaling suppression. Serum HMGB2 levels were significantly increased in patients with PA hypertension, and they correlated with disease severity, predicting worse survival. Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization.

Cytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors. Bidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty-one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome-wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate-to-vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta-GWAS and the UK Biobank, and sample sizes ranged from 69537 to 472174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut-off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5×10-6 and 5×10-8). Inverse-variance weighted, MR-Egger and weighted median were employed to estimate the causality. Twenty-seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin-16), CTACK (cutaneous T-cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet-derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956-0.998] for EWGSOP and 0.933 [0.874-0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995-1.000]) and AWCU10 (1.008 [1.003-1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007-1.019] for EWGSOP and 1.090 [1.041-1.142] for FNIH), AWCU10 (0.990 [0.986-0.994]) and telomere length (0.998 [0.983-0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001-1.063] for EWGSOP), AWCU10 (0.994 [0.988-1.000] and 0.993 [0.988-0.998]) and telomere length (1.006 [1.000-1.012]). PDGFbb may causally relate to AALM (1.016 [1.001-1.030]) and telomere length (1.011 [1.007-1.015]). Reserve MR analyses also proved their unidirectional causal effects. Twenty-seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor.

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.

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis.

Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-β and low levels of stem cell growth factor-β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, β-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Development of a Composite Hydrogel Containing Statistically Optimized PDGF-Loaded Polymeric Nanospheres for Skin Regeneration: In Vitro Evaluation and Stem Cell Differentiation Studies.

Platelet-derived growth factor-BB (PDGF-BB) is a polypeptide growth factor generated by platelet granules faced to cytokines. It plays a role in forming and remodeling various tissue types, including epithelial tissue, through interaction with cell-surface receptors on most mesenchymal origin cells. However, it breaks down quickly in biological fluids, emphasizing the importance of preserving them from biodegradation. To address this challenge, we formulated and evaluated PDGF-encapsulated nanospheres (PD@PCEC) using polycaprolactone-polyethylene glycol-polycaprolactone. PD@PCECs were fabricated through the triple emulsion methodology and optimized by using the Box-Behnken design. The encapsulation efficiency (EE) of nanoencapsulated PDGF-BB was investigated concerning four variables: stirring rate (X1), stirring duration (X2), poly(vinyl alcohol) concentration (X3), and PDGF-BB concentration (X4). The selected optimized nanospheres were integrated into a gelatin-collagen scaffold (PD@PCEC@GC) and assessed for morphology, biocompatibility, in vitro release, and differentiation-inducing activity in human adipose-derived stem cells (hADSCs). The optimized PD@PCEC nanospheres exhibited a particle size of 177.9 ± 91 nm, a zeta potential of 5.2 mV, and an EE of 87.7 ± 0.44%. The release profile demonstrated approximately 85% of loaded PDGF-BB released during the first 360 h, with a sustained release over the entire 504 h period, maintaining bioactivity of 87.3%. The study also included an evaluation of the physicochemical properties of the scaffolds and an assessment of hADSC adhesion to the scaffold's surface. Additionally, hADSCs cultivated within the scaffold effectively differentiated into keratinocyte-like cells (KLCs) over 21 days, evidenced by morphological changes and upregulation of keratinocyte-specific genes, including cytokeratin 18, cytokeratin 19, and involucrin, at both transcriptional and protein levels.

MiR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis.

By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3(P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)-induced osteoporosis. Results confirm OVX-induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole-body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor-BB and leukemia inhibitory factor, with downregulation of interleukin-1 R6, and receptor activator of nuclear factor kappa-B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor-beta/SMAD, and Wingless-related integration site/be-catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo-osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX-induced bone loss.