The growth factor content as an indicator of platelet counts in platelet-rich plasma.

BACKGROUND: Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and -AB), and transforming growth factor (TGF)-ß. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations. METHOD: In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- ß1 (TGF-ß1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis. RESULTS: Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively) CONCLUSIONS: There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-ß, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.

Immunological correlates of suicidality among adolescents with internalizing symptoms.

Background: Suicide is a leading cause of death in adolescents and young adults globally. Well-established risk factors for suicide are depression and past suicide attempts. People experiencing suicidality may represent a distinct neurobiological group of people with depression. Because converging evidence has implicated inflammation in depression, we sought to investigate relationships between suicidality and immune markers in youth experiencing diverse mood and anxiety symptoms. We hypothesized that adolescents with suicidality would exhibit a unique immune signature. Methods: Adolescents underwent semi-structured interviews and completed self-reported measures to assess psychopathology, including suicidality (suicidal ideation, plans, or attempts). Fasting blood samples were collected, cultured with and without lipopolysaccharide (LPS) to stimulate an inflammatory response, and analyzed for 41 immune analytes. To assess how immune function related to suicidality categorically and dimensionally, we conducted group comparisons and correlations while controlling for multiple comparisons using false discovery rate (FDR). To further uncover subtle immune-suicidality relationships, we employed a data-driven approach using factor analysis to extract major immune factors, each of which was subsequently correlated with suicidality measures. Results: Among 126 participants, 29 were healthy controls and 97 participants had internalizing symptoms; within the clinical group, 57 experienced suicidality. Three immune analytes differed between healthy controls, suicidal, and non-suicidal adolescents with internalizing symptoms in the LPS condition: Flt-3L (p FDR = 0.0246), GM-CSF (p FDR = 0.0246), and IFN-γ (p FDR = 0.0246). These analytes were negatively correlated with the Beck Scale for Suicide Ideation (BSSI): Flt-3L (ρ = -0.19, p = 0.04); GM-CSF (ρ = -0.26, p = 0.004); IFN-γ (ρ =-0.33, p = 0.0003). GM-CSF also negatively correlated with number of suicide attempts (ρ = -0.39, p = 0.003). Factor analysis reduced 41 analytes to several common immune factors across experimental conditions, with Flt-3L, GM-CSF, and IFN-γ all loading heavily onto immune factors that were hypoactive in suicidality. Through this data-driven approach, we detected further associations between suicidality and immune factors across all conditions. Conclusions: Peripheral immune function may be distinctly altered in adolescent suicidality. Future work should examine immune-suicidality relationships longitudinally.

Regeneration of combined severe periodontal defects and vertical ridge defects using recombinant human platelet-derived growth factor-BB: A case series.

Dental implants are a reliable treatment option for restoring missing teeth, but adequate bone quantity and quality are crucial for success. This case series presents four cases treated by different clinicians, all following very similar concepts for combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB. All cases involved a severe periodontal defect requiring either extraction of the adjacent tooth or periodontal regeneration. Different bone grafts and membrane types were utilised. Although true periodontal regeneration cannot be said categorically to have occurred due to a lack of histological evidence, the clinical and radiographic findings suggest almost complete bone fill in all cases. This case series demonstrates that combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB could be successful, but proper case selection and patient preparation for the possibility of multiple surgical procedures are recommended. Conflict-of-interest statement: At the time of preparing this manuscript, Dr Saleh was a clinical advisor for Lynch Biologics, Franklin, TN, USA. The other authors declare that they have no conflicts of interest relating to this study.

Lung epithelial-endothelial-mesenchymal signaling network with hepatocyte growth factor as a hub is involved in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is fundamentally characterized by the arrest of lung development and abnormal repair mechanisms, which result in impaired development of the alveoli and microvasculature. Hepatocyte growth factor (HGF), secreted by pulmonary mesenchymal and endothelial cells, plays a pivotal role in the promotion of epithelial and endothelial cell proliferation, branching morphogenesis, angiogenesis, and alveolarization. HGF exerts its beneficial effects on pulmonary vascular development and alveolar simplification primarily through two pivotal pathways: the stimulation of neovascularization, thereby enriching the pulmonary microvascular network, and the inhibition of the epithelial-mesenchymal transition (EMT), which is crucial for maintaining the integrity of the alveolar structure. We discuss HGF and its receptor c-Met, interact with various growth factors throughout the process of lung development and BPD, and form a signaling network with HGF as a hub, which plays the pivotal role in orchestrating and integrating epithelial, endothelial and mesenchymal.

Exploring endocrine FGFs - structures, functions and biomedical applications.

The family of fibroblast growth factors (FGFs) consists of 22 members with diverse biological functions in cells, from cellular development to metabolism. The family can be further categorized into three subgroups based on their three modes of action. FGF19, FGF21, and FGF23 are endocrine FGFs that act in a hormone-like/endocrine manner to regulate various metabolic activities. However, all three members of the endocrine family require both FGF receptors (FGFRs) and klotho co-receptors to elicit their functions. α-klotho and ß-klotho act as scaffolds to bring endocrine FGFs closer to their receptors (FGFRs) to form active complexes. Numerous novel studies about metabolic FGFs' structures, mechanisms, and physiological insights have been published to further understand the complex molecular interactions and physiological activities of endocrine FGFs. Herein, we aim to review the structures, physiological functions, binding mechanisms to cognate receptors, and novel biomedical applications of endocrine FGFs in recent years.

Spontaneous running wheel exercise during pregnancy prevents later neonatal-anoxia-induced somatic and neurodevelopmental alterations.

Introduction: About 15-20 % of babies that suffer perinatal asphyxia die and around 25 % of the survivors exhibit permanent neural outcomes. Minimization of this global health problem has been warranted. This study investigated if the offspring of pregnant female rats allowed to spontaneously exercise on running wheels along a 11-day pregnancy period were protected for somatic and neurodevelopmental disturbs that usually follow neonatal anoxia. Methods: spontaneous exercise was applied to female rats which were housed in cages allowing free access to running wheels along a 11-day pregnancy period. Their offspring were submitted to anoxia 24-36 h after birth. Somatic and sensory-motor development of the pups were recorded until postnatal day 21 (P21). Myelin basic protein (MBP)-stained areas of sensory and motor cortices were measured at P21. Neuronal nuclei (NeuN)-immunopositive cells and synapsin-I levels in hippocampal formation were estimated at P21 and P75. Results: gestational exercise and / or neonatal anoxia increased the weight and the size of the pups. In addition, gestational exercise accelerated somatic and sensory-motor development of the pups and protected them against neonatal-anoxia-induced delay in development. Further, neonatal anoxia reduced MBP stained area in the secondary motor cortex and decreased hippocampal neuronal estimates and synapsin-I levels at P21; gestational exercise prevented these effects. Therefore, spontaneous exercise along pregnancy is a valuable strategy to prevent neonatal-anoxia-induced disturbs in the offspring. Conclusion: spontaneous gestational running wheel exercise protects against neonatal anoxia-induced disturbs in the offspring, including (1) physical and neurobehavioral developmental impairments, and (2) hippocampal and cortical changes. Thus, spontaneous exercise during pregnancy may represent a valuable strategy to prevent disturbs which usually follow neonatal anoxia.

Role of Growth Factors in Nasal Cartilage Development and Molding: A Comprehensive Review.

This review aims to investigate the properties of growth factors concerning the morphogenesis and development of nasal cartilage, which is fundamentally important for facial form and appearance. Since cartilage lacks a blood supply, it is more difficult to regenerate, as cartilage tissue obtains sustenance by diffusion. Cytokines are signalling molecules that control chondrocyte metabolism and extracellular matrix formation, which is required for cartilage development, homeostasis, and healing. Some craniofacial illnesses alter the composition of the cartilage and the structural organization of growth factors, allowing for moulding. TGF-ß (transforming growth factor-ß) encourages chondrocyte differentiation, whereas IGF-1 (insulin-like growth factor-1) stimulates cartilage-forming collagen synthesis and chondrocyte multiplication. We used the scoping review approach to present current research on the role of growth factors in the creation and architecture of nasal cartilage. We generally observed this structure before conducting specific experiments to determine the impact of growth agents on the development of chondrocytes and cartilage. Prominent findings increase our understanding of how growth factors influence the extracellular matrix, cell activities and features, and cartilage growth rate; all are critical for cartilage tissue development and repair. Research into growth factors and their physiological interactions with cartilage may help improve treatment's functional and aesthetic outcomes and our understanding of the origins and consequences of nasal congenital anomalies. This study emphasizes the importance of expanding knowledge and experience, as well as the use of growth factors in clinical practice, to stimulate cartilage development.

Impact of inflammatory skin conditions on the biological profile of plasma rich in growth factor.

Plasma rich in growth factors (PRGF) can be used over patients suffering from dermatoses due to its anti-inflammatory effect. However, this population group might present soluble autoimmune components and there is limited information about the effect of chronic skin inflammation on PRGF bioactive properties. With the aim of characterizing PRGF composition, PRGF from healthy (H) donors and patients with atopic dermatitis (AD), psoriasis (PS), or lichen sclerosus (LS) was obtained. In order to reduce the inflammatory component, leukocyte exclusion and heat-inactivation (Immunosafe) were tested. Haematological-serological parameters, platelet functionality, clot microstructure, protein content and bioactivity were determined. Mean values and 95 % confidence intervals (mean[95 % CI]) were computed for key haematological parameters, such as platelet (410×103/mm3[371-449]) and leukocyte content (205×103/mm3[148-262]), platelet activation (resting: 4.3 %[3.1-5.5] and activated: 97.4 %[96.7-98.0]), the concentration of plasma proteins and morphogens, including immunoglobulins A (210.7 mg/dL[191.8-229.6]), G (933.1 mg/dL[887.2-978.9]), E (783.5 mg/dL[54.4-1512.6]), and M (115.0 mg/dL[97.1-133.0]), Complement Protein (31.6 mg/mL[26.6-36.6]), C-Reactive protein (3.1 mg/L[2.0-4.1]), TGF-ß1 (35975.6 pg/mL[34221.3-37729.8]), fibronectin (146410.0 ng/mL[136518.3-156301.7]), PDGF-AB (13308.5 pg/mL[12401.0-14216.0]), CD40L (2389.3 pg/mL[1887.7-2890.8]), IL-4 (0.12 pg/mL[0.07-0.18]), IL-13 (35.4 pg/mL[21.0-49.7]), IL-1ß (0.09 pg/mL[0.06-0.11]) and TNF-α (0.31 pg/mL[0.24-0.38]), and also for cell proliferation (332.9ngDNA/mL[317.4-348.3]), viability (135.6 %[132.0-139.2]) and migration (103.8cells/mm2[98.3-109.3]). Plasma from AD donors presented increased Immunoglobulin E (IgE) that was significantly reduced after Immunosafe along with the complement system and autoantibodies. Platelet functionality was altered for AD, but no microstructure differences were identified. Pathological groups presented reduced concentration of fibronectin (AD/LS) and Platelet-Derived Growth Factor (PDGF-AB) (P). Immunosafe treatment reduced Cluster of Differentiation 40 Protein (CD40L), interleukin 1ß (IL-1ß), and Tumor Necrosis Factor α (TNF-α) concentrations. Fibroblasts supplemented with PRGF obtained from pathological patients (PS/AD) showed reduced viability but Immunosafe increased cell proliferation and migration in SP (LS) and L-SP samples (PS/AD). In conclusion, PRGF derived from pathological patients present autoimmune components, but heat-inactivation or leukocyte exclusion could minimize local side effects.

Generating Cytokines and Growth Factors for Functional Activity: Feasibility of Method Using MIF Protein.

Cytokines and growth factors are signaling molecules that regulate a variety of biological processes. Understanding their role is essential for basic research and clinical utilization. Thus, cytokines and growth factors are widely used throughout research labs in a significant number of applications. Additionally, genetic polymorphisms result in variant forms of cytokines and growth factors, which can alter their function. Becoming more common, researchers will need to generate these important proteins and their variants themselves in functional forms for activity studies. The expression systems used to generate these proteins can have a major impact on their function. In some instances, post-translational modifications are needed to produce a functionally active protein, which can only be conducted using eukaryotic expression systems. Ideally, for functional relevance, a human expression system should be used for human-related research and applications. Most human cell-based expression systems primarily use HEK (Human Embryonic Kidney) cells; however, relying on just one cell type can lead to several issues, considering the variety of proteins derived from various cell sources. Here, we provide a protocol to effectively and efficiently generate functional recombinant proteins, taking into consideration the diverse range of proteins from different cell types throughout the human body.

The critical roles of IGFs in immune modulation and inflammation.

Insulin-like growth factors (IGFs) are crucial for embryonic and postnatal growth and development, influencing cell survival, metabolism, myogenesis, and cancer progression. Many studies have demonstrated that IGFs also play prominent roles in the modulation of both innate and adaptive immune systems during inflammation. Strikingly, IGFs dictate the phenotype and functional properties of macrophages and T cells. Furthermore, the interplay between IGFs and inflammatory cytokines may generate tissue-protective properties during inflammation. Herein, we review the recent advances on the dialogue between immune cells and IGFs, especially zooming in on the significance of immunomodulatory properties in inflammatory conditions, cancer and autoimmune diseases. The investigation of IGFs may have broad clinical implications.

Upregulation of Insulin-like Growth Factor-I in Response to Chemotherapy in Children with Acute Lymphoblastic Leukemia.

The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we included 114 patients (age: 1-17 years) with newly diagnosed ALL treated according to The Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2013 and 2018. The patients' plasma levels of IGF-I, and the primary binding protein, IGFBP-3, were measured weekly during the first six weeks of treatment, including the induction therapy. The patients' systemic inflammation was monitored by their C-reactive protein (CRP) and interleukin (IL)-6 levels and their intestinal epithelial damage by their plasma citrulline levels. IGF-I and IGFBP-3 were converted into sex-and age-adjusted standard deviation scores (SDS) using 1621 healthy children as reference. At ALL diagnosis, IGF-I levels were decreased (median (quartiles): -1.2 SDS (-1.9 to -0.5), p = 0.001), but increased significantly following the initiation of chemotherapy, peaking on day 8 (0.0 SDS (from -0.8 to 0.7), p < 0.001). This increase correlated with the levels of CRP (rho = 0.37, p < 0.001) and IL-6 (rho = 0.39, p = 0.03) on day 15, when these markers reached maximum levels. A larger IGF-I increase from day 1 to 15 correlated with a slower recovery rate of the intestinal damage marker citrulline from day 15 to 29 (rho = -0.28, p = 0.01). Likewise, IGFBP-3 was reduced at diagnosis, followed by an increase after treatment initiation, and was highly correlated with same-day IGF-I levels. This study demonstrates a chemotherapy-induced increase in IGF-I, with a response that appears to reflect the severity of tissue damage and systemic inflammation, preceding CRP and IL-6 increases. IGF-I may have potential as an early reactive biomarker for acute toxicity in patients with ALL.

Potential Diagnostic Role of Serum Fibroblast Growth Factor-19 in Hepatocellular Carcinoma.

INTRODUCTION: A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC. METHODS: This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19. RESULTS: The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity. CONCLUSION: FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.

Novel Molecular Mechanisms Underlying the Ameliorative Effect of Platelet-Rich Plasma against Electron Radiation-Induced Premature Ovarian Failure.

Radiotherapy is one of the risk factors for radiation-induced premature ovarian failure and infertility in cancer patients. The development of methods for ovarian radioprotection remains relevant. Moreover, electrons are a little-studied and promising method of radiation with the least toxic effect on normal tissues. The assessment of intracellular mechanisms regulating the protective effects of leukocyte-poor platelet-rich plasma in a model of radiation-induced premature ovarian failure caused by electron irradiation. Wistar rats were divided into four groups, namely a control group, irradiation group (electron exposure), irradiation + leukocyte-poor platelet-rich plasma group, and only leukocyte-poor platelet-rich plasma group. Fragments of ovaries were removed and hormonal, oxidant, histological, and morphometric studies were carried out. The cell cycle of ovarian follicles and the inflammatory and vascular response were assessed using immunohistochemistry. The activity of MAPK, ERK, and PI3K pathways was also assessed using the RT-qPCR. We found that electron irradiation causes a decrease in the functional activity of the ovaries and the death of follicular cells through apoptosis. The administration of LP-PRP led to a partial restoration of the cytokine balance. In addition, minor ovarian damage and mild inflammation were observed in this group. Leukocyte-poor platelet-rich plasma components have anti-inflammatory, angiogenetic, and radioprotective effects, reducing the activation of the NOX4, caspase and cytokine cascades, and inflammatory response severity through the MAPK/p38/JNK signaling pathway. This leads to the induction of endogenous antioxidant protection, the repair of post-radiation follicular damage, and slowing down the development of radiation-induced premature ovarian failure after electron irradiation.

Innovative Bioscaffolds in Stem Cell and Regenerative Therapies for Corneal Pathologies.

Corneal diseases, which can result in substantial visual impairment and loss of vision, are an important worldwide health issue. The aim of this review was to investigate the novel application of bioscaffolds in stem cell and regenerative treatments for the treatment of corneal disorders. The current literature reports that organic and artificial substances create bioscaffolds that imitate the inherent structure of the cornea, facilitating the attachment, growth, and specialization of stem cells. Sophisticated methods such as electrospinning, 3D bioprinting, and surface modification have been reported to enhance the characteristics of the scaffold. These bioscaffolds have been shown to greatly improve the survival of stem cells and facilitate the regrowth of corneal tissue in both laboratory and live animal experiments. In addition, the incorporation of growth factors and bioactive compounds within the scaffolds can promote a favorable milieu for corneal regeneration. To summarize, the advancement of these groundbreaking bioscaffolds presents a hopeful treatment strategy for the regeneration of the cornea, which has the potential to enhance the results for individuals suffering from corneal disorders. This study highlights the possibility of utilizing the fields of biomaterials science and stem cell treatment to tackle medical demands that have not yet been satisfied in the field of ophthalmology.

Evaluation of the efficacy of subtenon autologous platelet-rich plasma therapy in patients with retinitis pigmentosa and factors affecting response to the treatment.

PURPOSE: To evaluate the effect of subtenon platelet-rich plasma (PRP) treatment in retinitis pigmentosa (RP) patients and to determine the factors affecting the response to treatment. METHODS: For this purpose, 85 eyes of 43 RP patients with visual acuity of 1 logMAR and above were included in the study and subtenon autologous PRP treatment was applied 3 times at two-week intervals. In addition to a full ophthalmological examination, functional tests such as visual acuity, visual field, central retinal sensitivity measurement, and electroretinography (ERG) and structural measurements including the thickness of the outer retinal layers, and the length of the ellipsoid zone in optic coherence tomography, and the dimensions of the hyperautofluorescent ring in fundus autofluorescence imaging (FAF) were performed on the patients before and one month after the treatment. RESULTS: A statistically significant improvement was achieved in the patient's visual acuity, visual field MD and PSD index, and dark-adapted 10.0 ERG response b wave amplitude. There was no significant change in average central retinal sensitivity, fixation stability, outer retinal layer thickness and ellipsoid zone length. No statistically significant change was detected in the diameter and area of the hyperautofluorescence ring measured by FAF. It was found that the age of the patients and the age of onset of the disease were parameters affecting the treatment response. CONCLUSION: With PRP treatment applied periodically in RP patients, it may be possible to improve visual function and stop the progression of the disease, which can be detected by structural evaluations.

Effect of concentrated growth factor on wound healing, side effects, and postoperative complications following third molar surgery.

BACKGROUND: Third molar surgery often results in postoperative complications such as pain, trismus, and facial swelling due to surgical trauma. Concentrated Growth Factor (CGF), a third-generation platelet concentrate, is believed to enhance wound healing due to its rich content of growth factors and fibrin. METHODS: This systematic review followed PRISMA guidelines and included a search of PubMed, Embase, and Cochrane Library up to April 18, 2024. Randomized controlled trials involving CGF-treated versus non-CGF-treated patients undergoing third molar surgery were included. Risk of bias was assessed using the Cochrane Collaboration RoB 2.0. RESULTS: Ten studies were included. CGF significantly improved wound healing, with enhanced soft and hard tissue recovery. Pain relief was notable on postoperative days 3 and 7, although results varied. CGF reduced facial swelling significantly on days 3 and 7 post-surgery. Trismus outcomes were mixed, with some studies reporting significant alleviation and others showing no advantage. CGF showed potential in reducing dry socket incidence, though evidence was not robust. CONCLUSIONS: CGF appears to promote wound healing and reduce postoperative complications such as pain and swelling after third molar surgery. However, its effects on trismus and dry socket incidence remain controversial. Further research with standardized measures is needed to confirm these findings.

Fgf9 promotes incisor dental epithelial stem cell survival and enamel formation.

BACKGROUND: Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9-/-) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. METHODS: To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. RESULTS: The Fgf9S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. CONCLUSIONS: Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.

Effects of Temperature and Time on the Denaturation of Transforming Growth Factor Beta-1 and Cytokines from Bovine Platelet-Rich Gel Supernatants.

There is a lack of information about transforming growth factor beta-1 (TGF-ß1) and cytokines contained in pure platelet-rich plasma (P-PRP) and release from pure-platelet-rich gel supernatants (P-PRGS) might be affected by the temperature and time factors; P-PRP from 6 heifers was activated with calcium gluconate. Thereafter, P-PRG and their supernatants (P-PRGS) were maintained at -80, -20, 4, 21, and 37 °C and collected at 3, 6, 12, 24, 48, 96, 144, 192, 240, and 280 h for subsequent determination of TGF-ß1, tumor necrosis factor alfa (TNF-α), interleukin (IL)-2, and IL-6; TGF-ß1 concentrations were significantly (p < 0.05) higher in PRGS maintained at 21 and 37 °C when compared to PRGS maintained at 4, -20, and -80 °C; PRGS TNF-α concentrations were not influenced by temperature and time factors. However, PRGS maintained at 4 °C showed significantly (p < 0.05) higher concentrations when compared to PRGS maintained at -20, and -80 °C at 144, and 192 h. IL-6 concentrations were significantly (p < 0.05) higher in PRGS stored at -20, and -80 over the first 48 h and at 10 days when compared to PRGS stored at 4, 21, and 37 °C. These results could suggest that P-PRP/P-PRGS could be maintained and well preserved for at least 12 days at room temperature for clinical use in bovine therapeutic massive protocols.

Recent insights into contributing factors in the pathogenesis of cirrhotic ascites.

Cirrhotic ascites refers to the accumulation of fluid in the peritoneal cavity due to severe liver disease and impaired liver function, which leads to poor blood circulation in the body, increased pressure in the hepatic sinus wall, and the exudation of fluid from the plasma into the peritoneal cavity. Cirrhotic ascites is a common complication of cirrhosis and poses a threat to the health and lives of modern people, causing a heavy social burden worldwide. So far, there are no effective treatment methods available to improve the quality and quantity of life for patients and their partners; existing drugs can only alleviate the symptoms of cirrhotic ascites and slow down its progression. This article aims to carefully examine the pathogenesis of cirrhotic ascites by exploring various contributing factors such as portal hypertension, renal dysfunction, inflammation, growth factors, oxidative stress, immunocytes, and gut microbiota. The purpose is to gain better insights and deeper understanding of the mechanisms involved in this condition.

Regenerative therapies for lumbar degenerative disc diseases: a literature review.

This review aimed to summarize the recent advances and challenges in the field of regenerative therapies for lumbar disc degeneration. The current first-line treatment options for symptomatic lumbar disc degeneration cannot modify the disease process or restore the normal structure, composition, and biomechanical function of the degenerated discs. Cell-based therapies tailored to facilitate intervertebral disc (IVD) regeneration have been developed to restore the IVD extracellular matrix or mitigate inflammatory conditions. Human clinical trials on Mesenchymal Stem Cells (MSCs) have reported promising outcomes exhibited by MSCs in reducing pain and improving function. Nucleus pulposus (NP) cells possess unique regenerative capacities. Biomaterials aimed at NP replacement in IVD regeneration, comprising synthetic and biological materials, aim to restore disc height and segmental stability without compromising the annulus fibrosus. Similarly, composite IVD replacements that combine various biomaterial strategies to mimic the native disc structure, including organized annulus fibrosus and NP components, have shown promise. Furthermore, preclinical studies on regenerative medicine therapies that utilize cells, biomaterials, growth factors, platelet-rich plasma (PRP), and biological agents have demonstrated their promise in repairing degenerated lumbar discs. However, these therapies are associated with significant limitations and challenges that hinder their clinical translation. Thus, further studies must be conducted to address these challenges.