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.

Pectin methylesterase activity is required for RALF1 peptide signalling output.

The extracellular matrix plays an integrative role in cellular responses in plants, but its contribution to the signalling of extracellular ligands largely remains to be explored. Rapid alkalinisation factors (RALFs) are extracellular peptide hormones that play pivotal roles in various physiological processes. Here, we address a crucial connection between the de-methylesterification machinery of the cell wall component pectin and RALF1 activity. Pectin is a polysaccharide, contributing to the structural integrity of the cell wall. Our data illustrate that the pharmacological and genetic interference with pectin methyl esterases (PMEs) abolishes RALF1-induced root growth repression. Our data suggest that positively charged RALF1 peptides bind negatively charged, de-methylesterified pectin with high avidity. We illustrate that the RALF1 association with de-methylesterified pectin is required for its FERONIA-dependent perception, contributing to the control of the extracellular matrix and the regulation of plasma membrane dynamics. Notably, this mode of action is independent of the FER-dependent extracellular matrix sensing mechanism provided by FER interaction with the leucine-rich repeat extensin (LRX) proteins. We propose that the methylation status of pectin acts as a contextualizing signalling scaffold for RALF peptides, linking extracellular matrix dynamics to peptide hormone-mediated responses.

Blood Clots Used as Natural Biomaterials for Antibiotic Delivery in Vitro.

INTRODUCTION: The search for an optimal drug delivery system capable of addressing a wide range of wounds and defects in regenerative medicine remains a challenge. Blood clots (BCs) have been implicated as a promising candidate due to their natural occurrence, autologous nature, and potential for tissue repair. The aim of this study is to investigate BC as a vehicle for antibiotic delivery and its effectiveness in infection control. METHODS: BCs derived from murine and porcine models were used to study the in vitro release of gentamicin and vancomycin over a 7-d period. Moreover, BCs conjugated with mesenchymal stem cells and these antibiotics were assessed for antimicrobial activity via microdilution and agar well diffusion, and quantification of vascular endothelial growth factor release through enzyme-linked immunosorbent assay. RESULTS: Conjugated BCs maintained a sustained release of gentamicin and vancomycin throughout the 7-d period. Functional tests confirmed antimicrobial activity with zones of inhibition comparable to antibiotic controls. Vascular endothelial growth factor quantification revealed a pronounced and sustained release, especially from BCs conjugated with male mesenchymal stem cells, suggesting a gender influence on therapeutic outcomes. This sex-specific variance underscores the need for tailored therapeutic approaches in regenerative medicine applications. CONCLUSIONS: We demonstrated the remarkable potential of BC as a drug delivery system through sustained antibiotic and growth factor release, both of which are key in preventing infection and promoting tissue regeneration. The ease and cost effectiveness of BC preparation as well as its favorable federal regulatory profile support the potential translational application of BCs as a natural biomaterial in regenerative medicine.

TGF-ß2, EGF and FGF21 influence the suckling rat intestinal maturation.

Some of the growth factors present in breast milk, such as transforming growth factor-ß (TGF-ß), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-ß2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-ß2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established.. During the suckling period, the supplementation with TGF-ß2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.

Engineering growth factor ligands and receptors for therapeutic innovation.

Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.

Synthetic Antiangiogenic Vascular Endothelial Growth Factor-A Splice Variant Revascularizes Ischemic Muscle in Peripheral Artery Disease.

BACKGROUND: Alternative splicing in the eighth exon C-terminus of VEGF-A (vascular endothelial growth factor-A) results in the formation of proangiogenic VEGF165a and antiangiogenic VEGF165b isoforms. The only known difference between these 2 isoform families is a 6-amino acid switch from CDKPRR (in VEGF165a) to SLTRKD (in VEGF165b). We have recently shown that VEGF165b can induce VEGFR2-activation but fails to induce VEGFR1 (VEGF receptor 1)-activation. The molecular mechanisms that regulate VEGF165b's ability toward differential VEGFR2 versus VEGFR1 activation/inhibition are not yet clear. METHODS AND RESULTS: Hypoxia serum starvation was used as an in vitro peripheral artery disease model. Unilateral single ligation of the femoral artery was used as a preclinical peripheral artery disease model. VEGFR1 activating ligands have 2 arginine (RR) residues in their eighth exon C-terminus, that were replaced by lysine-aspartic acid (KD) in VEGF165b. A synthetic anti-angiogenic VEGF165b splice variant in which the KD residues were switched to RR (VEGF165bKD→RR) activated both VEGFR1- and VEGFR2-signaling pathways to induce ischemic-endothelial cell angiogenic capacity in vitro and enhance perfusion recovery in a severe experimental-peripheral artery disease model significantly higher than VEGF165a. Phosphoproteome arrays showed that the therapeutic efficacy of VEGF165bKD→RR over VEGF165a is due to its ability to induce P38-activation in ischemic endothelial cells. CONCLUSIONS: Our data shows that the KD residues regulate VEGF165b's VEGFR1 inhibitory property but not VEGFR2. Switching these KD residues to RR resulted in the formation of a synthetic/recombinant VEGF165bKD→RR isoform that has the ability to activate both VEGFR1- and VEGFR2-signaling and induce ischemic-endothelial cell angiogenic and proliferative capacity that matched the angiogenic requirement necessary to achieve perfusion recovery in a severe experimental-peripheral artery disease model.

Evaluating Autologous Platelet Aggregate as a Scaffold in the Treatment of Human Permanent Molars With Pulpitis: A Case Series.

This case series aims to investigate the radiographic and clinical results of pulpotomy using concentrated growth factor (CGF), a scaffold obtained from the host, on adult human permanent molars. A total of four cases diagnosed with symptomatic reversible pulpitis based on history, clinical examination, and investigation were planned for CGF pulpotomy. Blood required for the procedure was collected in a 10 ml test tube without anticoagulants to produce CGF. Subsequently, the sample was promptly centrifuged using a tabletop centrifuge. The clot-free pulp chamber was then shielded with a small CGF membrane fragment. A layer of mineral trioxide aggregate (MTA), approximately 2 mm thick, was applied over the CGF membrane. Following this, the tooth was temporized with glass ionomer cement. The patients were scheduled for a follow-up visit after a day to assess postoperative discomfort and to proceed with the final composite restoration. All the patients were recalled at 6 and 12 months for follow-up. Three of the patients were clinically and radiographically asymptomatic following the treatment. The tooth demonstrated a normal periodontal ligament space on radiographic inspection, and it passed pulp sensibility tests. One patient, though, complained of excruciating discomfort 24 hours after the procedure. The favorable results of the three instances imply that more investigation is required to validate the application of this biocompatible alternative to the management of pulpitis in permanent human molar teeth. More research with larger sample numbers and longer recollection periods is required. The use of concentrated growth factor (CGF), derived from the patient's own blood, serves as an excellent biological scaffold for the treatment of pulpal diseases.

Comprehensive in silico analysis of prognostic and immune infiltrates for FGFs in human ovarian cancer.

BACKGROUND: Fibroblast growth factors (FGFs) are cell signaling proteins that perform multiple biological processes in many biological processes (cell development, repair, and metabolism). The dynamics of tumor cells, such as angiogenesis, transformation, and proliferation, have a significant impact on neoplasia and are modulated by FGFs. FGFs' expression and prognostic significance in ovarian cancer (OC), however, remain unclear. METHODS: Through a series of in silico analysis, we investigated the transcriptional, survival data, genetic variation, gene-gene interaction network, ferroptosis-related genes, and DNA methylation of FGFs in OC patients. RESULTS: We discovered that while FGF18 expression levels were higher in OC tissues than in normal OC tissues, FGF2/7/10/17/22 expression levels were lower in the former, and that FGF1/19 expression was related to the tumor stage in OC patients. According to the survival analysis, the clinical prognosis of individuals with OC was associated with the aberrant expression of FGFs. The function of FGFs and their neighboring genes was mainly connected to the cellular response to FGF stimulus. There was a negative correlation between FGF expression and various immune cell infiltration. CONCLUSIONS: This study clarifies the relationship between FGFs and OC, which might provide new insights into the choice of prognostic biomarkers of OC patients.

Effect of madecassic acid on retinal oxidative stress, inflammation and Growth Factors in streptozotocin-induced diabetic rats.

Diabetic retinopathy (DR) is the leading cause of blindness and visual loss in people with diabetes. It has been suggested that the progression of DR is associated with chronic inflammation and oxidative stress. The aim of the present work was to evaluate the ability of the natural compound madecassic acid (MEA) to reverse the negative impact of streptozotocin (STZ) on retinal injury in rats. Diabetic rats induced by STZ were treated with MEA at the doses of 10 and 20 mg/kg bw for 8 weeks. The study compared the efficacy of the drug in controlling high blood sugar levels and its impact on therapeutic targets such as SOD, CAT, GPx, NF-κB, TNF-α, IL-6, IL-1ß, VEGF, IGF, bFGF and Keap1/Nrf-2 pathway. The results showed that the treatment with MEA significantly restored the retinal SOD, CAT, and GPx levels in diabetic rats to the near-normal levels. Moreover, the level of inflammatory mediators (TNF-α, IL-1ß, IL-6) and growth factors (VEGF, IGF, bFGF) was significantly lower in retinas of animals treated with MEA as compared to retinas of diabetic animals. The study also established that MEA administration reduced the NF-κB protein and altered the Nrf-2/Keap1 pathway thereby reducing oxidative stress and inflammation. Furthermore, the use of MEA prevented the progression of the retinal capillary basement membrane thickening. It has been found that MEA offers significant protection to the retina and therefore, the compound may be useful in the treatment of DR in humans.

IGF Signaling in the Heart in Health and Disease.

One of the most vital processes of the body is the cardiovascular system's proper operation. Physiological processes in the heart are regulated by the balance of cardioprotective and pathological mechanisms. The insulin-like growth factor system (IGF system, IGF signaling pathway) plays a pivotal role in regulating growth and development of various cells and tissues. In myocardium, the IGF system provides cardioprotective effects as well as participates in pathological processes. This review summarizes recent data on the role of IGF signaling in cardioprotection and pathogenesis of various cardiovascular diseases, as well as analyzes severity of these effects in various scenarios.

Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.

Alzheimer's disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.

Trends in the use of granulocyte colony stimulating factors for older patients with cancer, 2010 to 2019.

INTRODUCTION: Older patients with cancer receiving myelosuppressive treatment are at an increased risk for developing febrile neutropenia (FN) or having chemotherapy dose-reductions or delays, resulting in suboptimal health outcomes. Granulocyte colony stimulating factors (G-CSF) are effective medications to reduce these adverse events and are recommended for patients ≥65 years receiving chemotherapy with >10 % FN risk. We sought to characterize the trends and predictors of G-CSF use between the youngest-old (66-74 years), middle-old (75-84 years), and oldest-old (≥85 years) patients with cancer. MATERIALS AND METHODS: We used registry data from SEER-Medicare for breast, lung, ovarian, colorectal, esophageal, gastric, uterine, prostate, pancreatic cancer, and non-Hodgkin lymphoma (NHL) diagnoses from 2010 to 2019. Cox proportional hazard analysis was used. RESULTS: Overall, 41.4 % of patients received G-CSF from chemotherapy initiation to three days after completion of the first chemotherapy course. The use rate remained relatively stable for all cancers, except for an increase in use for those with pancreatic cancer. G-CSF use decreased as patients got older. The oldest-old were 43.0 % (95 % confidence interval: 40.7-45.2 %) less likely to receive G-CSF compared to the youngest-old. Patients with breast cancer or NHL were more likely to receive G-CSF than those with other cancers. Patients who were female, married, White or Hispanic, and had fewer comorbidities were more likely to receive G-CSF. DISCUSSION: G-CSF is used less often in populations at higher risk of developing FN and related complications. Improving adherence to recommendations can improve health outcomes, especially in the oldest adults, older males, and Black patients.

Exosome-mediated renal protection: Halting the progression of fibrosis.

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.

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.

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.

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.

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.

Effect of allogeneic pure platelet-rich plasma, sodium cloxacillin, and their combination for the treatment of subclinical mastitis in crossbred cows.

Introduction: Bovine subclinical mastitis (SCM) caused by Gram-positive bacteria is a major cause of economic loss in the dairy industry, exacerbated in situations where antimicrobial resistance is present. Pure platelet-rich plasma (P-PRP) may be a therapeutic alternative for SCM, when used alone or with antibiotics, such as sodium cloxacillin (SC). This study aimed 1) to evaluate the therapeutic efficacy of allogeneic P-PRP, SC, and their combination (P-PRP+SC) in cows with SCM caused by Staphylococcus aureus and by streptococci (Staphylococcus aureus and S. dysgalactiae); 2) to determine the concentrations of somatic cells (SCC), interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and TGF-ß1 in milk samples of the cows. Methods: 130 cows from 4 dairy herds completed the study, of which 40 cows were treated with P-PRP (10 mL), 28 cows with SC (5g), 36 with P-PRP+SC (10mL/5g), and 26 did not receive no treatment (negative control group, NCG). Results: The overall bacteriological cure was observed in 10/40 (25%) cows in the P-PRP group, 9/28 (32.14%) animals in the SC group, 26/36 (72.22%) cows in the P-PRP+SC group, and 10/26 (38.46%) animals in the NCG. SCM caused by S. aureus (82/130, 63.08%), was cured in 6/24 (25%) cows treated with P-PRP, 7/24 (29.2%) cows treated with SC, 8/16 (50%) animals treated with P-PRP+SC, and in 8/18 (44.4%) cows in NCG. For SCM caused by the streptococci (48/130, 36.91%), the cure was achieved in 4/12 (33.3%) cows treated with P-PRP, 2/4 (50%) cows treated with SC, 18/20 (90%) cows treated with P-PRP+SC, and in 2/8 (25%) cows of the NCG. SCC was significantly (p < 0.001) affected by the treatment, herd, cure, bacteria group, and number of calvings factors. IL-1ß milk concentrations were significantly (p < 0.001) influenced by treatment and farm factors, and the interaction between these factors. TNF-α milk concentrations were significantly (p < 0.001) influenced by time factor. TGF-ß1 milk concentrations were significantly affected by the time and cure factors. Conclusion: The combination of P-PRP and SC showed the best therapeutic response (90%) against bovine SCM caused by streptococci. However, none of the treatments showed an effective therapeutic response against S. aureus.