Efficacy and safety of platelet-rich plasma (PRP) in erectile dysfunction (ED): a systematic review and meta-analysis.

Background: Erectile dysfunction (ED) is a prevalent condition in aging men. Meanwhile, platelet-rich plasma (PRP), an emerging treatment alternative, has demonstrated potential in mitigating symptoms associated with ED. Our research aimed to explore the safety and effectiveness of employing PRP as a treatment strategy for ED. Methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our research involved a thorough search across multiple databases: PubMed, Web of Science, Embase, and the Cochrane Controlled Trials Register. To assess the methodological rigor of the studies selected, we applied the modified Jadad scale and the Methodological Index for Non-Randomized Studies (MINORS) scale as evaluation tools. Subsequent to these evaluations, data analysis was conducted. Results: Our analysis included seven non-randomized studies and three randomized controlled trials (RCTs). These studies showed that the International Index of Erectile Function-Erectile Function (IIEF-EF) scores improved significantly after 1, 3, and 6 months of PRP treatment, with increases of 4.05 [95% confidence interval (CI): 2.42, 5.68; P<0.001], 3.73 (95% CI: 2.93, 4.53; P<0.001), and 3.92 (95% CI: 3.00, 4.85; P<0.001) respectively, compared to the baseline scores. Additionally, compared to the placebo group, the PRP group showed significantly higher IIEF-EF scores. PRP treatment also had a beneficial impact on minimal clinically important difference (MCID) and peak systolic velocity (PSV). However, no significant differences were found between the PRP and placebo groups in terms of erectile hardness score (EHS) [mean difference (MD) =0.63; 95% CI: 0.26, 0.99; P<0.001] or visual analog scale (VAS) pain scores (MD =0.24; 95% CI: -0.05, 0.54; P=0.11). Conclusions: Our study results demonstrated significant efficacy and safety of PRP in treating ED. Due to the fact that most of the literature we included was single-arm studies, it was imperative for future research to provide higher-quality evidence for validation.

Clinical application of platelet rich plasma to promote healing of open hand injury with skin defect.

Background: Skin defects caused by open hand trauma are difficult to treat clinically and severely affect the recovery of hand function. Autologous platelet-rich plasma (PRP) has been widely used in the treatment of refractory chronic wounds, but its use in hand trauma skin defects remains scarce. Methods: This study compared the outcomes of 27 patients treated with PRP to 31 patients undergoing skin flap transplantation for hand wounds. We assessed several parameters, including healing times, duration of surgery, postoperative pain (VAS score), intraoperative amputation length, finger function, sensation restoration, nail bed preservation, and hospitalization expenses. Results: PRP-treated patients showed a mean healing time of 21.59 ± 3.17 days. Surgical times were significantly shorter in the PRP group (22.04 ± 7.04 min) compared to the flap group (57.45 ± 8.15 min, P < 0.0001). PRP patients experienced longer postoperative healing times (20.15 ± 2.16 days) than those in the skin flap group (12.84 ± 1.08 days, P < 0.0001), but reported lower pain scores (1.3 ± 1.44 vs 2.55 ± 2.06, P = 0.0119). Range of Motion (ROM) at the proximal interphalangeal joint was better in the PRP group (96.26° ± 6.69) compared to the flap group (86.16° ± 15.24, P = 0.0028). Sensory outcomes favored the PRP group, with a two-point discrimination of 2.37 ± 1.34 mm versus 2.52 ± 1.27 mm in the flap group (P = 0.0274). Costs were lower in the PRP group ($2081.6 ± 258.14 vs $2680.18 ± 481.15, P < 0.0001). Conclusion: PRP treatment for skin defects from hand trauma is effective, offering advantages in terms of reduced surgical time, pain, and cost, with comparable or superior functional outcomes to flap transplantation. Despite longer healing times, PRP may represent a preferable option for open hand injuries, preserving more nail beds and resulting in better sensation and joint motion.

The Efficacy of Local Autologous Platelet-Rich Plasma Prepared by Single and Double Spin Methods in the Treatment of Chronic Ulcer.

BACKGROUND: Chronic nonhealing ulcers present significant challenges in diabetic, dermatological, and surgical patients. Platelet-rich plasma (PRP), enriched with bioactive factors, offers promise for wound healing enhancement. This study evaluates PRP's efficacy, prepared via single and double spin methods in nonhealing chronic ulcers. METHODS:  Twenty-two patients aged 18-65 years participated and 100 mL of blood was drawn into citrate phosphate dextrose adenine (CPDA) bags with all aseptic precautions. PRP was prepared by single and double spin methods. Patient serum and 10% calcium gluconate were added to fibrin gel. PRP was injected around the ulcer and then dressed. Dressings were changed on the fifth, 15th, and 20th days with PRP. Evaluation occurred on day 30 using surface area and volume assessments by both methods. RESULTS: The single spin PRP group and double spin PRP group had 11 patients each with hemoglobin range of 10.79±1.88 to 12.63±2.22 g/dL. Initial lesions (16.27 cm²) significantly reduced to 14.76 cm² after double spin PRP sessions (p=0.005) and Initial lesions (9.87 cm²) significantly reduced to 7.65 cm² after single spin PRP sessions (p=0.005). Platelet count differences between whole blood and PRP were significant (p<0.05). CONCLUSIONS: The single spin PRP method exhibited considerable improvements in healing parameters, showcasing its potential for chronic ulcer management.

Chondroprotective Effects of a Single PRP Injection in a Spontaneous Osteoarthritis Model of Dunkin Hartley Guinea Pig: An Immunohistochemical Analysis.

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p-0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.

Platelet-Rich Plasma for Knee and Hip Osteoarthritis Pain: A Scoping Review.

PURPOSE OF REVIEW: Platelet-rich plasma (PRP) is an emerging biological intervention for osteoarthritis (OA), yet the outcomes remain uncertain. The purpose of this study was to review current literature regarding the use of PRP for knee and hip OA. RECENT FINDINGS: Recent systematic reviews have found significant clinical improvements in outcomes after the administration of PRP compared to hyaluronic acid (HA) in patients with knee OA. One of these reviews included bone marrow aspirate concentrate (BMAC) as a comparison group and found no significant differences in outcomes between PRP and BMAC. Currently, the literature is lacking on whether leukocyte-rich or leukocyte-poor PRP is superior in patients with knee OA. The literature on PRP for hip OA has not provided consistent results as it has for the knee. Two recent systematic reviews evaluated RCTs for patients undergoing treatment with either PRP or HA for hip OA and found no significant differences in clinical outcomes between groups at final follow-up. Current literature regarding the association between OA grade and PRP efficacy has found varying results. The use of PRP injections in the treatment of knee OA appears to be favorable, resulting in clinically comparable or superior outcomes compared to other injection treatments. However, the clinical efficacy of PRP injections in hip OA is far less consistent. Evidence is lacking to suggest that the presence of leukocytes significantly influences clinical outcomes. Further randomized controlled trials on larger cohorts, with longer follow-up, and with comparable formulations are required before recommendations can be made regarding use of PRP for hip OA, the effect of leukocyte concentration, and clinical efficacy based on OA grade.

How Intravesical Platelet-Rich Plasma Can Help Patients with Interstitial Cystitis/Bladder Pain Syndrome: A Comprehensive Scoping Review.

INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. METHODS: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. RESULTS: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. CONCLUSION: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.

Chondrotoxicity of Intra-Articular Injection Treatment: A Scoping Review.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Efficacy of using adipose-derived stem cells and PRP on regeneration of 40 -mm long sciatic nerve defect bridged by polyglycolic-polypropylene mesh in canine model.

BACKGROUND: Sciatic nerve repair becomes a focus of research in neurological aspect to restore the normal physical ability of the animal to stand and walk. Tissue engineered nerve grafts (TENGs) provide a promising alternative therapy for regeneration of large gap defects. The present study investigates the regenerative capacity of PRP, ADSCs, and PRP mixed ADSCs on a long sciatic nerve defect (40-mm) bridged by a polyglycolic polypropylene (PGA-PRL) mesh which acts as a neural scaffold. MATERIALS AND METHODS: The study was conducted on 12 adult male mongrel dogs that were randomly divided into 4 groups: Group I (scaffold group); where the sciatic defect was bridged by a (PGA-PRL) mesh only while the mesh was injected with ADSCs in Group II (ADSCs group), PRP in Group III (PRP group). Mixture of PRP and ADSCs was allocated in Group IV (PRP + ADSCs group). Monthly, all animals were monitored for improvement in their gait and a numerical lameness score was recorded for all groups. 6 months-post surgery, the structural and functional recovery of sciatic nerve was evaluated electrophysiologically, and on the level of gene expression, and both sciatic nerve and the gastrocnemius muscle were evaluated morphometrically, histopathologically. RESULTS: Numerical lameness score showed improvement in the motor activities of both Group II and Group III followed by Group IV and the scaffold group showed mild improvement even after 6 months. Histopathologically, all treated groups showed axonal sprouting and numerous regenerated fascicles with obvious angiogenesis in proximal cut, and distal portion where Group IV exhibited a significant remyelination with the MCOOL technique. The regenerative ratio of gastrocnemius muscle was 23.81%, 56.68%, 52.06% and 40.69% for Group I, II, III and IV; respectively. The expression of NGF showed significant up regulation in the proximal portion for both Group III and Group IV (P ≤ 0.0001) while Group II showed no significant difference. PDGF-A, and VEGF expressions were up-regulated in Group II, III, and IV whereas Group I showed significant down-regulation for NGF, PDGF-A, and VEGF (P ≤ 0.0001). CONCLUSION: ADSCs have a great role in restoring the damaged nerve fibers by secreting several types of growth factors like NGF that have a proliferative effect on Schwann cells and their migration. In addition, PRP therapy potentiates the effect of ADSCs by synthesis another growth factors such as PDGF-A, VEGF, NGF for better healing of large sciatic gap defects.

Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

Therapeutic Potential of Platelet-Rich Plasma in Fracture Healing: A Comprehensive Review.

Fracture healing is a dynamic process essential for the restoration of bone integrity and function. However, factors such as patient age, comorbidities, and the severity of the fracture can impede this process, leading to delayed healing or nonunion. Platelet-rich plasma (PRP) has emerged as a promising therapeutic option for enhancing fracture healing. PRP is an autologous blood product containing a concentrated mixture of platelets, growth factors, and cytokines known to promote tissue regeneration and repair. This comprehensive review provides an overview of the fracture healing process, emphasizing the importance of timely and efficient bone repair. We discuss the mechanisms underlying the purported efficacy of PRP in fracture healing, drawing upon both preclinical and clinical evidence. Preclinical studies in animal models have demonstrated the ability of PRP to accelerate fracture healing, stimulate osteogenesis, and enhance bone regeneration. Clinical studies have yielded mixed results, with some reporting positive outcomes in terms of accelerated healing and improved functional outcomes, while others have shown no significant benefits over standard treatments. Factors influencing the efficacy of PRP, such as timing of administration, PRP concentration, and patient-specific variables, are also examined. Furthermore, safety considerations and potential adverse effects associated with PRP therapy are discussed. Despite the promising preclinical findings, challenges remain in standardizing PRP formulations, optimizing administration protocols, and addressing unanswered questions regarding its long-term efficacy and safety. This review aims to provide insights into the therapeutic potential of PRP in fracture healing, informing future research directions and guiding clinical practice.

Platelet Power: Revitalizing Endodontics With Scaffolds.

This article provides an overview of a biologically based method for restoring damaged tooth structures and pulp tissues known as regenerative endodontics. It explores the concept of regenerative endodontics, its tissue engineering approach, and its application in maintaining vitality. The article discusses the significance of the factors affecting growth, scaffolds, and stem cells being the three tissue engineering components involved in the regeneration of pulp tissues. It also delves into the classification of scaffolds and the role of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) as biological scaffolds. The methodology section details the search process for relevant studies, and the review section presents research findings associated with PRF and its application in regeneration and repair of tissue. The article concludes by highlighting the potential of advanced PRF and injectable PRF in regenerative endodontics, with a focus on their impact on tissue regeneration and healing.

The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.

The use of platelet rich plasma in the treatment of degenerative joint disease in cats: an exploratory case series.

Objective: To evaluate the effectiveness of intra-articular autologous Platelet Rich Plasma (PRP) in managing Degenerative Joint Disease (DJD) in cats. Design: Prospective pilot clinical trial. Methods: Six domestic cats with clinically and radiographically diagnosed DJD received intra-articular injections of autologous PRP. Clinical assessments pre and post intra-articular injections were conducted using the Feline Musculoskeletal Pain Index (FMPI, owner assessed) and Visual Analog Scale (VAS, clinician assessed) at baseline, Day 14, Day 28, and Day 42-45. Results: Significant improvements were noted in both FMPI and VAS scores at the end of the study period, indicating enhanced joint function and reduced pain. Conclusion and clinical relevance: The study suggests the potential of PRP therapy as a safe and effective treatment for feline DJD, warranting further research with larger cohorts and longer follow-up to establish comprehensive treatment guidelines.

Synergistic Effect of Transmyocardial Revascularization and Platelet-Rich Plasma on Improving Cardiac Function After Coronary Artery Bypass Grafting.

Background Coronary artery disease (CAD) is a global health burden, contributing to mortality and morbidity. A proportion of patients with CAD suffer from diffuse CAD, where conventional revascularization techniques such as percutaneous coronary intervention and coronary artery bypass grafting (CABG) may be insufficient to adequately restore myocardial perfusion. Transmyocardial revascularization (TMR) uses a laser to create microscopic channels in the myocardium, inducing inflammation, angiogenesis, and neovascularization to improve perfusion to ischemic regions. Platelet-rich plasma (PRP) is an autologous concentrate of platelets that contains a myriad of growth factors and bioactive proteins, which have been shown to promote tissue regeneration and wound healing. The combination of TMR and PRP therapies has been proposed to synergistically enhance myocardial revascularization and functional recovery in patients with advanced CAD undergoing surgical revascularization. Methods This study evaluated the efficacy of combining TMR and PRP with CABG in improving cardiac function in diffuse CAD patients. Fifty-two patients were randomized to CABG alone (n = 16), CABG+TMR (n = 17), CABG+PRP (n = 10), and CABG+TMR+PRP (n = 9). TMR was performed using a holmium:YAG laser to create 10 channels in the inferolateral left ventricular wall. PRP was prepared from autologous whole blood and injected into the myocardium adjacent to the TMR channels. Cardiac function was assessed using speckle-tracking echocardiography preoperatively, postoperatively, and at one-year follow-up. Adverse events, including post-operative atrial fibrillation, acute kidney injury, and readmissions, were also recorded. Statistical analyses were performed to compare outcomes between the treatment groups. Results The CABG+TMR+PRP group showed significantly improved global longitudinal strain (GLS) at one year compared to CABG alone (mean GLS -15.96 vs -12.09, p = 0.02). Post-operative left ventricular ejection fraction trended higher in the TMR+PRP group (57.78%) vs other groups, but not significantly. Post-operative atrial fibrillation was higher in the TMR+PRP group (67% vs 25%, p = 0.04), potentially reflecting increased inflammation. No significant differences were observed in other adverse events. Conclusions The results of this study suggest a synergistic benefit of combining TMR and PRP therapies as an adjunct to CABG in patients with diffuse CAD. The significant improvement in GLS at one year in the TMR+PRP group compared to CABG alone indicates enhanced myocardial remodeling and functional recovery, which may translate to improved long-term outcomes. The higher incidence of postoperative atrial fibrillation in the TMR+PRP group warrants further investigation but may reflect the heightened inflammatory response necessary for angiogenesis and tissue regeneration. Prospective, randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings and optimize treatment protocols. Nonetheless, concomitant TMR+PRP therapy represents a promising approach to augmenting myocardial revascularization and recovery in patients with advanced CAD undergoing surgical revascularization.

Characterization of Cwc2, U6 snRNA, and Prp8 interactions destabilized by Prp16 ATPase at the transition between the first and second steps of splicing.

The spliceosome performs two consecutive transesterification reactions using one catalytic center, thus requiring its rearrangement between the two catalytic steps of splicing. The Prp16 ATPase facilitates exit from the first-step conformation of the catalytic center by destabilizing some interactions important for catalysis. To better understand rearrangements within the S. cerevisiae catalytic center, we characterize factors that modulate function of Prp16: Cwc2, N-terminal domain of Prp8, and U6-41AACAAU46 region. Alleles of these factors were identified through genetic screens for mutants that correct cs defects of prp16-302 allele. Several of the identified U6, cwc2, and prp8 alleles are located in close proximity of each other in cryo-EM structures of the spliceosomal catalytic conformations. Cwc2 and U6 interact with the intron sequences in the first step, but they do not seem to contribute to the stability of the second step catalytic center. On the other hand, the N-terminal segment of Prp8 not only affects intron positioning for the first step, but it also makes important contacts in the proximity of the active site for both the first and the second steps of splicing. By identifying interactions important for the stability of catalytic conformations, our genetic analyses indirectly inform us about features of the transition-state conformation of the spliceosome.

Simple 3D spheroid cell culture model for studies of prion infection.

Mouse neuronal CAD 5 cell line effectively propagates various strains of prions. Previously, we have shown that it can also be differentiated into the cells morphologically resembling neurons. Here, we demonstrate that CAD 5 cells chronically infected with prions undergo differentiation under the same conditions. To make our model more realistic, we triggered the differentiation in the 3D culture created by gentle rocking of CAD 5 cell suspension. Spheroids formed within 1 week and were fully developed in less than 3 weeks of culture. The mature spheroids had a median size of ~300 µm and could be cultured for up to 12 weeks. Increased expression of differentiation markers GAP 43, tyrosine hydroxylase, ß-III-tubulin and SNAP 25 supported the differentiated status of the spheroid cells. The majority of them were found in the G0/G1 phase of the cell cycle, which is typical for differentiated cells. Moreover, half of the PrPC on the cell membrane was N-terminally truncated, similarly as in differentiated CAD 5 adherent cells. Finally, we demonstrated that spheroids could be created from prion-infected CAD 5 cells. The presence of prions was verified by immunohistochemistry, western blot and seed amplification assay. We also confirmed that the spheroids can be infected with the prions de novo. Our 3D culture model of differentiated CAD 5 cells is low cost, easy to produce and cultivable for weeks. We foresee its possible use in the testing of anti-prion compounds and future studies of prion formation dynamics.

Comparing Prion Proteins Across Species: Is Zebrafish a Useful Model?

Despite the considerable body of research dedicated to the field of neurodegeneration, the gap in knowledge on the prion protein and its intricate involvement in brain diseases remains substantial. However, in the past decades, many steps forward have been taken toward a better understanding of the molecular mechanisms underlying both the physiological role of the prion protein and the misfolding event converting it into its pathological counterpart, the prion. This review aims to provide an overview of the main findings regarding this protein, highlighting the advantages of many different animal models that share a conserved amino acid sequence and/or structure with the human prion protein. A particular focus will be given to the species Danio rerio, a compelling research organism for the investigation of prion biology, thanks to its conserved orthologs, ease of genetic manipulation, and cost-effectiveness of high-throughput experimentation. We will explore its potential in filling some of the gaps on physiological and pathological aspects of the prion protein, with the aim of directing the future development of therapeutic interventions.

Application of biotechnologies in the treatment of haemorrhoidal disease and optimisation of patient management.

Introduction: Haemorrhoidal disease is one of the most common nowadays. It is often associated with a sedentary lifestyle. The leading cause of its development is also a functional disorder of the intestine and chronic constipation. To date, there is a steady growth rate of this disease, leading to its "rejuvenation". The current stage of development indicates the need for further improvement of surgical treatment and optimisation of patient management methods and the creation of uniform standards of care for this contingent of patients. Aim: To evaluate the clinical effectiveness of the use of platelet-rich plasma therapy and the biologically active substance "ozoyl" in the treatment of haemorrhoidal disease. Material and methods: The main group included 100 patients with chronic haemorrhoids who were operated on in the period from March 2021 to March 2022. For this group, autoplasma was used during surgery, and an ozoyl-based drug in the postoperative period. The remaining 100 participants of this study, assigned to the control group, underwent a conventional haemorrhoidectomy operation and standard patient management using a hydrophilic ointment based on chloramphenicol. Results: After the conducted clinical studies, it was established that in the main group, the pain syndrome decreased by about 30%, considering the period from the first day of the postoperative period compared to the control group. The postoperative wound healed in the main group in the third week after the operation, unlike the control group, in which this event was noted in the fourth week. The patients did not complain during the examination 3 months later. Conclusions: This study is of practical significance because haemorrhoidal disease today has a high prevalence, and an integrated approach is required for the treatment of such patients. Ozoyl is a powerful cell and tissue repairer.

The Implications of Brain-Derived Neurotrophic Factor in the Biological Activities of Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.

Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing.

The utilization of platelet-rich plasma (PRP) has exhibited potential as a therapeutic approach for the management of diabetic foot ulcers (DFUs). However, it is currently not well understood how the diabetic environment may influence PRP-derived exosomes (PRP-Exos) and their potential impact on neutrophil extracellular traps (NETs). This study aims to investigate the effects of the diabetic environment on PRP-Exos, their communication with neutrophils, and the subsequent influence on NETs and wound healing. Through bulk-seq and Western blotting, we confirmed the increased expression of MMP-8 in DFUs. Additionally, we discovered that miRNA-26b-5p plays a significant role in the communication between DFUs and PRP-Exos. In our experiments, we found that PRP-Exos miR-26b-5p effectively improved diabetic wound healing by inhibiting NETs. Further tests validated the inhibitory effect of miR-26b-5p on NETs by targeting MMP-8. Both in vitro and in vivo experiments showed that miRNA-26b-5p from PRP-Exos promoted wound healing by reducing neutrophil infiltration through its targeting of MMP-8. This study establishes the importance of miR-26b-5p in the communication between DFUs and PRP-Exos, disrupting NETs formation in diabetic wounds by targeting MMP-8. These findings provide valuable insights for developing novel therapeutic strategies to enhance wound healing in individuals suffering from DFUs.