Bioactive Peptides and Other Immunomodulators of Mushroom Origin.

For centuries, humans have used mushrooms as both food and pro-health supplements. Mushrooms, especially those related to the functions of the human immune system, are rich in dietary fiber, minerals, essential amino acids, and various bioactive compounds and have significant health-promoting properties. Immunoregulatory compounds in mushrooms include lectins, terpenes, terpenoids, polysaccharides, and fungal immunomodulatory proteins (FIPs). The distribution of these compounds varies from one species of mushroom to another, and their immunomodulatory activities depend on the core structures and chemical modifications in the composition of the fractions. In this review, we describe active compounds from medical mushrooms. We summarize potential mechanisms for their in vitro and in vivo activities and detail approaches used in developing and applying bioactive compounds from mushrooms. Finally, we discuss applications of fungal peptides and highlight areas that require improvement before the widespread use of those compounds as therapeutic agents and explore the status of clinical studies on the immunomodulatory activities of mushrooms and their products, as well as the prospect of clinical application of AMPs as 'drug-like' compounds with great potential for treatment of non-healing chronic wounds and multiresistant infections.

The activity of monocyte-derived macrophages after stimulation with platelet-rich and platelet-poor concentrates. Study on an ovine model of insertion of a tibial implant coated with silicon-doped diamond-like carbon.

Introduction: Macrophages are crucial immune cells that play a role in tissue repair and can exhibit pro- or anti-inflammatory behaviour based on environmental stimulation. Their functional phenotype can be affected by platelet-derived products as determined by those products' composition. When the inflammatory response caused by implantation is excessive, it can lead to rejection of the implant. Therefore, a thorough evaluation of implant haemocompatibility is necessary to minimise undesirable consequences. Material and Methods: In an in vitro study, monocyte-derived macrophages (MDMs) were obtained from the whole blood of sheep after a silicon-doped diamond-like carbon-coated implant insertion. These MDMs were then exposed to autologous platelet-derived products for functional marker analysis. Results: Platelet-poor plasma (PPP) and pure platelet-rich plasma (P-PRP) stimulation increased arginase-1 activity, while leukocyte-rich PRP stimulation produced a mixed response involving higher O2- (6.49 ± 2.43 nM vs non-stimulated 3.51 ± 1.23 nM, P-value < 0.05) and NO (3.28 ± 1.38 µM vs non-stimulated 2.55 ± 0.32µM, P-value < 0.05) generation. Conclusion: Using PPP and P-PRP stimulation in post-implantation procedures may contribute to the polarisation of macrophages towards the M2-like pro-resolving phenotype, thereby accelerating wound healing. This would also prevent implant degradation due to an excessive inflammatory process.

Analysis of In Vitro Leukocyte Responses to Biomaterials in the Presence of Antimicrobial Porcine Neutrophil Extract (AMPNE).

Implant insertion can evoke excessive inflammation which disrupts the healing process and potentially leads to complications such as implant rejection. Neutrophils and macrophages play a vital role in the early inflammatory phase of tissue repair, necessitating the study of cellular responses in host-implant interactions. In order to deepen the knowledge about these interactions, the response of neutrophils and macrophages to contact with selected biomaterials was examined in vitro on the basis of secretory response as well as reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. Porcine neutrophils exposed to hydroxyapatite (HA) released more enzymes and generated higher levels of ROS/RNS compared to the control group. The addition of AMPNE diminished these responses. Although the results from porcine cells can provide valuable preliminary data, further validation using human cells or clinical studies would be necessary to fully extrapolate the findings to human medicine. Our study revealed that human neutrophils after contact of with HA increased the production of nitric oxide (NO) (10.00 ± 0.08 vs. control group 3.0 ± 0.11 µM, p < 0.05), while HAP or FAP did not elicit a significant response. Human macrophages cultured with HA produced more superoxide and NO, while HAP or FAP had a minimal effect, and curdlan reduced ROS/RNS generation. The addition of AMPNE to cultures with all biomaterials, except curdlan, reduced neutrophil activity, regardless of the peptides' origin. These results highlight the potential of antimicrobial peptides in modulating excessive biomaterial/host cell reactions involving neutrophils and macrophages, enhancing our understanding of immune reactions, and suggesting that AMPNE could regulate leukocyte response during implantation.

Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies.

Osteoarthritis (OA) is a chronic, progressive, multifactorial disease resulting in a progressive loss of articular cartilage structure and function that is most common in middle-aged and older patients. OA is involved in the loss of extracellular matrix and cartilage as well as cell number decreases within the matrix, especially in the further stages of the disease. The immune system plays a pivotal role in the pathomechanism of this condition. Both humoral and cellular mediators contribute to cartilage destruction, abnormal bone remodeling, synovitis, and joint effusion. The increasing prevalence of this disease has led to a growing interest in using animal models as the primary way to broaden the knowledge of the pathogenesis of OA and possible therapies at each stage of disease development. This review aims to describe the signs, pathogenesis, and classification of OA as well as discuss the advantages and disadvantages of some animal models. The currently used treatment methods include mesenchymal stem cells, exosomes, gene therapies, and blood-derived products. In addition, exogenous growth factors, platelet-rich plasma (PRP), platelet lysate, and autologous conditioned serum (ACS) are discussed with the application of tissue engineering techniques and biomaterials.