Efferocytosis during Skeletal Muscle Regeneration

Efferocytosis, i.e., engulfment of dead cells by macrophages, is a crucial step during tissue repair after an injury. Efferocytosis delineates the transition from the pro-inflammatory phase of the inflammatory response to the recovery phase that ensures tissue reconstruction. We present here the role of efferocytosis during skeletal muscle regeneration, which is a paradigm of sterile tissue injury followed by a complete regeneration. We present the molecular mechanisms that have been described to control this process, and particularly the metabolic control of efferocytosis during skeletal muscle regeneration.

It takes all kinds: heterogeneity among satellite cells and fibro-adipogenic progenitors during skeletal muscle regeneration

ABSTRACT Vertebrate skeletal muscle is composed of multinucleate myofibers that are surrounded by muscle connective tissue. Following injury, muscle is able to robustly regenerate because of tissue-resident muscle stem cells, called satellite cells. In addition, efficient and complete regeneration depends on other cells resident in muscle – including fibro-adipogenic progenitors (FAPs). Increasing evidence from single-cell analyses and genetic and transplantation experiments suggests that satellite cells and FAPs are heterogeneous cell populations. Here, we review our current understanding of the heterogeneity of satellite cells, their myogenic derivatives and FAPs in terms of gene expression, anatomical location, age and timing during the regenerative process – each of which have potentially important functional consequences.

A Comparative Analysis of Gene and Protein Expression Throughout a Full 28-Day Retinal Regeneration Time-Course in Adult Zebrafish

Following photoreceptors ablation by intense light exposure, adult zebrafish are capable of complete regeneration due to the ability of their Müller glia (MG) to re-enter the cell cycle, creating progenitors that differentiate into new photoreceptors. The majority of previous reports on retinal regeneration focused on the first few days of the regenerative response, which include MG cell-cycle re-entry and progenitor cell proliferation. With this study, we analyzed the full 28-day time-course of regeneration by pairing a detailed morphological/immunological analysis with RNA-seq transcriptional profiling at 8 key time points during retinal regeneration. We observed several novel findings. First, we provide evidence for two separate peaks of MG gliosis, with the secondary gliotic peak occurring after MG cell-cycle re-entry. Second, we highlight a distinct transcriptional shift between 5- and 10-days post lesion that highlights the transition from progenitor proliferation to differentiation into new photoreceptors. Third, we show distinctly different patterns of transcriptional recovery of the photoreceptor opsins at 28 days post lesion. Finally, using differential gene expression analysis, we revealed that the established functional recovery of the retina at 28 days post lesion does not, in fact, return to an undamaged transcriptional state, potentially redefining what the field considers complete regeneration. Together, to our knowledge, this work represents the first histological and transcriptomic map of a 28-day time-course of retinal regeneration in adult zebrafish.

The environmental context of Early Neolithic cultural transformation in the Targowisko settlement region

The aim of this article is to provide information on environmental changes in the Targowisko region in the Early Neolithic as a natural response to settlement and economic activity of the human population in that area. The discussion is based on lithological, geochemical, and palynological analyses, as well as the analysis of Cladocera within strata inside the TRG (Targowisko) core, located in a small wetland in the immediate vicinity of the eastern edge of the Neolithic settlement in the Targowisko region. Settlement analysis points to the absence of stable microregions and to the mobility of human groups. This is confirmed by the sequence of settlement episodes and economic activity, reflected in the stratigraphy of the core sediments, where episodes of significant human interference are followed by phases of almost complete regeneration of the environment. No differences have been noticed between the Linienbandkeramik and Malice culture communities as regards their impact on the environment.

And Then There Were Three…: Extreme Regeneration Ability of the Solitary Chordate Polycarpa mytiligera

Extensive regenerative ability is a common trait of animals capable of asexual development. The current study reveals the extraordinary regeneration abilities of the solitary ascidian Polycarpa mytiligera. Dissection of a single individual into separate fragments along two body axes resulted in the complete regeneration of each fragment into an independent, functional individual. The ability of a solitary ascidian, incapable of asexual development, to achieve bidirectional regeneration and fully regenerate all body structures and organs is described here for the first time. Amputation initiated cell proliferation in proximity to the amputation line. Phylogenetic analysis demonstrated the close affinity of P. mytiligera to colonial species. This evolutionary proximity suggests the ability for regeneration as an exaptation feature for colonial lifestyle. P. mytiligera’s exceptional regenerative abilities and phylogenetic position highlight its potential to serve as a new comparative system for studies seeking to uncover the evolution of regeneration and coloniality among the chordates.

Characterization of Polycaprolactone Nanohydroxyapatite Composites with Tunable Degradability Suitable for Indirect Printing

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.

Investigation of the impact of a balanced diet according to the method of alfitherapy on the human body

In the late 1980s – early 1990s, General A.V. Shcherbakov and Professor I.V. Pronin, who participated in the creation of the Russian Rescue Corps, developed a new method for saving all living things during disasters, dangerous climatic conditions, deadly situations, using the latest developments of Professor I.V. Pronin, which have no analogues in the world and named it "Medicine of support in extreme situations". For civilians, this system, based on the intersection of microbiology, algology and herbal medicine, became known as Alphitherapy. Initially, the method was intended for special forces operating in rescue operations during man-made disasters, as well as disasters caused by natural disasters. Alphitherapy is a method of balanced nutrition of plant origin with biologically active substances of medicinal plants, algae, microorganisms due to a combination of essential oils and active substances in high concentrations. The composition of a balanced diet according to the method of alfitherapy includes a living bactericidal environment, which many times exceeds the therapeutic capabilities of drugs of chemical origin. Purpose of work – investigation of the effect of accelerating regenerative processes and a healing effect as a result of the use of a balanced diet according to the method of alfitherapy. It has been established that a course of balanced nutrition according to the method of alfitherapy has antibacterial, antiviral and antimetastatic effects, making it possible in some cases to dispense with operations or surgical intervention. In the process of completing a course of balanced nutrition in a period from several days to three months, many types of damaged tissues and organs are regenerated, blood vessels are restored and the blood supply to the brain is enhanced, the liver and other organs are cleared of toxins, isotopes (radiation) and heavy metals at the intracellular and intercellular levels. It is possible to restore the cognitive, speech and motor functions lost as a result of strokes due to the complete regeneration of the damaged vessels of the brain.

Regeneration of mandibular osteoradionecrosis with autologous cross-linked serum albumin scaffold

Osteoradionecrosis is one of the most severe complications of radiotherapy administered for head and neck tumors. We present the first two cases of advanced and refractory mandibular osteoradionecrosis treated by application of a novel autologous cross-linked 3D serum matrix. Patients were followed clinically and radiographically up to 24 months. Complete wound healing and intact mucosal cover were achieved in both cases. At 12 months, the radiographic values showed an almost complete regeneration of the bone defect, which continued a favourable progression increased to the maximum by 24 months after surgery. The use of an autologous serum-derived scaffold proved to be a quick, predictable, cost-effective and safe adjunct to the conservative surgical treatment of this pathology.