Correction to: Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity? The Authors regret forgetting in the original version of this article to mention that this work was also supported by the US National Institute of Health (NIH) (1OT2OD024899-01).

Correction to: "Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocyes during 36 weeks in rabbit model The published online of the original version contains mistakes.

Correction to: Circadian neurogenetics of mood disorders The original version of this article was revised: Figures 1 and 2 of the final PDF were not changed according to author's request during the proof corrections.

Immunocytochemical localization of a putative strychnine-sensitive glycine receptor in Hydra vulgaris Abstract Previous biochemical studies have identified strychnine-sensitive glycine receptors in membrane preparations of Hydra vulgaris (Cnidaria: Hydrozoa). Electrophysiological and behavioral evidence has shown that these receptors play a role in modulating pacemaker activity and feeding behavior. Here, we present our genomic analysis that revealed hydra proteins having strong homology with the strychnine-binding region of the human receptor protein, GlyRα1. We further present immunocytochemical evidence for the specific labeling of cell and tissue preparations of hydra by a commercially available polyclonal anti-GlyRα1 antibody, selected through our genomic analysis. Tissue pieces and cell macerates from the upper and lower thirds of the body and ablated tentacles were double-labeled with this antibody and with an antibody specific for α-tubulin, to identify the glycine receptors and microtubules, respectively. Extensive receptor labeling was evident on the membranes, cell bodies and myonemes of endodermal and ectodermal epithelial cells, cell bodies and neurites of nerve cells, cnidocytes and interstitial cells. Labeling of the membranes of epithelial cells frequently corresponded to conspicuous varicosities (presumptive presynaptic sites) in the associated nerve net. Our findings support the idea that glycine receptors form an integral part of the nerve and effector systems that control hydra behavior.

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing Abstract There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.

Cricket tympanal organ revisited: morphology, development and possible functions of the adult-specific chitin core beneath the anterior tympanal membrane Abstract Vertebrates and insects are phylogenetically separated by millions of years but have commonly developed tympanal membranes for efficiently converting airborne sound to mechanical oscillation in hearing. The tympanal organ of the field cricket Gryllus bimaculatus, spanning 200 μm, is one of the smallest auditory organs among animals. It indirectly links to two tympana in the prothoracic tibia via tracheal vesicles. The anterior tympanal membrane is smaller and thicker than the posterior tympanal membrane and it is thought to have minor function as a sound receiver. Using differential labeling of sensory neurons/surrounding structures and three-dimensional reconstructions, we revealed that a shell-shaped chitin mass and associated tissues are hidden behind the anterior tympanal membrane. The mass, termed the epithelial core, is progressively enlarged by discharge of cylindrical chitin from epithelial cells that start to aggregate immediately after the final molt and it reaches a plateau in size after 6 days. The core, bridging between the anterior tracheal vesicle and the fluid-filled chamber containing sensory neurons, is supported by a taut membrane, suggesting the possibility that anterior displacements of the anterior tracheal vesicle are converted into fluid motion via a lever action of the core. The epithelial core did not exist in tympanal organ homologs of meso- and metathoracic legs or of nymphal legs. Taken together, the findings suggest that the epithelial core, a potential functional homolog to mammalian ossicles, underlies fine sound frequency discrimination required for adult-specific sound communications.

Omentum acts as a regulatory organ controlling skeletal muscle repair of mdx mice diaphragm Abstract Duchenne muscular dystrophy is a lethal X-linked muscle wasting disease due to mutations of the dystrophin gene leading to distinct susceptibility to degeneration and fibrosis among skeletal muscles. This study aims at verifying whether intense mdx diaphragm remodeling could be attributed to influences from the omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. Mdx omentum produces growth factors HGF and FGF and increased amounts of VEGF with pleiotropic actions upon muscular progenitors and myoblast differentiation. Histology revealed that the absence of the omentum reduced inflammation and collagen deposition in the diaphragm. The diaphragm from omentectomized mdx mice presents impaired repair with a predominance of collagen type I deposition, decreased muscle regeneration and a reduction in collagen type IV and indication of altered basal lamina integrity in the diaphragm. Omentectomy further reduced inflammatory infiltration and NFκ-B activation but a change in the pattern of muscle inflammation with low numbers of the F4/80+CD206+ M-2 macrophage subset. Although omentectomized mice had high levels of Pax7, myogenin and TNF-α, the percentage of myofibers undergoing regeneration was low thus suggesting that a lack of the omentum halts the muscle differentiation program. Such results support that omentum exerts a regulatory function inducing an inflammatory process that favors regeneration and inhibits fibrosis selectively in the diaphragm muscle thus being a potential site for therapeutic interventions in DMD.

Expression and localization of MrgprD in mouse intestinal tract Abstract MrgprD, a Mas-related G protein-coupled receptor, is initially identified in sensory neurons of mouse dorsal root ganglia (DRG) and has been suggested to participate in somatosensation. However, MrgprD has recently been found to be expressed outside the nervous system such as in aortic endothelia cells and neutrophils. In this study, we used immunohistochemistry to detect the expression and localization of MrgprD in mouse intestinal tract. The immunoreactivity (IR) of MrgprD was found in the smooth muscle layers of small intestine, colon and rectum. In addition, MrgprD IR was colocalized with F4/80-positive macrophages and CD3-positive T lymphocytes resident in the lamina propria of intestinal mucosa. MrgprD was also found to be expressed in primary peritoneal macrophages and splenic T lymphocytes. Furthermore, the presence of MrgprD mRNA and its protein was detected in murine macrophage-like RAW 264.7 and human T lymphocyte Jurkat cell lines. Our study shows, for the first time, the expression and localization of MrgprD in the intestinal tract and in macrophages and T lymphocytes, indicating the potential roles of MrgprD in intestinal mobility and immunity.

The medicinal leech as a valuable model for better understanding the role of a TLR4-like receptor in the inflammatory process Abstract Despite extensive investigation focused on both the molecular characteristics and the expression level of Toll-like receptors (TLRs) during the inflammatory response in vertebrates, few data are available in the literature on the role of these proteins in invertebrate’s immune response. Here, we propose the medicinal leech as a valuable model to better elucidate the role of TLR4 and its related products, such as tumor necrosis factor (TNF-α), after activation of the leech peripheral immune system with the endogenous medicinal leech recombinant allograft inflammatory factor-1 (rHmAIF-1) or with an exogenous stimulus, such as lipopolysaccharide (LPS). Our results indicate that activated macrophages (HmAIF-1+) and granulocytes (CD11b+) express both TLR4 and its coreceptor CD14. Moreover, functional studies performed by injecting a cyanobacterium selective TLR4 antagonist CyP demonstrated that only the TLR4 pathway was blocked, while the immune response caused by lipoteichoic acid (LTA) treatment is not affected. These results are consistent with literature on vertebrates, indicating that TLR4 functions as a LPS receptor while the recognition of LTA may involve other pathways.

Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications Abstract Axonal regeneration and formation of tripartite (axo-glial) junctions at damaged sites is a prerequisite for early repair of injured spinal cord. Transplantation of stem cells at such sites of damage which can generate both neuronal and glial population has gained impact in terms of recuperation upon infliction with spinal cord injury. In spite of the fact that a copious number of pre-clinical studies using different stem/progenitor cells have shown promising results at acute and subacute stages, at the chronic stages of injury their recovery rates have shown a drastic decline. Therefore, developing novel therapeutic strategies are the need of the hour in order to assuage secondary morbidity and effectuate improvement of the spinal cord injury (SCI)-afflicted patients’ quality of life. The present review aims at providing an overview of the current treatment strategies and also gives an insight into the potential cell-based therapies for the treatment of SCI.