Current understanding of the mechanisms for clearance of apoptotic cells-a fine balance

Apoptosis is an important cell death mechanism by which multicellular organisms remove unwanted cells. It culminates in a rapid, controlled removal of cell corpses by neighboring or recruited viable cells. Whilst many of the molecular mechanisms that mediate corpse clearance are components of the innate immune system, clearance of apoptotic cells is an anti-inflammatory process. Control of cell death is dependent on competing pro-apoptotic and anti-apoptotic signals. Evidence now suggests a similar balance of competing signals is central to the effective removal of cells, through so called 'eat me' and 'don't eat me' signals. Competing signals are also important for the controlled recruitment of phagocytes to sites of cell death. Consequently recruitment of phagocytes to and from sites of cell death can underlie the resolution or inappropriate propagation of cell death and inflammation. This article highlights our understanding of mechanisms mediating clearance of dying cells and discusses those mechanisms controlling phagocyte migration and how inappropriate control may promote important pathologies. © the authors, publisher and licensee libertas academica limited

Effectiveness of transanal irrigation in low anterior resection syndrome

Background: Low anterior resection syndrome (LARS) is a frequent issue leading to bowel dysfunction after anterior resection surgery. NICE guidelines state that there is limited research around the management of LARS. Transanal irrigation (TAI) is a suggested treatment by guidelines; however, there is limited research surrounding the effectiveness of this treatment. Aim: The aim of this prospective study was to evaluate the effectiveness of TAI in reducing LARS score post anterior resection surgery. Methods: Patients who were referred to the pelvic floor nurse specialist team between 2019 and 2023 with bowel dysfunction post anterior resection surgery were evaluated. Bowel dysfunction was assessed using the LARS scoring system during the first assessment and on discharge. These patients were offered TAI and trained to perform TAI. Patients with missing LARS scores and those who were not using TAI were excluded from the study. Results: Of the total 37 patients who were referred and using TAI, 16 were excluded. In total, 21 patients were included (12 male, 9 female). At baseline, 33% of patients were recorded to have minor LARS, and 66% with major LARS. At discharge, there was a significant improvement in LARS score (80% of patients reported no LARS, 10% minor LARS and 10% major LARS). Overall, the LARS score at discharge was significantly lower among patients who underwent irrigation (mean 34.57 vs. 12.48, p = 0.0000000038). Conclusion: Our study shows the importance of TAI in the management of bowel dysfunction post anterior resection for rectal cancer, with more than two‐third of patients' symptom improvement

Can host reaction animal models be used to predict and modulate skin regeneration?

The study of host reactions in the biomedical and tissue engineering (TE) fields is a key issue but somehow set aside where TE constructs are concerned. Every day new biomaterials and TE constructs are being developed and presented to the scientific community. The combination of cells and biomolecules with scaffolding materials, as TE constructs, make the isolation and the understanding of the effect of each one those elements over the overall host reaction difficult. Eventually, all variables influence the host reaction and the performance of the constructs. For this reason, current assessment of the in vivo performance of TE constructs follows individual approaches, using specific animal models to independently provide insights regarding the contribution of the biomaterials/scaffolds towards the host reaction, and of all the constructs regarding their functionality. Skin wound healing progress into tissue regeneration or repair is highly dependent on the specificities of the inflammatory stage, as demonstrated by comparison between fetal and adult mechanisms. Thus, it would be expected that insights acquired from host tissue reaction evaluation to biomaterials/scaffolds would be explored to predict healing progression and improve the functionality of skin TE constructs. The rational of this review is to make a comprehensive analysis of to what extent the knowledge obtained from the evaluation of in vivo host reactions to implantable biomaterials/scaffolds has been used in the design of skin TE strategies, by promoting tissue regeneration rather than repair.T.C.S. acknowledges Grant No. RL3-TECT-NORTE-01-0124-FEDER-000020, co-financed by the North Portugal Regional Operational Programme (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund

Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage

We have generated the first transgenic chickens in which reporter genes are expressed in a specific immune cell lineage, based upon control elements of the colony stimulating factor 1 receptor (CSF1R) locus. The Fms intronic regulatory element (FIRE) within CSF1R is shown to be highly conserved in amniotes and absolutely required for myeloid-restricted expression of fluorescent reporter genes. As in mammals, CSF1R-reporter genes were specifically expressed at high levels in cells of the macrophage lineage and at a much lower level in granulocytes. The cell lineage specificity of reporter gene expression was confirmed by demonstration of coincident expression with the endogenous CSF1R protein. In transgenic birds, expression of the reporter gene provided a defined marker for macrophage-lineage cells, identifying the earliest stages in the yolk sac, throughout embryonic development and in all adult tissues. The reporter genes permit detailed and dynamic visualisation of embryonic chicken macrophages. Chicken embryonic macrophages are not recruited to incisional wounds, but are able to recognise and phagocytose microbial antigens

Epithelial delamination and migration: lessons from Drosophila

Metastasis is the most deadly phase of cancer progression, during which cells detach from their original niche to invade distant tissues, yet the biological processes underlying the spread of cancer are still poorly understood. The fruit fly Drosophila melanogaster provides important insights in our understanding of how epithelial cells migrate from their original location and find their way into surrounding and distant tissues in the metastatic process. Here we review recent studies on the mechanisms of migration of embryonic haemocytes, the macrophage-like immuno-surveillance cells, during normal development and wound healing. We highlight the interesting finding that hydrogen peroxide (H₂O₂) has been identified as the driving force for haemocyte chemotaxis. We also give a special emphasis to studies suggesting the concept that haemocytes, together with the tumor microenvironment, act as potential inducers of the epithelial de-lamination required for tumor invasion. We propose that cell delamination and migration could be uncoupled from loss of cell polarity via a tumor-related inflammatory response

Growth factors and cutaneous wound repair.

The healing of an adult skin lesion is a well studied but complex affair of some considerable clinical interest. Endogenous growth factors, including the EGF, FGF, PDGF and TGF beta families, are released at the wound site and presumed to be a necessary part of the natural wound healing machinery. Moreover, members of each of these families have been shown to enhance healing if added exogenously to a wound site. In this review we shall briefly discuss what is known about the mechanics and cell biology of adult wound healing, describe the normal cellular source of growth factors during the healing process and, with reference to their known capacities in tissue culture, speculate as to how particular growth factors might be able to enhance healing.sch_die4pub4516pub

A study of wound healing in the E11.5 mouse embryo by light and electron microscopy

In this paper we report our light and electron microscopic studies of the healing of a simple excisional lesion to the E11.5 mouse embryo hindlimb. The wounded living embryo is cultured in a roller bottle and under such conditions the lesion is completely re-covered with epithelium by 24 hr. We discuss how our studies of such a simple wound healing model may offer insight into the mechanisms of tissue repair generally.sch_die25pub4515pub