Space medicine: use of ex vivo human respiratory mucosa in the survey of the effects of microgravity on the respiratory system

In the near future, the length and scope of space travel is set to increase significantly. The number of individuals who will have access to extra-terrestrial travels is also increasing. In view of the growing international interest towards manned long-term space exploration, possible effects of exposure to microgravity conditions affecting the respiratory system are subject of interest by major space agencies (NASA and ESA primarily). Our team has developed an advanced 3d tissue model of the human bronchial mucosa within a wide research project involving several universities and space agencies at international level. The model will be used to study the structural/functional alterations of the bronchial mucosa that may arise from prolonged exposure to reduced gravity conditions. Among the different modifications to be evaluated: development and performance of the pulmonary barrier; possible ciliogenesis modification due to its effects on fluid mechanics and mechanotransduction; formation of multi-cellular structures (Cell-Cell and ECM-Cell Interactions). The design and realization of experiments aboard the International Space Station (ISS) often clashes with greater difficulties than at ground level. Our work was to check the resilience of the model to the prohibitive environmental conditions present on board the vectors that transport the samples to the ISS, and to adapt the model to engineering requirements for proper functionality within the BIOLAB of ISS itself. To verify this, cell cultures were subjected to various boundary conditions: temperatures lower than growth optimum, reduced concentrations of CO2, restriction of gas exchange, prolonged starvation and storage of the culture medium at high temperatures. The bronchial mucosa cultures were analysed at the end of the treatments and their morphology was evaluated. We also used the monitoring of the Trans Epithelial Electric Resistance to evaluate the state of health of the cultures. The data obtained demonstrated how this culture model is able to overcome the critical phases of the journey to ISS and how it can conform to restrictive engineering requirements. It is possible to assert that in addition to the accurate reproduction of the bronchial human mucosa, the cell culture model possesses the characteristics necessary to be used in studies in an extreme environment such as the ISS, being able to provide data that could be relevant for future manned spaceflights

Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives

The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers

Poorly differentiated synovial sarcoma: A case report

Poorly differentiated synovial sarcoma is a rare soft tissue tumor. We studied a case arising in the pleural cavity of a young subject, characterised by the presence of spindle cell, small cell, and large epithelioid cell areas. We performed stains for mucosubstances and analysed the expression of cytokeratins 5/6, 7, 8, 18, 19, CEA, CD34, Ber-Ep4 and calretinin to characterize the phenotype of this neoplasm. We furthermore assessed immunohistochemically the presence of p53, Bcl-2, Bax and caspase 3, four apoptotic markers, to evaluate a relationship between apoptotic activity and the behaviour of this tumor. Our findings showed a strong presence of calretinin, p53 and Bcl-2 in all three areas. The possibility that poorly differentiated synovial sarcoma could be calretinin-positive was a new data, to our knowledge, and it could be of some importance in diagnostic pathology. Moreover, the negligible positivity for Bax and caspase 3 suggested that the minor role of programmed cell death could be one of the causes of the aggressive behaviour of this tumor. These data also suggest that the reduction of apoptotic phenomena in poorly differentiated synovial sarcoma could be considered one of the major mechanisms of tumoral growth

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 ± 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation colocalized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD

The Microbiota Is Not an Organ: Introducing the Muco-Microbiotic Layer as a Novel Morphofunctional Structure

In this paper, we want to refute the notion that the microbiota should be considered an organ, given that an organ comprises tissue of similar or different embryological origin, while the microbiota is a pool of different microbial species originating individually from single replications and not from a common ancestral cellular element. Hence, we would like to propose a new morphological interpretation of its nature, based on the comprehensive context in which these microbes live: a muco-microbiotic layer of hollow organs, such as the airways and the bowel. The above concept should represent not only a new terminological annotation but also a more accurate portrayal of the physiology and pathophysiology of these organs. Indeed, a better understanding of the biological nature of this part of the human body can help scientists develop more specific experimental protocols, potentially leading to the establishment of better therapeutic strategies

Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses

Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers, exposed to cyclical mechanical strain using flexible silastic membranes. Samples were analyzed for proteoglycans, ?-smooth muscle actin (?SMA), collagens I and III, matrix metalloproteinase (MMP) 2 &amp; 9 and interleukin-8 (IL-8) by qRT-PCR, Western blot, zymography and ELISA. Mechanical strain caused a decrease in ?SMA mRNA but no change in either ?SMA protein or proteoglycan expression. In contrast the inflammatory mediator IL-8, MMPs and interstitial collagens were increased at both the transcriptional and protein level. The results demonstrate an adaptive response of bronchial fibroblasts to mechanical strain, irrespective of donor. The adaptation involves cytoskeletal rearrangement, matrix remodelling and inflammatory cytokine release. These results suggest that mechanical strain could contribute to disease progression in asthma by promoting inflammation and remodelling responses.<br/

Observations on midgut of Apis mellifera workers (Hymenoptera: Apoidea) under controlled acute exposures to a Bacillus thuringiensis-based biopesticide

International audienceAbstractMorphostructural investigations have been carried out on Apis mellifera workers treated with single controlled acute exposures to a biopesticide containing Bacillus thuringiensis (Bt), to detect midgut changes until 96 h. Our findings show concentration-dependence of these changes, reflecting in different degrees on both mortality and behaviour. In particular, some midgut changes are also found 96 h after treatment. Our results show that the tested product does not affect survival at presumable environmental concentrations, so confirming the lesser toxicity of Bt-based biopesticides compared to other pesticides. However, in the light of the discovered long-term changes, we discuss the opportunity of taking into account possible chronic exposures to Bt-based products on A. mellifera

The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review.

This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagno- sis, mainly because of the controversy regarding the signifi- cance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochem- ical detection in PC as well as in pre-cancerous lesions of the prostate. We will also discuss the possible functional interac- tions of these molecules in both dysplastic and neoplastic cell