p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes.

p75 neurotrophin receptor (p75NTR) belongs to the TNF-receptor superfamily and signals apoptosis in many cell settings. In human epidermis, p75NTR is mostly confined to the transit-amplifying (TA) sub-population of basal keratinocytes. Brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), which signals through p75NTR, induces keratinocyte apoptosis, whereas β-amyloid, a ligand for p75NTR, triggers caspase-3 activation to a greater extent in p75NTR transfected cells. Moreover, p75NTR co-immunoprecipitates with NRAGE, induces the phosphorylation of c-Jun N-terminal kinase (JNK) and reduces nuclear factor kappa B (NF-κB) DNA-binding activity. p75NTR also mediates pro-NGF-induced keratinocyte apoptosis through its co-receptor sortilin. Furthermore, BDNF or β-amyloid cause cell death in TA, but not in keratinocyte stem cells (KSCs) or in p75NTR silenced TA cells. p75NTR is absent in lesional psoriatic skin and p75NTR levels are significantly lower in psoriatic than in normal TA keratinocytes. The rate of apoptosis in psoriatic TA cells is significantly lower than in normal TA cells. BDNF or β-amyloid fail to induce apoptosis in psoriatic TA cells, and p75NTR retroviral infection restores BDNF- or β-amyloid-induced apoptosis in psoriatic keratinocytes. These results demonstrate that p75NTR has a pro-apoptotic role in keratinocytes and is involved in the maintenance of epidermal homeostasis

Role of neurotrophins on dermal fibroblast survival and differentiation

Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of \u3b1-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue remodelling and wound healin

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage

MIcrogreens: Functional food with antiproliferative cancer properties influenced by light

The anti-proliferative/pro-oxidant efficacy of green pea, soybean, radish, Red Rambo radish, and rocket microgreens, cultivated under either fluorescent lighting (predominant spectral peaks in green and orange) or combination light-emitting diode (LED, predominant spectral peak in blue) was investigated using Ewing sarcoma lines, RD-ES and A673, respectively. All aqueous microgreen extracts significantly reduced cell proliferation (cancer prevention effect) to varying extents in two-dimensional sarcoma cell cultures. The effect of the polyphenol fraction in the aqueous food matrix was unrelated to total polyphenol content, which differed between species and light treatment. Only Pisum sativum (LED-grown) extracts exercised anti-proliferative and pro-apoptotic effects in both three-dimensional RD-ES and A673 spheroids (early tumor progression prevention), without cytotoxic effects on healthy L929 fibroblasts. A similar anti-tumor effect of Red Rambo radish (LED and fluorescent-grown) was evident only in the RD-ES spheroids. Aside from the promising anti-tumor potential of the polyphenol fraction of green pea microgreens, the latter also displayed favorable growth quality parameters, along with radish, under both light treatments over the 10 day cultivation period

Insect-based aquafeeds modulate the fatty acid profile of zebrafish: a comparison on the different life stages

Insects are considered as an alternative and sustainable ingredient for feed production. In this study, Hermetia illucens (Hi) prepupae (fed on coffee roasted by-product added with 10% Schyzochytrium sp., a marine protist rich in polyunsaturated fatty acids) was processed into meal and included at graded levels in five experimental diets to replace dietary fish meal (0, 25, 50, 75, 100%) offered to zebrafish (Danio rerio) as experimental model. The fatty acids (FAs) profile of fish larvae (20 days), juveniles (2 months, deprived of the viscera) and adults (6 months, male and female, deprived of the viscera) specimens was investigated to evaluate the impact of dietary FM replacement with full-fat Hi prepupae meal. For the first time, the quantification of FAs in Danio rerio, performed by gas chromatography-mass spectrometry, was computed in absolute terms (mg 100g-1 dw), identifying the real variation in the content of any single FA. In fish, quantified total FAs in larvae, juvenile, adult male and adult female were 134±2, 235±8, 266±3 and 266±8 mg g-1 dw, respectively. With respect to zebrafish fed the control diet, specimens fed diet with increasing level of Hi prepupae meal showed significantly higher content of saturated and omega6 FAs, and significantly lower content of poly-unsaturated and omega3 FAs, reflecting partially the FAs composition of the administered diets. At the same time, the docosahexaenoic/eicosapentaenoic acid ratio increased significantly. Moreover, adult female showed a higher content of PUFA with respect to adult male, which could be justified by the needs of physiological reproductive processes. The principal component analysis demonstrated that the FAs composition in Danio rerio depends on both the life stage and the diet

Unlocking the elemental signature of European tea gardens: Implications for tea traceability

This study presents a comprehensive analysis of the elemental profiles of tea leaves coming from plants grown in several European gardens, with a focus on the bioaccumulation of essential and potentially toxic trace elements in relation to processing and location of tea garden. Samples were collected from various gardens across Europe, including Portugal, the Azores, Germany, the Netherlands, and Switzerland. Elemental analysis was conducted on fresh tea leaves, dried leaves, and leaves processed for the production of green and black tea, along with soil samples from the root zones of tea plants. The results reveal no significant differences in elemental content based on the processing of tea leaves. However, distinct elemental profiles were observed among tea leaves of plants grown in gardens from different European regions. Utilizing chemometric and machine learning tools, the study highlights the potential of these elemental profiles for enhancing the traceability of tea products

Short- and long-term effects of essential oils on swine spermatozoa during liquid phase refrigeration

The application of essential oils as potential alternatives to antibiotics in swine semen storage is promising, due to their antioxidant and antibacterial properties. However, detrimental effects on spermatozoa should be clarified first. The aim of this study was to evaluate 9 essential oils (EOs; Satureja montana, Pelargonium graveolens, Cymbopogon nardus, Melaleuca leucadendron, Eucaliptus globulus, Citrus limon, Lavandula angustifolia, Lavandula hybrida, Mentha piperita) and a blend (GL mix) on key morpho-functional parameters of swine spermatozoa. Test compounds were firstly chemo-characterized and experimental doses were prepared by suspending a fixed number of spermatozoa with 3 different concentrations (0.1, 0.5, 1 mg/mL) of EOs. Experimental doses were stored at 16 °C and sampled after 3 and 120 h for analysis. Overall, S. montana, P. graveolens and L. angustifolia EOs induced the strongest alterations, with C. nardus and E. globulus EOs being the best tolerated. Swine spermatozoa represent a good preliminary testing platform to screen toxicity and its different patterns. The comprehensive overview on the potential mechanisms of action of some of the most common EOs, despite of the direct aim of the study being swine reproduction, may be exploited in other fields of research within both veterinary and human medicine

Male infertility in spinal cord trauma

Every year there are 10 thousand new cases of patients victimized by spinal cord trauma (SCT) in the United States and it is estimated that there are 7 thousand new cases in Brazil. Eighty percent of patients are fertile males. Infertility in this patient group is due to 3 main factors resulting from spinal cord lesions: erectile dysfunction, ejaculatory disorder and low sperm counts. Erectile dysfunction has been successfully treated with oral and injectable medications, use of vacuum devices and penile prosthesis implants. The technological improvement in penile vibratory stimulation devices (PVS) and rectal probe electro-ejaculation (RPE) has made such procedures safer and accessible to patients with ejaculatory dysfunction. Despite the normal number of spermatozoa found in semen of spinal cord-injured patients, their motility is abnormal. This change does not seem to be related to changes in scrotal thermal regulation, frequency of ejaculation or duration of spinal cord damage but to factors related to the seminal plasma. Despite the poor seminal quality, increasingly more men with SCT have become fathers through techniques ranging from simple homologous insemination to sophisticated assisted reproduction techniques such as intracytoplasmic sperm injection (ICSI).Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Department of UrologySan Francisco Home School Section of UrologyUNIFESP, EPM, Department of UrologySciEL

Evaluation of Growth Performance and Environmental Impact of Hermetia illucens Larvae Reared on Coffee Silverskins Enriched with Schizochytrium limacinum or Isochrysis galbana Microalgae

Hermetia illucens is a promising insect due to its ability to convert low-value substrates as food chain by-products into highly nutritious feed. Its feeding and nutrition are important issues. The aim of this work was to investigate the effect of different substrates consisting of coffee silverskin, a by-product of the roasting process, enriched with different inclusions of microalgae (5%, 10%, 20%, and 25%), Schizochytrium limacinum, and Isochrysis galbana, combined with the assessment of environmental sustainability by LCA. In general, the addition of microalgae led to an increase in larval growth performance due to the higher content of protein and lipids, although S. limacinum showed the best results with respect to larvae fed with coffee silverskin enriched with I. galbana. A higher prepupal weight was observed in larvae fed with 10%, 20%, and 25% S. limacinum; shorter development times in larvae fed with 25% of both S. limacinum and I. galbana; and a higher growth rate in larvae fed with 25% S. limacinum. The 10% S. limacinum inclusion was only slightly different from the higher inclusions. Furthermore, 10% of S. limacinum achieved the best waste reduction index. The greater the inclusion of microalgae, the greater the environmental impact of larval production. Therefore, the addition of 10% S. limacinum appears to be the best compromise for larval rearing, especially considering that a higher inclusion of microalgae did not yield additional benefits in terms of the nutritional value of H. illucens prepupae