Flavonoid and non-flavonoid compounds of autumn royal and egnatia grape skin extracts affect membrane PUFA's profile and cell morphology in human colon cancer cell lines

Grapes contain many flavonoid and non-flavonoid compounds with anticancer effects. In this work we fully characterized the polyphenolic profile of two grape skin extracts (GSEs), Autumn Royal and Egnatia, and assessed their effects on Polyunsaturated Fatty Acid (PUFA) membrane levels of Caco2 and SW480 human colon cancer cell lines. Gene expression of 15-lipoxygenase-1 (15-LOX-1), and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as cell morphology, were evaluated. The polyphenolic composition was analyzed by Ultra-High-Performance Liquid Chromatography/Quadrupole-Time of Flight mass spectrometry (UHPLC/QTOF) analysis. PUFA levels were evaluated by gas chromatography, and gene expression levels of 15-LOX-1 and PPAR-γ were analyzed by real-time Polymerase Chain Reaction (PCR). Morphological cell changes caused by GSEs were identified by field emission scanning electron microscope (FE-SEM) and photomicrograph examination. We detected a different profile of flavonoid and non-flavonoid compounds in Autumn Royal and Egnatia GSEs. Cultured cells showed an increase of total PUFA levels mainly after treatment with Autumn Royal grape, and were richer in flavonoids when compared with the Egnatia variety. Both GSEs were able to affect 15-LOX-1 and PPAR-γ gene expression and cell morphology. Our results highlighted a new antitumor mechanism of GSEs that involves membrane PUFAs and their downstream pathways

Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients

Background: The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). Methods: Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic-phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc patients. The adipose tissue-derived cell fraction, the so-called stromal vascular fraction (SVF), was coinjected with PRP in the perioral area of SSc patients. Results: Histopathological and phenotypical analysis of adipose tissue from SSc patients revealed a disorganization of its distinct architecture coupled with an altered cell composition. Although AD-MSCs derived from SSc patients showed high multipotency, they failed to sustain a terminally differentiated progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors in their MSC-like traits coupled with an aberrant cytokine production profile. Finally, the administration of PRP in combination with autologous SVF improved buccal's rhyme, skin elasticity and vascularization for all of the SSc patients enrolled in this study. Conclusions: This innovative regenerative therapy could be exploited for the treatment of chronic connective tissue diseases, including SSc

Distinct phenotypes associated with mangrove and lagoon habitats in two widespread caribbean corals, porites astreoides and porites divaricata.

AbstractAs coral reefs experience dramatic declines in coral cover throughout the tropics, there is an urgent need to understand the role that non-reef habitats, such as mangroves, play in the ecological niche of corals. Mangrove habitats present a challenge to reef-dwelling corals because they can differ dramatically from adjacent reef habitats with respect to key environmental parameters, such as light. Because variation in light within reef habitats is known to drive intraspecific differences in coral phenotype, we hypothesized that coral species that can exploit both reef and mangrove habitats will exhibit predictable differences in phenotypes between habitats. To investigate how intraspecific variation, driven by either local adaptation or phenotypic plasticity, might enable particular coral species to exploit these two qualitatively different habitat types, we compared the phenotypes of two widespread Caribbean corals, Porites divaricata and Porites astreoides, in mangrove versus lagoon habitats on Turneffe Atoll, Belize. We document significant differences in colony size, color, structural complexity, and corallite morphology between habitats. In every instance, the phenotypic differences between mangrove prop root and lagoon corals exhibited consistent trends in both P. divaricata and P. astreoides. We believe this study is the first to document intraspecific phenotypic diversity in corals occupying mangrove prop root versus lagoonal patch reef habitats. A difference in the capacity to adopt an alternative phenotype that is well suited to the mangrove habitat may explain why some reef coral species can exploit mangroves, while others cannot.Published versio

Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant

Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of colorectal (CR) cancer stem cell (CSC) as the cell compartment responsible for tumor initiation and propagation may provide new opportunities for the development of new therapeutic strategies. Given the reduced sensitivity of CR-CSCs to chemotherapy and the ability of bone morphogenetic proteins (BMP) to promote colonic stem cell differentiation, we aimed to investigate whether an enhanced variant of BMP7 (BMP7v) could sensitize to chemotherapy-resistant CRC cells and tumors. Thirty-five primary human cultures enriched in CR-CSCs, including four from chemoresistant metastatic lesions, were used for in vitro studies and to generate CR-CSC-based mouse avatars to evaluate tumor growth and progression upon treatment with BMP7v alone or in combination with standard therapy or PI3K inhibitors. BMP7v treatment promotes CR-CSC differentiation and recapitulates the cell differentiation-related gene expression profile by suppressing Wnt pathway activity and reducing mesenchymal traits and survival of CR-CSCs. Moreover, in CR-CSC-based mouse avatars, BMP7v exerts an antiangiogenic effect and sensitizes tumor cells to standard chemotherapy regardless of the mutational, MSI, and CMS profiles. Of note, tumor harboring PIK3CA mutations were affected to a lower extent by the combination of BMP7v and chemotherapy. However, the addition of a PI3K inhibitor to the BMP7v-based combination potentiates PIK3CA-mutant tumor drug response and reduces the metastatic lesion size. These data suggest that BMP7v treatment may represent a useful antiangiogenic and prodifferentiation agent, which renders CSCs sensitive to both standard and targeted therapies

The projected degradation of subtropical coral assemblages by recurrent thermal stress

1. Subtropical coral assemblages are threatened by similar extreme thermal stress events to their tropical counterparts. Yet, the mid‐ and long‐term thermal stress responses of corals in subtropical environments remain largely unquantified, limiting our capacity to predict their future viability. 2. The annual survival, growth and recruitment of 311 individual corals within the Solitary Islands Marine Park (Australia) was recorded over a 3‐year period (2016–2018), including the 2015/2016 thermal stress event. These data were used to parameterise integral projection models quantifying the effect of thermal stress within a subtropical coral assemblage. Stochastic simulations were also applied to evaluate the implications of recurrent thermal stress scenarios predicted by four different Representative Concentration Pathways. 3. We report differential shifts in population growth rates (λ) among coral populations during both stress and non‐stress periods, confirming contrasting bleaching responses among taxa. However, even during non‐stress periods, the observed dynamics for all taxa were unable to maintain current community composition, highlighting the need for external recruitment sources to support the community structure. 4. Across all coral taxa, projected stochastic growth rates (λs) were found to be lowest under higher emissions scenarios. Correspondingly, predicted increases in recurrent thermal stress regimes may accelerate the loss of coral coverage, species diversity and structural complexity within subtropical regions. 5. We suggest that these trends are primarily due to the susceptibility of subtropical specialists and endemic species, such as Pocillopora aliciae, to thermal stress. Similarly, the viability of many tropical coral populations at higher latitudes is highly dependent on the persistence of up‐current tropical systems. As such, the inherent dynamics of subtropical coral populations appear unable to support their future persistence under unprecedented thermal disturbance scenarios

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoingcardiac surgery may be especially vulnerable to the adverse effects of transfusion