Catalpol synergistically potentiates the anti-tumour effects of regorafenib against hepatocellular carcinoma via dual inhibition of PI3K/Akt/mTOR/NF-κB and VEGF/VEGFR2 signaling pathways

Molecular Biology Reports - Hepatocellular carcinoma (HCC) is the most common primary liver cancer characterized by dysregulation of several crucial cellular signaling pathways such as...     

Metabolomic Profiling and Neuroprotective Effects of Purslane Seeds Extract Against Acrylamide Toxicity in Rat’s Brain

Neurochemical Research - Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study...     

Identifying key biodiversity areas as marine conservation priorities in the greater Caribbean

Increasing rates of Anthropocene biodiversity extinctions suggest a possible sixth mass extinction event. Conservation planners are seeking effective ways to protect species, hotspots of biodiversity, and dynamic ecosystems to reduce and eventually eliminate the degradation and loss of diversity at the scale of genes, species, and ecosystems. While well-established, adequately enforced protected areas (PAs) increase the likelihood of preserving species and habitats, traditional placement methods are frequently inadequate in protecting biodiversity most at risk. Consequently, the Key Biodiversity Area (KBA) Partnership developed a set of science-based criteria and thresholds that iteratively identify sites where biodiversity is most in need of protection. KBA methodology has been rarely applied in the marine realm, where data are often extremely limited. We tested the feasibility of KBA population metrics in the Greater Caribbean marine region using occurrence and population data and threat statuses for 1669 marine vertebrates. These data identified areas where site-specific conservation measures can effectively protect biodiversity. Using KBA criteria pertaining to threatened and irreplaceable biodiversity, we identified 90 geographically unique potential KBAs, 34 outside and 56 within existing PAs. These provide starting points for local conservation managers to verify that KBA thresholds are met and to delineate site boundaries. Significant data gaps, such as population sizes, life history characteristics, and extent of habitats, prevent the full application of the KBA criteria to data-poor marine species. Increasing the rate and scope of marine sampling programs and digital availability of occurrence datasets will improve identification and delineation of KBAs in the marine environment.

     

Modelling the effect of birth and feeding modes on the development of human gut microbiota

The human gut microbiota is transmitted from mother to infant through vaginal birth and breastfeeding. Bifidobacterium, a genus that dominates the infants’ gut, is adapted to breast milk in its ability to metabolize human milk oligosaccharides; it is regarded as a mutualist owing to its involvement in the development of the immune system. The composition of microbiota, including the abundance of Bifidobacteria, is highly variable between individuals and some microbial profiles are associated with diseases. However, whether and how birth and feeding practices contribute to such variation remains unclear. To understand how early events affect the establishment of microbiota, we develop a mathematical model of two types of Bifidobacteria and a generic compartment of commensal competitors. We show how early events affect competition between mutualists and commensals and microbe-host-immune interactions to cause long-term alterations in gut microbial profiles. Bifidobacteria associated with breast milk can trigger immune responses with lasting effects on the microbial community structure. Our model shows that, in response to a change in birth environment, competition alone can produce two distinct microbial profiles post-weaning. Adding immune regulation to our competition model allows for variations in microbial profiles in response to different feeding practices. This analysis highlights the importance of microbe–microbe and microbe–host interactions in shaping the gut populations following different birth and feeding modes.     

The acute systemic toxicity of thallium in rats produces oxidative stress: attenuation by metallothionein and Prussian blue

BioMetals - Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental...     

The Impact of Variants in Four Genes: MC4R,FTO, PPARG and PPARGC1A in Overweight and Obesity in a Large Sample of the Brazilian Population

Biochemical Genetics - Obesity and overweight are worldwide public health problems with an evident genetic predisposition that is still poorly understood. In addition, great variability has been...     

Quercetin and hydroxytyrosol as modulators of hepatic steatosis: A NAFLD‐on‐a‐chip study

Organs‐on‐chip (OoCs) are catching on as a promising and valuable alternative to animal models, in line with the 3Rs initiative. OoCs enable the creation of three‐dimensional (3D) tissue microenvironments with physiological and pathological relevance at unparalleled precision and complexity, offering new opportunities to model human diseases and to test the potential therapeutic effect of drugs, while overcoming the limited predictive accuracy of conventional 2D culture systems. Here, we present a liver‐on‐a‐chip model to investigate the effects of two naturally occurring polyphenols, namely quercetin and hydroxytyrosol, on nonalcoholic fatty liver disease (NAFLD) using a high‐content analysis readout methodology. NAFLD is currently the most common form of chronic liver disease; however, its complex pathogenesis is still far from being elucidated, and no definitive treatment has been established so far. In our experiments, we observed that both polyphenols seem to restrain the progression of the free fatty acid‐induced hepatocellular steatosis, showing a cytoprotective effect due to their antioxidant and lipid‐lowering properties. In conclusion, the findings of the present work could guide novel strategies to contrast the onset and progression of NAFLD.