The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies

Pollen-based reconstruction of Holocene vegetation and climate in Southern Italy: the case of Lago di Trifoglietti

International audienceA high-resolution pollen record from Lago Trifoglietti in Calabria (southern Italy) provides new insights into the paleoenvironmental and palaeoclimatic changes which characterise the Holocene period in the southern Italy. The chronology is based on 11 AMS radiocarbon dates from terrestrial organic material. The Holocene history of the vegetation cover shows the persistence of an important and relatively stable Fagus forest present over that entire period, offering a rare example of a beech woodstand able to withstand climate changes for more than 11 000 yr. Probably in relation with early Holocene dry climate conditions which affected southern Italy, the Trifoglietti pollen record supports a southward delay in thermophyllous forest expansion dated to ca. 13 500 cal BP at Monticchio, ca. 11 000 cal BP at Trifoglietti, and finally ca. 9800 cal BP in Sicily. Regarding the human impact history, the Trifoglietti pollen record shows only poor imprints of agricultural activities and anthopogenic indicators, apart from those indicating pastoralism activities beneath forest cover. The selective exploitation of Abies appears to have been the strongest human impact on the Trifoglietti surroundings. On the basis of (1) a specific ratio between hygrophilous and terrestrial taxa, and (2) the Modern Analogue Technique, the pollen data collected at Lago Trifoglietti led to the establishment of two palaeoclimatic records tracing changes in (1) lake depth and (2) annual precipitation. On a millennial scale, these records give evidence of increasing moisture from ca. 11 000 to ca. 9400 cal BP and maximum humidity from ca. 9400 to ca. 6200 cal BP, prior to a general trend towards the drier climate conditions that have prevailed up to the present. In addition, several successive centennial-scale oscillations appear to have punctuated the entire Holocene. The identification of a cold dry event around 11 300 cal BP, responsible for a marked decline in timberline altitude and possibly equivalent to the PBO, remains to be confirmed by further investigations verifying both chronology and magnitude. Two cold and possibly drier Boreal oscillations developed at ca. 9800 and 9200 cal BP. At Trifoglietti, the 8.2 kyr event corresponds to the onset of cooler and drier climatic conditions which persisted until ca. 7500 cal BP. Finally, the second half of the Holocene was characterised by dry phases at ca. 6100–5200, 4400–3500, and 2500–1800 cal BP, alternating with more humid phases at ca. 5200–4400 and ca. 3500–2500 cal BP. Considered as a whole, these millennial-scale trends and centennial-scale climatic oscillations support contrasting patterns of palaeohydrological changes recognised between the north- and south-central Mediterranean

Quality and consumer acceptance of meat from rabbits fed diets in which soybean oil is replaced with black soldier fly and yellow mealworm fats

This trial investigated the effect of the dietary inclusion of Hermetia illucens (H) and Tenebrio molitor (T) fats as alternative lipid sources for growing rabbits, and assessed the carcass characteristics, proximate composition, lipid peroxidation, and fatty acid profile of the meat, as well as consumer acceptance. At weaning, 200 crossbred rabbits (1051\ub1138 g initial body weight) were allotted to five isolipidic (4% dry matter (DM)) dietary treatments: a control diet (C) containing 1.5% of soybean oil, and four experimental diets in which soybean oil was partially (50%) or totally (100%) substituted by H (H50 and H100) or T (T50 and T100) fats. The carcass characteristics, the meat quality traits, and the consumer acceptance of the cooked meat were not affected. The fat content of Longissimus thoracis et lumborum muscle of the rabbits was 1.1% on average. In the case of rabbit fed the H diets (average of diets H50 and H100), the same muscles revealed a higher saturated fatty acid proportion (47.1% vs. 39.7% and 40.8%, respectively) and a lower polyunsaturated fatty acid proportion than the rabbits fed the C and T diets (average of diets T50 and T100) (26.5% vs. 31.7% and 29.7%) (p<0.001). The meat of the rabbits fed the diets containing insect fat (average for H and T diets) was less susceptible to oxidation (0.24 vs. 0.39 mg malondialdehyde/kg meat in the C group; p<0.01)