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Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in syngeneic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.

Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5-/- and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium, enriched in Rnf5-/- mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5-/- mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth.

In the context of climate change, extreme meteorological events such as severe storms produced by an isolated high-level atmospheric depression (known in Spanish as "Depresión Aislada en Niveles Altos"—DANA) are becoming increasingly frequent in the Mediterranean region, posing significant risks to ecosystems and human infrastructure. This study evaluates the impact of a DANA event in October 2024 on the water quality of Albufera Lake (Spain), a crucial Mediterranean wetland. A comprehensive evaluation was conducted by combining field data on physicochemical and biological parameters with satellite observations (Sentinel-2 and Landsat-8) to assess alterations before and after the event. Variables such as conductivity, nitrate, and total solids exhibited significant reductions immediately following the DANA, with conductivity decreasing by 82% compared to pre-event levels. These alterations signify a substantial renewal of the lake system driven by heavy rainfall and subsequent water releases. However, the lake demonstrated signs of recovery toward pre-event conditions over the following month. These results are consistent with previous findings, underscoring the system's resilience and the necessity of periodic water releases to maintain ecological balance. The use of remote sensing tools effectively captured these dynamics, offering valuable insights for the long-term monitoring of water quality. This study highlights the urgent need for proactive management strategies to mitigate the effects of increasingly intense meteorological disturbances. [ABSTRACT FROM AUTHOR]

The mechanisms underlying the establishment of asymmetric structures during development remain elusive. The wing of Drosophila is asymmetric along the Anterior-Posterior (AP) axis, but the developmental origins of this asymmetry is unknown. Here, we investigate the contribution of cell recruitment, a process that drives cell fate differentiation in the Drosophila wing disc, to the asymmetric shape and pattern of the adult wing. Genetic impairment of cell recruitment in the wing disc results in a significant gain of AP symmetry, which results from a reduction of the region between longitudinal vein 5 and the wing margin (L5-M) in the adult wing. Morphometric analysis confirms that blocking of cell recruitment results in a more symmetric wing with respect to controls, suggesting a contribution of cell recruitment to the establishment of asymmetry in the adult wing. In order to verify if this phenotype is originated during the time in which cell recruitment occurs during larval development, we examined the expression of a reporter for the selector gene vestigial (vg) in the corresponding pro-vein regions of the wing disc, but our findings could not explain our findings in adult wings. However, the circularity of the Vg pattern significantly increases in recruitment-impaired wing discs, suggesting that cell recruitment may contribute to AP asymmetries in the adult wing shape by altering the roundness of the Vg pattern. We conclude that cell recruitment, a widespread mechanism that participates in growth and patterning of several developing systems, may contribute, at least partially, to the asymmetric shape of the Drosophila wing. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia results in morphological and functional alterations of the kidney and microvascular damage, leading to diabetic nephropathy (DN). Since DN progresses to irreversible renal damage, it is important to elucidate a pharmacological strategy aimed for treating DN in the early stage. Here, we used the type 2 diabetic rat model to induce DN and show a nephroprotective effect following the stimulation of PPAR-α, which stabilized renal tight junction components claudin-2, claudin-5, and claudin-16. At 14 weeks old, streptozotocin-induced DN, evidenced by elevated creatinine clearance, proteinuria, and electrolyte excretion, was followed by an elevation in oxidative stress and increasing MMP activities affecting the integrity of claudin-2 and claudin-5. Treatment with a PPAR-α agonists decreased glucose levels in diabetic rats. In addition, we found that the expressions of CLDN-5 in glomeruli, CLDN-2 in proximal tubules, and CLDN-16 in the thick ascending limb of the loop of Henle were increased after treatment. As a result, renal function improved, while the oxidative stress and enzymatic activity of MMP-2 and MMP-9 decreased. In conclusion, PPAR-α stimulation prevented the decrease in claudins through a mechanism involving a correction of hyperglycemia, decreasing it in kidney oxidative stress and MMP-2 and MMP-9 activities, showing a promising nephroprotective action in the early stage of DN. [ABSTRACT FROM AUTHOR]

SUMMARY: Saffron spice owes its commercial appreciation to its specific apocarotenoids: crocins, picrocrocin, and safranal. In Crocus sativus, these compounds are biosynthesized from zeaxanthin through oxidative cleavage by the carotenoid cleavage dioxygenase 2 (CCD2). Transgenic tomato plants expressing CsCCD2 in the fruit, named Tomaffron, accumulate high levels of saffron apocarotenoids despite the low substrate availability for CsCCD2. In the present study, CsCCD2 has been introduced into Xantomato; this tomato variety accumulates high levels of zeaxanthin and β‐carotene in ripe fruit due to a combination of four mutant alleles. Xantomato and Tomaffron genotypes have been combined to optimize apocarotenoid production. The best transgenic lines accumulated 15 and 14 times more crocins and picrocrocin than Tomaffron, alongside a fourfold increase in β‐carotene compared to Xantomato, albeit at a cost in fruit yield. Segregation of the four mutations has been carried out to find the best combination for obtaining high levels of saffron apocarotenoids without adverse effects on fruit yield. Plants harboring the high‐pigmented 3 (hp3) and BETA (BSh) mutations accumulated 6 and 15 times more crocins and picrocrocin than Tomaffron, without observable pleiotropic effects. Additionally, those high levels of saffron apocarotenoids were obtained in fruit accumulating high levels of both lycopene and β‐carotene independently or in combination, suggesting a regulatory role for the apocarotenoids produced and indicating that it is possible to increase the levels of both types of healthy promoting molecules simultaneously. [ABSTRACT FROM AUTHOR]