Angiogenesis in the Normal Adrenal Fetal Cortex and Adrenocortical Tumors

Simple Summary Pharmacological angiogenesis modulation was robustly demonstrated to be a powerful clinical resource in oncotherapy. Adrenocortical carcinomas (ACC) often have a poor prognosis for which therapeutic options are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis both under physiological conditions and in ACC could provide important clues on how these processes could be modulated for clinical purposes. This report summarizes the current knowledge on adrenal cortex angiogenesis regulation in physiological conditions and ACC. Embryonic adrenal angiogenesis is regulated by VEGF and Ang-Tie signaling pathways. VEGF angiogenic pathway was initially considered a promising therapeutic target for improving ACC prognosis. However, every single VEGF pathway-targeting clinical trial in ACC so far conducted yielded disappointing results. In contrast, the potential of Ang-Tie pathway-targeting in ACC is yet to be explored. Therefore, further investigation on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is still an unmet need. Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed

Full survival of Galleria mellonella infected with Staphylococcus aureus after treatment with Nisin Z

Diabetes mellitus affects nearly 6.4% of the worldwide population, and this number may double by 2030. Up to 25% of diabetic patients may develop diabetic foot ulcers (DFUs). Among DFU patients, 80% will suffer lower-limb amputations due to diabetic foot infections (DFIs), which are generally colonized by polymicrobial biofilms. Staphylococcus aureus is the DFIs’ predominant pathogen, frequently found together with Pseudomonas aeruginosa in chronic and severe infections. Due to their high virulence and antibiotic resistant profile, it is crucial to find alternatives to conventional antibiotics for DFI treatment. Previous studies showed that Nisin Z supplemented with EDTA (0.4%) had higher antibacterial, antibacteriostatic, and antibiofilm efficiency towards S. aureus and P. aeruginosa DFI isolates. Therefore, we aimed to confirm these data in a Galleria mellonella model. G. mellonella wax moth larvae were reared at 25 °C in the dark, and worms of the final- instar larval stage were selected (10 larvae for each experiment). The larvae were injected with a lethal dose of each bacterium via the hindmost left proleg. After approximately 1 hour, the larvae were injected with Nisin Z (200 μg/ml) in the penultimate right proleg. Then, they were kept in Petri dishes and maintained in the dark at 37 °C for 120 hours. Each larva was scored daily on the G. mellonella health index: survival, melanization, mobility, and cocoon formation. Experiments were performed with three independent replicates. Nisin Z treatment led to 100% survival of the larvae infected with S. aureus but had no antibacterial activity against P. aeruginosa. Unexpectedly, EDTA supplementation did not increase antipseudomonal activity. Nisin Z was not cytotoxic to the larvae. Nisin Z may be used as a complement to conventional antibiotic therapy against S. aureus in DFI. G. mellonella is a valuable model before proceeding to preclinical studies in mammals. Congress of Microbiology and Biotechnology 2023 385 MicroBiotec 2023 - Covilhã, Portugal Acknowledgements: Authors would like to acknowledge: CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisbon, Portugal (Project UIDB/00276/2020); AL4AnimalS-Laboratório Associado para a Ciência Animal e Veterinária (LA/P/0059/2020); iBB Institute for Bioengineering and Biosciences (UIDB/04565/2020 and UIDP/04565/2020), i4HB Associate Laboratory Institute for Health and Bioeconomy (LA/P/0140/2020); and GHTM - (UID/04413/2020 and LA-REAL – LA/P/0117/2020).otherpublishe

Holographic Superconductors with Power-Maxwell field

With the Sturm-Liouville analytical and numerical methods, we investigate the behaviors of the holographic superconductors by introducing a complex charged scalar field coupled with a Power-Maxwell field in the background of $d$-dimensional Schwarzschild AdS black hole. We note that the Power-Maxwell field takes the special asymptotical solution near boundary which is different from all known cases. We find that the larger power parameter $q$ for the Power-Maxwell field makes it harder for the scalar hair to be condensated. We also find that, for different $q$, the critical exponent of the system is still 1/2, which seems to be an universal property for various nonlinear electrodynamics if the scalar field takes the form of this paper.Comment: 14 pages, 1 figure, and 2 table

Virulence potential of biofilm producing Staphylococcus pseudintermedius, Staphylococcus aureus and Staphylococcus coagulans causing skin infections in companion animals

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Stand dynamics modulate water cycling and mortality risk in droughted tropical forest

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Transpiration from the Amazon rainforest generates an essential water source at a global and local scale. However, changes in rainforest function with climate change can disrupt this process, causing significant reductions in precipitation across Amazonia, and potentially at a global scale. We report the only study of forest transpiration following a long-term (>10 year) experimental drought treatment in Amazonian forest. After 15 years of receiving half the normal rainfall, drought-related tree mortality caused total forest transpiration to decrease by 30%. However, the surviving droughted trees maintained or increased transpiration because of reduced competition for water and increased light availability, which is consistent with increased growth rates. Consequently, the amount of water supplied as rainfall reaching the soil and directly recycled as transpiration increased to 100%. This value was 25% greater than for adjacent nondroughted forest. If these drought conditions were accompanied by a modest increase in temperature (e.g., 1.5°C), water demand would exceed supply, making the forest more prone to increased tree mortality.This work is a product of UK NERC grant NE/J011002/1 to PM and MM, CNPQ grant 457914/2013-0/MCTI/CNPq/FNDCT/LBA/ESECAFLOR to ACLD, an ARC grant FT110100457 to PM and a UK NERC independent fellowship grant NE/N014022/1 to LR. It was previously supported by NERC NER/A/S/2002/00487, NERC GR3/11706, EU FP5-Carbonsink and EU FP7-Amazalert to PM. RP acknowledges support of MINECO (Spain), grant CGL2014-5583-JIN

Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 +/- 0.58 kg/m(2)) or class 3 (n = 8; BMI 47.79 +/- 1.52 kg/m(2)) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

2-Methoxyestradiol-3,17-O,O-bis-sulfamate (STX140) inhibits proliferation and invasion via senescence pathway induction in human BRAFi-resistant melanoma cells

The endogenous estradiol derivative 2-Methoxyestradiol (2-ME) has shown good and wide anticancer activity but suffers from poor oral bioavailability and extensive metabolic conjugation. However, its sulfamoylated derivative, 2-methoxyestradiol-3,17-O,O-bis-sulfamate (STX140), has superior potential as a therapeutic agent, acts by disrupting microtubule polymerization, leading to cell cycle arrest and apoptosis in cancer cells and possesses much better pharmaceutical properties. This study investigated the antiproliferative and anti-invasive activities of STX140 in both SKMEL-28 naïve melanoma (SKMEL28-P) cells and resistant melanoma cells (SKMEL-28R). STX140 inhibited cell proliferation in the nanomolar range while having a less pronounced effect on human melanocytes. Additionally, STX140 induced cell cycle arrest in the G2/M phase and sub-G1, reduced migration, and clonogenic potential in monolayer models, and inhibited invasion in a 3D human skin model with melanoma cells. Furthermore, STX140 induced senescence features in melanoma and activated the senescence machinery by upregulating the expression of senescence genes and proteins related to senescence signaling. These findings suggest that STX140 may hold potential as a therapeutic agent for melanoma treatment