A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer

\ua9 2024 The Author(s). Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies

Characterisation of Dermanyssus gallinae glutathione S-transferases and their potential as acaricide detoxification proteins

BACKGROUND: Glutathione S-transferases (GSTs) facilitate detoxification of drugs by catalysing the conjugation of the reduced glutathione (GSH) to electrophilic xenobiotic substrates and therefore have a function in multi-drug resistance. As a result, knowledge of GSTs can inform both drug resistance in, and novel interventions for, the control of endo- and ectoparasite species. Acaricide resistance and the need for novel control methods are both pressing needs for Dermanyssus gallinae, a highly economically important haematophagous ectoparasite of poultry. METHODS: A transcriptomic database representing D. gallinae was examined and 11 contig sequences were identified with GST BlastX identities. The transcripts represented by 3 contigs, designated Deg-GST-1, −2 and −3, were fully sequenced and further characterized by phylogenetic analysis. Recombinant versions of Deg-GST-1, −2 and −3 (rDeg-GST) were enzymically active and acaricide-binding properties of the rDeg-GSTs were established by evaluating the ability of selected acaricides to inhibit the enzymatic activity of rDeg-GSTs. RESULTS: 6 of the identified GSTs belonged to the mu class, followed by 3 kappa, 1 omega and 1 delta class molecules. Deg-GST-1 and −3 clearly partitioned with orthologous mu class GSTs and Deg-GST-2 partitioned with delta class GSTs. Phoxim, permethrin and abamectin significantly inhibited rDeg-GST-1 activity by 56, 35 and 17 % respectively. Phoxim also inhibited rDeg-2-GST (14.8 %) and rDeg-GST-3 (20.6 %) activities. CONCLUSIONS: Deg-GSTs may have important roles in the detoxification of pesticides and, with the increased occurrence of acaricide resistance in this species worldwide, Deg-GSTs are attractive targets for novel interventions

In Vitro and In Vivo Development of Horse Cloned Embryos Generated with iPSCs, Mesenchymal Stromal Cells and Fetal or Adult Fibroblasts as Nuclear Donors

The demand for equine cloning as a tool to preserve high genetic value is growing worldwide; however, nuclear transfer efficiency is still very low. To address this issue, we first evaluated the effects of time from cell fusion to activation (<1h, n = 1261; 1-2h, n = 1773; 2-3h, n = 1647) on in vitro and in vivo development of equine embryos generated by cloning. Then, we evaluated the effects of using different nuclear donor cell types in two successive experiments: I) induced pluripotent stem cells (iPSCs) vs. adult fibroblasts (AF) fused to ooplasts injected with the pluripotency-inducing genes OCT4, SOX2, MYC and KLF4, vs. AF alone as controls; II) umbilical cord-derived mesenchymal stromal cells (UC-MSCs) vs. fetal fibroblasts derived from an unborn cloned foetus (FF) vs. AF from the original individual. In the first experiment, both blastocyst production and pregnancy rates were higher in the 2-3h group (11.5% and 9.5%, respectively), respect to <1h (5.2% and 2%, respectively) and 1-2h (5.6% and 4.7%, respectively) groups (P<0.05). However, percentages of born foals/pregnancies were similar when intervals of 2-3h (35.2%) or 1-2h (35.7%) were used. In contrast to AF, the iPSCs did not generate any blastocyst-stage embryos. Moreover, injection of oocytes with the pluripotency-inducing genes did not improve blastocyst production nor pregnancy rates respect to AF controls. Finally, higher blastocyst production was obtained using UC-MSC (15.6%) than using FF (8.9%) or AF (9.3%), (P<0.05). Despite pregnancy rates were similar for these 3 groups (17.6%, 18.2% and 22%, respectively), viable foals (two) were obtained only by using FF. In summary, optimum blastocyst production rates can be obtained using a 2-3h interval between cell fusion and activation as well as using UC-MSCs as nuclear donors. Moreover, FF line can improve the efficiency of an inefficient AF line. Overall, 24 healthy foals were obtained from a total of 29 born foals

Group 2 Innate Lymphoid Cell Proportions Are Diminished in Young Helminth Infected Children and Restored by Curative Anti-helminthic Treatment

BACKGROUND:Group 2 Innate lymphoid cells (ILC2s) are innate cells that produce the TH2 cytokines IL-5 and IL-13. The importance of these cells has recently been demonstrated in experimental models of parasitic diseases but there is a paucity of data on ILC2s in the context of human parasitic infections and in particular of the blood dwelling parasite Schistosoma haematobium. METHODOLOGY/PRINCIPAL FINDINGS:In this case-control study human peripheral blood ILC2s were analysed in relation to infection with the helminth parasite Schistosoma haematobium. Peripheral blood mononuclear cells of 36 S. haematobium infected and 36 age and sex matched uninfected children were analysed for frequencies of ILC2s identified as Lin-CD45+CD127+CD294+CD161+. ILC2s were significantly lower particularly in infected children aged 6-9 years compared to healthy participants. Curative anti-helminthic treatment resulted in an increase in levels of the activating factor TSLP and restoration of ILC2 levels. CONCLUSION:This study demonstrates that ILC2s are diminished in young helminth infected children and restored by removal of the parasites by treatment, indicating a previously undescribed association between a human parasitic infection and ILC2s and suggesting a role of ILC2s before the establishment of protective acquired immunity in human schistosomiasis

Status and recommendations for sustainable freshwater aquaculture in Brazil

Brazil is a megadiverse country and is participant of fundamental environmental agreements for biodiversity conservation. However, the internal politics and the cultures that affect negatively the ecological integrity in Brazilian freshwater need to be improved on the condition of sustainable management. Scientific community, the government and stakeholders are in constant conflicts of goals. Meanwhile, the current model for Brazilian aquaculture shows problems of ecological impact due to the lack of appropriated planning and legislation to the aquatic biota. The non-recognition of sustainable census incorporated in its environmental politics reflects in an archaic and unsustainable management, with the following characters: a non-specific approach for technical management, the indiscriminate use of interspecific hybrids and non-native species and the lack of skilled labour. The potential impact on native species and the introduction of pathogens are the main negative effects on aquatic biota. This way, the aim of this article is to elucidate the conflicts of interests and ecological effects of fish aquaculture in Brazil, besides providing good practices and sustainable alternatives for management.Departmento de Morfologia Instituto de Biociências Universidade Estadual PaulistaLaboratório de Ecologia Pesca e Ictiologia Departamento de Biodiversidade Programa de Pós-Graduação em Aquicultura e Desenvolvimento Sustentável Universidade Federal do ParanáLaboratory of Ecology and Conservation Department of Environmental Engineering Federal University of ParanáDepartment of Agroecology Flakkebjerg Research Centre Aarhus UniversityLaboratório de Ecologia de Peixes e Invasões Biológicas Departamento de Biologia Animal e Vegetal Centro de Ciências Biológicas Rodovia Celso Garcia Cid Universidade Estadual de LondrinaWater Research Group Unit for Environmental Sciences and Management Potchefstroom Campus North-West UniversityDepartment of Parasitology Institute of Biosciences São Paulo State University (UNESP)Laboratório de Genética de Peixes Faculdade de Ciências Universidade Estadual PaulistaFederal Technological University of Paraná (UTFPR)Department of Biology and Animal Science School of Engineering São Paulo State University (UNESP)Departmento de Morfologia Instituto de Biociências Universidade Estadual PaulistaDepartment of Parasitology Institute of Biosciences São Paulo State University (UNESP)Laboratório de Genética de Peixes Faculdade de Ciências Universidade Estadual PaulistaDepartment of Biology and Animal Science School of Engineering São Paulo State University (UNESP