241 research outputs found

    A comparison of small rodent assemblages after a 20 year interval in the Alps

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    Human-induced environmental alterations in the Alps may importantly affect small mammal species, but evidence in this sense is limited. We live-trapped small rodents in the Central-Eastern Italian Alps in three close-by habitat types (rocky scree, alpine grassland, and heath) at 2100 m a.s.l. during summer-fall, in 1997 and 2016. We compared small rodent assemblages through a Redundancy Detrended Analysis (RDA). In both surveys, we detected two specialist species, i.e., the common vole (Microtus arvalis) and the snow vole (Chionomys nivalis), and, unexpectedly, the forest generalist bank vole (Myodes glareolus). In 1997, grassland was mainly occupied by the common vole, while the bank vole and the snow vole were sympatric in the other habitats. In 2016, the snow vole was detected only in the scree, while other species did not show distribution changes. We discuss a series of hypotheses that might have driven the differences observed across decades, among which is a species-specific response to abiotic and biotic environmental alterations, with the alpine habitat specialist moving out of sub-optimal habitats. We encourage further research on this topic, e.g., via long-term longitudinal studies

    Biological effects of EF24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines

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    Background: Curcumin has numerous properties and is used in many preclinical conditions, including cancer. It has low bioavailability, while its derivative EF24 shows enhanced solubility. However, its effects have never been explored in adrenocortical tumor cell models. The efficacy of EF24 alone or combined with mitotane (reference drug for adrenocortical cancer) was evaluated in two adrenocortical tumor cell lines, SW13 and H295R. Method and Results: EF24 reduced cell viability with an IC50 (half maximal inhibitory concentration) of 6.5 \ub1 2.4 \ub5M and 4.9 \ub1 2.8 \ub5M for SW13 and H295R cells, respectively. Combination index (EF24 associated with mitotane) suggested an additivity effect in both cell lines. Cell cycle analysis revealed an increase in subG0/G1 phase, while motility assay showed a decrease in migratory cell capacity, and similarly, clonogenic assay indicated that EF24 could reduce colony numbers. Furthermore, Wnt/\u3b2-catenin, NF-\u3baB, MAPK, and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with EF24 alone or combined with mitotane. In addition, intracellular reactive oxygen species levels increased in both cell lines. Conclusion: This work analyzed EF24 in adrenocortical tumor cell lines for the first time. These results suggest that EF24 could potentially impact on adrenocortical tumors, laying the foundation for further research in animal models

    Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models

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    Mint [Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%\u201330% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumor cell models (H295R and SW13 cells). Chemical composition of ME was assessed by gas-chromatography/mass spectrometry and NMR spectroscopy analysis. Brine shrimp lethality assay showed ME effects at >0.5 \ub5g/\ub5l (p 0.5 \ub5g/\ub5l, p 0.5 \ub5g/\ub5l, p < 0.05), while Wright staining demonstrated the presence of both necrotic and apoptotic cells. Cell cycle analysis showed a strong increase in subG0/G1 phase, related to cell death. Furthermore, MAPK and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with ME alone or combined with mitotane. The crude methanolic extract of wild mountain mint can decrease cell viability, vitality and survival of adrenocortical tumor cell models, in particular of SW13 cells. These data show the potential anticancer effects of ME, still more work is needed to corroborate these findings

    Inositol administration reduces oxidative stress in erythrocytes of patients with polycistic ovary syndrome.

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    OBJECTIVE: Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations in erythrocytes and anti-inflammatory effects of inositol in women with PCOS before and after treatment with myo-inositol (MYO). METHODS: Twenty-six normal-weight PCOS patients were investigated before and after MYO administration (1200 mg/day for 12 weeks; n=18) or placebo (n=8) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, insulin area under the curve (AUC), and glucose AUC after oral glucose tolerance test and homeostasis model of assessment-IR. In erythrocytes, band 3 tyrosine phosphorylation (Tyr-P) level, glutathione (GSH) content, and glutathionylated proteins (GSSP) were also assessed. RESULTS: Data show that PCOS patients' erythrocytes underwent oxidative stress as indicated by band 3 Tyr-P values, reduced cytosolic GSH content, and increased membrane protein glutathionylation. MYO treatment significantly improved metabolic and biochemical parameters. Significant reductions were found in IR and serum values of androstenedione and testosterone. A significant association between band 3 Tyr-P levels and insulin AUC was found at baseline but disappeared after MYO treatment, while a correlation between band 3 Tyr-P and testosterone levels was detected both before and after MYO treatment. CONCLUSIONS: PCOS patients suffer from a systemic inflammatory status that induces erythrocyte membrane alterations. Treatment with MYO is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR

    Steroid Regulation of T Cell Function Appears Unaltered in Borderline Personality Disorder

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    Borderline personality disorder (BPD) is characterized by instability of interpersonal relationships and affection, impulsivity, and cognitive disruptions. Increasing evidence suggests hypothalamic-pituitary-adrenal (HPA) axis alterations in BPD. Changed glucocorticoid sensitivity of peripheral blood mononuclear cells is known in mood and posttraumatic stress disorders, representing frequent comorbidities in BPD. However, to the authors' knowledge, in BPD glucocorticoid sensitivity at the receptor level remains unexplored. Sixteen age-matched female BPD patients were compared to sixteen female healthy controls. In vitro steroid sensitivity of T cell proliferation was tested using aldosterone, dexamethasone, and hydrocortisone. Steroid sensitivity of BPD patients and healthy controls appeared comparable. Psychiatric comorbidities such as major depressive disorder or posttraumatic stress disorder and early life stress seemed to have had no influence on steroid sensitivity parameters. The data suggest unaltered GC sensitivity of T cell function in BPD

    Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations

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    Funding This work was supported by NIH NHGRI grant R01HG005220, NIDDK grant R24DK110499, NIDDK grant U54DE023798, and CMIT grant 6935956 to C.H., and by the European Research Council (ERC-STG project MetaPG-716575), MIUR “Futuro in Ricerca” RBFR13EWWI_001, the European Union (H2020-SFS-2018-1 project MASTER-818368 and H2020-SC1-BHC project ONCOBIOME-825410), and the National Cancer Institute of the National Institutes of Health (1U01CA230551) to N.S. Further support was provided by the Programma Ricerca Budget prestazioni Eurac 2017 of the Province of Bolzano, Italy to F.M., and by the EU-H2020 (DiMeTrack-707345) to E.P. and N.S. D.B., S.H.D., P.L., A.W.W. and The Rowett Institute received core funding support from the Scottish Government Rural and Environmental Sciences and Analytical Services (SG-RESAS). Availability of data and materials All datasets used in this study are publicly available and matched with their respective PMID (Additional file 5). The high-quality E. rectale MAGs in fasta format and a metadata file are available at http://segatalab.cibio.unitn.it/data/Erectale_Karcher_et_al.html and in the following Zenodo repository: https://doi.org/10.5281/zenodo.3763191 [80]. The two new isolate genomes L2–21 and T3BWe13 have been uploaded to NCBI and can be found in RefSeq under the accession numbers GCF_008122485.1 [81] and GCF_008123415.1 [82], respectively.Peer reviewedPublisher PD

    Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population

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    The human microbiome seeding starts at birth, when pioneer microbes are acquired mainly from the mother. Mode of delivery, antibiotic prophylaxis, and feeding method have been studied as modulators of mother-to-infant microbiome transmission, but other key influencing factors like modern westernized lifestyles with high hygienization, high-calorie diets, and urban settings, compared with non-westernized lifestyles have not been investigated yet. In this study, we explored the mother-infant sharing of characterized and uncharacterized microbiome members via strain-resolved metagenomics in a cohort of Ethiopian mothers and infants, and we compared them with four other cohorts with different lifestyles. The westernized and non-westernized newborns’ microbiomes composition overlapped during the first months of life more than later in life, likely reflecting similar initial breast-milk-based diets. Ethiopian and other non-westernized infants shared a smaller fraction of the microbiome with their mothers than did most westernized populations, despite showing a higher microbiome diversity, and uncharacterized species represented a substantial fraction of those shared in the Ethiopian cohort. Moreover, we identified uncharacterized species belonging to the Selenomonadaceae and Prevotellaceae families specifically present and shared only in the Ethiopian cohort, and we showed that a locally produced fermented food, injera, can contribute to the higher diversity observed in the Ethiopian infants’ gut with bacteria that are not part of the human microbiome but are acquired through fermented food consumption. Taken together, these findings highlight the fact that lifestyle can impact the gut microbiome composition not only through differences in diet, drug consumption, and environmental factors but also through its effect on mother-infant strain-sharing patterns

    The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology

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    The last decade has witnessed tremendous progress in the understanding of the mineralocorticoid receptor (MR), its molecular mechanism of action, and its implications for physiology and pathophysiology. After the initial cloning of MR, and identification of its gene structure and promoters, it now appears as a major actor in protein-protein interaction networks. The role of transcriptional coregulators and the determinants of mineralocorticoid selectivity have been elucidated. Targeted oncogenesis and transgenic mouse models have identified unexpected sites of MR expression and novel roles for MR in non-epithelial tissues. These experimental approaches have contributed to the generation of new cell lines for the characterization of aldosterone signaling pathways, and have also facilitated a better understanding of MR physiology in the heart, vasculature, brain and adipose tissues. This review describes the structure, molecular mechanism of action and transcriptional regulation mediated by MR, emphasizing the most recent developments at the cellular and molecular level. Finally, through insights obtained from mouse models and human disease, its role in physiology and pathophysiology will be reviewed. Future investigations of MR biology should lead to new therapeutic strategies, modulating cell-specific actions in the management of cardiovascular disease, neuroprotection, mineralocorticoid resistance, and metabolic disorders
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