| 1. |
- Di Nicola, Matteo R., et al.
(författare)
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Ophidiomyces ophidiicola detection and infection : a global review on a potential threat to the world's snake populations
- 2022
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Ingår i: European Journal of Wildlife Research. - : Springer. - 1612-4642 .- 1439-0574. ; 68:5
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Forskningsöversikt (refereegranskat)abstract
- Ophidiomyces ophidiicola (Oo) is one of the most relevant fungal pathogens for snakes. It is the etiological agent of ophidiomycosis, an emerging disease causing dysecdysis, skin abnormalities, crusting cutaneous lesions, and ulcerations. Despite this major tegumentary "tropism", Oo infection can be systemic and it is capable of inducing visceral lesions. Moreover, ophidiomycosis may lead to abnormalities of reproductive physiology, hunting behavior, and thermoregulation, thus increasing the risks of sublethal effects and predation on affected snakes. Oo seems horizontally transmitted and can induce postnatal mortality. This article reviews published data on Oo detection and infection in all snake species in countries around the world and categorizes these data using new classification parameters. The presence of this fungus has been recorded in 11 states (considering the USA as a whole); however, in four states, the mycosis has only been reported in snakes held in captivity. Detection and/or infection of Oo has been ascertained in 62 snake species, divided into nine families. The taxa have been categorized with diagnostic criteria in order to report, for each species, the highest rank of categorization resulting from all cases. Therefore, 20 species have been included within the class "Ophidiomycosis and Oo shedder", 11 within "Ophidiomycosis", 16 in "Apparent ophidiomycosis", and 15 within "Ophidiomyces ophidiicola present". We also discuss the significance and limits of case classifications and Oo's impact on wild populations, and we suggest methods for preliminary surveillance. Standardized methods, interdisciplinary studies, and cooperation between various research institutions may facilitate further Oo screening studies, elucidate the unclear aspects of the disease, and protect ophidiofauna from this emerging threat at the global level.
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| 2. |
- Mancina, Rosellina Margherita, et al.
(författare)
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PSD3 downregulation confers protection against fatty liver disease.
- 2022
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
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Tidskriftsartikel (refereegranskat)abstract
- Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.
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| 3. |
- Maranesi, Margherita, et al.
(författare)
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Resistin in endocrine pancreas of sheep : Presence and expression related to different diets
- 2024
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Ingår i: General and Comparative Endocrinology. - : Elsevier. - 0016-6480 .- 1095-6840. ; 348
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Tidskriftsartikel (refereegranskat)abstract
- Resistin (RETN), a recently discovered adipokine, is a cysteine-rich and secretory protein produced by adipocytes. RETN has been detected in several tissues, including human and laboratory animals' pancreas, wherein impairs glucose tolerance and insulin (INS) action and causes INS resistance. This study aims to evaluate the presence and expression of RETN in the pancreas of 15 adult female sheep reared on Apennine pastures, which show a decrease in their nutritional value due to the drought stress linked to the increasing summer aridity. The sheep were divided into 3 groups according to the diet they were subjected to: maximum pasture flowering (MxF) group, maximum pasture dryness (MxD) group, and experimental (Exp) group which received a feed supplementation in addition to the MxD group feeding. Immunohistochemistry and immunofluorescence were performed on formalin-fixed and paraffin-embedded sections of the pancreas to detect the RETN presence and to evaluate the co-localization of RETN with both glucagon (GCG)- and INS-producing cells. In addition, the expression of the three molecules was evaluated also in relation to different diets. RETN was observed only in the endocrine pancreas, showing a wide distribution throughout the pancreatic islets with few negative cells and the RETN producing cells colocalized with both alpha cells and ss cells. No differences in distribution and immunostaining intensity of RETN, GCG and INS were observed among the three groups. Quantitative PCR showed the expression of RETN, GCG and INS in all tested samples. No significant differences were observed for RETN and GCG among all three groups of sheep. Instead, a high statistically significant expression of INS was detected in the MxF group with respect to the Exp and MxD groups. These results highlight the localization of RETN in GCG- and INS-secreting cells involved in glucose homeostasis suggesting a modulatory role for RETN. Furthermore, the RETN expression is not influenced by food supplementation and thus is not affected by diet.
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| 4. |
- Marini, Daniele, et al.
(författare)
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Pilot survey reveals ophidiomycosis in dice snakes Natrix tessellata from Lake Garda, Italy
- 2023
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Ingår i: Veterinary research communications. - : Springer. - 0165-7380 .- 1573-7446. ; 47:3, s. 1707-1719
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Tidskriftsartikel (refereegranskat)abstract
- Ophidiomycosis is an emerging infectious disease caused by the fungus Ophidiomyces ophidiicola (Oo). To date, Oo presence or associated disease condition has been recorded in wild and/or captive snakes from North America, Europe, Asia and Australia, but the data is still scarce outside the Nearctic. Although Italy is a country with a high snake biodiversity in the European panorama, and animals with clinical signs compatible with Oo infection have been documented, to date no investigations have reported the disease in the wild. Therefore, a pilot survey for the Italian territory was performed in conjunction with setting up a complete diagnostic workflow including SYBR Green-based real-time PCR assay for the detection of Oo genomic and mitochondrial DNA combined with histopathology of scale clips. Oo presence was investigated in 17 wild snake specimens from four different species. Four snakes were sampled in a targeted location where the mycosis was suspected via citizen science communications (i.e. North of the Lake Garda), whereas other ophidians were collected following opportunistic sampling. Oo genomic and mitochondrial DNA were detected and sequenced from all four Lake Garda Natrix tessellata, including three juveniles with macroscopic signs such as discolouration and skin crusts. From histopathological examination of scale clips, the three young positive individuals exhibited ulceration, inflammation and intralesional hyphae consistent with Oo infection, and two of them also showed the presence of arthroconidial tufts and solitary cylindrical arthrospores, allowing "Ophidiomycosis and Oo shedder" categorisation. For the remaining snake samples, the real-time PCR tested negative for Oo. This pilot survey permitted to localise for the first time Oo infection in free-ranging ophidians from Italy. Ophidiomycosis from Lake Garda highlights the need to increase sampling efforts in this area as well as in other northern Italian lakes to assess the occurrence of the pathogen, possible risk factors of the infection, its impact on host population fitness and the disease ecology of Oo in European snakes.
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| 5. |
- Marini, Daniele, et al.
(författare)
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Screening of Ophidiomyces ophidiicola in the free-ranging snake community annually harvested for the popular ritual of San Domenico e dei Serpari (Cocullo, AQ, Italy)
- 2023
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Ingår i: Acta Herpetologica. - : Firenze University Press. - 1827-9635 .- 1827-9643. ; 18:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- In the Abruzzi village of Cocullo (Italy), each year, on May 1st, local snake hunters (known as Serpari) display colubrids, captured in the wild, to commemorate the ancient ritual of San Domenico. The ascomycete Ophidiomyces ophidiicola (Oo) is the causative agent of ophidiomycosis, an emerging disease with sublethal effects. Skin lesions, such as dysecdysis, edematous, crusty or necrotic scales, swellings, nodules, and ulcers, are the most common clinical manifestation of the disease. The pathogen and its associated disease are well characterized in wild snakes in North America, whereas broad screenings of free ranging wild ophidians in Europe are rare. In 2019, as part of a multi-year snake health monitoring project, all the Cocullo ophidians were carefully examined for integumentary affections and those showing signs consistent with ophidiomycosis were dry swabbed on the skin and on any visible cutaneous lesions with a single applicator. The extracted DNA underwent a broad-range panfungal PCR targeting the D1-D2 region, as well as two conventional PCRs specific to the ITS2 and IGS regions of Oo DNA. Twenty-three out of 129 snakes (13/82 Elaphe quatuorlineata; 7/31 Hierophis viridiflavus; 3/15 Zamenis longissumus; 0/1 Natrix helvetica) resulted clinically affected, but no specific Oo genomic DNA was detected by PCR. The Cocullo ritual celebration provided a unique opportunity for the first systematic testing of a large sample size of a local snake community for the monitoring of this pathogen in Italy.
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| 6. |
- Pippione, Agnese Chiara, et al.
(författare)
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Potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the benzoisoxazole moiety: application of a bioisosteric scaffold hopping approach to flufenamic acid.
- 2018
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Ingår i: European journal of medicinal chemistry. - : Elsevier BV. - 1768-3254 .- 0223-5234. ; 150, s. 930-945
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Tidskriftsartikel (refereegranskat)abstract
- The aldo-keto reductase 1C3 (AKR1C3) isoform plays a vital role in the biosynthesis of androgens and is considered an attractive target in prostate cancer (PCa). No AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid and indomethacine are non-steroidal anti-inflammatory drugs known to inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. Recently, we employed a scaffold hopping approach to design a new class of potent and selective AKR1C3 inhibitors based on a N-substituted hydroxylated triazole pharmacophore. Following a similar strategy, we designed a new series focused around an acidic hydroxybenzoisoxazole moiety, which was rationalised to mimic the benzoic acid role in the flufenamic scaffold. Through iterative rounds of drug design, synthesis and biological evaluation, several compounds were discovered to target AKR1C3 in a selective manner. The most promising compound of series (6) was found to be highly selective (up to 450-fold) for AKR1C3 over the 1C2 isoform with minimal COX1 and COX2 off-target effects. Other inhibitors were obtained modulating the best example of hydroxylated triazoles we previously presented. In cell-based assays, the most promising compounds of both series reduced the cell proliferation, prostate specific antigen (PSA) and testosterone production in AKR1C3-expressing 22RV1 prostate cancer cells and showed synergistic effect when assayed in combination with abiraterone and enzalutamide. Structure determination of AKR1C3 co-crystallized with one representative compound from each of the two series clearly identified both compounds in the androstenedione binding site, hence supporting the biochemical data.
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| 7. |
- Rovai, Daniele, et al.
(författare)
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Myocardial perfusion abnormalities by intravenous administration of the contrast agent NC100100 in an experimental model of coronary artery occlusion and reperfusion
- 1998
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Ingår i: Echocardiography. - : Wiley. - 0742-2822 .- 1540-8175. ; 15:8, s. 731-740
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the study of myocardial perfusion. In eight anesthetized open-chest dogs, this agent was injected intravenously under baseline conditions, during acute coronary thrombosis, and after reperfusion, using both fundamental (FI) and harmonic (HI) imaging, both continuous and intermittent imaging, and both ultrasound (US) and integrated backscatter (IBS) imaging. Contrast injections did not modify the hemodynamic parameters. With all imaging modalities, myocardial contrast enhancement (MCE) was higher with intermittent than with continuous imaging (134 vs 82 gray level/pixel using FI, P = 0.02; 62 vs 32 acoustic units using US HI, P = 0.02; and 52 vs 12 dB using IBS, P = 0.05). MCE equally increased using either US or IBS imaging. The accuracy of MCE in detecting perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis was very good (sensitivity and specificity = 93% and 95% and 89% and 93%, respectively). The extent of myocardial perfusion defects by echo contrast showed a closer correlation with microspheres using HI (r = 0.82) than FI (r = 0.53). Thus, the intravenous administration of NC100100 during intermittent HI allows myocardial perfusion abnormalities to be accurately detected during acute myocardial infarction.
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| 8. |
- Svanholm, Sofie, 1992-, et al.
(författare)
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Impaired spermatogenesis and associated endocrine effects of azole fungicides in peripubertal Xenopus tropicalis
- 2024
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier. - 0147-6513 .- 1090-2414. ; 270
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Tidskriftsartikel (refereegranskat)abstract
- Early life exposure to endocrine disrupting chemicals (EDCs) has been suggested to adversely affect reproductive health in humans and wildlife. Here, we characterize endocrine and adverse effects on the reproductive system after juvenile exposure to propiconazole (PROP) or imazalil (IMZ), two common azole fungicides with complex endocrine modes of action. Using the frog Xenopus tropicalis, two short-term (2-weeks) studies were conducted. I: Juveniles (2 weeks post metamorphosis (PM)) were exposed to 0, 17 or 178 µg PROP/L. II: Juveniles (6 weeks PM) were exposed to 0, 1, 12 or 154 µg IMZ/L. Histological analysis of the gonads revealed an increase in the number of dark spermatogonial stem cells (SSCs)/testis area, and in the ratio secondary spermatogonia: dark SSCs were increased in all IMZ groups compared to control. Key genes in gametogenesis, retinoic acid and sex steroid pathways were also analysed in the gonads. Testicular levels of 3β-hsd, ddx4 were increased and cyp19 and id4 levels were decreased in the IMZ groups. In PROP exposed males, increased testicular aldh1a2 levels were detected, but no histological effects observed. Although no effects on ovarian histology were detected, ovarian levels of esr1, rsbn1 were increased in PROP groups, and esr1 levels were decreased in IMZ groups. In conclusion, juvenile azole exposure disrupted testicular expression of key genes in retinoic acid (PROP) and sex steroid pathways and in gametogenesis (IMZ). Our results further show that exposure to environmental concentrations of IMZ disrupted spermatogenesis in the juvenile testis, which is a cause for concern as it may lead to impaired fertility. Testicular levels of id4, ddx4 and the id4:ddx4 ratio were associated with the number of dark SSCs and secondary spermatogonia suggesting that they may serve as a molecular markers for disrupted spermatogenesis.
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| 9. |
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| 10. |
- Svanholm, Sofie, et al.
(författare)
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Pubertal sexual development and endpoints for disrupted spermatogenesis in the model Xenopus tropicalis
- 2023
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- Peripubertal models to determine effects of anti-androgenic endocrine disrupting chemicals are needed. Using the toxicological model species Xenopus tropicalis, the aims of the study were to 1) provide data on sexual maturation and 2) characterise effects of short-term exposure to an anti-androgenic model substance. Juvenile (2.5 weeks post metamorphosis old) X. tropicalis were exposed to 0, 250, 500 or 1000 & mu;g flutamide/L (nominal) for 2.5 weeks. Upon exposure termination, histology of gonads and Mullerian ducts was characterised in detail. New sperm stages were identified: pale and dark spermatogonial stem cells (SSCs). The testes of control males contained spermatozoa, indicating pubertal onset. The ovaries were immature, and composed of non-follicular and pre-vitellogenic follicular oocytes. The Mullerian ducts were more mature in females than males indicating development/regression in the females and males, respectively. In the 500 & mu;g/L group, the number of dark SSCs per testis area was decreased and the number of secondary spermatogonia was increased. No treatment effects on ovaries or Mullerian ducts were detected. To conclude, our present data provide new knowledge on spermatogenesis, and pubertal onset in X. tropicalis. New endpoints for evaluating spermatogenesis are suggested to be added to existing assays used in endocrine and reproductive toxicology.
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