Publications by authors named "Orsini V"

Article Synopsis
  • The YAP/Hippo pathway regulates organ growth and helps maintain stem cell function, with LATS kinases playing a critical role by inactivating YAP.
  • A new small-molecule inhibitor, NIBR-LTSi, has been developed that selectively targets LATS kinases, activating YAP signaling and promoting tissue regeneration in laboratory settings.
  • While NIBR-LTSi shows promise by enhancing liver regeneration and supporting stem cell characteristics, prolonged use may lead to excessive cell proliferation and dedifferentiation, which could limit its therapeutic benefits.
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The roof plate-specific spondin-leucine-rich repeat-containing G-protein coupled receptor 4/5 (LGR4/5)-zinc and ring finger 3 (ZNRF3)/ring finger protein 43 (RNF43) module is a master regulator of hepatic Wnt/β-catenin signaling and metabolic zonation. However, its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. The current study investigated whether hepatic epithelial cell-specific loss of the Wnt/β-catenin modulator Lgr4/5 promoted NAFLD.

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Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking.

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The Caatinga is an exclusively Brazilian biome, and is the largest and most biodiverse Seasonal Tropical Dry Forest in the world. Despite that, the mammalian fauna, especially small mammals, is the least studied of all Brazilian biomes. In order to fill gaps and provide detailed information on small mammals (Didelphimorphia, Rodentia) in the Caatinga biome, we compiled reliable records focusing on richness, composition and some biometric data.

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Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip® miRNA 4.

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Background: Current studies focus primarily on skeletal injuries following cardiopulmonary resuscitation (CPR). Few studies report on intrathoracic injuries (ITI) and none, to our knowledge, focus exclusively on cardiovascular injuries related to cardiac massage. This study was based on autopsy findings and assessed the incidence of non-skeletal CPR related injuries related to chest compression.

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The Hippo/YAP pathway controls cell proliferation through sensing physical and spatial organization of cells. How cell-cell contact is sensed by Hippo signaling is poorly understood. Here, we identified the cell adhesion molecule KIRREL1 as an upstream positive regulator of the mammalian Hippo pathway.

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Human organoids allow the study of proliferation, lineage specification, and 3D tissue development. Here we present a genome-wide CRISPR screen in induced pluripotent stem cell (iPSC)-derived kidney organoids. The combination of inducible genome editing, longitudinal sampling, and endpoint sorting of tubular and stromal cells generated a complex, high-quality dataset uncovering a broad spectrum of insightful biology from early development to "adult" epithelial morphogenesis.

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AXIN2 and LGR5 mark intestinal stem cells (ISCs) that require WNT/β-Catenin signaling for constant homeostatic proliferation. In contrast, AXIN2/LGR5+ pericentral hepatocytes show low proliferation rates despite a WNT/β-Catenin activity gradient required for metabolic liver zonation. The mechanisms restricting proliferation in AXIN2+ hepatocytes and metabolic gene expression in AXIN2+ ISCs remained elusive.

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Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae.

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Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown.

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The existence of specialized liver stem cell populations, including AXIN2 pericentral hepatocytes, that safeguard homeostasis and repair has been controversial. Here, using AXIN2 lineage tracing in BAC-transgenic mice, we confirm the regenerative potential of intestinal stem cells (ISCs) but find limited roles for pericentral hepatocytes in liver parenchyma homeostasis. Liver regrowth following partial hepatectomy is enabled by proliferation of hepatocytes throughout the liver, rather than by a pericentral population.

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Biliary epithelial cells (BECs) form bile ducts in the liver and are facultative liver stem cells that establish a ductular reaction (DR) to support liver regeneration following injury. Liver damage induces periportal LGR5+ putative liver stem cells that can form BEC-like organoids, suggesting that RSPO-LGR4/5-mediated WNT/β-catenin activity is important for a DR. We addressed the roles of this and other signaling pathways in a DR by performing a focused CRISPR-based loss-of-function screen in BEC-like organoids, followed by in vivo validation and single-cell RNA sequencing.

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Xenarthrans-anteaters, sloths, and armadillos-have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths.

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Rationale And Objectives: The study aimed to validate magnetic resonance imaging (MRI)-based liver volumetry as a quantitative measure of hepatic regeneration in mice subjected to partial hepatectomy, in view of routine in vivo pharmacologic studies characterizing compounds aiming to accelerate liver regeneration.

Materials And Methods: Partial hepatectomy was performed in male B6 mice (n = 47). Images were acquired in 14.

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LGR4/5 receptors and their cognate RSPO ligands potentiate Wnt/β-catenin signalling and promote proliferation and tissue homeostasis in epithelial stem cell compartments. In the liver, metabolic zonation requires a Wnt/β-catenin signalling gradient, but the instructive mechanism controlling its spatiotemporal regulation is not known. We have now identified the RSPO-LGR4/5-ZNRF3/RNF43 module as a master regulator of Wnt/β-catenin-mediated metabolic liver zonation.

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The Yap-Hippo pathway has a significant role in regulating cell proliferation and growth, thus controlling organ size and regeneration. The Hippo pathway regulates two highly conserved, transcription coactivators, YAP and TAZ. The upstream regulators of the Yap-Hippo pathway have not been fully characterized.

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Unlabelled: The Yes-associated protein (YAP)/Hippo pathway has been implicated in tissue development, regeneration, and tumorigenesis. However, its role in cholangiocarcinoma (CC) is not established. We show that YAP activation is a common feature in CC patient biopsies and human CC cell lines.

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Lgr4 and Lgr5 are known markers of adult and embryonic tissue stem cells in various organs. However, whether Lgr4 and Lgr5 are important for embryonic development remains unclear. To study their functions during intestinal crypt, skin and kidney development we now generated mice lacking either Lgr4 (Lgr4KO), Lgr5 (Lgr5KO) or both receptors (Lgr4/5dKO).

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Platinum combinations are the mainstay of treatment for non-small cell lung cancer (NSCLC), while for pancreatic cancer platinum combinations are being given to good-performance status patients. These platinum combinations consist of cis- or carboplatin with gemcitabine, while, for non-squamous NSCLC and mesothelioma, of pemetrexed. The combination of gemcitabine and cisplatin is based on gemcitabine-induced increased formation and retention of DNA-platinum adducts, which can be explained by a decrease of excision repair cross-complementing group-1 (ERCC1)-mediated DNA repair.

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A rare case of Solitary fibrous tumor (SFT) of the pelvis is reported. A 76-years-old man presented with a low abdominal pain, acute urine retention and constipation. Imaging studies (US, CT MR) showed an 17 x 10 x 9 ovoid mass in the pelvis, dislocating bladder and rectum.

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Bochdalek diaphragmatic hernia usually begins during childhood, but may be an occasional finding even in adults. The treatment of choice is surgical repair to avoid herniated bowel complications. The operation often requires a combined approach consisting in thoracotomy and laparotomy.

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Background: The AA. compared the preliminary results of two different methods of inguinal hernioplasty: one using only the mesh (Lichtenstein) and the other one using both mesh and plug (Rutkow-Robbins).

Patients And Methods: Seventy consecutive patients were randomly allocated into two groups, 35 patients each one, to receive either a Licthenstein mesh or a Rutkow-Robbins plug and mesh for primary monolateral groin hernia.

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