ESG and reputation. The case of sanctioned italian banks

The aim of this paper is to investigate whether banks adopt Environmental, Social, and Governance (ESG) practices to reduce reputational damage due to financial pen- alties and whether the adoption of ESG factors can reduce the probability to receive sanctions. This study extends a previous research (Guerello et al., North American Journal of Economics and Finance, 2018, 48, 591–612) by including ESG scores as determinant of the probability to be sanctioned. The econometric analyses in this paper are based on a sample of 13 Italian banks for the years 2008–2018 and includes ESG scores provided by both Thomson Reuters and Bloomberg. The research shows that ESG score and the probability of sanctions are positively related. However, a careful analysis of causal directions clarifies the meaning of such positive relationship: receiving financial penalties is detrimental for banks reputations, there- fore it's necessary for banks to improve their reputation through the adoption of ESG practices

L’impatto delle sanzioni sulla probabilità di default. Il caso delle banche italiane

In questo articolo cerchiamo di identificare gli effetti delle sanzioni sul rischio di insolvenza impiegando uno stimatore di tipo diff-in-diff. L’analisi si basa su dati raccolti in una banca dati proprietaria (OASI e CASMEF Luiss Guido Carli), mediante la quale è stato possibile confrontare simultaneamente le azioni di contrasto del regolatore e le prestazioni delle banche. I risultati dell'analisi empirica suggeriscono l’esistenza sia di un attrition bias sia di un randomization bias. Una volta filtrato l’effetto indiretto che gli indicatori selezionati esercitano sulla redditività attraverso la probabilità di insolvenza, concludiamo che l’attività sanzionatoria non ha alcun impatto diretto significativo sulla probabilità di default

Serum micrornas as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma

The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC

Prevalence and clinical outcome of hepatic haemangioma with specific reference to the risk of rupture: a large retrospective cross-sectional study.

BACKGROUND: Prevalence and incidence of hepatic haemangioma are estimated from autopsy series only. Although benign and generally asymptomatic, hepatic haemangioma can cause serious complications. AIMS: The aim of the study was to assess the prevalence of hepatic haemangioma and to attempt to quantify the risk of major complications such as spontaneous rupture. METHODS: We retrospectively analyzed the radiology database of a Regional University Hospital over a 7-year period: the radiological records of 83,181 patients who had an abdominal computed tomography or magnetic resonance scan were reviewed. Diagnoses made at imaging were reviewed and related to clinical course. RESULTS: Hepatic haemangioma was diagnosed in 2071 patients (2.5% prevalence). In 226 patients (10.9%), haemangioma had diameter of 4 cm or more (giant haemangioma). The risk of bleeding was assessed on patients without concomitant malignancies. Spontaneous bleeding occurred in 5/1067 patients (0.47%). All 5 patients had giant haemangioma: 4 had exophytic lesions and presented with haemoperitoneum; 1 with centrally located tumour experienced intrahepatic bleeding. CONCLUSION: Giant haemangiomas have a low but relevant risk of rupture (3.2% in this series), particularly when peripherally located and exophytic. Surgery might be considered in these cases

Endoplasmic Reticulum stress induces hepatic stellate cell apoptosis and contributes to fibrosis resolution.

BACKGROUND: Survival of hepatic stellate cells (HSCs) is a hallmark of liver fibrosis, while the induction of HSC apoptosis may induce recovery. Activated HSC are resistant to many pro-apoptotic stimuli. To this issue, the role of Endoplasmic Reticulum (ER) stress in promoting apoptosis of HSCs and consequently fibrosis resolution is still debated. AIM: To evaluate the potential ER stress-mediated apoptosis of HSCs and fibrosis resolution METHODS: HSCs were incubated with the ER stress agonists, tunicamycin or thapsigargin. In vivo, HSC were isolated from normal, bile duct-ligated (BDL) and bile duct-diverted (BDD) rats. RESULTS: In activated HSC, the specific inhibitor of ER stress-induced apoptosis, calpastatin, is significantly increased vs. quiescent HSCs. Calpain is conversely reduced in activated HSCs. This pattern of protein expression provides HSCs resistance to the ER stress signals of apoptosis (apoptosis-resistant phenotype). However, both tunicamycin and thapsigargin are able to induce apoptosis in HSCs in vitro, completely reversing the calpain/calpastatin pattern expression. Furthermore, in vivo, the fibrosis resolution observed in rat livers subjected to bile duct ligation (BDL) and subsequent bile duct diversion (BDD), leads to fibrosis resolution through a mechanism of HSCs apoptosis, potentially associated with ER stress: in fact, BDD rat liver shows an increased number of apoptotic HSCs associated with reduced calapstatin and increased calpain protein expression, leading to an apoptosis-sensible phenotype. CONCLUSIONS: ER stress sensitizes HSC to apoptosis both in vitro and in vivo. Thus, ER stress represents a key target to trigger cell death in activated HSC and promotes fibrosis resolution

EASL Clinical Practice Guidelines:The diagnosis and management of patients with primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in end-stage biliary cirrhosis. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse and risk stratification is important to ensure all patients receive a personalised approach to their care. The goals of treatment and management are the prevention of end-stage liver disease, and the amelioration of associated symptoms. Pharmacologic approaches in practice, to reduce the impact of the progressive nature of disease, currently include licensed therapies (ursodeoxycholic acid and obeticholic acid) and off-label therapies (fibric acid derivatives, budesonide). These clinical practice guidelines summarise the evidence for the importance of a structured, life-long and individualised, approach to the care of patients with PBC, providing a framework to help clinicians diagnose and effectively manage patient

Prolactin stimulates the proliferation of normal female cholangiocytes by differential regulation of Ca2+-dependent PKC isoforms

<p>Abstract</p> <p>Background</p> <p>Prolactin promotes proliferation of several cells. Prolactin receptor exists as two isoforms: long and short, which activate different transduction pathways including the Ca²⁺-dependent PKC-signaling. No information exists on the role of prolactin in the regulation of the growth of female cholangiocytes. The rationale for using cholangiocytes from female rats is based on the fact that women are preferentially affected by specific cholangiopathies including primary biliary cirrhosis. We propose to evaluate the role and mechanisms of action by which prolactin regulates the growth of female cholangiocytes.</p> <p>Results</p> <p>Normal cholangiocytes express both isoforms (long and short) of prolactin receptors, whose expression increased following BDL. The administration of prolactin to normal female rats increased cholangiocyte proliferation. In purified normal female cholangiocytes, prolactin stimulated cholangiocyte proliferation, which was associated with increased [Ca²⁺]_ilevels and PKCβ-I phosphorylation but decreased PKCα phosphorylation. Administration of an anti-prolactin antibody to BDL female rats decreased cholangiocyte proliferation. Normal female cholangiocytes express and secrete prolactin, which was increased in BDL rats. The data show that prolactin stimulates normal cholangiocyte growth by an autocrine mechanism involving phosphorylation of PKCβ-I and dephosphorylation of PKCα.</p> <p>Conclusion</p> <p>We suggest that in female rats: (i) prolactin has a trophic effect on the growth of normal cholangiocytes by phosphorylation of PKCβ-I and dephosphorylation of PKCα; and (iii) cholangiocytes express and secrete prolactin, which by an autocrine mechanism participate in regulation of cholangiocyte proliferation. Prolactin may be an important therapeutic approach for the management of cholangiopathies affecting female patients.</p

Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3-kinase–dependent pathway in rats

Abstract: Background & Aims: We tested the hypothesis that during bile duct obstruction, increased biliary bile acids trigger cholangiocyte proliferation and secretion by a phosphatidylinositol 3-kinase (PI3-K)-dependent pathway. Metho : In bile duct-incannulated (BDI) rats, bile duct obstruction present for 7 days was relieved for 24 hours by external bile drainage. During the 24-hour drainage period, animals received either Krebs Ringer Henseleit (the bile-depleted group), or sodium taurocholate (the bile-depleted, taurocholate-infused group). We evaluated cholangiocyte proliferation and secretin-stimulated ductal secretion. Apical bile acid transporter (ABAT) expression and bile acid transport activity was determined. In pure preparations of cholangiocytes, we examined the effect of taurocholate (in the absence or presence of wortmannin or PI 3,4-bisphosphate the lipid product of PI3-K) on cholangiocyte proliferation and secretin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels. Results: Bile depletion reduced cholangiocyte proliferation and secretin-stimulated ductal secretion and ABAT expression and bile acid transport activity compared with 1-week BDI control rats. In bile-depleted, taurocholate-infused rats, cholangiocyte proliferation and secretion and ABAT expression and bile acid transport activity were maintained at levels similar to those seen in BDI control rats. In vitro, taurocholate stimulation of DNA replication and secretin-stimulated cAMP levels was blocked by wortmannin. The inhibitory effect of wortmannin on taurocholate stimulation of cholangiocyte proliferation and secretion was prevented by PI 3,4-bisphosphate. Conclusions: Bile acid uptake by ABAT and the PI3-K pathway are important for bile acids to signal cholangiocyte proliferation. In bile duct obstruction, increased biliary bile acid concentration and ABAT expression initiate increased cholangiocyte proliferation and secretion

Targeting UBC9-Mediated Protein Hyper-SUMOylation in Cystic Cholangiocytes Halts Polycystic Liver Disease in Experimental Models

BACKGROUND & AIMS: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple fluid-filled biliary cysts. Most PLD-causative genes participate in protein biogenesis and/or transport. Post-translational modifications (PTMs) are implicated in protein stability, localization and activity, contributing to human pathobiology; however, their role in PLD is unknown. Herein, we aimed to unveil the role of protein SUMOylation in PLD and its potential therapeutic targeting. METHODS: Levels and functional effects of SUMOylation, along with response to S-adenosylmethionine (SAMe, inhibitor of the SUMOylation enzyme UBC9) and/or short-hairpin RNAs (shRNAs) against UBE2I (UBC9), were evaluated invitro, invivo and/or in patients with PLD. SUMOylated proteins were determined by immunoprecipitation and proteomic analyses by mass spectrometry. RESULTS: Most SUMOylation-related genes were found overexpressed (mRNA) in polycystic human and rat liver tissue, as well as in cystic cholangiocytes in culture compared to controls. Increased SUMOylated protein levels were also observed in cystic human cholangiocytes in culture, which decreased after SAMe administration. Chronic treatment of polycystic (PCK: Pkdh1-mut) rats with SAMe halted hepatic cystogenesis and fibrosis, and reduced liver/body weight ratio and liver volume. Invitro, both SAMe and shRNA-mediated UBE2I knockdown increased apoptosis and reduced cell proliferation of cystic cholangiocytes. High-throughput proteomic analysis of SUMO1-immunoprecipitated proteins in cystic cholangiocytes identified candidates involved in protein biogenesis, ciliogenesis and proteasome degradation. Accordingly, SAMe hampered proteasome hyperactivity in cystic cholangiocytes, leading to activation of the unfolded protein response and stress-related apoptosis. CONCLUSIONS: Cystic cholangiocytes exhibit increased SUMOylation of proteins involved in cell survival and proliferation, thus promoting hepatic cystogenesis. Inhibition of protein SUMOylation with SAMe halts PLD, representing a novel therapeutic strategy. LAY SUMMARY: Protein SUMOylation is a dynamic post-translational event implicated in numerous cellular processes. This study revealed dysregulated protein SUMOylation in polycystic liver disease, which promotes hepatic cystogenesis. Administration of S-adenosylmethionine (SAMe), a natural UBC9-dependent SUMOylation inhibitor, halted polycystic liver disease in experimental models, thus representing a potential therapeutic agent for patients.Spanish Carlos III Health Institute (ISCIII) [J.M. Banales (FIS PI12/00380, PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008); M.J. Perugorria (FIS PI14/00399, PI17/00022 and PI20/00186); P.M. Rodrigues (Sara Borrell CD19/00254)] cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); Ministerio de Ciencia, Innovación y Universidades (MICINN; M.L. Martinez-Chantar: SAF2017-87301-R); “Instituto de Salud Carlos III” [CIBERehd: J.M. Banales, M.J. Perugorria, M.L. Martinez-Chantar and L. Bujanda], Spain; “Diputación Foral Gipuzkoa” (J.M. Banales: DFG15/010, DFG16/004), Department of Health of the Basque Country (M.J. Perugorria: 2019111024, 2015111100 and J.M. Banales: 2017111010), “Euskadi RIS3” (J.M. Banales: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J.M. Banales and M.L. Martinez-Chantar) and Department of Industry of the Basque Country (J.M. Banales: Elkartek: KK-2020/00008). La Caixa Scientific Foundation (J.M. Banales and M.L. Martinez-Chantar: HR17-00601). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to J.M. Banales and M.L. Martinez-Chantar). “Ayudas para apoyar grupos de investigación del Sistema Universitario Vasco” (IT971-16 to P.A.). Università Politecnica delle Marche PSA2017_UNIVPM grant (to M. Marzioni). National Institutes of Health (NIH) of United States of America (DK24031 to N.F. LaRusso). MJ Perugorria was funded by the Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC-2015-17755), P.Y. Lee-Law by the European Association for the Study of the Liver (EASL; Sheila Sherlock Award 2017), F.J. Caballero-Camino by the Spanish Ministry of Science and Innovation (BES-2014-069148), and P. Olaizola and A. Santos-Laso by the Basque Government (PRE_2016_1_0269, PRE_2015_1_0126). We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). The funding sources had no involvement in study design, data collection and analysis, decision to publish, or preparation of the article