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Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell's original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

Background: In Italy, data on long-term survivors after liver transplantation are lacking., Materials and Methods: We conducted a hybrid design study on a cohort of 359 adult recipients who received transplants between 1996 and 2002 to identify predictors of survival and the prevalence of co-morbidities among long-term survivors., Results: The actuarial (95% CI) patient survival was 96% (94.6-98.3%), 69% (64.2-73.6%), 55% (49.8-59.9%), 42.8% (37.6-47.8%), and 34% (29.2-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The leading causes of death were hepatitis C virus recurrence (24.6%), extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The factors associated with the survival probability were younger donor and recipient ages ( p = 0.001 and 0.004, respectively), female recipient sex ( p < 0.001), absence of HCV ( p < 0.01), absence of HCC ( p = 0.001), and absence of diabetes mellitus at one year ( p < 0.01). At the latest follow-up, the leading comorbidities were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication., Conclusions: Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

Vaccination against SARS-CoV-2 has played a critical role in controlling the spread of the pandemic. The main side effects of SARS-CoV-2 vaccination include fever and fatigue; however, the potential impacts on menstrual cycles are to be determined. Given the limited number of studies suggesting menstrual changes post vaccination, this study investigates the correlation between COVID-19 vaccines and menstrual cycle changes in fertile-aged Italian women. A questionnaire was distributed from 1 October to 31 November 2022, focusing on menstrual rhythm and flow changes post vaccination. The analysis involved 471 participants. The study observed a shift from a regular to an irregular menstrual rhythm ( p < 0.001), and changes in menstrual duration ( p = 0.008 and p < 0.001 for first and second doses, respectively) and flow volume ( p < 0.001). Most patients with irregular rhythms were vaccinated in the proliferative phase of their cycle. Within six months post vaccination, 74.2% of women with irregular post-vaccination rhythms reported a return to normality. These findings indicate primarily transient menstrual changes following mRNA COVID-19 vaccination, suggesting the vaccines' safety for women of reproductive age.

The aims of our study were to evaluate the maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP). In this observational, retrospective case-control study, we included all pregnant women who gave birth with a diagnosis of ICP between January 2010 and December 2020 at the Unit of Obstetrics and Gynecology, University Hospital of Messina. The data were compared with those from a control group of pregnant women who did not have ICP. One hundred twenty-nine and eighty-five patients were included, respectively, in the study and in the control group. There was a significant difference between the two groups in the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm delivery, which were more frequent in the ICP patients. No neonatal adverse events were recorded, although a significant difference in the meconium-stained amniotic fluid condition was noted. After a 24-month follow-up, 48/129 patients with ICP accepted to be reassessed by liver ultrasound, elastographic examination, and liver function blood tests. No patient showed signs of chronic liver disease. This study confirmed a higher probability of adverse short-term maternal outcomes in ICP pregnant patients, but a lower probability of adverse short-term fetal outcomes and the absence of a long-term maternal risk of chronic liver disease.

Diagnostic procedures for the diagnosis of gestational diabetes mellitus (GDM) are not uniformly defined worldwide. We retrospectively applied two diagnostic procedures (i.e., the IADPSG and the Indian) to the same pregnant women in order to compare the clinical characteristics and the prevalence of risk factors for GDM. Overall, 1015 pregnant women were evaluated. GDM was diagnosed in 113 cases (11.1%) by the IADPSG criteria and in 105 cases (10.3%) by the Indian criteria. The women diagnosed with GDM according to the IADPSG criteria had higher pre-gestational BMIs, higher previous macrosomia rates, higher first trimester fasting blood glucose levels, higher fasting and 1 h glucose levels after glucose load at OGTT, and lower 2 h glucose levels at OGTT compared with the women with GDM diagnosed according to the Indian criteria. Only 49.6% of the women who were diagnosed by the IADPSG criteria were also diagnosed with GDM by the Indian diagnostic criteria. For 47.8% of the women who were diagnosed by the IADPSG criteria, a diagnosis of GDM was missed by applying the Indian diagnostic criteria. Interestingly, 49 women were diagnosed with GDM by the Indian criteria but were normal according to the IADPSG criteria. Different diagnostic criteria could lead to different GDM detection rates with different practical approaches.

Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GBM is characterized by an extremely poor prognosis and a high rate of recurrence. PDT is a physical process that induces tumor cell death through the genesis and accumulation of reactive oxygen species (ROS) produced by light energy interaction with a photosensitizing agent. In this contribution, we explored the potentiality of the plant alkaloid berberine (BBR) as a photosensitizing and cytotoxic agent coupled with a PDT scheme using a blue light source in human established astrocytoma cell lines. Our data mainly indicated for the combined BBR-PDT scheme a potent activation of the apoptosis pathway, through a massive ROS production, a great extent of mitochondria depolarization, and the sub-sequent activation of caspases. Altogether, these results demonstrated that BBR is an efficient photosensitizer agent and that its association with PDT may be a potential anticancer strategy for high malignant gliomas.

Existing therapies for Parkinson's disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP + ) and in vivo (C57BL/6J mice administered with MPTP) PD models. EPO restores cell viability in both protective and restorative layouts, enhancing the dopaminergic recovery. Specifically, EPO rescues the PD-induced damage to mitochondria, as shown by transmission electron microscopy, Mitotracker assay and PINK1 expression. Moreover, EPO promotes a rescue of mitochondrial respiration while markedly enhancing the glycolytic rate, as shown by the augmented extracellular acidification rate, contributing to elevated ATP levels in MPP + -challenged cells. In PD mice, EPO intrastriatal infusion markedly improves the outcome of behavioral tests. This is associated with the rescue of dopaminergic markers and decreased neuroinflammation. This study demonstrates cellular and functional recovery following EPO treatment, likely mediated by the 37 Kda isoform of the EPO-receptor. We report for the first time, that EPO-neuroprotection is exerted through restoring ATP levels by accelerating the glycolytic rate. In conclusion, the redox imbalance and neuroinflammation associated with PD may be successfully treated by EPO.

Aims: A considerable proportion of patients affected by coronavirus respiratory disease (COVID-19) develop cardiac injury. The viral impact in cardiomyocytes deserves, however, further investigations, especially in asymptomatic patients., Methods: We investigated for SARS-CoV-2 presence and activity in heart tissues of six consecutive COVID-19 patients deceased from respiratory failure showing no signs of cardiac involvement and with no history of heart disease. Cardiac autopsy samples were collected within 2 h after death, and then analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays., Results: The presence of SARS-CoV-2 into cardiomyocytes was invariably detected in all assays. A variable pattern of cardiomyocyte injury was observed, spanning from absence of cell death and subcellular alterations hallmarks, to intracellular oedema and sarcomere ruptures. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike RNA., Conclusions: In this autopsy analysis of patients with no clinical signs of cardiac involvement, the presence of SARS-CoV-2 in cardiomyocytes has been detected, determining variable patterns of intracellular damage. These findings suggest the need for cardiologic surveillance in surviving COVID-19 patients not displaying a cardiac phenotype.