Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.

The JAK-STAT pathway is an important physiologic regulator of different cellular functions including proliferation, apoptosis, differentiation, and immunological responses. Out of six different STAT proteins, STAT5 plays its main role in hematopoiesis and constitutive STAT5 activation seems to be a key event in the pathogenesis of several hematological malignancies. This has led many researchers to develop compounds capable of inhibiting STAT5 activation or interfering with its functions. Several anti-STAT5 molecules have shown potent STAT5 inhibitory activity in vitro. However, compared to the large amount of clinical studies with JAK inhibitors that are currently widely used in the clinics to treat myeloproliferative disorders, the clinical trials with STAT5 inhibitors are very limited. At present, a few STAT5 inhibitors are in phase I or II clinical trials for the treatment of leukemias and graft vs host disease. These studies seem to indicate that such compounds could be well tolerated and useful in reducing the occurrence of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia. Of interest, STAT5 seems to play an important role in the regulation of hematopoietic stem cell self-renewal suggesting that combination therapies including STAT5 inhibitors can erode the cancer stem cell pool and possibly open the way for the complete cancer eradication. In this review, we discuss the implication of STAT5 in hematological malignancies and the results obtained with the novel STAT5 inhibitors.

What is known and objective Mebendazole (MBZ) is a broad‐spectrum antihelminthic agent of the benzimidazole type. Although MBZ has been reported to cause hepatic injury, case reports of severe hepatic injury are very rare. We report a case of severe hepatitis after administration of MBZ in a patient with Gilbert's syndrome affected by pinworms infestation. Case summary Differently from other cases of hepatitis due to MBZ reported in the scientific literature, our patient received standard doses of MBZ for a short period of time. After 18 days from the start of therapy, he developed hepatomegaly, and increases in hepatic enzymes and bilirubin. Hepatic enzymes returned to normal over the following 5 weeks. What is new and conclusion This is the first case report of important liver injury after administration of MBZ in a patient with Gilbert's syndrome. We suspected that a diminished hepatic glucuronidation of MBZ due to the reduced activity of the glucuronosyltransferase enzyme in our patient could have caused an increase in unconjugated toxic metabolites of MBZ and the consequent liver damage.

Background and Clinical Significance: Men who engage in anal fisting may experience full rectal and colon thickness injury resulting in an endoscopic emergency. The endoscopist does not routinely question patients about their sexual habits, nor are patients compliant with counseling during the endoscopy procedure as indicated by the infectious disease clinician. Case Presentation: A 47-years-old HIV- and monkeypox virus (MPXV)-negative Caucasian gay man underwent colonoscopy because of changes in bowel habits with anal discomfort and rectal bleeding. The first colonoscopy showed a vegetative annular neoformation of the anal canal. There was a concentric stenosis of the lumen. The endoscopist suspected the diagnosis of anal squamous cell carcinoma and a histopathology investigation was requested. Biopsy histology excluded a frank neoplasm or anal intraepithelial neoplasia (AIN). Then, the patient was referred to a multidisciplinary team. With adequate counseling, the patient disclosed his habitual anal fisting. Laboratory identification of L1–L3 Chlamydia trachomatis (CT) genovars was positive for CT L1, L2, real-time PCR for Neisseria gonorrhoeae (NG), and Mycoplasma hominis. Human Papillomavirus (HPV)-DNA detection identified HPV type 70, 68, and 61. We illustrate this case with plenty of histology and immunohistochemistry. We also review the differential diagnosis of AIN according to the 5th edition (2019) WHO Classification of Digestive System Tumours. Conclusions: Our patient emphasizes two important aspects of endoscopy and pathology: first, the significance of understanding patients’ sexual behaviors in diagnosing rectal and colon injuries, as well as the need for sexually transmitted infections (STI) screening especially for CT; and second, the effectiveness of a multidisciplinary communication model that encourages private discussions to alleviate patients’ fears and improve prevention efforts.