Aim: Hepatocellular carcinoma (HCC) accounts for 90% of liver tumors and is the fourth leading cause of cancer-related deaths worldwide. Current treatments have poor outcomes for HCC, highlighting the urgent need for new and effective therapies. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, regulates differentiation, proliferation, and migration processes, effects observed in cancer, including HCC. In this study, we aimed to investigate the chemosensitizing effects on human liver cancer cells. Methods: We pre-treated Huh7 and Hep3B cells with GDF11 50 ng/mL for 72 h in the presence of sorafenib (Sfb) or cisplatin (CDDP) and evaluated cellular response. Results: Pre-treatment with GDF11 lowered the IC50 of CDDP and Sfb in Huh7 cells. Similar effects were observed in Hep3B cells. Additionally, combining GDF11 with CDDP or Sfb significantly reduced cell viability and decreased the size and number of spheroids. Furthermore, we found that the chemosensitizing effect is initiated by GDF11 binding to the type I receptor ALK5. Inhibition of ALK5 abolished SMAD2 activation, impacting the chemosensitizing effects. Finally, GDF11, combined with Sfb or CDDP, reduced the activity of drug transporters MRP2, MRP3, and MRP4, which explains its chemosensitizing properties. Conclusions: GDF11 increases the sensitivity of HCC-derived cell lines to Sfb and CDDP by modulating the drug-efflux transporters MRP2, MRP3, and MRP4.

Diverticulitis is one of the most common gastrointestinal causes of hospitalization in Western society. While previously characterized as a disease of older patients, new literature highlights an increasing incidence among the younger population. Over the past few decades, the understanding of etiology and management of diverticulitis has changed drastically. New data refute past beliefs while promoting other novel recommendations to mitigate incidence and subsequent complications. Data now confirms the safety and possible protective benefit of particulate food, while highlighting evidence-based approaches for the use of diagnostic imaging and antibiotics. We recognize modifiable and non-modifiable risk factors that are commonly seen throughout the literature and play a significant role in the management and prevention of diverticulitis. Emerging evidence also links chronic inflammation with subsequent microbial dysbiosis and alterations in the neuroendocrine system, leading to visceral hypersensitivity and perturbation of the gut-brain axis. This review provides a comprehensive update on acute uncomplicated diverticulitis according to the most recent evidence-based literature, encompassing the risks, diagnostic modalities, and management treatment regimens.

Pediatric cirrhosis differs significantly from adult liver disease in terms of etiology, progression, and management. The unique physiological, nutritional, and developmental needs of children require specialized diagnostic and therapeutic strategies. This review underscores the distinct challenges in diagnosing and managing pediatric cirrhosis, focusing on its complications, management, and outcomes. Unlike adults, where cirrhosis often results from viral hepatitis or alcohol use, pediatric cases are predominantly cholestatic, with biliary atresia being the most common cause. Complications mainly involve portal hypertension and impaired liver function, leading to malnutrition and neurodevelopmental delay. Nutritional management is complex and requires increased caloric and protein intake, supplementation with fat-soluble vitamins, and the use of medium-chain triglycerides. Although hepatocellular carcinoma is rare in children, it remains a severe complication with a higher incidence in certain genetic and metabolic disorders. Surveillance is challenging due to diagnostic limitations and the lack of standardized pediatric screening protocols. Treatment is further complicated by constraints related to size and developmental stage, particularly in the management of portal hypertension. Pediatric cirrhosis requires an individualized multidisciplinary approach to address the interplay between growth, nutrition, and liver function. Early diagnosis, nutritional optimization, malignancy surveillance, and timely referral for liver transplantation are crucial. Ongoing research on pediatric-specific therapies and outcomes is essential for improving prognosis and quality of life.