Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium.
Published: March 2020
AI Article Synopsis
Article Abstract
Predicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage.
The increasing occurrence of infections caused by multidrug-resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to the current lack of antibiotic discovery and development, new strategies to fight MDR bacteria are urgently needed. Efforts to develop new antibiotic adjuvants to increase the effectiveness of existing antibiotics and design delivery systems are essential to address this issue.
Antimicrobial peptides (AMPs) offer potential as antibiotic alternatives, but high cost, off-site cytotoxicity, and poor stability limit their application. Combining AMPs with adjuvants holds promise in surmounting these limitations. Among potentiators, terpenoids account for the highest proportion, yet their potential to enhance the AMPs efficacy and underlying mechanism remain unclear.
Background/aims: Phenobarbital (PB), commonly used for epilepsy management, is associated with testicular dysfunction after prolonged use. This study aimed to evaluate the ameliorative effects of cranberry (CB) and vitamin C (Vit-C) on PB-induced reproductive toxicity in rats.
Methods: Forty male Wistar rats were divided into five groups.
Background/aims: Gestational Diabetes Mellitus (GDM), a prevalent complication in pregnancy, is characterized by the Diabetes Association as diabetes diagnosed in the second or third trimester, often remaining asymptomatic. This study investigates the intricate effects of Streptozotocin on pregnant rats, unraveling its impact on Gestational Type 2 Diabetes (GTD). The research delves into the potential therapeutic roles of mesenchymal stem cells (MSCs) and olive leaf extract (OLE) in mitigating the consequences of Streptozotocin-induced pancreatic impairment.
Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA.
