Zeitschrift für klinische Forschung

The discovery of effective AutoTaXin (ATX) inhibitors is crucial for developing therapies targeting various diseases, including cancer, inflammation and fibrosis. Structure-based drug design has emerged as a powerful strategy to identify and optimize ATX inhibitors with enhanced potency and selectivity. This comprehensive review explores recent advancements in structure-based approaches for discovering ATX inhibitors, encompassing computational modeling, structural biology insights and medicinal chemistry strategies. Key findings highlight successful examples of ATX inhibitor development, including structure-activity relationship studies and mechanism-based drug design. The review discusses challenges, opportunities and future directions in leveraging structure-based approaches to accelerate the discovery of next-generation ATX inhibitors for clinical applications.

This review examines the potential of vinorelbine, a vinca alkaloid with established cytotoxic properties, to enhance the efficacy of radiotherapy in HepatoCellular Carcinoma (HCC). Radiotherapy plays a critical role in the management of HCC, especially in cases where surgical resection or liver transplantation is not feasible. However, the inherent radio resistance of HCC often limits treatment outcomes. Vinorelbine's ability to sensitize cancer cells to radiation through various mechanisms, including cell cycle modulation, DNA damage repair inhibition and apoptosis induction, is explored. The review synthesizes current literature to elucidate the molecular mechanisms underlying the synergistic effects of vinorelbine and radiotherapy in HCC treatment. Insights gained from this review may guide future research and clinical strategies aimed at optimizing combination therapies for improved outcomes in HCC patients.

The relationship between dietary-induced weight loss and bone marrow fat composition is a complex interplay that impacts both metabolic health and skeletal integrity. This comprehensive review synthesizes current literature to explore the effects of various dietary interventions on Bone Marrow Adipose Tissue (BMAT), encompassing changes in quantity, distribution, lipid composition and metabolic activity. Evidence suggests that while weight loss generally reduces total BMAT volume, qualitative shifts in BMAT dynamics and their implications for bone health are nuanced and multifactorial. Understanding these effects is crucial for optimizing weight loss strategies that preserve skeletal integrity amidst metabolic changes associated with obesity and caloric restriction.

Placebo response in clinical trials for Fragile X Syndrome (FXS) presents a significant challenge in evaluating treatment efficacy and understanding the underlying mechanisms influencing patient outcomes. This paper provides a comprehensive initial analysis of placebo responses observed across various FXS clinical trials, highlighting trends, factors contributing to placebo effects, neurobiological mechanisms, methodological considerations and implications for future research and clinical practice.