A growing health concern, metabolic dysfunction-associated steatotic liver disease (MASLD), impacts nearly 30% of adults globally. This condition can progress to severe complications like metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. A recent review in eGastroenterology explores the role of long non-coding RNAs (lncRNAs) in MASLD and liver fibrosis. These molecules, which do not code for proteins but regulate gene expression, are emerging as crucial players in metabolic and fibrotic pathways. The review highlights how lncRNAs influence lipid metabolism, inflammation, and fibrogenesis, offering new therapeutic avenues.
lncRNAs play a pivotal role in modulating various metabolic processes within liver cells. They impact lipid accumulation, inflammatory responses, and fibrotic changes by interacting with key cellular mediators. Studies have shown that specific lncRNAs can either promote or inhibit these processes, making them potential targets for therapeutic intervention. For instance, H19 has been linked to increased hepatic lipid buildup and fibrosis, while protective lncRNAs like Gas5 and MEG3 can mitigate hepatocyte lipid accumulation and prevent the activation of hepatic stellate cells.
The intricate interplay between lncRNAs and other molecular entities such as microRNAs and transcription factors is critical in understanding liver disease progression. H19's interaction with miR-130a and hnRNPA1 exemplifies how lncRNAs can drive steatosis. Conversely, HOTAIR's regulation of DNA methylation through miR-148b and DNMT1 showcases the complexity of these networks. This knowledge underscores the potential for developing lncRNA-based therapies that could revolutionize the treatment of MASLD.
While the therapeutic promise of lncRNAs is compelling, several challenges must be addressed. Species-specific variations in lncRNAs complicate translational research, necessitating the identification of conserved lncRNAs across different species. Additionally, developing efficient delivery mechanisms, such as nanoparticle-mediated RNA delivery, is essential for advancing this field. Overcoming these hurdles will pave the way for clinical applications of lncRNA-targeted therapies.
The review emphasizes the need for further investigation into the regulatory roles of lncRNAs in liver disease. As MASLD prevalence continues to rise, harnessing the therapeutic potential of lncRNAs could represent a significant shift in managing liver diseases. Researchers at Queen’s University Belfast highlight the dual approach of suppressing pathogenic lncRNAs and enhancing protective ones, opening new doors for innovative treatments. The ongoing exploration of lncRNAs promises to bring about transformative advancements in the field of hepatology.
An ambitious international research initiative, coordinated by Heidelberg University, is tackling the challenge of highly dangerous viral diseases. This project seeks to develop innovative molecular strategies that can disrupt viral entry into cells and hinder replication processes. By focusing on flavivirus, mammarenavirus, and henipavirus, the team aims to design entry inhibitors and understand immune evasion mechanisms. The European Union has committed nearly eight million euros over five years to support this collaborative effort involving ten universities and research institutions across Europe.
The EU-backed project, titled "Molecular Strategies against Viral Entry and Glycan Shielding" (SHIELD), targets pathogens known for their severe impact on human health. Researchers are investigating how viruses penetrate host cells and replicate, with a particular emphasis on glycan shielding—a phenomenon where sugar chains on the cell surface influence immune responses. Prof. Dr Christian Klein, leading the Pharmaceutical and Medicinal Chemistry department at Heidelberg University, explains that understanding these processes could enhance immune defenses and improve vaccine efficacy. The study will explore various molecular substances designed computationally and tested in biological systems ranging from in-vitro assays to mouse models.
The research encompasses a broad spectrum of expertise, including bioinformatics, computational drug design, chemistry, immunology, structural biology, and virology. At Heidelberg University, scientists are synthesizing new entry inhibitors and glycan-binding substances tailored to different viral pathogens. Meanwhile, at Heidelberg University Hospital, Dr Vibor Laketa's team is employing advanced imaging techniques to observe viral entry into host cells and assess the effects of molecular interventions such as biological substances, nanoparticles, and antibodies. This multi-faceted approach aims to identify promising candidates for robust vaccines and potential clinical studies.
To kickstart the consortium, a meeting was held in mid-February 2025 at Heidelberg University, bringing together experts from Denmark, France, Germany, the Netherlands, Poland, Portugal, Sweden, and Switzerland. The SHIELD project falls under the "Health" cluster of the Horizon Europe research framework program, reflecting the EU's commitment to advancing medical science and public health.
This pioneering research not only promises to deepen our understanding of viral mechanisms but also paves the way for developing novel therapeutic approaches. By integrating diverse scientific disciplines, the project seeks to uncover innovative solutions that could lead to more effective treatments and preventive measures against dangerous viral diseases. The long-term goal is to identify reference substances and potential candidates for initial clinical trials, ultimately enhancing global health security.