The severe heart disease of old age, characterized by aortic valve narrowing (aortic stenosis) combined with cardiac amyloidosis, has long been associated with a high risk of death. For years, treatment has focused on replacing the narrowed heart valve, while often leaving the amyloid deposits in the heart muscle untreated. A groundbreaking international study led by MedUni Vienna and University College London has now demonstrated that combining heart valve replacement with specific drug therapy can significantly prolong life for patients with this condition.

Led by Christian Nitsche (Department of Medicine II, Clinical Division of Cardiology, MedUni Vienna) and Thomas Treibel (Department of Cardiovascular Imaging, University College London), the research team analyzed data from 226 patients with aortic stenosis and concomitant cardiac amyloidosis from ten countries. Their study revealed that both aortic valve replacement and treatment with the drug tafamidis for amyloidosis were associated with a lower risk of death.

Most impressively, the survival benefit was highest in patients who received both forms of treatment. “Our results show that patients with both conditions who received valve replacement and specific amyloidosis therapy had similar long-term survival rates to people with aortic stenosis without amyloidosis,” emphasized study leader Christian Nitsche.

The targeted therapy can slow the progression of amyloidosis, while valve replacement treats the mechanical stress caused by the narrowed heart valve. The research suggests that around ten percent of patients with aortic stenosis also have amyloidosis, but this is often not diagnosed in everyday clinical practice.

“Our findings also suggest that patients with severe aortic valve stenosis should be screened for amyloidosis so that we can offer them targeted life-prolonging treatment options,” Christian Nitsche emphasized.

This study offers new hope for patients with severe heart disease and highlights the importance of combining therapy to improve outcomes. By targeting both the mechanical stress caused by aortic stenosis and the debilitating effects of cardiac amyloidosis, doctors can now provide their patients with more effective life-prolonging treatment options.

The treatment of chronic inflammatory bowel diseases has long been a challenge, particularly in young patients where disease manifestation often coincides with critical periods of education and early career development. Prompt diagnosis and treatment are crucial to prevent complications, including the development of bowel cancer. Researchers at Charité – Universitätsmedizin Berlin have made a groundbreaking discovery that significantly contributes to halting ongoing inflammatory processes, published in Nature Immunology.

Crohn’s disease and ulcerative colitis, the two most common chronic inflammatory bowel diseases, can be debilitating and life-altering. While traditional treatments focus on suppressing the immune system as a whole, newer therapies aim to interrupt the inflammatory process by blocking specific messenger substances that drive inflammation in the body.

Prof. Ahmed Hegazy has been studying inflammatory processes in the gut and the immune system’s defense mechanisms for several years. He has identified the interaction between two immune messenger substances – interleukin-22 and oncostatin M – as the driving force behind chronic intestinal inflammation. This uncontrolled chain reaction amplifies inflammation, drawing more immune cells into the intestine like a fire that spreads.

The research team spent five years uncovering how the immune messenger oncostatin M triggers inflammatory responses. They used animal models and examined tissue samples from patients to study the different stages of chronic intestinal diseases. State-of-the-art single-cell sequencing showed that in inflamed gut tissue, there are many unexpected cell types with binding sites for oncostatin M.

Interestingly, interleukin-22 normally protects tissue but also makes the gut lining more sensitive to oncostatin M by increasing its receptors. This interaction between the two immune messengers works together and amplifies inflammation, much like a fire getting more fuel and spreading.

In their models, the researchers specifically blocked the binding sites for oncostatin M and saw a clear reduction in both chronic inflammation and cancer associated with it. The team’s experimental findings may soon translate into real-world therapy by disrupting the harmful interaction between interleukin-22 and oncostatin M.

A clinical trial is already underway to test an antibody that blocks the receptors for oncostatin M. This targeted treatment has the potential to revolutionize the management of chronic inflammatory bowel diseases, particularly in patients with more severe forms of the illness. The discovery offers a new era in chronic inflammation treatment, providing hope for those affected by these debilitating conditions.

Cohesin, a protein complex that forms loops in the human genome, plays a crucial role in determining the architecture of our genetic material and regulating gene expression. However, its function and behavior have remained somewhat mysterious until now.

Researcher Professor Eva Estébanez-Perpiñá from the University of Barcelona, along with her team and international collaborators, has made significant strides in understanding how cohesin works. Their study, published in Nucleic Acids Research, sheds light on the protein’s interaction with chromatin structure and its role in altering gene expression.

Cohesin consists of four subunits: SMC1, SMC3, SCC1/RAD21, and STAG (also known as SA or SCC2). Previous studies had identified 25 proteins that regulate these subunits and their biological function. Estébanez-Perpiñá’s team has now discovered how the NIPBL protein interacts with both MAU2 and the glucocorticoid receptor (GR), a transcription factor essential for cellular functions.

This ternary complex, comprising NIPBL, MAU2, and GR, modulates transcription by facilitating the interaction of GR with these two proteins. When GR interacts with NIPBL and MAU2, it alters chromatin structure and affects gene expression. This discovery has significant implications for understanding Cornelia de Lange syndrome, a rare disease caused by mutations in genes involved in cohesin formation.

The researchers used advanced microscopic techniques to visualize real-time molecular complexes binding to chromatin, as well as biochemical and biophysical methods to analyze the complex from different structural and cellular perspectives.

Their findings not only improve our comprehension of cohesin’s role but also highlight its potential involvement in other diseases, such as asthma and autoimmune pathologies. As research continues, scientists will likely uncover more about this enigmatic protein and its intricate relationships with chromatin structure and gene expression.