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Chronic Illness

Mimicking Embryonic Growth to Break Barriers in Organoid Research

Organoids are made to model human organs and are promising for research and therapy, but there are limitations in their growth and function. A recent study found that placenta-derived IL1 under hypoxic conditions, can greatly increase growth of human stem cell-derived liver organoids. By promoting liver progenitor cell expansion through a specific signaling pathway, this method offers a promising route to improve organoid models and regenerative medicine.

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Organoids are small-scale models that mimic human organs. These models have the potential to revolutionize medical research by allowing scientists to understand diseases and test treatments more effectively. Unfortunately, growing organoids that are large and functional enough to be truly useful is a significant challenge. One of the main limitations in organoid growth is the intricate chemical signaling and cellular interactions that occur during fetal development.

Researchers at The University of Tokyo have made an important discovery in this field by finding that placenta-derived IL1α under hypoxic conditions can greatly increase the growth of human stem cell-derived liver organoids. By promoting liver progenitor cell expansion through a specific signaling pathway, this method offers a promising route to improve organoid models and regenerative medicine.

The researchers studied mouse embryo development and found that during a specific stage of liver development (between embryonic days 10 and 11), mouse embryos experience a unique environment characterized by localized blood perfusion and hypoxic conditions. Critically, during this stage, the placenta releases various growth factors that play a pivotal role in the development of the liver.

By identifying and isolating these placental factors, the team focused on a specific protein called IL1α. They introduced this factor to human induced pluripotent stem cell (hiPSC)-derived liver organoids under carefully controlled hypoxic conditions and followed it with controlled oxygenation, mimicking the natural developmental environment. This approach led to remarkable results, as the organoids grew up to five times larger than controls and exhibited improved functional characteristics.

The team demonstrated that placenta-derived IL1α significantly enhanced the proliferation of liver progenitor cells called hepatoblasts. They also performed single-cell RNA sequencing analysis, which revealed that IL1α influences hepatoblast expansion through the SAA1-TLR2-CCL20-CCR6 signaling pathway. These insights provide a clearer understanding of how external factors regulate liver development and offer a novel approach to enhancing organoid growth.

These findings could have significant implications in the medical field. By refining techniques to deliver placenta-derived factors in a controlled manner, future research could pave the way for more advanced organoid-based disease models and potentially facilitate the development of lab-grown organs for transplantation. The team suggests that similar approaches might be applicable to developing organoids for other organ types, opening new frontiers in personalized medicine and regenerative therapies.

While the researchers acknowledge that their approach does not yet fully replicate the dynamic in vivo conditions of fetal liver development, their work marks a critical step toward overcoming existing barriers in organoid research. They suggest that future studies should focus on designing perfusion-based culture systems that can continuously supply placenta-derived factors and oxygen, better simulating the physiological conditions of developing organs.

Overall, by leveraging insights from developmental biology, this research not only enhances our understanding of liver growth but also highlights new pathways for improving the scalability and functionality of hiPSC-derived organoids.

Animal Learning and Intelligence

Harnessing the Power of Nature: How Black Tea and Berries Can Promote Healthy Aging

Higher intakes of black tea, berries, citrus fruits and apples could help to promote healthy aging, new research has found.

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As we age, our bodies undergo various changes that can impact our physical and mental well-being. While some of these changes are inevitable, research suggests that incorporating certain foods into our diet can help promote healthy aging.

A recent study conducted by researchers from Edith Cowan University, Queen’s University Belfast, and Harvard T.H. Chan School of Public Health found that consuming higher intakes of black tea, berries, citrus fruits, and apples could lower the risk of key components of unhealthy aging, including frailty, impaired physical function, and poor mental health.

The study analyzed data from 62,743 women and 23,687 men over a period of 24 years. The findings revealed that women with the highest flavonoid intakes had a 15% lower risk of frailty, a 12% lower risk of impaired physical function, and a 12% lower risk of poor mental health compared to those with the lowest intakes.

While fewer associations were observed in men, higher flavonoid intake was still linked to a lower risk of poor mental health. The researchers suggested that regularly consuming flavonoid-rich foods could support healthier aging by reducing the risk of frailty, physical decline, and poor mental health.

The study’s lead author, Dr. Nicola Bondonno from Edith Cowan University, emphasized the importance of medical research in promoting healthy aging. “Our goal is not just to help people live longer but to ensure they stay healthy for as long as possible,” she said.

Professor Aedin Cassidy from Queen’s University Belfast added that flavonoids have been shown to reduce oxidative stress and inflammation, supporting blood vessel health, and even helping to maintain skeletal muscle mass – all of which are crucial for preventing frailty and maintaining physical function and mental health as we age.

The researchers noted that incorporating three servings of flavonoid-rich food into one’s diet could lead to a 6% to 11% lower risk across all three aging outcomes in females, and a 15% lower risk of poor mental health in males. This highlights the potential for simple dietary modifications to impact overall quality of life and contribute to the optimisation of healthy aging.

Overall, this study underscores the importance of incorporating flavonoid-rich foods into our diet to promote healthier aging. As Professor Eric Rimm from Harvard T.H. Chan School of Public Health noted, “These findings underscore the potential for simple dietary modifications to impact overall quality of life and contribute to the optimisation of healthy aging.”

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Unlocking the Secrets of Human Longevity: A Decade of Discovery

Researchers participating in the Cilento Initiative on Aging Outcomes or CIAO study will gather in Acciaroli (Pollica-Cilento) Salerno, Italy to review a decade of work and plan their next steps. Launched in 2016, the CIAO study seeks to identify key factors (biological, psychological and social) that promote healthy aging and extreme longevity.

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The Cilento Initiative on Aging Outcomes (CIAO) study has been a decade in the making, and this month, researchers will gather in Acciaroli, Italy to review their progress and plan their next steps. Launched in 2016, the CIAO study seeks to identify key factors that promote healthy aging and extreme longevity.

The region of Cilento in southern Italy is home to a remarkable 300 residents who are over 100 years old and in robust health. This area was also the original source of research for Ancel Keys, the American physiologist who studied the influence of diet on health and promoted the benefits of the Mediterranean diet.

Scientists hope to reveal the longevity secrets of the Cilento region by using an array of tools to measure metabolomics, biomes, cognitive dysfunction, and protein biomarkers for risk of heart disease, Alzheimer’s, kidney disease, and cancer. They will also conduct psychological, social, and lifestyle surveys to gain a more comprehensive understanding.

“There is no single secret to living a long, healthy life,” said Salvatore Di Somma, MD, the study’s lead Italian investigator. “It is many secrets, most of which we are only beginning to understand and more importantly, learn how they might be applied to the well-being of everybody.”

The CIAO study is a multi-institution collaboration that includes Sanford Burnham Prebys, an independent nonprofit biomedical research institute in San Diego, the Sanford Stem Cell Institute at University of California San Diego, University La Sapienza in Rome, and Great Health Science.

A symposium will take place on May 22-23, featuring scientists describing their work and findings. The event is titled “CIAO Study: A decade of science on healthy aging, stem cells, and the revealed secrets of longevity.” Understanding how we age and how we might age better is a timeless pursuit, said David Brenner, MD, president and CEO of Sanford Burnham Prebys.

Current CIAO projects are leveraging genetic, epigenetic, transcriptomic, metabolic, proteomic, and environmental analyses to identify key contributors to extreme longevity. Researchers are using induced pluripotent stem cell (iPSC) derived from the centenarians to model age-related and metabolic stresses in human 3D organoids.

“This study will provide new insights into the development of regenerative medicine strategies for promoting healthy aging and treating age-related conditions,” said Tatiana Kisseleva, MD, PhD, professor of surgery at UC San Diego School of Medicine. Preliminary findings are expected to be presented at the symposium.

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Chronic Illness

The Immune System’s Hidden Role in Mental Health Conditions

Depression, schizophrenia and other mental health conditions affect 1 in 4 people in their lifetime, but mechanisms underlying these conditions are poorly understood. New research has linked the body’s immune response with schizophrenia, Alzheimer’s disease, depression, and bipolar disorder. The study demonstrates mental health conditions might be affected by the whole body as well as changes in the brain. The findings could pave the way for better treatments of some mental health conditions.

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The world of psychology has long been dominated by the idea that mental health conditions such as depression, schizophrenia, and bipolar disorder are solely the result of imbalances in brain chemistry. However, new research suggests that there is more to it than meets the eye – or rather, more to the body. A groundbreaking study led by researchers at the University of Bristol has made a startling discovery: the immune system plays a significant role in these conditions.

The study, which was published in a recent scientific paper, used a computational approach called Mendelian randomization to examine the relationship between immunological proteins and seven neuropsychiatric conditions, including depression, anxiety, schizophrenia, bipolar disorder, Alzheimer’s disease, autism, and ADHD. The researchers found that 29 immune response-related proteins were potentially involved in these conditions.

One of the most significant findings was that overactivity of the immune system could contribute to the cause of mental health conditions. This challenges the traditional view that depression and schizophrenia are solely caused by imbalances in brain chemicals such as serotonin and dopamine. In fact, the study suggests that a new paradigm is needed – one where mental health conditions are viewed as affecting the whole person, not just the mind.

The implications of this research are profound. It could lead to the development of novel therapeutics for mental health conditions by targeting immune response-related proteins. Furthermore, it challenges the centuries-old dichotomy between body and mind, suggesting that we should consider depression and schizophrenia as conditions affecting the whole person.

As Professor Golam Khandaker, one of the researchers involved in the study, noted: “Our study demonstrates that inflammation in the brain and the body might influence the risk of mental health conditions.” The next step is to further evaluate causality, understand precise mechanisms from inflammation to symptoms, and therapeutic potential – does modulating immune pathways improve symptoms of these conditions?

This research has far-reaching implications for our understanding of mental health conditions and their treatment. It highlights the importance of considering the immune system as a vital component in understanding and addressing these disorders.

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