JUST PUBLISHED: the roles of protein s-palmitoylation in cancers: from dynamic modulation to therapeutic potential.
Category: biotech/medical – Page 6
Designed to remember
In a new Science study, researchers report that specific regions dense in cytosine and guanosine dinucleotides are epigenetically modified during inflammation to enable gene expression and that these changes persist during the animal’s lifetime.
The finding has implications for understanding how the genome determines the longevity of memory, which affects tissue fitness.
Learn more in a new Science Perspective.
Specific DNA sequence features encode the persistence of epigenetic memory of inflammation.
Guillaume Blot and Przemyslaw Sapieha Authors Info & Affiliations
Science
How stimulating the vagus nerve could protect the brain from Alzheimer’s disease
Developing tau tangles doesn’t mean a person has Alzheimer’s disease – in fact, it happens to nearly everyone to varying degrees. But because these changes start in the locus coeruleus, some brain researchers – myself included – see this area as a canary in the coal mine for developing Alzheimer’s disease.
We are exploring whether stopping or slowing down tau tangles in this brain region, or otherwise maintaining its health, may be a way to interrupt how the disease ultimately unfolds and to prevent other aspects of cognitive aging.
Emerging research from my lab and others is investigating the idea that a therapy called vagus nerve stimulation, which is already widely used for other health conditions, could be one way of keeping the locus coeruleus functioning properly.
Longevity Isn’t Equal: Why Life-Extending Treatments May Be a “Biological Lottery”
Extending life is only part of the goal in aging research. Scientists also want more people to reach old age in good health, with fewer differences in when individuals die. This ideal outcome is often described as “squaring the survival curve,” where most deaths are pushed into a narrow window late in life rather than spread out across many years.
To test how close current science comes to that goal, University of Sydney researchers revisited a large meta-analysis of studies in vertebrates. They focused on three widely studied interventions: dietary restriction, rapamycin, and metformin. While all are linked to longevity, they work in different ways.
Dietary restriction involves reducing calorie intake without causing malnutrition. It has been known for more than a century to extend lifespan in animals and is thought to act in part by dialing down a key cellular growth pathway called mTORC1, which helps regulate metabolism and aging. Because strict diets are difficult to maintain, scientists have searched for drugs that mimic these effects. Rapamycin directly blocks mTORC1 activity, while metformin, a common diabetes medication, influences the same pathway indirectly by altering how cells sense energy levels.
Mesothelioma: a systemic therapy clinical trials snapshot
Systemic therapy targets in mesothelioma.
Recent changes to clinical practice have made modest improvements in 1– 2-year survival, but longer-term survival remains unchanged, and durable benefit is very rare.
Combining immunotherapy with chemotherapy, particularly with novel bispecific agents, may result in more therapeutic modalities being administered together in the first-line setting. The current evidence for second-line treatments is sparse.
New targeted-therapy strategies are promising. Early-phase clinical trials are showing signals of efficacy in mesotheliomas harboring MTAP loss or inactivation of the Hippo pathway.
Further studies will be needed to robustly confirm clinical benefit. sciencenewshighlights ScienceMission https://sciencemission.com/Mesothelioma
Mesothelioma is a rare cancer that has seen few incremental improvements in survival over the past two decades. However, a significantly improved understanding of the underlying biology has led to new therapeutic advances with the potential to improve clinical outcomes. In this review, we take a snapshot of the current systemic therapy research landscape, with our goal to forecast the trajectory of drug development for mesothelioma over the next half-decade. In our current census, we identify 106 active trials including systemic therapies: 20 (19%) are molecularly targeted, 26 (25%) include immunomodulation, and 12 (11%) combining immunotherapy with antiangiogenic therapies. Collectively, the landscape of therapeutic innovation for mesothelioma is expanding, bringing hope that improvements in life expectancy may follow.
Molecular Markers of Blood Cell Populations Can Help Estimate Aging of the Immune System
Aging of the immune system involves functional changes in individual cell populations, in hematopoietic tissues and at the systemic level. They are mediated by factors produced by circulating cells, niche cells, and at the systemic level. Age-related alterations in the microenvironment of the bone marrow and thymus cause a decrease in the production of naive immune cells and functional immunodeficiencies. Another result of aging and reduced tissue immune surveillance is the accumulation of senescent cells. Some viral infections deplete adaptive immune cells, increasing the risk of autoimmune and immunodeficiency conditions, leading to a general degradation in the specificity and effectiveness of the immune system in old age.
Mineral and bone effects of EPT
Highlighting the potential of PTH1R receptor agonist therapy in autosomal dominant hypocalcemia type 1
https://doi.org/10.1172/JCI201759 In this Research Letter, Rajesh V. Thakker & team report on the use of Eneboparatide in mice with ADH1, which increased serum calcium levels without increasing urine calcium.
3Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, United Kingdom.
4Endocrine Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
5William Harvey Research Institute, London School of Medicine, Queen Mary University of London, London, United Kingdom.
Advancements in organoid models emulating metastatic niches
Metastatic niche in organoid models.
The mortality rate of cancer patients remains high, mainly due to the lack of metastasis-tailored treatments, highlighting the need for alternative experimental approaches that capture metastatic development in a human context.
Human-induced pluripotent stem cell derived organoids cocultured with cancer cells (‘chimeroids’) have the potential to emulate aspects of colonized organ specific microenvironments and offer an alternative platform for target identification and drug discovery, as these models are amenable to scalable genetic and chemical perturbation screens.
Conceptually, organoid models have progressed from epithelial-only organoids to multilineage, niche enriched systems incorporating stromal, vascular, and tissue-resident immune components, thereby bringing in vitro models closer to organ-specific metastatic microenvironments.
Yet no single organoid model fully recapitulates the entire complexity of an organ in vivo; thus, model selection must be driven by the specific scientific question, ensuring that the relevant stage of metastatic development and organ microenvironment are appropriately represented. ScienceMission sciencenewshighlights https://sciencemission.com/organoid-models-emulating-metastatic-niches
Metastases cause most cancer-related deaths, underscoring the need for therapies targeting metastatic stages, including the tumor microenvironment. Yet translating biological insights into treatments remains difficult. Preclinical metastasis research largely relies on rodent models, which have species-specific limitations and are incompatible with large-scale perturbation screens in a human context. Human organoids aim to emulate organ microenvironments in vitro and, when cocultured with cancer cells, can provide complementary models. These ‘chimeroids’ may enable scalable studies of cancer–microenvironment interactions and support genetic and pharmacological screens to discover new targets, offering insights into the final, often lethal step of metastasis—tissue colonization.
Effects of Exercise and Intensive Vascular Risk Reduction on Cognitive Function in Older Adults: A Randomized Clinical Trial
In this multicenter randomized clinical trial, 24 months of moderate to vigorous aerobic exercise, intensive pharmacological reduction of blood pressure and serum LDL cholesterol, or the combination of these interventions did not significantly improve global cognitive function compared to usual care in older adults with hypertension and either family history of dementia or subjective cognitive decline.
Exercise and intensive vascular risk reduction each improved cardiovascular parameters, but no group differences were observed for changes in the Preclinical Alzheimer Cognitive Composite or NIH Toolbox Cognition Battery scores.
Question Can exercise, intensive pharmacological reduction of blood pressure (BP) and serum low-density lipoprotein cholesterol (LDL-C), or the combination of these interventions improve cognitive function in older adults with family history of dementia and/or self-reported subjective cognitive decline?
Findings In this randomized clinical trial of 513 participants, moderate to vigorous aerobic exercise training, intensive pharmacological lowering of BP and serum LDL-C, or both did not result in statistically significant differences in improvements in global cognitive function over 24 months.
Meaning The findings do not provide evidence in support of exercise, intensive reduction of BP and serum LDL-C, or both for improving cognitive function in older adults with family history of dementia and/or self-reported subjective cognitive decline.
Rebuilding the bridge: Functional AVN cells for cardiac repair
Directing the differentiation of human pluripotent stem cells into atrioventricular node-like cells is a critical strategy for restoring atrioventricular node dysfunction in patients. In this issue, Lohbihler et al. define a BMP2-driven protocol to engineer functional conduction bridges that recapitulate the heart’s native “gatekeeper” properties in vivo.