Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog – Page 3

Get the latest international news and world events from around the world.

Log in for authorized contributors

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.

Continue reading “Advancements in organoid models emulating metastatic niches” | >

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.

Electrons in moiré crystals explore higher-dimensional quantum worlds

The electrons that power our society flow left and right through the circuitry in our electronics, back and forth along the transmission lines that make up our power grid, and up and down to light up every floor of every building. But the electrons in newly discovered “moiré crystals” move in much stranger ways. They can move left and right, back and forth, or up and down in our three-dimensional world, but these electrons also act as if they can teleport in and out of a mysterious fourth dimension of space that is perpendicular to our perceivable reality. Physicists have found that this strange, newly discovered quantum behavior has nothing to do with the electrons themselves and everything to do with the strange material environment in which they live.

The electrons in moiré crystals leap into a fourth dimension through a process called “quantum tunneling.” While a soccer ball sitting at the bottom of a hill will stay put until someone retrieves it, a quantum particle in a valley can jump out all on its own. Quantum tunneling may seem magical to us, but it is quite commonplace in the microscopic quantum world, on the length scales of atoms. Quantum tunneling is also important on larger length scales, particularly in large superconducting circuits that underlie an emerging landscape of quantum technology, as recognized by the 2025 Nobel Prize in Physics.

However, quantum tunneling in moiré crystals is different, in that once an electron tunnels, physicists have now measured that it acts as if it had tunneled into a completely different world and come back again, as if it had been transported through a fourth “synthetic” dimension.

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.

Targeting metabolism to combat anticancer and antibacterial drug resistance

Combating anticancer and antibacterial drug resistance by metabolic targeting.

Bacteria and cancer cells activate defense mechanisms driven by central carbon and amino acid metabolism to overcome drug-induced stress.

Drug tolerance and persistence are driven by a dormant state in bacteria, whereas cancer cells upregulate energy metabolism to withstand prolonged drug exposure.

Biofilms, granulomas, and the tumor microenvironment share hypoxic and acidic conditions, where cells rely on anaerobic and lipid metabolism for survival.

Macrophage immunometabolism influences disease progression in tuberculosis and cancer. Common approaches for overcoming drug resistance include blocking metabolic targets that enhance drug lethality and synergistic drug combinations.

Drug repurposing, dietary interventions, and immunotherapy have shown use in cancer, but their antibacterial potential remains underexplored. sciencenewshighlights ScienceMission https://sciencemission.com/Targeting-metabolism-to-combat-anticancer

Continue reading “Targeting metabolism to combat anticancer and antibacterial drug resistance” | >

Restoring mitochondrial function in dendritic cells to treat cancer

To counteract this effect, researchers introduced dendritic cells with high mitochondrial activity into tumors in preclinical mouse models, restoring immunogenic activity and improving tumor control.

Immunotherapies for cancer, such as immune checkpoint blockade, have greatly improved care for many malignancies, but have not been successful in all cancers. To determine if their findings could help make immunotherapy more effective in tumor-bearing mice, the investigators compared the therapeutic effects of administering dendritic cells with high mitochondrial activity in combination with immune checkpoint blockade with those of either treatment alone.

“We saw the most pronounced therapeutic effect in mice treated with the combination of dendritic cells that had high mitochondrial activity and immune checkpoint blockade,” said co-first author. “Those combinations synergistically slowed or stopped tumor growth and extended survival far more than either treatment alone.”

To test one combination therapy’s long-term effects, the researchers exposed treated mice to a new tumor months later. Those mice also stopped the new tumor’s growth, indicating durable, long-term immune memory was successfully established.

To better understand the relationship between mitochondrial function and dendritic cells, the researchers examined key metabolic pathways affected by the tumor microenvironment. They identified a signaling axis composed of two proteins, OPA1 and NRF1, that regulate communication between mitochondria and the nucleus. Their expression was greatly downregulated in dendritic cells during tumor progression. Within tumors, that circuit’s downregulation acts as a metabolic switch, in effect telling the cell that it is in an energy crisis, leading dendritic cells to shut down their nonessential functions, including immunogenic activity. Science Mission sciencenewshighlights.

Scientists have discovered how tumors disable immune “gatekeeper” cells that alert the rest of the immune system to the presence of cancer — and how restoring their energy production can improve immunotherapy. Dendritic cells activate the cytotoxic immune cells that destroy cancer. The researchers found that tumors reduce dendritic cell function by decreasing their mitochondrial fitness, thus preventing formation of the anticancer immune response.

Continue reading “Restoring mitochondrial function in dendritic cells to treat cancer” | >

A new era in childhood obesity

Childhood obesity!

Obesity associated with the melanocortin system can be diagnosed in childhood, including both monogenic and syndromic forms.

Genetic obesity is characterized by early onset and extreme hyperphagia, although there is no precise definition for these features.

Numerous polymalformative syndromes include obesity among their main phenotypic traits. Among these are ciliopathies, in which alterations in the neuronal ciliary system can disrupt hypothalamic proopiomelanocortin neuron signaling, helping to explain the hyperphagia and obesity frequently observed in some of these disorders.

Pharmacological treatment of patients with impairment of the leptin– melanocortin pathway can be classified into specific and nonspecific treatments.

The use of these therapies is expanding to new indications, and additional treatments are under clinical investigation for both monogenic and polygenic obesity sciencenewshighlights ScienceMission https://sciencemission.com/childhood-obesity-19506

Continue reading “A new era in childhood obesity” | >

Less is more: Reducing zinc to boost derived islet function and survival

Less is more: Reducing zinc to boost stem cell-derived islet function and survival.

Zinc is required for insulin packaging into secretory granules, yet reduced zinc transporter activity paradoxically enhances beta cell function. In this issue, Wang et al. show that pharmacologic inhibition of zinc transport in stem cell-derived islets activates AMPK signaling and improves maturation, hypoxia resistance, VEGFA expression, and graft performance.

/* */