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Universal Vaccines: Targeting Multiple Coronaviruses with T Cell Immunity

by Dr. Michael Lee – Health Editor August 8, 2025

written by Dr. Michael Lee – Health Editor

Scientists Identify Key Targets for “Universal” Coronavirus Vaccine, Boosting Hope for Future Pandemic Defense

La Jolla, CA – In a significant breakthrough published this week in Cell, researchers at the La Jolla Institute for Immunology (LJI) have pinpointed highly conserved regions within coronaviruses that consistently trigger a robust T cell response across multiple strains – including those yet to emerge.This revelation paves the way for the progress of next-generation vaccines capable of providing broader, more durable protection against a wide range of coronaviruses, perhaps mitigating the impact of future pandemics.

The ongoing threat of evolving viruses like SARS-CoV-2 has underscored the limitations of current vaccines, which primarily focus on generating neutralizing antibodies. While antibodies are crucial for preventing initial infection, they are frequently enough less effective against new variants. This new research highlights the critical role of T cells, a component of the immune system that recognizes infected cells and clears the virus, offering a more stable and long-lasting defense.

“It is important to induce a neutralizing antibody response,” explains LJI researcher Alessandra Grifoni, “But we’ve shown that T cells are much more stable in the context of viral variants, and that is because T cells look at all the proteins of the virus.”

The team, led by Grifoni, leveraged the power of data science and the publicly available Immune epitope Database (IEDB) – a resource maintained by LJI scientists – to analyze data on over 200 coronavirus epitopes (the parts of a virus that trigger an immune response) identified by researchers globally.By comparing these epitopes across different coronaviruses, and utilizing bioinformatic tools including artificial intelligence, they identified conserved regions – areas of the viral genome that remain largely unchanged despite mutations.

these conserved regions, including some within the “spike” protein but also extending beyond it, consistently elicited a strong T cell response. Understanding which of these regions spark the strongest response is key to designing vaccines that can induce broad cross-reactivity.

“the idea is that if a new coronavirus emerges, we might not be able to protect from the infection, but we might be able to protect from hospitalization,” Grifoni stated. This suggests that even if a future coronavirus evades initial antibody defenses, a strong T cell response could prevent severe illness.The research isn’t limited to SARS-CoV-2. Grifoni emphasizes the potential to apply this “research pipeline” to other respiratory viruses like measles, Nipah virus, and enteroviruses, and also viruses causing hemorrhagic fevers like Lassa and Junin. Her lab is already collaborating with research groups exploring applications across diverse viral families.

“We need to fill the knowledge gaps,” Grifoni said, highlighting the ongoing need for thorough data collection and analysis to prepare for future viral threats.

Study details:

Title: Highly conserved Betacoronavirus sequences are broadly recognized by human T cells
Authors: Tertuliano Alves Pereira Neto, Christian Zmaseck, Liliana Avalos, John Sidney, Raphael Trevizani, Elizabeth Phillips, Simon Mallal, April Fraizer, Gene S. Tan, Richard H. Scheuermann, and Alessandro Sette.
Journal: Cell
DOI: doi.org/10.1016/j.cell.2025.07.015
* Source: La Jolla Institute for Immunology (https://www.lji.org/news-events/news/post/lji-covid-universal-vaccine-research/)

August 8, 2025 0 comments

Health

Starfish compound overcomes drug resistance in prostate cancer models

by Dr. Michael Lee – Health Editor August 5, 2025

written by Dr. Michael Lee – Health Editor

Starfish Compound Shows Promise Against Drug-Resistant Prostate Cancer

Marine Glycoside Could Enhance Chemotherapy Efficacy

A novel compound extracted from starfish, pacificusoside C (PaC), is showing significant potential in combating aggressive prostate cancer. Researchers have found it can effectively kill treatment-resistant cancer cells and may boost the effectiveness of existing chemotherapy drugs.

Exploring Marine Molecules for Cancer Therapy

Prostate cancer affects over 1.3 million men globally each year, and many cases become resistant to standard treatments like androgen deprivation therapy (ADT). This resistance often stems from complex cellular pathways such as NF-κB and PI3K/AKT/mTOR, which are difficult to target. Scientists are now investigating marine organisms, like starfish, for naturally occurring compounds with therapeutic properties. These marine triterpene glycosides, like those studied from the starfish Solaster pacific, can disrupt cancer cell membranes and influence survival mechanisms.

Groundbreaking Study Details Potent Cytotoxicity

A recent study published in Scientific Reports explored the anticancer effects of pacificusoside C (PaC) and cucumariosides C1 (CuC1)/C2. These compounds were tested against various prostate cancer cell lines, including those resistant to docetaxel (PC3-DR) and aggressive variants like DU145. The results highlighted CuC1 as the most potent, demonstrating effectiveness across multiple cancer types with low micromolar concentrations. Importantly, CuC1 showed minimal cross-resistance with docetaxel-resistant cells.

The study also examined the compound’s interaction with key cellular processes. Researchers observed that CuC1 activates stress and cell death pathways, including necroptosis and apoptosis, by targeting specific kinases like p38 and ERK1/2. This mechanism appears to precede cell death, suggesting a multi-pronged attack on cancer cells.

Furthermore, CuC1 effectively bypassed the P-glycoprotein (P-gp) efflux pump, a common mechanism of drug resistance. This finding is crucial as it means the compound is not actively expelled from cancer cells, a common problem with conventional chemotherapy.

Synergistic Effects with Chemotherapy

A key finding of the research is CuC1’s ability to enhance the efficacy of established chemotherapy drugs. When combined with agents like cisplatin, carboplatin, docetaxel, and cabazitaxel, CuC1 demonstrated significant synergistic effects, particularly in resistant cell lines. This suggests a potential for combination therapies that could overcome treatment failures.

“The multifaceted mechanism involving membrane effects plus coordinated stress-kinase rewiring may slow resistance evolution,” the study authors noted. This dual action—directly killing cancer cells and sensitizing them to other treatments—offers a promising new avenue for managing difficult-to-treat prostate cancers.

Future Directions and Clinical Hope

While the results are encouraging, the study acknowledges a limitation: CuC1 showed limited selectivity, being slightly more toxic to non-cancerous cells than some other compounds tested. However, it avoided the DNA cross-linking associated with platinum-based drugs.

The global burden of drug-refractory prostate cancer is substantial. According to the National Cancer Institute, approximately 10-20% of men with advanced prostate cancer develop metastatic castration-resistant prostate cancer (mCRPC), highlighting the urgent need for new therapeutic strategies (National Cancer Institute, 2024).

Further research, including in vivo studies, is essential to confirm the safety and efficacy of these marine triterpene glycosides. If successful, these compounds could become valuable additions to the therapeutic arsenal, potentially improving survival rates and the quality of life for patients battling resistant prostate cancer.

August 5, 2025 0 comments

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Scientists reveal how rare gene mutations drive schizophrenia risk

by Dr. Michael Lee – Health Editor August 4, 2025

written by Dr. Michael Lee – Health Editor

New Genes Linked to Schizophrenia Risk Uncovered

Genetic Breakthrough Offers Clues to Brain Signaling Disruptions

A significant study has pinpointed rare genetic variations that can disrupt brain signaling and structure, potentially unlocking new avenues for treating schizophrenia.

Unraveling Genetic Links

Researchers have identified specific genes that carry a higher risk of contributing to schizophrenia. This comprehensive analysis, published in Nature Communications, utilized whole-exome sequencing to examine these genetic factors.

Scientists reveal how rare gene mutations drive schizophrenia risk. Image Credit: magic pictures / Shutterstock

Schizophrenia, a severe mental health condition affecting cognition and behavior, is known to have a complex genetic basis. While common genetic variants play a role, this research delves into the impact of less frequent, but more potent, genetic alterations.

Key Findings Emerge

The study analyzed data from thousands of individuals, comparing schizophrenia cases with control groups. A significant finding was the identification of two novel genes, ZNF136 and STAG1, as exome-wide significant risk factors for schizophrenia. STAG1, involved in organizing the 3D structure of the genome, may impair neurodevelopment when its function is disrupted.

Additionally, six other genes—SLC6A1 (a GABA transporter), PCLO, ZMYND11, BSCL2, KLC1, and CGREF1—were found to be associated with an increased risk at a false discovery rate of less than 5%.

The research also highlighted convergence between these rare genetic variants and common genetic signals associated with schizophrenia, particularly for STAG1 and KLC1. Certain variants within these genes have also been linked to other neurological conditions.

Broader Implications for Neurological Disorders

Notably, several of the newly identified schizophrenia risk genes showed associations with rare genetic variants in conditions such as bipolar disorder, developmental disorders, epilepsy, and autism spectrum disorder. This suggests potential pleiotropic effects, where a single gene can influence multiple traits or conditions, hinting at shared underlying biological mechanisms.

For instance, SLC6A1 missense variants were associated with a range of disorders, including epilepsy, ASD, DD, and schizophrenia. Similarly, STAG1, ZMYND11, and CGREF1 showed significant overlaps in their associations across these diverse neurodevelopmental and psychiatric conditions.

The study underscores the critical role of chromatin organization and GABAergic signaling in the neurobiology of schizophrenia, offering a more refined understanding of the disorder’s origins.

As of 2023, approximately 1 in 300 people worldwide will develop schizophrenia in their lifetime, according to the World Health Organization (WHO).

August 4, 2025 0 comments

Health

UCSF discovery points to new strategies for Alzheimer’s treatment

by Dr. Michael Lee – Health Editor July 28, 2025

written by Dr. Michael Lee – Health Editor

Alzheimer’s Protein Breakdown Mechanism Uncovered

Brain’s Immune Cells Hold Key to Clearing Toxic Buildup

A groundbreaking discovery by UCSF scientists sheds light on how the brain’s own immune cells can combat Alzheimer’s disease by clearing harmful protein clumps.

Microglia’s Crucial Role Revealed

Researchers have identified a specific molecular receptor, ADGRG1, that acts as a crucial “on-switch” for microglia, the brain’s primary immune cells. This receptor enables them to effectively engulf and digest amyloid beta, a protein notorious for forming damaging plaques in Alzheimer’s patients.

Without ADGRG1, microglia show a significantly diminished ability to clear these toxic proteins. Studies using a mouse model of Alzheimer’s disease demonstrated that the absence of this receptor led to a rapid accumulation of amyloid plaques, resulting in neurodegeneration and impaired learning and memory.

“We think this receptor helps microglia do their job of keeping the brain healthy over many years.”

—Xianhua Piao, MD, PhD, Physician-Scientist, Department of Pediatrics, University of California – San Francisco

Genetic Clues Link Receptor to Disease Severity

Further analysis of human brain gene expression data revealed a strong correlation between ADGRG1 levels and Alzheimer’s severity. Individuals with milder forms of the disease exhibited microglia rich in ADGRG1, suggesting effective plaque clearance. Conversely, those with severe Alzheimer’s had significantly lower ADGRG1 levels, correlating with widespread plaque proliferation.

According to the Alzheimer’s Association, over 6 million Americans are currently living with Alzheimer’s disease, a number projected to rise significantly in the coming years (Alzheimer’s Association 2024).

Therapeutic Potential for ADGRG1

ADGRG1 belongs to the G protein-coupled receptor family, a class of molecules frequently targeted in drug development. This characteristic bodes well for the potential translation of this discovery into novel Alzheimer’s therapies.

“Some people are lucky to have responsible microglia,” stated **Piao**. “But this discovery creates an opportunity to develop drugs to make microglia effective against amyloid-beta in everyone.”

July 28, 2025 0 comments

Health

Gene-Edited Mosquitoes Drive Near-Zero Malaria Transmission

by Dr. Michael Lee – Health Editor July 25, 2025

written by Dr. Michael Lee – Health Editor

Here’s a breakdown of the provided text, focusing on the key findings and implications:

Core Finding:

The study demonstrates that a specific genetic modification in the mosquito Anopheles stephensi, specifically a single amino acid change in the FREP1 gene (FREP1Q224), can make the mosquitoes largely resistant to malaria parasites. This resistance is achieved by biasing the inheritance of this protective allele through a “linked allelic drive” mechanism.

Key Results:

Malaria Refractoriness:
The FREP1Q224 allele considerably reduced the number of Plasmodium falciparum (human malaria) sporozoites in mosquito salivary glands, effectively preventing transmission.
It also reduced oocyst development in the midgut.
this refractoriness was observed even against a different rodent malaria parasite (Plasmodium berghei), suggesting broad-spectrum activity.
The resistance was homozygous-dependent, meaning both copies of the FREP1 gene needed to have the protective allele for full effect.Heterozygotes showed no significant protection.

Efficient Allelic Drive:
A gene-editing system (guide RNA + Cas9) was used to convert the natural allele (FREP1L224) to the protective allele (FREP1Q224) in mosquitoes.
This conversion process was highly efficient, achieving protective allele frequencies of up to 93% in the second generation.
In population cages, the protective allele rapidly increased in frequency, reaching over 90% within 10 generations, starting from a 25% initial frequency.
The drive mechanism was so effective that it outcompeted other alleles, even those on congenic chromosomes, indicating it wasn’t due to a general fitness advantage of the protective allele itself.

Mechanism of Spread:
Bayesian modeling suggested that the rapid spread of the protective allele was driven by a combination of:
High allelic conversion rates.
Low rates of non-functional resistance alleles.
“Lethal sterile mosaicism,” where mosquitoes with onyl one copy of the protective allele (heterozygotes) and exposed to the gene-editing machinery experienced severe fitness penalties due to mutations in their own genes.

Population-Level Impact:
Mosquito populations that had undergone the allelic drive showed near-complete suppression of Plasmodium falciparum oocysts,confirming they had become largely transmission-refractory.

Conclusions and Implications:

Realistic Malaria Control strategy: The study presents a promising and realistic strategy for malaria control by genetically modifying mosquitoes to be refractory to the parasite.
Population-Kind Approach: The protective allele preserves normal mosquito biology and doesn’t impose significant fitness costs on the mosquitoes themselves, making it a perhaps “population-friendly” approach.
Complementary to Existing Methods: This genetic approach can complement existing malaria control tools like bed nets, indoor spraying, and drugs, which are increasingly threatened by resistance.
Broader Applications: The same genetic framework could be used to reintroduce insecticide sensitivity or deploy other beneficial host traits in mosquitoes.
Pre-Deployment Considerations: The authors emphasize the critical need for rigorous ecological, ethical, and governance frameworks, and also confinement strategies, before any real-world deployment.

In essence, the study successfully engineered mosquitoes to be malaria-resistant and demonstrated a method to rapidly spread this resistance through a mosquito population using gene drive technology.

July 25, 2025 0 comments

Health

Gut bacteria send direct signals to the brain to stop you from overeating

by Dr. Michael Lee – Health Editor July 24, 2025

written by Dr. Michael Lee – Health Editor

Gut Bacteria Signal Brain to Curb Appetite

New Study Reveals Direct Microbial Feedback Loop

A groundbreaking study has unveiled a direct communication pathway from gut microbes to the brain, influencing our decision to stop eating. This discovery opens exciting new avenues for understanding appetite and metabolic health.

The Neurobiotic Sense Uncovered

Researchers have identified a novel gut-brain sensory mechanism, dubbed the “neurobiotic sense.” This system allows the body to interpret microbial patterns, directly impacting feeding behavior. The findings, published in the journal Nature, suggest a sophisticated interplay between our internal microbiome and our brain’s satiety signals.

Gut bacteria send direct signals to the brain to curb appetite, a new study reveals.

While the gut’s neural network for sensing nutrients is known, a direct neural circuit for microbial signals remained elusive. This new research pinpoints specific cells in the small intestine, known as PYY-labeled neuropod cells, which express Toll-like receptor 5 (TLR5). This receptor is crucial for detecting bacterial flagellin, a common component of bacterial flagella.

Flagellin: The Microbial Signal

Flagellin levels have been observed to increase in stool after meals. The study demonstrated that these PYY-labeled cells, rather than vagal neurons themselves, utilize TLR5 to sense flagellin. This sensing triggers the release of peptide YY (PYY), a satiety-inducing protein.

When researchers genetically removed TLR5 from these PYY-labeled cells in mice, the animals exhibited increased meal sizes and longer feeding durations. This weight gain was observed independently of immune responses or metabolic disruptions, highlighting the specific role of this microbial sensing pathway.

Experiments confirmed that higher colonic flagellin levels correlate with feeding, and this signal is transmitted via the PYY-labeled cells to the vagus nerve. Blocking the PYY receptor (Y2R) on vagal neurons abolished this nerve activity in response to flagellin, confirming the signaling cascade.

Real-Time Appetite Regulation

Further investigation into real-time feeding behavior showed that administering flagellin via enema significantly reduced food intake in mice within 20 minutes. This effect was absent in mice lacking TLR5 in their PYY-labeled cells, proving the pathway’s direct impact.

Even in germ-free mice, flagellin alone was sufficient to suppress food intake, indicating that the sensing of this specific microbial pattern can regulate appetite without the presence of a full microbiome. This suggests that flagellin sensing is a potent, standalone signal for satiety.

The findings are particularly relevant given that obesity rates continue to rise globally. In the United States, over 42% of adults aged 20 and over have obesity, according to the CDC’s latest available data (CDC 2024).

This discovery of the “neurobiotic sense” provides a critical insight into how our gut microbiome directly communicates with our brain to regulate fundamental behaviors like eating. Future research may explore how manipulating this pathway could offer novel therapeutic strategies for appetite control and metabolic disorders.

July 24, 2025 0 comments

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