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Category: biotech/medical – Page 129

Bacteria’s ‘mix-and-match’ code could create new cancer-fighting drugs

A team of researchers at the University of Warwick and Monash University has solved a puzzle that has stumped drug developers for decades: how bacteria naturally create multiple versions of powerful cancer therapies. The breakthrough could accelerate the development of new treatments for hard-to-treat cancers.

Harnessing bacterial enzymes to create drug variants, a strategy known as combinatorial biosynthesis, has long been a goal for scientists. But without understanding how these enzymes interact, progress has stalled.

Published in Nature Communications, the researchers have finally revealed how bacterial enzymes communicate and work together to assemble a family of related anticancer compounds. This family includes romidepsin (Istodax), a clinically approved blood cancer treatment. By understanding this “mix-and-match” process and replicating the principle in the lab, the researchers have established an approach to designing new therapies.

Haptoglobin phenotypes and structural variants associate with post-exertional malaise and cognitive dysfunction in myalgic encephalomyelitis

Myalgic encephalomyelitis (ME) is a chronic, multisystem illness characterized by post-exertional malaise (PEM) and cognitive dysfunction, yet the molecular mechanisms driving these hallmark symptoms remain unclear. This study investigated haptoglobin (Hp) as a potential biomarker of PEM severity and cognitive impairment in ME, with a focus on Hp phenotypes and structural proteoforms.

A longitudinal case–control study was conducted in 140 ME patients and 44 matched sedentary healthy controls. In the discovery phase, global plasma proteomic profiling was performed in 61 ME patients and 20 controls before and after a standardized, non-invasive stress protocol in order to induce PEM. Associations between Hp levels, phenotype, and cognitive performance were assessed. In the validation phase, plasma Hp concentrations and proteoform composition were analyzed in an independent cohort of 89 ME patients and 24 controls using high-performance liquid chromatography (HPLC).

ME patients demonstrated a significant reduction in Hp levels following post-exertional stress. Lower baseline Hp concentrations were associated with impaired cognitive performance. Hp phenotypes were differentially associated with symptom burden, with the Hp2-1 phenotype enriched in ME and linked to greater PEM severity and cognitive deficits compared to Hp1-1 and Hp2-2. HPLC analysis revealed altered Hp proteoform profiles in the Hp2-1 subgroup, including increased high-mass tetrameric and pentameric forms and shorter retention times indicative of structural changes. In contrast, the Hp1-1 phenotype was associated with milder symptoms and greater cognitive resilience.

Melatonin can be a safe and effective sleep aid for all ages but improper dosing leads to real harms

Melatonin—a go-to sleep aid for kids and adults alike in many households in America— continues to create media buzz, with conflicting messages that leave people uncertain about its safety.

Some headlines point to melatonin’s supposed immunity-boosting power, while others point to unestablished links between melatonin and heart failure.

I’m a pediatrician and sleep medicine doctor specializing in children, adolescents and adults.

New postnatal gene therapy offers hope for congenital hearing loss

Hereditary hearing loss affects millions globally, with mutations in the SLC26A4 gene among the most common genetic triggers, particularly across Asian populations. This condition leads to severe-to-profound deafness accompanied by inner ear malformations, such as an abnormally enlarged vestibular aqueduct and endolymphatic sac.

While gene replacement therapies have long held immense potential, experimental interventions have historically been restricted to the embryonic stage. Delivering genetic material before birth presents steep ethical and practical hurdles, creating a critical roadblock for real-world medical applications.

Brain aneurysm map reveals cell types tied to rupture risk

A new study from UC San Francisco shows how certain cells in the brain may cause aneurysms to weaken and rupture. It helps explain why some aneurysms burst while others do not and could lead to new ways of predicting and possibly preventing strokes.

Brain aneurysms are bulges in blood vessels that can go unnoticed for years. If they rupture, they can cause a severe and often deadly type of stroke. About one in 50 Americans has a brain aneurysm, but doctors still struggle to predict which ones are most dangerous.

The new study helps to unpack the biology behind these events by mapping the cells in artery walls and the interactions that weaken them.

Gold-laced nanoparticles could eventually spot and treat endometriosis without surgery

Endometriosis is a painful, common condition affecting women worldwide, but treatment and diagnosis options are scarce. A new University of Mississippi-led study may have found an answer to both problems.

Early results from a study published in Communications Chemistry show that gold-laced nanoparticles can hitchhike on white blood cells. By using those cells as a delivery vehicle, the team hopes to identify and treat endometriosis without repeated surgeries.

“Lots of women go through their lives being in enormous amounts of pain and thinking that it’s normal, and it’s not normal,” said Eden Tanner, assistant professor of chemistry and biochemistry, who authored the study with a team of Ole Miss researchers.

Fish-inspired sensor tracks how human heart tissue responds to disease and treatment

Engineers have developed a new way to monitor how tiny lab-grown human heart tissues beat—by effectively “listening” to the ripples they create. The team has created a wireless, noninvasive sensing platform that can biomechanically measure how strongly the miniature heart tissues, known as cardiac organoids, beat in real time. The research could help accelerate drug development, improve disease modeling and reduce reliance on animal testing, offering a more human-relevant way to study how the heart works.

Cardiac organoids are 3D clusters of human heart cells grown in a laboratory that are used to evaluate the safety and efficacy of new drugs prior to clinical trials, as well as study disease. While they don’t replicate the full structure of a human heart, they mimic key behaviors, especially how heart muscles contract when drugs are administered.

They are increasingly seen as a powerful alternative to animal models, which often fail to fully capture how human biology works.

Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC

BACKGROUND: Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis by undergoing phenotypic modulation from a quiescent, contractile state to a range of synthetic phenotypes, including fibroblast-like, macrophage-like, and lipid-laden foam cell–like states. However, a comprehensive multimodal characterization and understanding of the transcriptional programs driving these transitions remain incomplete. METHODS: To comprehensively define the phenotypic diversity of VSMCs during atherosclerosis progression, we performed in-depth profiling using cellular indexing of transcriptomes and epitopes by sequencing and bulk RNA sequencing in a VSMC-lineage–tracing atherosclerotic mouse model. Insights from these data sets guided the design of targeted in vitro experiments to investigate candidate regulatory mechanisms.

Rethinking mRNA vaccines: Liver targeting can suppress immunity, while muscle boosts it

A new study by researchers at the Icahn School of Medicine at Mount Sinai overturns a longstanding assumption about how mRNA vaccines generate immunity, revealing that certain non-immune cells help determine vaccine effectiveness.

The study, published in Nature Biotechnology, also introduces a powerful and versatile technology to control the expression of mRNA drugs, which the researchers demonstrate can enhance the effectiveness of mRNA cancer vaccines in preclinical studies of lymphoma. The paper is titled “mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.”

The findings provide a new framework for designing mRNA vaccines and mRNA therapeutics, with immediate implications for cancer immunotherapy, infectious disease vaccines, and gene-editing treatments.

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