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Category: biotech/medical – Page 156

Ultrasound-based technology to deliver large therapeutics into cancer cells

In the study, the authors equipped these microbubbles with synthetic nucleic acid strands designed to bind with specific biochemical receptors that appear on the cell membranes of cancer cells but not healthy cells. They then tried several combinations of ultrasound frequencies and intensities to find the perfect pairing for opening pores in the cell membranes to allow the PROTACs to enter.

Once the optimal settings were identified, the researchers validated the platform by attaching fluorescent molecules to the PROTACs. They conducted separate experiments on cancer cells and healthy cells to compare the delivery efficiency. After a minute of ultrasound exposure, the cells treated with SonoPIN glowed seven times brighter than those treated with traditional PROTAC delivery methods, indicating that they were taking in many PROTACs. This resulted in half of the cancer cells self-destructing, while 99% of the healthy cells remained viable.

Moving forward, the researchers plan to test this approach in mouse models and have already applied for a patent covering the work. By injecting the PROTACs and cancer-seeking microbubbles into their veins and focusing the ultrasound waves on tumor locations, they believe SonoPIN could form a highly potent cancer-killing technology with few side effects. sciencenewshighlights ScienceMission.

Engineers have demonstrated a technique that uses microbubbles and ultrasound to help relatively large cancer drugs enter tumor cells and cause them to self-destruct.

Dubbed “Sonoporation-assisted Precise Intracellular Nanodelivery”—or SonoPIN for short—the technology caused 50% of targeted cancer cells in a benchtop experiment to self-destruct, while leaving 99% of non-targeted cells healthy. The results show promise for precisely delivering a wide variety of large-molecule therapeutics to cells with few off-target effects.

The research appears in the journal Proceedings of the National Academy of Sciences.

Continue reading “Ultrasound-based technology to deliver large therapeutics into cancer cells” | >

Frontiers: Cardiovascular diseases are the leading cause of death in the world

This is partly due to the low regenerative capacity of adult hearts. mRNA therapy is a promising approach under development for cardiac diseases. In mRNA therapy, expression of the target protein is modulated by delivering synthetic mRNA therapy benefits cardiac regeneration by increasing cardiomyocyte proliferation, reducing fibrosis, and promoting angiogenesis. Because mRNA is translated in the cytoplasm, the delivery efficiency of mRNA into the cytoplasm and nucleus significantly affects its therapeutic efficacy. To improve delivery efficiency, non-viral vehicles such as lipid nanoparticles have been developed. Non-viral vehicles can protect mRNA from enzymatic degradation and facilitate the cellular internalization of mRNA. In addition to non-viral vehicles, viral vectors have been designed to deliver mRNA templates into cardiac cells. This article reviews lipid nanoparticles, polymer nanoparticles, and viral vectors that have been utilized to deliver mRNA into the heart. Because of the growing interest in lipid nanoparticles, recent advances in lipid nanoparticles designed for cardiac mRNA delivery are discussed. Besides, potential targets of mRNA therapy for myocardial infarction are discussed. Gene therapies that have been investigated in patients with cardiac diseases are analyzed. Reviewing mRNA therapy from a clinically relevant perspective can reveal needs for future investigations.

Cardiovascular diseases are a group of diseases related to heart muscles, blood vessels, and valves. The death caused by cardiovascular diseases worldwide in 2019 was 17.9 million, which accounts for approximately 30% of total death in the year (DofE and SAPD, 2019; World Heath Organization, 2021). Myocardial infarction and strokes result in over 80% of deaths from cardiovascular diseases. Percutaneous coronary intervention treatment has significantly lowered mortality after acute myocardial infarction. However, the cardiac function will be permanently impaired. Newborn mammals can regenerate the injured heart, but this regenerative capacity disappears in adults (Porrello et al., 2011; Ye et al., 2018). The declined regenerative capacity in aged hearts is partly due to decreased cardiomyocyte proliferation, lowered angiogenesis, and increased fibrosis (Rivard et al., 1999; Senyo et al., 2012; Notari et al., 2018).

TY2 is protective in a rat model of MI and in a model of cecal ligation and puncture–induced sepsis

This Research Letter offers a creative approach to sepsis based on a naturally occurring efferocytosis-enhancing RNA

Small noncoding RNA TY2 enhances efferocytosis and improves outcomes in a mouse model of sepsis by Alessandra Ciullo & team: https://doi.org/10.1172/jci.insight.

The image shows exposure to TY2 increases E. coli clearance by bone-marrow derived macrophages as indicated by fluorophore as a reporter of efferocytosis (green).

Address correspondence to: Alessandra Ciullo, Smidt Heart Institute, Cedars-Sinai Medical Center, 8,700 Beverly Blvd., Los Angeles, California 90,048, USA. Email: [email protected].

Find articles by Ciullo, A. in: | Google Scholar

Smidt heart institute, cedars-sinai medical center, los angeles, california, USA.

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Association of Brain Network Perturbations With Response to Vagus Nerve Stimulation in Children With Drug-Resistant Focal Epilepsy

This study investigated whether preimplantation functional network perturbations in relation to interictal epileptiform discharges are associated with vagus nerve stimulation response in children with focal drug-resistant epilepsy.

Background and Objectives.

Boy, 7, dies of brain condition caused by world’s most contagious disease — years after he had it as a baby

Measles is a highly contagious viral infection that causes high fever, cough, red/watery eyes, and a characteristic blotchy rash, spreading through airborne droplets. It primarily affects children but can strike anyone, with severe cases leading to pneumonia, brain swelling, or death. Prevention is primarily through the MMR vaccine, which is 97% effective.

//He had contracted measles as a baby of just 7 months old — but fast-forward years later to when he was 6 and experiencing cognitive deterioration and seizures.

Doctors eventually diagnosed him with subacute sclerosing panencephalitis (SSPE), a neurological disease that can develop years after a measles infection.

This brain disorder usually starts with subtle personality changes, like memory loss, irritability or mood swings. Over time, it can progress to involuntary muscle spasms, loss of coordination, severe brain damage, coma — and almost always death.\
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What is subacute sclerosing panencephalitis (SSPE): Subacute sclerosing panencephalitis (SSPE) is a rare, fatal, progressive neurodegenerative disorder of the central nervous system caused by a persistent, mutated measles virus infection. Typically affecting children or adolescents years after an initial infection, it causes cognitive decline, myoclonic jerks, and seizures, leading to death within 1–3 years. There is no cure, though prevention via measles vaccination is highly effective.

Even those who make a full recovery from the initial infection face a lurking threat: a deadly disease that remains latent until striking — and killing — years later.

Continue reading “Boy, 7, dies of brain condition caused by world’s most contagious disease — years after he had it as a baby” | >

C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA: RNA hybrid G-quadruplexes

Transcriptional dysregulation hexanucleotide repeats in ALS

Repeat hexanucleotide RNAs in C9orf72 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia disease pathogenesis but the mechanisms of action remain incompletely understood.

The researchers demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form DNA: RNA hybrid G-quadruplexes (HQs) structures with DNA.

These structures obstruct RNA polymerase II and transcription factors, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD. sciencenewshighlights ScienceMission https://sciencemission.com/hexanucleotide-repeat

Liu et al. demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form HQ structures with DNA. These structures obstruct key transcription machinery, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD.

A single-cell transcriptional reference for the functional and developmental diversity of neonatal innate lymphoid cells

Mononuclear cells (MNCs) were isolated from fresh umbilical cord blood (CB) via a Ficoll gradient (n = 3). Unwanted cells were depleted using biotinylated antibodies (anti-CD3, anti-CD14, anti-CD19, and CD66b) and magnetic beads. The cells were stained to faithfully sort cILC1s (Lin−CD94−CD127+CD117−CRTH2−), cILC2s (Lin−CD94−CD127+CD117−/+ CRTH2+), cILC3s (Lin−CD94−CD127+CD117+CRTH2−), and NK cells (Lin−CD94+), as previously described.5,7,33 The four individual populations were individually multiplexed, pooled, and stained with Ab-Seq antibodies.

(A) scRNA-seq was performed via the BD Rhapsody protocol.

(B and C) UMAP visualization of sorted populations (B) and individual clusters of CB cILCs and NK cells with color coding of the individual cluster 0–10. The following clusters were identified: 0, CD56dim NK cells (GZMBhigh); 1, CD56dim NK cells (GZMBlow); 2, cILC2s (GATA3); 3, cILC progenitor (KIT); 4, CD56bright NK cells (GZMK); 5, intermediate zone (NK/cILCs); 6, cILC1s (CD5); 7, activated CD56dim NK cells (PCNA); 8, cycling CD56dim NK cells (MKI67); 9, cILC3s (RORC); and 10, CD56dim NK cells (FOXP2) ©.

Cell-type specific TDP-43 pathology in the motor cortex

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions.

‘Bugs delivering drugs’: A new approach to colorectal cancer treatment using common food-borne bacteria

Baylor University researchers have developed a novel approach to fight colorectal cancer, using modified bacteria as a courier to deliver potent cancer-killing proteins into tumor cells. Michael S. VanNieuwenhze, Ph.D., FRSC, University Distinguished Professor and chair of the Department of Biology, along with Baylor doctoral students and a colleague at Texas Tech University Health Sciences Center, have published their research in Cell Chemical Biology.

Colorectal cancers accounted for the second-most deaths caused by cancer in 2025, according to the National Cancer Institute, highlighting the importance of new strategies for therapy and treatment.

Building on growth in the use of bacteria as a tool in fighting cancer, VanNieuwenhze and his team attached saporin, a known cancer-killing toxin, to the surface Listeria monocytogenes, which delivers the toxin to tumor cells. Listeria, commonly recognized as a food-borne bacteria, can be modified for express therapeutic purposes while maintaining its ability to penetrate human cells—making it, VanNieuwenhze said, a particularly promising agent in the fight against colorectal cancer.

CSF Proteomic Profiles Associated With White Matter Integrity in Cognitively Normal Older Adults With and Without Amyloid Pathology

Background and ObjectivesIncreasing evidence indicates a potential role of white matter (WM) damage in the onset and progression of Alzheimer disease (AD). However, the biological processes underlying in vivo WM imaging biomarkers remain unclear. We…

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