This study represents a characterization of pediatric Charcot-Marie-Tooth disease in a Canadian cohort and demonstrates that disease onset, severity, and manifestations are highly variable even in childhood.
Background and Objectives.
Category: biotech/medical – Page 3
Opposing functions of distinct regulatory T cell subsets in colorectal cancer
For this study, the researchers focused on a type of colorectal cancer that accounts for 80% to 85% of all colorectal cancers — microsatellite stable (MSS) with proficient mismatch repair (MMRp), meaning the tumors’ DNA is relatively stable. These cancers are largely resistant to checkpoint inhibitor immunotherapies.
Previous groundbreaking research found checkpoint inhibitors alone could successfully treat rectal cancer and several other cancers with the opposite tumor type — those with high microsatellite instability (MSI-H) and mismatch repair deficiency (MMRd). This allows doctors to spare many patients from surgery, chemotherapy, and radiation.
Here the team employed an mouse model that accurately recreates the common mutations, behaviors, and immune cell composition of human colorectal cancer. They found that the regulatory T cells associated with the cancer are split between two types: Cells that make a signaling molecule (cytokine) called interleukin‑10 (IL-10) and cells that don’t.
Through a series of sophisticated experiments that selectively eliminated each type of cell, the researchers discovered:
When IL-10-positive cells were removed, tumor growth accelerated.
In most solid tumors, high numbers of regulatory T (Treg) cells are associated with poorer outcomes because they dampen the immune system’s ability to fight against a tumor.
Tumbling stem cells? Watch how movement plays a part in their fate
By Nina Bai
Stanford Medicine researchers recorded stem cells performing a previously unknown type of movement, dubbed cell tumbling, which may help them differentiate.
Programmable Macrophage Mimics for Inflammatory Meniscus Regeneration via Nanotherapy
JUST PUBLISHED: programmable macrophage mimics for inflammatory meniscus regeneration via nanotherapy
Click here to read the latest free, Open Access Article from Research.
The meniscus is a fibrocartilaginous tissue and organ in the human knee joint that serves critical functions, including load transmission, shock absorption, joint stability, and lubrication. Meniscal injuries are among the most common knee injuries, typically caused by acute trauma or age-related degeneration [1– 3]. Minor meniscal injuries are usually treated with in situ arthroscopic procedures or conservative methods, whereas larger or more severe injuries often necessitate total meniscus replacement. Recent advances in materials science and manufacturing techniques have enabled transformative tissue-engineering strategies for meniscal therapy [4, 5]. Several stem cell types, including synovium-derived mesenchymal stem cells, bone-marrow-derived mesenchymal stem cells, and adipose-derived stem cells (ADSCs), have been investigated as candidate seed cells for meniscal regeneration and repair. Notably, ADSCs are clinically promising because of their ease of harvest, high inducibility, innate anti-inflammatory properties, and potential to promote fibrocartilage regeneration [6– 8]. Our group has developed a series of decellularized matrix scaffolds for auricular, nasal, tracheal, and articular cartilage repair using 3-dimensional (3D) bioprinting techniques, successfully repairing meniscus defects and restoring physiological function [9– 12]. However, current tissue-engineering strategies for meniscus defect repair commonly rely on a favorable regenerative microenvironment. Pathological conditions such as osteoarthritis (OA) [13 – 16], the most prevalent joint disorder, often create inflammatory environments that severely hinder meniscus regeneration [17 – 21]. Moreover, meniscal injury exacerbates the local inflammatory milieu, further impeding tissue healing and inevitably accelerating OA progression. Therefore, there is an urgent need to establish a cartilaginous immune microenvironment that first mitigates early-stage inflammation after meniscal injury and then sequentially promotes later-stage fibrocartilage regeneration [22 – 25].
Currently, targeted regulation using small-molecule drug injections is commonly employed to treat inflammatory conditions in sports medicine [26,27]. Most of these drugs exhibit broad-spectrum anti-inflammatory effects and inevitably cause varying degrees of side effects by activating nonspecific signaling pathways. Polyethyleneimine is a highly cationic polymer. It is widely used to modulate inflammation by adsorbing and removing negatively charged proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), via electrostatic interactions [28–31]. Notably, modifying polyethyleneimine into its branched form (branched polyethyleneimine [BPEI]) has been shown to improve cytocompatibility and enhance in vivo metabolic cycling.
Pancreatic organoid study reveals key factors shaping complex lumen formation
Organs often have fluid-filled spaces called lumens, which are crucial for organ function and serve as transport and delivery networks. Lumens in the pancreas form a complex ductal system, and its channels transport digestive enzymes to the small intestine. Understanding how this system forms in embryonic development is essential, both for normal organ formation and for diagnosing and treating pancreatic disorders. Despite their importance, how lumens take certain shapes is not fully understood, as studies in other models have largely been limited to the formation of single, spherical lumens. Organoid models, which more closely mimic the physiological characteristics of real organs, can exhibit a range of lumen morphologies, such as complex networks of thin tubes.
Researchers in the group of Anne Grapin-Botton, director at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, and also Honorary Professor at TU Dresden, teamed up with colleagues from the group of Masaki Sano at the University of Tokyo (Japan), Tetsuya Hiraiwa at the Institute of Physics of Academia Sinica (Taiwan), and with Daniel Rivéline at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (France) to explore the processes involved in complex lumen formation. Working with a combination of computational modeling and experimental techniques, the scientists were able to identify the crucial factors that control lumen shape.
Three-dimensional pancreatic structures, also called pancreatic organoids, can form either large spherical lumen or narrow complex interconnected lumen structures, depending on the medium in the dish. By adding specific chemical drugs altering cell proliferation rate and pressure in the lumen, we were able to change lumen shape. We also found that making the epithelial cells surrounding the lumen more permeable reduces pressure and can change the shape of the lumen as well.
New Israeli study may unlock key clues to autism and brain development
A study being conducted at The Hebrew University of Jerusalem, led by Professor Sagiv Shifman, found that many genes are essential for healthy brain cell development, but only a small share are currently connected to recognized neurodevelopmental disorders.
Read more from ynet here.
The researchers also identified clear patterns in how different genes contribute to disease. Genes that regulate other genes, such as transcription and chromatin regulators, were more often linked to dominant disorders, where a mutation in a single copy of a gene can cause illness. In contrast, genes involved in metabolic processes were typically associated with recessive disorders, requiring mutations in both copies of the gene.
To validate their findings, the team studied eight genes in mouse models — including PEDS1, EML1 and SGMS1 — and found major abnormalities in brain structure. In four of the cases, the mice developed microcephaly, a condition marked by an abnormally small brain.
One gene, PEDS1, emerged as particularly significant. The gene plays a key role in producing plasmalogens, a class of lipids essential to cell membranes and nerve tissue. When PEDS1 was disabled in mice, brain cells exited the cell cycle too early and failed to properly differentiate and migrate, severely impairing brain development.
Cribriform Plate
The cribriform plate represents a transition from the base of the skull to the face at the upper aspect of the nose. The cribriform plate plays a role in the passage of olfactory nerves and disruption of this can lead to partial or total anosmia. A review of the incidence and factors involved in this sensory loss caused by trauma has been summarized.10 It is therefore intuitive to understand that disruption of the sensory fibers passing through this region can lead to permanent smell alteration. Fig. 5 demonstrates a Lefort II fracture whereby the nasal bone separated from the cranial base and was displaced 1-cm posteriorly as the maxilla-nasal complex rotated up and back as a single unit. This patient had resultant permanent anosmia.
ScienceDirect.
Genetic resistance to leukemia
A newly identified and rare genetic variant slows the growth of mutated blood stem cells, researchers report in Science, and it reduces the risk of leukemia.
The findings offer insight into why some people are naturally more resistant to clonal expansion and age-related blood cancers despite acquiring risky mutations.
Learn more in a new Science Perspective.
A genome-wide association study identifies a genetic variant that reduces the risk of leukemia.
Francisco Caiado and Markus G. Manz Authors Info & Affiliations
Science
What Are Cancer Vaccines?
Using mRNA is a promising new way to make [vaccines to help treat cancer](https://www.cancer.org/cancer/managing-cancer/treatment-type…nes.html).
Vaccines are substances that help your immune system learn to fight off something that doesn’t belong there. We’re most familiar with vaccines that help prevent some types of infections, such as the flu vaccine. But vaccines might also be helpful in treating cancer, if the vaccine can get the immune system to see and attack cancer cells. It’s been hard to make effective cancer vaccines for several reasons, but mRNA might provide a way to make cancer vaccines that are more effective and easier to create.
https://www.cancer.org/cancer/managing-cancer/treatment-type…cines.html
Some vaccines help protect against viruses that cause cancer, while others are used to treat cancer. Learn more about cancer vaccines here.
This years biggest breakthroughs in longevity!
Wrap up for 2025.
Every year I compile what I think were some important contributions to longevity research. Here is my list for 2025!!
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Support the channel.
through PayPal — https://paypal.me/sheekeyscience?coun… through Patreon — / thesheekeyscienceshow TIMESTAMPS: 00:00 – Intro & “What is aging?” / Hallmarks 2025 02:07 – Cellular reprogramming 05:47 – Senescent cells 11:45 – GLP‑1 agonists & ITP 13:43 – Elastin fragments & ECM aging 15:22 – Cardiac ‘age‑switch’ experiment 16:18 – Systemic environment: FOXO3 cells, antler EVs, plasma exchange 19:26 – Things you wouldn’t have thought of: AI-predicted antibodies REFERENCES: What is aging / hallmarks Hallmarks of aging update 2025 (14 hallmarks, ECM + psychosocial isolation) https://www.sciencedirect.com/science… reprogramming Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming – Cell 2025 https://doi.org/10.1016/j.cell.2025.0… A single factor for safer cellular rejuvenation (SB000) – bioRxiv 2025 https://doi.org/10.1101/2025.06.05.65… https://www.biorxiv.org/content/10.11… OpenAI x Retro Biosciences: AI‑designed reprogramming factors https://openai.com/index/accelerating… Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche – Nature Aging 2024 (YouthBio’s scientific basis) https://doi.org/10.1038/s43587-024-00… Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan in Caenorhabditis elegans – EMBO Molecular Medicine 2025 https://doi.org/10.1038/s44321-025-00… https://pmc.ncbi.nlm.nih.gov/articles… Senescent cells An unbiased cell‑culture selection yields DNA aptamers as senescence‑specific reagents – Aging Cell 2025 https://doi.org/10.1111/acel.70245 Senolytic CAR T cells reverse senescence‑associated pathologies – Amor et al., Nature 2020 https://doi.org/10.1038/s41586-020-24… Anti‑uPAR CAR T cells reverse and prevent aging‑associated defects in intestinal regeneration and fitness – Nature Aging 2025 https://doi.org/10.1038/s43587-025-01… Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low‑Frequency Ultrasound – Aging Cell 2025 https://pmc.ncbi.nlm.nih.gov/articles… Supplements, ITP & GLP‑1s Are GLP‑1s the first longevity drugs? – Nature Biotechnology 2025 https://doi.org/10.1038/s41587-025-02… GLP‑1 receptor agonists at the crossroads of metabolism and longevity – Nature Aging https://www.nature.com/articles/s4151… Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female UM‑HET3 mice – GeroScience 2025 https://doi.org/10.1007/s11357-025-01… https://pubmed.ncbi.nlm.nih.gov/40973… ECM, elastin & cardiac environment Elastin‑derived extracellular matrix fragments drive aging through innate immune activation – Nature Aging 2025 https://doi.org/10.1038/s43587-025-00… Sun, A.R., Ramli, M.F.H., Shen, X. et al. Hybrid hydrogel–extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing. Nat. Mater. 24, 1489–1501 (2025). https://doi.org/10.1038/s41563-025-02… Systemic environment: stem cells, EVs, plasma Senescence‑resistant human mesenchymal progenitor cells counter aging in primates – Cell 2025 https://doi.org/10.1016/j.cell.2025.0… Attenuation of primate aging via systemic infusion of senescence‑resistant cells – https://pmc.ncbi.nlm.nih.gov/articles… Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging‑related phenotypes – Nature Aging 2025 https://pmc.ncbi.nlm.nih.gov/articles… Human clinical trial of plasmapheresis effects on biomarkers of aging – Aging Cell 2025 https://pmc.ncbi.nlm.nih.gov/articles… “Things you wouldn’t think of” – AI antibodies Atomically accurate de novo design of antibodies with atomic precision – Baker Lab, Nature 2025 https://doi.org/10.1038/s41586-025-09… Computational design of human antibodies targeting any antigen – https://doi.org/10.1016/j.cell.2025.1… Please note that The Sheekey Science Show is distinct from Eleanor Sheekey’s teaching and research roles. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed. Icons in intro; “https://www.freepik.com/free-photos-v…“Background vector created by freepik — www.freepik.com.
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