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Category: biotech/medical – Page 11

Scientists report new immune insights and targets into LRRK2 mutations in Parkinson’s disease

Parkinson’s disease (PD) is a debilitating and progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra, a brain region essential for motor control. Clinically, it is marked by tremor, rigidity, bradykinesia and postural instability, symptoms that progressively erode independence and quality of life.

PD affects millions of people worldwide, including nearly one million individuals in the United States, making it one of the fastest-growing neurological disorders. In the U.S. alone, the disease imposes a profound health care and socioeconomic burden, with annual costs reaching tens of billions of dollars due to medical care, lost productivity and long-term disability.

While environmental factors contribute to disease risk, genetic drivers are increasingly recognized, with mutations in the leucine-rich repeat kinase 2 (LRRK2) gene representing one of the most common causes of both familial and sporadic PD. Understanding how LRRK2 mutations drive disease is therefore central to developing therapies that go beyond symptoms control.

Tissue repair slows in old age. These proteins speed it back up

As we age, we don’t recover from injury or illness like we did when we were young. But new research from UCSF has found gene regulators—proteins that turn genes on and off—that could restore the aging body’s ability to self-repair.

The scientists looked at fibroblasts, which build the scaffolding between cells that give shape and structure to our organs.

Fibroblasts maintain this scaffolding in the face of normal wear, disease, and injury. But over time, they slow down, and the body suffers.

Association Between Circadian Rest-Activity Rhythms and Incident Dementia in Older AdultsThe Atherosclerosis Risk in Communities Study

Weaker and more fragmented circadian rest-activity rhythms and later peak activity time were associated with elevated dementia risk in this study.

First Therapy Chatbot Trial Yields Mental Health Benefits

face_with_colon_three Year 2025

Dartmouth researchers conducted the first-ever clinical trial of a generative AI-powered therapy chatbot and found that the software resulted in significant improvements in participants’ symptoms, according to results published March 27 in NEJM AI.

People in the study also reported they could trust and communicate with the system, known as Therabot, to a degree that is comparable to working with a mental health professional.

The trial consisted of 106 people from across the United States diagnosed with major depressive disorder, generalized anxiety disorder, or an eating disorder. Participants interacted with Therabot through a smartphone app by typing out responses to prompts about how they were feeling or initiating conversations when they needed to talk.

Autologous T cell therapy targeting multiple antigens shows promise in treating pancreatic cancer

A recent publication in Nature Medicine describes a novel immunotherapy targeting pancreatic cancer that has shown promising results in a first in-human phase 1/2 trial.

The TACTOPS trial, which investigated the safety and clinical effects of autologous T cell therapy targeting multiple tumor antigens, was a collaboration among researchers at Baylor College of Medicine, the Dan L Duncan Comprehensive Cancer Center, the Center for Cell and Gene Therapy, Texas Children’s Hospital and Houston Methodist Hospital.

“We wanted to develop a targeted therapeutic that would hone the immune system on tumor-associated antigens (TAAs) that were present on malignant cells. We targeted five different antigens to deal with the polyclonal nature of the disease,” said co-corresponding author Dr. Ann Leen, professor of pediatrics–hematology and oncology in the Center for Cell and Gene Therapy.

Pediatric Cohort of Charcot-Marie-Tooth DiseaseClinical Features and Genetic Distribution

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.

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.

Continue reading “Opposing functions of distinct regulatory T cell subsets in colorectal cancer” | >

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.

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