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Category: biotech/medical – Page 53

How much the immune system sees may shape how well we fight infections

Why does the same infection cause only mild symptoms in one person but more serious disease in another? A new study led by the HUN-REN BRC Szeged Momentum Systems Immunology Research Group, together with several international collaborators, suggests that part of the answer lies in how broadly the immune system can present fragments of pathogens to its own immune cells.

Defense against infections does not begin with the immune system attacking the pathogen. The immune system first has to recognize what it is facing. At the center of this recognition process are HLA class II molecules. These molecules present small protein fragments, called peptides, to immune cells. This step is essential for activating helper T cells, which in turn support B cells in producing targeted antibodies.

However, not all HLA-II molecules present the same range of peptides. These molecules have exceptional genetic variability. Consequently, it is likely that two individuals carry different variants. Some variants can bind and present a broad diversity of pathogen-derived peptides, while others are more selective. This property is known as HLA-II peptide-binding promiscuity, or more simply, peptide-binding diversity.

Reverse the progression of Alzheimer’s disease through NanoERASERbased adult neuroregeneration

Neurodegeneration in Alzheimer’s disease outpaces the brain’s ability to regenerate neurons. Wang et al. develop a Nano-ERASER platform that delivers anti-PTBP1 antibodies into astrocytes, enabling proteasome-mediated PTBP1 degradation and activating neuronal reprogramming. This nanotechnology-based Trim-Away system induces functional neurogenesis in vitro, in human brain organoids, and in AD mouse brains, thereby improving learning and memory. The study introduces a regenerative therapeutic paradigm in which biomaterials and endogenous glia collaborate to rebuild neural circuits in Alzheimer’s disease.

Deep brain stimulation shows potential to improve communication after traumatic brain injury

Deep brain stimulation, or DBS, may help improve speech and swallowing problems caused by traumatic brain injury (TBI), according to a new University of Pittsburgh School of Medicine study published in Nature Communications.

The proof-of-concept study found that low-frequency electrical stimulation of the motor thalamus, a deep brain region connected to the motor cortex, improved control of facial and tongue muscles involved in speaking and swallowing. The findings suggest that DBS may be able to strengthen remaining communication pathways between the brain and muscles after TBI, with the potential to improve and partially restore a person’s ability to communicate verbally.

The study, led by Elvira Pirondini, Ph.D., assistant professor of physical medicine and rehabilitation at Pitt’s Rehab Neural Engineering Laboratory, and Jorge A. Gonzalez-Martinez, M.D., Ph.D., professor of neurological surgery at Pitt, builds on the group’s previous work using neuromodulation to improve arm and hand movement after brain injury.

InPatient Multimodal Intensive Neurorehabilitation and Care Improve Motor and NonMotor Functions in the Moderately Advanced Stages of Parkinson’s Disease: A Retrospective Study in a U.S. Facility

Background: Previous studies, mostly performed in European centers, have shown that in-patient multimodal intensive rehabilitation treatments lasting for two to four weeks can improve both motor and non-motor symptoms of Parkinson’s disease (PD) with long-lasting effects. Here, we ascertain the effects of a similar in-patient program in a U.S. center with a retrospective study in a cohort of 153 patients in the moderately advanced stage of PD. Methods: We compared indices of motor and non-motor functions before and immediately after such treatment and investigated the possible differences between men and women. We used the available records of the Beck Depression Inventory, PDQ39, PD Sleep Scale, Timed Up and Go, Vocal Volume, Voice Handicap, and total UPDRS scores. Results: We found that at the end of treatment, which lasted an average of 14 days, all outcome measures significantly improved independently of sex. Conclusions: These results confirm the previous findings with a similar in-patient approach in European centers. They further suggest that this in-patient treatment is a care model that is feasible in U.S. centers and can provide a more immediate benefit to the motor function and quality of life of patients with moderately advanced PD.

Removing immune ‘brake’ improves CAR T-cell therapy for pediatric bone cancer

Scientists at St. Jude Children’s Research Hospital have discovered that removing the gene for Regnase-1 from engineered immune cells makes them more effective at treating relapsed osteosarcoma. There is a great clinical need for new therapies for childhood osteosarcoma, for which there are very few effective treatments for relapsed disease. The approach improved the cells’ ability to control osteosarcoma growth and prevent metastasis to the lungs in preclinical models. The findings support the development of an early-phase clinical trial and were published today in Cell Reports Medicine.

Chimeric antigen receptor (CAR) T-cell therapy reprograms a patient’s own immune cells to recognize and attack cancer. The treatment has shown success in some relapsed childhood leukemias, but it has not worked as well against solid tumors, including osteosarcoma. One major reason is that the tumor microenvironment, the local area around the tumor, can suppress anticancer immune activity and cause CAR T cells to become less functional.

To overcome these barriers, the St. Jude group removed the gene for Regnase-1 (which normally acts as a “brake” on immune function) from CAR T cells, then tested the modified cells in mouse models of osteosarcoma.

Developing a genetic toolkit for manipulating abundant intestinal microbes

Weill Cornell Medicine investigators have developed a set of molecular tools to regulate the activity of specific genes in one of the most common classes of intestinal bacteria. The ability to genetically manipulate these microbes could lead to a better understanding of the role they play in human physiology and disease.

In healthy individuals, species of Clostridia comprise half of the bacteria found in the gut. Many produce metabolites that are likely beneficial for human health and immune regulation. However, some are associated with disease—from botulism and inflammatory intestinal conditions to metabolic disorders such as diabetes or even cancer.

Exactly how Clostridia contribute to disease onset or progression is not well understood. For example, do the bacteria produce a specific toxin or disease-affecting metabolite? Or could changes in their abundance alter other gut bacteria and influence health or disease?

Blocking cellular ‘freecycling’ may slow bone marrow scarring in myelofibrosis

In a new study published in Nature Communications, Boston Children’s Hospital researchers identified a new target responsible for scar formation in the bone marrow of patients with a type of blood cancer known as myelofibrosis. Combining traditional myelofibrosis therapy with drugs that block scar formation may be a more effective treatment for patients with the disease.

“The current gold standard treatment for myelofibrosis targets the symptoms but is not curative,” says Joseph Italiano Jr., Ph.D., principal investigator in the Vascular Biology Program at Boston Children’s. “Based on our findings, we believe that if we can delay scarring, it may give people more time and improve lives.”

Machine learning method uncovers hidden patterns in DNA methylation

In a study recently published in Nature Communications, researchers from Berlin, Potsdam, and Jena present a new method for analyzing the epigenome. The machine-learning method identifies differentially methylated DNA regions without sample labels—a prerequisite for many existing algorithms. This makes it possible to identify previously hidden biological patterns as well as new subgroups of cells or diseases.

The activity of our genes is not determined by DNA sequence alone. The attachment of small chemical compounds—known as methyl groups—influences which genes are active and which remain silenced. DNA methylation is thus a central component of the epigenome.

Changes to the epigenome play a crucial role in the development of our bodies, influence the aging process and are relevant to numerous diseases, such as cancer. To understand such changes, researchers specifically search for differentially methylated DNA regions (DMRs). However, existing methods usually require samples under investigation to be assigned to known groups—such as healthy or diseased tissue. With complex clinical datasets, however, this information is often unknown.

Scientists resurrect ancient proteins, offering new antibiotic leads

University of Oregon biologists have resurrected prehistoric proteins up to 160 million years old that carry natural antimicrobial properties. The revived molecules could inspire the design of new treatments for antibiotic-resistant infections, a pressing global health issue.

Described in a paper published in PLOS Biology on Aug. 25, the scientists worked their way up the tree of life, reconstructing peptides—short protein fragments—dating back to the earliest placental mammals, the diverse lineage that includes humans and nearly all mammals alive today. In laboratory tests, the researchers found that some of the extinct peptides were more potent against drug-resistant bacteria than some of their present-day counterparts.

Evolution’s ancient remedies could offer new starting points for scientists designing treatments that supplement or replace antibiotics that no longer work, said Matt Barber, senior author of the paper and evolutionary biologist at the UO College of Arts and Sciences.

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