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Category: biotech/medical – Page 48

Regeneration: Wound healing, reprogramming and tissue engineering

BMC Biology is calling for submissions to our Collection on Regeneration: wound healing, reprogramming, and tissue engineering. This Collection aims to bring together cutting-edge research exploring the cellular and molecular mechanisms of wound healing and repair, cellular reprogramming as a means of achieving tissue regeneration in vivo or in vitro, as well as advances in tissue engineering, aiming at replacing damaged cells and organs via transplantation.

We welcome studies on:

- Investigating processes involved in wound healing, including inflammation, re-epithelialization, cell fusion, fibroblast activation, scar formation, angiogenesis, and extracellular matrix (ECM) remodeling.

Microbiota derived nicotinic acid protects colon tissue

Prior research has shown that the four sections of the colon—ascending, transverse, descending and sigmoid—have different functions and risks for disease, but it wasn’t clear why these variations exist.

In this study, the investigators showed that the identity of distinct regions of the colon are regulated by the gut microbiome. They identified nicotinic acid, a molecule produced by certain bacteria in the gut microbiome, as a main driver of these regional differences in the colon’s sections. Nicotinic acid, also known as niacin, part of the vitamin B3 family, helps the body convert food into energy and supports the health of cells.

The researchers compared laboratory mice with and without a microbiome. They found that production of nicotinic acid by bacteria in the upper colon activates a protective mechanism in colon cells by the induction of Pparα expression to establish proximal colonocyte identity. In mice without a microbiome, minimal nicotinic acid was produced, and cells in the upper colon became more vulnerable to damage and disease.

Investigators also studied human colon tissue samples. They found that the different sections of the human colon showed regional characteristics similar to patterns observed in mice. And in samples from human patients with Crohn’s disease— a type of bowel disease in which abnormal immune system activity causes inflammation—this protective mechanism was reduced. ScienceMission sciencenewshighlights.

The gut microbiome—the trillions of bacteria and other microbes that inhabit the gastrointestinal tract—drives a process vital for protecting the colon against tissue injury, according to the findings of a new study.

The discovery, published in Cell, has important implications for understanding how a wide variety of intestinal disorders may develop.

Continue reading “Microbiota derived nicotinic acid protects colon tissue” | >

Abstract: Uncovering a novel disease mechanism in partial lipodystrophy syndrome disease

Here, Elif A. Oral & team describe a nonsense variant in EBF2 in a patient with an atypical form of partial lipodystrophy and establish a mouse model—linking the EBF2 p. E165X variant to impaired adipogenesis and adipose tissue function.

The image shows inguinal adipose tissue from the EBF2 p. E165X knock-in mouse, demonstrating prominent accumulation of collagen fibers (blue) and elastin-rich eosinophilic material (purple).

1Caswell Diabetes Institute and Metabolism, Endocrinology and Diabetes Division, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.

2Department of Clinical and Translational Sciences, University of Pisa, Pisa, Italy.

3Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, USA.

Precision radio waves may help counter brain diseases

A study has found that precise application of radio waves can change the activity of brain cells in ways that could counter neurological conditions. Led by researchers at NYU Langone Health, the work introduces a technique called transcranial radio frequency stimulation (TRFS), which promises to treat neurological diseases with neither the invasiveness of surgery nor the frequent failure of drugs as patients (e.g., 30% of people with depression and epilepsy) develop resistance.

Published online recently in the journal Brain Stimulation, the study describes the use of radio frequency (RF) energy, which is effective at penetrating biological tissue. The study says TRFS could overcome the limits of older technologies because it can, depending on the nature of the disease, target either a small part of the brain or the entire organ, and it can dial nerve signaling up or down.

“Our study is the first to demonstrate in live mice the potential of the technology to be highly effective for adjusting neural activity,” said senior study author György Buzsáki, MD, Ph.D., the Biggs Professor of Neuroscience in the Department of Neuroscience at NYU Grossman School of Medicine. “The need for better, noninvasive techniques is becoming ever more urgent, with one in three people globally affected by some form of brain disorder during their lifetime,” said Dr. Buzsáki, also faculty at the Institute for Translational Neuroscience.

FOXJ3 gene variants linked to drug-resistant focal epilepsy

Researchers have discovered that mutations in the FOXJ3 gene act as a “master switch” failure, disrupting how the brain builds its layers and leading to FCD, a primary cause of drug-resistant epilepsy. The study reveals how FOXJ3 controls the formation of brain cortical layers during brain development by regulating the PTEN–mTOR signaling pathway.

The PTEN-mTOR signaling pathway acts as a critical control system for cell growth, proliferation, metabolism, and survival. When this system malfunctions, it causes many neurological disorders including FCD, tuberous sclerosis complex and neurofibromatosis. The discovery of FOXJ3, a transcription factor (a protein that regulates gene activity), as a new cause of these “mTOR pathway diseases” (mTORpathies) provides new insight into the biological origins of epilepsy and cortical malformations, as well as potential new treatments.

The research team by studying families with inherited focal epilepsy alongside mouse and single-cell analysis, uncovered how FOXJ3 mutations disrupt how brain cells move to their correct locations and take on their proper roles during early brain development.

“Focal cortical dysplasia is one of the most common causes of epilepsy that does not respond to medication, yet in many patients the underlying cause remains unknown,” said the corresponding author. “Our findings identify FOXJ3 as the critical genetic and molecular link between abnormal brain development and epilepsy.” ScienceMission sciencenewshighlights.

A Review of How the Heart Ages

The European Heart Journal has published a review of what happens to the human heart as it ages, noting the cellular effects of mitochondrial dysfunction and cellular senescence along with more visible changes such as hypertrophy and fibrosis.

A constantly working organ

The reviewers begin this paper by noting the constant work of the heart, as it must unceasingly pump blood for us to be able to live. Unfortunately, this organ is well-known to fail with age; while only roughly 1% of people under 55 suffer heart failure, it occurs in over 10% of people over 70 [1].

Dendritic cell immunotherapy induces anti-tumor effect in a transgenic mouse model of pancreatic ductal adenocarcinoma

The promise of dendritic cell (DC)-based immunotherapy has been established by two decades of translational research. However, long-term benefits of DC vaccination are reported in only scattered patients with pancreatic ductal adenocarcinoma (PDAC). Here we optimize DC vaccination and evaluate its safety and antitumor efficacy in the genetically engineered PDAC model (KrasLSL-G12D p53LSL-R172H Pdx-1-Cre (KPC mice)). KPC transgenic mice and orthotopic models using KPC cell lines were treated with DC vaccine via an intraperitoneal route. Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Histological analysis and flow cytometry were used to evaluate tumor-directed T cell immunity of these mice. DC vaccine via intraperitoneal injection suppressed tumor progression (P = 0.030) and significantly prolonged survival time (P = 0.028) in KPC mice. Vaccinated KPC mice displayed an increased antitumor T cell response indicated by a higher IFN-γ production (P = 0.016) and tumor-specific cytotoxicity (P = 0.027). Particularly, the mean apparent diffusion coefficient (ADC) values of KPC tumor calculated from diffusion weighted MRI (DW-MRI) were significantly higher in DC vaccine group than that in control group (P < 0.001). More interestingly, we observed that ADC positively correlated with fibrosis in KPC tumor (R2 = 0.463, P = 0.015). Our study demonstrated that the immunization with our improved DC vaccine can elicit a strong tumor-specific immune response and tumor suppression in PDAC.

A new model for alveolar macrophage-Mycobacterium tuberculosis (TB) interactions!

A new model for alveolar macrophage–Mycobacterium tuberculosis (TB) interactions!

https://doi.org/10.1172/jci.insight.

Michael S. Glickman & team establish a stem cell–derived lung alveolar macrophage model to reveal itaconate functions differently between human macrophage types in the host defense against Mtb:

The figure: Brightfield and stained images of two macrophage populations.

1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

2Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, New York, USA.

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