TGFβ1 Restores Energy Homeostasis of Human Trophoblast Cells Under Hyperglycemia In Vitro by Inducing PPARγ Expression, AMPK Activation, and HIF1α Degradation.

Elevated glucose levels at the fetal-maternal interface are associated with placental trophoblast dysfunction and increased incidence of pregnancy complications. Trophoblast cells predominantly utilize glucose as an energy source, metabolizing it through glycolysis in the cytoplasm and oxidative respiration in the mitochondria to produce ATP. The TGFβ1/SMAD2 signaling pathway and the transcription factors PPARγ, HIF1α, and AMPK are key regulators of cell metabolism and are known to play critical roles in extravillous trophoblast cell differentiation and function.

Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.

Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.

Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.

HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.

We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.

Core-Shell Bottlebrush Polymers: Unmatched Delivery of Small Active Compounds Deep Into Tissues.

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers-characterized by variations in backbone length, grafting density, and self-assembly morphology-offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a "grafting-from" strategy.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy.

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties.

Exposure to brominated flame retardants and through lactation delays the development of DMBA-induced mammary cancer: potential effects on subtypes?

Introduction: Brominated flame retardants (BFRs) are chemical compounds used to reduce the flammability of various products; some BFRs exhibit endocrine-disrupting properties and can leach into the environment leading to human and wildlife exposure. The mammary gland has specific vulnerability windows during which it is more sensitive to the effects of endocrine disrupting compounds (EDCs), such as the life, puberty and pregnancy. Our previous studies revealed precocious mammary gland development, disruptions in junctional proteins, and altered proliferation-apoptosis balance during puberty in rats exposed to BFRs and through lactation.

Epidemiology of Tomato Brown Rugose Fruit Virus (ToBRFV) in Commercial Greenhouses.

The tomato brown rugose fruit virus (ToBRFV) poses a considerable threat to tomato production worldwide. Substantial experimental evidence supports the role of infected seeds as a contamination route, but the epidemiologic portrait of the virus has received less attention. This study reports the first survey of ToBRFV prevalence in commercial greenhouses.

Investigating the stability of a cerebral vasodilator drug using chromatographic methods: Evaluation of methods' practicality and environmental aspects.

A vinca alkaloid; vinburnine (VNB) is utilized as an effective vasodilator. As a cyclic amide-containing drug, it is likely susceptible to hydrolytic degradation. This study examined the degradation profile of VNB, findings indicated that VNB undergoes degradation solely in the presence of alkali, generating a carboxylic acid derivative (DEG).

In Vitro Assessment of the Neuroprotective Effects of Pomegranate ( L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress.

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer's disease (AD).

Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts).

Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells.

Adaptation of a Model Spike Aptamer for Isothermal Amplification-Based Sensing.

Isothermal amplification (IA) techniques like rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP) have gained significant attention in recent years due to their ability to rapidly amplify DNA or RNA targets at a constant temperature without the need for complex thermal cycling equipment. Such technologies, combined with colorimetric systems rendering visual confirmation of the amplification event, are ideal for the development of point-of-need detection methods suitable for field settings where access to specialized laboratory equipment is limited. The utility of these technologies, thus far limited to DNA and RNA targets, could be broadened to a wide range of targets by using aptamers.

Exposure to an environmentally representative mixture of polybrominated diphenyl ethers (PBDEs) alters zebrafish neuromuscular development.

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.

infection induces the expression of the chemokine CXCL16 in macrophages to promote chemoattraction of CXCR6 cells.

CXCL16 is a multifaceted chemokine expressed by macrophages and other immune cells in response to viral and bacterial pathogens. However, few studies have investigated its role in parasitic infections. The obligate intracellular parasite () is the causative agent of toxoplasmosis, an infection with potentially deleterious consequences in immunocompromised individuals and the developing fetus of acutely infected pregnant women.

Early life exposures and risk of inflammatory bowel disease: A nested case-control study in Quebec, Canada.

Background: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota.

Aim: We investigated the associations between early exposures and inflammatory bowel disease.

Methods: This case-control study was nested within the CO·MMUNITY cohort.

Synthesis and pharmacological evaluation of nature-inspired phenacyl glycosides.

Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4'-hydroxyphenacyl glycosides.

Canada's contributions to RNA research: past, present, and future perspectives.

The field of RNA research has provided profound insights into the basic mechanisms modulating the function and adaption of biological systems. RNA has also been at the center stage in the development of transformative biotechnological and medical applications, perhaps most notably was the advent of mRNA vaccines that were critical in helping humanity through the Covid-19 pandemic. Unbeknownst to many, Canada boasts a diverse community of RNA scientists, spanning multiple disciplines and locations, whose cutting-edge research has established a rich track record of contributions across various aspects of RNA science over many decades.

Exploring fluorinated heptose phosphate analogues as inhibitors of HldA and HldE, key enzymes in the biosynthesis of lipopolysaccharide.

The growing threat of bacterial resistance to antibiotics has led to the rise of anti-virulence strategies as a promising approach. These strategies aim to disarm bacterial pathogens and improve their clearance by the host immune system. Lipopolysaccharide, a key virulence factor in Gram-negative bacteria, has been identified as a potential target for anti-virulence agents.

Leukemia inhibitory factor drives transcriptional programs that promote lipid accumulation and M2 polarization in macrophages.

Leukemia inhibitory factor, a member of the interleukin-6 cytokine family, plays a central role in homeostasis and disease. Interestingly, some of the pleiotropic effects of leukemia inhibitory factor have been attributed to the modulation of macrophage functions although the molecular underpinnings have not been explored at a genome-wide scale. Herein, we investigated leukemia inhibitory factor-driven transcriptional changes in murine bone marrow-derived macrophages by RNA sequencing.

Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update.

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.

Expanding Structure-Activity Relationships of Human Urotensin II Peptide Analogues: A Proposed Key Role of the N-Terminal Region for Novel Urotensin II Receptor Modulators.

While the urotensinergic system plays a role in influencing various pathologies, its potential remains untapped because of the absence of therapeutically effective urotensin II receptor (UTR) modulators. Herein, we developed analogues of human urotensin II () peptide in which, along with well-known antagonist-oriented modifications, the Glu residue was subjected to single-point mutations. The generated library was tested by a calcium mobilization assay and ex vivo experiments, also in competition with selected ligands.

2D:4D digit ratio as a potential marker for prostate cancer risk.

Background: The second-to-fourth digit ratio (2D:4D) is thought to reflect prenatal exposure to sex steroids. We investigated the relationship between 2D:4D and odds of prostate cancer.

Method: Data were collected in PROtEuS, a population-based case-control study conducted in Montréal, Canada (2005-2012), including 1931 incident prostate cancer cases aged < 76 years and 1994 population controls.