Endothelialization of coronary stents after intra-luminal adenoviral VEGF-A gene transfer in a preclinical porcine restenosis model - Studies with optical coherence tomography, angioscopy, multiphoton and scanning electron microscopy.

Background: Coronary stenting operations have become the main option for the treatment of coronary heart disease. Vessel recovery after stenting has emerged as a critical factor in reducing possible complications. In this study, we evaluated the feasibility, safety and efficacy of locally administered intraluminal gene therapy delivered using a specialized infusion balloon catheter.

Real-Time Tractography-Assisted Neuronavigation for Transcranial Magnetic Stimulation.

State-of-the-art navigated transcranial magnetic stimulation (nTMS) systems can display the TMS coil position relative to the structural magnetic resonance image (MRI) of the subject's brain and calculate the induced electric field. However, the local effect of TMS propagates via the white-matter network to different areas of the brain, and currently there is no commercial or research neuronavigation system that can highlight in real time the brain's structural connections during TMS. This lack of real-time visualization may overlook critical inter-individual differences in brain connectivity and does not provide the opportunity to target brain networks.

Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE).

Chlorinated paraffins in particulate matter associated with asthma and its relative symptoms in school-aged children and adolescents: A cross-sectional survey in South China.

Particulate matter (PM) and contaminants attached to PM can increase the risk of respiratory diseases. However, the health risk assessment of chlorinated paraffins (CPs), an emerging pollutant occupying a high proportion of persistent organic pollutants (POPs) in PM, remains scarce. This study aimed to evaluate the association between PM-bound CPs and asthma, along with relative symptoms, in school-aged children and adolescents.

QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples.

Single-nuclei RNA sequencing remains a challenge for many human tissues, as incomplete removal of background signal masks cell-type-specific signals and interferes with downstream analyses. Here, we present Quality Clustering (QClus), a droplet filtering algorithm targeted toward challenging samples. QClus uses additional metrics, such as cell-type-specific marker gene expression, to cluster nuclei and filter empty and highly contaminated droplets, providing reliable filtering of samples with varying number of nuclei and contamination levels.

Plasma microRNAs as prognostic biomarkers for development of severe epilepsy after experimental traumatic brain injury-EpiBioS4Rx Project 1 study.

Objective: To test a hypothesis that acutely regulated plasma microRNAs (miRNAs) can serve as prognostic biomarkers for the development of post-traumatic epilepsy (PTE).

Methods: Adult male Sprague-Dawley rats (n = 245) were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, United States). Video-electroencephalography (vEEG) was performed on the seventh post-injury month to detect spontaneous seizures.

Roles of the gut microbiota in human neurodevelopment and adult brain disorders.

Growing evidence demonstrates the connection between gut microbiota, neurodevelopment, and adult brain function. Microbial colonization occurs before the maturation of neural systems and its association with brain development. The early microbiome interactions with the gut-brain axis evolved to stimulate cognitive activities.

The mechanisms of Chr.9p21.3 risk locus in coronary artery disease - where are we today?

Despite the advancements and release of new therapeutics in the past few years, cardiovascular diseases (CVDs) have remained the number one cause of death worldwide. Genetic variation of a 9p21.3 genomic locus has been identified as the most significant and robust genetic CVD risk marker on the population level, with the strongest association with coronary artery disease (CAD) and other diseases, including diabetes and cancer.

Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen.

Drug conjugates of tamoxifen and melatonin linked through the amide side chain of melatonin (,) were reported as promising agents for future treatment of breast cancer, possibly reversing the adverse effects of tamoxifen. Here, we report the synthesis and pharmacological evaluation of a novel series of anticancer drug conjugates linking melatonin with tamoxifen through polymethylene spacers through the ether oxygen of melatonin (-, -, ) and compare them to the previously reported amide-linked analogues and . All hybrid ligands are antagonists of estrogen receptor alpha and agonists of the melatonin MT receptor with variable potencies.

Circular RNA circ_0061183 regulates microglial polarization induced by airborne ultrafine particles in HMC3 cells via sponging miR-98-5p.

Airborne ultrafine particulate matter (PM) can enter the brain, induce microglia activation, and promote the development of Alzheimer's disease (AD). Circular RNAs (circRNAs) are also involved in AD pathogenesis. However, the role of AD-related circRNAs in PM-induced microglia activation remains unclear.

The emerging roles of particulate matter-changed non-coding RNAs in the pathogenesis of Alzheimer's disease: A comprehensive in silico analysis and review.

Research on epigenetic‒environmental interactions in the development of Alzheimer's disease (AD) has accelerated rapidly in recent decades. Numerous studies have demonstrated the contribution of ambient particulate matter (PM) to the onset of AD. Emerging evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs, circular RNAs, and microRNAs, play a role in the pathophysiology of AD.

System Genetics Analysis Reveals Sex Differences in Human Aortic Smooth Muscle Gene Expression.

Background: Coronary artery disease (CAD) is one of the leading causes of death worldwide. The buildup of atherosclerotic plaque, including lipids and cellular waste, characterizes this disease. Smooth muscle cells (SMCs) can migrate and proliferate to form a fibrous cap that stabilizes the atherosclerotic plaque in response to plaque buildup.

Adverse outcome pathway for the neurotoxicity of Per- and polyfluoroalkyl substances: A systematic review.

Per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors with unambiguous neurotoxic effects. However, due to variability in experimental models, population characteristics, and molecular endpoints, the elucidation of mechanisms underlying PFAS-induced neurotoxicity remains incomplete. In this review, we utilized the adverse outcome pathway (AOP) framework, a comprehensive tool for evaluating toxicity across multiple biological levels (molecular, cellular, tissue and organ, individual, and population), to elucidate the mechanisms of neurotoxicity induced by PFAS.

Whisker stimulation with different frequencies reveals non-uniform modulation of functional magnetic resonance imaging signal across sensory systems in awake rats.

Primary sensory systems are classically considered to be separate units, however there is current evidence that there are notable interactions between them. We examined the cross-sensory interplay by applying a quiet and motion-tolerant zero echo time functional magnetic resonance imaging (fMRI) technique to elucidate the evoked brain-wide responses to whisker pad stimulation in awake and anesthetized rats. Specifically, characterized the brain-wide responses in core and non-core regions to whisker pad stimulation by the varying stimulation-frequency, and determined whether isoflurane-medetomidine anesthesia, traditionally used in preclinical imaging, confounded investigations related to sensory integration.

Blood cytokines in major depressive disorder in drug-naïve adolescents: A systematic review and meta-analysis.

Background: Major depressive disorder (MDD) is the most common mental health problem worldwide. Increased levels of inflammation are associated with MDD, though this relationship has been suggested to be bidirectional. The first incidence of a depressive episode usually occurs during adolescence.

Association between the dietary inflammatory index and risk of lung cancer: a multi-centered case-control study.

Purpose: Dietary factors might contribute to the risk of lung cancer by increasing the concentration of inflammatory markers. The literature-derived Dietary Inflammatory Index (DII) has been established to evaluate the inflammatory potential of diet correlated with inflammatory markers. The association between DII scores and the risk of lung cancer has been conflicting.

In vivo rat brain mapping of multiple gray matter water populations using nonparametric D(ω)-R-R distributions MRI.

Massively multidimensional diffusion magnetic resonance imaging combines tensor-valued encoding, oscillating gradients, and diffusion-relaxation correlation to provide multicomponent subvoxel parameters depicting some tissue microstructural features. This method was successfully implemented ex vivo in microimaging systems and clinical conditions with tensor-valued gradient waveform of variable duration giving access to a narrow diffusion frequency (ω) range. We demonstrate here its preclinical in vivo implementation with a protocol of 389 contrast images probing a wide diffusion frequency range of 18 to 92 Hz at b-values up to 2.

GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls.

Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is common among patients with cardiovascular diseases, but the underlying mechanisms remain largely unknown. Using the human MESA cohort, here we show that plasma glutamine-glutamate ratio is an independent risk factor for carotid plaque progression. Mice deficient in glutaminase-2 (Gls2), the enzyme that mediates hepatic glutaminolysis, developed accelerated atherosclerosis and susceptibility to catastrophic cardiac events, while Gls2 overexpression partially protected from disease progression.

Single-cell RNA sequencing analysis identifies acute changes in the tumor microenvironment induced by interferon α gene therapy in a murine bladder cancer model.

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Atheroma transcriptomics identifies ARNTL as a smooth muscle cell regulator and with clinical and genetic data improves risk stratification.

Background And Aims: The role of vascular smooth muscle cells (SMCs) in atherosclerosis has evolved to indicate causal genetic links with the disease. Single cell RNA sequencing (scRNAseq) studies have identified multiple cell populations of mesenchymal origin within atherosclerotic lesions, including various SMC sub-phenotypes, but it is unknown how they relate to patient clinical parameters and genetics. Here, mesenchymal cell populations in atherosclerotic plaques were correlated with major coronary artery disease (CAD) genetic variants and functional analyses performed to identify SMC markers involved in the disease.

Mutated LRRK2 induces a reactive phenotype and alters migration in human iPSC-derived pericyte-like cells.

Background: Pericytes play a crucial role in controlling inflammation and vascular functions in the central nervous system, which are disrupted in Parkinson's disease (PD). Still, there is a lack of studies on the impact of pericytes on neurodegenerative diseases, and their involvement in the pathology of PD is unclear. Our objective was to investigate the molecular and functional differences between healthy pericytes and pericytes with the LRRK2 G2019S mutation, which is one of the most common mutations associated with PD.