The bile acid chenodeoxycholic acid associates with reduced stroke in humans and mice.

Bile acids are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a bile acid synthesis enzyme. In these Cyp8b1, and in Wt mice administered CDCA, stroke infarct area was reduced.

Polar Lipids Supplementation Enhances Basal Excitatory Synaptic Transmission in Primary Cortical Neuron.

Scope: Polar lipids, such as gangliosides and phospholipids, are fundamental structural components that play critical roles in the development and maturation of neurons in the brain. Recent evidence has demonstrated that dietary intakes of polar lipids in early life are associated with improved cognitive outcomes during infancy and adolescence. However, the specific mechanisms through which these lipids impact cognition remain unclear.

A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment.

The etiology of hearing impairment is multifactorial, with contributions from both genetic and environmental factors. Although genetic studies have yielded valuable insights into the development and function of the auditory system, the contribution of gene products and their interaction with alternate environmental factors for the maintenance and development of auditory function requires further elaboration. In this review, we provide an overview of the current knowledge on the role of redox dysregulation as the converging factor between genetic and environmental factor-dependent development of hearing loss, with a focus on understanding the interaction of oxidative stress with the physical components of the peripheral auditory system in auditory disfunction.

Nuanced contribution of gut microbiome in the early brain development of mice.

The complex symbiotic relationship between the mammalian body and gut microbiome plays a critical role in the health outcomes of offspring later in life. The gut microbiome modulates virtually all physiological functions through direct or indirect interactions to maintain physiological homeostasis. Previous studies indicate a link between maternal/early-life gut microbiome, brain development, and behavioral outcomes relating to social cognition.

iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain. Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues. The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development.

Liver's influence on the brain through the action of bile acids.

The liver partakes as a sensor and effector of peripheral metabolic changes and a regulator of systemic blood and nutrient circulation. As such, abnormalities arising from liver dysfunction can influence the brain in multiple ways, owing to direct and indirect bilateral communication between the liver and the brain. Interestingly, altered bile acid composition resulting from perturbed liver cholesterol metabolism influences systemic inflammatory responses, blood-brain barrier permeability, and neuron synaptic functions.

Alterations of presynaptic proteins in autism spectrum disorder.

The expanded use of hypothesis-free gene analysis methods in autism research has significantly increased the number of genetic risk factors associated with the pathogenesis of autism. A further examination of the implicated genes directly revealed the involvement in processes pertinent to neuronal differentiation, development, and function, with a predominant contribution from the regulators of synaptic function. Despite the importance of presynaptic function in synaptic transmission, the regulation of neuronal network activity, and the final behavioral output, there is a relative lack of understanding of the presynaptic contribution to the pathology of autism.

Microplastics released from food containers can suppress lysosomal activity in mouse macrophages.

The ingestion and accumulation of microplastics is a serious threat to the health and survival of humans and other organisms given the increasing use of daily-use plastic products, especially during the COVID-19 pandemic. However, whether direct microplastic contamination from plastic packaging is a threat to human health remains unclear. We analyzed the market demand for plastic packaging in Asia-Pacific, North America, and Europe and identified the commonly used plastic food packaging products.

Ermin deficiency leads to compromised myelin, inflammatory milieu, and susceptibility to demyelinating insult.

Ermin is an actin-binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although Ermin has been predicted to play a role in the formation and stability of myelin sheaths, this has not been directly examined in vivo. Here, we show that Ermin is essential for myelin sheath integrity and normal saltatory conduction.

Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response.

Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only a relatively small proportion of recipients show a durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive tumours are a critical unmet need. Persistent and durable immunological responses are associated with the generation of memory T cells.

Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes.

SignificanceWith obesity on the rise, there is a growing appreciation for intracellular lipid droplet (LD) regulation. Here, we show how saturated fatty acids (SFAs) reduce fat storage-inducing transmembrane protein 2 (FIT2)-facilitated, pancreatic β cell LD biogenesis, which in turn induces β cell dysfunction and death, leading to diabetes. This mechanism involves direct acylation of FIT2 cysteine residues, which then marks the FIT2 protein for endoplasmic reticulum (ER)-associated degradation.

Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases.

Despite recent leaps in modern medicine, progress in the treatment of neurological diseases remains slow. The near impermeable blood-brain barrier (BBB) that prevents the entry of therapeutics into the brain, and the complexity of neurological processes, limits the specificity of potential therapeutics. Moreover, a lack of etiological understanding and the irreversible nature of neurological conditions have resulted in low tolerability and high failure rates towards existing small molecule-based treatments.

Mapping Drug-Induced Neuropathy through In-Situ Motor Protein Tracking and Machine Learning.

Chemotherapy can induce toxicity in the central and peripheral nervous systems and result in chronic adverse reactions that impede continuous treatment and reduce patient quality of life. There is a current lack of research to predict, identify, and offset drug-induced neurotoxicity. Rapid and accurate assessment of potential neuropathy is crucial for cost-effective diagnosis and treatment.

Association of Gut Microbiome Dysbiosis with Neurodegeneration: Can Gut Microbe-Modifying Diet Prevent or Alleviate the Symptoms of Neurodegenerative Diseases?

The central nervous system was classically perceived as anatomically and functionally independent from the other visceral organs. But in recent decades, compelling evidence has led the scientific community to place a greater emphasis on the role of gut microbes on the brain. Pathological observations and early gastrointestinal symptoms highlighted that gut dysbiosis likely precedes the onset of cognitive deficits in Alzheimer's disease (AD) and Parkinson's disease (PD) patients.

A neural circuit for excessive feeding driven by environmental context in mice.

Despite notable genetic influences, obesity mainly results from the overconsumption of food, which arises from the interplay of physiological, cognitive and environmental factors. In patients with obesity, eating is determined more by external cues than by internal physiological needs. However, how environmental context drives non-homeostatic feeding is elusive.

Unique dynamics and exocytosis properties of GABAergic synaptic vesicles revealed by three-dimensional single vesicle tracking.

Maintaining the balance between neuronal excitation and inhibition is essential for proper function of the central nervous system. Inhibitory synaptic transmission plays an important role in maintaining this balance. Although inhibitory transmission has higher kinetic demands compared to excitatory transmission, its properties are poorly understood.

Stromal vascular fraction promotes fibroblast migration and cellular viability in a hyperglycemic microenvironment through up-regulation of wound healing cytokines.

Diabetic wounds have impaired healing and a propensity for further morbidity, which may result in amputations. Stromal vascular fraction (SVF) is an autologous source of heterogeneous cell population obtained from adipose tissue, which is rich in stem cells and presents little immunogenicity to the host. In this study, we hypothesized that murine fibroblasts subjected to hyperglycemic conditions co-treated with SVF exhibit greater functional activity through the colorimetric MTT assay and a cell-monolayer in-vitro scratch assay.