RNAscope

A planar culture model of human absorptive enterocytes reveals metformin increases fatty acid oxidation and export

Fatty acid oxidation by absorptive enterocytes has been linked to the pathophysiology of type 2 diabetes, obesity, and dyslipidemia. Caco-2 and organoids have been used to study dietary lipid-handling processes including fatty acid oxidation but are limited in physiological relevance or preclude simultaneous apical and basal access.

Traumatic-noise-induced hair cell death and hearing loss is mediated by activation of CaMKKβ

The Ca2+/calmodulin-dependent protein kinase kinases (CaMKKs) are serine/threonine-directed protein kinases that are activated following increases in intracellular calcium, playing a critical role in neuronal signaling. Inner-ear-trauma-induced calcium overload in sensory hair cells has been well documented in the pathogenesis of traumatic noise-induced hair cell death and hearing loss, but there are no established pharmaceutical therapies available due to a lack of specific therapeutic targets.

Neuron Subtype Specific Molecular Mechanisms in Fentanyl Abstinence

Background Opioid withdrawal or abstinence generates a negative affective state and causes dendritic atrophy in nucleus accumbens (NAc) medium spiny neurons (MSNs). Based on our previous work, we hypothesized that opioid abstinence-induced atrophy is MSN subtype-specific, and blocking the subtype-specific molecular mediators can reverse behavioral changes caused by opioid abstinence. Methods All experiments were conducted in 8-10-week-old mice using sex as a biological variable.

Regulatory guidelines and preclinical tools to study the biodistribution of RNA therapeutics

The success of the messenger RNA-based COVID-19 vaccines of Moderna and Pfizer/BioNTech marks the beginning of a new chapter in modern medicine. However, the rapid rise of mRNA therapeutics has resulted in a regulatory framework that is somewhat lagging. The current guidelines either do not apply, do not mention RNA therapeutics, or do not have widely accepted definitions. This review describes the guidelines for preclinical biodistribution studies of mRNA/siRNA therapeutics and highlights the relevant differences for mRNA vaccines.

Clinical and translational values of spatial transcriptomics

The combination of spatial transcriptomics (ST) and single cell RNA sequencing (scRNA-seq) acts as a pivotal component to bridge the pathological phenomes of human tissues with molecular alterations, defining in situ intercellular molecular communications and knowledge on spatiotemporal molecular medicine. The present article overviews the development of ST and aims to evaluate clinical and translational values for understanding molecular pathogenesis and uncovering disease-specific biomarkers.

Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?

Almost all currently available treatments for inflammatory bowel disease (IBD) act by inhibiting inflammation, often blocking specific inflammatory molecules. However, given the infectious and neoplastic disease burden associated with chronic immunosuppressive therapy, the goal of attaining mucosal healing without immunosuppression is attractive. The absence of treatments that directly promote mucosal healing and regeneration in IBD could be linked to the lack of understanding of the underlying pathways. The range of potential strategies to achieve mucosal healing is diverse.

Células e tecidos humanos em estudos pré-clínicos: gânglios raquidianos humanos

A dor é uma experiência sensorial e emocional, comumente iniciada em resposta a um estímulo nóxico. Um grupo de neurónios sensoriais periféricos, conhecidos como nociceptores, são os primeiros neurónios a serem ativados pelo estímulo nóxico. Os corpos celulares dos neurónios sensoriais estão alojados no gânglio do trigémeo (TG) ou no gânglio raquidiano dorsal (DRG), situados bilateralmente e adjacentes ao tronco cerebral ou coluna vertebral.

Unilateral loss of maxillary molars in young mice leads to bilateral condylar adaptation and degenerative disease

The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in pre-pubertal, 3-week-old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle three weeks later.

Contemporary Approaches to the Study of Pain

This volume contains experimental approaches that are currently revolutionizing our understanding of the neurobiology of pain.

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