Background: Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs) are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date.
Results: We applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424) and medium-confidence (353) miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks.
Conclusions: Our data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974652 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089755 | PLOS |
Background: Focused ultrasound (FUS)-induced blood-brain barrier opening (BBBO) is a technique for safely, non-invasively, and transiently opening the blood brain barrier in a targeted area of the brain. Pre-clinical and clinical studies have shown that FUS is capable of decreasing amyloid plaque load and stimulating neurogenesis in Alzheimer's Disease (AD) models, in addition to being safe for use in human patients. However, the effect of FUS-BBBO on neurons has not yet been characterized, despite its crucial role in cognition and regulating brain function.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Federal University of Technology, Akure, Ondo, Nigeria.
Background: In recent decades, epidemiological and experimental studies have looked into the role of pesticides, particularly the herbicide paraquat, in the development of Parkinson's disease. Horseradish tree (Moringa oleifera) is an ethnobotanical plant with lots of therapeutic potential, but there is a dearth of information on the bioactive properties of the seed alkaloid extracts.
Method: This study examined the modulatory effects of various concentrations of an alkaloid extract from the seeds of Horseradish Tree (Moringa oleifera) on the survival rate of flies exposed to paraquat, as well as certain biochemical and molecular markers related to Parkinson's disease in the heads of the flies.
Alzheimers Dement
December 2024
Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China;, Beijing, China.
Background: Individuals with type 2 diabetes mellitus (T2DM) face an increased risk of dementia. Recent discoveries indicate that SGLT2 inhibitors, a newer class of anti-diabetic medication, exhibit beneficial metabolic effects beyond glucose control, offering a potential avenue for mitigating the risk of Alzheimer's disease (AD). However, limited evidence exists regarding whether the use of SGLT2 inhibitors effectively reduces the risk of AD.
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