Neuroprotective effects of lovastatin in the pilocarpine rat model of epilepsy according to the expression of neurotrophic factors

Sabunciyan²,

Florea

2022

Genome Biol

Tools for differential splicing detection have failed to provide a comprehensive and consistent view of splicing variation. We present MntJULiP, a novel method for comprehensive and accurate quantification of splicing differences between two or more conditions. MntJULiP detects both changes in intron splicing ratios and changes in absolute splicing levels with high accuracy, and can find classes of variation overlooked by other tools. MntJULiP identifies over 29,000 differentially spliced introns in 1398 GTEx brain samples, including 11,242 novel introns discovered in this dataset. Highly scalable, MntJULiP can process thousands of samples within hours to reveal splicing constituents of phenotypic differentiation.

Section: Resultsmentioning

confidence: 99%

Comprehensive and scalable quantification of splicing differences with MntJULiP

Sabunciyan²,

Florea

2022

Genome Biol

“…21,23 Animals were excluded from the study if they did not kindle (animals score less than stage 4 according to the Racine) after 28 days. 24,25…”

Section: Ptz Kindlingmentioning

confidence: 99%

Baicalin Rescues Cognitive Dysfunction, Mitigates Neurodegeneration, and Exerts Anti-Epileptic Effects Through Activating TLR4/MYD88/Caspase-3 Pathway in Rats

Jia

Xiao

et al. 2021

DDDT

This study aims to evaluate the beneficial effects of anti-epileptic mechanisms of baicalin (BA) on cognitive dysfunction and neurodegeneration in pentylenetetrazol (PTZ)induced epileptic rats. Methods: First, PTZ-induced epileptic rats were administered intraperitoneally a subconvulsive dose of PTZ (40 mg/kg) daily, and the seizure susceptibility (the degree of seizures and latency) was evaluated using Racine's criterion. Then, classical behavioral experiments were performed to test whether BA ameliorated cognitive dysfunction. Neurodegeneration was assessed using Fluoro Jade-B (FJB), and NeuN staining was used to determine whether BA offered a neuroprotective role. After BA had been proven to possess anti-epileptic effects, its possible mechanisms were analyzed through network pharmacology. Finally, the key targets for predictive mechanisms were experimentally verified.Results: The epileptic model was successfully established, and BA had anti-epileptic effects. Epileptic rats displayed significant cognitive dysfunction, and BA markedly ameliorated cognitive dysfunction. Further, we also discovered that BA treatment mitigated neurodegeneration of the hippocampus CA3 regions, thereby ameliorated cognitive dysfunction of epileptic rats. Subsequent network pharmacology analysis was implemented to reveal a possible mechanism of BA in the anti-epileptic process and the TLR4/MYD88/Caspase-3 pathway was predicted. Finally, experimental studies showed that BA exerted an antiepileptic effect by activating the TLR4/MYD88/Caspase-3 pathway in PTZ-induced epileptic rats. Conclusion:In conclusion, BA had a protective effect against PTZ-induced seizures. BA improved cognitive dysfunction and exerted a neuroprotective action. The anti-epileptic effects of BA may be potentially through activation of the TLR4/MYD88/Caspase-3 pathway.

“…Therefore, the increase in abundance appears to be due to the change in the expression of Cntf, which owing to the special sharing of gene structure was missed by DESeq2. Cntf is a survival factor for multiple neuronal cell types, and an increase in its levels was shown to be involved in attenuating epilepsy-related brain damage 16,17 .…”

Section: Performance Evaluation On Real Datamentioning

confidence: 99%

Comprehensive and scalable quantification of splicing differences with MntJULiP

Sabunciyan²,

Florea

2020

Preprint

Alternative splicing of mRNA is an essential gene regulatory mechanism with important roles in development and disease. We present MntJULiP, a method for comprehensive and accurate quantification of splicing differences between two or more conditions. MntJULiP implements novel Dirichlet-multinomial and zero-inflated negative binomial models within a Bayesian framework to detect both changes in splicing ratios and in absolute splicing levels of introns with high accuracy, and can find classes of variation overlooked by reference tools. Additionally, a mixture model allows multiple conditions to be compared simultaneously. Highly scalable, it processed hundreds of GTEx samples in <1 hour to reveal splicing constituents of tissue differentiation.