Objectives: In this report we focus on angiogenesis, as one component of a complex molecular relations in the process of neovascularisation in the low-grade intraepithelial changes (LSIL). Increasing number of publications indicates that the interrelation between isoforms of VEGF (VEGF121, VEGF145, VEGF165, VEGF183, VEGF189, VEGF206) but not total VEGF is responsible for angiogenesis, both in physiological and pathological processes. The molecular co-operation of the said isoforms and their receptors results in morphological presentation of "de novo" created vascular network that dynamically involves the entire connective tissue stroma of the uterine cervix.
Method: The selection of intraepithelial pathology 38 cases to assess molecular activity of the given genes was based on colposcopy examination. Tissue specimens were taken for pathological investigation and to analyse transcriptional activity and mRNA alternative splicing of the angiogenesis genes. VEGF, Flt-1, Flk-1. To analyse quantitative gene expression RT-PCR TaqMan was performed. To estimate the dependence transcriptional activity of Flt-1 and Flk-1 on VEGF gene expression Spearman's correlation rank was performed. Differences with p < 0.05 were considered significant.
Results: The comparison of transcriptional activity of VEGF and its receptors revealed significant correlation between increase in the number of Flt-1 mRNA copies and enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF165 (p < 0.05), VEGF183 (p < 0.05), VEGF189 (p < 0.05), and VEGF206 (p < 0.05). Significant increase in the number of Flk-1 mRNA copies was observed in case of enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF183 (p < 0.05), VEGF189 (p < 0.05) and VEGF206 (p < 0.05). The number of sFlt-1 mRNA copies significantly correlated only with enhanced VEGF145 mRNA expression (p < 0.05).
Conclusion: Changing intensification of transcriptional activity of VEGF gene and its receptors indicates on autocrine mechanism regulation of angiogenic genes activity in the first steep of carcinogenesis--LSIL.
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Brain
January 2025
Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100, Ankara, Turkey.
Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation.
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Department of Hepatic Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis.
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January 2025
Intensive Care Unit, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, PR China.
Background: Shenfu injection (SFI), derived from a traditional Chinese medicine (TCM) prescription, is an effective drug for the treatment of sepsis-induced myocardial injury (SIMI) with good efficacy, but its exact therapeutic mechanism remains unclear.
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J Neurochem
January 2025
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the potential of using OGA inhibition to treat neurodegenerative diseases. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using the OGA inhibitor Thiamet G (TG), in normal mouse brains.
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January 2025
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.
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