ABSTRACT
Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
Subject(s)
Rats , Animals , Posterior Horn Cells/pathology , Spinal Cord Dorsal Horn/metabolism , Neuralgia , Synaptic TransmissionABSTRACT
Objective To investigate the curative effects of various infusion volumes on liver-related metabolic mechanism in the treatment of hemorrhagic shock.Methods A severe hemorrhagic shock rabbit model was established in 30 rabbits.The rabbits were randomly divided into three groups:non-infusion group (A), conventional infusion group (B), and excessive infusion group (C) (n=10 in each group).Taking group B as the control, groups A and C were observed for the damage of non-infusion and excessive infusion, respectively.The outcomes in the three groups and their relations with liver tissue metabolism changes were analyzed with gas chromatograph-mass spectrometer (GC-MS).Results The mortality in groups A, B, and C group were 80％, 0％, and 70％, respectively.The liver tissue metabolic profile in group B showed statistically significant difference compared with that in groups A and B.In group C, the levels of 21 metabolites were lower than those in group B, and the levels of8 metabolites were lower than those in group A.The relative contents of various metabolites were correlated with infusion volumes, and the succinic acid content was associated with death events (P＜0.05).Conclusion The conventional infusion has significant curative effect on hemorrhagic shock.The metabolites of liver tissues with excessive infusion are generally decompensated and have longer survival time than those in non-infusion group, which may caused by the excessive infusion-induced blood volume increase after hemorrhagic shock.Tissue fluid dilution is an important cause of death.
ABSTRACT
ESE-3 belongs to the epithelium-specific ETS transcription factor subfamily of ETS (E26) located in chromosome 11p12. It belongs to the transcriptional regulation factor which forms transcription complexes with its effector molecules, enhancing or inhibiting transcription of different downstream target genes. The expression of ESE-3 is abnormal in many kinds of tumors, such as colon cancer, pancreatic cancer, prostate cancer, breast cancer and so on. It suggests that ESE-3 plays an important role on the pathogenesis of various tumors.
ABSTRACT
OBJECTIVES@#To explore the metabolic characteristics of lethal bradycardia induced by myocardial ischemia in rat's serum.@*METHODS@#A rat myocardial ischemia-bradycardia-sudden cardiac death （MI-B-SCD） model was established, which was compared with the sham-operation group. The metabolic profile of postmortem serum was analyzed by gas chromatography-mass spectrometry （GC-MS）, coupled with the analysis of serum metabolic characteristics using metabolomics strategies.@*RESULTS@#The serum metabolic profiles were significantly different between the MI-B-SCD rats and the control rats. Compared to the control rats, the MI-B-SCD rats had significantly higher levels of lysine, ornithine, purine, serine, alanine, urea and lactic acid; and significantly lower levels of succinate, hexadecanoic acid, 2-ketoadipic acid, glyceraldehyde, hexendioic acid and octanedioic acid in the serum. There were some correlations among different metabolites.@*CONCLUSIONS@#There is obvious metabolic alterations in the serum of MI-B-SCD rat. Both lysine and purine have a high value in diagnosing MI-B-SCD. The results are expected to provide references for forensic and clinical applications of prevention and control of sudden cardiac death.