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【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.
ABSTRACT
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Subject(s)
Animals , Rabbits , Atrial Fibrillation/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Signal Transduction , NF-E2-Related Factor 2/pharmacology , Molecular Docking Simulation , Oxidative Stress , Energy Metabolism , Mitochondria/metabolism , Inflammation/metabolism , Heme Oxygenase-1ABSTRACT
Objective To observe the regulation of Panx1 on ATP/IP3 signaling pathway and its mechanism during cisplatin-induced apoptosis of lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line A549 was used as the research object and carbenoxolone (CBX) was used as a drug interference tool. A549 cells were divided into normal control group, the CBX group, the cisplatin (DDP) group and the CBX+DDP group. MTT assay and Annexin V/PI assay were used to detect the survival and apoptosis rates of A549 cells. The relative concentrations of extracellular adenosine triphosphate (ATP) and intracellular inositol triphosphate (IP3) were measured by Chemiluminescence and ELISA. Results Compared with DDP group, the cell survival rate of CBX+DDP group increased, while the early and late apoptotic rates and the release concentration of extracellular ATP and intracellular IP3 decreased (all P < 0.01). Conclusion Panx1 can increase the sensitivity of lung adenocarcinoma cells to cisplatin by regulating the ATP/IP3 signaling pathway.
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Currently, coronavirus disease 2019 (COVID-19) literature has been increasing dramatically, and the increased text amount make it possible to perform large scale text mining and knowledge discovery. Therefore, curation of these texts becomes a crucial issue for Bio-medical Natural Language Processing (BioNLP) community, so as to retrieve the important information about the mechanism of COVID-19. PubAnnotation is an aligned annotation system which provides an efficient platform for biological curators to upload their annotations or merge other external annotations. Inspired by the integration among multiple useful COVID-19 annotations, we merged three annotations resources to LitCovid data set, and constructed a cross-annotated corpus, LitCovid-AGAC. This corpus consists of 12 labels including Mutation, Species, Gene, Disease from PubTator, GO, CHEBI from OGER, Var, MPA, CPA, NegReg, PosReg, Reg from AGAC, upon 50,018 COVID-19 abstracts in LitCovid. Contain sufficient abundant information being possible to unveil the hidden knowledge in the pathological mechanism of COVID-19.
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Prediction of the relations among drug and other molecular or social entities is the main knowledge discovery pattern for the purpose of drug-related knowledge discovery. Computational approaches have combined the information from different resources and levels for drug-related knowledge discovery, which provides a sophisticated comprehension of the relationship among drugs, targets, diseases, and targeted genes, at the molecular level, or relationships among drugs, usage, side effect, safety, and user preference, at a social level. In this research, previous work from the BioNLP community and matrix or tensor decomposition was reviewed, compared, and concluded, and eventually, the BioNLP open-shared task was introduced as a promising case study representing this area.
Subject(s)
ComprehensionABSTRACT
According to the project of WFCMS about carrying out the comparative study on different English versions of textbooks in TCM core courses, this study has done the research for one year. The selected English versions of HUANG DI NEI JING have been compared with the Chinese version sentences by sentences, paragraphs by paragraphs. It is found that the characteristics and diversities of the English versions home and abroad with the common problems of translation have been summarized. Thus, the solution of improvement has been provided and such results could be cited as the references for the translation and external-oriented teaching of HUANG DI NEI JING.
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OBJECTIVE@#To observe the change of auditory brainstem response (ABR) in hearing deprivation rat model induced by bilateral cochlears ablation at different time points.@*METHOD@#Forty SD rats were randomly divided into four experiment groups including 2-week group, 4-week group, 6-week group, 8-week group and four control groups with 5 rats (n = 10) in each group. Then bilateral cochlears ablation was applied to experiment groups. The threshold value of ABR was measured at different time and latent period of each wave was compared.@*RESULT@#The threshold of ABR in experiment group was elevated significantly. The latent period of each wave was pro longed significantly (P < 0.01). In experiment group, the threshold value of ABR in 2-week and 4-week group was significantly greater than that in 6-week group and 8-week group (P < 0.01).@*CONCLUSION@#Bilateral cochlears ablation surgery could elevate the threshold of ABR and latent period of each wave prolonged. The effect of hearing deprivation became apparent after surgery for 4 weeks.
Subject(s)
Animals , Male , Rats , Auditory Threshold , Cochlea , General Surgery , Disease Models, Animal , Evoked Potentials, Auditory, Brain Stem , Physiology , Hearing Loss , Rats, Sprague-DawleyABSTRACT
Objective To investigate the morphological change and SHP -2(src -homology domain contai-ning protein tygosine phosphatase type 2) gene expression in auditory cortical neuron after auditory deprivation in rat .Methods A total of 48 SD rats were randomly divided into 2-week group ,4-week group ,6-week group ,8-week group and 4 corresponding control groups with 6 rats in each group .Bilateral cochlear ablation was done to traumatized groups to ensure their postoperative ABR threshold was above 90 dB SPL .Then paraffin sectioning and HE and Nissl staining were used to detect morphological change of auditory cortical neuron ,simultaneously the RT-PCR was used to measure the expression of SHP -2 gene in auditory cortical neuron of each group ,and relative quantitative analysis was used .Results The HE and Nissl staining revealed that apoptotic shape of auditory cortical neuron became serious by time ,with the diversified cellular morphology .The relative quantity of SHP -2 gene showed statistical differences between any two groups by the method of one -way ANOVA ,showing a rising trend by time (P<0 .05) .Conclusion Along with time ,auditory cortex ,auditory deprivation showed increasing neuronic apoptosis and neuronic proliferation .Apoptosis was the final result from the mutual antagonism by the 2 factors .