Electroacupuncture at PC6 Acupoint Adjusts Genome-Wide Gene Expressions and Alters Carfilzomib-Induced Cardiotoxicity in Mice
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PROVIDER: PRJNA1020202 | ENA |
REPOSITORIES: ENA
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Project description:Carfilzomib (CFZ) is a proteasome inhibitor commonly used in the treatment of multiple myeloma, but its clinical application is limited due to its cardiotoxicity. The Neiguan acupoint (PC6) stimulation has been reported to effectively improve cardiac function, but its regulatory mechanism remains unclear. The aim of this study was to investigate the effect and underlying mechanism of electroacupuncture (EA) against CFZ-induced cardiotoxicity in C57BL/6 mice. According to our results, EA treatment significantly reversed CFZ-induced ejection fraction and fractional shortening reduction, which showed great potential effect for heart protection. By using RNA-sequencing, we compared the transcriptome profile of heart samples from DMSO control, CFZ injection, and EA treatment mice, and nearly 40,000,000 valid sequence reads aligned with 20,000 genes from six libraries were obtained. A total of 770 differentially expressed genes (DEGs) were identified in the CFZ (vs. Control) group, including 65 up-regulated and 705 down-regulated genes. Meanwhile, 329 DEGs were obtained in the EA (vs. CFZ) group, including 251 up-regulated and 78 down-regulated genes. Our results shed new insights into the regulatory mechanism of EA at PC6 against CFZ-induced cardiotoxicity, which could further provide theoretical basis for clinical EA therapy.
2025-09-01 | GSE243878 | GEO
Project description:Carfilzomib Suppresses SENP1 to Trigger Cardiotoxicity by DDX17 Destabilization
| PRJNA1144389 | ENA
Project description:Whole Exome Sequencing Analysis of Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients
| PRJNA975677 | ENA
Project description:Whole Exome Sequencing Analysis of Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients
| PRJNA975678 | ENA
Project description:Carfilzomib has a good effect in treating multiple myeloma, but more and more clinical studies have shown that the drug can cause cardiac toxicity during use, but the mechanism of action is unclear. This study aimed to comprehensively elucidate the mechanism of CFZ-induced cardiomyopathy by constructing a C57BL/6 mouse model and combining cell experiments. The research results showed that the hearts of mice treated with CFZ appeared significantly enlarged, and the cardiac function indicators decreased. The serum enzyme LDH, AST, and CK-MB levels significantly increased, suggesting severe myocardial injury. RNA extraction and QPCR detection of the heart showed that the expression of heart hypertrophy and fibrosis markers increased. Meanwhile, histological staining found that there were fewer cardiomyocytes, damaged myofibrils, and cardiac fibrosis. In the cell experiments, CFZ treatment caused the release of more LDH from rat cardiomyocytes and H9C2 cells, increased CASPASE 3/7 activity, abnormal cell morphology, enlarged cell size, myocardial hypertrophy and fibrosis marker gene expression in cardiomyocytes. Through the study of the SUMOYLATION pathway, it was found that CFZ's effects on cardiomyocyte structure and function were related to the expression of SENP genes, especially SENP1, which showed a significant downregulation in cardiomyocytes and mouse heart tissue, and was positively correlated with the levels of cardiac injury marker genes. This study further explored the mechanism of action by specifically altering the expression of SENP1 in cardiomyocytes. The results show that the knockdown of SENP1 in cardiomyocytes leads to more severe myocardial damage after CFZ treatment, suggesting that the expression of SENP1 can potentially affect the cardiotoxicity caused by CFZ. Further, by using silver staining and mass spectrometry to identify the interacting proteins with SENP1 after CFZ treatment, we found that the knockdown of DDX17 had a similar myocardial injury effect as SENP1. Subsequently, through Co-IP, protein stability experiments, and ubiquitination analysis experiments, we determined that SENP1 can maintain the protein stability of DDX17 by inhibiting its SUMO modification, thereby preventing cardiomyocyte injury and apoptosis. We hope to provide a new perspective and potential cardioprotective strategy for clinical use.
2024-08-10 | GSE273971 | GEO
Project description:Interventions: C groups:Acupoint electroacupuncture stimulation from one day to 30 minutes before operation;A group:Intravenous anesthesia;B group:Acupoint electroacupuncture stimulation one day before operation
Primary outcome(s): awake score;VAS score
Study Design: Parallel
| 48297 | ecrin-mdr-crc
Project description:KMS-11 and KMS-34 cells were exposed to stepwise increasing concentrations of carfilzomib over a period of 18 weeks: cells adapted to growth in 4 nM carfilzomib by 4 weeks, in 6 nM in another 6 weeks and in 12 nM after a further 8 weeks. The resulting cell cultures, denoted KMS-11/Cfz and KMS-34/Cfz, respectively, retained resistance to carfilzomib even when tested after removal of selective pressure for approximately 8 weeks. KMS-11/Cfz and KMS-34/Cfz cells were profiled for gene expression after 1 week of growth in the absence of carfilzomib together with parental KMS-11 and KMS-34 cells which had not been selected in the drug (triplicate samples).
2015-07-09 | E-GEOD-69078 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) ranks among one of the most prevalent and lethal cancers affecting humans. Currently, there are limited effective treatments available for HCC. In the search for potential anti-HCC agents, we found that carfilzomib, a proteasome inhibitor, exerts anti-HCC activities. However, the underlying mechanisms of action are main unclear. In this study, we evaluated the effectiveness of carfilzomib against HCC capability and explored its underlying mechanisms. Cell Counting Kit 8 (CCK8), EdU (5-ethynyl-2-deoxyuridine) staining, and colony formation assays were employed to analyze the antiproliferative ability of carfilzomib on MHCC-97H and Huh7 cells. Additionally, flow cytometry was used to assess the effect on the cell cycle. Western blotting was utilized to examine the protein expression levels associated with cell cycle arrest. Furthermore, short hairpin RNA (shRNA) transfection was used to investigate the role of GADD45a (growth arrest and DNA damage 45a) on carfilzomib-induced cell cycle arrest. A xenograft tumor model using nude mouse was employed to evaluate the anti-HCC activity of carfilzomib in vivo. The finding demonstrated that carfilzomib inhibited the proliferation, invasion, and migration in both MHCC-97H and Huh7 cells. In addition, carfilzomib caused cell cycle arrest by suppressing the expression of cyclin A1, cyclin E1, cyclin-dependent kinases 2 (CDK2), and cyclin-dependent kinases 4 (CDK4). It also upregulated the expression of GADD45a, and inhibition of GADD45a through shRNA abolished carfilzomib-induced cell cycle arrest in HCC cells. Importantly, carfilzomib demonstrated its ability to inhibit the Huh7 cell growth in vivo. Our research has revealed, for the first time, that carfilzomib inhibited the progression of HCC cells by upregulating GADD45a expression. These findings suggest that carfilzomib could be a potential chemotherapeutic agent against HCC.
2024-12-18 | GSE284346 | GEO
Project description:The electroacupuncture-induced analgesic effect has been used widely to alleviate diverse pains. However, significant individual variations in analgesic effect of EA for both experiments and clinics were reported. According to the sensitivity of the analgesic response to EA stimulation, the subjects could be categorized into high responders (HR) and low responders (LR). However, the molecular mechanism of individual variability in the analgesic response to acupuncture stimulation is still uncertain. This study aims to investigate the potential gene expression in spinal dorsal horn induced by 2Hz/100Hz electroacupuncture in HR and LR rats. Rats were given 2Hz or 100Hz electroacupuncture for 30 min and using cDNA microarrays to compare different gene expression in dorsal horn. Transcriptome profiling analysis found that some co-regulated genes related with electroacupuncture or 2Hz or 100Hz freqencies. These co-regulated genes were plasticity-related by GO analysis. We also found some special regulated genes in HR vs. LR in 2Hz/100Hz electroacupuncture stimulation. These results suggested that neurotransmitter system and cytokine different between HR with LR in 2Hz electroacupuncture. But in 100Hz electroacupunture, there were many different regulated genes related with ribosome between HR with LR, which needs more studies to research the function and may play an important role in HR vs. LR by 100Hz electroacupuncture. Keywords: Transcriptome analysis Rats were exposed to different frequencies (2Hz or 100Hz) electroacupuncture stimlation for 30 min and nociceptive testing and returned to home cages for 1 hours before sacrificed. According to the sensitivity of the analgesic response to 2Hz or 100Hz EA stimulation, the rats divided into four groups: 2Hz-HR group, 2Hz-LR group, 100Hz-HR group and 100Hz-LR group. Subsequently analyzed their dorsal horn transcript profile using cDNA microarrays, the rats were without receiving electroacupuncture as control. The tissue of dorsal horn (DH) of the fifth and sixth lumbar (L5 and L6) of four or five rats were selected for transcript analysis in each group. The five control rats were mixed and labeled with cy5, each rat of experiment groups was labeled with cy3.
2010-04-11 | E-GEOD-21258 | biostudies-arrayexpress
Project description:The electroacupuncture-induced analgesic effect has been used widely to alleviate diverse pains. However, significant individual variations in analgesic effect of EA for both experiments and clinics were reported. According to the sensitivity of the analgesic response to EA stimulation, the subjects could be categorized into high responders (HR) and non responders (NR). However, the molecular mechanism of individual variability in the analgesic response to acupuncture stimulation is still uncertain. This study aims to investigate the potential gene expression in arcuate nucleus induced by 2Hz/100Hz electroacupuncture in HR and NR rats. Rats were given 2Hz or 100Hz electroacupuncture for 30 min and using cDNA microarrays to compare different gene expression in arcuate nucleus. Rats were exposed to different frequencies (2Hz or 100Hz) electroacupuncture stimulation for 30 min and nociceptive testing and returned to home cages for 1 hour before sacrificed. According to the sensitivity of the analgesic response to 2Hz or 100Hz EA stimulation, the rats divided into four groups: 2Hz-HR group, 2Hz-NR group, 100Hz-HR group and 100Hz-NR group. Subsequently analyzed their dorsal horn transcript profile using cDNA microarrays, the rats were without receiving electroacupuncture as control. The tissue of arcuate nucleus (Arc) of three rats was selected for transcript analysis in each group. The three control rats were mixed and labeled with cy5, each rat of experiment groups was labeled with cy3.
2011-07-07 | E-GEOD-30365 | biostudies-arrayexpress