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1.
Prev Med ; 172: 107540, 2023 07.
Article in English | MEDLINE | ID: mdl-37164163

ABSTRACT

When the body damages its own tissues in response to an infection, sepsis develops. Medical treatments are limited. It's important to understand the molecular mechanism behind sepsis pathogenesis and identify potential molecular treatment targets. We made two modules based on how genes work together by using WGCNA analysis. The light-green GSE131761 module and the blue GSE137342 module had the strongest links to sepsis. A gene ontology (GO) analysis showed that most of the genes in the lightgreen module were involved in the inflammatory response, specific granule, and immune receptor activity. Most of the genes in the blue module were significantly more likely to have the GO terms proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. The KEGG analysis showed that the genes in module lightgreen were mostly involved in the TNF signaling pathway, while the genes in module blue were mostly involved in the Prion disease pathway. There were two hub genes that were found. In the end, ANKRD22 and VNN1 were singled out as crucial genes. This study used WGCNA to investigate sepsis-associated susceptibility modules and genes. Our study identified two modules and two key genes as essential components in sepsis etiology, which may improve our understanding of its molecular mechanisms.


Subject(s)
Sepsis , Humans , Sepsis/genetics , Gene Ontology
2.
Front Oncol ; 11: 796152, 2021.
Article in English | MEDLINE | ID: mdl-34900747

ABSTRACT

Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

3.
Eur J Pharmacol ; 907: 174222, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34087221

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive system, and shows an especially high incidence in some regions of China. Octamer transcription factors are a family of transcription factors whose DNA-binding domain is a POU domain. OCT transcription factors (OCT-TFs) mediate maintenance of the pluripotency of embryonic stem cells. We measured expression of OCT-TFs in ESCC clinical specimens. Among the OCTs tested, OCT1 showed the highest expression in ESCC tissues. Using molecular docking, we discovered a small-molecule inhibitor, which we named "novel inhibitor of OCT1" (NIO-1), for OCT1. Treatment with NIO-1 inhibited recruitment of OCT1 to the promoter region of its downstream genes and, consequently, repressed OCT1 activation. Treatment with NIO-1 enhanced the susceptibility of ESCC cells to chemotherapeutic agents. Therefore, OCT1 may be a valuable target for ESCC treatment, and NIO-1 could be a promising therapeutic agent.


Subject(s)
Esophageal Squamous Cell Carcinoma , Antineoplastic Agents , Cell Line, Tumor , DNA-Binding Proteins , Humans , Molecular Docking Simulation , Octamer Transcription Factor-1
4.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 15(2): 103-5, 2003 Feb.
Article in Chinese | MEDLINE | ID: mdl-12857471

ABSTRACT

OBJECTIVE: To determine the feasibility, security and clinical effects of the combination of plasma exchange(PE) and high-flow hemodiafiltration (HDF) in the treatment of liver failure caused by severe hepatitis. METHODS: Fifty-eight treatments with combined therapy were taken in 26 patients with severe hepatitis. The changes of clinical symptom, liver function, plasma thrombinogen activity and ammonia were observed to determine the clinical effects. The feasibility and security were determined by therapy related adverse reactions and tolerance of the patients. RESULTS: After the treatment, the clinical symptoms such as conscious disturbance, jaundice, inertia, abdominal distention were taken better turn. The serum bilirubin decreased [(190.8+/-93.6) micromol/L] and PTA increased [(19.7+/-8.9)%]. The major adverse reaction was hypersensitive to plasma, no severe hemorrhage, shock and superinfection happened. All patients tolerated the combined therapy. CONCLUSION: The combined therapy is a safe treatment and can significantly improve the symptoms, blood parameters and recently mortality in hepatic failure patients with severe hepatitis. The therapy is worth to spread.


Subject(s)
Hemodiafiltration , Hepatitis/therapy , Liver Failure/therapy , Plasma Exchange , Adult , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Treatment Outcome
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