1.CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.
Zhuo ZHENG ; Yongfang LIN ; Hua GUO ; Zheng LIU ; Xiaoliang JIE ; Guizhen WANG ; Guangbiao ZHOU
Frontiers of Medicine 2025;19(2):318-328
The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans
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Lung Neoplasms/metabolism*
;
Histone-Lysine N-Methyltransferase/metabolism*
;
Carcinoma, Squamous Cell/metabolism*
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Gene Expression Regulation, Neoplastic
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Disease Progression
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Cell Proliferation/genetics*
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Cell Line, Tumor
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Chromatin Assembly Factor-1/metabolism*
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Animals
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Mice
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Male
;
Female
2.Analysis of infection and related risk factors after heart transplantation in a third-grade class-A hospital from 2018 to 2023
Linlin GUO ; Lu XIE ; Yongfang LIU ; Panpan LI ; Lin GUO
Journal of Clinical Medicine in Practice 2024;28(6):104-107
Objective To investigate the infection status after heart transplantation (HT) in a third-grade class-A hospital from 2018 to 2023, and explore its risk factors. Methods A retrospective analysis was conducted on the data of 314 patients who underwent HT surgery from January 2018 to July 2023, they were divided into infection group and control group according to postoperative infection situation, the possible influencing factors of HT postoperative infection were analyzed by univariate analysis, and the risk factors of HT postoperative infection were screened by multivariate Logistic regression analysis. Results A total of 91 patients(28.98%)developed postoperative infections, with infection sites of respiratory tract and blood. Logistic regression analysis showed that the main risk factors for postoperative infection in HT patients included complicating with chronic lung disease, surgical time ≥5 h, long retention time of postoperative thoracic drainage tube, long postoperative urinary tube retention time, long postoperative mechanical ventilation time, and preoperative Alb < 35 g/L. Conclusion Complicating chronic lung disease, surgical time ≥5 h, long postoperative thoracic drainage tube retention time, long postoperative urinary tube retention time, long postoperative mechanical ventilation time, preoperative Alb < 35 g/L are related to postoperative infection of HT. Therefore, active intervention should be carried out for the above factors in patients to reduce the risk of infection.
3.Analysis of the association of CYP450 gene polymorphisms with ischemic stroke.
Lin QI ; Yongfang LIU ; Meng QI ; Yingjuan PENG ; Guangming SUN ; Ying YUE
Chinese Journal of Medical Genetics 2023;40(4):500-504
OBJECTIVE:
To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS).
METHODS:
From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People's Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed.
RESULTS:
The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and Apo-A1 (APO-A1) were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P = 0.02), LD-C (95%CI = 1.03-2.25, P = 0.03), Apo-A1 (95%CI = 1.05-2.08, P = 0.04), Apo-B (95%CI = 1.7-4.22, P < 0.01) and Hcy (95%CI = 1.12-1.83, P = 0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS.
CONCLUSION
TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.
Humans
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Cytochrome P-450 CYP3A/genetics*
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Cytochrome P-450 CYP2C19/genetics*
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Ischemic Stroke
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Cholesterol, LDL/genetics*
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Polymorphism, Single Nucleotide
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Genotype
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Apolipoproteins B/genetics*
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Gene Frequency
4.Entery of calcium into ECV304 endothelial cell via CaCa~(2+) activated non-selective cation channel
Dejie YU ; Guanghong BAO ; Lin LIN ; Yongfang ZHENG ;
Chinese Pharmacological Bulletin 2003;0(07):-
AIM To investigate the pathways of Ca 2+ entry into ECV304 endothelial cell and the effect of angiotensin Ⅱ(AⅡ) on calcium activated non setective cation channel(CAN). METHODS The cell attachment and whole cell configurations of patch clamp technique were used to record channel activity. RESULTS (1) The single channel conductance is ? o=(12 90?2 11) pS( n =4) for Ca 2+ passing through CAN of ECV304 cell in condition of pipette solution without K + and Na + but composed 120 mmol?L -1 CaCl 2. The channel current amplitude and open time can be enhanced by 1?10 -7 mol?L -1 AⅡ. The enhanced conductance in CAN is ? 1=(22 18?2 29) pS( n =4). The results of whole cell recording are identified with single channel recording. (2) The whole cell configuration was carried out for recording voltage dependent Ca 2+ channel in ECV304 cell. The peak current amplitude was (29 32?3 56) pA( n =4). This current was inhibited to (6 00?3 94) pA( n =4) by nifedipine and activated by BayK8644. CONCLUSIONS (1)Ca 2+ enters ECV304 cell via Ca 2+ activated non selective cation channel and voltage dependent L type calcium channel. (2) AⅡ can significantly enhance the calcium entry via CAN in ECV304 cell.


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