Objective:To explore the correlation between ferroptosis-related proteins SLC7A11, GPX4, ACSL4 and the radiosensitivity and prognosis of nasopharyngeal carcinoma. And to investigate the potential of these proteins as molecular markers for predicting the radiosensitivity of nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted on 52 cases of nasopharyngeal carcinoma （nasopharyngeal carcinoma group） and 20 cases of chronic nasopharyngiti s（control group）. The relevant clinical data were reviewed, and paraffin-embedded tissue blocks were collected for study. The expressions of SLC7A11, GPX4, and ACSL4 in pathological specimens were detected by immunohistochemical staining. The expression differences of ferroptosis-related proteins between the nasopharyngeal carcinoma group and the control group were analyzed. The nasopharyngeal carcinoma group was further divided based on the protein expression levels into high and low expression subgroups for SLC7A11, GPX4, and ACSL4. Subsequently, a differential analysis of clinical data and survival analysis was conducted for each of these subgroups. Finally, logistic regression analysis was performed to identify the factors influencing radiotherapy resistance in nasopharyngeal carcinoma. Results:①The differential analysis revealed that, compared to the control group, the nasopharyngeal carcinoma group exhibited significantly higher expression of SLC7A11 and GPX4, and lower expression of ACSL4 （P<0.05）. ②Notably, the proportion of patients displaying radioresistance was higher in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups （P<0.05）. However, the proportion of radioresistance in the ACSL4 high expression group was lower than that in the ACSL4 low expression group （P<0.05）. Survival analysis indicated that the 5-year overall survival rate was lower in the SLC7A11 and GPX4 high expression groups compared to their respective low expression groups（P<0.05）. However, the 5-year overall survival rate of the ACSL4 high expression group was higher than that of the ACSL4 low expression group（P<0.05）. ③logistic regression analysis showed that SLC7A11 and GPX4 was an independent risk factor for radioresistance in patients with nasopharyngeal carcinoma（P<0.05）. Conclusion:Nasopharyngeal carcinoma tissues over-express SLC7A11, GPX4, and under-express ACSL4. Over-expression of SLC7A11 and GPX4 are independent risk factors for radioresistance in patients with nasopharyngeal carcinoma. The inhibition of ferroptosis may be related to the occurrence, progression and radioresistance of nasopharyngeal carcinoma. Detection of the expression of SLC7A11, GPX4, and ACSL4 has guiding significance for the evaluation of radiosensitivity and prognosis of patients with nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/pathology* ; Coenzyme A Ligases/metabolism* ; Radiation Tolerance ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Prognosis ; Long-Chain-Fatty-Acid-CoA Ligase ; Retrospective Studies ; Ferroptosis ; Male ; Female ; Middle Aged

Objective:To report a case of autosomal recessive dyskeratosis congenita, and to detect mutations in its causative genes.Methods:Peripheral blood samples were collected from the proband and her parents, genomic DNA was extracted, and 100 unrelated healthy individuals served as controls. The Illumina Nextseq500 sequencer was used to detect sequence variations in coding regions of exons of the skin disease-related genes in the proband′s family, and the causative mutation was verified by PCR-Sanger sequencing. The conservation and pathogenicity of gene mutation sites and corresponding protein structure changes were predicted by using bioinformatics softwares Clustalw2.0, PyMOL, PolyPhen-2, SIFT and FATHMM.Results:The proband clinically presented with reticular poikilodermatous patches on the neck and chest, punctate pigmentation on the axilla, atrophy of some toenails, rough skin and oral leukoplakia, accompanied by abnormality in some indicators of routine blood tests and liver function. Genetic testing showed that the proband carried compound heterozygous mutations c.2452G>A (p.Val818Met) and c.2594G>A (p.Arg865His) in the TERT gene, and the c.2452G>A mutation was not included in the Human Gene Mutation Database. The proband′s mother carried a heterozygous mutation c.2452G>A, and no mutation was identified in the TERT gene of her father or 100 healthy controls. Bioinformatics analysis showed that the amino acid positions 818 and 865 of TERT proteins in multiple species were highly conserved and completely conserved respectively, and the corresponding protein structures changed after the above gene mutations. Based on the clinical manifestations, genetic testing, auxiliary examinations, and bioinformatics analysis results, the patient was finally diagnosed with autosomal recessive dyskeratosis congenita.Conclusion:The compound heterozygous mutations c.2594G>A (p.Arg865His) and c.2452G>A (p.Val818Met) in the TERT gene may be responsible for the clinical phenotype of the proband.

AIM: To explore the effects of kaempferol on the proliferation, invasion and migration abilities of HBx-HepG2 cells and to examine the underlying molecular mechanisms.METHODS: The expression levels of related genes at mRNA and protein levels were determined by RT-qPCR and Western blot.The cell apoptotic rate was analyzed by flow cytometry.The cell proliferation, growth, invasion and migration abilities were measured by MTT assay, colony formation assay, Transwell invasion assay and wound healing assay, respectively.RESULTS: Kaemferol inhibited HBx-HepG2 cell proliferation in a concentration-and time-dependent manner.Kaempferol at 100 μmol/L significantly inhibited the colony formation, invasion and migration abilities of the HBx-HepG2 cells.Kaemferol at 100 μmol/L also increased cell apoptotic rate, increased the protein levels of cleaved caspase-3, cleaved caspase-9 and Bax, and decreased the expression level of Bcl-2.In addition, kaemferol at 100 μmol/L suppressed the mRNA and protein expression levels of β-catenin, c-Myc and cyclin D1 in the HBx-HepG2 cells.Kaemferol at 100 μmol/L also suppressed the protein level of p-GSK-3β and the β-catenin protein levels in both cytoplasm and nucleus.LiCl treatment reversed the inhibitory effect of kaempferol on the growth, invasion and migration of the HBx-HepG2 cells.CONCLUSION: Kaempferol inhibits cell proliferation, invasion and migration via activating Wnt/β-catenin signaling in HBx-HepG2 cells.

OBJECTIVE: To investigate the prevalence of human papillomavirus in nasopharyngeal carcinomas of Fujian province in China. METHOD: Samples from 70 patients with NPC and 25 controls. All samples were detected HPV DNA by polymerase chain reaction (PCR) suing GP5+/6+ and MY09/11 primers and genotyped by surface plasmon resonance (SPR) and HPV 16/18 E6 and LMP-1 using immunohistochemistry and EBER using in situ hybridization. RESULT: Only 2 cases of 70 patients were showed evidence of HPV DNA by PCR, the 2 HPV positive cases subtype HPV-70 and HPV-18 were genotyped by SPR, both the 2 HPV positive cases are non-keratinizing carcinomas (the HPV-70 positive one is differentiated and the HPV-18 positive one is undifferentiated), both the 2 HPV positive cases do not show any evidence of EBV. Data showed that 57 of 70 NPC detected EBER positive, but only 25 out of 70 NPC samples were detected LMP-1 positive. CONCLUSION Our study showed a low prevalence of human papillomavirus in NPC patients of Fujian province in Southern China, there is no evidence about HPV and EBV co-infection.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma ; China ; epidemiology ; DNA, Viral ; isolation & purification ; Epstein-Barr Virus Infections ; epidemiology ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; epidemiology ; virology ; Papillomaviridae ; classification ; isolation & purification ; Papillomavirus Infections ; epidemiology ; Young Adult