Eukaryotic initiation factor 3a promotes the development of diffuse large B-cell lymphoma through regulating cell proliferation.

BACKGROUND: One-third of diffuse large B-cell lymphoma (DLBCL) patients suffer relapse after standard treatment. Eukaryotic initiation factor 3a (eIF3a) is a key player in the initial stage of translation, which has been widely reported to be correlated with tumorigenesis and therapeutic response. This study aimed to explore the biological role of eIF3a, evaluate its prognostic and therapeutic potential in DLBCL. METHODS: RNA-seq datasets from GEO database were utilized to detect the expression and prognostic role of eIF3a in DLBCL patients. Protein level of eIF3a was estimated by western blot and immunohistochemical. Next, DLBCL cells were transfected with lentiviral vector either eIF3a-knockdown or empty to assess the biological role of eIF3a. Then, samples were divided into 2 clusters based on eIF3a expression and differentially expressed genes (DEGs) were identified. Function enrichment and mutation analysis of DEGs were employed to detect potential biological roles. Moreover, we also applied pan-cancer and chemosensitivity analysis for deep exploration. RESULTS: eIF3a expression was found to be higher in DLBCL than healthy controls, which was associated with worse prognosis. The expression of eIF3a protein was significantly increased in DLBCL cell lines compared with peripheral blood mononuclear cells (PBMCs) from healthy donors. eIF3a knockdown inhibited the proliferation of DLBCL cells and the expression of proliferation-related proteins and increase cell apoptosis rate. Besides, 114 DEGs were identified which had a close linkage to cell cycle and tumor immune. eIF3a and DEGs mutations were found to be correlated to chemosensitivity and vital signal pathways. Pan-cancer analysis demonstrated that high eIF3a expression was associated with worse prognosis in several tumors. Moreover, eIF3a expression was found to be related to chemosensitivity of several anti-tumor drugs in DLBCL, including Vincristine and Wee1 inhibitor. CONCLUSIONS: We firstly revealed the high expression and prognostic role of eIF3a in DLBCL, and eIF3a might promote the development of DLBCL through regulating cell proliferation and apoptosis. eIF3a expression was related to immune profile and chemosensitivity in DLBCL. These results suggest that eIF3a could serve as a potential prognostic biomarker and therapeutic target in DLBCL.

[Effect of miR-125b on T Cell Activation in Aplastic Anemia by Targetting B7-H4].

OBJECTIVE: To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism. METHODS: A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein. RESULTS: Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4+CD69+ T cells and CD8+CD69+ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4+ and CD8+ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4+ and CD8+ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05). CONCLUSION: MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.

Corneal Collagen Cross-Linking Inhibits Corneal Blood and Lymphatic Vessels Temporarily in Alkali-Burned Rabbits.

PURPOSE: This study aimed to explore whether corneal cross-linking (CXL) could regress corneal blood vessels (CBV) and corneal lymphatic vessels (CLV) in alkali-burned rabbits. METHODS: A total of 80 rabbits 2-3 months old weighing 1.5-2.0 kg were randomly divided into four groups: CXL7 group; CTL7 group; CXL14 group; and CTL14 group. Then, 3% sodium pentobarbital 1 ml/kg and tetracaine eye drop 5 g/L were administered before surgery. NaOH 2 mol/L was topically applied to the central cornea to establish the alkali burning model. Then CXL was administered within 2 h in groups CXL7 and CXL14. Corneal opacity and edema, CBV and CLV volume, cluster differentiation 31 (CD31), and lymphatic vessel endothelial receptor 1 (LYVE-1) expression levels were analyzed on days 7 and 14. RESULTS: CXL reduced cornea opacity, CNV, and CLV volumes on day 7 in alkali-burned rabbits. However, CNV and CLV volumes were increased on day 14. CXL also showed down- and upregulation of CD31 and LYVE-1 expression levels on days 7 and 14, respectively. CONCLUSIONS: CXL effectively regulated CBV and CLV in alkali-burned rabbits. The transient angioregression and lymphangioregression induced by CXL may be potentially helpful in vascularized high-risk eyes.

[Galectin-3 Expression and Its Clinical Significance in Acute Myeloid Leukemia with Positive AML1/ETO Fusion Gene].

OBJECTIVE: To investigate the mRNA expression of galectin-3 and its clinical significance in acute myeloid leukemia (AML) patients carrying AML1/ETOfusion gene. METHODS: RQ-PCR method was used to detect the expression of galectin-3 mRNA in bone marrow mononuclear cells of 53 AML patients with AML1/ETO+, ELISA was used to detect the expression of galectin-3 protein in peripheral blood, and the correlations of galectin-3 expression with clinical and laboratory features and outcomes were analyzed. RESULTS: The mRNA and protein levels of galectin-3 were significantly higher in newly diagnosed AML1/ETO+ AML patients compared with the control ( P<0.001). Galectin-3 mRNA and protein expressions were positively correlated (r=0.732, P<0.001). Galectin-3 protein was significantly decreased during the period of complete remission (CR)( P<0.001). The mRNA expression of galectin-3 was negatively correlated with the count of white blood cells ( P=0.014), and positively correlated with CD34 expression and additional cytogenetic aberrations (ACA) ( P=0.001, P=0.026). There was no significant difference in CR, partial remission (PR), induction death (early mortality) between galectin-3 high-expression group and low-expression group ( P>0.05), but there was significant difference in recurrence rate between the two groups ( P=0.029). The median overall survival (OS) rate and disease-free survival (DFS) rate were shortened in the high-expression group ( P=0.007, P=0.015) and the cumulative incidence of relapse was increased ( P=0.045), but there was no significant difference in the cumulative incidence of CM(155mm]mortality ( P>0.05). Cox regression analysis suggested galectin-3 mRNA level an independent indicator of OS and DFS in AML1/ETO+ AML patients. CONCLUSION: Bone marrow galectin-3 mRNA level may be an important reference index for evaluating the prognosis and guiding the treatment of AML1/ETO+ AML patients.

Association study of single nucleotide polymorphisms in XRCC1 gene with the risk of gastric cancer in Chinese population.

Gastric cancer is one of highly cancer-related deaths in the world. Previous evidence suggests that the X-ray repair cross-complementing group 1 gene (XRCC1) is one of the most important candidate genes for influencing gastric cancer risk. The objective of this study was to detect the potential association of genetic variants in XRCC1 gene with gastric cancer risk in Chinese Han population. In total, we enrolled 395 gastric cancer patients and 398 cancer-free controls in this study. The genotyping of c.910A>G and c.1804C>A genetic variants in XRCC1 gene were investigate by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and created restriction site-PCR (CRS-PCR) methods, respectively. We found the genotypes/alleles from these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.910A>G, GG versus (vs.) AA: OR = 2.00, 95% CI 1.21-3.31; AG vs. AA: OR = 1.50, 95% CI 1.12-2.02; GG/AG vs. AA: OR = 1.59, 95% CI 1.20-2.10; GG vs. AG/AA: OR = 1.68, 95% CI 1.03-2.73; G vs. A: OR = 1.47, 95% CI 1.18-1.83; for c.1804C>A, AA vs. CC: OR = 2.68, 95% CI 1.46-4.94; AA vs. CA/CC: OR = 2.62, 95% CI 1.44-4.76; A vs. C: OR = 1.33, 95% CI 1.06-1.66). The allele-G of c.910A>G and allele-A of c.1804C>A genetic variants may contribute to gastric cancer susceptibility. These preliminary results indicate that these XRCC1 genetic variants are potentially related to gastric cancer susceptibility in Chinese Han population, and might be used as molecular markers.

Association between single genetic polymorphisms of MDR1 gene and gastric cancer susceptibility in Chinese.

Gastric cancer is a common cancer worldwide. The multidrug resistance 1 gene (MDR1) is one of the most important candidate genes for influencing gastric cancer susceptibility. This study aimed to analyze the association between genetic variants of MDR1 gene and the susceptibility to gastric cancer in Chinese Han population. A total of 365 gastric cancer patients and 367 cancer-free controls were enrolled in this study. The single genetic polymorphisms (SNPs) of MDR1 gene were genotyped by the created restriction site-polymerase chain reaction method. Our data suggested that the allele and genotype frequencies of c.159G > T and c.1564A > T were statistically different between gastric cancer patients and cancer-free controls. Association analyses indicated that these two SNPs were statistically associated with the increased risk of gastric cancer (for c.159G > T, TT versus (vs.) GG: OR 2.34, 95 % CI 1.31-4.19; TT vs. GT/GG: OR 2.32, 95 % CI 1.32-4.08; T vs. G: OR 1.27, 95 % CI 1.01-1.59; for c.1564A > T, TT vs. AA: OR 2.27, 95 % CI 1.31-3.93; TT vs. AT/AA: OR 2.21, 95 % CI 1.30-3.75; T vs. A: OR 1.30, 95 % CI 1.04-1.62). The allele-T of both these two SNPs may contribute to the susceptibility to gastric cancer in Chinese Han population. The c.159G > T and c.1564A > T genetic variants might be used as molecular markers for detecting gastric cancer susceptibility.