RESUMEN
Objective: To investigate the diagnostic value of serum lipoprotein associated phospholipase A2 (Lp-PLA2), amyloid A (SAA) and immunoglobulin E (IgE) in patients with type 2 diabetes (T2DM) mellitus complicated with atherosclerotic disease. Methods: From June to December 2019, 224 patients with T2DM in the Second Hospital of Lanzhou University were selected, including 144 males and 80 females, aged (61±11) years. According to the results of imaging examination, the patients were divided into T2DM with AS group (T2DM-AS group, n=160) and T2DM group (n=64); Healthy subjects in the same period were selected as healthy control group (n=160). Lp-PLA2, IgE, SAA, hs-CRP, TC, TG, HDL-C, LDL-C and Hcy were detected in all patients and healthy controls. The correlation between the above indexes, gender, age and T2DM with AS was analyzed; Multivariate logistic regression was used to analyze the risk factors of T2DM with AS. Results: Compared with the healthy control group, the levels of IgE and Lp-PLA2 in T2DM-AS group and T2DM group were increased, and the levels of SAA in T2DM-AS group were increased (all P<0.05); Compared with T2DM group, the levels of Lp-PLA2, IgE and SAA were increased in T2DM-AS group (all P<0.05). T2DM with AS was positively correlated with age, IgE, Lp-PLA2 and SAA (r=0.468, 0.269, 0.486, 0.418, all P<0.05), and negatively correlated with HDL-C (r=-0.338, P<0.05). Multivariate logistic regression analysis showed that age (OR=0.865, 95%CI: 0.763-0.982, P<0.05), IgE (OR=0.910, 95%CI: 0.840-0.987, P<0.05) and Lp-PLA2 (OR=0.942, 95%CI: 0.910-0.986, P<0.05) were risk factors of T2DM with AS. ROC curve showed that the combined detection of Lp-PLA2, SAA and IgE could improve the diagnostic efficiency of T2DM with AS (AUC=0.895, P<0.05), the sensitivity was 80.0%, and the specificity was 93.7%. Conclusion: The levels of Lp-PLA2, IgE and SAA increase in T2DM patients with AS. The combined detection of Lp-PLA2, SAA and IgE can improve the diagnostic efficiency of T2DM patients with AS.
Asunto(s)
Aterosclerosis , Diabetes Mellitus Tipo 2 , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Aterosclerosis/diagnóstico , Biomarcadores , Proteína C-Reactiva , Preescolar , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.
Asunto(s)
Pérdida Auditiva Provocada por Ruido/sangre , MicroARNs/sangre , Proteína Quinasa 1 Activada por Mitógenos/análisis , Enfermedades Profesionales/sangre , Exposición Profesional/efectos adversos , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Regulación de la Expresión Génica , Ontología de Genes , Pérdida Auditiva Provocada por Ruido/genética , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Enfermedades Profesionales/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: To explore the effect of let-7 miRNA silencing on Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication and the underling mechanism. METHODS: The pEGFP-C2-let-7 sponge vector was transfected into BCBL-1 and 293T cells with Lipofectamine 2000 to silence the expression of let-7 miRNAs. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of let-7 miRNAs, the transcriptional levels of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), cyclooxygenase-2 (COX-2) and matrix metalloproteinase 13 (MMP-13), and the DNA copy numbers of KSHV open reading frame 50 (ORF50) and open reading frame 72 (ORF72). Western blot was used to detect the total and phosphorylated protein levels of MAP4K4, COX-2, extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK. RESULTS: The expression of let-7 miRNAs was dramatically decreased in the let-7 sponge transfected BCBL-1 and 293T cells compared with that in the vector-transfected cells (P<0.05 for all). The gene copy number and mRNA transcriptional level of KSHV ORF50 were significantly increased in the let-7 sponge transfected BCBL-1 cells compared with that in the vector-transfected cells (1.00±0.10 vs. 2.33±0.18 and 1.08±0.48 vs 3.22±0.27, respectively,P<0.001 for both). The gene copy number and mRNA transcriptional level of KSHV ORF72 were also significantly increased in let-7 sponge transfected BCBL-1 cells compared with those in the vector-transfected cells(1.07±0.49 vs 1.67±0.45 and 1.01±0.19 vs 1.54±0.11, respectively,P<0.05 for both). Furthermore, the mRNA transcriptional levels of MAP4K4, COX-2 and MMP-13 were significantly increased in the let-7 sponge transfected BCBL-1 cells compared with those in the vector-transfected cells (1.00±0.05 vs 5.73±0.96, 1.00±0.05 vs 2.68±0.19, 1.00±0.02 vs 2.69±0.25, respectively,P<0.001 for all). Let-7 miRNAs silencing also increased the protein expression levels of MAP4K4, COX-2 and phospho-ERK1/2, while the phospho-JNK and phospho-p38 were not changed in the BCBL-1 and 293T cells. CONCLUSIONS: Let-7 silencing may activate the replication of KSHV, possibly through up-regulating MAP4K4 and its downstream molecules COX-2, MMP-13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma.