RESUMO
What is already known about this topic?: Many regions in China have recently reported outbreaks of the coronavirus disease 2019 (COVID-19) caused by the Omicron variant. What is added by this report?: Wuchuan County, Guizhou Province reacted quickly and implemented accurate intervention measures to effectively control the outbreak. The susceptible-exposed-infectious-asymptomatic-removed (SEIAR) model was applied to evaluate the effectiveness of intervention measures. What are the implications for public health practice?: Fast response measures should be taken to prevent the spread of outbreaks caused by the Omicron variant.
RESUMO
Lanthanides possess diverse biological effect and have been shown to promote cell proliferation and induce apoptosis. Our previous studies showing that lanthanide citrate complex has significant antitumor activity in human cervical cancer HeLa cells. This study aims at determining if [LaCit(2)](3-) have the activity against another type of human cervical cancer cell line SiHa and the changes in protein expression that contribute to the mechanism(s) of [LaCit(2)](3-)-mediated apoptosis in SiHa cells. Cell growth inhibition was measured by MTT method, and apoptosis was detected by means of Hoechst 33258 staining and flow cytometry analysis. After [LaCit(2)](3-)-treatment the results show that the growth of SiHa cells was inhibited, the cells displayed typical apoptosis morphological changes, and increase in the rates of apoptosis. Using proteomics approaches, a variety of differentially expressed proteins were identified in SiHa cells before and after treatment with [LaCit(2)](3-). There were profound changes in 10 proteins relating to mitochondrial function and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in [LaCit(2)](3-)-induced apoptosis. This was confirmed by a decrease in the mitochondrial transmembrane potential (Δψ(m)), and increases in H(2)O(2) generation in [LaCit(2)](3-)-treated cells. Among them the alerted proteins, Prx I, ANXA1 and TRAF5 were validated by western blotting analyses. These results suggest that there is an intrinsic molecular pathway of cell apoptosis in [LaCit(2)](3-)-treated SiHa cells. This observation is in accordance with our previous reports about the effects of [LaCit(2)](3-) and [YbCit(2)](3-) on HeLa cells and it provide a molecular mechanism underlying lanthanide citrate complex-mediated cell apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Citratos/farmacologia , Lantânio/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To explore the effects of ytterbium citrate on human liver carcinoma HepG2 cell line and the potential mechanisms. METHODS: The HepG2 cells were cultured with DMEM medium and divided into different groups in the following media, in serum-free medium as control, different concentration (0.01 - 5.00 mmol/L) [YbCit(2)](3-)+serum-free medium as treatment group, MTT assay was used to measure the viability of the cells; 2.00 mmol/L [YbCit(2)](3-)+serum-free medium was used as treatment group, and Hoechst 33258 staining was used to detect apoptosis in HepG2 cells. Differential proteomic analysis, assay of intracellular H(2)O(2) levels and mitochondrial transmembrane potential were performed to study the effects of [YbCit(2)](3-) on HepG2 cells and the potential mechanisms. RESULTS: The data showed that 72 h treatment of [YbCit(2)](3-) at 2.00 - 5.00 mmol/L significantly inhibited cell proliferation, and the IC(50) was (2.46 ± 0.23) mmol/L. After treatment with 2.00 mmol/L [YbCit(2)](3-) for 48 h and 72 h, Hoechst 33258 staining demonstrated that [YbCit(2)](3-) induced significantly increased apoptosis in HepG2 cells. After treatment with 2.00 mmol/L [YbCit(2)](3-) for 72 h, two dimensional gel electrophoresis and MALDI-TOF mass spectrometry analysis revealed 14 differentially expressed proteins between [YbCit(2)](3-)-treated cells and the control cells. These proteins mainly included cofilin1, peroxiredoxin6, S100 calcium-binding protein A6, and proteasome 26S non-ATPase subunit 13 isoform 3 and so on. These proteins played important roles in the processes of anti-apoptosis, oxidation reduction, cell proliferation and protein degradation. The mitochondrial membrane potential were investigated, the results showed the red and green fluorescence ratio was 2.45 ± 0.28 in the control group, 1.56 ± 0.23 in 24 h group, 1.16 ± 0.18 in 48 h group, compared with the control, the differences were significant (F = 23.97, P = 0.001). The results of H(2)O(2) detection showed the fluorescence intensity was 20.00 ± 2.08 in the control group, 40.00 ± 5.50 in 24 h group, and 48.00 ± 2.03 in 48 h group, compared with the control, the differences were significant (F = 48.40, P = 0.000). The results indicated a significant reduction in mitochondrial transmembrane potential and significant increase in H2O2 generation were observed in [YbCit(2)](3-)-treated cells. CONCLUSION: These results suggested that [YbCit(2)](3-) could induce apoptosis of HepG2 cells through the mechanisms involving oxidative stress and mitochondrial dysfunction.