1.The neuroprotective effect of curcumin by inhibiting the aggregation of α-synuclein on lipopolysaccharide-induced Parkinson's disease model
Xiaokui GAN ; Xiaowei SONG ; Ming ZHANG ; Yiming FANG ; Longbiao MA ; Baosheng HUANG
China Pharmacist 2024;27(5):779-787
Objective To explore the neuroprotective effect of curcumin(Cur)on Parkinson's disease model and its mechanism.Methods Sprague-Dawley rats were randomly divided into the control(CON)group,the model(PD)group,and the low-,medium-,and highdose curcumin(Cur)groups,with ten rats in each group.Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model.Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg,40 mg/kg,and 60 mg/kg daily for 21 days.α-synuclein(α-syn),nuclear transcription factor κB proteins(NF-κB,IKBα,p-NF-κB,p-IKBα)and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry(IHC).mRNA levels of pro-inflammatory cytokines(TNF-α,IL-β,IFN-γ,IL-6),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NADPH oxidase complex(gp47phox,gp91phox,gp67phox),and apoptosis-related factors(Bax,Bcl-2,Caspase-3,and Caspase-9)were measured by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.Results Compared to the CON group,PD rats showed significantly increased levels of α-syn,p-NF-κB,p-IKBα proteins,activation of astrocytes,TNF-α,IL-β,IFN-γ,IL-6,iNOS,COX-2,Bax,Caspase-3,Caspase-9,gp47phox,gp91phox and gp67phox mRNA levels(P<0.05);while the Bcl-2 level was significantly decreased(P<0.05).Compared with the PD group,the medium-and high-dose Cur treatment groups inhibited the aggregation of α-syn protein,reduced the activation of the NF-κB pathway,and the expression of inflammatory and apoptosis-related factors(P<0.05).Moreover,medium and high doses of Cur significantly improved the motor coordination in rats,and compared with the PD group,the performance of rotarod and pole climbing tests was significantly improved(P<0.05).Conclusion cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses,thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.
2.Analysis of the potential role of TMOD3 in recurrence and metastasis of hepatocellular carcinoma
Longbiao Luo ; Hui Jiang ; Dandan Ma ; Hangwei Fu ; Weiwei Sun
Acta Universitatis Medicinalis Anhui 2024;59(12):2094-2102
Objective:
To investigate the relationship between tropomodulin 3(TMOD3) and the malignant biological characteristics of hepatocellular carcinoma, and the predictive potential of TMOD3 as a biomarker for the recurrence and metastasis of hepatocellular carcinoma.
Methods:
Firstly, the structure of TMOD3 and its subcellular localization in cells and tissues were analyzed using database of Human Protein Atlas. Then explored the differential expression of TMOD3 in hepatocellular carcinoma tissues and normal liver tissues and its impact on clinical pathological characteristics and prognosis using TCGA and GEO datasets. Subsequently, the STRING database was utilized to explore the interacting proteins of TMOD3, followed by enrichment analysis conducted using the Metascape database. Finally, Logistic regression was used to analyze the independent risk factors for metastasis of hepatocellular carcinoma and evaluated the importance of predictive variables using ROC curves and Wald tests. Survival analysis was conducted using the Kaplan-Meier curve and the Log-rank test.
Results:
TMOD3 was localized to actin filaments in cells, and compared with normal tissues, the expression level of TMOD3 in liver cancer tissues is higher(P<0.05), and high expression of TMOD3 was closely related to lymph node metastasis and distant metastasis of hepatocellular carcinoma patients(P<0.05). Enrichment analysis results revealed that TMOD3 and its interacting proteins mainly function and signaling pathways related to tumor invasion and migration. Logistic regression found that TMOD3 was an independent risk factor for recurrence and metastasis of hepatocellular carcinoma(OR: 4.359, 95%CI: 1.235-15.384,P=0.022). Survival analysis revealed that high expression of TMOD3 was associated with poor OS, DFS, and RFS of hepatocellular carcinoma patients(P<0.05). Both ROC analysis and Wald test indicated that TMOD3 has good predictive characteristics for recurrence and metastasis of hepatocellular carcinoma.
Conclusion
TMOD3 is closely associated with the invasion and metastasis of hepatocellular carcinoma and is an independent risk factor for the recurrence and metastasis of liver cancer. TMOD3 performs well in predicting the recurrence and metastasis of hepatocellular carcinoma and has the potential to become a biomarker for predicting the recurrence and metastasis of hepatocellular carcinoma.