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Elucidating the active components of traditional Chinese medicine(TCM)is essential for understanding the mechanisms of TCM and promote its rational use as well as TCM-derived drug development.Recent studies have shown that surface plasmon resonance(SPR)technology is promising in this field.In the present study,we propose an SPR-based integrated strategy to screen and analyze the major active components of TCM.We used Radix Paeoniae Alba(RPA)as an example to identify the compounds that can account for its anti-inflammatory mechanism via tumor necrosis factor receptor type 1(TNF-R1).First,RPA extraction was analyzed using an SPR-based screening system,and the potential active in-gredients were collected,enriched,and identified as paeoniflorin and paeonol.Next,the affinity con-stants of paeoniflorin and paeonol were determined as 4.9 and 11.8 μM,respectively.Then,SPR-based competition assays and molecular docking were performed to show that the two compounds could compete with tumor necrosis factor-α(TNF-α)while binding to the subdomain 1 site of TNF-R1.Finally,in biological assays,the two compounds suppressed cytotoxicity and apoptosis induced by TNF-α in the L929 cell line.These findings prove that SPR technology is a useful tool for determining the active in-gredients of TCM at the molecular level and can be used in various aspects of drug development.The SPR-based integrated strategy is reliable and feasible in TCM studies and will shed light on the eluci-dation of the pharmacological mechanism of TCM and facilitate its modernization.
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Objective:To analyze the expression of mucin 1 (MUC1) and Ki67 in intrahepatic cholangiocarcinoma (ICC), and to explore the correlations between the expression of MUC1 and Ki67 and the clinicopathological features and prognosis of ICC patients.Methods:Clinical data of 398 patients with ICC admitted to Henan Provincial People's Hospital from January 2013 to March 2020 were retrospectively analyzed. A total of 104 patients were included in this study, including 67 males and 37 females, aged (56.6±9.3) years. Immunohistochemistry was used to detect the expression of MUC1 and Ki67 in cancer tissues. Univariate and multivariate Cox regression analysis were used to study the prognostic factors of ICC patients.Results:The expression of MUC1 was low in 65 patients and high in 39 patients. Ki67 expression was low in 52 patients and high in 52 patients. High expression of MUC1 was correlated with lymph node metastasis ( P<0.05), while high expression of Ki67 was correlated with tumor nodes number, lymph node metastasis and vascular invasion (all P<0.05). Multivariate analysis showed that ICC patients with high MUC1 expression ( HR=2.321, 95% CI: 1.420-3.792, P<0.001) and high Ki67 expression ( HR=2.012, 95% CI: 1.247-3.247, P=0.004) showed a poor prognosis after hepatectomy. ICC patients with high MUC1 expression ( HR=1.664, 95% CI: 1.058-2.618, P=0.028) and high Ki67 expression ( HR=1.883, 95% CI: 1.168-3.035, P=0.009) had a poor prognosis after hepatectomy. Conclusion:High expression of MUC1 and Ki67 is correlated with tumor growth and metastasis. MUC1 and Ki67 are independent risk factors for prognosis of ICC patients after hepatectomy.
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Objective:To analyze the clinicopathological features, diagnosis and treatment of neuroendocrine carcinoma of gallbladder (GB-NEC).Methods:The clinical data of 17 patients with GB-NEC confirmed by postoperative pathology managed at the People's Hospital of Zhengzhou University from March 2013 to January 2020 were analyzed retrospectively. There were 9 males and 8 females, with an age of (68.9±11.2) years. The clinical and follow-up data were analyzed.Results:The main clinical manifestations were abdominal pain ( n=9, 52.9%), anorexia ( n=5, 29.4%), jaundice ( n=2, 11.8%), abdominal mass ( n=2, 11.8%), and asymptomatic ( n=2, 11.8%). Radical resection of gallbladder carcinoma was performed in 9 patients, and palliative resection in 8 patients. Postoperative chemotherapy was given to 4 patients. Postoperative pathology showed small cell type in 11 patients and large cell type in 6 patients. Immunohistochemical staining showed synaptophysin positivity in 17 patients (100.0%), chromogranin A positivity in 12 (70.6%), Ki67 positivity in 17 patients (100%, >50% was defined as positive). All 17 patients were followed-up from 78 to 745 days, with a median of 237 days. At the time of censor of this study, 13 patients had died. The 1-and 2-year cumulative survival rates were 26.5% and 19.9%, respectively. The 1- and 2-year cumulative survival rates of radical gallbladder carcinoma resection ( n=9) were 44.4% and 33.3%, respectively. Eight patients underwent palliative resection, and the longest follow-up time was 276 days. Conclusion:This study showed the incidence of GB-NEC was low. There was no specific clinical manifestations, and the diagnosis mainly depended on immunohistochemistry. Patients with GB-NEC had high expressions of Ki67 and had poor prognosis. Early radical resection was helpful to improve survival of these patients.
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Objective:To investigate the induction mechanism of cisplatin on hepatoma senescence.Methods:2 μg/ml cisplatin was applied to affect hepatocellular carcinoma cell line HepG2. Cell proliferation of tumor cells was detected by MTS method. The cell cycle was detected by flow cytometry. The RT-PCR and Western blot were used to detect the expression of senescence regulation genes, p19 and p21. The expression of p21 was detected by cell immunofluorescence. Nude mouse model of human hepatocellular carcinoma was intraperitoneally injected with specific drug to measure the growth, metastasis of tomor and expression of p21 protein.Results:Cell proliferation rate in cisplatin group was lower than that of the control group( t=8.958, P<0.05). Flow cytometry showed the percentage of G 2 phase were19.90%±0.42%, 12.57%±0.84% in the cisplatin and control group, respectively. Cells were arrested in G 2 phase ( t=14.415, P<0.05). In the cisplatin group and control group, the relative expression of p19 were(2.23±0.05), (1.00±0.02); the relative expression of p21 were (3.26±0.11), (1.00±0.02). The expression of p19 and p21 increased(respectively t=43.750, 56.541, all P<0.05). The tumor size of cisplatin group was smaller than that of the control group, and the expression level of p21 protein was higher than that of the control group ( P<0.05). Conclusion:Cisplatin can induce senescence of hepatocellular carcinoma cells through the p19/p21 pathway.