[Study on effects of Corydalis yanhusuo and L-THP on dopamine of reward circuitry in conditioned place preference rats and comparison].

OBJECTIVE: To study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects. METHOD: The CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors. RESULT: Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05). CONCLUSION: The down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Knockdown of LMNA inhibits Akt/ß-catenin-mediated cell invasion and migration in clear cell renal cell carcinoma cells.

The LMNA gene encoding lamin A/C is amplified in some clear cell renal cell carcinoma (ccRCC) samples. Our data showed that depletion of the tumor suppressor PBRM1 can upregulate lamin A/C levels, and lamin A/C could interact with PBRM1. However, the role of lamin A/C in ccRCC is not yet fully understood. Our functional assays showed that although the proliferation ability was slightly impaired after LMNA depletion, the migration and invasion of ccRCC cells were significantly inhibited. This suppression was accompanied by a reduction in MMP2, MMP9, AKT/p-AKT, and Wnt/ß-catenin protein levels. Our data therefore suggest that lamin A/C, as an interaction partner of the tumor suppressor PBRM1, plays a crucial role in tumor invasion and metastasis in ccRCC.

Association of CK19 expression with the efficacy of adjuvant transarterial chemoembolization after hepatic resection in hepatocellular carcinoma patients at high risk of recurrence.

BACKGROUND AND AIM: This study retrospectively explored the potential association between CK19 expression and efficacy of adjuvant conventional transarterial chemoembolization (TACE) after hepatic resection in patients with hepatocellular carcinoma (HCC) at high risk of recurrence. METHODS: Patients (n = 508) who underwent hepatic resection between January 2012 and December 2017 were enrolled. Overall survival (OS) and recurrence-free survival (RFS) were compared between groups. Survival analysis was performed using the Kaplan-Meier method, and groups were compared using the log-rank test. RESULTS: OS and RFS were worse for CK19-positive patients than for CK19-negative patients, regardless of whether patients were matched on the basis of propensity scores. Among CK19-positive patients in the absence of propensity score matching, TACE was associated with better RFS. Among CK19-negative patients in the absence of propensity matching, TACE was associated with better OS and RFS. Among patients treated with TACE, CK19-positive patients showed worse OS but similar RFS as CK19-negative patients. Multivariate analysis identified the following independent predictors of worse OS: CK19 positivity, no adjuvant TACE, macrovascular invasion, microvascular invasion, tumor size >5 cm, alanine transaminase >80 U/L, and aspartate transaminase >80 U/L. Multivariate analysis identified the following predictors of worse RFS: CK19 positivity, no adjuvant TACE, age ≥60 years, alpha-fetoprotein ≥400 ng/ml, and Barcelona Clinic Liver Cancer stage B/C. CONCLUSION: This study suggests that among HCC patients at high risk of recurrence, adjuvant TACE can significantly prolong OS and RFS of CK19-negative patients, while it may prolong only RFS of CK19-positive patients. RELEVANCE FOR PATIENTS: Not all patients will benefit from adjuvant TACE, therefore, it is necessary to select the best benefit subsets before TACE. By studying the relationship between CK19 expression and TACE benefit, it will be possible to help guide decision-making about adjuvant TACE in HCC patients at high risk of recurrence.

New pyrazinoquinazoline alkaloids Isolated from a culture of Stenotrophomonas maltophilia QB-77.

Two new pyrazinoquinazoline alkaloids, epi-fiscalin D (1) and epi-fiscalin E (2), as well as three known analogues, norquinadoline A (3), quinadoline A (4), and fiscalin C (5), were isolated from ethyl acetate extract of the fermentation broth of Stentrophomonas maltophilia QB-77. The structures of new compounds were elucidated on the basis of extensive spectroscopic data analysis including UV, HRESIMS, and 1D and 2D NMR experiments. All the isolated compounds were tested for their in vitro cytotoxicity against five human cancer cell lines (SMMC-7721, MCF-7, HL-60, SW480, and A-549) and antibacterial activities against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus.