The effects of imperatorin (Imp) and iso-imperatorin(Isi) on tumor necrosis factor (TNF) release from mouse peritoneal macrophages were investigated. It was found that Imp and lsi significantly inhibited TNF release from mouse peritoneal macrophages. At the concentration of 10-6～10-4 mol?L-1, the inhibitory effects were presented by Imp and Isi in a dose dependent manner. At 10-4 mol/L TNF release was entirely inhibited by each drug.

Specific receptors for leukotriene C4 LTC4 have been identified on intact smooth muscle cells derived from bovine cerebral microvasculatures. Specific pHJLTC4, binding at a fixed input at 25 ℃ was rapid , reaching the maximum at 20min With incremental inputs of radioligand and a constant cell number, specific [3H]LTC4 binding reached a plateau indicative of a saturable binding site. Analysis of Scatchard plots demonstrated a single high affinity binding site with a dissociation constant (Kd) of 2.01?0.4 nmol/L and Bmax = 156.6?13.1 fmol/106 cells. The specific [3H]LTC4 binding could be inhibited by unlabted LTC4, LTD4 and FPL-55712 with an inhibitory rate of 96.9%, 73.9% and 44.9% at 10-5 mol/L, respectively.

The release of platelet activating factor (PAF) induced 14C-arachidonic acid (14C-AA) in the bovine cerebral microvascular endothdial cells (CMEC) and arterior cerebral artery smooth muscle cells (ACASMC) and the antagonism of SZ-1 are described. The results showed that 14C-AA incorporated into the cells rapidly and PAF 0.1-20?mol/L dose-dependently stimulated the AA release significantly. It indicated that the action of PAF on the cerebrovascular system was associated with the stimulation of AA release. SZ-1 0.2-20?nol/L dose-dependently inhibited the PAF induced AA release in CMBC and ACASMC, and PAF induced aggregation of washed rabbit platelets, but did not inhibited ADP or AA induced aggregation of platelet-rich plasma(PRP), and PAF production in CMEC, indicating the specific antagonism of SZ-1 on PAF receptor.

27 rabbits were divided into normal group(n = 4),control group (n = 5), silybin group (n = 6), hyperbaric oxygen (HBO) group (n = 6), and HBO combined with silybin group (n = 6). Circulation of hindlimb was interrupted completely for 6 h and reperfused for 1 h. Malondialdehyde (MDA) and superoxide dismutase(SOD) in plasma from ischemic-reperfused injured limb were measured. Adenosine triphosphate (ATP) and creatine phosphate (CP) in samples taken from anterior tibial muscle were determined. Ultrastructural changes of injured muscle were observed. The results showed that HBO combined with silybin treatment had a favourable effect on ischemic and reperfused injured limb muscle with reduction of the lipid peroxidated injury, increase of the SOD activity and the high energy phosphate compounds (ATP and CP), and a promoting recovery of injured muscle cells. HBO and silybin had a synergistic action. It suggests that HBO combined with silybin is an effective method for treatment of ischemic and reperfused injured limb.

ObjectiveTo investigate the expression of the neutral cholesterol ester hydrolase 1 (NCEH1) gene in liver cancer tissue and human hepatoma cell lines and the effect of NCEH1 gene knockdown on the proliferation, apoptosis, invasion, and metastasis abilities of human hepatoma SMMC-7721 cells. MethodsLiver cancer tissue samples and adjacent tissue samples were collected from 32 patients with liver cancer who underwent surgical treatment in Guangzhou Red Cross Hospital Affiliated to Jinan University from January 2013 to June 2019, and quantitative real-time PCR was used to measure the relative expression level of the NCEH1 gene. Gene expression data of liver cancer samples up to September 2020 were downloaded from the ICGC database, and R software was used to analyze the data and obtain the expression level of the NCEH1 gene in each sample. The paired Wilcoxon signed-rank test and the Wilcoxon rank-sum test were used to investigate the differences between liver cancer tissue and adjacent tissue. Quantitative real-time PCR was used to measure the expression level of the NCEH1 gene in human hepatoma SMMC-7721, Bel-7402, HepG2, and Hep3B cells and normal human HL7702 liver cells. The lentivirus-mediated small interfering RNA (siRNA) technique was used to establish a human hepatoma SMMC-7721 cell line with NCEH1 gene knockdown, and the cells were divided into NCEH1 knockdown group (KD group) and negative control group (NC group); quantitative real-time PCR was used to measure the knockdown efficiency of the NCEH1 gene, and then MTT assay, flow cytometry with Annexin V-APC single staining, wound healing assay, Transwell assay, and Transwell chamber invasion assay were used to measure the proliferation, apoptosis, metastasis, and invasion abilities of SMMC-7721 cells in both groups. The t-test was used for statistical analysis of data between the two groups. ResultsThe mean expression level of the NCEH1 gene in liver cancer tissue was significantly higher than that in adjacent tissue (specimens from our hospital: Z=2.263, P=0.024; ICGC database: U=18 768, P＜0.001). SMMC-7721 cell line with moderate potential of invasion and metastasis had the highest expression level of the NCEH1 gene, followed by BEL-7402 and HepG2 cell lines with low potential of invasion and metastasis, and Hep3B cell line without the potential of invasion and metastasis had the lowest expression level. The KD group had a significantly lower expression level of the NCEH1 gene than the NC group (t=11.578, P=0000 3), and the knockdown efficiency of the NCEH1 gene was as high as 74.0%. Compared with the NC group, the KD group had a significant reduction in cell growth rate, a significant increase in apoptosis rate, and significant reductions in migration rate and the number of metastatic and invasive cells (t=32.100, 27.303, 9.51, 38.123, and 22.331, all P＜0.001). Conclusion There is a significant increase in the expression of the NCEH1 gene in liver cancer tissue and cell lines, and the NCEH1 gene can promote the growth, proliferation, invasion, and metastasis of hepatoma cells and inhibit their apoptosis, suggesting that it may be a potential therapeutic target for liver cancer.

OBJECTIVE: To explore the relationship between extend types and distant metastasis of nasopharyngeal carcinoma (NPC). METHOD: Retrospective analyze 260 patients with nasopharyngeal carcinoma, among which 162 cases were distant metastasis (metastasis group) and 98 cases were neither distant metastasis nor recurrence (disease-free group) over 5 years after radiotherapy. All these patients were staged depending on CT or MRI image before treatment and divided into local-regional type(T(1-2)N(0-1)) for 36 cases and upward invasion type (T(3-4)N(0-1)) for 68 cases and downward invasion type (T(1-2)N(2-3)) for 75 cases and mixed type (T(3-4)N(2-3)) for 81 cases. The differences between two groups was analyzed using Chi-square test. RESULT: The local-regional type and upward invasion type was 25.3% for the metastasis group and 64.3% for the disease-free group. The downward and mixed invasion was 74.7% for the metastasis group and 35.7% for the disease-free group. The rate(proportion) of N(2-3) was significantly higher in metastasis group than in disease-free group with limited extension (84.4% vs. 33.3%, P < 0.01). The rates(proportion) of N(0-1) and N(2-3) were also significantly higher in metastasis group than in disease-free group with severity extension (T(3-4) (60% vs. 36.1% and 68.4% vs. 40%, P < 0.01). CONCLUSION The extent of cervical lymph node metastases is one of the most important factors of NPC with distant metastasis, severity extension of primary disease should also be in consideration. Even the limitations of primary disease, once cervical lymph node metastasis occurs, the risk of distant metastasis is significantly increased.
Adolescent ; Adult ; Aged ; Carcinoma ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Neck ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult

Objective:Methamphetamine(METH)is an illicit psychoactive substance that can damage various organs,with the urinary system being one of its significant targets.This study aims to explore the role of microtubule affinity-regulating kinase 4(MARK4)in METH-induced acute kidney injury(AKI). Methods:A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group,5 mice in each group.The METH group was administered METH(20 mg/kg,intraperitoneally,once daily for 3 consecutive days),while the control group received an equal volume of physiological saline.The mice were executed 24 hours after the final injection,and the success of the AKI model was detected by blood serum creatinine,blood urea nitrogen,and renal HE staining.Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and bioinformatics analysis.The accuracy of proteomic data was validated using Western blotting,and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured.We further explored the role of MARK4 in METH-induced AKI.Firstly,a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment;the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. Results:The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins,of which 11 were up-regulated and 6 were down-regulated(all P＜0.05).The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice(both P＜0.05).The activity of BUMPT cells gradually decreased with increasing METH treatment concentration(all P＜0.05),where the viability of BUMPT cells decreased to about 60％after METH treatment at 4 mmol/L.Compared with the control group,expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration-and time-dependent manner(all P＜0.05).Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity,down-regulated the expression of cleaved caspase-3,and decreased the apoptosis of BUMPT cells induced by METH. Conclusion:MARK4 is highly expressed in a mouse model of METH-induced AKI,and MARK4 mediates METH-induced AKI by regulating cell apoptosis.