Quercetin Inhibits the Migration and Invasion of HCCLM3 Cells by Suppressing the Expression of p-Akt1, Matrix Metalloproteinase (MMP) MMP-2, and MMP-9.

BACKGROUND Quercetin is a natural bioactive flavonoid that is present in a wide variety of vegetables and fruits and exhibits a promising anti-metastasis property in various human cancer cells. However, the effect of quercetin on human HCCLM3 cells is unclear. MATERIAL AND METHODS In the current study, a wound-healing assay was performed using quercetin-treated HCCLM3 cells to further explore whether quercetin affects the motility of human HCCLM3 cells. Transwell assay was used to explore the potential effect of quercetin in HCCLM3 cells on cell migration and cell invasion. Western blotting analysis was used to explore the expression of p-Akt1, MMP-2, and MMP-9 in quercetin-treated HCCLM3 cells. RESULTS The wound-healing time was delayed in quercetin-treated HCCLM3 cells, and the ability to migrate and invade was inhibited in quercetin-treated human HCCLM3 cells. Moreover, the protein levels of p-Akt1, MMP-2, and MMP-9 were down-regulated in quercetin-treated HCCLM3 cells, as detected by Western blotting. CONCLUSIONS Our data show that quercetin attenuated cell migration and invasion by suppressing the protein levels of p-Akt1, MMP-2, and MMP-9 in HCCLM3 cells.

[Effect of Echinococcus multilocularis Infection on the Activities of Drug-metabolizing Enzymes in Gerbil Liver].

Objective: To study the effect of Echinococcus multilocularis infection on the activities of drug-metabolizing enzymes in gerbil liver. Methods: Ten gerbils （Meriones unguiculatus） were randomly divided into 2 groups, the experimental group in which each animal was intraperitoneally injected with 300 µl E. multilocularis cyst homogenates （containing about 600 protoscoleces）, and the control group in which each animal received 300 µl saline（i.p.）. Five months after infection, the animals were sacrificed by cervical dislocation, and livers were collected. The liver microsomal and cytosolic fractions were obtained by differential centrifugation. Protein concentration was measured by the BCA method. CYP450 and Cyt b5 contents in the microsomal fraction were measured with differential spectroscopy. Activities of 7-ethoxyresorufin（EROD） and 7-methoxyresorufin（MROD） were measured by fluorescence spectrometry. The activities of NADPH-cytochrome C reductase（NCR）, glutathione-S-transferase （GST）, and flavine monooxygenases （FMO） were measured by UV-visible spectrophotometry. Results: The protein content of cytosolic fractions and liver microsomes in experimental group was （11.089±1.277） and （3.212±0.924） mg/ml， those in control group was （12.459±1.625） and （3.894±0.395） mg/ml， respectively. The contents of CYP450 and Cyt b5 in the experimental group [（0.508±0.142）, （0.515±0.077） nmol/mg protein, respectively] were both significantly lower than those in the control [（0.647±0.090）, （0.596±0.051） nmol/mg protein]（P<0.05）. The GST activity decreased significantly in the experimental group ［（1.766±0.339）×103 nmol/（mg·min）］ compared with the control ［（2.001±0.160）×103 nmol/（mg·min）］（P<0.05）. But the FMO and NCR activities increased significantly in the experimental group ［（1.142±0.327） nmol/（mg·min） and （0.602±0.162）×103 nmol/（mg·min）, respectivelyï¼½ compared with the control ［（0.882±0.150） nmol/（mg·min） and （0.442±0.082）×103 nmol/（mg·min）］（P<0.05）. However, there were no significant differences in EROD and MROD activities between the two groups (P>0.05). Conclusion: The activities of FMO and NCR markedly increase, while that of GST significantly decreases in the gerbil liver after E. multilocularis infection.

Immune cell inflammatory cytokine responses differ between central and systemic compartments in response to acute exercise in mice.

BACKGROUND: Exhaustive exercise induces apoptosis and oxidative stress in systemic organs and tissues and is associated with increased levels of pro-inflammatory cytokines. The effects of acute exercise on cytokine expression and apoptosis of immune cells in the central nervous system (CNS) have not been well characterized. PURPOSE: We investigated the effects of a single bout of strenuous exercise on the expression of TNF-alpha, IL-6, and IL-beta, as well as the apoptotic status of cells in the hippocampus of healthy mice. To compare central vs. systemic differences, cytokine expression in the intestinal lymphocytes of a subset of mice were also assessed. METHODS: Female C57BL/6 mice were divided into three groups: sedentary controls (NOTREAD) (n = 22), treadmill exercise with immediate sacrifice (TREAD-Imm) (n = 21), or treadmill exercise with sacrifice after 2 hours (TREAD-2h). TNF-alpha, IL-6, and IL-1beta expression in the hippocampus and intestinal lymphocytes were measured by Western blot analysis. Percentages of hippocampal cells undergoing apoptosis (Annexin+) or necrosis (Propidium Iodide+) were determined through flow cytometry. Plasma levels of 8-isoprostane and corticosterone were measured using commercially available EIA kits. RESULTS: Acute treadmill exercise led to significant decreases in TNF-alpha (p<0.05) and increases in IL-6 (p<0.05) expression in the hippocampus of healthy mice. No effects of acute exercise on the apoptotic status of hippocampal cells were observed. In intestinal lymphocytes, the exercise bout led to significant increases in TNF-alpha (p<0.05), IL-6 (p<0.05), and IL-1beta (p<0.05). Acute exercise was associated with a significant increase in both plasma 8-isoprostane (p<0.05) and corticosterone (p<0.05) levels. CONCLUSION: Acute exercise differentially affects the pattern ofpro-inflammatory cytokine expression in the hippocampus compared to intestinal lymphocytes and, further, does not induce apoptosis in hippocampal cells.

A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma.

BACKGROUND: The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival. METHODS: A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model. RESULTS: Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy. CONCLUSIONS: This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.