GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling.

Lung cancer (LC) is a leading cause of cancer-related deaths worldwide. Its rapid growth requires hyperactive catabolism of principal metabolic fuels. It is unclear whether fructose, an abundant sugar in current diets, is essential for LC. We demonstrated that, under the condition of coexistence of metabolic fuels in the body, fructose was readily used by LC cells in vivo as a glucose alternative via upregulating GLUT5, a major fructose transporter encoded by solute carrier family 2 member 5 (SLC2A5). Metabolomic profiling coupled with isotope tracing demonstrated that incorporated fructose was catabolized to fuel fatty acid synthesis and palmitoleic acid generation in particular to expedite LC growth in vivo. Both in vitro and in vivo supplement of palmitoleic acid could restore impaired LC propagation caused by SLC2A5 deletion. Furthermore, molecular mechanism investigation revealed that GLUT5-mediated fructose utilization was required to suppress AMPK and consequently activate mTORC1 activity to promote LC growth. As such, pharmacological blockade of in vivo fructose utilization using a GLUT5 inhibitor remarkably curtailed LC growth. Together, this study underscores the importance of in vivo fructose utilization mediated by GLUT5 in governing LC growth and highlights a promising strategy to treat LC by targeting GLUT5 to eliminate those fructose-addicted neoplastic cells.

The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer.

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment.

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC).

BACKGROUND: The aim of our study was to investigate the clinical features and expression levels of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC). METHODS: We retrospectively investigated the clinical features of 26 consecutive patients with LGSC who underwent primary staging or debulking surgery between April 2005 and June 2013 in our center; concomitant primary high-grade serous ovarian cancer (HGSC) patients were randomly selected at a 2:1 ratio for comparison. Tissue microarrays were constructed from the LGSC and HGSC specimens, and the expression levels of six hormone receptors in the hypothalamic pituitary-gonadal axis were analyzed by immunohistochemistry. RESULTS: The median (range) age of patients with LGSC was 54 (27-77) years. According to the FIGO staging system, the cases were distributed as follows: stage I, 6 (23.1%); stage II, 0 (0%); stage III, 19 (73.1%); and stage IV, 1 (3.8%). The 2-year and 5-year overall survival rates for LGSC were 91.8% and 67.5%, respectively. The expression levels of the hormone receptors were as follows: ER, 80.8%; PR, 34.6%; AR, 53.8%; FSHR, 84.0%; LHR, 65.4%; and GnRHR, 100%. Hormone receptor-positive patients had a better prognosis compared with hormone receptor-negative patients, but the difference was not significant. CONCLUSIONS: Our study presented a higher overall survival rate and distinctive hormone receptor expression levels of LGSC patients compared with the HGSC cohort. Patients with positive hormone receptor expression tended to have a better prognosis than the corresponding hormone receptor negative patients.

Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

OBJECTIVE: To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). METHODS: Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. RESULTS: Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. CONCLUSION: Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

[Comparative study on pharmacokinetics of curcumin extract of rhizoma curcumae longae and rhizoma wenyujin concisum in rats].

OBJECTIVE: To compare the pharmacokinetics of curcumin extracted from Rhizoma Curcumae Longe and Rhizoma Wenyujin Concisum in rats. METHODS: Sprague Dawley rats were administrated extracts of Rhizoma Curcumae Longae and Rhizoma Wenyujin Concisum. The pharmacokinetic parameters were calculated with 3P97 program. RESULTS: The plasma concentration-time curves of curcumin that extracted from Rhizoma Curcumae Longae and Rhizoma Wenyujin Concisum were fitted with one-compartment model respectively. The AUC and Cmax of curcumin extracted from Rhizoma Curcumae Longae were much greater than of extracted from Rhizoma Wenyujin Concisum. CONCLUSION: There were significantly difference in pharmacokinetic parameters of curcumin in Rhizoma Curcumae Longae and Rhizoma Wenyujin Concisum in rats.

[Study on effect of demethoxycurcumin in Curcuma long on stability of curcumin].

OBJECTIVE: To investigate effect of demethoxycurcumin on stability of curcumin. METHODS: To add the demethoxycurcumin to pure curcumin, the change of curcumin was determined by HPLC and the dynamics of curcumin degradation was investigated. RESULT: The stability both obtained from alcohol and demethoxycurcumin improved the stabilization of curcumin, the demi-period of curcumin prolonged with the addition of demethoxycurcumin. CONCLUSION: The commixture of curcumin and demethoxycurcumin are more stable than pure curcumin at the same conditions. Stability of curcumin is improved by demethoxycurcumin,it is crude stabilizing agent.

[Study on stability of curcumine, demethoxycurcumin and bisdemethoxycurcumin].

OBJECTIVE: To investigate the stability of curcumin, demethoxycurcumin and bisdemethoxycurcumin in different buffer solution. METHOD: To determine concentration of curcumin by HPLC when added curcumin, demethoxycurcumin and bisdemethoxycurcumin into the buffer solution the equation of degradation was established. RESULT: The sequence of stability are bisdemethoxycurcumin > or = demethoxycurcumin > or =curcumin at the same condition. CONCLUSION: The demethoxycurcumin can stabilize curcumin more strong than the others. The demethoxycurcumin is a nature stabilizing agent for curcumin.