Role of lncRNA NEAT1 mediated by YY1 in the development of diabetic cataract via targeting the microRNA-205-3p/MMP16 axis.

OBJECTIVE: We aimed at investigating the possible role and mechanism of NEAT1 in the pathogenesis of diabetic cataract. PATIENTS AND METHODS: YY1 and NEAT1 expressions in anterior lens capsule collected from diabetic cataract (DC) patients and normal controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was analyzed. The binding site between YY1 and NEAT1 sequences was predicted by JASPAR and detected by Dual-Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. The proliferation and apoptosis of high-glucose-induced cells with NEAT1 knockdown were detected. Potential downstream targets of NEAT1 were predicted by bioinformatics and detected by Dual-Luciferase reporter assay. RESULTS: YY1 and NEAT1 expressions in the anterior capsule tissue of DC lens were remarkably reduced and positively correlated. Dual-Luciferase reporter assay and ChIP confirmed that YY1 could bind to locus 2 of NEAT1. Knockdown of NEAT1 inhibited proliferation while promoted apoptosis under high glucose conditions. Further mechanism studies revealed that knockdown of NEAT1 could upregulate microRNA-205-3p, and MMP16 was a potential target of miR-205. CONCLUSIONS: The low expression of YY1 induces NEAT1 downregulation, which regulates microRNA-205-3p/MMP16 axis and thus participates in the development of DC.

Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells.

Triptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In the present study we investigated the potential therapeutic effects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with different p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were observed as to cell growth inhibition and induction of apoptosis in response to triptolide treatment. We showed that triptolide inhibited cell growth, induced apoptosis and suppressed NK-kappaB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21(waf1/cip1), bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G(0)/G(1) phase. To examine the role of p53 in these functions, we showed that suppression of p53 level with antisense oligonucleotide abrogated triptolide-induced apoptosis and over-expression of dominant negative p53 abolished the inhibitory effect on NF-kappaB activation. Furthermore, we demonstrated that triptolide had differential effects on gastric cancer cells with different p53 status. We showed that triptolide also inhibited cell growth and induced apoptosis in MKN-45 with wild-type p53, whereas it had no significant growth-inhibition and apoptosis induction effects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest that triptolide exhibits anti-tumor and anti-inflammatory effects by inhibiting cell proliferation, inducing apoptosis and inhibiting NF-kappaB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-inflammatory and anti-tumor effects.

A novel eleven-membered-ring triterpene dilactone, pseudolarolide F and A related compound, pseudolarolide E, from Pseudolarix kaempferi.

A novel eleven-membered-ring triterpene dilactone, pseudolarolide F (1), and a related compound, pseudolarolide E (2), were isolated from the seeds of Pseudolarix kaempferi, a plant indigenous to eastern China. Their structures and stereochemistry were established by spectroscopic studies, which included UV, IR, HREIMS, 2D NMR correlation methods (1H-1H COSY, 13C-H COSY, NOESY, HMQC, and HMBC), and single-crystal X-ray analysis.

Fast repairing of oxidized OH radical adducts of dAMP and dGMP by phenylpropanoid glycosides from Scrophularia ningpoensis Hemsl.

AIM: To investigate the antioxidative activity of the constituents of the roots of Scrophularia ningpoensis (Chinese name: Xuanshen). METHODS: The main compounds from the roots of Scrophularia ningpoensis were isolated and identified by chromatography and FABMS, NMR etc. Using the techniques of pulse radiolysis, the electron transfers from iridoid glycosides (IG) or phenylpropanoid glycosides (PG) to oxidized OH radical adducts of 2'-deoxyadenosine-5'-monophosphate acid (dAMP) or 2'-deoxyguanosine-5'-monophosphate acid (dGMP) were observed. RESULTS: Two IG: harpagoside and harpagide, two PG: angoroside C and acteoside were obtained as the main hydrophilic constituents of the plant. At 0.1 mmol/L concentration, angoroside C and acteoside were able to repair the oxidized OH adducts dAMP and dGMP significantly. However, harpagoside and harpagide had no such effect. The electron transfer rate constants of angoroside C with dAMP and dGMP were 4.2 x 10(8) and 10.3 x 10(8) L.mol-1.s-1; the electron transfer rate constants of acteoside with dAMP and dGMP were 5.3 x 10(8) and 20.2 x 10(8) L.mol-1.s-1. CONCLUSION: PG from Scrophularia ningpoensis have a potent antioxidative activity for reducing of the oxidized OH adducts of dAMP and dGMP.

Differential responses of two inbred rat strains to a choline-deficient diet during liver carcinogenesis.

We examined the effect of a choline-devoid (CD) diet on the development of gamma-glutamyltranspeptidase (GGT)-positive foci in both sexes of the inbred rat strains Fischer 344 and PVG/R8. Following partial hepatectomy, 7 to 8 week old animals were given a choline-supplemented diet for 1 week. Two groups were then formed: one remained on choline-supplemented diet as control, and the other was switched to the CD diet. The animals were killed 10, 16 and 24 weeks later. Liver samples were then stained with hematoxylin-eosin and Masson's trichromic, and histochemically analyzed for GGT. Fatty degeneration and collagen formation was severe in F344 males while it was mild or absent in F344 females and in both sexes of PVG rats. Stereochemical quantitation showed that F344 males had a significantly greater increase in the number of positive liver foci (as well as in their mean volume and the percentage of liver occupied by them) than F344 females and PVG animals of either sex (P < 0.01). These results suggest that not only sex but also the genotype of the host plays a role in the different responses to a CD diet. In depth analysis of these factors should prove valuable to investigate this dietary model of hepatocarcinogenesis further.