FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K/Akt/HK2-mediated glycolysis.

FoxA2 is an essential transcription factor for liver organogenesis and homeostasis. Although reduced expression of FoxA2 has been associated with chronic liver diseases, hepatic progenitor cells (HPCs) that are activated in these circumstances express FoxA2. However, the functional effects and underlying mechanism of FoxA2 in HPCs are still unknown. As revealed by immunostaining, HPCs expressed FoxA2 in human cirrhotic livers and in the livers of choline-deficient diet supplemented with ethionine (CDE) rats. Knocking down FoxA2 in HPCs isolated from CDE rats significantly increased cell proliferation and aerobic glycolysis. Moreover, gene transcription, protein expression, and the enzyme activities of hexokinase 2 (HK2) were upregulated, and blocking HK2 activities via 2-deoxyglucose markedly reduced cell proliferation and aerobic glycolysis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that FoxA2 knockdown enhanced the transcription of genes involved in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway and triggered downstream Akt phosphorylation. Blocking the PI3K/Akt pathway by Ly294002 inhibited HK2 activities, aerobic glycolysis, and cell proliferation in FoxA2-knockdown cells. Therefore, FoxA2 plays an important role in the proliferation and inhibition of HPCs by suppressing PI3K/Akt/HK2-regulated aerobic glycolysis.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Sesquiterpenoids and triterpenoids from Abies holophylla and their bioactivities.

Six previously unreported and 11 known terpenoids were isolated from Abies holophylla. The structures of the six compounds were established as two unusual bisabolane sesquiterpenoids, three nortriterpenoids, and one 3,4-seco-triterpenoid based on the detailed analysis of their 1D and 2D NMR spectroscopic data. In addition, electronic circular dichroism (ECD) calculations and molecular orbital (MO) analysis were used to assign the absolute configuration of one bisabolane sesquiterpenoid, abiesesquine A. Abiesesquine A showed the strongest inhibitory effects against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with an IC(50) value of 113.1 µM. Lanosta-7,9(11),24-trien-26-oic acid showed potent cytotoxic activity against COLO-205, LOVO, and QGY-7703 tumor cells with IC(50) values of 0.9, 4.2, and 2.0 µM, respectively. (23R,25R)-3,4-seco-9ßH-Lanosta-4(28),7-dien-26,23-olid-3-oic acid, exhibited a significant antiproliferation effect against A549 cells (IC(50)=14.7 µM).

Mono- and sesquiterpenoids, flavonoids, lignans, and other miscellaneous compounds of Abies georgei.

A systematic phytochemical investigation of the aerial parts of Abies georgei yielded nine new and 72 known compounds, including four monoterpenes, four sesquiterpenes, 25 flavonones, 14 lignans, and 34 other chemical constituents. The new compounds included two monoterpenes (1 and 2), two sesquiterpenes (3 and 4), three flavonones (5, 6, and 7), and two other components (8 and 9). Their chemical structures were established on the basis of various spectroscopic data. All the isolates were tested for antitumor and anti-inflammatory activities. The new compound 9,4'-dihydroxy-5,7-dimethoxy-8-methylchalcone (7) demonstrated a moderate antiproliferative effect on QGY-7703 tumor cells (IC (50)  = 17.6 µg/mL). The known compound isoferulaldehyde (67) exhibited the strongest inhibitory activity against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages (IC (50) = 19.0 µg/mL). Abies georgei may be a significant source of beneficial pharmaceutical compounds.