Circular RNA circSOX4 promotes the proliferation, migration and apoptosis of hepatocellular carcinoma cells by down regulating microRNA-432 expression.

OBJECTIVE: As the research of circular RNAs (circRNAs) in human malignant tumors has been increasing, multiple circRNAs have been discovered to be engaged in the modulation of the liver cancer cell functions. This study aims at exploring how circSOX4 affects the progression of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: CircSOX4 levels in HCC tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the relationship between circSOX4 expression and HCC patients' prognosis was analyzed. CircSOX4 expression was knocked down by transfection of small interfering RNA. The effects of circSOX4 on cell functions including proliferation, invasiveness and migration ability were examined by cell counting kit-8 (CCK-8), transwell, cell wound healing test and flow cytometry experiments, respectively. The target RNA of circSOX4 was predicted through searching bioinformatics website, and the binding between the two was verified through Luciferase assay. RESULTS: CircSOX4 was abnormally highly expressed either in HCC tissues or in cell lines, which was positively correlated with the poor prognosis of HCC patients. Transfection of small interfering RNA against circSOX4 in HCC cells resulted in inhibited migration and proliferation of HCC cells, while an increase in cell apoptosis. Bioinformatics analysis revealed that microRNA-432 contained the binding site pairing to circSOX4 3'UTR, and their binding relationship was confirmed by Luciferase assay. Their expression levels were negatively correlated. In addition, downregulation of microRNA-432 can partially reverse the effect of silenced circSOX4 on regulating apoptosis, proliferation and migration of HCC cells. CONCLUSIONS: CircSOX4, highly expressed in HCC, indicates a poor prognosis. CircSOX4 may mediate the progression of HCC by binding to microRNA-432.

MicroRNA-195-5p inhibits malignant progression of gallbladder cancer by regulating Wnt3a.

OBJECTIVE: We aimed at investigating whether microRNA-195-5p inhibits the malignant proliferation of gallbladder cancer (GBC) via regulating Wnt3a; meanwhile, its relationship with the clinicopathological parameters and prognosis of patients with GBC was also explored. PATIENTS AND METHODS: In this study, the tumor tissues and adjacent tissues of 47 GBC patients were tested for microRNA-195-5p expression level by real-time quantitative polymerase chain reaction (qPCR); the relationship between microRNA-195-5p expression and clinical indicators of GBC patients was further analyzed. Control group (NC mimic or NC inhibitor), microRNA-195-5p overexpression group (microRNA-195-5p mimic), and microRNA-195-5p knockdown group (microRNA-195-5p inhibitor) were set in GBC cell lines, respectively. In GBC cell lines GBC-SD and NOZ, cell counting kit-8 (CCK-8), plate cloning experiments and flow cytometry were carried out to assess microRNA-195-5p's effect on proliferation and apoptosis of GBC cells. Further, the interaction between microRNA-195-5p and its downstream gene Wnt3a was explored through Luciferase reporting assay. RESULTS: Our data showed that microRNA-195-5p expression in tumor tissues of GBC patients was remarkably lower than that in adjacent ones. In comparison to patients in highly expressed microRNA-195-5p group, those in lowly expressed microRNA-195-5p had more advanced pathological stage and larger tumor size. Overexpression of microRNA-195-5p markedly attenuated the proliferation capacity of GBC cells as compared to the NC mimic group; in contrast, knockdown of microRNA-195-5p enhanced GBC cell proliferation function of GBC cells in comparison to NC inhibitor group. At the same time, the opposite tendency in cell apoptosis was observed in the above four groups. In GBC tissue specimens, Wnt3a showed an increased expression, which was negatively correlated with microRNA-195-5p. Meanwhile, Luciferase assay verified a binding relationship between microRNA-195-5p and Wnt3a. In addition, we found that over-expressing Wnt3a counteracted the influence of upregulation of microRNA-195-5p on proliferation and apoptosis of GBC cells and thus modulate the malignant progress of GBC cells. CONCLUSIONS: In summary, the above studies suggest that low expression of microRNA-195-5p is remarkably relevant to pathological stage and tumor size of patients with GBC. In addition, microRNA-195-5p may suppress the malignant progression of GBC through down-regulating Wnt3a.

Isodon eriocalyx and its bioactive component Eriocalyxin B enhance cytotoxic and apoptotic effects of gemcitabine in pancreatic cancer.

BACKGROUND: Pancreatic cancer, associated with poor prognosis and low survival rate, has been the fourth leading cause of cancer-related death in the US. Although gemcitabine (Gem) is the first-line chemotherapeutic drug in the management of pancreatic cancer, the median survival extension is only 1.5 months, indicating unsatisfactory clinical results. Therefore, exploring agents that can enhance the anti-cancer activity of Gem would be an attractive strategy. PURPOSE: Our previous studies have demonstrated that eriocalyxin b (EriB), an ent­kaurane diterpenoid isolated from Isodon eriocalyx (Dunn.) Hara, possesses anti-pancreatic cancer effects, thus acting as a potential therapeutic agent. In this study, we further investigated whether EriB or the ethanol extract of I. eriocalyx (Isodon) could potentiate the cytotoxic activity of Gem in human pancreatic adenocarcinoma cells. In addition, the mechanism associated with their effects was also studied. METHODS: The anti-proliferation effect was assessed by MTT assay and Ki-67 immunostaining. The combination effect (addition, synergism and antagonism) of various agents was calculated by the Calcusyn software (Biosoft), utilizing the T.C. Chou Method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Protein expression regulated by various treatments was analyzed by western blotting. RESULTS: The combination index revealed that Gem and EriB (or Isodon extract) had synergistic anti-proliferative effect. Both cellular apoptotic and anti-proliferative effects of Gem were significantly increased after combination with EriB (or Isodon extract). The underlying mechanisms involved in the combination effects were elucidated, which include: (1) increased activation of the caspase cascade; (2) reduction of PDK1 and AKT phosphorylation; (3) induction of JNK phosphorylation by Isodon and Gem combination. CONCLUSION: Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.

Graphene oxide/graphene vertical heterostructure electrodes for highly efficient and flexible organic light emitting diodes.

The relatively high sheet resistance, low work function and poor compatibility with hole injection layers (HILs) seriously limit the applications of graphene as transparent conductive electrodes (TCEs) for organic light emitting diodes (OLEDs). Here, a graphene oxide/graphene (GO/G) vertical heterostructure is developed as TCEs for high-performance OLEDs, by directly oxidizing the top layer of three-layer graphene films with ozone treatment. Such GO/G heterostructure electrodes show greatly improved optical transmittance, a large work function, high stability, and good compatibility with HIL materials (MoO3 in this work). Moreover, the conductivity of the heterostructure is not sacrificed compared to the pristine three-layer graphene electrodes, but is significantly higher than that of pristine two-layer graphene films. In addition to high flexibility, OLEDs with different emission colors based on the GO/G heterostructure TCEs show much better performance than those based on indium tin oxide (ITO) anodes. Green OLEDs with GO/G heterostructure electrodes have the maximum current efficiency and power efficiency, as high as 82.0 cd A(-1) and 98.2 lm W(-1), respectively, which are 36.7% (14.8%) and 59.2% (15.0%) higher than those with pristine graphene (ITO) anodes. These findings open up the possibility of using graphene for next generation high-performance flexible and wearable optoelectronics with high stability.

Sb-induced phase control of InAsSb nanowires grown by molecular beam epitaxy.

For the first time, we report a complete control of crystal structure in InAs(1-x)Sb(x) NWs by tuning the antimony (Sb) composition. This claim is substantiated by high-resolution transmission electron microscopy combined with photoluminescence spectroscopy. The pure InAs nanowires generally show a mixture of wurtzite (WZ) and zinc-blende (ZB) phases, where addition of a small amount of Sb (∼2-4%) led to quasi-pure WZ InAsSb NWs, while further increase of Sb (∼10%) resulted in quasi-pure ZB InAsSb NWs. This phase transition is further evidenced by photoluminescence (PL) studies, where a dominant emission associated with the coexistence of WZ and ZB phases is present in the pure InAs NWs but absent in the PL spectrum of InAs0.96Sb0.04 NWs that instead shows a band-to-band emission. We also demonstrate that the Sb addition significantly reduces the stacking fault density in the NWs. This study provides new insights on the role of Sb addition for effective control of nanowire crystal structure.

Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.

Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.

Eriocalyxin B-induced apoptosis in pancreatic adenocarcinoma cells through thiol-containing antioxidant systems and downstream signalling pathways.

Thiol-containing antioxidant systems play an important role in regulating cellular redox homeostasis. Several anti-cancer agents act by targeting these systems by inducing the production of reactive oxygen species (ROS). Our earlier studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The present study further demonstrated that only thiol-containing antioxidants, N-acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant systems, thus increasing the intracellular ROS levels and regulating the MAPK, NFκB pathways. Treatment with EriB depleted the intracellular thiol-containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude mice with increased superoxide levels. Taken together, our results shed important new light on the molecular mechanisms of EriB acting as an apoptogenic agent and its therapeutic potential for pancreatic cancer.

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in human HCC cell lines. LK-A also suppressed tumor growth in SMMC-7721 xenograft models, without inducing any notable major organ-related toxicity. LK-A treatment led to reduced expression of the proto-oncogene S phase kinase-associated protein 2 (Skp2) in SMMC-7721 cells. Lower Skp2 levels correlated with increased expression of p21 and p-cdc2 (Try15), and a corresponding decrease in protein levels of Cyclin B1 and cdc2. Overexpression of Skp2 significantly inhibited LK-A-induced cell cycle arrest in SMMC-7721 cells, suggesting that LK-A may target Skp2 to arrest cells at the G2/M phase. LK-A also induced reactive oxygen species (ROS) production and apoptosis in SMMC-7721 cells. LK-A induced phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase and P38 MAP kinase. Treatment with, the JNK inhibitor SP600125 prevented LK-A-induced apoptosis in SMMC-7721 cells. Moreover, the antioxidant N-acetylcysteine prevented phosphorylation of both JNK and c-Jun. Taken together, these data indicate that LK-A induces cell cycle arrest and apoptosis in cancer cells by dampening Skp2 expression, and thereby activating the ROS/JNK/c-Jun signaling pathways. LK-A is therefore a potential lead compound for development of antitumor drugs targeting HCC.

Nanosecond colloidal quantum dot lasers for sensing.

Low-threshold, gain switched colloidal quantum dot (CQD) distributed-feedback lasers operating in the nanosecond regime are reported and proposed for sensing applications for the first time to the authors' knowledge. The lasers are based on a mechanically-flexible polymeric, second order grating structure overcoated with a thin-film of CQD/PMMA composite. The threshold fluence of the resulting lasers is as low as 0.5 mJ/cm² for a 610 nm emission and the typical linewidth is below 0.3 nm. The emission wavelength of the lasers can be set at the design stage and laser operation between 605 nm and 616 nm, while using the exact same CQD gain material, is shown. In addition, the potential of such CQD lasers for refractive index sensing in solution is demonstrated by immersion in water.

UV light emitting transparent conducting tin-doped indium oxide (ITO) nanowires.

Multifunctional single crystalline tin-doped indium oxide (ITO) nanowires with tuned Sn doping levels are synthesized via a vapor transport method. The Sn concentration in the nanowires can reach 6.4 at.% at a synthesis temperature of 840 °C, significantly exceeding the Sn solubility in ITO bulks grown at comparable temperatures, which we attribute to the unique feature of the vapor-liquid-solid growth. As a promising transparent conducting oxide nanomaterial, layers of these ITO nanowires exhibit a sheet resistance as low as 6.4 Ω/[Symbol: see text] and measurements on individual nanowires give a resistivity of 2.4 × 10(-4) Ω cm with an electron density up to 2.6 × 10(20) cm(-3), while the optical transmittance in the visible regime can reach ∼ 80%. Under the ultraviolet excitation the ITO nanowire samples emit blue light, which can be ascribed to transitions related to defect levels. Furthermore, a room temperature ultraviolet light emission is observed in these ITO nanowires for the first time, and the exciton-related radiative process is identified by using temperature-dependent photoluminescence measurements.

A first-principle analysis on the phase stabilities, chemical bonds and band gaps of wurtzite structure A(x)Zn(1-x)O alloys (A = Ca, Cd, Mg).

The phase stabilities and structural and electronic properties of three zinc-based oxide alloy systems (Ca(x)Zn(1-x)O, Cd(x)Zn(1-x)O and Mg(x)Zn(1-x)O) are studied by first-principle methods. We examine all alloy configurations in three 16-atom supercells (1 × 1 × 2 B1 phase structure, 2 × 2 × 1 and 2 × 1 × 2 B4 phase structures) and utilize symmetry of the bulk materials to reduce the amount of calculation. Taking into account the contribution of the alloy statistics, we have drawn the regions of phase stability for Ca(x)Zn(1-x)O (0.25

Femtosecond pulse generation around 1500 nm using a GaInNAsSb SESAM.

The operation of a femtosecond Cr(4+):YAG laser that incorporates a novel GaInNAsSb semiconductor saturable Bragg reflector is reported. In the mode-locked regime 230 fs pulses centred at 1528 nm were generated at an average output power of 280 mW. The SESAM exhibited a low saturation fluence of 10 microJ/cm(2) and a short recovery time of 12 ps.

Three new triterpenoid saponins from the rhizomes of Impatiens pritzellii var. hupehensis.

Three new triterpenoid saponins, impatiprins A-C (1-3), together with a known triterpenoid (4) and two known triterpenoid saponins (5, 6), were isolated from the rhizomes of Impatiens pritzellii Hook. f. var. hupehensis Hook. f. The structures of 1-3 were determined by 1D and 2D NMR, FAB-MS techniques and chemical methods. Compounds 1 and 2 showed weak cytotoxicities against S-180, HeLa and HepG2 cell lines.

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.

Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

Two new rearranged abietane diterpenoids from tropical Isodon coetsa.

Two new rearranged abietane diterpenoids, sincoetsin A (1) and sincoetsin B (2), were isolated from the aerial part of Isodon coetsa (Buth-Ham ex D.Don) Hara collected in Singapore, and their structures were determined by spectroscopic methods, especially 2D NMR techniques.

Two new triterpenoids from Picria fel-terrae.

Two new triterpenoids, picfeltarraegenin VII (1) and picfeltarraenin X (2), have been isolated from Picria fel-terrae Lour., along with three known ones, picfeltarraegenin VI (3), picfeltarraenins VI (4) and VII (5). Their structures have been elucidated by means of spectroscopic methods.

Coumarins from Coriaria nepalensis.

Two new coumarins (1) and (2), along with seven known coumarins 3-9, were isolated from the leaves and stems of Coriarianepalensis Wall. The two new compounds were established as 7-hydroxy-6-methoxy-3,8-bis(3-methyl-2-butenyl) coumarin (1) and 7-hydroxy-6-methoxy-3-(3-methyl-2-butenyl) coumarin (2), on the basis of 1D and 2D NMR techniques. The known compounds 3, 6-9 were isolated from this plant for the first time.

Chemical constituents of Selinum cryptotaenium.

A new pyranocoumarin, named secryptotaenin A, determined as 3'(S)-angeloyloxy-3',4'-dihydroseselin, was isolated from the roots of Selinum cryptotaenium, along with thirteen known compounds, umbelliferone, osthol, coumurrayin, (+)-heraclenol, longshengensin A, anomalin, ferulic acid, galactitol, stearic acid, melissic acid, lignoceric acid, beta-sitosterol and daucosterol. Their structures were determined on the basis of spectroscopic methods.

Chemical constituents from Schisandra plena.

The chemical constituents of the leaves and stems of Schisandra plena are described for the first time. This investigation has resulted in the isolation of a new sesquiterpenoid, plenoxide (1). In addition, eleven known compounds, including sesquiterpenoids, coumarins, flavanones, triterpenoids and steroids have also been isolated. The structure and stereochemistry of 1 has been determined on the basis of spectroscopic analysis. Detailed analysis of 2D NMR data led to the conclusion that the chemical shifts of earlier compounds similar to bullatantriol need revision.