Interferon-gamma inducible protein 10 (IP10) induced cisplatin resistance of HCC after liver transplantation through ER stress signaling pathway.

Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort. The role of IP10 on HCC cell proliferation and tumor growth under chemotherapy was studied both in vitro and in vivo. The underlying mechanism was revealed by detecting the activation of endoplasmic reticulum (ER) stress signaling pathways. Moreover, the effect of IP10 neutralizing antibody sensitizing cisplatin treatment was further explored. In rat liver transplantation model, significant up-regulation of IP10 associated with multidrug resistant genes was found in small-for-size liver graft. Clinically, high expression of circulating IP10 was significant correlated with tumor recurrence in HCC patients underwent LDLT. Overexpression of IP10 promoted HCC cell proliferation and tumor growth under cisplatin treatment by activation of ATF6/Grp78 signaling. IP10 neutralizing antibody sensitized cisplatin treatment in nude mice. The overexpression of IP10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway. IP10 neutralizing antibody could be a potential adjuvant therapy to sensitize cisplatin treatment

Potential effectiveness of traditional Chinese medicine for cardiac syndrome X (CSX): a systematic review and meta-analysis

BACKGROUND: Treatment of cardiac syndrome X with unknown pathological mechanism remains a big challenge for clinicians. Complementary and alternative medicine may bring a new choice for its management. The aim of this study is to evaluate the clinical effects of traditional Chinese medicine on cardiac syndrome X patients. METHODS: We systematically searched databases such as Cochrane CENTRAL, PubMed, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP, and handsearched relevant journals to identify randomized controlled trials. Following the steps of systematic review recommended by the Cochrane group, we assessed the quality of included studies, extracted valid data and undertook meta-analysis. RESULTS: Twenty one moderate-to low-quality randomized controlled trials involving 1143 patients were included. The results showed that traditional Chinese medicine could improve angina [OR=1.34, 95% CI: 1.2 to 1.50], electrocardiogram (ECG), endothelin-1 (ET-1) levels, prolong exercise duration in treadmill tests, and reduce angina frequency per week compared with routine treatment. No other side effect was reported except two cases of stomach pain. CONCLUSION: Compared with conventional treatment, traditional Chinese medicine shows the potential of optimizing symptomatic outcomes and improving ECG and exercise duration. The efficacy of TCM may find explanation in its pharmacological activity of adjusting the endothelial function. TCM, as a kind of alternative and complementary medicine, may provide another choice for CSX patients

Detection and identification of NAP-2 as a biomarker in hepatitis B-related hepatocellular carcinoma by proteomic approach

<p>Abstract</p> <p>Background</p> <p><b>A </b>lack of sensitive and specific biomarkers is a major reason for the high rate of Primary hepatocellular carcinoma (HCC)-related mortality. The aim of this study was to investigate potential proteomic biomarkers specific for HCC.</p> <p>Methods</p> <p>81 patients with hepatitis B-related HCC and 33 healthy controls were randomly divided into a training set (33 HCC, 33 controls) and a testing set (48 HCC, 33 controls). Serum proteomic profiles were measured using Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS).) A classification tree was established by Biomarker Pattern Software (BPS). Candidate SELDI peaks were isolated by tricine-SDS-PAGE, identified by HPLC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues.</p> <p>Results</p> <p>A total of 6 proteomic peaks (3157.33 m/z, 4177.02 m/z, 4284.79 m/z, 4300.80 m/z, 7789.87 m/z, and 7984.14 m/z) were chosen by BPS to establish a classification tree with the highest discriminatory power in the training set. The sensitivity and specificity of this classification tree were 95.92%, and 100% respectively in the testing set. A candidate marker of about 7984 m/z was isolated and identified as neutrophil-activating peptide 2 (NAP-2). IHC staining showed that NAP-2 signals were positive in HCC tissues but negative in adjacent tissues.</p> <p>Conclusion</p> <p>The NAP-2 may be a specific proteomic biomarker of hepatitis B-related HCC.</p

EFFECTS OF POLLEN TYPHAE TOTAL FLAVONE ON β-ARRESTIN-2/SRC/ AKT SIGNALING IN ADIPOSE TISSUES OF TYPE 2 DIABETIC RATS

Background: Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, a Chinese herbal medicine, has been reported to improve insulin resistance in type 2 diabetic rats, but the potential mechanisms keep unclear. Materials and Methods: Type 2 diabetic model rats were induced by high-fat diet and low-dose streptozotocin, and then were administered PTF by intragastrical gavage. After treatment for 4 weeks, insulin receptor-β level in adipose tissues was determined by ELISA, and the protein expression was analyzed by western blotting. Results: Administration of PTF increased insulin receptor-β level and enhanced β-arrestin-2 protein expression in adipose tissues of type 2 diabetic rats. Although having no effect on the protein expression of Src or Akt, PTF promoted phosphorylation of Src at Tyr416 and Akt at Ser473. Conclusion: The results indicate that PTF has beneficial effects on the β-arrestin-2/Src/Akt signaling in adipose tissues of type 2 diabetic rats, implying the underlying mechanisms of PTF in ameliorating insulin resistance

Epicuticular wax of sweet sorghum influenced the microbial community and fermentation quality of silage

Epicuticular wax, as secondary metabolites (hydrophobic compounds) covering plant surface, plays important roles in protecting plants from abiotic and biotic stresses. However, whether these compounds will influence fermentation process of silage is still not clear. In this study, two sweet sorghum cultivars with varying epicuticular wax on sheath (bloom), Yajin 2 (YJ, less bloom), and Jintian (JT, dense bloom), were harvested at flowering and maturing stages, and ensiled with or without bloom, aiming to evaluate the effects of bloom on fermentation quality, feed nutrition and microbial community. The bloom was collected manually with de-waxed cotton and extracted with chloroform. The results showed that the bloom reduced the concentrations of water-soluble carbohydrate and crude protein of the two cultivars at both stages, reduced lactic acid (LA) for YJ at both stages and for JT at flowering stage, and increased LA for JT at mature stage. The α-diversity of bacterial communities of the silage fermentation with bloom was significantly lower than that without bloom. Bloom increased the abundance of Lactobacillus, reduced that of Bacillus and Weissella, and significant correlations were observed between fermentative qualities and bacterial abundances. However, decreased diversity of bacterial community and the contents of LA implied that shifts in bacterial community might exert negative effects on silage fermentation. Our results suggest that bloom wax could alter the microbial community composition of ensiled sweet sorghums, which thus influence the fermentation qualities

Evaluation of reference genes for quantitative expression analysis in Mylabris sibirica (Coleoptera, Meloidae)

Mylabris sibirica is a hypermetamorphic insect whose adults feed on oilseed rape. However, due to a shortage of effective and appropriate endogenous references, studies on molecular functional genes in Mylabris sibirica, have been tremendously limited. In this study, ten internal reference genes (ACT, ARF1, AK, EF1α, GAPDH, α-TUB, RPL6, RPL13, RPS3 and RPS18) were tested and assessed under four selected treatments including adult ages, adult tissues, temperatures, and sex by RT-qPCR based on five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). Our findings showed that RPL6 and RPL13 were the most optimal internal reference gene combination for gene expression during various adult ages and under diverse temperatures; The combination of RPL6 and RPS18 was recommended to test gene transcription levels under different adult tissues. AK and RPL6 were the best reference genes in male and female adults. RPL6 and RPL13 were the most appropriate reference gene pair to estimate gene expression levels under four different tested backgrounds. The relative transcript levels of a uridine diphosphate (UDP)-N-acetylglucosamine-pyrophosphorylase (MsUAP), varied greatly according to normalization with the two most- and least-suited reference genes. This study will lay the basis for further molecular physiology and biochemistry studies in M. sibirica, such as development, reproduction, sex differentiation, cold and heat resistance

Single-shot spatial instability and electric control of polariton condensates at room temperature

In planar microcavities, the transverse-electric and transverse-magnetic (TE-TM) mode splitting of cavity photons arises due to their different penetration into the Bragg mirrors and can result in optical spin-orbit coupling (SOC). In this work, we find that in a liquid crystal (LC) microcavity filled with perovskite microplates, the pronounced TE-TM splitting gives rise to a strong SOC that leads to the spatial instability of microcavity polariton condensates under single-shot excitation. Spatially varying hole burning and mode competition occurs between polarization components leading to different condensate profiles from shot to shot. The single-shot polariton condensates become stable when the SOC vanishes as the TE and TM modes are spectrally well separated from each other, which can be achieved by application of an electric field to our LC microcavity with electrically tunable anisotropy. Our findings are well reproduced and traced back to their physical origin by our detailed numerical simulations. With the electrical manipulation our work reveals how the shot-to-shot spatial instability of spatial polariton profiles can be engineered in anisotropic microcavities at room temperature, which will benefit the development of stable polariton-based optoeletronic and light-emitting devices