The new role of riluzole in the treatment of pancreatic cancer through the apoptosis and autophagy pathways.

Pancreatic cancer is always diagnosed at an advanced stage. Hence, chemotherapy becomes the best choice for patients. Therefore, new anticancer drugs for pancreatic cancer are needed. Riluzole (RIL) is mainly used to treat amyotrophic lateral sclerosis clinically, but many previous studies have shown that RIL could inhibit tumors. However, no report has explored the association between RIL and pancreatic cancer. To validate this association, we performed this study. Our data showed that RIL could induce cytotoxicity, block the cell cycle, and inhibit clone formation, apoptosis, and migration in pancreatic cancer cells. Moreover, we demonstrated that RIL could suppress autophagy. However, more experiments will be needed to validate the reliability of our conclusions. In summary, our data suggest that RIL might provide clues for the development of a treatment for human pancreatic cancer in the future.

Evidence from 40 Studies that 2 Common Single-Nucleotide Polymorphisms (SNPs) of RNASEL Gene Affect Prostate Cancer Susceptibility: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Compliant Meta-Analysis.

BACKGROUND Numerous studies have evaluated the relationship between RNASEL gene polymorphisms (rs486907 G>A and rs627928 T>G) and the risk of cancer. However, many of the results have been controversial. To explore the role of RNASEL gene polymorphisms in prostate cancer, we carried out the present meta-analysis. MATERIAL AND METHODS The qualified articles were collected from PubMed, Web of Science, Scopus, CNKI, and WanFang databases to August 2018. A total 23 articles with 40 studies were incorporated into our analysis. RESULTS Our data show that rs486907 was not associated with the risk of prostate cancer in any populations. Nevertheless, rs627928 was reported to promote the development of prostate cancer (T vs. G: OR=1.08, 95% CI=1.01-1.15; TT+TG vs. GG: OR=1.14, 95% CI=1.03-1.25) in allele and recessive models in overall populations. Stratified analyses showed that similar results were obtained in white populations. CONCLUSIONS We report the effect of rs627928 on the development of prostate cancer and confirm that rs486907 is not involved in the risk of prostate cancer in the current meta-analysis. However, research in larger populations is needed to validate our conclusions.

Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPß-regulated atrogin1 expression in cancer cachexia.

Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPß), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPß-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPß, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPß binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia.

Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity.

When encountering target cells, NK (natural killer) cells exocytose Pfn (perforin) and granzyme B to kill challengers. We previously reported that granzyme B is recycled and reused by NK cells via clathrin-dependent endocytosis. However, whether Pfn, a main secretory vesicle content, indispensible to granzyme B killing, undergoes endocytosis remains unknown. We demonstrate that Pfn is recaptured by early endosomes of NK cells via a clathrin-dependent endocytosis after target cell stimulation. Inhibition of clathrin-dependent endocytosis significantly attenuated the cytotoxicity of NK cells. The data suggest that the recovery of Pfn contributes to the cytotoxicity of NK cells. The assay of endocytosis of lytic molecule presents a particular focus for exploring the mechanism of abnormal cytotoxicity of NK cells.

One-Pot Ethyl Acetate Production from Ethanol Photooxidation on Rutile TiO2(110): Strong Photon Energy Dependence.

Ethyl acetate (EA) production from sequential ethanol (EtOH) photooxidation on a rutile(R)-TiO2(110) surface has been investigated by the temperature-programmed desorption (TPD) method at 355 and 266 nm. Significant EA product is detected under 266 nm irradiation, which is most likely to be formed via cross-coupling of primary dissociation products, aldehyde (CH3CHO) and ethoxy groups. On the contrary, EA formation at 355 nm is negligible. In addition, the initial rate of EA formation from EtOH at 266 nm is nearly 2 orders of magnitude faster than that at 355 nm. Quantitative analysis suggests that EA formation from sequential EtOH photooxidation on R-TiO2(110) is strongly dependent on photon energy or the energy of hot holes. This experimental result raises doubt about the traditional photocatalysis model on TiO2 where charge carriers relax to their respective band edges prior to charge transfer to adsorbates during the photocatalytic process, leading to no dependence on photon energy in TiO2 photocatalysis.

Hydrogen Production on Pt/TiO2: Synergistic Catalysis between Pt Clusters and Interfacial Adsorbates.

Understanding the mechanism of hydrogen (H2) formation from the conversion of water (H2O) and renewables on TiO2 surfaces with cocatalysts via either photocatalysis or other catalytic processes is of significant importance to the successful design of efficient catalysts. Herein, we have investigated H2 production from H2O, CH3OH, and C2H5OH on a Pt cluster covered rutile (R)-TiO2(110) surface (Ptclut/R-TiO2(110)) to address the mechanism of H2 production. Experimental results demonstrate that surface adsorbates not only help H atom diffusion on Ptclut/R-TiO2(110) but also take part in H2 production directly. Further density functional theory (DFT) calculations suggest that H2 production on Ptclut/R-TiO2(110) occurs via a synergistic catalysis process between Pt clusters and interfacial adsorbates rather than a recombination reaction of H atoms on Pt clusters. This work provides new insight into H2 production from H2O and renewables with Pt/TiO2 catalysts, which may be applicable to H2 production on other Pt cluster deposited metal oxide catalysts.

-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: a meta-analysis.

BACKGROUND: Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α -308 were implicated in MS risk in several case-control association studies. However, the studies have shown inconsistent results. OBJECTIVES: To address the association of G/A polymorphisms of TNF-α -308 with MS risk by meta-analysis. METHODS: Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that -308 A allele is significantly associated with reduced risk of MS compared with -308 G allele (A vs. G, p=0.022). The same pattern of the result was also obtained in the contrasts of AA+ GA vs. GG (p=0.008) and GA vs. GG (p=0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies. CONCLUSIONS: TNF-α -308 A allele is associated with reduced risk of MS.

Lung cancer-derived extracellular vesicles induced myotube atrophy and adipocyte lipolysis via the extracellular IL-6-mediated STAT3 pathway.

Cancer-associated cachexia (CAC) constitutes a metabolic dysfunction characterized by systemic inflammation and body weight loss. Muscle atrophy and adipose tissue lipolysis might explain weight loss in CAC. Specific functions of numerous hormones and cytokines derived from tumours can provoke cachexia. Extracellular vesicles (EVs) can be involved in intercellular communication. However, whether EVs participate in this process has not been investigated thoroughly. Using Lewis lung carcinoma (LLC) cell cultures, we tested whether LLC-derived EVs induced C2C12 myotube atrophy and 3T3-L1 adipocyte lipolysis. EVs derived from LLC cells and serum from patients with lung cancer, non-lung cancer controls, tumour-bearing mice, and non-tumour-bearing control mice were isolated and characterized biochemically and biophysically. LLC cell-derived EVs induced dose-dependent effects of atrophy in C2C12 myotubes and lipolysis in 3T3-L1 adipocytes. Mechanistically, EVs directly fused with target C2C12 myotubes and 3T3-L1 adipocytes, and transferred interleukin-6 (IL-6) activates the STAT3 signalling pathway in C2C12 myotubes and 3T3-L1 adipocytes. Neutralization of extracellular IL-6 prevented the atrophy and lipolysis effects of EVs. Inhibiting the STAT3 signalling pathway also prevented the atrophy and lipolysis effects of EVs. PKH67-labelled (PKH 67 is a lipid dye that can be used to label extracellular vesicles) LLC-EVs were readily internalized into myotubes and adipocytes. Our data showed that LLC cell-derived EVs induced myotube atrophy and adipocyte lipolysis via the extracellular IL-6-mediated STAT3 pathway in target cells. These findings represent a potentially novel basis for further research in this field towards identifying targets and developing strategies for maintaining weight in CAC.

Association between the polymorphisms in XPG gene and gastric cancer susceptibility in Chinese populations: A PRISMA-compliant meta-analysis.

BACKGROUND: Several previous studies were carried out on the association between xeroderma pigmentosum group G (XPG) gene polymorphisms (including rs873601 G>A, rs2094258 C>T, rs2296147 T>C, and rs751402 C>T) and the risk of gastric cancer in Chinese populations. However, their conclusions were not consistent. Therefore, this meta-analysis was performed by us to investigate the association between the 4 potentially functional single nucleotide polymorphisms (SNPs) of XPG gene and gastric cancer risk. METHODS: The eligible literatures were identified through PubMed, Embase, Ovid MEDLINE, Web of Science, CNKI, and Wan fang databases up to July 2017. Finally, 5 studies for rs873601, 7 studies for rs2094258, 4 studies for rs2296147, and 8 studies for rs751402 were used for the current meta-analysis. RESULTS: Of the 4 included SNPs, only rs751402 was showed to be associated with the risk of gastric cancer [C vs T, odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.04-1.29; CC + CT vs TT, OR = 1.23, 95% CI = 1.00-1.52; CC vs CT + TT, OR = 1.15, 95% CI = 1.05-1.27; CC vs TT, OR = 1.35, 95% CI = 1.06-1.72; CC vs CT, OR = 1.13, 95% CI = 1.02-1.25]. CONCLUSION: The current meta-analysis demonstrated that the XPG gene polymorphism rs751402 was associated with increased susceptibility to gastric cancer in Chinese populations. However, studies with a larger number of subjects among different ethnic groups are needed to further validate the results.

The Reference Intervals of Thyroid Hormones for Pregnant Women in Zhejiang Province.

Gestation-specific reference intervals for thyroid hormones are used to estimate thyroid function in pregnant women. This study was to establish the reference intervals for pregnant women in Zhejiang province, China. A total of 9038 cases were recruited. The values of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, total thyroxine, and total triiodothyronine were determined by Beckman Coulter DxI-800 analyzers. Our results indicated that the level of TSH declined in the first trimester and then rose as pregnancy progressed. Conversely, the level of free triiodothyronine rose in the first trimester and then declined. The ranges of free thyroxine kept the decreasing trend crossing the gestation period. For total triiodothyronine, the ranges increased as pregnancy progressed and declined in the third trimester. The variation trends of total triiodothyronine and total thyroxine were similar. Our data confirmed the importance of the reference intervals of thyroid hormones for pregnant women.

miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC. METHODS AND MATERIALS: The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues. RESULTS: We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage. CONCLUSIONS: Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC.

Comparative molecular analysis of early and late cancer cachexia-induced muscle wasting in mouse models.

Cancer-induced muscle wasting, which commonly occurs in cancer cachexia, is characterized by impaired quality of life and poor patient survival. To identify an appropriate treatment, research on the mechanism underlying muscle wasting is essential. Thus far, studies on muscle wasting using cancer cachectic models have generally focused on early cancer cachexia (ECC), before severe body weight loss occurs. In the present study, we established models of ECC and late cancer cachexia (LCC) and compared different stages of cancer cachexia using two cancer cachectic mouse models induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC). In each model, tumor-bearing (TB) and control (CN) mice were injected with cancer cells and PBS, respectively. The TB and CN mice, which were euthanized on the 24th day or the 36th day after injection, were defined as the ECC and ECC-CN mice or the LCC and LCC-CN mice. In addition, the tissues were harvested and analyzed. We found that both the ECC and LCC mice developed cancer cachexia. The amounts of muscle loss differed between the ECC and LCC mice. Moreover, the expression of some molecules was altered in the muscles from the LCC mice but not in those from the ECC mice compared with their CN mice. In conclusion, the molecules with altered expression in the muscles from the ECC and LCC mice were not exactly the same. These findings may provide some clues for therapy which could prevent the muscle wasting in cancer cachexia from progression to the late stage.