Visualizing chiral structures in cellulose nanocrystal films by a Mueller matrix microscope.

Visualizing chiral structures in solid materials is crucial but difficult in chiral analysis. The three-dimensional structures in the helicoidal nano-assemblies in cellulose nanocrystal (CNC) films were visualized using a Mueller matrix microscope (MMM). Optical analysis of the assembly of CNCs through structural reconstruction by optical simulation revealed the complex structures in CNC films.

Study on the changes of CT texture parameters before and after HCC treatment in the efficacy evaluation and survival predication of patients with HCC.

Objective: To investigate texture parameters of contrast-enhanced computed tomography (CT) images before and after transarterial chemoembolization (TACE) as a tool for assessing the therapeutic response and survival predication in hepatocellular carcinoma (HCC). Materials and methods: Data of 77 HCC patients who underwent three-phase dynamic contrast-enhanced CT examination within 4 weeks before and 4-8 weeks after TACE were collected and efficacy evaluation was performed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) standard. The remission group consisted of 31 patients (12 with complete remission+19 with partial remission), while the non-remission group consisted of 46 patients (27 with stable disease+19 with progressive disease). Full-volume manual delineation of the region of interest (ROI) and texture analysis of the ROI were performed on the CT images using FireVoxel software. Changes in the 48 texture parameters from three-phase CT images before and after TACE were calculated and compared between the two groups. The receiver operating characteristic (ROC) curve and the areas under the curve (AUC) were used to analyze the diagnostic performance of texture parameters. A multifactorial Cox model was used for predicting survival. The C-indices of texture parameter difference values with predictive value, texture features model, and texture features combined with mRECIST in predicting OS were compared with those of mRECIST. Results: A total of 41 changes in texture parameters were statistically significant between the remission and non-remission groups. The receiver operating characteristic (ROC) curve showed that the AUC of changes in the 90th percentile in the arterial phase was the largest at 0.842. When the cut-off value was 70.50, the Youden index was the largest (0.621), and the sensitivity and specificity were 0.710 and 0.911, respectively. Three changes in texture parameters were independent factors associated with patient survival, with a hazard of 0.173, 2.068, and 1.940, respectively. The C-index of the OS predicted by the texture features model was not statistically different from that of the mRECIST (0.695 vs. 0.668, p=0.493). While the C-indices of skewness in the portal venous phase combined with mRECIST (0.729, p=0.015), skewness in the delayed phase combined with mRECIST (0.715, p=0.044), and skewness in both two phases combined with mRECIST (0.728, p=0.017) were statistically different. Conclusion: Changes in the texture parameters of CT images before and after TACE treatment can be used to obtain relevant grayscale histogram parameters for evaluating the early efficacy of TACE in HCC treatment. And the texture analysis combined with mRECIST may be superior to the mRECIST alone in predicting survival in HCC after TACE treatment.

Type-2 11ß-hydroxysteroid dehydrogenase promotes the metastasis of colorectal cancer via the Fgfbp1-AKT pathway.

Type-2 11ß-hydroxysteroid dehydrogenase (HSD11B2) is a key enzyme which converts cortisol to inactive cortisone and is involved in tumor progression and metastasis. Several studies have shown that the promotion of tumor progression and metastasis by HSD11B2 resulted from its physiological function of inactivating glucocorticoids (GC). However, the underlying molecular mechanisms by which HSD11B2 drives metastasis, in addition to inactivating GC, are still unclear. In our study, a series of in vivo and in vitro assays were performed to determine the function of HSD11B2 and the possible mechanisms underlying its role in CRC metastasis. mRNA transcriptome array analysis was used to identify the possible downstream targets of HSD11B2. We found that the ectopic expression of HSD11B2 significantly promoted the migration, invasion and metastasis of colorectal cancer (CRC) cells both in vitro and in vivo, while it did not affect their proliferation in either case. Mechanically, HSD11B2 appeared to enhance cell migration and invasion by upregulating the expression of fibroblast growth factor binding protein 1 (Fgfbp1), and subsequently increasing the phosphorylation of AKT. Furthermore, AKT activation partially mediated the increased expression of Fgfbp1 induced by HSD11B2. HSD11B2 expression was positively correlated with Fgfbp1 and p-AKT expression in clinical samples of CRC. Additionally, knockdown of either Fgfbp1 or AKT impaired the migration and invasion capability of CRC cells with HSD11B2 overexpression, suggesting that HSD11B2 promoted the migration, invasion and metastasis of CRC cells via the Fgfbp1-AKT pathway. Therefore, targeting HSD11B2 or Fgfbp1 may be a novel treatment strategy for inhibiting the metastasis of CRC.

Astrocyte elevated gene 1 (AEG-1) promotes anoikis resistance and metastasis by inducing autophagy in hepatocellular carcinoma.

Astrocyte elevated gene 1 (AEG-1) is overexpressed in hepatocellular carcinoma (HCC) and is strongly associated with tumor metastasis. Anoikis resistance and autophagy may play an important role in the survival of circulating tumor cells. However, the relationship among AEG-1, anoikis resistance, autophagy, and metastasis in HCC is still not clear. The results of this study indicate that AEG-1 expression is increased in HCC cell lines grown in suspension culture. AEG-1 could enhance anoikis resistance to promote the survival of detached HCC cells. Moreover, the anoikis resistance appears to be partly dependent on autophagy. Regulating AEG-1 expression changed the autophagy levels to modulate anoikis resistance, likely acting via the protein kinase RNA-like ER kinase (PERK)-eIF2α-ATF4-CHOP signaling axis. Finally, inhibiting autophagy by RNA interference prevented the AEG-1-promoted metastasis of HCC xenografts to the liver and lungs of nude mice. Taken together, AEG-1 is a key contributor to anoikis resistance and metastasis by inducing autophagy in vitro and in vivo, and it may be a potential target for therapeutic intervention in HCC.

DEPTOR induces a partial epithelial-to-mesenchymal transition and metastasis via autocrine TGFß1 signaling and is associated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: DEPTOR is an endogenous inhibitor of mTORC1 and mTORC2 that plays a vital role in the progression of human malignances. However, the biological function of DEPTOR in HCC metastasis and the underlying molecular mechanisms are still unclear. METHODS: Western blot analysis and immunohistochemistry(IHC) were employed to examine DEPTOR expression in HCC cell lines and tissues. A series of in vivo and in vitro assays were performed to determine the function of DEPTOR and the possible mechanisms underlying its role in HCC metastasis. RESULTS: We found that DEPTOR was frequently overexpressed in HCC tissues, and its high expression was associated with high serum AFP levels, increased tumor size, vascular invasion and more advanced TMN and BCLC stage, as well as an overall poor prognosis. Functional experiments demonstrated that DEPTOR silencing inhibited the proliferation and mobility of HCC cells in vitro and suppressed tumor growth and metastasis of HCC cells in vivo. Accordingly, DEPTOR overexpression promoted the invasion and metastasis of HCC cells in vitro and in vivo, but had no effect on cell proliferation in vitro. Overexpression of DEPTOR induced EMT by snail induction. Conversely, knockdown of snail expression impaired the DEPTOR-induced migration, invasion and EMT of HCC cells. Furthermore, we found that the increase of snail expression by DEPTOR overexpression was due to an activation of TGF-ß1-smad3/smad4 signaling possibly through feedback inhibition of mTOR. CONCLUSION: DEPTOR promotes the EMT and metastasis of HCC cells by activating the TGF-ß1-smad3/smad4-snail pathway via mTOR inhibition. Therefore, targeting DEPTOR may be an ideal treatment strategy for inhibiting the growth and metastasis of HCC.

The prediction value of scoring systems in Mallory-Weiss syndrome patients.

Mallory-Weiss syndrome (MWS) is a relatively less common cause of nonvariceal upper gastrointestinal bleeding. There is limited data on whether scoring systems could be used to predict the clinical outcomes in patients with bleeding due to MWS. The aim of our study is to evaluate whether the Glasgow-Blatchford score (GBS), AIMS65, and shocking index are effective in predicting the clinical outcomes of MWS.One hundred twenty-eight patients from January 2010 to January 2017 with MWS in middle China were enrolled. Clinical features such as age, gender, causes of vomiting, endoscopic findings, GBS, AIMS65, and shocking index were recorded. The clinical outcomes including endoscopic treatment and transfusion were analyzed.MWS accounted for 6.1% of nonvariceal upper gastrointestinal bleeding. Male-to-female ratio was 3.6:1 and median age was 51 years. Patients between 40 and 60 years were more commonly affected; 43.8% of MWS was caused by overdrinking followed by underlying gastric diseases (33.6%). However, for female patients alone, underlying gastric diseases were the leading cause (42.9%). The tears were usually single and most frequently located on the left lateral wall. In receiver-operating characteristic curve analyses, GBS system and shocking index were useful in predicting transfusion (0.856 vs 0.675). But for endoscopic intervention, these scoring systems are not helpful (P > .05).Apart from drinking, underlying gastric disease is another important cause of MWS especially for female patients and should be paid more attention under endoscopy examination. GBS system and shocking index can be used to predict transfusion.

Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux.

Nonalcoholic fatty liver disease (NAFLD) is a kind of liver lipid synthesis and degradation imbalance related with metabolic syndrome. Celecoxib shows the function of ameliorating NAFLD, but the underlying mechanisms remain unknown. Here, we discuss the possible mechanisms of celecoxib alleviating NAFLD by restoring autophagic flux. Lipids were accumulated in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. Western blot showed that LC3 II/I was higher and p62 was lower on the early stage of steatosis while on the late stage both of them were higher, indicating that autophagic flux was activated on the early stage of steatosis, but blocked on the late stage. Rapamycin alleviated steatosis with activating autophagic flux while chloroquine aggravated steatosis with inhibiting autophagic flux. COX-2 siRNA and celecoxib were used to inhibit COX-2. Western blot and RFP-GFP-LC3 double fluorescence system indicated that celecoxib could ameliorate steatosis and restore autophagic flux in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. In conclusion, celecoxib partially restores autophagic flux via downregulation of COX-2 and alleviates steatosis in vitro and in vivo.