Anlotinib inhibits the progress of colorectal cancer cells by antagonizing VEGFR/JAK2/STAT3 axis.

OBJECTIVE: Anlotinib, a novel tyrosine kinase receptor inhibitor (TKI), targets multi-targets, including vascular endothelial growth factor receptor (VEGFR). Increasing evidence suggests that anlotinib exhibits effective anti-tumor activity in various cancer types, such as liver cancer. However, the biological function of anlotinib in the treatment of colorectal cancer (CRC) remains largely unknown. This investigation aims to investigate the function and possible molecular mechanism of anlotinib in CRC therapy. MATERIALS AND METHODS: Human colorectal cancer cells (HCT-116 and LOVO) were cultured and treated with anlotinib alone or combined with cisplatin (DDP). Thereafter, CCK8 assay, CyQUANT NF assay, and colony formation were used to determine the cytotoxicity property and cell proliferation of colorectal cancer. To evaluate the invasion and metastasis of colorectal cancer cells, we conducted wound healing and trans-well assay. Hoechst33342 fluorescence staining and Flow Cytometry analysis were applied for apoptosis detection. Real-time qPCR and Western blot were used to measure the mRNA or protein level. RESULTS: Our results showed anlotinib alone or combined with cisplatin inhibited cell proliferation, migration, and invasion and activated apoptosis in colorectal cancer cells. Furthermore, we found that anlotinib inhibiting the phosphorylation level of VEGFR, Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3). Combination chemotherapy of anlotinib with cisplatin is more sensitive to colorectal cancer. CONCLUSIONS: These findings suggested that anlotinib might benefit colorectal cancer therapy by antagonizing VEGFR/JAK2/STAT3 signaling. Our study may provide new insights into novel molecular therapeutic strategies for colorectal cancer.

[A promoter polymorphism of CD55 effect on the risk of esophageal cancer].

Objective: This study aimed to investigate the relationship between the genetic variation of CD55 promoter and the risk of esophageal cancer. Methods: A total of 700 esophageal cancer patients recruited between April 2008 and December 2012 at Tangshan Grongren Hospital and Tangshan Renmin Hospital, and 700 frequency matched controls were randomly selected from a pool of cancer free subjects recruited from a nutritional survey. Genotypes of CD55 rs2564978 polymorphism among all subjects were conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The OR and 95%CI were calculated by non-conditional Logistic regression to evaluate the association of CD55 rs2564978T/C polymorphism with the risk of esophageal cancer. Results: The average age of cases and control was (60.04±9.19) and (59.21±9.98) years old. Compared with CD55 rs2564978 TT carriers, the individuals with CC genotype had a significantly higher risk of esophageal cancer (OR=1.94, 95%CI:1.42-2.66) . When stratified by sex, this genetic variation affected the risk of esophageal cancer among both males (OR=1.92, 95%CI:1.37-2.70) and females (OR=2.34, 95%CI:1.04-5.27). When stratified by age, the CD55 rs2564978 CC was associated with the susceptibility of developing esophageal cancer among younger individuals (OR=1.79, 95%CI:1.19-2.68) and older people (OR=2.32, 95%CI:1.41-3.83).When stratified by drinking status, CC genotype carriers increase the risk of esophageal cancer when drinking (OR=1.93, 95%CI:1.03-3.63) or not drinking (OR=1.95, 95%CI:1.36-2.80). When stratified by smoking status, CC genotype was associated with the risk of esophageal cancer among non-smokers (OR=1.79, 95%CI: 1.13-2.83), light smokers (less than 30 packs/year, OR=1.86, 95%CI:1.31-2.64) and heavy smokers (more than 30 packs/year, OR=2.67, 95%CI:1.28-5.57). Gene-environmental interaction analysis showed that CD55 rs2564978T/C polymorphism interacted with smoking status to increase the risk of esophageal cancer. Conclusion: CD55 rs2564978 polymorphism effects on the risk of esophageal cancer.

Effect of probiotics and xylo-oligosaccharide supplementation on nutrient digestibility, intestinal health and noxious gas emission in weanling pigs.

OBJECTIVE: This study was conducted to evaluate the effect of probiotics (Bacillus subtilis and Enterococcus faecium) and xylo-oligosaccharide (XOS) supplementation on growth performance, nutrient digestibility, serum profiles, intestinal health, fecal microbiota and noxious gas emission in weanling pigs. METHODS: A total of 240 weanling pigs ([Yorkshire×Landrace]×Duroc) with an average body weight (BW) of 6.3±0.15 kg were used in this 28-day trial. Pigs were randomly allocated in 1 of the following 4 dietary treatments in a 2×2 factorial arrangement with 2 levels of probiotics (0 and 500 mg/kg probiotics) and XOS (0 and 200 mg/kg XOS) based on the BW and sex. RESULTS: Administration of probiotics or XOS improved average daily gain (p<0.05) during 0 to 14 d and the overall period, while pigs that were treated with XOS had a greater average daily gain and feed efficiency (p<0.05) compared with unsupplemented treatments throughout 15 to 28 d and the whole experiment. Either probiotics or XOS treatments increased the apparent total tract digestibility of nutrients (p<0.05) during 0 to 14 d. No effects on serum profiles were observed among treatments. The XOS increased villus height: crypt depth ratio in jejunum (p<0.05). The supplementation of probiotics (500 mg/kg) or XOS (200 mg/kg) alone improved the apparent total tract digestibility of dry matter, nitrogen and gross energy on d 14, the activity of trypsin and decreased fecal NH3 concentration (p<0.05). Administration of XOS decreased fecal Escherichia coli counts (p<0.05), while increased lactobacilli (p<0.05) on d 14. There was no interaction between dietary supplementation of probiotics and XOS. CONCLUSION: Inclusion of XOS at 200 mg/kg or probiotics (Bacillus subtilis and Enterococcus faecium) at 500 mg/kg in diets containing no antibiotics significantly improved the growth performance of weanling pigs. Once XOS is supplemented, further providing of probiotics is not needed since it exerts little additional effects.

Predicative values of serum microRNA-22 and microRNA-126 levels for non-small cell lung cancer development and metastasis: a case-control study.

Presented study aims to explore the predictive values of serum microRNA-22 (miR-22) and miR-126 levels for non-small cell lung cancer (NSCLC) development and metastasis.A total of 127 NSCLC patients who were admitted in the First People's Hospital of Yancheng City from May, 2013 to May, 2015 were selected as the case group, including 71 cases of adenocarcinoma and 56 cases of squamous cell carcinoma. There were 112 healthy individuals selected as the control group. The qRT-PCR was performed to testify the serum miR-22 and miR-126 levels. Logistic regression analysis was conducted to analyze independent factors influencing NSCLC metastasis and receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of serum miR-22 and miR-126 levels in predicting NSCLC developments and metastasis.The serum miR-22 level was significantly higher in the case group than that in the control group, while the serum miR-126 level was lower in the case group as compared with that in the control group. Compared with squamous cell carcinoma patients, serum miR-22 level significantly increased, while serum miR-126 level decreased in patients with adenocarcinoma. Patients at III + IV stage showed increased serum miR-22 level and relatively decreased serum miR-126 level as compared to patients at I + II stage. Serum miR-22 level elevated in patients with metastasis; in contrast serum miR-126 level reduced in comparison to those without metastasis. In patients with familial inheritance, serum miR-22 level increased but serum miR-126 level decreased as compared to those without familial inheritance. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC development were 99.11%, 84.30%, 82.68% and 96.40%, respectively. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC metastasis were 59.74%, 96.00%, 84.00% and 62.30%, respectively.Results indicated that serum miR-22 and miR-126 levels may be used as the predicative biomarkers for NSCLC development and metastasis.

Enhancement of bandgap emission of Pt-capped MgZnO films: important role of light extraction versus exciton-plasmon coupling.

We present on a systematic study of the contribution of surface plasmon (SP) coupling and light extraction toward emission enhancement of Platinum (Pt) nano-patterns capped MgZnO films. Time resolved Photoluminescence (PL) results indicate that the Pt coating can greatly reduces the non-radiative recombination rate by passivation of surface states, making the decay slow down. Temperature dependence of the integrated photoluminescence intensity reveals that the Pt nano-patterns can offer a large amount of light transfer and scattering, which enormously increase the light extraction efficiency up to 3.8-fold. These results indicate that the increased light extraction efficiency caused by surface modification via Pt coating rather than SP coupling plays a dominant role in increasing bandgap emission of MgZnO film.

Temperature effect of the local structure in liquid Sb studied with x-ray absorption spectroscopy.

The temperature dependence of the local structure of liquid Sb has been studied by x-ray absorption spectroscopy. It is shown that about 10% of the atoms with coordination of 3 and weak Peierls distortion exist in liquid Sb just above its melting point. The Peierls distortion weakens gradually with increasing temperature and vanishes at about 750 degrees C. This structural variation in liquid Sb is different from the normal liquid-liquid phase transition. This work reveals the relationship between the variation in the local structure and the change in the physical properties, such as the electrical resisitvity of liquid Sb, with temperature. The complete agreement between the measured electrical resistivity values during heating and cooling processes suggests that the structural units with the features of a rhombohedron appear above the melting point of Sb during solidification.

Effects of lanthanum on composition, crystal size, and lattice structure of femur bone mineral of Wistar rats.

The application of lanthanum (La) in industry, medicine, and agriculture may cause accumulation of the element in human body. This article examines the effects of La on the femur bone mineral of male Wistar rats after administration of La(NO3)3 by gavage at the dose of 2.0 mg La(NO3)3.kg(-1).day(-1) over a 6-month period. Chemical analysis confirmed La accumulation in bone and loss in bone mineral. Thermogravimetric analysis showed a decrease in the mineral-to-matrix ratio and an increase in carbonate content. Fourier-transform infrared spectrometry revealed elevation in the contents of labile carbonate and acidic phosphate. The synchrotron radiation small-angle X-ray scattering study presented a smaller mean thickness of the mineral crystals in the bone of La-treated rats. The synchrotron radiation-extended X-ray absorption fine structure analysis indicated that the La treatment resulted in a lowered disorder in the crystals. The smaller size, more adsorbed labile carbonate, and more acidic phosphate made the bone mineral easier to dissolve, as revealed in the kinetic measurement of bone demineralization. These findings suggest that La retards bone maturation of rats.

An abnormal rate of actin myosin cross-bridge cycling in colonic smooth muscle associated with experimental colitis.

Previous studies showed that colonic smooth muscle develops less contractile force to neurohumoral stimulation when associated with mucosal inflammation. This study evaluated 1) the Ca2+ dependence for colonic smooth muscle contraction, 2) the maximum velocity of muscle shortening (Vmax), and 3) changes in 20-kDa myosin light-chain (MLC) phosphorylation in distal circular colonic muscle from healthy rabbits and from rabbits with experimental colitis, induced by Formalin and immune complexes. The isometric tension of unskinned muscle stimulated with bethanechol or KCl was less (P less than 0.05) in animals with colitis compared with the control group. In saponin-skinned muscle, the amplitude of the maximal tension at [Ca2+] of 3 x 10(-7) M was decreased (P less than 0.05) in colitis animals (4.3 +/- 0.9 x 10(4) N/m2, n = 7) compared with healthy animals (10.5 +/- 2.4 x 10(4) N/m2, n = 6). However, the ED50 for Ca2+ stimulation was similar (P greater than 0.05) in both groups. When MLC was thiophosphorylated with ATP gamma S, the tension development was decreased in colitis (2.1 +/- 0.3 x 10(4) N/m2, n = 5; P less than 0.01) compared with normals (5.0 +/- 1.4 x 10(4) N/m2, n = 5). In healthy animals, phosphorylation of 20-kDa MLC increased rapidly to 51.2 +/- 3.1% within 15 s after stimulation and subsequently declined to 19.0 +/- 2.1% at 5 min. Vmax was maximal (0.14 Lo/s) 13 s after stimulation and declined before maximal active isometric stress. In colitis animals, the 20-kDa MLC phosphorylation (P less than 0.05) and the Vmax (P less than 0.01) were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of cAMP-mediated relaxation of distal circular muscle in rabbit colon.

Photolytic release of free adenosine 3',5'-cyclic monophosphate (cAMP) from its caged form was used to evaluate the physiological role of several proposed mechanisms of cAMP-mediated relaxation of circular smooth muscle in the distal rabbit colon. Photolysis of caged cAMP produced a rapid relaxation of bethanechol-contracted distal circular muscle strips that was dependent on ultraviolet exposure time. An increase in release of free cAMP, associated with increased ultraviolet exposure, was confirmed with high-performance liquid chromatography. Vanadate (an ATPase inhibitor) (3 mM) caused a 48% decrease in cAMP-mediated relaxation, while ouabain and a zero K+ bath solution failed to affect relaxation. cAMP-mediated relaxation of KCl-contracted strips was significantly less effective than that of bethanechol-contracted strips. Although this finding suggested that cAMP-mediated relaxation may involve K+ channel modulation, specific (glibenclamide, charybdotoxin) and nonspecific (TEA) K+ channel blockade failed to affect cAMP-mediated relaxation of bethanechol-contracted strips. The photolytic release of cAMP failed to relax Ca(2+)-contracted saponin skinned muscle strips. These studies suggest 1) modulation of Ca2+ pumps plays an important role in this model of relaxation of distal colonic circular muscle in the rabbit colon, 2) modulation of the Na+ pump or sarcolemmal K+ channels may not play an important physiological role in relaxation induced by a rapid rise in intracellular cAMP, and 3) cAMP does not seem to have a significant physiological effect on the Ca2+ sensitivity contractile apparatus.

Ascitic fluid analysis for the differentiation of malignancy-related and nonmalignant ascites. Proposal of a diagnostic sequence.

The authors tried to differentiate malignancy-related from nonmalignant ascites with a sequence of sensitive followed by specific ascitic-fluid parameters. There were four results of this study. First, of nine parameters investigated in a first series of 48 patients, 28 with nonmalignant and 20 with malignancy-related ascites, ascitic-fluid cholesterol and fibronectin yielded the best negative predictive value of 92% each. Carcinoembryonic antigen (CEA) and cytologic examination both showed a positive predictive value of 100%. Second, combining cytologic examination (sensitivity, 70%) and CEA determination (sensitivity, 45%) increased the sensitivity to 80%. Third, cytologic findings were negative in all ascitic-fluid samples with a cholesterol concentration below the cutoff value of 45 mg/100 ml. Fourth, based on the results of the first series of 48 patients, the diagnostic sequence with cholesterol as a sensitive parameter, followed by the combination of cytologic examination and CEA determination as specific parameters, was tested in a second series of 71 patients, 37 with nonmalignant and 34 with malignancy-related ascites. Again cytologic examination was negative in all samples with cholesterol levels below 45 mg/100 ml. In the total of 119 patients, this diagnostic sequence did not identify 9% of patients with malignancy-related ascites, and 82% of samples classified as malignancy related by cholesterol levels above 45 mg/100 ml were confirmed by positive cytologic examination and/or CEA level above 2.5 ng/ml. Thus, a diagnostic sequence with ascitic-fluid cholesterol determination, followed by cytologic examination and CEA determination, in samples with cholesterol levels above 45 mg/100 ml should permit a cost-efficient routine differentiation of malignancy-related from nonmalignant ascites.

Ascitic fluid concentrations of fibronectin and cholesterol: comparison of differential diagnostic value with the conventional protein determination.

Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy-related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy-related ascites.