Thermal-Assisted Multiscale Patterning of Nonplanar Colloidal Nanostructures for Multi-Modal Anti-Counterfeiting.

Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

Prognostic Implications of Endoscopic Obstruction in Patients with Pathological Stage II Colon Cancers: a Single-Center Retrospective Cohort Study.

BACKGROUND: The prognostic effect of endoscopic obstruction (eOB) on the survival of stage II colon cancer patients and the role of eOB in guiding postoperative adjuvant chemotherapy of stage II colon cancer are little known. METHODS: In this retrospective, single-center cohort study, patients who had undergone curative surgery and preoperative colonoscope for stage II colon carcinoma were included. The eOB was defined as severe luminal colon obstruction that prevented the standard colonoscope from passing beyond the tumor. The association between eOB and stage II colon cancer survival and the predictive role of eOB for adjuvant chemotherapy were evaluated using multivariate Cox regression analysis. RESULTS: Of 1102 included patients, 616 (55.9%) had eOB and 486 (44.1%) had no eOB. The median follow-up was 49 months (interquartile range, 38-68 months). Kaplan-Meier curves showed that patients with eOB had poor 5-year overall survival (OS; 85.3% vs. 95.3%, p < 0.001) compared to patients without eOB. Five-year disease-free survival (DFS; 78.5% vs. 87.6%, p = 0.004) was also poor in these patients. Multivariate analysis demonstrated eOB was a significant prognostic factor for poor OS (hazard ratio [HR] = 2.531, p < 0.001), but not for DFS (p = 0.081). Even when patients with clinical colonic obstruction were excluded from the population with eOB, the worse OS (HR = 2.262, p = 0.001) was observed. The OS and DFS of eOB patients improved slightly after adjuvant chemotherapy, but there was no statistical significance. CONCLUSIONS: Stage II colon cancer patients with eOB have a poor prognosis. However, whether eOB can guide adjuvant chemotherapy still needs further study.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

CD73 promotes colitis-associated tumorigenesis in mice.

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumorigenesis. A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumor formation were assessed macroscopically. Inflammatory cytokine measurement and RNA sequencing on colon tissues were performed. Inhibition of CD73 by adenosine 5'-(α,ß-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumor number and smaller tumor size compared with the model group. Activation of adenosine receptors using 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-ß-D-ribofuranuronamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced, while activation of adenosine receptors exacerbated, the histological damage of the colon. Increased expression of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6) in colonic tissue was detected in the NECA group. According to RNA sequencing results, potential oncogenes such as arachidonate 15-lipoxygenase (ALOX15), Bcl-2-like protein 15 (Bcl2l15) and N-acetylaspartate synthetase (Nat8l) were downregulated in the APCP group and upregulated in the NECA group compared with the model group. Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l.

Risk factors for recurrence after bowel resection for Crohn's disease.

BACKGROUND: Complications of Crohn's disease such as intestinal obstruction, fistula or perforation often need surgical treatment. Nearly 70%-80% patients with Crohn's disease would receive surgical treatment during the lifetime. However, surgical treatment is incurable for Crohn's disease. The challenge of recurrence postoperatively troubles both doctors and patients. Over 50% patients would suffer recurrence postoperatively. Some certain risk factors are associated with recurrence of Crohn's disease. AIM: To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn's disease. METHODS: Patients diagnosed Crohn's disease and received intestinal resection between April 2007 and December 2013 were included in this study. Data on the general demographic information, preoperative clinical characteristics, surgical information, postoperative clinical characteristics were collected. Continuous data are expressed as median (inter quartile range), and categorical data as frequencies and percentages. Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence, then log-rank test was applied to test the homogeneity of those clinical variables. Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence. RESULTS: A total of 64 patients were included in this study. The median follow-up time for the patients was 17 (9.25-25.75) mo. In this period, 41 patients (64.1%) had endoscopic recurrence or clinical recurrence. Endoscopic recurrence occurred in 34 (59.6%) patients while clinical recurrence occurred in 28 (43.8%) patients, with the interval between the operation and recurrence of 13.0 (8.0-24.5) months and 17.0 (8.0-27.8) mo, respectively. In univariate analysis, diagnosis at younger age (P < 0.001), disease behavior of penetrating (P = 0.044) and preoperative use of anti-tumor necrosis factor (TNF) (P = 0.020) were significantly correlated with endoscopic recurrence, while complication with perianal lesions (P = 0.032) and preoperative use of immunomodulatory (P = 0.031) were significantly correlated with clinical recurrence. As to multivariate analysis, diagnostic age (P = 0.004), disease behavior (P = 0.041) and preoperative use of anti-TNF (P = 0.010) were independent prognostic factors for endoscopic recurrence, while complication with perianal lesions (P = 0.023) was an independent prognostic factor for clinical recurrence. CONCLUSION: Diagnostic age, disease behavior, preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn's disease.

Hypoglycaemic effect of a novel insulin buccal formulation on rabbits.

Transmucosal delivery is a suitable route for insulin non-injection administration. In this study, the hypoglycaemic effect of INSULIN BUCCAL SPRAY (IBS), a formulation with soybean lecithin and propanediol combined as absorption enhancer for insulin on diabetic rabbits and rats, were investigated. The hypoglycaemic rate was calculated and the pharmacodynamics and pharmacokinetics of the formulation in rabbits were studied. The results show that when the diabetic rabbits were administrated with IBS in dosages of 0.5, 1.5 and 4.5Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 5h. The blood glucose decreasing rates are 22.4, 48.1 and 53.5%, respectively. The average bioavailability of IBS by buccal delivery versus subcutaneous injection is 29.2%. Meanwhile, the diabetic rats were administrated with IBS in dosages of 1.0, 3.0 and 9.0Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 4h. The blood glucose decreasing rates are 24.6, 47.5 and 59.6%, respectively. Furthermore, the penetration of fluorescein isothiocyanate (FITC)-labelled insulin through rabbit buccal mucosa was investigated by scanning the distribution of the fluorescent probe in the epithelium using confocal laser scanning microscopy. The results revealed that FITC-insulin can pass through the buccal mucosa promoted by the enhancer and the passage of insulin across the epithelium includes both intracellular and paracellular routes. From the rabbit and rat experimental results showed that IBS is an effective buccal delivery system, which is promising for clinical trial and the future clinical application.