Xiaowen He

A 5-fluorouracil-loaded polydioxanone weft-knitted stent for the treatment of colorectal cancer

In-stents restenosis caused by tumour ingrowth is a major problem for patients undergoing stent displacement because the conventional stents often lack a sustained anti-tumour capability. The aim of this paper was to develop a weft-knitted polydioxanone stent which can slow release 5-fluorouracil (5-FU). In order to determine the most suitable drug concentration, the 5-FU safe concentration in vivo and appropriate loading percentage in the membranes were investigated, and then 5-FU-loaded poly-l-lactide membranes at concentration of 3.2%, 6.4% and 12.8% were coated onto the stent using electro-spinning method, respectively. The morphology, chemical structure and in vitro drug release property of the coating membranes were subsequently examined. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human colorectal cancer cell line HCT-116 and tumour-bearing BALB/c nude mice. The half maximal inhibitory concentration (IC50) and the median lethal dose (LD50) demonstrated that the 6.4% and 12.8% membranes had better anti-tumour effects than pure 5-FU due to the sustainable drug releasing property of the coated membranes on the stent. The membranes possessing appropriate drug loading doses, such as 6.4% or 12.8% also provided better anti-in-stents restenosis effects than other groups tested. Therefore, it is concluded that the drug-loaded stents have great potential for the use in the treatment of intestinal cancers in the future.

Nano-curcumin prepared via supercritical: Improved anti-bacterial, anti-oxidant and anti-cancer efficacy

Curcumin (CM) possesses multiple biological activities. However, poor water solubility and low bioavailability limit its application in biomedical fields. CM nanoparticles (NPs) (230-240nm) were prepared by solution-enhanced dispersion via supercritical CO2 (SEDS) (22-22.5MPa pressure, 31-32.5°C temperature) and its biological functions were evaluated in this study. The Minimum inhibitory concentration of CM NPs against S. aureus (∼250μg/mL) was lower than CM-DMSO (∼500μg/mL). Meanwhile, CM NPs showed effective anti-oxidant ability at a concentration raging from 125 to 2000μg/mL. CM NPs showed time-dependent intracellular internalization ability, resulting in an enhanced anti-cancer effect on colorectal cancer cells (HCT116), and the mechanism could be explained by cell cycle arrest in G2/M phase associated with inducing apoptotic cells. Moreover, CM NPs exhibited reduced cytotoxicity on normal cells (NCM460) compared to CM-DMSO and 5-Fu. In conclusion, CM NPs prepared via SEDS showed potentials in biomedical applications.

Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. METHODS MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. RESULTS MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. CONCLUSION MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.

Biodegradable weft‐knitted intestinal stents: Fabrication and physical changes investigation in vitro degradation

Biodegradable stents can alleviate intestinal obstruction and stenosis in patients. The objective of this study was to develop a biodegradable polydioxanone (PDO) stent using weft-knitting technology and then investigate its biodegradation behaviors in vitro. PDO monofilament with linear density of 100 ± 10 tex was knitted into a tubular stent using a tubular weft-knitting machine. The physical and mechanical properties were evaluated according to the British standard BS EN 13895:2003 and ISO 7198:1998. The biodegradation behaviors of PDO weft-knitted stent in a phosphate buffer solution (pH = 6.8 ± 0.2, 37 ± 0.5 °C) were then investigated. The results showed that the stent maintained more than 60% of its original radial force above 12 weeks. During the 16 weeks of degradation, weight, crystallization, and pH change indicated the degradation medium was diffused into the chain segments of low molecular weight due to the rupture of ester bonds in the monofilament. Fourier transform infrared spectroscopy results demonstrated that the chemical structure of PDO polymer is stable during the in vitro degradation. In conclusion, this biodegradable stent can find valuable applications in treatment of intestinal obstruction and stenosis clinically.

Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn’s Disease

BackgroundMesenchymal stromal cells (MSCs) have been used in the treatment of Crohn’s disease (CD) because of the immunomodulatory ability.AimThe aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD.MethodsMurine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs.ResultsIntraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs.ConclusionsThe therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.

Polydioxanone weft-knitted intestinal stents: fabrication and mechanics optimization:

This paper presents the fabrication of polydioxanone weft-knitted stents and the mechanical properties optimization on process parameters. The stents can be used for treatment of intestinal obstruction and stenosis. Patients diagnosed with different phases require different mechanical stents. So, the mechanical properties of stents, radial force and circumferential strength are important for the safety and efficiency of stents. The aim of this paper was to identify the effect of process parameters on the mechanical properties of stents using the statistical modeling method, then propose optimum parameter settings. The intra-abdominal and intra-intestinal pressures of the human intestine were investigated through an intestine physical model; a full factorial experiment was employed to identify the most suitable factors and find the optimum processing parameters according to the two pressures identified. The results showed that optimum stents with radial force in the range of 1.3–2.5 cN/mm and circumferential strength in the range of 20–50 cN/mm could be obtained at a stitch cam setting ranging from 3.2 to 3.4 mm, with fabric tension in the range of 140–160 cN if the yarn tension and yarn linear density were held at 1.2 cN and 150 tex, respectively. The model validation results showed that stents with different mechanical properties could be tailored through the statistical method and proposed model. In conclusion, such stents, and optimization method, may find broad applications clinically.

Changes of T Cells and Cytokines TGF-β1 and IL-10 in Mice During Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity

BackgroundThe local and systemic regulation of the immune system may play important roles in the process of liver metastasis of colorectal carcinoma. The aim of this study was to establish a reproducible experimental liver metastasis model, to identify changes in T cells and cytokines TGF-β1 and IL-10, and to explore a possible mechanism of liver metastasis of colon carcinoma.MethodsWe used a colon carcinoma liver metastasis model, in which different numbers of CT-26 murine colon carcinoma cells (1 × 103, 5 × 103, 1 × 104, 5 × 104, and 1 × 105) were injected into the spleen. The liver and spleen tissues were examined for T cell markers using flow cytometry. Liver tissues were analyzed for IL-10 and transforming growth factor beta 1 (TGF-β1) expression using immunohistochemistry.ResultsSpleen injection of colon carcinoma cells is a reproducible animal model for liver metastases, which resulted in quantity-dependent metastatic growth. We provided a snapshot of the hepatic immune microenvironment in the mouse liver metastasis model. Injection of A large number of tumor cells (5 × 104 and 1 × 105) decreased anti-tumor cell counts, such as CD4+ and CD8+ T cells, and increased immune-suppressive cell counts (CD4+CD25+ Treg cells). In addition, the expression levels of immunosuppressive cytokines IL-10 and TGF-β1 were also increased with the number of tumor cells.ConclusionsChanges in the systemic and local immunological environment contribute to immunological escape mechanisms during liver metastasis of colon carcinoma, and therapies aiming at immune microenvironment may prove a useful strategy in the treatment of metastatic disease in the future.

Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways

Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with chronic inflammatory processes. Carnosol has been demonstrated to possess anti-inflammatory properties. This study examined the suppressive effect of carnosol on the expression of cell adhesion molecules (CAMs) and chemokines in human umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism. The effect of carnosol on CAM and chemokine expression in HUVECs was identified by western blotting and ELISA, respectively. nuclear factor (NF)-κB activation of HUVECs was analyzed using the TransAM NF-κB Family kit. The effect of carnosol on the tumor necrosis factor (TNF)-α-induced activation of the NF-κB and mitogen-activated protein kinase (MAPK) pathways, and was subsequently analyzed using western blotting. Carnosol not only inhibited TNF-α-induced protein expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, carnosol inhibited the TNF-α-induced phosphorylation of p-65 and IκB-α, as well as the activation of NF-κB. The same result was observed in TNF-α-stimulated phosphorylation of ERK1/2 and p-38. It was demonstrated that carnosol inhibited TNF-α-induced CAM and chemokine expression in HUVECs. The underlying mechanism may be associated with the blocking of the NF-κB and MAPK pathways. These results indicate that carnosol may be a novel therapeutic agent for targeting endothelial cells in IBDs.

Safety and Efficacy of Sodium Hyaluronate Gel and Chitosan in Preventing Postoperative Peristomal Adhesions After Defunctioning Enterostomy: A Prospective Randomized Controlled Trials

AbstractPeristomal adhesions complicate closure of defunctioning enterostomy. The efficacy and safety of sodium hyaluronate gel and chitosan in preventing postoperative adhesion have not been extensively studied. This study aims to evaluate the safety and efficacy of sodium hyaluronate gel and chitosan in the prevention of postoperative peristomal adhesions.This was a prospective randomized controlled study. One hundred and fourteen patients undergoing defunctioning enterostomy were enrolled. Patients were randomly assigned to receive sodium hyaluronate gel (SHG group) or chitosan (CH group) or no antiadhesion treatment (CON group) during defunctioning enterostomy. The safety outcomes included toxicities, stoma-related complications, and short-term and long-term postoperative complications. Eighty-seven (76.3%) of the 114 patients received closure of enterostomy, during which occurrence and severity of intra-abdominal adhesions were visually assessed by a blinded assessor.Incidence of adhesion appears to be lower in patients received sodium hyaluronate gel or chitosan but differences did not reach a significant level (SHG group vs CH group vs CON group: 62.1% vs 62.1% vs 82.8%, P = 0.15). Compared with the CON group, severity of postoperative adhesion was significantly decreased in the SHG and CH group (SHG group vs CH group vs CON group: 31.0% vs 27.6% vs 62.1%; P = 0.01). There was no significant difference in the occurrence of postoperative complications and other safety outcomes among the 3 groups.Sodium hyaluronate gel or chitosan smeared around the limbs of a defunctioning enterostomy was safe and effective in the prevention of postoperative peristomal adhesions.

Male gender is associated with an increased risk of anastomotic leak in rectal cancer patients after total mesorectal excision

Abstract Background The impact of a patient’s gender on the development of anastomotic leak (AL) in rectal cancer patients following total mesorectal excision (TME) remains controversial. The aim of this study was to evaluate the association between patients’ gender and the risk of AL. Methods All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined. Comparisons of the post-operative AL incidence rate between male and female patients were performed. Results Of all patients examined (n = 956), 587 (61.4%) were males and 369 (38.6%) were females. Male patients were more likely to have a history of smoking and drinking alcohol, but less likely to have a history of abdominal surgery compared to female patients. A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study. Of all the patients, 81 (8.5%) developed post-operative AL. More male patients (n = 62, 10.6%) suffered from AL than females (n = 19, 5.1%) (P = 0.003). Multivariate logistic regression analyses confirmed the association between male gender and AL [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.37–4.23, P = 0.002]. Similar results were also obtained in patients who underwent laparoscopic TME (OR: 2.11, 95% CI: 1.15–3.89, P = 0.016). Conclusions Male patents were found to have an increased risk for AL following TME with a primary anastomosis. A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.