Dejun Fan

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.

Preoperative Percutaneous Drainage of Spontaneous Intra-Abdominal Abscess in Patients With Crohn's Disease: A Meta-Analysis.

Goals: We aimed to compare clinical outcomes between percutaneous drainage (PD) with or without further elective surgery and initial surgery for patients with Crohn’s disease (CD)-related spontaneous intra-abdominal abscess. Background: Intra-abdominal abscess is common in patients with CD leading to significant morbidity. The role of PD before abdominal surgery in patients with CD remains controversial. Study: We performed a meta-analysis comparing PD and surgery as the initial approach to CD-related spontaneous intra-abdominal abscess. Overall complication and recurrent abscess were assessed. Subgroup analyses on initial PD were performed including preoperative PD and PD alone. Results: A total of 9 studies including 513 patients with CD-related spontaneous intra-abdominal abscesses were included. The overall complication rate was significantly higher in patients undergoing initial surgery compared with those undergoing initial PD [odds ratio (OR)=0.58; 95% confidence interval (CI), 0.35-0.96; P=0.03]. In a subgroup analysis, preoperative PD was associated with a significant reduction in overall complication (OR=0.44; 95% CI, 0.23-0.83; P=0.01) as compared with initial surgery. The risk for recurrent abscess was higher in patients who underwent PD alone than those who underwent initial surgery (OR=2.16; 95% CI, 1.03-4.54; P=0.04). No significance difference in postoperative recurrent abscess was found between preoperative PD group and initial surgery group. Conclusion: Although abdominal surgery appeared to be inevitable in the majority of the patients with CD who develop intra-abdominal abscess, preoperative PD may decrease overall complication after surgery.

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.

MicroRNA 26b promotes colorectal cancer metastasis by downregulating phosphatase and tensin homolog and wingless-type MMTV integration site family member 5A

Invasion and metastasis are crucially important factors in the survival of malignant tumors. Epithelial‐mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Herein we report that ectopic overexpression of microRNA 26b (miR‐26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell‐like phenotypes in vitro. Furthermore, miR‐26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless‐type MMTV integration site family member 5A (WNT5A). Notably, miR‐26b is markedly upregulated in tumor samples from patients with lymphatic metastases. These results indicate that miR‐26b promotes CRC metastasis by downregulating PTEN and WNT5A, and may represent a therapeutic target for metastatic CRC.

Activation of KLF4 expression by small activating RNA promotes migration and invasion in colorectal epithelial cells: KLF4 promotes cell migration and invasion

RNA activation mediated by small double‐stranded RNAs targeting promoter sequence named small activating RNAs (saRNAs) is one of the mechanisms for gene activation. Artificial regulation of gene expression through RNA activation does not affect the alteration of the genomic DNA sequences or exogenous plasmid DNA, therefore it is a relative manageable approach for gene perturbation. KLF4 is a member of zinc‐finger transcription factors and its functions in colorectal cells are still controversial. In order to elucidate the functions of KLF4, we synthesized saRNAs that target the promoter regions of KLF4 and transfected into varied colorectal epithelial cell lines. We found the KLF4 gene expression is specifically increased in the human normal epithelial cell NCM460 and colorectal epithelial cancer cell Caco‐2 and HCT116, but not in other human colorectal epithelial cell lines. In addition, we observed that saRNAs induced overexpression of KLF4 could promote cell migration/invasion in NCM460 and HCT116 cell lines. This effect is mediated partly by inducing EMT and facilitating nuclear translocation of β‐catenin.

Supercritical carbon dioxide-developed silk fibroin nanoplatform for smart colon cancer therapy

Purpose To deliver insoluble natural compounds into colon cancer cells in a controlled fashion. Materials and methods Curcumin (CM)–silk fibroin (SF) nanoparticles (NPs) were prepared by solution-enhanced dispersion by supercritical CO2 (SEDS) (20 MPa pressure, 1:2 CM:SF ratio, 1% concentration), and their physicochemical properties, intracellular uptake efficiency, in vitro anticancer effect, toxicity, and mechanisms were evaluated and analyzed. Results CM-SF NPs (<100 nm) with controllable particle size were prepared by SEDS. CM-SF NPs had a time-dependent intracellular uptake ability, which led to an improved inhibition effect on colon cancer cells. Interestingly, the anticancer effect of CM-SF NPs was improved, while the side effect on normal human colon mucosal epithelial cells was reduced by a concentration of ~10 μg/mL. The anticancer mechanism involves cell-cycle arrest in the G0/G1 and G2/M phases in association with inducing apoptotic cells. Conclusion The natural compound-loaded SF nanoplatform prepared by SEDS indicates promising colon cancer-therapy potential.