Shengchun Dang

Shape-controlled synthesis of F-substituted hydroxyapatite microcrystals in the presence of Na2EDTA and citric acid.

We present a facile strategy for the shape-controlled synthesis of F-substituted hydroxyapatite (FHAp) microcrystals based upon using a combination of Na(2)EDTA and citric acid (CA). Novel, well-defined FHAp microcrystals of various shapes, such as hexagonal disks with predominant (0 0 0 1) faces, hexagonal shuttles, hexagonal prisms, icosahedrons, and hexagonal microrods with tunable aspect ratios, were fabricated. In particular, FHAp hollow microcrystals with tunable shapes were fabricated directly without using any additional template. The central features of our approach are the use of both Na(2)EDTA and CA as two distinct chelating reagents and the use of substitution ions (F(-)) itself as a growth inhibitor for the FHAp crystals. F(-) ions were found to play a critical role in the formation of hexagonally shaped FHAp microcrystals, and in the one-pot formation of hollow microcrystals, which relies on the addition order of F(-) ions in the synthesis.

Application of liposomes in drug development — focus on gastroenterological targets

Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer.

FOXC2 is up-regulated in pancreatic ductal adenocarcinoma and promotes the growth and migration of cancer cells

The transcriptional factor Forkhead box protein C2 (FOXC2) was recently demonstrated to be up-regulated in various cancer types. However, its expression profile and the biological functions in pancreatic cancer remain unknown. In this study, we examined the expression pattern of FOXC2 in pancreatic ductal adenocarcinoma (PDAC) tissues and investigated the functions of FOXC2 in the progression of PDAC. It was found that the expression of FOXC2 was up-regulated in PDAC samples. Forced expression of FOXC2 promoted the growth and migration of the PDAC cells, while knocking down the expression of FOXC2 inhibited the growth and migration of the PDAC cells. Moreover, FOXC2 was found to interact with beta-catenin and promote cell growth by activating beta-catenin/TCF signaling. Taken together, this study demonstrated the oncogenic roles of FOXC2 in PDAC, and FOXC2 might be a therapeutic target for PDAC.

Clodronate-containing Liposomes Attenuate Lung Injury in Rats with Severe Acute Pancreatitis

ObjectivesSevere acute pancreatitis (SAP) can lead to acute lung injury (ALI). The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI in rats with SAP.MethodsThe thin film method was used to prepare liposomes. Sprague-Dawley rats were randomly divided into three groups. After the SAP model was established by injecting 5% (w/v) sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreata, normal saline was administered to the control (C) group, phosphate buffer solution (PBS)-containing liposome to the P group, and clodronate-containing liposome to the T group through tail veins. Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Morphological changes in the pancreata and lung were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). In addition, the macrophage marker cluster of differentiation 68 (CD68) in lung tissue was detected with immunohistochemistry.ResultsBlood levels of amylase, IL-6, and TNF-α were significantly increased in the P group compared to those in the T group (P<0.05). In the T group, large numbers of TUNEL-positive cells were observed, but no or few in the C and P groups. Gross inspection and H&E staining of pancreata and lung showed dramatic tissue damage, including inflammation and necrosis in the P group. Less remarkable changes were noted in the T group, and the C group exhibited normal histology. The histological scores according to Kaiser’s criteria were consistent with H&E findings. The number of CD68-positive macrophages decreased in the T group.ConclusionsClodronate-containing liposomes have a protective effect against ALI in rats with SAP. Blockade of macrophages may represent a novel therapeutic strategy in SAP.

CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma.

Overactivation of Ras signaling is very common in the hepatocellular carcinoma (HCC) due to its constitutive active mutation, which makes it a big challenge to target Ras signaling. Therefore, identifying effectors downstream of Ras signaling would benefit the development of novel therapeutic strategies. In this study, it was found that the expression of CARF (collaborate of ARF) was induced by oncogenic RasV12. The expression of CARF was up-regulated in both HCC mouse model (Alb-Cre; P53f/f; Loxp-Stop-Loxp-RasG12D) and human HCC clinical samples. Overexpression of CARF promoted the growth and migration of HCC cells, while knocking down the expression of CARF inhibited the growth and migration of HCC cells. In the mechanism study, CARF was found to interact with beta-catenin, impaired the interaction between beta-catenin and ICAT, and activated beta-catenin/TCF signaling. Moreover, knocking down the expression of CARF inhibited the tumorigenesis in the HCC mouse model. Taken together, this study revealed the oncogenic functions of CARF in the tumorigenesis of HCC by activating beta-catenin/TCF signaling, and suggested CARF might be a therapeutic target in the treatment of HCC.

Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis *

Background and objective: It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis. Methods: Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry. Results: The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01). Conclusions: Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.

Comparison between uncut Roux-en-Y and Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: A meta-analysis

AIM To compare uncut Roux-en-Y (U-RY) gastrojejunostomy with Roux-en-Y (RY) gastrojejunostomy after distal gastrectomy (DG) for gastric cancer. METHODS A literature search was conducted in Pubmed, Embase, Web of Science, Cochrane Library, Science Direct, Chinese National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database to identify studies comparing U-RY with RY after DG for gastric cancer until the end of December 2017. Pooled odds ratio or weighted mean difference with 95% confidence interval was calculated using either fixed- or random-effects models. Perioperative outcomes such as operative time, intraoperative blood loss, and hospital stay; postoperative complications such as anastomotic bleeding, stricture and ulcer, reflux gastritis/esophagitis, delayed gastric emptying, and Roux stasis syndrome; and postoperative nutritional status (serum hemoglobin, total protein, and albumin levels) were the main outcomes assessed. Meta-analyses were performed using RevMan 5.3 software. RESULTS Two randomized controlled trials and four nonrandomized observational clinical studies involving 403 and 488 patients, respectively, were included. The results of the meta-analysis showed that operative time [weighted mean difference (WMD): -12.95; 95%CI: -22.29 to -3.61; P = 0.007] and incidence of reflux gastritis/esophagitis (OR: 0.40; 95%CI: 0.20-0.80; P = 0.009), delayed gastric emptying (OR: 0.29; 95%CI: 0.14-0.61; P = 0.001), and Roux stasis syndrome (OR: 0.14; 95%CI: 0.04-0.50; P = 0.002) were reduced; and the level of serum albumin (WMD: 0.71; 95%CI: 0.24-1.19; P = 0.003) was increased in patients undergoing U-RY reconstruction compared with those undergoing RY reconstruction. No differences were found with respect to intraoperative blood loss, hospital stay, anastomotic bleeding, anastomotic stricture, anastomotic ulcer, the levels of serum hemoglobin, and serum total protein. CONCLUSION U-RY reconstruction has some clinical advantages over RY reconstruction after DG.

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

Netrin‑1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types of cancer; however, its role in the growth of gastric cancer (GC) cells has not been described in detail. In the present study, the data suggested that NTN1 knockdown significantly decreased the proliferation of GC cells, whereas NTN1 overexpression had an opposing effect. Furthermore, the use of focal adhesion kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK), but did not induce the phosphorylation of P38. In addition, the expression of ERK and JNK was markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the expression of NTN1 in samples collected from nude mice was downregulated in the NTN1 knockdown group and upregulated in the NTN1 overexpression group compared with the control short hairpin RNA group. These results suggest that NTN1‑induced GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via the distinct activation of FAK.

Liposomes and Nanotechnology in Drug Development: Focus On Pancreatic Cancer

Pancreatic cancer usually has high morbidity and mortality and rests one of the most challenging cancers to treat. 5 years survival rate is less than 6 percent overall for people with pancreatic cancer, because of very late diagnosis and absence of effective treatment. In a western world, pancreatic tumor is the fourth most common cause of death in a western world. The pancreatic tumor needs selective delivery of drugs to target cells, with no side effects is major goals of the recent investigations for the real treatment of the pancreatic tumor. Medication which targets pancreatic tumor cells specially and carriers which deliver medications to specific cells which are quickly dividing, development of these kind drugs is considered as magic for the management of pancreatic cancer. In latest years, liposomes and nanotechnology can show a vital character in the treatment of pancreatic tumor. Liposomes contain multiple characteristics, such as the ability to protect the material from degradation, the capacity for encapsulating many materials and capability for delivering materials intracellularly fusion with plasma membrane. Nanoparticles as a carrier offer a new style of delivery of the medications to target cells of a tumor and allow drugs for the binding to tumor cell membrane, to cytoplasmic and to nuclear receptor sites. It delivers high medication concentrations to specific cells with few side effects to other normal tissues. The general importance of this evaluation is to increase overall understanding of development of the therapeutic nanomedicine for the treatment of pancreatic tumors, agents delivered by nanoliposomes, liposomal nanomedicine in targeting cancer and safety issues.