A novel electrospun polylactic acid silkworm fibroin mesh for abdominal wall hernia repair.

Objective: Abdominal wall hernias are common abdominal diseases, and effective hernia repair is challenging. In clinical practice, synthetic meshes are widely applied for repairing abdominal wall hernias. However, postoperative complications, such as inflammation and adhesion, are prevalent. Although biological meshes can solve this problem to a certain extent, they face the problems of heterogeneity, rapid degradation rate, ordinary mechanical properties, and high-cost. Here, a novel electrospinning mesh composed of polylactic acid and silk fibroin (PLA-SF) for repairing abdominal wall hernias was manufactured with good physical properties, biocompatibility and low production cost. Materials and methods: FTIR and EDS were used to demonstrate that the PLA-SF mesh was successfully synthesized. The physicochemical properties of PLA-SF were detected by swelling experiments and in vitro degradation experiments. The water contact angle reflected the hydrophilicity, and the stress‒strain curve reflected the mechanical properties. A rat abdominal wall hernia model was established to observe degradation, adhesion, and inflammation in vivo. In vitro cell mesh culture experiments were used to detect cytocompatibility and search for affected biochemical pathways. Results: The PLA-SF mesh was successfully synthesized and did not swell or degrade over time in vitro. It had a high hydrophilicity and strength. The PLA-SF mesh significantly reduced abdominal inflammation and inhibited adhesion formation in rat models. The in vitro degradation rate of the PLA-SF mesh was slower than that of tissue remodeling. Coculture experiments suggested that the PLA-SF mesh reduced the expression of inflammatory factors secreted by fibroblasts and promoted fibroblast proliferation through the TGF-ß1/Smad pathway. Conclusion: The PLA-SF mesh had excellent physicochemical properties and biocompatibility, promoted hernia repair of the rat abdominal wall, and reduced postoperative inflammation and adhesion. It is a promising mesh and has potential for clinical application.

Visual Observation of Abdominal Adhesion Progression Based on an Optimized Mouse Model of Postoperative Abdominal Adhesions.

Background: There is no clear description of the evolution of the progression of abdominal adhesions over time.Method: The optimized model was selected using different adhesion scoring systems. Then, this model was used to observe the progression of abdominal adhesions. Visualized observation of abdominal adhesion evolution was performed by laparoscopy and computed tomography. The inflammatory cell infiltration and collagen fibers in adhesion tissues at different times were evaluated by hematoxylin-eosin and picrosirius red staining. RNA sequencing was used to predict potential key targets of abdominal adhesions at different times.Results: The abdominal adhesion model showed the highest reproducibility when it was established using a circular tool and an electric brush. Based on this model, we found that the inflammatory response was activated early in the process of adhesion formation, peaking on day 3 and then gradually decreasing until stabilization on day 7. Collagen and fibronectin formed on day 1 and gradually increased until remaining stable on day 7. In addition, the characteristic changes in the adhesion zone from initial congestion, edema and fragile tissue to later dense and stable tissue could be vividly observed in live mice by laparoscopy and artificial pneumoperitoneum CT. The RNA sequencing results revealed that Hck on day 1, Ndufs3 and Ndufs8 on day 3 and Aif1 on day 7 might play key roles in abdominal adhesion formation.Conclusion: The construction of a standard process for describing the evolution of abdominal adhesions based on an optimized mouse model will help to facilitate subsequent adhesion-related studies.

Activating SIRT3 in peritoneal mesothelial cells alleviates postsurgical peritoneal adhesion formation by decreasing oxidative stress and inhibiting the NLRP3 inflammasome.

Peritoneal adhesions (PAs) are a serious complication of abdominal surgery and negatively affect the quality of life of millions of people worldwide. However, a clear molecular mechanism and a standard therapeutic strategy for PAs have not been established. Here, we developed a standardized method to mimic the pathological changes in PAs and found that sirtuin 3 (SIRT3) expression was severely decreased in adhesion tissues, which was consistent with our bioinformatics analysis and patient adhesion tissue analysis. Thus, we hypothesized that activating SIRT3 could alleviate postsurgical PAs. Sirt3-deficient (Sirt3-/-) mice exhibited many more PAs after standardized abdominal surgery. Furthermore, compared with wild-type (Sirt3+/+) mice, Sirt3-deficient (Sirt3-/-) mice showed more prominent reactive oxygen species (ROS) accumulation, increased levels of inflammatory factors, and exacerbated mitochondrial damage and fragmentation. In addition, we observed NLRP3 inflammasome activation in the adhesion tissues of Sirt3-/- but, not Sirt3+/+ mice. Furthermore, mesothelial cells sorted from Sirt3-/- mice exhibited impaired mitochondrial bioenergetics and redox homeostasis. Honokiol (HKL), a natural compound found in several species of the genus Magnolia, could activate SIRT3 in vitro. Then, we demonstrated that treatment with HKL could reduce oxidative stress and the levels of inflammatory factors and suppress NLRP3 activation in vivo, reducing the occurrence of postsurgical PAs. In vitro treatment with HKL also restored mitochondrial bioenergetics and promoted mesothelial cell viability under oxidative stress conditions. Taken together, our findings show that the rescue of SIRT3 by HKL may be a new therapeutic strategy to alleviate and block postsurgical PA formation.

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation.

BACKGROUND: Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model. MATERIALS AND METHODS: A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum. RESULTS: Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics (P < 0.05). CONCLUSION: NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.

A combination of hybrid polydopamine-human keratinocyte growth factor nanoparticles and sodium hyaluronate for the efficient prevention of postoperative abdominal adhesion formation.

Postoperative abdominal adhesion (PAA) is one of the more universal complications of abdominal surgery with a frequent incidence. Currently available keratinocyte growth factor (KGF)-based glues for the prevention of adhesions remain a great bottleneck since their long-term biological activity in vivo is insufficient. In this study, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs) by using an in situ self-assembly and polymerization method. The physicochemical properties of the PDA-KGF nanoparticles were systematically characterized. The effect of preventing PAA in rats was evaluated by using hybrid PDA-KGF NPs combined with hyaluronate (Ha). The expression levels of inflammatory factors and the degree of inflammatory cell infiltration in the injured peritoneum were evaluated by enzyme-linked immunosorbent assays and hematoxylin-eosin staining, respectively. The levels of phospho-Src expression were revealed by Western blotting. The degree of fibrosis and the density of deposited collagen fibers were measured with real-time reverse-transcription polymerase chain reaction and picrosirius red staining. The results indicated that the PDA-KGF NPs combined with Ha greatly prevented the incidence of abdominal adhesion s and promoted the repair of mesothelial cells in injured peritoneum. More importantly, the PDA-KGF NPs combined with Ha obviously reduced collagen deposition and fibrosis and inhibited the inflammatory response. Our results suggest that PDA-KGF NPs combined with Ha are promising barrier-like biomaterials for the effective prevention of postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesion (PAA) as an inevitable postoperative complication affected the quality of life of patients. Currently available methods for preventing adhesions mainly employ degradable biomaterials. Previous research demonstrated that a hybrid keratinocyte growth factor (KGF)-sodium hyaluronate (Ha) gel could prevent the formation of PAAs. However, its clinical outcomes are not satisfactory since their bioactivity in vivo is too short. In this article, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs), which extend KGF bioactivity, effectively prevent PAA. Moreover, PDA-KGF NPs could remarkably reduce both collagen deposition and fibrosis, inhibit the inflammatory response, and promote mesothelial regeneration. Overall, the PDA-KGF NPs combined with Ha exhibit efficient antiadhesion properties, may provide a promising clinical protocol for the prevention of PAA.

TMIGD1 Inhibited Abdominal Adhesion Formation by Alleviating Oxidative Stress in the Mitochondria of Peritoneal Mesothelial Cells.

BACKGROUND: Postoperative abdominal adhesion remains one of the frequent complications after abdominal surgery and lacks effective intervention. Peritoneal mesothelial cell injury and healing play crucial roles in the process of adhesion formation, and identifying this mechanism might provide new insight into possible new therapeutic strategies for this disease. Transmembrane and immunoglobulin domain-containing 1 (TMIGD1) has been proven to protect renal epithelial cells from injury induced by oxidative stress and has also been identified as a novel adhesion molecule. Here, we investigated the role of TMIGD1 and its possible mechanism in adhesion formation. MATERIALS AND METHODS: Immunohistochemistry (IHC), qPCR, and immunofluorescence (IHF) were used to detect the expression of TMIGD1. The grade and tenacity score of adhesion were used to evaluate the adhesion formation conditions. A TMIGD1-overexpressing HMrSV5 cell line was established. MTT assay, Western blotting, Annexin V apoptosis analysis, and CK19 staining were used to measure mesothelial cell viability, apoptosis, and completeness. ROS and MDA detection were used to measure mesothelial cell oxidative stress levels. JC-1 staining, IHF, and transmission electron microscopy were performed to assess mitochondrial function. Scratch-wound and adhesion assays were used to evaluate the adhesion ability of mesothelial cells. RESULTS: First, we showed that TMIGD1 was decreased in mouse abdominal adhesion tissue and peritoneal mesothelial cells. Second, TMIGD1 overexpression inhibited adhesion formation. Third, TMIGD1 overexpression protected mesothelial cells from hydrogen peroxide- (H2O2-) induced oxidative stress injury. Fourth, TMIGD1 overexpression alleviated oxidative stress by protecting the mitochondrial function of mesothelial cells. In addition, TMIGD1 overexpression enhanced mesothelial cell adhesion. CONCLUSION: Our findings suggest that TMIGD1 protects mesothelial cells from oxidative stress injury by protecting their mitochondrial function, which is decreased in regular abdominal adhesion tissue. In addition, TMIGD1 enhances peritoneal mesothelial cell adhesion to promote healing.

Novel technique to manage refractory chylous ascites with carbon nanoparticle suspension in infants.

OBJECTIVE: Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. In infants, CA is mostly caused by lymphatic malformation or unknown reasons. The creation of a shunt for the lymphorrhea is the last option for patients unresponsive to all other conservative treatments. Localization of the leakage is a critical problem during surgery. We applied a carbon nanoparticle suspension (CNS) in CA patients to locate the external lymphatic leakage and evaluated its utility during surgery. PATIENTS AND METHODS: Twelve infants with CA were treated in our center recently. Ten patients received laparotomy, one refused therapy, and one was cured after undergoing conservative treatment. Recently, two infants with CA received CNS in the visceral peritoneum during laparotomy. The results of the traditional procedure were compared to our innovative technique for CA to evaluate the use of CNS in treating CA. RESULTS: The features of the baseline data did not differ substantially. Location of the leakage with CNS was employed in 2 of the 10 patients whose lymphatic leakages were identified with the resolution of the refractory CA. Overall, in 5 patients, ascites was resolved successfully. The refractory CA was resolved more effectively in patients in whom the leakage site was identified with CNS than in patients in whom the leakage site could not be identified under conventional surgery. CONCLUSIONS: Injecting CNS improved the accuracy of lymphorrhagia leakage site identification and the outcomes of infants who underwent surgical treatment for refractory CA. LEVEL OF EVIDENCE: II-III.

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

BACKGROUND: Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model. MATERIALS AND METHODS: Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress. RESULTS: The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-ß1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs. CONCLUSION: DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2.

BACKGROUND Hepatocellular carcinoma (HCC) is a commonly occurring liver malignancy. Its prognosis remains unsatisfactory. Accumulating evidence has revealed that exosomal microRNAs (miRNAs) act as biomarkers and play crucial roles in the advancement of HCC. The current study explored the biological role and fundamental mechanism of exosomal miR-744 in HCC. MATERIAL AND METHODS The serum exosomes of HCC patients were isolated by differential ultracentrifugation. MiR-744 expression in HCC tissues, cell lines and serum exosomes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU (5-ethynyl-2'-deoxyuridine) assay and Cell Counting Kit-8 (CCK-8) assay were conducted to show the impacts of miR-744 or exosomal miR-744 on proliferation and sorafenib resistance in HepG2 cells. The target of miR-744 was ascertained by regulating the level of miR-744 in HepG2 cells. RESULTS MiR-744 is downregulated in HCC tissues and cell lines as well as in exosomes derived from patient serum and HepG2 cells. Additionally, downregulated miR-744 promotes HepG2 cell proliferation and inhibits the chemosensitivity of HepG2 cells to sorafenib. PAX2 was identified as the functional target of miR-744. Interestingly, miR-744 is decreased in exosomes derived from sorafenib-resistant HepG2 cells. Furthermore, when treated with the miR-744-enriched exosomes, the proliferation of HepG2 cells was significantly suppressed, and the sorafenib resistance was reduced. CONCLUSIONS MiR-744 has an imperative role in the propagation and chemoresistance of HCC. Serum exosomal miR-744 might act as a biomarker of HCC, and exosomal miR-744 might offer an innovative strategy for HCC treatment.

miR-148a inhibits cell proliferation and migration through targeting ErbB3 in colorectal cancer.

Colorectal cancer is a common gastrointestinal cancer ranking in third place of all cancers. Downregulation of miR-148a has been observed in many tumors, and miR-148a was found to be an oncogene in colorectal cancer. The aim of our study was to investigate the molecular mechanisms by which miR-148a and ErbB3 proliferate and migrate in colorectal cancer. The expression of miR-148a and ErbB3 were measured by western blot analysis and RT-qPCR. MTT and transwell assays were performed to analyze the proliferative and migratory abilities. The dual luciferase reporter assay was employed to confirm miR-148a regulated the expression of ErbB3 in colorectal cancer. It was discovered that miR-148a was overexpressed while ErbB3 expression was low in colorectal cancer, and the mRNA level of miR-148a had a negative correlation with the expression of ErbB3. Upregulation of miR-148a suppressed the proliferation and migration in colorectal cancer cells. Furthermore, ErbB3 was identified as a direct target of miR-148a, which suppressed the proliferation and migration through directly binding to the 3'UTR of ErbB3 mRNA. This study established that miR-148a inhibited the proliferative and migratory abilities through mediating the expression of ErbB3. The newly identified miR-148a/ErbB3 axis provides novel insight into the pathogenesis of colorectal cancer, and represents a potential target for treatment of colorectal cancer.

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

Upregulation of microRNA­300 induces the proliferation of liver cancer by downregulating transcription factor FOXO1.

In the present study, we investigated whether miRNA­300 (miR­300) is an oncogene in human liver cancer and sought to determine the mechanism underlying its activity. We also investigated the effect of miRNA­300 on the growth in liver cancer. To identify its target molecule, we performed luciferase assays. The downstream signaling pathway was detected by immunohistochemical (IHC) analysis in human HCC tissues, and the protein levels of AKT, 4E­BP1, S6K1, SNAIL and MMP2 were determined using western blotting. miR­300 levels were higher in patients with high­stage HCC, and miR­300 promoted cell growth both in vitro and in vivo. miRNA­300 inhibited the luciferase activity of FOXO1 by targeting its 3'­untranslated region (UTR), and overexpression of miR­300 upregulated the protein levels of phospho­AKT, phospho­4E­BP1, phospho­S6K1, SNAIL and MMP2. These data revealed that miRNA­300 functions as an oncogene in liver cancer by inhibiting FOXO1 and interacting with the AKT/mTOR signaling pathway.

MicroRNA­181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A.

MicroRNA (miR)­181a is a member of the miR­181 family that serves a key role in the pathogenesis of various cancer types. The present study aimed to investigate the interaction between miR­181a and Ras association domain family protein1 isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction between miR­181a and RASSF1A was assessed in cell lines and cancer tissues. The direct binding of miR­181a and RASSF1A was identified using a luciferase reporting gene system. The effects of miR­181a and RASSF1A on gastric cancer cell growth, cell cycle and apoptosis were assessed with a Cell Counting Kit­8 assay and flow cytometry. The effects of miR­181a on cell division cycle 25A (CDC25A), cyclin A2, cyclin D1, p21, Bcl­2­associated X protein (Bax) and B­cell lymphoma­2 (Bcl­2) protein levels were assessed in gastric cancer cell lines. miR­181a directly interacted with the 3'­untranslated region of RASSF1A and downregulated RASSF1A protein expression. In tissues from patients with gastric cancer, the miR­181a level was significantly higher in the tumor tissues and was negatively correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell proliferation and G1/S transition, and promoted apoptosis; whereas miR­181a promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis. RASSF1A knockdown attenuated the effects of miR­181a downregulation on cell proliferation and apoptosis. Furthermore, miR­181a upregulated CDC25A, cyclin A2 and Bcl­2, and downregulated Bax protein expression in gastric cancer cell lines. These data indicate that miR­181a promotes gastric carcinogenesis, possibly through a direct interaction with RASSF1A.

Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/ß-Catenin Signaling in Human Hepatocellular Carcinoma.

BACKGROUND: MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. RESULTS: In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/ß-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear ß-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. CONCLUSION: Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

Paeoniflorin prevents postoperative peritoneal adhesion formation in an experimental rat model.

Although materials and modern surgical techniques have been developed to suppress postoperative adhesions, adhesion formation can still occur, and thus, a novel effective anti-adhesion drug is greatly needed. In the present study, we explored the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions and examined the anti-oxidative stress and anti-inflammatory properties of PE. Forty-eight male Sprague-Dawley rats were randomly divided into 6 groups for the study: the sham, control, hyaluronan and three concentrations (10, 20 and 40 mg/kg/d) paeoniflorin groups. Abdominal adhesions were created by abrasion of the caecum and its opposite abdominal wall. In the paeoniflorin groups, the rats were administered daily oral doses of paeoniflorin for 7 days. The abdominal cavities of the rats were reopened with a U-shaped incision to macroscopically grade the adhesions. Histologic analysis was performed, and oxidative stress, inflammatory cytokine, collagen fiber degradation and cytokeratin levels were measured. Macroscopic and histopathological measurements revealed that paeoniflorin reduced peritoneal adhesion and inflammation. Notably, treatment with paeoniflorin reduced the protein levels of TGF-ß1, IL-6 and COX-2. The collagen fiber fractions were distinctly lower in the PE groups than in the control group. Western blotting analyses showed that paeoniflorin increased MMP-9 and superoxide dismutase-2 protein expression and sharply reduced α-SMA and COX-2 protein expression. Peritoneal mesothelium cells were more continuous and complete in animals treated with paeoniflorin. Our study suggests that paeoniflorin can be used to ameliorate peritoneal adhesions via anti-oxidative stress and anti-inflammatory actions during the postoperative period.

Ginkgolic acid inhibits the invasiveness of colon cancer cells through AMPK activation.

Tumor cell invasion and metastasis are important processes in colorectal cancer that exert negative effects on patient outcomes; consequently, a prominent topic in the field of colorectal cancer study is the identification of safe and affordable anticancer drugs against cell invasion and metastasis, with limited side effects. Ginkgolic acid is a phenolic acid extracted from ginkgo fruit, ginkgo exotesta and ginkgo leaves. Previous studies have indicated that ginkgolic acid inhibits tumor growth and invasion in a number of types of cancer; however, limited studies have considered the effects of ginkgolic acid on colon cancer. In the present study, SW480 colon cancer cells were treated with a range of concentrations of ginkgolic acid; tetrazolium dye-based MTT, wound-scratch and transwell migration assays were performed to investigate the effects on the proliferation, migration and invasion of colon cancer cells, and potential mechanisms for the effects were explored. The results indicated that ginkgolic acid reduced the proliferation and significantly inhibited the migration and invasion of SW480 cells in a concentration-dependent manner. Additional experiments indicated that ginkgolic acid significantly decreased the expression of invasion-associated proteins, including matrix metalloproteinase (MMP)-2, MMP-9, urinary-type plasminogen activator and C-X-C chemokine receptor type 4, and activated adenosine monophosphate activated protein kinase (AMPK) in SW480 cells. Small interfering RNA silencing of AMPK expression reversed the effect of ginkgolic acid on the expression of invasion-associated proteins. This result suggested that ginkgolic acid inhibited the proliferation, migration and invasion of SW480 colon cancer cells by inducing AMPK activation and inhibiting the expression of invasion-associated proteins.

Effect of Emodin on Preventing Postoperative Intra-Abdominal Adhesion Formation.

BACKGROUND: Postoperative intra-abdominal adhesions are a major complication after abdominal surgery. Although various methods have been used to prevent and treat adhesions, the effects have not been satisfactory. Emodin, a naturally occurring anthraquinone derivative and an active ingredient in traditional Chinese herbs, exhibits a variety of pharmacological effects. In our study, we demonstrated the effect of emodin treatment on preventing postoperative adhesion formation. MATERIALS AND METHODS: A total of 48 rats were divided into six groups. Abdominal adhesions were created by abrasion of the cecum and its opposite abdominal wall. In the experimental groups, the rats were administered daily oral doses of emodin. On the seventh day after operation, the rats were euthanized, and blood and pathological specimens were collected. Abdominal adhesion formation was evaluated by necropsy, pathology, immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay analyses. RESULTS: Abdominal adhesions were markedly reduced by emodin treatment. Compared with the control group, collagen deposition was reduced and the peritoneal mesothelial completeness rate was higher in the emodin-treated groups. Emodin had anti-inflammatory effects, reduced oxidative stress, and promoted the movement of the intestinal tract (P < 0.05). CONCLUSION: Emodin significantly reduced intra-abdominal adhesion formation in a rat model.

Comparative study of short- and long-term outcomes of laparoscopic-assisted versus open rectal cancer resection during and after the learning curve period.

Laparoscopic-assisted rectal resection (LAR) has been widely used to treat rectal cancer. However, it has a steep learning curve. In this study, we aimed to investigate the effects of the learning curve on the outcomes of LAR. All consecutive patients with rectal cancer undergoing LAR or open resection (OR) between 2010 and 2015 were included in this retrospective analysis. The learning curve was determined, and patients were divided into 2 phases: the learning curve and the expert period. The short-term perioperative data in the 2 phases and the long-term survival in the learning phase were compared between the LAR and OR groups. A total of 491 patients were included in this study. Inflection of the learning curve based on the operation time of LAR was at the 40th case. A total of 233 patients underwent surgery (112 LAR and 121 OR) during the learning period. In this period, LAR had a longer operation time, less blood loss, and a higher total cost (all P < .05). The 3-year overall survival rates between the LAR and OR groups were similar (69.74% vs 75%; P = .32). A total of 258 patients underwent surgery (169 LAR and 89 OR) during the expert period. Significant differences in total cost, estimated blood loss, postoperative hospital stay, and recovery of bladder and bowel functions were identified in this period (all P < .05). LAR during the learning period has fewer benefits in terms of postoperative recovery than OR. However, the long-term outcomes are equivalent.

Resveratrol inhibits hepatocellular carcinoma progression driven by hepatic stellate cells by targeting Gli-1.

Hepatocellular carcinoma (HCC) is characterized by hypervascularity. Hepatic stellate cells (HSCs) play very important roles in HCC malignant progression, as these cells facilitate HCC tumorigenesis and metastasis. We demonstrated that HSCs induce angiogenesis in HCC by upregulating the expression of Gli-1, which stimulates reactive oxygen species (ROS) production and potentiates increases in HCC cell invasiveness. Resveratrol abolished HSC-induced angiogenesis and suppressed ROS production and IL-6 and CXCR4 receptor expression in HepG2 cells by down-regulating Gli-1 expression. These findings indicate that Gli-1 may be a target for the prevention of angiogenesis in HCC and that resveratrol may have beneficial effects with respect to preventing HCC progression.