miR-574-3p inhibits proliferation and invasion in esophageal cancer by targeting FAM3C and MAPK1.

Esophageal cancer is considered as one of the leading malignancies. MicroRNA-574-3p (miR-574-3p) was used as a postoperative prognostic indicator in patients with esophageal squamous cell carcinoma. However, the underlying mechanism miR-574-3p involvement in esophageal cancer remains unclear. In this study, the expression of miR-574-3p was reduced in esophageal cancer tissues and cells. In vitro, miR-574-3p mimics and inhibitor were transfected into esophageal cancer cells (TE-1 and TE-8 cells) to up- or downregulating of miR-574-3p. miR-574-3p inhibited proliferation, migration and invasion, and promoted apoptosis in esophageal cancer cells. In addition, miR-574-3p was confirmed to target family with sequence similarity 3 member C (FAM3C) and mitogen-activated protein kinase 1 (MAPK1). miR-574-3p suppressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling via regulating FAM3C and MAPK1. In vivo, overexpression of miR-574-3p suppressed tumor growth in mice. Our findings indicated that miR-574-3p repressed proliferation and invasion of esophageal cancer via regulation of FAM3C and MAPK1, which provides a new biomarker for esophageal cancer treatment.

Corilagin Interferes With Toll-Like Receptor 3-Mediated Immune Response in Herpes Simplex Encephalitis.

Herpes simplex encephalitis (HSE) is the most common infectious disease of the central nervous system worldwide. However, the pathogenesis of HSE is not clear. Research has shown that the immune response mediated by the toll-like receptor 3 (TLR3) signaling pathway is essential to protect the central nervous system against herpes simplex virus (HSV) infection. However, an excessive immune response may cause tissue damage accompanied by pathological changes. The aim of this study was to explore the molecular mechanism via which corilagin controls HSE through the TLR3 signaling pathway in vitro and in vivo. Cells and mice were pre-treated with polyriboinosinic polyribocytidylic acid [poly(I:C)] or HSV type 1, and then treated with corilagin. After treatment, the mRNA and protein levels of TLR3, TLR-like receptor-associated interferon factor (TRIF), tumor necrosis factor (TNF) receptor type 1-associated DEATH domain protein (TRADD), TNF receptor-associated factor (TRAF) 3 and 6, nuclear factor-kappa-B (NF-κB) essential modulator (NEMO), P38, and interferon regulatory factor 3 (IRF3) were decreased. Interleukin-6 (IL-6), TNF-α, and type 1 interferon-ß were also decreased. When TLR3 expression was silenced or increased, corilagin still inhibited the expression of TLR3 and its downstream mediators. Hematoxylin-eosin (HE) staining and immunohistochemical examinations of mouse brain tissues revealed that corilagin lessened the degree of brain inflammation. Altogether, these results suggest that corilagin may regulate the immune response in HSE and relieve inflammatory injury by interfering with the TLR3 signaling pathway.

BODIPY-Decorated Nanoscale Covalent Organic Frameworks for Photodynamic Therapy.

Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment.

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo.

Aims: Emodin is an anthraquinone with potential anti-inflammatory properties. However, the possible molecular mechanisms and protective effects of emodin are not clear. The objective of this study was to investigate the possible molecular mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in the Raw264.7 cell line and in Balb/c mice. Methods: This study established an inflammatory cellular model and induced an ALI animal model. TLR4 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. The mRNA and protein levels of TLR4 and downstream molecules were detected in cells and liver tissue. The tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA. The distribution and expression of mannose receptor C type 1 (CD206) and arginase 1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and histopathological observations were assessed. Results: Administration of emodin reduced the protein and/or mRNA levels of TLR4 and its downstream molecules following LPS challenge in Raw264.7 cells and in an animal model. Additionally, emodin suppressed the expression of TNF-α and IL-6 in cell culture supernatant and serum. The inhibitory effect of emodin was also confirmed in RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally, ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum ALT and AST levels and alleviated the liver histopathological damage induced by LPS. Conclusion: Emodin showed excellent hepatoprotective effects against LPS-induced ALI, possibly by inhibiting TLR4 signaling pathways.

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial.

INTRODUCTION: Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as 'tension' repair or 'tension-free' repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. METHODS AND ANALYSIS: This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). ETHICS AND DISSEMINATION: This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015-027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: NCT02984917; preresults.

Hemocoagulase agkistrodon-induced anaphylactic shock: A case report and literature review.

Hemocoagulase agkistrodon for injection is the national first-class new drug of China with good hemostatic function and safety for capillary hemorrhage in abdominal incision of surgical patients. Adverse drug reactions (ADRs) to hemocoagulase agkistrodon are rarely reported. In this paper, we describe a case of a 41-year-old woman who developed anaphylactic shock attributed to hemocoagulase agkistrodon before colon cancer surgery. Based on the Naranjo ADR probability score, a "probable" cause and effect relationship existed for this case. Although the cause of anaphylactic reaction (hemocoagulase or excipient) and exact mechanism of hemocoagulase agkistrodon-induced anaphylactic reaction are unknown, attention should be drawn to potential ADRs in clinical use.

High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Whether microRNA-130b(miR-130b) can serve as a prognostic biomarker of hepatocellular carcinoma (HCC) has not been investigated. In the present study, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC. METHODS: We retrospectively investigated 97 patients diagnosed with HCC who underwent routine curative surgery between May 2007 and July 2012. miR-130b expression in HCC tissues and paired normal adjacent liver tissues was measured by reverse transcription and real-time PCR (RT-PCR). Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. RESULTS: miR-130b expression level was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-130b expression group was significantly shorter than that of low miR-130b expression group (43.6% vs. 71.5%; P=0.022). Moreover, the 5-year disease-free survival (DFS) of high miR-130b expression group was also significantly shorter than that of low miR-130b expression group (25.9% vs. 63.9%; P=0.012). In a multivariate Cox model, we found that miR-130b expression was an independent prognostic factor for both 5-year OS (hazards ratio [HR] =2.523, 95% confidence interval [CI] =1.024-7.901, P=0.011) and 5-year DFS (HR=4.003, CI=1.578-7.899, P=0.005) in HCC. CONCLUSION: The results indicated that high expression of microRNA-130b was correlated with significant characteristics of patients with HCC, and it might be useful as a novel prognostic biomarker for HCC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_160.

miR-21 expression predicts prognosis in hepatocellular carcinoma.

PURPOSE: The aim was to investigate the expression level of miR-21 in HCC tissues and its prognostic value among Asian population. METHODS: In the present study, expression of miR-21 was evaluated by qRT- PCR in tumor and adjacent non-neoplastic tissues in 119 HCC patients. The association of miR-21 expression with clinicopathological factors and the prognosis of HCC patients was also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: We found that miR-21 expression was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-21 expression group was significantly shorter than that of low miR-21 expression group (40.2% vs. 70.7%; P=0.007). Moreover, the 5-year disease-free survival (DFS) of high miR-21 expression group was also significantly shorter than that of low miR-21 expression group (17.4% vs. 57.3%; P=0.001). Furthermore, in a multivariate Cox model, we found that miR-21 expression was an independent poor prognostic factor for both 5-year OS (hazards ratio [HR]=3.189, 95% confidence interval [CI]=1.911-10.012, P=0.03) and 5-year DFS (HR=5.897, CI=3.009-13.763, P<0.001) in HCC. CONCLUSIONS: The results of the present study suggested miR-21 expression level could be a novel potential biomarker for HCC prognosis.

Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Repeated hepatic resection (HR) and thermal ablation therapy (TAT) are increasingly being used to treat recurrent intrahepatic cholangiocarcinoma (RICC). This study compared the efficacy and safety of these procedures for RICC treatment. METHODS: Patients were studied retrospectively after curative resection of RICCs by repeated HR (n = 32) or TAT (n = 77). Treatment effectiveness and prognosis were compared between the two treatment groups. RESULTS: The repeated HR and TAT groups did not differ in their overall survival (OS; p = 0.996) or disease-free survival (DFS; p = 0.692) rates. However, among patients with recurrent tumors >3 cm in diameter, patients in the repeated HR group had a higher OS rate than patients in the TAT group (p = 0.037). The number of recurrent tumors and the recurrence interval were significant prognostic factors for OS. The major complications incidence rate was greater in the repeated HR group than in the TAT group (p < 0.001). CONCLUSIONS: Repeated HR and TAT are both effective treatments for RICC with similar overall efficacies. TAT should be preferred in any cases when the RICC is ≤3 cm in diameter and technically feasible. However, for large tumors (>3 cm), repeated HR may be a better choice.

[Effect of electroacupuncture on the biochemical indices of bone and bone collagen metabolism and TNF-alpha in osteoporosis model rats without ovaries].

OBJECTIVE: To explore the mechanisms of electroacupuncture (EA) on postmenopausal osteoporosis (PMO). METHODS: Sixty female SD rats aged 6 months were selected, resected double ovaries and fed for 90 days in order to make the model of experimental osteoporosis, and then, they were randomly divided into a model control group (without any therapy), a routine acupoints applying group, which were treated with EA at "Pishu" (BL 20), "Weishu" (BL 21), "Shenshu" (BL 23) and "Qihaishu" (BL 24), and an EA with tonification method (EAT) group at "Guanyuan" (CV 4) and "Zusanli" (ST 36), and an EA with dispersing blood stasis method (EAD) group at "Shenshu" (BL 23), "Geshu" (BL 17) and "Dazhu" (BL 11), and an EA with tonification and dispersing blood stasis method (EATD) group at "Guanyuan" (CV 4), "Zusanli" (ST 36), "Shenshu" (BL 23), "Geshu" (BL 17) and "Dazhu" (BL 11), 12 rats in each group. EA therapy was performed once a day, 30 min each time. Then these rats rested for 1 day after consecutive treatment for 6 days. The treatment lasted for 12 weeks. Enzyme linked immunosorbent assay (ELISA) was used to examine the level of TNF-alpha, and the level of E2, osteocalin (BGP) and carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I lollagen (ICTP) by radioimmunoassay, and alkaline phosphatase by p-nitrophenylphosphate method, and Ca, P, Deoxypyridinoline (DPD) and creatinine (Cr) in urine were detected by automatic biochemistry analyzer. RESULTS: Compared with model control group, the level of DPD/Cr, Ca/Cr, and the serum contents of ALP, BGP, TNF-alpha and ICTP in all EA groups decreased significantly (all P < 0.01), the level of E2 and PICP in serum increased significantly (all P < 0.01). Compared with EATD group, the level of DPD/Cr and Ca/Cr in the other three EA groups had no statistical differences (all P > 0.05), but the level of ALP, BGP, TNF-alpha and ICTP in serum increased significantly (all P < 0.01), the level of E2 and PICP in serum decreased significantly (all P < 0.01). CONCLUSION: Acupuncture can reduce significantly the level of DPD/Cr, Ca/Cr, and the serum contents of ALP, BGP, TNF-alpha and ICTP, increase significantly the level of E2 and PICP in PMO model rats and EA with tonification and dispersing blood stasis method is superior significantly to the other routine acupuncture methods.

Role of coxsackievirus and adenovirus receptor in the pathogenesis of dilated cardiomyopathy and its influencing factor.

BACKGROUND: Although clinical treatment for heart failure and sudden death has been improved over the last few decades, the morbidity and mortality of dilated cardiomyopathy (DCM) have increased. So a better understanding of the underlying molecular events leading to DCM is urgent. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and DCM has never been neglected by experts. Recent data indicate that the up-regulation of coxsackievirus and adenovirus receptor (CAR) in viral cardiomyopathy contributes to viral infection as a key factor in the pathogenesis of this disease. This study aimed to investigate the role and regulatory mechanism of CAR in DCM by the bioinformatic method. METHODS: We identified the clusters of genes co-expressed with CAR by clustering algorithm based on the public available microarray dataset of DCM (Kittleson, et al. 2005), and mapped these genes into the protein-protein interaction networks to investigate the interaction relationship to each other at the protein level after confirming that the samples are characterized by the cluster of genes in correctly partitioning. RESULTS: The gene cluster GENESET 11 containing 33 genes including CAR with similar expression pattern was identified by cluster algorithm, of which 19 genes were found to have interaction information of the protein encoded by them in the current human protein interaction database. Especially, 12 genes present as critical nodes (called HUB node) at the protein level are involved in energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis, cell proliferation, tissue repair, etc. CONCLUSIONS: The genes in GENESET 11 together with CAR may play a pathogenic role in the development of DCM, mainly involved in the mechanism of energy metabolism, signal transduction, viral infection, immuno-response, cell apoptosis and tissue repair.

[The initial approach of two sides hypogastric artery ligation and isolation with laparoscope before excision of presacral tumor].

OBJECTIVE: To observe the significance of excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope. METHODS: Twenty-one patients with sacral tumor were performed excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope. RESULTS: All sacral tumor were removed successfully, the mean volume of operative blood was 800 ml (range 500-1900 ml), and all the patients were followed up 3-25 months, averaged time 11 months. One patient was recurred after 2 months of operation (the patient was Ewing's sarcoma, and refused to accept radiotherapy and chemotherapy after operation), 1 patents died of brain metastases after 9 months of operations. There were no recurrence in the others patients. CONCLUSIONS: The excision of presacral tumor after two sides hypogastric artery ligation and tissue dissociation with laparoscope is an effective operation method, with the advantages of decreasing the operative blood and difficulty of sacral tumor excision, and diminishing the operation wound.

Effects of angiotensin II receptor antagonist on expression of collagen III, collagen V, and transforming growth factor beta1 in the airway walls of sensitized rats.

BACKGROUND: Repeated attacks of bronchial asthma lead to different degrees of airway remodeling, the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some growth promotion factors. Angiotensin II is a polypeptide that may be involved in airway remodeling. To evaluate its role in airway remodeling in asthma, we observed the effects of an angiotensin II type 1 receptor antagonist (valsartan) on the expression of collagen III, collagen V, and transforming growth factor beta1 (TGF-beta1) mRNA and protein in the airway walls of sensitized rats. METHODS: Forty Wistar rats were randomly divided into 5 groups: control group, sensitized group, and valsartan groups 1, 2, and 3. The rats in the sensitized group and in valsartan groups 1, 2, and 3 were sensitized and challenged with ovalbumin. Rats in control group were sensitized and challenged with 0.9% NaCl. Rats from valsartan groups 1, 2, and 3 were drenched with valsartan (10 microg, 20 microg, or 30 microg, respectively) at the time of the ovalbumin challenges. The expression of collagen III, collagen V, and TGF-beta1 protein were detected using immunohistochemical method in combination with image analysis methods. The expression of TGF-beta1 mRNA was detected by in situ hybridization. RESULTS: The expression in the airways of collagen III and collagen V was significantly higher in rats from the sensitized group (7.73 +/- 0.81, 1.34 +/- 0.28) and from valsartan groups 1, 2, and 3 (5.73 +/- 0.64, 1.13 +/- 0.15; 4.96 +/- 0.51, 0.98 +/- 0.08; 4.43 +/- 0.35, 0.93 +/- 0.06, respectively) than those in the control group (2.65 +/- 0.38, 0.67 +/- 0.08, P < 0.05). In addition, collagen levels were significantly lower in valsartan groups 1, 2, and 3 than those from the sensitized group (P < 0.05). The expression of TGF-beta1 mRNA and protein in the airways was significantly higher in rats from the sensitized group (20.49% +/- 3.46%, 29.73% +/- 3.25%) and from valsartan groups 1, 2, and 3 (16.47% +/- 1.94%, 19.41% +/- 1.87%; 14.38% +/- 1.58%, 18.29% +/- 1.43%; 12.96% +/- 1.73%, 18.63% +/- 1.11%, respectively) than that from the control group (7.84% +/- 1.61%, 5.63% +/- 1.07%, P < 0.05). TGF-beta1 mRNA and protein levels were significantly lower in valsartan groups 1, 2, and 3 than that in the sensitized group (P < 0.05). CONCLUSIONS: Angiotensin II receptor antagonist valsartan can suppress synthesis of collagen III and collagen V by downregulating TGF-beta1 mRNA and protein expression. Valsartan can decrease airway remodeling and could play a role in asthma therapy.