Root extractive from Daphne genkwa benefits in wound healing of anal fistula through up-regulation of collagen genes in human skin fibroblasts.

Wound healing is the main problem in the therapy of anal fistula (AF). Daphne genkwa root has been traditionally used as an agent to soak sutures in operation of AF patients, but its function in wound healing remains largely unclear. The aim of the present study was to illuminate mechanisms of D. genkwa root treatment on AF. In the present study, 60 AF patients after surgery were randomly divided into two groups, external applied with or without the D. genkwa extractive. Wound healing times were compared and granulation tissues were collected. In vitro, we constructed damaged human skin fibroblasts (HSFs) with the treatment of TNF-α (10 µg/ml). Cell Count Kit-8 (CCK-8) and flow cytometry analysis were used to determine the effects of D. genkwa root extractive on cell viability, cell cycle and apoptosis of damaged HSFs. Furthermore, protein levels of TGF-ß, COL1A1, COL3A1, Timp-1, matrix metalloproteinase (MMP)-3 (MMP-3) and MEK/ERK signalling pathways were investigated both in vivo and in vitro Results showed that D. genkwa root extractive greatly shortens the wound healing time in AF patients. In granulation tissues and HSFs, treatment with the extractive significantly elevated the expressions of COL1A1, COL3A1, Timp-1, c-fos and Cyclin D1, while reduced the expression of MMP-3 Further detection presented that MEK/ERK signalling was activated after the stimulation of extractive in HSFs. Our study demonstrated that extractive from D. genkwa root could effectively improve wound healing in patients with AF via the up-regulation of fibroblast proliferation and expressions of COL1A1 and COL3A1.

Cancer Cell Membrane-Coated Upconversion Nanoprobes for Highly Specific Tumor Imaging.

Cancer cell membrane-coated upconversion nanoprobes (CC-UCNPs) with immune escape and homologous targeting capabilities are used for highly specific tumor imaging. The combination of UCNPs with biomimetic cancer cell membranes embodies a novel materials design strategy and presents a compelling class of advanced materials.

Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake.

Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle 'stealth'. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.

Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.

For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.

Approaches to the evaluation of malaria elimination at county level: case study in the Yangtze River Delta region.

As the progress on transition from malaria control to malaria elimination in the People's Republic of China (P.R. China), four counties/districts, namely Zhabei District and Songjiang District of Shanghai municipality, and Anji County and Haiyan County of Zhejiang Province, representatives of the Yangtze River Delta region, were included in the pilot project of the national malaria elimination programme in P.R. China. A baseline survey was conducted first. The main measures performed were blood examination of febrile cases, improving the information management system of malaria cases, providing standard diagnosis and treatment, standardized disposal of epidemic focus, and health education and health promotion, strengthening the management of mobile population, etc. All the measures were assessed and evaluated through data examination and on-site investigation. In the whole process of the pilot project, quality control was especially emphasized. During the implementation of pilot project, the three-level control system was improved, professional staff was enriched and the working fund was ensured (a total fund of RMB 2,923,600). Thirty-nine training courses were conducted. Among 102,451 febrile cases receiving blood examination, all of the 23 malaria cases were confirmed as imported from other provinces or foreign countries. All the epidemic foci were surveyed and some control measures were carried out. Various health education and promotion activities were carried out including publicizing malaria control knowledge through news media, newspapers and periodicals and networks. Assessment and evaluation of the project was done by the Zhejiang and Shanghai Government, comprehensive score was >95 points under the evaluation system which indicated all four pilot counties/districts had first achieved the goal of elimination of malaria in P.R. China. Experiences and lessons about the measures carried out in the project were discussed.

Core-shell supramolecular gelatin nanoparticles for adaptive and "on-demand" antibiotic delivery.

The treatment of bacterial infection is one of the most challenging tasks in the biomedical field. Antibiotics were developed over 70 years and are regarded as the most efficient type of drug to treat bacterial infection. However, there is a concern that the overuse of antibiotics can lead to a growing number of multidrug-resistant bacteria. The development of antibiotic delivery systems to improve the biodistribution and bioavailability of antibiotics is a practical strategy for reducing the generation of antibiotic resistance and increasing the lifespan of newly developed antibiotics. Here we present an antibiotic delivery system (Van⊂SGNPs@RBC) based on core-shell supramolecular gelatin nanoparticles (SGNPs) for adaptive and "on-demand" antibiotic delivery. The core composed of cross-linked SGNPs allows for bacterial infection-microenvironment responsive release of antibiotics. The shell coated with uniform red blood cell membranes executes the function of disguise for reducing the clearance by the immune system during the antibiotic delivery, as well as absorbs the bacterial exotoxin to relieve symptoms caused by bacterial infection. This approach demonstrates an innovative and biomimetic antibiotic delivery system for the treatment of bacterial infection with a minimum dose of antibiotics.

Supramolecular gelatin nanoparticles as matrix metalloproteinase responsive cancer cell imaging probes.

We demonstrate the on-chip preparation of size-controllable supramolecular gelatin nanoparticles (SGNs) with a quantum dot (QD) payload as matrix metalloproteinase (MMP) responsive cancer cell imaging probes.

[Expression of JAG1 and DLL1 genes in colorectal cancer and its clinical significance].

OBJECTIVE: To study the expression of JAG1 and DLL1 in colorectal cancer and its clinical significance. METHODS: Patients with colorectal cancer were treated in the Center of Colorectal Surgery of the Third Affiliated Hospital of Nanjing University of TCM were collected prospectively and followed up. A tissue microarray was made and expressions of JAG1 and DLL1 were detected by immunohistochemical staining. RESULTS: A total of 146 cases with colorectal cancer were included. The differences in JAG1 expression were significant among different tumor differentiation types and the differences in DLL1 expression were significant among different tumor locations(all P<0.05). There were no significant differences in the expression of the two genes and microsatellite instability(MSI)(P>0.05). One hundred and thirty-four (91.8%) cases were followed up and the mean follow-up time was (42.3±13.3) months. Tumor-free survival was noticed in 86 patients. The overall survival was 93% at 1 year, 74% in 3 years, and 67% in 5 years. Multivariate analysis showed that long-term survival rate was related to TMN stage, pathology types, MSI status and expression of JAG1. The prognosis of patients with high expression of JAG1 was better than those with low and negative expression(P<0.05). CONCLUSIONS: The expressions of JAG1 and DLL1 are related to tumor differentiation and tumor location. The expression of JAG1 gene is associated with long-term survival.

Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF-kB pathway.

Zinc finger proteins (ZNF) play important roles in various physiological processes. Here we report that ZNF300, a novel zinc finger protein, identified specifically in humans, promotes tumour development by modulating the NF-κB pathway. Inflammatory factors were found to induce ZNF300 expression in HeLa cell line, and ZNF300 expression further enhanced NF-κB signalling by activating TRAF2 and physically interacting with IKKß. Furthermore, ZNF300 overexpression increased ERK1/2 phosphorylation and the expression of c-myc, IL-6, and IL-8 but decreased the expression of p21(waf-1) and p27(Kip1) ; whose down-regulation led to the opposite effect. Most importantly, ZNF300 overexpression stimulated cancer cell proliferation in vitro and significantly enhanced tumour development and metastasis in mouse xenograft model, while knocking down ZNF300 led to the opposite effects. We have identified a novel function for ZNF300 in tumour development that may uniquely link inflammation and NF-κB to tumourigenesis in humans but not in mice.

[Expression pattern and clinical significance of hairy enhancer of split 1 in colorectal cancer].

OBJECTIVE: To explore the roles of hairy enhancer of split 1 (Hes1) gene in colorectal cancer and analyze its clinical significance. METHODS: A total of 146 cases with colorectal cancer at our hospital were collected prospectively and followed up. There were 84 males and 62 females with an average age of (61 ± 11) years old. Tissue microarray was prepared and the expression of Notch signal genes were detected by immunohistochemical staining. RESULTS: The differential expressions of Hes1 were significant among various types [negative or weakly positive: 8% (12/146), positive(+): 77% (112/146), positive(++): 15% (22/146)]. Among all, 134 were followed up successfully for an average duration of (42 ± 13) months. According to the Kaplan-Meier life curve, the overall 1, 3 and 5-year survival rates were 93% (136/146), 74% (108/146) and 67% (98/146) respectively. The long-term survival rate was correlated with TNM stage and pathological types (all P = 0.000), but not with Hes1 (P = 0.267). CONCLUSION: The expression of Hes1 is correlated with pathological types and differentiation types. However the long-term survival rate is not correlated with its expression.

PU.1 can regulate the ZNF300 promoter in APL-derived promyelocytes HL-60.

ZNF300, which plays the role in human embryonic development and some diseases, is a typical KRAB/C2H2 zinc finger gene expressed only in higher mammalians. Our data showed that expression of ZNF300 changed significantly in various leukemia blasts in the bone marrow aspirates of newly diagnosed leukemia patients. To investigate the potential relationship between expression of ZNF300 and the progression of leukemia development and hematopoietic differentiation, we cloned and characterized the putative human ZNF300 gene promoter and identified its transcription start sites (TSSs). Deletion and mutagenesis analysis demonstrated that a myeloid-specific transcription factor PU.1 binding site was responsible for myeloid-specific regulation of ZNF300 promoter activity. Furthermore, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that PU.1 bound to the PU.1 binding site within ZNF300 promoter region in vitro and in vivo. Overexpression of PU.1 elevated ZNF300 promoter activity, whereas silencing of PU.1 expression significantly reduced the activity in myeloid-derived HL-60 cell but not in T-cell Jurkat. In vitro induced HL-60 cells into CD11b expressing cells by DMSO demonstrated that ZNF300 was upregulated along with upregulation of PU.1 expression. These results demonstrated that ZNF300 was activated by PU.1 and suggested that the regulation may be involved in the progression of leukemia development and hematopoietic differentiation.

The expression and significance of IDH1 and p53 in osteosarcoma.

BACKGROUND: To detect the expression of isocitrate dehydrogenase 1 (IDH1) and transformation-related protein 53 (p53) in osteosarcoma and analyze the correlation between them and the clinico-pathological features. METHODS: The expressions of IDH1 and p53 were detected in human osteosarcoma cell lines (MG-63 and U2OS) by immunocytochemistry, Real-time PCR and Western Blotting. The expressions of IDH1 and p53 in formalin-fixed paraffin-embedded tissue sections from 44 osteosarcoma patients were determined by immunohistochemistry, and the correlation between them and clinicopagthological features were analyzed. None of these patients received chemotherapy prior to surgery. RESULTS: IDH1 is detected in osteosarcoma cell lines and biopsies. IDH1 expresses higher in U2OS cells with wild type p53 than in MG-63 cells with mutation p53. IDH1 correlates with histological Rosen grade and metastasis negatively. P53 correlates with histological Rosen grade, metastasis and overall survival in clinical osteosarcoma biopsies. Osteosarcoma patients with High IDH1 expression have a very high p53 expression. CONCLUSION: IDH1 may correlate with p53 and be a candidate biomarker for osteosarcoma correlate with histological Rosen grade and metastasis.

[Clinical multi-manifestation, diagnosis and treatment of non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions].

OBJECTIVE: To investigate the clinical multimanifestation, diagnosis and treatment of non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions. METHODS: 58 cases of non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions were retrospected in this study. RESULTS: The manifestation of 58 cases was complicated. Non-Hodgkin's lymphoma treatment was synthetical therapy or chemical therapy. CONCLUSION: Non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions had multi-manifestation and higher malignant. The final diagnosis relied on pathological examination. Both of sythetical therapy and chemical therapy were effective to non-Hodgkin's lymphoma in oral, maxillofacial and cervical regions.