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Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.
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Objective:To explore any differential effect of training wearing a unilateral exoskeleton on the lower-limb motor function of stroke survivors.Methods:Forty stroke survivors were randomly divided into an exoskeleton group ( n=20) and a control group ( n=20). The control group performed conventional lower extremity exercise training while the exoskeleton group received exoskeleton-assisted lower-limb physical therapy. Each participant received eighteen 40-minute training sessions over three weeks. Before and after the intervention, the walking ability, lower-limb function, balance and ability in the activities of daily living of both groups were evaluated. Integrated electromyography (iEMG) of the rectus femoris and tibialis anterior of both legs was also recorded during sit-to-stand transitions to assess the activation of the affected muscles and the symmetry of bilateral muscle activation. Results:After the three weeks, significant improvement was observed in all of the measurements in both groups, but with the exoskeleton group scoring significantly better on average in functional ambulation category grading (1.63±0.72). Both groups′ iEMGs had also improved significantly compared with before treatment, but the exoskeleton group′s average result was by that time significantly better than the control group′s average.Conclusions:A wearable exoskeleton can effectively improve the rehabilitation of walking, lower limb movement, balance and skill in the activities of daily living of persons with subacute stroke. It better activates the affected lower limb muscles and improves the symmetry of bilateral lower limb muscle activation.
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Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane (CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol (PEG) was used to modifying magnetic graphene oxide (MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine (TCM). With this strategy, the constructed PEGylated MGO (PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of HeLa cell membrane (HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity (116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin, and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surface engineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.
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Bone infection is an osteal disorder with bone damage resulting from infection of bone marrow，cortex，periosteum and surrounding tissues，characterized by a high incidence and severe symptoms. The treatment is often complicated and prolonged. Regardless of the method used，the goal is to reduce bone defect caused by infection，control infection，rebuild impaired tissues，and promote bone healing，so as to restore bone homeostasis. Starting from bone homeostasis，the authors review the research progress in the commonly used drugs and molecular mechanisms that affect bone formation-related pathways caused by bone infection，activate bone resorption-related mechanisms，and regulate bone homeostasis，in order to provide a theoretical basis for reducing bone defect caused by bone infection and promoting bone healing.
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Objective To explore the value of MSCT enhanced scanner in diagnosis and differential diagnosis of spleen tumor. Methods The MSCT enhanced feautures of 23 cases of spleen tumor proved by imaging examination,follow-up and pathologically were anlayzed retrospectively,the features of MSCT enhanced scanner in spleen tumor were analyzed.Results All cases included 12 benign tumor (5 cysts,6 hemangiomas,1 lymphangioma).1 1 malignant tumor(2 primary lymphomas,3 secondary lymphomas,6 metastatic tumors).Conclusion MSCT enhanced scanning for the qualitative diagnosis of spleen tumors with high value.
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Objective This study aimed to explore the clinical value of human papilloma virus ( HPV) E6/E7 mRNA tests in identifying precancerous lesions of the uterine cervix-cervical intraepithelial neoplasia 2 or more CIN2+( CINⅡand CINⅢ).Methods This study is a cross-sectional survey design , between December 2011 to December 2013.The specimens were collected from the First People′s Hospital of Huizhou and the Third People′s Hospital of Huizhou in Department of Obstetrics and Gynecology outpatient and inpatient of cervical disease suspected patients , with thin-prep cytologic test ( TCT ) and histopathological results as reference , detected 345 patients of exfoliated cervical epithelial cells by using the branched DNA (b-DNA) technology to evaluate the application value of high risk HPV E 6 /E7mRNA in the clinical diagnosis of CIN.Using spss 19.0 software for data analysis.Results (1)Compared with TCT, the positive rate of E6/E7 mRNA in 325 samples were grading by cytology as follows: no intraepithelial lesion cells (NILM) 21.1%(40/190), atypical squamous cells (ASC) 38.5%(15/39 ), low-grade squamous intraepithelial lesions ( LSIL ) 76.9% ( 30/39 ) , atypical squamous cells can not exclude high-grade intraepithelial lesions (ASC-H) (8/10), high-grade squamous intraepithelial lesions (HSIL) 72.3%(34/47), TCT grades and HPV E6/E7 mRNA positive rate showed linear association (χ2 =67.654,P<0.01;r=0.497, P<0.01 ); and with HPV E6/E7 mRNA copy number was also relevant ( r =0.511, P <0.01).(2) Compared with pathological results , the positive rate of E6/E7 mRNA in 164 women samples were grading by pathology as follows:with NILM was 27.8%(10/36), with CIN Ⅰwas 65.9%(29/44), with CINⅡwas 80.6%(54/67), and with CINⅢwas 82.4%(14/17), pathological grades and HPV E6/E7 mRNA positive rate showed a linear correlation (χ2 =26.426, P<0.01; r=0.438, P<0.01); and the number of copies correlated with the increase of pathological grades too (r=0.543, P<0.01).(3) Screening effectiveness analysis results showed , the sensitivity of HPV E6 /E7mRNA was 84.6% while TCT was 47.7%.The sensitivity and specificity were 40.0% and 91.1% respectively when HPV E6/E7 mRNA and TCT processed as sequential detection test.The CIN2 +( CINⅡand CIN Ⅲ) best diagnostic critical point of 890.26 copies/ml,was established using receiver operating characteristic ( ROC) curve.The sensitivity and specificity were 58.5% and 93.7%, respectively.Conclusions The sensitivity of HPV E6/E7 mRNA test is better than TCT, the specificity is high in HPV E6/E7 mRNA and TCT processed as sequential detection test.Using the optimal cut-off value of ROC curve to detect CIN 2+has high sensitivity and specificity, so the detection of HPV E6/E7 mRNA may have some clinical value in screening and risk assessment of precancerous lesions of the uterine cervix.
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A total of 189 stool samples from swine with diarrhea, collected in various porcine farms in the central region of China were tested for porcine enteric caliciviruses (PEC) member porcine sapoviruses (SaV) by reverse transcription polymerase chain reaction (RT-PCR) amplification using primers designed to detect porcine SaV. Selected amplicons were sequenced to establish phylogenetic relationships with reference strains. Porcine SaV were detected in 12.70% (24/189) of the samples. Phylogenetic studies based on partial RNA polymerase gene sequences indicated that the field strains of viruses isolated in China were closely related (75.6 88.3% identity) to the porcine SaV Cowden reference strain. These results provide evidence that caliciviruses of the genus sapovirus circulate in piglets in China, but further studies are needed to clarify their importance as cause of diarrhea. This is the first report of PEC in China.