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Shi N.-Q.,Jilin Medical College | Shi N.-Q.,Peking University | Qi X.-R.,Peking University | Xiang B.,Peking University | And 3 more authors.
Journal of Controlled Release | Year: 2014

Cell-penetrating peptides (CPPs), often vividly termed as the "Trojan Horse" peptides, have attracted considerable interest for the intracellular delivery of a wide range of cargoes, such as small molecules, peptides, proteins, nucleic acids, contrast agents, nanocarriers and so on. Some preclinical and clinical developments of CPP conjugates demonstrate their promise as therapeutic agents for drug discovery. There is increasing evidence to suggest that CPPs have the potential to cross several bio-barriers (e.g., blood-brain barriers, intestinal mucosa, nasal mucosa and skin barriers). Despite revolutionary process in many aspects, there are a lot of basic issues unclear for these entities, such as internalization mechanisms, translocation efficiency, translocation kinetics, metabolic degradation, toxicity, side effect, distribution and non-specificity. Among them, non-specificity remains a major drawback for the in vivo application of CPPs in the targeted delivery of cargoes. So far, diverse organelle-specific CPPs or controlled delivery strategies have emerged and improved their specificity. In this review, we will look at the opportunities of CPPs in clinical development, bio-barriers penetration and nanocarriers delivery. Then, a series of basic problems of CPPs will be discussed. Finally, this paper will highlight the use of various controlled strategies in the organelle-specific delivery and targeted delivery of CPPs. The purpose of this review will be to emphasize most influential advance in this field and present a fundamental understanding for challenges and utilizations of CPPs. This will accelerate their translation as efficient vectors from the in vitro setting into the clinic arena, and retrieve the entry art to "Troy". © 2014 Elsevier B.V.

Liu T.,Jilin University | Yu C.-P.,Jilin Medical College
Evidence-based Complementary and Alternative Medicine | Year: 2011

Invasive procedures, such as surgery and acupuncture, are likely better than the others in terms of eliciting placebo analgesia. Understanding how invasive procedures can elicit enhanced placebo responses may provide new insights into mechanisms underlying placebo analgesia. In this essay, it is argued that sensory, cognitive and emotional factors are major determinants of the magnitude of placebo analgesia. Sham surgery and acupuncture are good examples of placebo interventions, which generate robust placebo responses through simultaneously manipulating such three factors. Copyright 2011 Tao Liu and Cui-ping Yu.

Coder B.D.,University of North Texas Health Science Center | Wang H.,Jilin Medical College | Ruan L.,Wenzhou University | Su D.-M.,University of North Texas Health Science Center
Journal of Immunology | Year: 2015

Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non- lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging). Copyright © 2015 by The American Association of Immunologists, Inc.

Zhang Y.,Jilin Medical College
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2013

To explore the efficacy of Schizandra Chinensis polysaccharide (SCP) on cyclophosphamide (CTX) induced dyszoospermia of rats and its effects on reproductive hormones. SCP was extracted by ethanol-alkali solution. Fifty male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the low dose SCP group (100 mg/kg), the middle dose SCP group (200 mg/kg), and the high dose SCP group (400 mg/kg). Except the normal control group, the dyezoospermia rat model was established by peritoneal injection of CTX at the daily dose of 80 mg/kg, once daily for 5 successive days. After modeling, SCP was intragastrically administered at corresponding dose to the three SCP groups. Equal volume of normal saline was given to rats in the normal control group and the model group by gastrogavage. All the medication was performed once daily for 60 successive days. The blood serum and testis were withdrawal 24 h after the last intragastric administration. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in the testis homogenate were determined by enzyme linked immunosorbent assay. The sperm count, the motility rate, and the teratospermia rate were compared. The morphology of the testis was observed using HE staining. Compared with the normal control group, the sperm count and the motility rate decreased, the teratospermia rate increased, the serum levels of FSH and LH increased, the T content in the testis homogenate decreased in the model group, showing statistical difference (P <0.01). Compared with the model group, the sperm count and the motility rate increased, the teratospermia rate decreased, the serum levels of FSH and LH decreased, the T content in the testis homogenate increased in the model group, showing statistical difference (P <0.01, P <0.05). All the indices showed dose-dependent manner in the SCP groups. The histological results showed the pathological injury in the testicular tissue was improved in all SCP groups. SCP showed obvious therapeutical effects on CTX induced dyszoospermia in rats, and its mechanisms might be correlate with recovering the regulation function of hypothalamus-hypophysis-gonad axis.

Guan J.,Jilin Medical College
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To investigate the pharmacokinetics and tissue distribution of Schisandra chinensis in mice. Schisandrin in mice plasma and tissues including heart, liver, spleen, lung and kidney was quantitatively determined by HPLC. The concentration-time curve of Schisandra chinensis extract was described by a single compartment model, Cmax was (2.17 +/- 0.27) mg/ mL, t(max) was (1.00 +/- 0.32) h, AUC0-->infinity, was (4.07 +/- 0.62) mg x h/mL. The sequence of distribution of schisandrin in mice body was as follows: liver > plasma > kidney > lung > heart > spleen. The distribution of extract in the body is abroad. Liver has relative high concentration of schisandrin, which is beneficial to the treatment of hepatic disease.

Wang Y.Y.,Jilin Medical College
Applied Mechanics and Materials | Year: 2014

This article describes the virtual reality technology, distance education in the virtual reality environment and applications of distance education based on virtual reality technology in power system teaching and power production. Compared with the traditional teaching it broke through the restrictions of time and space and virtual classrooms were established, it perfected power system teaching, promoted electricity production and improved the efficiency of electrical equipment maintenance exercises. It can bring new energy to the power system and play a promoting role in sustainable development of energy and economy in the certain degree. © (2014) Trans Tech Publications, Switzerland.

Zhang F.-Z.,Jilin Medical College
National Medical Journal of China | Year: 2012

Objective: To determine the effects of disease activity and other risk factors on bone mineral density (BMD) in untreated systemic lupus erythematosus (SLE). Methods: Lumbar and hip BMD were determined by dual energy X-ray absorptiometry (DXA) in 50 healthy controls and 120 premenopausal SLE females from Department of Rheumatology & Immunology, Third Hospital of Medical College of Jilin University during the period of 2010-2012. The SLE patients were divided into 2 groups, i. e. untreated and treated with glucocorticoid and immunosuppressives. Simple and multiple linear regression analyses were performed to determine the associations between BMD and disease-related variables. To completely eliminate the influences of glucocorticoid treatment on the results, the untreated SLE patients were chosen to investigate the risk factors with regression analysis. Results: In femoral neck, greater trochanter and total hip, both the treated and untreated SLE patients had significantly lower BMD than the healthy controls (P < 0.01). In greater trochanter, the treated SLE group had significantly lower BMD than the untreated group. The BMD of left and right femoral neck of the former were botj -0.06 while that of the later -0.11 and -0.12 respectively (P < 0.05). Regression analysis showed that long disease duration and high (SLE disease activity index) SLEDAI were the risk factors of low BMD (P < 0.05), especially high SLEDAI. Conclusion: SLE itself may result in low BMD, especially in patients with high SLEDAI. Hip joints are predominatly affected. Long disease duration is also closely associated with low BMD in SLE.

Feng X.M.,Jilin Medical College
Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases | Year: 2010

To inhibit the expression of pyruvate kinase (PK) mRNA in Giardia lamblia by specific hammerhead ribozyme. The constructed hammerhead-GCV vector (pGCV-PKH) which aims to PK mRNA was electroporated into G. lamnblia trophozoites (group A). Electroporated trophozoites (group B) and normal trophozoites (group C) served as control Trophozoites in each group were collected at 24, 48, 72 and 96 h post-electroporation, respectively. The concentrations of trophozoites were calculated and the growth curves were constructed. At 24, 48, 72 and 96 h post-electroporation, mRNA of each group was detected by RT-PCR and real-time PCR, respectively. The PK activity was tested by ultraviolet spectrophotometry. The growth curve showed that the growth of trophozoites was considerably depressed after 96 h post-electroporation. RT-PCR result displayed that the specific ribozyme mRNA was detected in group A from 24 h to 96 h post-electroporation. At 24 and 48 h after transfection, the PK mRNA level of group A decreased to 5% (5 +/- 0.17) and 8% (8 +/- 0.19) of the level in group C, respectively; and the PK activity of group A decreased to 32% (32 +/- 0.64) and 38% (38 +/- 0.65) of the level in group C. PK mRNA expression in G. lamblia has been inhibited by specific hammerhead ribozyme.

Jiang Y.,Jilin Medical College
Asian Pacific Journal of Cancer Prevention | Year: 2015

Background: Objective Myocardin-related transcription factor (MRTF)-A is a Rho signaling-responsive co-activator of serum response factor (SRF). The purpose of this study is to investigate the role of MRTF-A and AQP1 (aquaporin 1) in pathological vascular remodeling. Materials and Methods: MRTF-A, AQP1 and neointima expression was detected both in the wire injured femoral arteries of wild-type mice and the atherosclerotic aortic tissues of ApoE-/- mice. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin β1 were also assayed. The intercourse relationship between the molecules were investigated by interfering RNA and inhibitor assay. Results: MRTF-A and AQP1 expression were significantly higher in the wire injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE-/- mice than in healthy control tissues. Both in wire-injured femoral arteries in MRTF-A knockout (Mkl1-/-) mice and atherosclerotic lesions in Mkl1-/-; ApoE-/- mice, neointima formation were significantly attenuated and the expression of AQP1 were significantly decreased. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin β1, three SRF targets and key regulators of cell migration, and AQP1 in injured arteries was significantly weaker in Mkl1-/- mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs were the down-regulation of microRNA-300. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. Conclusions: MRTF-A could be a novel therapeutic target for the treatment of vascular diseases.

Yuan Z.H.,Jilin Medical College
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

This study was aimed to investigate the impact of vWF A1381T polymorphism (rs216311) and ABO blood group on von Willebrand factor level in plasma. 120 healthy volunteers, aging from 19 to 33 years (average 24) were recruited. The vWF:Ag level in plasma was determined by ELISA. vWF gene A1381T polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequenced when necessary. The data were grouped by gender, blood group and/or genotype. The difference of plasma vWF level between male and female were analyzed by independent sample t test. One way ANOVA were used to analyze the difference of vWF level in each blood group of genotype while factorial design ANOVA were used to test the difference of vWF level in plasma between A1381T genotype and/or ABO blood groups. The results showed that analysis of plasma vWF level in 120 volunteers of both male (60) and female (60) demonstrated no statistical difference (t = 1.039, p = 0.301). The vWF level was lower in blood type O group than that in non-O group (p < 0.001); the plasma vWF level in AA mutant of vWF A1381T gene polymorphism was lower than that in AG and GG mutant (p = 0.003 and 0.019, respectively). In blood type O group, the vWF plasma level in AG mutant of vWF A1381T gene polymorphism resulted in non-difference (p = 0.070) compared with AA or AG mutant, while there was significant difference in vWF of plasma level when contrast tests were applied (t = 2.321 and p = 0.028, respectively). In non-O group, the plasma vWF level in AG mutant of vWF A1381T gene polymorphism were significantly different from AA mutant (p = 0.032). It is concluded that plasma vWF level unrelated with gender but interrelates with ABO blood groups. Plasma vWF level in vWF gene A1381T polymorphism with AA mutant is significantly lower than that with AG and GG mutant. In blood type O group, plasma vWF level in vWF gene A1381T polymorphism with AG mutant is higher than that with AA and GG mutant. In non-O group, the vWF plasma level in A1381T gene polymorphism with AG mutant is significantly higher than that with AA mutant. This change may be beneficial to understand some diseases, especially cardio-cerebral vascular diseases.

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