OBJECTIVE: To review the progress on cell-penetrating peptides(CPPs). METHODS: Based on the original researches in recent years, the structure properties, classification, internalization mechanism, application and novel research orientation of CPPs were introduced in the present paper. RESULTS: Cell-penetrating peptides(CPPs) consisted of 30 or less amino acids. CPPs, generally categorized as amphipathic or cationic depending on their sequences, are increasingly drawing attention as a non-invasive delivery technology for macromolecules. Delivery of a diverse set of cargoes has been attempted using different types of CPPs in vitroand in vivo. Additionally, the relative lack of toxicity and cell specificity has enabled its widespread use in preclinical models. This paper reviewed the studies on the structure properties, classification, internalization mechanism, application and novel research orientation of CPPs. CONCLUSION: Although the internalization mechanism of CPPs will be studied deeply, CPPs, as a novel drug delivery tool, has promising application for the delivery of diverse drugs and cargoes.

Objective To investigate the effects of antioxidant response element (ARE) activator- 5,6-dihydrocyclopenta[ C ]-1,2-dithiole-3-thione (CPDT) on organotypic spinal cord cultures and to study whether this activation can protect motor neurons from oxidative stress.Methods Organotypic spinal cord cultures were prepared using lumbar spinal cord slices from 8-day-old rat.Threo-hydroxyaspartate (THA) was continuously added into the culture medium for 3 weeks,which caused selective motor neuron death. Thus,the in vitro model of amyotrophic Lateral sclerosis (ALS) was established.15,30 ?mol/L of CPDT were added into the culture medium respectively.Ventral motor neurons survival was evaluated by immunohistochemical staining with monoclonal antibody SMI-32,a nonphosphorylated neurofilament marker. Ultrastructure was observed with electronic microscope.Results The pretreatment of organotypic spinal cord cultures with different concentrations of CPDT significantly increase the total number of ventral motor neurons (15?mol/L:(15.81?6.97) perexplant;30?mol/L:(16.25?6.74) perexplant respectively) compared with THA group ((5.31?5.76) perexplant) and the former had plentiful neurite extensions (n= 15,P

As a basic amino acid, histidine has a pK_a close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved, 36 male Sprague-Dawley rats were randomly divided into control group, adriamycin nephropathy (AN) group and eplerenone-treated group (100 mg·kg(-1)·d(-1) eplerenone). Blood pressure, 24-h urinary protein, serum potassium, sodium and creatinine were measured 28 days after adriamycin injection (a single tail intravenous injection of 6.5 mg/kg adriamycin). The morphological changes of renal tissues were observed by light and electron microscopy. Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β(1) and desmin in renal cortex. The results showed that 28 days after adriamycin injection, there were no significant changes in the level of serum potassium, sodium, creatinine concentrations and blood pressure values in the rats of the three groups. Meanwhile, the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group (P<0.01), but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group (P<0.05). Mild mesangial cell proliferation and matrix expansion, diffuse deformation and confluence of foot processes in podocytes were found in the AN group. By contrast, rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions. The protein expression of TGF-β(1) and desmin in the AN group was markedly up-regulated in contrast to that in the control group (P<0.01), whereas that in the eplerenone-treated group was much lower than in the AN group (P<0.05). It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release, and restore the morphology of podocytes independent of its blood pressure-lowing effects.

Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma were widely used in strengthening spleen under different disease conditions, and were easily and often misused each other. Therefore, DNA barcode was used to distinguish Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma from their adulterants to ensure the safe use. The sequence lengths of ITS2 of Atractylodes macrocephala, Atractylodis Rhizoma (A. lancea, A. japonica and A. coreana) were both 229 bp. Among the ITS2 sequences of A. macrocephala, only one G/C transversion was detected at site 98, and the average GC content was 69.42%. No variable site was detected in the ITS2 sequences of A. lancea. The maximum K2P intraspecific genetic distances of both A. japonica and A. coreana were 0.013. The maximum K2P intraspecific genetic distances of A. macrocephala, A. lancea, A. japonica and A. coreana were less than the minimum interspecific genetic distance of adulterants. The ITS2 sequences in each of these polytypic species were separated into pairs of divergent clusters in the NJ tree. DNA barcoding could be used as a fast and accurate identification method to distinguish Atractylodis Macrocephalae Rhizoma, Atractylodis Rhizoma, from their adulterants to ensure its safe use.
Atractylodes ; classification ; genetics ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Drug Contamination ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; classification ; Molecular Sequence Data ; Phylogeny ; Quality Control ; Rhizome ; classification ; genetics

Objective: To explore the structural and functional changes of femoral and popliteal arteries in hypertension patients before and after drug therapy. Methods: A total of 201 hypertension patients treated in our hospital from 2010-03 to 2016-01 were studied. Based on blood pressure levels, the patients were divided into 3 groups: Grade-1 group,n=72, Grade-2 Group,n=68 and Grade-3 group,n=61. The patients were treated for 3 months and blood pressure was reduced below 140/90 mmHg. The intima-media thickness (IMT) of femoral and popliteal arteries was measured by two-dimensional ultrasound, blood vessel elasticity parameters of β, Ep, AC and PWV were determined by ET technology. The differences were compared between pre- and post-medication. Results: Compared with pre-medication, post-medication IMT in femoral artery was decreased in 3 groups, allP<0.05 and IMT in popliteal artery was similar,P>0.05; blood vessel elasticity parameters of β, Ep, PWV were decreased in 3 groups and AC was increased, allP<0.05. Conclusion: Drug therapy could effectively improve the elasticity of femoral and popliteal arteries in hypertension patients; two-dimensional ultrasound combining ET technology may dynamically monitor vascular elasticity of lower extremity which provides an objective basis for evaluating medication efifcacy in clinical practice.

Objective To compare effection of two kinds of bowel preparation for enteroscopy in aged patients. Methods 100 patients who would receive enteroseopy were divided into two groups. 50 cases in each group. Patients in experimental group received colon dialysis, patients in control group received oral medication. Observed the effectiveness of two kind of bowel preparations and adverse reaction. Results The effectiveness of colon dialysis was superior to oral medication(P <0. 05) ,there was no significant deviation the adverse reaction of two groups. Conclusions Colon dialysis is a suitable method in bowel preparation for enteroscopy in aged patients.

This study was aimed to construct eukaryotic expression vectors carrying the small hairpin RNA (shRNA) targeting TRPC6 gene and investigate the effect of TRPC6 knockdown on puromucin aminonucleoside (PAN)-induced podocyte injury. Two DNA sequences containing the small hairpin structure targeting TRPC6 were designed, synthesized and then inserted into the green fluorescence protein (GFP)-contained plasmids (pGC) to establish the plasmids pGCsi-TRPC6A and pGCsi-TRPC6B. Plasmids expressing scrambled shRNA were used as negative control and named pGCsi-NC. These plasmids were transfected into a conditionally immortalized murine podocyte cell line by using liposome. Flow cytometry was used to examine the transfection efficiency. TRPC6 mRNA and protein expression levels were detected by RT-PCR and Western blotting. Cultured podocytes were divided into four groups: control group, PAN treatment group, PAN+TRPC6 shRNA transfected group and PAN+scrambled shRNA transfected group. The paracelluar permeability to BSA was evaluated by Millicell-PCF Inserts and cell viability was measured by the trypan blue assay. Immunofluorescent assay was used to observe the distribution of α-actinin-4 and α-tubulin. The results showed that the transfection efficiency of the shRNA expression vector was about 45%. Expression levels of TRPC6 mRNA and protein were downregulated after transfection with pGCsi-TRPC6A and pGCsi-TRPC6B. Knocking down TRPC6 gene could effectively reverse the PAN-induced increase in the paracelluar permeability to BSA. The distribution of α-actinin-4 and α-tubulin was disrupted after treatment with PAN, which was reversed by knocking down TRPC6 gene. It was concluded that knocking down TRPC6 gene could effectively prevent podocytes from the permeability increase induced by PAN, which may be related to the regulation of podocyte cytoskeleton.

BackgroundDiabetic retinopathy (DR) is the result of the cytokine network disorders,the imbalance of angiogenic factor and vascular inhibitory factor is the start factor.ObjectiveTo analyze the levels of CXC chemotatic factors of type 2 diabetes mellitus patients,evaluate the clinical application value of them in different clinical types of DR using receiver operating characteristic (ROC)analysis and to approach the new way of individualized treatment.Methods This was a prospective research.The gold standard was ophthalmolscope and fundus fluorescein angiography.The levels of CXC chemotatic factors and multiplicaiton factors were measured in 96 cases with type 2 diabetes mellitus (66 cases with retinopathy and 30 cases without retinopathy as control).The assessment tasks were performed for these index and courses of DR with ROC curve.Results The expression of age,course of disease has significant difference in different courses of DR ( F =8.507,P =0.001 ; F =28.143,P =0.000).Compared with the control group,the expression of growth-related oncogene-α ( GROα ) ( t =- 2.172,P =0.035,AUC =0.625 ),whole blood viscosity 200 ( t =- 3.724,P =0.001,AUC =0.904 ) and neutrophilic leukocyte (t=-2.562,P =0.013,AUC =0.577 ) has significant difference in the group of mild NPDR.Compared with the control group,the expression of interferon-γ-inducible protein 10 ( IP-10 ) ( t =-3.591,P =0.001,AUC =0.592 ),platelet derivation growth factor-BB ( PDGF-BB ) ( t =- 3.233,P =0.003,AUC =0.735 ),vascular endothelial growth factor(VEGF) ( t =- 3.617,P =0.001,AUC =0.776 ),C peptide ( t =- 3.366,P =0.002,AUC =0.962 ),leukocyte ( t=-3.201,P =0.003,AUC =0.852) and neutrophilic leukocyte(t =-4.201,P=0.000,AUC =0.852) has significant difference in the group of moderate and severe NPDR.ConclusionsCXC chemotatic factors may act as reactivator in the pathogenesis of DR,GROα and IP-10 may be useful for clinical monitoring of the severity of DR,and evaluating the imbalance state of chemotatic factors maybe a new approach to clinical monitoring and prognosis of DR.

Head and Neck Neoplasms ; diagnosis ; therapy ; Humans ; Neck ; Paraganglioma ; diagnosis ; therapy