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 develop different methods for determining siRNA content and the entrapment efficiency of siRNA loaded liposomes, SYBR Gold electrophoresis method and Ribogreen fluorospectrophotometry method were used respectively. SYBR Gold electrophoresis method has a good linear relation in a range at 0.2-2.0 micromol x L(-1) (R = 0.9930), and the recovery at the high, middle and low concentrations were 96.35%, 96.92%, and 100.74%, respectively (n = 3). The intra-day and inter-day RSD were far below 5% (n = 5). Ribogreen fluorospectrophotometry method has a good linear relation in a range at 10-50 nmol x L(-1) (R = 0.9971), and the recovery at the high, middle and low concentrations were 98.22%, 99.88% and 99.64%, respectively (n = 3). The intra-day and inter-day RSD were far below 5% (n = 5). The content and the entrapment efficiency of three batches of siRNA cationic liposomes were 98.52%, 97.85% and 99.20%, 96.45%, respectively, with these two methods. And there is no significant difference by ANOVA. Both of the two methods are accurate, sensitive, convenient method for determination of the siRNA content and the entrapment efficiency of siRNA loaded cationic liposomes.
Drug Carriers ; Drug Delivery Systems ; Electrophoresis ; Liposomes ; chemistry ; RNA, Small Interfering ; analysis ; Spectrometry, Fluorescence

In this study, indomethacin (IND) loaded solidified-polymeric micelles (IND-SPM) were prepared. Their in vitro characteristics were investigated. Methoxy-poly(ethylene glycol) poly(D, L-lactide) copolymer (mPEG-PDLLA) was used as IND carrier. The preparation of IND-SPM was conducted by solution-absorption method and evaporation by rotary evaporator. Polyplasdone XL-10 was used as adsorbent. The solution-absorption method was conducted by the following procedure; IND and mPEG-PDLLA were dissolved in acetone, followed by addition of polyplasdone XL-10 and stirred to obtain a suspension. The powder of IND-SPM was simply obtained after the organic solvent was completely evaporated. More than 90% (w/w) of IND (20 mg) in the powder was dissolved in 250 mL PBS within 30 min. DSC, 1H NMR and SEM results proved that IND was encapsulated within mPEG-PDLLA. The solubility of IND in the system increased 4.6 times with the highest amount of copolymer. The solidified particles were found to be suitable for the formulation of tablets or capsules.
Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Drug Carriers ; chemistry ; Drug Compounding ; Drug Delivery Systems ; Indomethacin ; administration & dosage ; chemistry ; Micelles ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Povidone ; chemistry ; Solubility

OBJECTIVETo study the related proteins of apoptosis initiation induced by homoharringtonine (HHT) in HL-60 cells.

METHODSAfter establishment of an apoptosis initiation model induced by HHT in HL-60 cells, proteins of untreated and HHT treated HL-60 cells were extracted, and the two-dimensional polyacrylamide gel electrophoresis (2-DE) maps of the extracted proteins were established by using the immobilized pH gradient (IPG) two-dimensional electrophoresis respectively. The alteration protein spots were identified with assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database searching.

RESULTSProteomics analysis showed that proteins including MHC class I antigen, calbindin D-28K, chloride channel protein 6, oncoprotein 18, zinc finger protein Helios and apoptosis inhibitor like protein 2 were involved in apoptosis initiation induced by HHT.

CONCLUSIONThe present study might conduce to the researches of HL-60 cells carcinogenesis and pave the way to exploit drug precursor related to HHT and initiation of apoptosis in HL-60 cells.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Calbindins ; Chloride Channels ; analysis ; DNA-Binding Proteins ; analysis ; Electrophoresis, Gel, Two-Dimensional ; methods ; HL-60 Cells ; Harringtonines ; pharmacology ; Histocompatibility Antigens Class I ; analysis ; Humans ; Ikaros Transcription Factor ; Inhibitor of Apoptosis Proteins ; Microtubule Proteins ; Phosphoproteins ; analysis ; Proteins ; analysis ; Proteome ; analysis ; S100 Calcium Binding Protein G ; analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stathmin ; Transcription Factors ; analysis

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.
Animals ; Antitrichomonal Agents ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; methods ; Endotoxins ; Gingival Crevicular Fluid ; metabolism ; Injections ; Periodontal Pocket ; metabolism ; Periodontitis ; chemically induced ; metabolism ; Polyesters ; chemical synthesis ; pharmacokinetics ; Polyethylene Glycols ; chemical synthesis ; pharmacokinetics ; Rabbits ; Random Allocation ; Rheology ; Tinidazole ; administration & dosage ; pharmacokinetics

OBJECTIVETo study the association between two single nucleotide polymorphisms (SNP), rs2295080 and rs2536, in mammalian target of rapamycin (mTOR) gene and the susceptibility to pediatric epilepsy.

METHODSA case- control study was performed on 480 children with epilepsy (116 cases of refractory epilepsy) and 503 healthy children. SNP rs2295080 and rs2536 in the mTOR gene were detected by polymerase chain reaction restriction and fragment length polymorphisms (PCR-RFLP). Genotype and allele frequencies of SNP rs2295080 and rs2536 were compared between the children with epilepsy and healthy controls.

RESULTSThere were no significant differences in the genotype and allele frequencies of SNP rs2295080 between the children with epilepsy and healthy controls. There were no significant differences in the genotype frequencies of SNP rs2536 between the two groups either, but the frequency of G allele of SNP rs2536 was higher in children with epilepsy than that in healthy controls (P=0.042, OR=1.344, 95%CI: 1.010-1.789).

CONCLUSIONSSNP rs2536 of mTOR gene may be associated with the risk of pediatric epilepsy.

Epilepsy ; etiology ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Risk ; TOR Serine-Threonine Kinases ; genetics

OBJECTIVETo study the mechanism of hepatic carcinoma cell apoptosis induced by small interfering RNA (siRNA)-mediated nuclear factor-kappaB (NF-kappaB) P65 silencing.

METHODSHepatic carcinoma SMMC-7721 cells were exposed to liposome-mediated transfection with NF-kappaB P65 siRNA synthesized by in vitro transcription, and the cells with empty liposome transfection and those without particular treatment served as the control groups. The expression of NF-kappaB P65 in the cells was detected by Western blotting, the cell viability examined by MTT assay, and the cell apoptosis assessed by flow cytometry. Immunohistochemistry was used to examine the expressions of Bcl-2 and Bax.

RESULTSsiRNA transfection significantly inhibited the expression of NF-kappaB P65 in SMMC-7721cells, with inhibition rates of 64.74% compared with the untreated cells and of 34.52% compared with the liposome-treated cells. The siRNA-treated SMMC-7721 cells also exhibited significant decrease in cell proliferation by 33.39% and 27.23% in comparison with the untreated and liposome-treated cells, respectively. NF-kappaB P65 siRNA induced obvious cell apoptosis with down-regulated Bcl-2 and up-regulated Bax expressions.

CONCLUSIONNF-kappaB p65 siRNA can induce SMMC-7721 cell apoptosis via the Bcl-2/Bax pathway.

Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Liposomes ; Liver Neoplasms ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Small Interfering ; pharmacology ; Transcription Factor RelA ; metabolism ; Transfection ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the effect of joint mobilization on postoperative wrist joint function, pain and grip strength for elderly patients with distal radius fracture.

METHODSFrom January 2015 to June 2016, a total of 67 elderly patients with distal radius fracture were randomly divided into routine exercise group and joint mobilization group. Among them, 37 patients in the routine exercise group underwent conventional distal radius fracture postoperative joint function exercise regimen, including 16 males and 21 females with a mean age of (67.8±3.2) years old ranging from 60 to 72 years old;the injured side was dominant in 23 cases and non-dominant in 14 cases;injury mechanism was fall in 26 cases, traffic accident in 11 cases; for AO type, 6 cases were type B3, 18 cases were type C1, 7 cases were type C2, 6 cases was type C3. Other 30 patients in the joint mobilization group underwent joint mobilization on the basis of the routine exercise group including 14 males and 16 females with a mean age of (67.1±4.0) years old ranging from 61 to 74 years old; the injured side was dominant in 21 cases and non-dominant in 9 cases;injury mechanism was fall in 25 cases, traffic accident in 5 cases;for AO type, 8 cases were type B3, 13 cases were type C1, 6 cases were type C2, 9 cases were type C3. The wrist joint activity, Gartland-Werley wrist joint function score, VAS pain score and grip strength were observed at 3 months afrer treatment.

RESULTSAfter 3 months' treatment, the VAS in the routine exercise group was higher than that of the joint mobilization group (<0.05). The grip strength of affected side in both groups were lower than that of contralateral side, but the average grip strength of affected side in joint mobilization group was higher than that in routine exercise group(<0.05). In routine exercise group, the average angle of flexion, extension, radial deviation were significantly higher than those of joint mobilization group(<0.05). But ulnar deviation angle in routine exercise group compared with joint mobilization group had no significant difference (>0.05). In the comparison of each item of Gartland-Werley, there was no significant difference between two groups in residual deformity and complication(>0.05); the average score of subjective score, objective score and total score in routine exercise group were significantly higher than those of the joint mobilization group (<0.05). The wrist function Gartland-Werley score in routine exercise group after treatment was excellent in 21 cases, good in 10, 6 in fair, while in joint mobilization group, excellent in 23, good in 6, fair in 1(<0.05).

CONCLUSIONSThe application of joint mobilization in the treatment of elderly patients with distal radius fracture can improve the joint activity and obtain better wrist function after surgery.

White-rot fungus manganese peroxidase (MnP) oxidizes a wide range of substrates, rendering it an interesting enzyme for potential applications. The stability of MnP can be improved by immobilization. With sodium alginate, gelatin, or chitosan as a carrier, and glutaraldehyde as the crosslinking agent, MnP was co-immobilized using the embed-crosslinked method and the adsorb-crosslinked method. The immobilization conditions and the partial properties of the three immobilized enzymes were investigated. When compared with the free enzyme, the optimum pH values and the temperatures of the three immobilized MnPs carried by alginate, gelatin, and chitosan were respectively shifted from 7.0 to 5.0, 5.0, 3.0 and from 35 degrees C to 75 degrees C , 55 degrees , 75 degrees C . The thermostabilities of the three immobilized MnPs were considerably better than that of the native enzyme. The chitosan-decreased by less than 5% even after repeated use for 6 - 9 times. The ability of decolorizing azo dyes in static and shaky situation by gelatin-immobilized MnP approached to the free enzyme, and there was no loss of enzyme activity during 2 repeated batch reactions.
Adsorption ; Alginates ; chemistry ; metabolism ; Biocatalysis ; drug effects ; Chitosan ; chemistry ; metabolism ; Dose-Response Relationship, Drug ; Enzymes, Immobilized ; chemistry ; metabolism ; Fungal Proteins ; chemistry ; metabolism ; Gelatin ; chemistry ; metabolism ; Glucuronic Acid ; chemistry ; metabolism ; Glutaral ; pharmacology ; Hexuronic Acids ; chemistry ; metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Peroxidases ; chemistry ; metabolism ; Schizophyllum ; enzymology ; Substrate Specificity ; Temperature