Lactoferrin (Lf) is one of the food protein belonged to the innate immune system. Apart from its main biological function of binding and transport of iron ions, lactoferrin also has many other functions and properties such as antibacterial, antiviral, antiparasitic, catalytic, anti-cancer, anti-allergic and radioprotecting. Lf is usually used as additives of food and cosmetics. The research of lactoferrin has been increasingly reported, and the application of lactoferrin as a drug carrier has drawn extensive attention over the recent year. In this paper, researches of lactoferrin as drug carriers are classified and summarized in brain targeting, liver tumor targeting, lung tumor targeting and oral delivery systems according to their different characteristics.
Administration, Oral ; Brain ; Drug Carriers ; Humans ; Lactoferrin ; chemistry ; Neoplasms

Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.
Animals ; Antineoplastic Agents ; therapeutic use ; Drug Carriers ; Energy Metabolism ; Glucose ; analogs & derivatives ; chemistry ; metabolism ; therapeutic use ; Glycoconjugates ; chemistry ; therapeutic use ; Glycolysis ; Glycosides ; chemistry ; Humans ; Ifosfamide ; analogs & derivatives ; chemistry ; therapeutic use ; Neoplasms ; diagnosis ; drug therapy ; metabolism ; Nitroimidazoles ; chemistry ; Radiation-Sensitizing Agents ; chemistry

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects

To investigate the rat intestinal absorption of stearic acid-octaarginine (SA-R8) modified solid lipid nanoparticles containing paclitaxel (SA-R8-PTX-SLN), compared with the commercially available preparation of PTX (Taxol) and PTX-loaded solid lipid nanoparticles (PTX-SLN), the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique. The absorptions of the preparations were investigated at different intestinal segments, different drug concentrations and in the presence of P-glycoprotein inhibitor (verapamil). The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum. The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN > PTX-SLN > Taxol (P < 0.05). SA-R8-PTX-SLN showed a liner absorption manner at the duodenum in the examined drug concentration range. The cumulative absorptions of Taxol and PTX-SLN were significantly promoted after the addition of P-glycoprotein inhibitor (verapamil) into the preparation (P < 0.05), but absorption of SA-R8-PTX-SLN existed no significantly difference compared with the preparation without verapamil (P > 0.05). SA-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; pharmacokinetics ; Cell-Penetrating Peptides ; chemistry ; Drug Carriers ; Intestinal Absorption ; drug effects ; Lipids ; chemistry ; Male ; Nanoparticles ; Oligopeptides ; chemistry ; Paclitaxel ; administration & dosage ; chemistry ; pharmacokinetics ; Perfusion ; Rats ; Rats, Sprague-Dawley ; Stearic Acids ; chemistry ; Verapamil ; pharmacology

China has richly and inexpensive fat and oils from animal and plants, but these resources could not get effectively utilization. In order to make the best of these resources, lipase-catalyzed acidolysis of lard with caprylic acid to produce functional lipid in solvent free system was investigated. Of the five lipases that were tested in the initial screening, immobilized lipase TL IM fromca T. languginosa resulted in the highest incorporation of capry lic acid into lard. This enzyme was further studied for the effect of enzyme load, substrate ratib, reaction time, reaction temperature and added water content on the incorporation of caprylic acid into lard. HPLC analyzed the products from the acidolysis reaction. The highest incorporation was attained at 20% enzyme load. Time course studied suggest that the incorporation of caprylic acid into lard was increased up to 38.77 mol% after 24h. Desirable mole ratio of substrates was 1:2 (lard: caprylic acid), caprylic acid incorporation up to 30.95 mol%. In the range of 45 - 60 degrees C , temperature had no significant effect on enzyme activity and caprylic acid incorporation changed little. When temperature was above 60 degrees C, incorporation of caprylic acid into lard was decreased. The highest incorporation of caprylic acid into lard 35.76 mol% was attained when added water content was 2.5%.
Caprylates ; chemistry ; Catalysis ; Chromatography, High Pressure Liquid ; Dietary Fats ; metabolism ; Enzymes, Immobilized ; metabolism ; Lipase ; metabolism ; Lipids ; chemical synthesis ; Solvents

OBJECTIVETo explore the application value of the high-frequency ultrasound examination of the normal adult sciatic nerve.

METHODSThe high frequency ultrasound was used to examine 60 cases ,a total of 120 normal adult sciatic nerve (28 males and 32 females ranging in age from 19 to 38 years old, averaged 23.8 years old). The age between men and women, height and weight showed no significant difference. The cross-sectional scanning and longitudinal scanning, if necessary, Panoramic Imaging were conducted. The cross section area of sciatic nerve was measured at the hip line, the middle of the thigh, the edge of the popliteal fossa, and the relationship betwen the sciatic nerve and surrounding muscle group was observed in each cross-section. Probe was rotated 90 degree to display the long axis of sciatic nerve, to get the longitudinal section along the long axis from top to bottom. So the sciatic nerve in the vertical axis and the surrouunding muscles was displayed by above method combined with panoramic imaging. The data of coss-sectional area of sciatic nerve were obtained at the central of hip line, the middle of the thigh, the edge of the popliteal fossa, and then were divided into different groups by gender and sides to do statistical analysis.

RESULTSThe applicatic nerve in thigh can be clearly displayed by high-frequency ultrasound in this group of 60 people with 120 nerves, but low display rate of sciatic nerve in hip, approximatley 31.4% (21/66). The longitudinal section of the sciatic nerve displayed as the banded isoechoic or slightly hyperechoic, parallel partial hyperechoic line could be seen in it; in the cross-section, it showed a clear edge of the sieve-like isoechoic or slightly hyperechnie, which could be oval ,trapezoidal, triangular and irregular in shape; the sciatic nerve bad visible passive movement and shape change when muscle contracted. There were statistically significant differences of cross-sectional area of sciatic nerves at the hip line ,the middle of thigh and edge of the popliteal fossa between 56 sciatic nerves in 28 males and 64 sciatic nerves in 32 females (P< 0.05); but there were no significant differences between left and right sides (P>0.05).

CONCLUSIONHigh frequency ultrasound can be used as the first choice of the sciatic nerve when an imaging method preferred.

Adult ; Female ; Humans ; Male ; Sciatic Nerve ; diagnostic imaging ; Ultrasonography

This study was aimed to detect the expression of leukemia stem/progenitor cell (LSPC) related genes (ABCB1, BMI-1, HOXB4) in the patients with acute leukemia, and to explore its clinical significance in acute leukemia. Bone marrow samples were collected from de novo acute leukemia patients (41 cases), patients with complete remission (CR, 16 cases) and the patients with non-malignant hematologic diseases (10 cases) respectively. And the expressions of ABCB1, BMI-1, HOXB4 genes were detected by comparative real-time quantitative PCR (RQ-PCR) with SYBR Green assay. The results showed that the expressions of ABCB1, BMI-1, HOXB4 were not detected in the patients with non-malignant hematologic diseases, but were higher (relative expressive level: 4.26 ± 2.26, 3.72 ± 1.91, 3.74 ± 2.38) in de novo acute leukemia patients and lower (relative expressive level: 2.14 ± 1.47, 2.07 ± 0.99, 1.47 ± 0.89) in the acute leukemia patients with CR (p < 0.05). The expressions of LSPC related genes were lower (relative expressive level: 1.77 ± 1.29, 2.09 ± 1.26, 1.78 ± 1.49) in the patients acquired CR/partial remission (PR) than those in the patients not acquired CR/PR (relative expressive level: 7.23 ± 1.78, 3.96 ± 0.92, 4.48 ± 2.57) (p < 0.01). Univariate analysis revealed that there were more cases with the expression of LSPC immunophenotype (CD34(+)CD38(-)CD96(+) and CD34(+)CD38(-)CD123(+)) and more hyperleukocytosis cases in patients with any higher expression of LSPC related gene (p < 0.05). Analysis of multiple parameters discovered larger significance (p < 0.01). It is concluded that there is a good relationship between LSPC related genes (ABCB1, BMI-1, HOXB4) and LSPC immunophenotype. The expression of LSPC-related genes is higher in de novo acute leukemia patients, and lower in patients acquired CR/PR. The patients with higher expressed LSPC-related genes display worse response to chemotherapy, lower CR/PR rate and higher leukocytosis, the analysis of multiple parameters may be a good method for assessing the therapeutic efficacy/prognosis of acute leukemia.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Adolescent ; Adult ; Aged ; Female ; Gene Expression ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; Neoplastic Stem Cells ; metabolism ; Polycomb Repressive Complex 1 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the in vitro effect of iron overload on the generation of reactive oxygen species (ROS) and of bone marrow (BM) cell function.

METHODSBM mononuclear cells (BMMNCs) were cultured with ferric citrate (FAC) at different concentrations and for different time to create iron overload and confirmed by the detection of cellular labile iron pool (LIP). The changes of ROS, apoptosis, hematopoietic colony formation (CFU-E, BFU-E, CFU-GM and CFU-mix) and the percentage of the CD34 + cells percentage were analyzed. The differences of these index were tested after the iron overload treated with deferasirox (DFO) or antioxidants (N-acetyl-L-cysteine, NAC).

RESULTS1) When BMMNCs were cultured with FAC, the LIP was found to increase in a time and concentration dependent manner. The intracellular LIP reached maximum at 400 micromol/L of FAC for 24 hours. 2) The ROS of total cells, leukocytes and erythrocytes increased to 1.77, 1.75 and 2.12 fold respectively compared with that of normal control when cells were cultured at 400 micromol/L of FAC for 24 hours . DFO and NAC could reduce the ROS efficiently (P<0.05). 3) The apoptotic rates of the FAC treated cells [(24.80 +/- 2.99)%] increased significantly compared with that of normal control [(8.90 +/- 0.96)%]. The capacity of hematopoietic colony formation in FAC treated cells decreased markedly compared with that of normal control (P<0.05). The percentage of CD34+ cells of FAC treated cells [(0.39 +/- 0.07)%] also decreased significantly compared with that of normal control [(0.91 +/- 0.12)%]. And these changes could be recovered by addition of NAC or DFO.

CONCLUSIONIron overload can affect the hematopoiesis by inducing the generation of ROS and this damage could be corrected by removing the excess iron and ROS of the BM cells. These findings might improve the treatment of dyshematopoiesis in patients with iron overload.

Bone Marrow Cells ; physiology ; Cells, Cultured ; Culture Media ; chemistry ; Erythrocytes ; Ferric Compounds ; pharmacology ; Hematopoiesis ; Humans ; Iron Overload ; Reactive Oxygen Species ; metabolism

OBJECTIVETo evaluate the expression of CD117 in human testicular germ cell tumors and its value in the differential diagnosis of seminoma and nonseminoma.

METHODSSeventy-four human testicular germ cell tumor specimens were studied by ABC kit immunohistochemical staining detection using CD117 monoclonal antibodies. The immunoreaction scores (IRS) of all the specimens were calculated and analysed for their clinical significance.

RESULTSAmong the 74 germ cell tumors, 31 out of 32 (9 6.9%) seminomas showed positive staining of the CD117 mostly on the cell membrane. Four of 31 (12.9%) nonseminomas displayed a weak positive staining of CD117 only in the cytoplasm of a few cells. In 10 of 11 mixed germ cell tumors, a relatively weak expression of CD117 was shown only in the seminoma component. The CD117 expression was diagnostically decreased from seminoma to mixed seminoma and to nonseminoma successively, with IRS of 6.82 +/- 2.76, 1.25 +/- 0.42 and 0.60 +/- 0.16, respectively. There was a significant difference in the CD117 expression between seminoma and nonseminoma (P < 0.05). CD 117 proteins were positively expressed in all the 20 specimens of the normal testis.

CONCLUSIONThe detection of CD117 by immunohistochemical staining using CD117 monoclonal antibodies is a newly developed useful method for differentiating seminoma and nonseminoma.

Adolescent ; Adult ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; metabolism ; Predictive Value of Tests ; Proto-Oncogene Proteins c-kit ; biosynthesis ; Seminoma ; diagnosis ; metabolism ; Testicular Neoplasms ; diagnosis ; metabolism

OBJECTIVETo investigate the epidemiological characteristus of human caliciviruses (HuCVs) among children under 5 years of age with acute diarrhea and to estimate the disease burden in Lulong county.

METHODSHuCVs were detected by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Some PCR amplicons were cloned and sequenced. Phylogenetic tree was constructed for strain characterization. The rate of HuCVs-attributed hospitalization was estimated according to the positive rate of HuCVs detection in fecal specimens collected from hospitalized diarrhea patients.

RESULTSBetween July 1999 and June 2001, 708 fecal specimens were collected, of which 393 rotavirus-negative and 5 rotavirus-positive specimens were detected for HuCVs. Thirty-one point six percentage of fecal specimens from patients with diarrhea was HuCVs positive. Among inpatients, HuCVs positive rate was 17.5%. HuCVs detection was mainly distributed in 3 - 17 mouth-old children, in winter. All 11 strains belonged to NLV GII in which 6 strains GII-3, 2 strains GII-4 and 3 strains GII-7, and they shared 55.1% - 100% nucleotide identity. NLV GII-4 and GII-7 were identified in 2000, while NLV GII-3 and GII-7 in 2001. The preliminary estimate of HuCVs-attributed hospitalization rate was 3.6 per thousand.

CONCLUSIONHuman caliciviruses with different genotypes circulated among children in Lulong county with GII NLVs were the prevalent strains. The disease burden of HuCVs was second to rotavirus.

Acute Disease ; Age Factors ; Caliciviridae ; genetics ; immunology ; Caliciviridae Infections ; complications ; epidemiology ; Child, Preschool ; China ; epidemiology ; Dysentery ; epidemiology ; etiology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Infant ; Inpatients ; statistics & numerical data ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Seasons