1.Research progress of delivery strategies related mucus barrier in mucosal drug delivery
Feng-mei LÜ ; Li SUI ; Zhe-peng LIU
Acta Pharmaceutica Sinica 2022;57(3):670-680
The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.
2.Clinicopathological significance of X-ray repair cross complementing gene 1 expression in colorectal carcinoma
Lu FENG ; Bo HU ; Mei LI ; Zhaohui WANG ; Xiaoyue PEI ; Shen Lü
Cancer Research and Clinic 2010;22(9):604-606
Objective To explore the clinicopathological value of X-ray repair cross complementing gene 1(XRCC1) expression in colorectal carcinoma. Methods The XRCC1 gene expression in 107 cases of colorectal carcinomas, 25 cases of adjacent mucosa and 36 cases of normal colorectal mucosa was detected immunohistochemically, and the correlation between the expression and clinicopathological factors was analyzed. Results The positive rates of XRCC1 expression in colorectal carcinoma and adjacent mucosa,87.8 % (94/107) and 84.0 % (21/25) respectively, were significantly higher than that in the normal colorectal mucosa [27.8 %(10/36) (P=0.000, P =0.000)]. In colorectal carcinoma, the positive rate of XRCC1 expression in the group of poor differentiation [44.4 % (4/9)] was significantly lower than that in the groups of moderate and well differentiation [94.8 % (50/58)(P=0.000) and 87.5 %(35/40) (P=0.015)], while the positive rate of XRCC1 expression was not related to sex, age, location, infiltration depth and lymph node metastasis (P >0.05). Conclusion The results indicated that XRCC 1 protein can be used as a marker to diagnose colorectal carcinoma.
3.Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery
Feng-mei LÜ ; Hui-min LIANG ; Li SUI ; Zhe-peng LIU
Acta Pharmaceutica Sinica 2022;57(2):500-506
The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.
4.Clinical study on the improvement of ischemia condition with stem cell transplantation in 122 cases necrosis of femoral head.
Xiao-Feng YANG ; Hong-Mei WANG ; Yi-Feng XU ; Yi-Bin ZANG ; Yan-Xiang WU ; Xin LÜ ; Nai-Wu LÜ ; Hong SHAN
Chinese Journal of Surgery 2007;45(20):1428-1431
OBJECTIVETo observe the curative effects of bone marrow stem cell (BMSC) and peripheral blood stem cell (PBSC) transplantations on the avascular necrosis of femoral head (ANFH).
METHODSTotally 122 ANFH patients (211 coxae) treated by BMSC or PBSC transplantations were enrolled from July 2004 to December 2006. All of them were classed to different stages according to the ARCO. Control group were desired as themselves before and after treatment. The puncture of femoral artery was conducted with digital subtraction angiography (DSA), and the tubes were inserted into medial femoral circumflex artery, lateral femoral circumflex artery and obturator artery with the cell suspensions were gradually poured into the arteries.
RESULTSThe joint pain, joint functions and walking distance of 122 patients were detected for the follow-up. Compared with before treatment, the calibers thickened; vessels increased and blood velocity quickened of femoral head blood-supply artery were observed in 15 patients after 6 months checked by DSA. The reduced areas of femoral head necrosis in 8 patients indicated the new bone formation between 12 and 24 months.
CONCLUSIONSAutologous BMSC and PBSC transplantation results in the new bone formation and improvement of ischemia in areas of femoral head necrosis at 6 months. The change of angiography was observed about 12 to 24 months after cell transplantation. The stem cell transplantation is convenient, safe and effective in the treatment of the ANFH with no adverse reaction, and can be considered as a new therapy of ANFH.
Bone Marrow Transplantation ; Femur Head ; blood supply ; pathology ; surgery ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Ischemia ; surgery ; Peripheral Blood Stem Cell Transplantation ; Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Treatment Outcome
5.Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities.
Tian-tian WANG ; Eldo E FREZZA ; Rong MA ; San-yuan HU ; Chong-zhong LIU ; Guang-yong ZHANG ; Mitchell S WACHTEL ; Xiao-mei LÜ ; Jin-bo FENG ; Cui-xia LÜ
Chinese Medical Journal 2008;121(20):1969-1974
BACKGROUNDWWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.
METHODSReverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.
RESULTSCompared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).
CONCLUSIONExpression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.
Acid Anhydride Hydrolases ; analysis ; genetics ; Breast ; pathology ; Breast Neoplasms ; genetics ; Chromosome Fragile Sites ; Female ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins ; analysis ; genetics ; Oxidoreductases ; analysis ; genetics ; Tumor Suppressor Proteins ; analysis ; genetics ; WW Domain-Containing Oxidoreductase
6.An introduction of different positioning tests of benign paroxysmal positional vertigo and their clinical values.
Xiao Feng MEI ; Shu Fang JI ; Xue Bing LÜ ; Liwen KUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2010;24(19):872-879
OBJECTIVE:
To explore the clinical value of different positioning tests for different benign paroxysmal positional vertigo (BPPV).
METHOD:
This research applies Dix-Hallpike test and Side-lying test for PC-BPPV, Roll test and WRW test for HC-BPPV, Dix-Hallpike test, Side-lying test and Rahko T maneuvers for SC-BPPV. Six hundred and thirteen cases, who were tested with different positioning tests in the sequence of firstly PC-BPPV then HC-BPPV and finally SC-BPPV, were randomly divided into 2 groups. The order of positioning tests for PC-BPPV and HC-BPPV in the two groups was reversed.
RESULT:
There's no significant difference between the detection rate of Dix-Hallpike test and Side-lying test for PC-BPPV (P > 0.05). Similarly, there's no difference in statistics between the detection rate of Roll test and WRW test for HC-BPPV (P > 0.05). However, the detection rate of Rahko T maneuver was higher than the other two tests for SC-BPPV and the differences were statistically significant (P < 0.05). The detection rates of different positioning tests for PC-BPPV and HC-BPPV between the two groups were not different in statistics (P > 0.05), which implies that the different order had no effect on the sensitivity of each positioning test.
CONCLUSION
Dix-Hallpike test is recommended as the first choice for PC-BPPV for its more efficient stimulus to the posterior semicircular canal, and Side-lying test is recommended as a prior choice to the patients with suspected PC-BPPV but unable to receive Dix-Hallpike test because of its similar sensitivity and more convenient manipulation. The detection rate of Both Roll test and WRW test were higher than 90% and there's no significant difference between the two tests. In addition, Roll test is easier to perform and helpful for the therapy, so its considered as the preferred test for HC-BPPV with WRW test as the supplement test. Nevertheless, for SC-BPPV the sensitivity of Rahko T maneuver was higher than that of the other two tests, so it can be used to confirm the suspected SC-BPPV patients detected or missed diagnosed by the two other tests. To avoid misdiagnosis or missed diagnosis, the judgment of affected semicircular canal is determined not only by positioning test but also by the feature of nystagmus.
Adolescent
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Adult
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Aged
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Benign Paroxysmal Positional Vertigo
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Female
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Humans
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Male
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Middle Aged
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Patient Positioning
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Retrospective Studies
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Vertigo
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diagnosis
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Young Adult
7.Media optimization for the novel antimicrobial peptide by Bacillus sp. fmbJ224.
Juan SHEN ; Zhao-Xin LU ; Xiao-Mei BIE ; Feng-Xia LÜ ; Xian-Qing HUANG
Chinese Journal of Biotechnology 2005;21(4):609-614
The novel antimicrobial peptide in submerged fermentation by Bacillus sp. fmbJ224 is strongly influenced by many internal and external factors, namely medium constituents and fermentation conditions. In this study, Plackett-Burman design was undertaken to evaluate the effects of the seventeen factors. By the statistical regression analysis, the significant factors affecting the novel antimicrobial peptide in submerged fermentation by Bacillus sp. fmbJ224 were determined as follows: glucose, NH4NO3, glutamic acid, CaCl2, MnSO4. In the second phase of the optimization process, a response surface methodology (RSM) was used to optimize the above critical internal factors, and to find out the optimization concentraction levels and the relationships between these factors. By solving the quadratic regression model equation using appropriate statistic methods, the optimal concentration of the variables were determined as: 8.13 g/L glucose, 6.14 g/L NH4NO3, 4.2 g/L glutamic acid, 3.98 mg/L CaCl2, 4.87 mg/L MnSO4. The content of the novel antimicrobial peptide was increased from 1304.21 microg/mL to 1487.58 microg/mL. The experimental data under various conditions have validated the theoretical values.
Anti-Infective Agents
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metabolism
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Bacillus
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growth & development
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metabolism
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Cell Culture Techniques
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methods
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Culture Media
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Fermentation
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Peptides
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metabolism
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Regression Analysis
8.Production of functional lipids by lipase-catalyzed acidolysis of lard in solvent free system.
Hai-Zhen ZHAO ; Zhao-Xin LU ; Xiao-Mei BIE ; Feng-Xia LÜ ; Zhan-Min LIU
Chinese Journal of Biotechnology 2005;21(3):493-496
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
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chemistry
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Catalysis
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Chromatography, High Pressure Liquid
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Dietary Fats
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metabolism
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Enzymes, Immobilized
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metabolism
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Lipase
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metabolism
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Lipids
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chemical synthesis
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Solvents
9.Identification of protein peroxiredoxin 2 related to crystalline NiS-induced neoplastic transformation.
Wei-dong JI ; Jia-kun CHEN ; Jia-chun LÜ ; Zhong-liang WU ; Su-mei FENG ; Fei YI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(4):267-270
OBJECTIVETo provide evidence for illustrating the molecular mechanism of nickel carcinogenesis, and to identify the differential expression of protein in crystalline NiS-induced neoplastic transformation of human bronchial epithelial cell by proteomics technology.
METHODSTwo dimensional electrophoresis (2-DE) and the ImageMaster 3.10 software were used to analyze the differential expression of protein, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) combined with database search was applied to identify protein peroxiredoxin 2 (PDX2) related to malignant transformation.
RESULTSThe good 2-DE pattern including resolution and reproducibility was obtained. Nearly 700 expressed proteins per 2-D gel were isolated with molecular weights (MW) ranging from 14,400 to 94,000 KD and pI 3 - 10. A protein PDX2 with MW 21,890 KD, pI 5.66, which was highly expressed in malignantly transformed cell, was identified using MALDI-TOF-MS.
CONCLUSIONPDX2 was involved in malignant transformation of human bronchial epithelial cell induced by crystalline nickel sulfide.
Bronchi ; cytology ; Cell Line ; Cell Transformation, Neoplastic ; chemically induced ; metabolism ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Nickel ; toxicity ; Peroxiredoxins ; metabolism ; Proteome
10.Isolation and identification of lipopeptides produced by Bacillus subtilis fmbJ.
Xiao-Mei BIE ; Feng-Xia LÜ ; Zhao-Xin LU ; Xian-Qing HUANG ; Juan SHEN
Chinese Journal of Biotechnology 2006;22(4):644-649
Isolation and idenfication of lipopeptides from Bacillus subtilis fmbJ was carried out in this paper. With HPLC method, it was determined that the antimicrobial substance was composed of many components, and one of them had the similar retention time similar to surfactin. In addition, the antimicrobial substance was proved to include the closed cycle peptide bind by TLC, and one of them had the migrating rate similar to surfactin. Furthermore, ESI-MS analysis showed that the antimicrobial substance contained five homologues of fengycin, such as m/z1449.9, m/zl1463.8, m/zl1477.8, m/z1491.9 and m/z1505.9, and three homologues of surfactin, such as m/z1008.8, m/z1022.8 and m/z1036.8.
Anti-Infective Agents
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chemistry
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isolation & purification
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Bacillus subtilis
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metabolism
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Chromatography, High Pressure Liquid
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Chromatography, Thin Layer
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Lipopeptides
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chemistry
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isolation & purification
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Spectrometry, Mass, Electrospray Ionization