Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 30
Filter
Add more filters

Publication year range
1.
Sensors (Basel) ; 21(1)2020 Dec 22.
Article in English | MEDLINE | ID: mdl-33375146

ABSTRACT

Sensitivity and reliability are essential factors for the practical implementation of a wearable sensor. This study explores the possibility of using a hybrid high-resolution Bragg grating sensor for achieving a fast response to dynamic, continuous motion and Bragg signal pattern monitoring measurement. The wavelength shift pattern for real-time monitoring in picometer units was derived by using femtosecond laser Bragg grating processing on an optical wave path with long-period grating. The possibility of measuring the demodulation system's Bragg signal pattern on the reflection spectrum of the femtosecond laser precision Bragg process and the long-period grating was confirmed. By demonstrating a practical method of wearing the sensor, the application of wearables was also explored. It is possible to present the applicability of sophisticated micro transformation measurement applications in picometer units.


Subject(s)
Fiber Optic Technology , Optical Fibers , Lasers , Reproducibility of Results
2.
BMC Genomics ; 20(1): 514, 2019 Jun 21.
Article in English | MEDLINE | ID: mdl-31226927

ABSTRACT

BACKGROUND: Polyploidization, pervasive among higher plant species, enhances adaptation to water deficit, but the physiological and molecular advantages need to be investigated widely. Long non-coding RNAs (lncRNAs) are involved in drought tolerance in various crops. RESULTS: Herein, we demonstrate that tetraploidy potentiates tolerance to drought stress in cassava (Manihot esculenta Crantz). Autotetraploidy reduces transpiration by lesser extent increasing of stomatal density, smaller stomatal aperture size, or greater stomatal closure, and reducing accumulation of H2O2 under drought stress. Transcriptome analysis of autotetraploid samples revealed down-regulation of genes involved in photosynthesis under drought stress, and less down-regulation of subtilisin-like proteases involved in increasing stomatal density. UDP-glucosyltransferases were increased more or reduced less in dehydrated leaves of autotetraploids compared with controls. Strand-specific RNA-seq data (validated by quantitative real time PCR) identified 2372 lncRNAs, and 86 autotetraploid-specific lncRNAs were differentially expressed in stressed leaves. The co-expressed network analysis indicated that LNC_001148 and LNC_000160 in autotetraploid dehydrated leaves regulated six genes encoding subtilisin-like protease above mentioned, thereby result in increasing the stomatal density to a lesser extent in autotetraploid cassava. Trans-regulatory network analysis suggested that autotetraploid-specific differentially expressed lncRNAs were associated with galactose metabolism, pentose phosphate pathway and brassinosteroid biosynthesis, etc. CONCLUSION: Tetraploidy potentiates tolerance to drought stress in cassava, and LNC_001148 and LNC_000160 mediate drought tolerance by regulating stomatal density in autotetraploid cassava.


Subject(s)
Acclimatization/genetics , Manihot/genetics , RNA, Long Noncoding/physiology , RNA, Plant/physiology , Droughts , Gene Expression Profiling , Gene Expression Regulation, Plant , Manihot/physiology , Photosynthesis/genetics , Plant Stomata/genetics , Plant Stomata/physiology , Stress, Physiological , Tetraploidy
3.
Phytother Res ; 32(12): 2560-2567, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30306659

ABSTRACT

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection-induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.


Subject(s)
Antiviral Agents/pharmacology , Berberine/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Virus Replication/drug effects , A549 Cells , Animals , Antiviral Agents/therapeutic use , Berberine/therapeutic use , Chick Embryo , Humans , Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/virology , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections/diagnosis , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumonia/virology , Prognosis , Signal Transduction/drug effects
4.
Breed Sci ; 68(2): 227-232, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29875606

ABSTRACT

Apomixis, or asexual seed formation, is of great value for plant breeding and seed production, and is desirable in modern agriculture, but natural apomixis occurs in cassava at very low frequency. In present study, apomixis was induced by the treatments of female flower buds with 1%, 1.5% and 2% (v/v) dimethyl sulfoxide (DMSO) and the results showed that 1.5% DMSO treatment was most effective for the induction of apomictic seed formation in cassava cultivar SC5 with the highest percentages of fruit set and true apomictic seeds. The germinated seedlings resembled their parents and displayed no morphological characteristics of cassava polyploid. Flow cytometry and chromosome counting showed that these plants were uniform diploids. Analysis of 34 DMSO-induced cassava progenies by the expressed sequence tag-simple sequence repeat (EST-SSR) and sequence-related amplified polymorphism (SRAP) markers showed that three true apomictic seeds were obtained from the group of SC5 treated with 1.5% DMSO.

5.
Phytopathology ; 105(12): 1612-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26606587

ABSTRACT

A new method of direct detection of pathogenic fungi in infected soybean tissues has been reported here. The method rapidly diagnoses soybean seedling blight caused by Rhizoctonia solani and soybean charcoal rot caused by Macrophomina phaseolina, and features loop-mediated isothermal amplification (LAMP). The primers were designed and screened using internal transcribed spacers (ITS) as target DNAs of both pathogens. An ITS-Rs-LAMP assay for R. solani and an ITS-Mp-LAMP assay for M. phaseolina that can detect the pathogen in diseased soybean tissues in the field have been developed. Both LAMP assays efficiently amplified the target genes over 60 min at 62°C. A yellow-green color (visible to the naked eye) or intense green fluorescence (visible under ultraviolet light) was only observed in the presence of R. solani or M. phaseolina after addition of SYBR Green I. The detection limit of the ITS-Rs-LAMP assay was 10 pg µl⁻¹ of genomic DNA; and that of the ITS-Mp-LAMP assay was 100 pg µl⁻¹ of genomic DNA. Using the two assays described here, we successfully and rapidly diagnosed suspect diseased soybean samples collected in the field from Jiangsu and Anhui provinces.


Subject(s)
Glycine max/microbiology , Nucleic Acid Amplification Techniques , Rhizoctonia/isolation & purification , Plant Diseases , Rhizoctonia/genetics , Seedlings/microbiology
6.
Hepatogastroenterology ; 61(136): 2395-401, 2014.
Article in English | MEDLINE | ID: mdl-25699390

ABSTRACT

The present study aimed to investigate the mechanism and the possible approaches of solving drug resistance by silencing hypoxia-inducible factor-1 alpha of human pancreatic cancer cell line Patu8988/5-Fu cultured in hypoxia. The effective jamming fragment screened by RT-PCR for silencing HIF-1α gene was transfected into pancreatic cancer cells Patu8988/5-Fu through lentivirus. RT-PCR results showed that the effective jamming fragments for HIF-1α in lentivirus transfection was Wtl-mus-1202(C546). Combined MTT with JC-1 fluorescence staining flow cytometric analysis, the concentration of 200 µmol/L CoCl2 for 8 h was chosen to mimic hypoxia cell environment. The drug resistance significantly enhanced in response to hypoxia in Patu8988/5-Fu (p<0.05), and silence HIF-1α could reverse the multidrug resistance (P<0.05). In the Patu8988/5-Fu cells, HIF-1α and MDR1 significantly increased in response to hypoxia (p<0.05). The inhibition of HIF-1α expression synergistically downregulated the expression of the MDR1 gene in Patu8988/5-Fu cells (p<0.05). HIF-1α expression was positively correlated with the MDR1 expression (p<0.05). The upregulation of the HIF-1α and MDR1 gene expression caused by hypoxia was related with the generation of multi-drug resistance of Patu8988/5-Fu, targeted silencing HIF-1α may be a kind of way to reverse the chemotherapy drug resistance.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/physiology , Pancreatic Neoplasms/drug therapy , ATP Binding Cassette Transporter, Subfamily B/genetics , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Fluorouracil/therapeutic use , Gene Silencing , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Pancreatic Neoplasms/pathology
7.
Nature ; 450(7169): E12-4, 2007 Nov 22.
Article in English | MEDLINE | ID: mdl-18004280

ABSTRACT

Somatic cell nuclear transfer (SCNT) into enucleated oocytes has emerged as a technique that can be used to derive mouse embryonic stem cell lines with defined genotypes. In this issue Byrne et al. report the derivation of two SCNT Rhesus macaca male stem cell lines designated CRES-1 and CRES-2. Molecular studies detailed in their paper provides supporting evidence that the chromosome complement of CRES-1 and CRES-2 was genetically identical to the male cell donor nucleus and that the mitochondrial DNA originated from different recipient oocytes. In this validation paper, we independently confirm that both stem cell lines were indeed derived by SCNT.


Subject(s)
Macaca mulatta/genetics , Nuclear Transfer Techniques , Pluripotent Stem Cells/metabolism , Animals , Cell Line , Female , Genetic Markers/genetics , Genotype , Humans , Male , Polymorphism, Single Nucleotide/genetics , Reproducibility of Results
8.
Sheng Li Ke Xue Jin Zhan ; 44(4): 281-6, 2013 Aug.
Article in Zh | MEDLINE | ID: mdl-24228520

ABSTRACT

Cell death is one of the basic life properties. A new type of cell death named necroptosis was discovered and became increasingly noticed attention in recent years. Necroptosis has similar morphological characteristics with cell necrosis and is controlled by special signal pathways. The interaction of the receptor interacting protein 1 (RIP1) and 3 (RIP3) plays a crucial important role in the necroptosis signal pathway. The RIP1 determines whether a cell goes survival and death, and the RIP3 determines the pathway of cell death apoptosis or necrosis. This paper summarizes the knowledge about the necroptosis signal pathways and explores its significance in the organ ischemic injury, inflammation and tumor pathogenesis briefly.


Subject(s)
Apoptosis , Necrosis , Receptor-Interacting Protein Serine-Threonine Kinases/physiology , Humans , Inflammation , Signal Transduction
9.
Exp Ther Med ; 25(5): 200, 2023 May.
Article in English | MEDLINE | ID: mdl-37090080

ABSTRACT

The serology test of SARS-CoV-2 is one of the critical assays to make a diagnosis of SARS-CoV-2 infection. The gold immunochromatography assay (GICA) is a common measure to test SARS-CoV-2 specific IgG and IgM. The sensitivity and specificity of the assay are ~>80%. It has been reported that the result of GICA could be compromised in various situations, such as auto-immune diseases, Kawasaki disease, pregnancy or other conditions. However, following the European Hematology Association's consensus statement on the management of Waldenström's Macroglobulinemia (WM) patients, serological tests for SARS-CoV-2 specific IgM should not be affected by the total IgM or paraprotein levels. The present study reports a patient with duplicate positive serology tests of SARS-CoV-2 which is hypothesized to be due to monoclonal IgM caused by WM.

10.
J Am Soc Nephrol ; 22(7): 1213-20, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21566060

ABSTRACT

Glomerular injury and podocyte loss leads to secondary tubulointerstitial damage and the development of fibrosis. The possibility of genetically reprogramming adult cells, termed induced pluripotent stem cells (iPS), may pave the way for patient-specific stem-cell-based therapies. Here, we reprogrammed normal human mesangial cells to pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4 and c-Myc). The kidney iPS (kiPS) cells resembled human embryonic stem-cell-like colonies in morphology and gene expression: They were alkaline phosphatase-positive; expressed OCT3/4, TRA-1 to 60 and TRA-1 to 81 proteins; and showed downregulation of mesangial cell markers. Quantitative (qPCR) showed that kiPS cells expressed genes analogous to embryonic stem cells and exhibited silencing of the retroviral transgenes by the fourth passage of differentiation. Furthermore, kiPS cells formed embryoid bodies and expressed markers of all three germ layers. The injection of undifferentiated kiPS colonies into immunodeficient mice formed teratomas, thereby demonstrating pluripotency. These results suggest that reprogrammed kidney induced pluripotent stem cells may aid the study of genetic kidney diseases and lead to the development of novel therapies.


Subject(s)
Induced Pluripotent Stem Cells , Kidney/cytology , Mesangial Cells/physiology , Adolescent , Animals , Cell Differentiation , Cells, Cultured , Gene Transfer Techniques , Humans , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , Male , Octamer Transcription Factor-3/genetics , Proto-Oncogene Proteins c-myc/genetics , SOXB1 Transcription Factors/genetics
11.
Sheng Li Ke Xue Jin Zhan ; 43(1): 11-6, 2012 Feb.
Article in Zh | MEDLINE | ID: mdl-22582592

ABSTRACT

Organic anion transporters (OATs) belong to a family of poly-specific transporters mainly located in barrier epithelia such as renal proximal tubule, brain, liver and placenta. OATs interact with endogenous metabolic end products such as urate and acidic neutrotransmitter metabolites, as well as with a multitude of widely used drugs, including antibiotics, diuretics, antihypertensives and anti-inflammatory drugs. Thereby, OATs play an important role in renal drug elimination and have an impact on pharmacokinetics. This review summarizes current knowledge of the properties and functional roles of the cloned OAT family members detailed in tissue differences in expression and physiologic function, drug-drug interactions, and finally, gender-dependent regulation in health and diseased states.


Subject(s)
Organic Anion Transporters/physiology , Animals , Anti-Bacterial Agents/pharmacokinetics , Antihypertensive Agents/pharmacokinetics , Diuretics/pharmacokinetics , Humans , Kidney Tubules, Proximal/metabolism , Liver/metabolism , Organic Anion Transporters/genetics , Organic Anion Transporters/metabolism , Uric Acid/metabolism
12.
Nuklearmedizin ; 50(3): 116-21, 2011.
Article in English | MEDLINE | ID: mdl-21246162

ABSTRACT

UNLABELLED: The AIM of this study was to evaluate the prognostic significance of maximum standardized uptake value (SUVmax) of primary cutaneous malignant melanoma (CMM) lesions by (18)F-FDG positron emission tomography/computerized tomography (PET/CT) in terms of recurrence. PATIENTS, METHODS: 37 CMM patients (17 men, mean age: 61.7 ± 13.6 years) that underwent PET/CT at presentation were enrolled in this study. Recurrence was determined by histological confirmation or by radiological and clinical follow-up for at least 8 months after curative surgery. Clinical variables such as age, sex, clinical stage, and primary lesion location, thickness, and ulceration, and SUVmax values were analyzed with respect to their usefulness for predicting recurrence. RESULTS: SUVmax was found to be significantly higher in patients with ulceration of primary lesion of CMM (p = 0.004) and in patients with a stage ≥ III (p < 0.000). Patients that experience recurrence had a significantly higher mean SUVmax value (4.9 ± 2.9) than patients who did not (2.1 ± 1.5, p = 0.024). ROC analysis showed that a SUVmax cut-off value 2.2 had high sensitivity (88.9%) and specificity (67.9%) for predicting recurrence. Kaplan-Meier analysis identified ulceration of primary lesion (p = 0.034), stage ≥ III (p = 0.019) and SUVmax ≥ 2.2 (p = 0.002) as predictors of recurrence. However, Cox proportional-hazards analysis showed that only SUVmax (p = 0.025, relative risk 11.063) significantly predicted recurrence. CONCLUSION: Preoperative SUVmax of primary lesion was found to be the most potent predictor of recurrence in CMM patient. Patients with high SUV max of primary lesion should be followed meticulously for recurrence.


Subject(s)
Fluorodeoxyglucose F18 , Melanoma/diagnosis , Neoplasm Recurrence, Local/diagnosis , Positron-Emission Tomography/methods , Skin Neoplasms/diagnosis , Tomography, X-Ray Computed/methods , Female , Humans , Male , Melanoma/therapy , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Skin Neoplasms/therapy , Subtraction Technique , Treatment Outcome
13.
Ann Plast Surg ; 65(3): 326-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20661129

ABSTRACT

Reconstruction of the large lumbar defect is a challenge for plastic surgeons. We report our experience with the reverse latissimus dorsi myocutaneous flap for the coverage of large lumbar wounds in 2 oncologic patients. Meanwhile, a pedicled ascending scapular flap was used to aid the donor closure of the musculocutaneous flap. This allows for easy closure of both the donor sites and reduces the donor site morbidity to the minimum. The procedure is highly reliable, and in our opinion, the first option in reconstruction of large lumbar defects, particularly when a large surface coverage is needed.


Subject(s)
Lumbosacral Region/surgery , Muscle, Skeletal/transplantation , Plastic Surgery Procedures/methods , Surgical Flaps , Adult , Back/surgery , Female , Humans , Middle Aged , Muscle, Skeletal/surgery , Treatment Outcome
14.
15.
Article in English | MEDLINE | ID: mdl-32184895

ABSTRACT

BACKGROUND: Abelmoschus manihot (L.) Medic flower is a medicinal plant for the treatment of diseases in China. The present study was carried out to scientifically validate the gastroprotective activity and clarify the possible mechanism of the total flavones from Abelmoschus manihot (L.) Medic flower is a medicinal plant for the treatment of diseases in China. The present study was carried out to scientifically validate the gastroprotective activity and clarify the possible mechanism of the total flavones from. METHODS: Gastric ulcer was induced in mice by oral administration of ethanol. The gastroprotective activity of TFA was evaluated by the gastric ulcer index and histological examinations. The gastric tissue was collected in the form of homogenate. The level of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD), and protein content were measured. Western blotting for the expression of Bax, Bcl-2, TNF-α, and NF-κB(p65) was also carried out. The effect of TFA was compared with that of standard antiulcer drug omeprazole (100 mg/kg). RESULTS: This gastroprotective effect of TFA could be attributed to the increase in the activity of SOD and GSH and decrease in the levels of MDA and also decrease in the levels of Bax, TNF-α, and NF-κB(p65) was also carried out. The effect of TFA was compared with that of standard antiulcer drug omeprazole (100 mg/kg). CONCLUSION: The findings of this study demonstrated that TFA could significantly attenuate ethanol-induced gastric injury via antioxidative, anti-inflammatory, and antiapoptotic effects.

16.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 9): o2187, 2009 Aug 19.
Article in English | MEDLINE | ID: mdl-21577591

ABSTRACT

In the title compound, C(11)H(17)ClNO(+)·Cl(-), the side chain of the ethyl-amine group is orientated approximately perpendicular to the benzene ring, the dihedral angle between the C/C/N plane of the ethyl-amine group and the benzene plane being 83.5 (3)°. In the crystal structure, inter-molecular O-H⋯Cl and N-H⋯Cl hydrogen bonds are observed. The crystal studied was an inversion twin with a 0.51 (10):0.49 (10) domain ratio.

17.
Hum Reprod ; 23(8): 1748-59, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18477572

ABSTRACT

BACKGROUND: Currently there are no markers fully predictive of developmental competence of human IVF embryos. The present study investigated a novel strategy involving blastocyst biopsy and DNA fingerprinting to link developmental competence with gene expression patterns. METHODS: Patient's blastocysts were biopsied to remove 8-20 trophectoderm (TE) cells for molecular analysis prior to transfer. Biopsy samples were amplified and gene expression was evaluated using microarrays. Sibling TE biopsies and cells from resulting offspring were subjected to DNA fingerprinting to identify which blastocyst(s) in the transfer cohort developed to term. RESULTS: Blastocyst biopsy did not appear to impair developmental competence. Comparative microarray analysis of cDNA from pooled 'viable' and 'non-viable' TE samples identified over 7000 transcripts expressed exclusively in 'viable' blastocysts. The most significant of these included transcripts involved in cell adhesion and cell communication, key processes that have been associated with mammalian implantation. DNA fingerprinting of three cohorts of sibling blastocysts identified those blastocyst(s) that produced term pregnancies. CONCLUSIONS: The combination of blastocyst biopsy, microarray gene expression profiling and DNA fingerprinting is a powerful tool to identify diagnostic markers of competence to develop to term. This strategy may be used to develop a rapid diagnostic assay or for refining existing criteria for the selection of the single most viable blastocyst among a cohort developing in vitro.


Subject(s)
Blastocyst/physiology , Embryonic Development/physiology , Fertilization in Vitro/methods , Biopsy , DNA Fingerprinting , Embryo Culture Techniques , Embryo Implantation , Female , Gene Expression Profiling , Gene Expression Regulation, Developmental , Humans , Pregnancy
18.
Hum Reprod ; 23(5): 1138-44, 2008 May.
Article in English | MEDLINE | ID: mdl-18346995

ABSTRACT

BACKGROUND: Immature human oocytes matured in vitro, particularly those from gonadotrophin stimulated ovaries, are developmentally incompetent when compared with oocytes matured in vivo. This developmental incompetence has been explained as poor oocyte cytoplasmic maturation without any determination of the likely molecular basis of this observation. METHODS: Replicate whole human genome arrays were generated for immature and mature oocytes (matured in vivo and in vitro, prior to exposure to sperm) recovered from women undertaking gonadotrophin treatment for assisted reproduction. RESULTS: More than 2000 genes were identified as expressed at more than 2-fold higher levels in oocytes matured in vitro than those matured in vivo (P < 0.05, range 4.98 x 10(-2) -2.22 x 10(-4)) and 162 of these are expressed at 10-fold or greater levels (P < 0.05, range 4.98 x 10(-2)-1.38 x 10(-3)). Many of these genes are involved in transcription, the cell cycle and its regulation, transport and cellular protein metabolism. CONCLUSIONS: Global gene expression profiling using microarrays and bioinformatics analysis has provided a molecular basis for differences in the developmental competence of oocytes matured in vitro compared with in vivo. The over-abundance of transcripts identified in immature germinal vesicle stage oocytes recovered from gonadotrophin stimulated cycles and matured in vitro is probably due to dysregulation in either gene transcription or post-transcriptional modification of genes. Either mechanism would result in an incorrect temporal utilization of genes which may culminate in developmental incompetence of any embryos derived from these oocytes.


Subject(s)
Gene Expression Profiling , Oocytes/physiology , Female , Genome, Human/physiology , Humans , In Vitro Techniques , Oligonucleotide Array Sequence Analysis , Superovulation
19.
Yao Xue Xue Bao ; 40(10): 950-3, 2005 Oct.
Article in Zh | MEDLINE | ID: mdl-16408816

ABSTRACT

AIM: To survey the uptake behavior and subcellular distribution of antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer its mechanism in MGC cell lines. METHODS: MGC cells were incubated at certain concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C. Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow cytometer and the intracellular fluorescence intensity was determined after incubated with chloroquine for 2 h. RESULTS: Cellular uptake of oligodeoxynucleotides was significantly increased following application of AS-ODN-SMP and total intracellular fluorescence intensity was enhanced by 683 folds with the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells profoundly with temperature-dependent manner. Rare cells took on fluorescence when incubated at 4 degrees C, while 37 degrees C they were significantly increased. But the intracellular fluorescence intensity appeared same level in present or absent of chloroquine. CONCLUSION: With the help of polyacrylate submicroparticles, oligonucleotides efficiently entranced the cells via endocytosis and could successfully escape the degradation in lysosome.


Subject(s)
Drug Delivery Systems , Endocytosis/drug effects , Giant Cells/cytology , Oligodeoxyribonucleotides, Antisense , Polymethacrylic Acids/pharmacology , Animals , Cell Line , Drug Carriers , Lysosomes/metabolism , Nanoparticles , Oligodeoxyribonucleotides, Antisense/administration & dosage , Oligodeoxyribonucleotides, Antisense/pharmacokinetics , Particle Size , Polymethacrylic Acids/chemistry , Temperature
20.
J Drug Target ; 10(3): 239-45, 2002 May.
Article in English | MEDLINE | ID: mdl-12075825

ABSTRACT

Human basic fibroblast growth factor (bFGF) is a potent neuroprotective agent. The clinical efficacy of this neurotrophin, however, is restricted by poor permeability across the blood-brain barrier (BBB). This study was designed to test the hypotheses that bFGF will retain its biological activity and have an enhanced BBB transport after re-formulation and conjugation to a BBB peptide drug delivery vector. The BBB delivery vector is comprised of a conjugate of streptavidin (SA) and the murine OX26 monoclonal antibody against the rat transferrin receptor, and the conjugate of biotinylated bFGF (bio-bFGF) bound to a vector is designated bio-bFGF/OX26-SA. A radioreceptor binding assay shows that the native bFGF, bio-bFGF, and bio-bFGF/OX26-SA conjugate have IC50 values of 0.12, 0.40, and 0.56 nM, respectively. After an IV bolus injection to the rat, [125I]-bio-bFGF is avidly taken up by peripheral organs, with low brain uptake at 60 min, 0.010+/-0.004% of injected dose (ID)/g brain. By contrast, the brain uptake of the [125I]-bio-bFGF/OX26-SA is increased 5-fold to 0.050+/-0.011%ID/g, although the uptake of the conjugate by peripheral tissues was decreased relative to the unconjugated bio-bFGF. In conclusion, conjugation of bio-bFGF to a BBB drug delivery vector (a) causes only a minor decrease in affinity for the bFGF receptor, (b) decreases the peripheral organ uptake of the bFGF, and (c) increases the brain uptake of the neurotrophin. The re-formulation of bFGF to enable receptor-mediated transcytosis across the BBB may improve the therapeutic index of this neurotrophin as a neuroprotective agent.


Subject(s)
Blood-Brain Barrier/physiology , Brain/metabolism , Drug Delivery Systems/methods , Fibroblast Growth Factor 2/pharmacokinetics , Algorithms , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/pharmacokinetics , Area Under Curve , Binding Sites , Biotinylation/methods , Blood-Brain Barrier/drug effects , Brain/drug effects , Carotid Arteries , Fibroblast Growth Factor 2/administration & dosage , Fibroblast Growth Factor 2/chemistry , Humans , Infusions, Intra-Arterial , Iodine Radioisotopes , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Male , Mice , Myocardium/metabolism , Nerve Growth Factors/metabolism , Radioligand Assay , Rats , Rats, Sprague-Dawley , Receptors, Transferrin/immunology , Streptavidin/administration & dosage , Streptavidin/chemistry , Streptavidin/pharmacokinetics , Tissue Distribution
SELECTION OF CITATIONS
SEARCH DETAIL