1.Application of hyaluronic acid microneedles in insulin intelligent delivery system for the treatment of diabetes.
Yongcheng XIAO ; Xiaobin WANG ; Deming XIE
Chinese Journal of Biotechnology 2022;38(9):3433-3442
In this study, insulin (insulin, INS)/Ca3PO4 complex and glucose oxidase (glucose oxidase, GOx)/Cu3(PO4)2 complex were prepared by coprecipitation method. The mineralized insulin (mineralized insulin, m-INS) showed irregular crystalline clusters, and the mineralized glucose oxidase (m-GOx) showed flower spherical morphology, with a diameter of about 1-2 μm. In vitro simulated release experiment showed that m-INS released INS as the pH value of the medium decreased. When the pH value was 4.5, the release amount reached 96.68%. The enzyme activity detection experiment showed that the enzyme activity stability of m-GOx was higher than that of free GOx. It still maintained high activity after 10 days at room temperature, while the activity of GOx was less than 60%. The glucose solution was prepared to simulate the state of normal blood glucose (5.6 mmol/L) and hyperglycemia (22.2 mmol/L). When m-INS and m-GOx were added to the glucose solution, the release amount of INS showed a significant glucose concentration dependence. The higher the glucose concentration, the greater the release amount and release rate of INS. Finally, m-INS, m-GOx and hyaluronic acid (HA) solution were mixed to prepare HA microneedle arrays loaded with m-INS and m-GOx. Type 1 diabetes mice were constructed to evaluate the effect of drug-loaded HA microarray on blood glucose control in diabetic rats. The results show that the HA microneedles loaded with m-INS/m-GOx could deliver drugs effectively. The average blood glucose concentration in diabetic rats dropped to about 7 mmol/L within 1 h, normal blood glucose concentration could be maintained for 10 h, and the overall blood glucose concentration was lower than the level before administration for 36 hours. Compared with HA microneedles loaded with INS only, m-ins microneedles showed better glucose tolerance, longer-lasting glucose control effect and less risk of hypoglycemia. Compared with other sustained-release systems, the preparation process of the core components in this study is simple, efficient, safe and effective, and has great commercial potential.
Animals
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Blood Glucose
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Delayed-Action Preparations/therapeutic use*
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Diabetes Mellitus, Experimental/drug therapy*
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Drug Delivery Systems/methods*
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Glucose Oxidase/chemistry*
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Hyaluronic Acid
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I Blood-Group System
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Insulin/therapeutic use*
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Mice
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P Blood-Group System
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Rats
2.Serological and genetic study of a pedigree featuring a rare p phenotype.
Ling WEI ; Yan-li JI ; Hong LUO ; Chun-yan MO ; Run-qing ZHANG ; Yang ZHAO ; Zhen WANG ; Guang-ping LUO
Chinese Journal of Medical Genetics 2012;29(6):701-704
<p>OBJECTIVETo explore genetic background of a pedigree with a rare p phenotype from Guangdong province.p><p>METHODSThe rare p phenotype was identified by a conventional serologic method. With genomic DNA of proband and family members extracted, exon 3 of alpha-(1,4)galactosyltransferase (A4GALT) gene was amplified with PCR and analyzed by direct sequencing. The mutation found in the pedigree was screened in a normal population using direct sequencing.p><p>RESULTSThe proband and 4 family members with the rare p phenotype have all carried a point mutation c.100G>A (p.Val34Ile) in combination with a deletion-insertional mutation c.418_428del11ins34(p.Gln139Trpfs*72), which renders a compound mutation of A4GALT gene. One family member with P2 phenotype has carried a same heterozygous mutation. Of the 100 healthy donors, 5 have carried a heterozygous point mutation c.100G>A, and none carried the deletion-insertional mutation c.418_428del11ins34.p><p>CONCLUSIONThe rare p phenotype of the pedigree has resulted from a compound mutation of the A4GALT gene, which is in keeping with a recessive inheritance pattern of the p phenotype.p>
Adult
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Base Sequence
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Blood Grouping and Crossmatching
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Exons
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Female
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Galactosyltransferases
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genetics
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Genotype
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Humans
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Mutation
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P Blood-Group System
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genetics
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immunology
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Pedigree
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Phenotype
3.Anti-PP₁P(k) (Tj(a)) Antibody in a Korean Female Patient with p Phenotype Confirmed by Genotyping
Boyeon KIM ; Seung Jun CHOI ; Duck CHO ; Sinyoung KIM ; Hyun Ok KIM
Laboratory Medicine Online 2020;10(1):84-87
P(k) (Tj(a)) alloantibody with p phenotype detected and confirmed in a 20-year-old Korean woman diagnosed with anemia during long-term rehabilitation treatment due to mental retardation. She did not have any transfusion history, except two exchange transfusions received 6 days after she was born. Her blood type was B, RhD+, and findings from antibody screening and identification tests showed strong reactivity (3+ to 4+) in all panel cells except in her autologous cells. Based on these results, we concluded that she had an alloantibody to a high-prevalence antigen. Anti-PP₁P(k) alloantibody with p phenotype was identified by additional serological tests in a foreign reference laboratory. To confirm the patient's p phenotype, polymerase chain reaction and sequencing of the A4GALT gene were performed on her blood sample. She was homozygous for c.301delG in the A4GALT gene, which finally confirmed that she had the anti-PP₁P(k) antibody with p phenotype. Fortunately, her anemia caused due to iron deficiency could be treated with iron supplementation without the need for any transfusion. However, it remains extremely difficult to find compatible red blood cells in such settings in Korea. Moreover, there has been very little research on the prevalence of the p phenotype in the Korean population. Therefore, additional research is needed on rare blood group antibodies and high-prevalence antigens, including anti-PP₁P(k) cases.]]>
Anemia
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Antibodies
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Blood Transfusion
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Erythrocytes
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Female
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Humans
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Intellectual Disability
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Iron
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Isoantibodies
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Korea
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Mass Screening
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P Blood-Group System
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Phenotype
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Polymerase Chain Reaction
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Prevalence
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Rehabilitation
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Serologic Tests
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Young Adult
4.Association of polymorphism of the prostacyclin synthase gene with myocardial infarction in Uigur population of Xinjiang.
Xiang XIE ; Yitong MA ; Zhenyan FU ; Yining YANG ; Yinghong WANG ; Bangdang CHEN ; Fen LIU
Chinese Journal of Medical Genetics 2008;25(6):708-711
<p>OBJECTIVETo investigate the association between the polymorphism of the prostacyclin synthase gene and Uigur patients with myocardial infarction in Xinjiang.p><p>METHODSThree hundred and ten patients with myocardial infarction (MI) and 306 healthy control subjects were detected by polymerase chain reaction and restriction fragment length polymorphism. The serum 6-keto-PGF(1alpha ) was detected with radioimmunoassay kit in all subjects.p><p>RESULTSThe genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium(chi (2)= 0.442, 1.867, P> 0.05). The frequencies of CC, CA and AA were 0.70, 0.26 and 0.03 in the MI group and 0.62, 0.32 and 0.06 in the controls. There was significant difference in frequencies of CC genotype and C allele but no difference in frequencies of CA and AA genotypes between the controls and the MI cases. There was significant difference in serum 6-keto-PGF(1alpha ) level between the MI group and control group (P< 0.05), as well as among the three genotypes (P< 0.05). In the cases with CC genotype the serum 6-keto-PGF(1alpha ) level was lower than that of others (P< 0.05).p><p>CONCLUSIONThe CC genotype and C allele of the prostacyclin synthase gene might be a risk factor of MI in Uigur population in Xinjiang, which may lead to the decreased serum 6-keto-PGF(1alpha ) level.p>
6-Ketoprostaglandin F1 alpha
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blood
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Asian Continental Ancestry Group
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genetics
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Base Sequence
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Case-Control Studies
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Cytochrome P-450 Enzyme System
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genetics
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Ethnic Groups
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genetics
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Exons
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genetics
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Female
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Gene Frequency
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Genotype
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Humans
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Intramolecular Oxidoreductases
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genetics
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Logistic Models
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Male
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Middle Aged
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Myocardial Infarction
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blood
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genetics
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Polymorphism, Genetic