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1.
Colloids Surf B Biointerfaces ; 236: 113803, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38367289

ABSTRACT

The core to the treatment of gout is the elimination of pathologic crystal, monosodium urate monohydrate (MSUM). The primary treatment available is to gradually dissolve the "culprit crystals" by lowering the blood uric acid concentration with medications, which often takes a long time and in severe cases must still be treated surgically. Herein, we developed a dynamic bionic platform based on a hydrogel composite membrane (HCM) to screen the direct facilitated solubilization of MSUM crystals by small organic molecules in bionic saturated, or even supersaturated, solutions. The customized and biologically safe (NAGA/PEGDA/NIPAM) HCM, which is consistent with the main amino acid composition of articular cartilage, well mimics the entire process of organic molecules leading to the dissolution of MSUM crystals in the joint system. With the verifications of this platform, it is shown that l-aspartic acid (ASP) significantly promotes the dissolution of MSUM crystals not only in saturated but also in supersaturated solutions. Furthermore, a novel mechanism called "crane effect" was used to explain this "dissolution effect" of ASP on MSUM, which stems from the ability of ASP to lock onto the surface of MSUM crystals through hydrogen bonding by virtue of its two carboxyl groups, and simultaneously its amino group lifts the uric acid molecules from the surface of MSUM crystals by virtue of interactions of hydrogen bonding. The results of bulk crystallization, scanning electron microscopy (SEM), powder X-diffraction (PXRD), and density-functional theory (DFT) studies are quantitatively consistent with this hypothetical "crane effect" mechanism. Hence, this HCM-based functional platform could provide entirely novel ideas and methods for drug design and screening for the treatment of pathological crystal diseases of gout.


Subject(s)
Gout , Uric Acid , Humans , Uric Acid/chemistry , Bionics , Gout/drug therapy , Gout/metabolism , Crystallization , Hydrogels
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(5): 534-538, 2017 May.
Article in Chinese | MEDLINE | ID: mdl-28506344

ABSTRACT

OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology. METHODS: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families. RESULTS: Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused early termination of translation and produced the truncated protein p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which caused the skipping of exon 15 and produced an incomplete amino acid chain. Their parents had normal gene phenotypes. CONCLUSIONS: c.931dupC and IVS14+1G>A are two novel mutations of the PHEX gene and might be the new pathogenic mutations of XLH.


Subject(s)
Familial Hypophosphatemic Rickets/genetics , Mutation , PHEX Phosphate Regulating Neutral Endopeptidase/genetics , Child , Child, Preschool , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Retrospective Studies
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(7): 1573-6, 2010 Jul.
Article in Chinese | MEDLINE | ID: mdl-20650769

ABSTRACT

OBJECTIVE: To observe the effect of 1,25(OH)2D3 on thyroid inflammation and Th1/Th2 cells in rats with experimental autoimmune thyroiditis (EAT). METHODS: Forty-eight female Wistar rats were randomly divided into 4 groups, namely the prevention group treated with 1, 25-(OH)2D3 from 0 to the 6th week (n=10), treatment group with 1,25(OH)2D3 treatment from the 2nd to the 8th week (n=10) after immune sensitization, positive control group (n=12) and the negative control group (n=16). All the rats were challenged with porcine thyroglobulin for immune sensitization until the 6th or 8th week except for those in the negative control group. In the prevention group and treatment group, the rats received 1,25(OH)2D3 at 5 microg/kg by intraperitoneal injection every other day, while those in the positive and negative control groups were given peanut oil instead. The thyroid pathologies, serum autoantibody level and cytokine levels were examined after the treatments. RESULTS: The thyroid gland remained structurally intact in the negative control group. In the positive control group, the thyroid showed obvious inflammatory change with structural disruption and even disappearance of the thyroid follicle. The structure of the thyroid gland follicles was intact in the prevention group and treatment group. No significant differences were found in the autoantibody and cytokine levels between the prevention group and negative control group (P>0.05). Compared with the positive control groups, the autoantibody and IFN-gamma and IL-12 levels decreased significantly in the treatment group, but the levels of IL-4 and IL-10 were markedly increased (P<0.05). CONCLUSION: 1,25(OH)2D3 given before the establishment of the EAT model helps maintain structural integrity of the thyroid gland and normal levels of the antibodies and cytokines in rats. 1,25(OH)2D3 can ameliorate the pathological changes of the thyroid gland and correct the cytokine disequilibrium in rats with EAT.


Subject(s)
Thyroiditis, Autoimmune/drug therapy , Thyroiditis, Autoimmune/metabolism , Vitamin D/analogs & derivatives , Animals , Autoantibodies/blood , Female , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-12/blood , Rats , Rats, Wistar , Th1 Cells/cytology , Th2 Cells/cytology , Vitamin D/therapeutic use
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