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TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism
Zhang Hai-Yang,Wu Feng-Yao,Li Xue-Song,Tu Ping-Hui,Zhang Cao-Xu,Yang Rui-Meng,Cui Ren-Jie,Wu Chen-Yang,Fang Ya,Yang Liu,Song Huai-Dong,Zhao Shuang-Xia 대한진단검사의학회 2024 Annals of Laboratory Medicine Vol.44 No.4
Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.
Sheng-hai Zhang,Ying-zi Wang,Fan-yun Meng,You-lin Li,Cai-xia Li,Fei-peng Duan,Qing Wang,Xiu-ting Zhang,Chun-ni Zhang 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5
Flavonoid glycosides are metabolized byintestinal bacteria, giving rise to a wide range of phenolicacids that may exert systemic effects in the body. Themicrobial metabolism of flavonoids extracted from theleaves of Diospyros kaki (FLDK) by intestinal bacteria wasinvestigated in vitro. High-performance liquid chromatography/linear trap quadrupole orbitrap mass spectrometrywas performed to analyze the metabolites of flavonoidsin vivo using Xcalibur2.1 software. The results showed thatthe levels of flavonoid glycosides and flavonoid aglyconesdecreased rapidly in the process of microbial metabolismby intestinal bacteria in vitro, and the metabolic rate maybe related to the concentration of intestinal bacteria in theculture solution. In vivo metabolites of FLDK weredetected in rat plasma and urine after oral administration ofFLDK. Eight flavonoids were identified in the urine, andthree were identified in the plasma; however, flavonoidaglycones were not found in the plasma.
Zhang, Yu,Yu, Li-Ke,Lu, Guo-Jun,Xia, Ning,Xie, Hai-Yan,Hu, Wei,Hao, Ke-Ke,Xu, Chun-Hua,Qian, Qian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19
Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.
Zhang Jun Qing,Duan Jin Ao,Wang Yong,Li Yong Hui,Lai Wei Yong,Li Hai Long,Pei Li Xia 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.12
Chemical investigation of the fruits of Alpinia oxyphylla led to an isolation of the two new natural products, 9-hydroxy epinootkatol (1) and (S)-2-pentanol-2-O-β-D-glucopyranoside (2), in addition to the nine known compounds, pinocembrin (3), tectochrysin (4), izalpinin (5), nookatone (6), yakuchinone A (7), protocatechuic acid (8), β-sitosterol (9), daucosterol (10) and β-sitosterol palmitate (11). Their structures were elucidated on the basis of physicochemical constants and NMR spectral data analysis. The effects of the isolated components on nitric oxide production in LPS-induced RAW 264.7 macrophages were examined. The two new natural compounds showed inhibitory activities with IC50 values of 21.8 and 32.8 μg/mL, respectively.
Hai-Yan Chen,Yue-Feng Guan,Xue-Yong Huang,Yu-Ting Wu,Fen-Fei Wang,Ju-Fang Gao,Que Zhou,Zhong-Nan Yang,Jia-Yao Liu,Hong-Xia Zhang 한국식물학회 2012 Journal of Plant Biology Vol.55 No.3
We have characterized a new male-sterile mutant in Arabidopsis that exhibits conditional sterility but has restored fertility when drought-stressed. This mutant,multiple impairments in male reproduction 1 (mimr1),shows pleiotropic defects in both vegetative and reproductive development. Examination with dissecting and scanning electron microscopes revealed that its pollen grains are not effectively released from the anther locule after dehiscence, and anther differentiation is defective. Growth of the style and stamen filaments are also abnormal. Histological analysis demonstrated that these phenomena are due not only to a noticeably reduced extension of the stamen but also greater elongation of the pistil. Genetic analysis indicated that mimr1 is a single locus recessive nuclear mutant. The mutation can be mapped to a locus strongly linked to a 1200-kb region on Chromosome 3. Meta-analysis of expression patterning presented several candidate genes in that region. No mutants with similar phenotypes have previously been reported, suggesting that mimr1 is a novel male-sterile locus. Characterization of MIMR1 will provide further insights into the molecular basis for the development of plant reproductive organs.
Zhang, Qian,Gao, Yang,Zhang, Hai-xia,Xu, Fei,Li, Feng Techno-Press 2018 Structural monitoring and maintenance Vol.5 No.1
The stability of cutting slope influences the safety of railway operation, and how to identify the stability of the slope quickly and determine the rational monitoring plan is a pressing problem at present. In this study, the attribute recognition model of risk assessment for high cutting slope stability in the heavy haul railway is established based on attribute mathematics theory, followed by the consequent monitoring scheme design. Firstly, based on comprehensive analysis on the risk factors of heavy haul railway loess slope, collapsibility, tectonic feature, slope shape, rainfall, vegetation conditions, train speed are selected as the indexes of the risk assessment, and the grading criteria of each index is established. Meanwhile, the weights of the assessment indexes are determined by AHP judgment matrix. Secondly, The attribute measurement functions are given to compute attribute measurement of single index and synthetic attribute, and the attribute recognition model was used to assess the risk of a typical heavy haul railway loess slope, Finally, according to the risk assessment results, the monitoring content and method of this loess slope were determined to avoid geological disasters and ensure the security of the railway infrastructure. This attribute identification- risk assessment- monitoring design mode could provide an effective way for the risk assessment and control of heavy haul railway in the loess plateau.
( Xia Lu Wan ),( Zhang Jing Hai ),( Ying Chen ),( You Lei Ma ),( Wen Jun Zou ),( Guo Yuan Ding ),( Wei Li ),( Ming Yi Zhao ),( Chun Fu Wu ) 생화학분자생물학회 2013 BMB Reports Vol.46 No.7
In this paper, we firstly reported a C-type lectin cDNA clone of 1029 bps from the larvae of A. Pernyi (Ap-CTL) using PCR and RACE techniques. The full-length cDNA contains an open reading frame encoding 308 amino acid residues which has two different carbohydrate-recognition domains (CRDs) arranged in tandem. To investigate the biological activities in the innate immunity, recombinant Ap-CTL was expressed in E. coli with a 6-histidine at the amino-terminus (Ap-rCTL). Besides acted as a broad-spectrum recognition protein binding to a wide range of PAMPs and microorganisms, Ap-rCTL also had the ability to recognize and trigger the agglutination of bacteria and fungi. In the proPO activation assay, Ap-rCTL specifically restored the PO activity of hemolymph blocked by anti- Ap-rCTL antibody in the presence of different PAMPs or microorganisms. In summary, Ap-rCTL plays an important role in insect innate immunity as an pattern recognition protein.
Zhang, Yun-Xia,Abliz, Guzalnur,Ye, Wei-Jun,Mutalipu, Zuohelaguli,Li, Xiao-Wen,Wang, Hai-Qin,Buranjiang, Gulimire,Upur, Halmurat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2
Objective: To investigate the effects of abnormal Savda Munziq (ASMq) total phenolics combined with cisplatin and docetaxel on the Hela cell growth. Methods: In vivo cultured Hela cells were treated with cisplatin, docetaxel, total phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was performed to assess inhibition of cell proliferation, flow cytometry to detect apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2 expression. Results: The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early apoptotic rates of $12.8{\pm}0.70%$, $18.9{\pm}3.79%$ and $15.8{\pm}3.8%$; the total phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl-2 and survivin (all P<0.01), especially when used in combination. Conclusion: ASMq total phenolics, combined with cisplatin and docetaxel, could promote the apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and survivin.