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Hua Yao

Publications and source records attributed to Hua Yao.

13 recordsLinked to original sources

T2T and chromosome-level genome assemblies provide insights into the genetic basis of bioactive compound biosynthesis and environmental adaptation in licorice.

Licorice is an important medicinal herb worldwide, including three Chinese Pharmacopoeia species (Glycyrrhiza uralensis, G. inflata, G. glabra), with bioactive compounds crucial for disease treatment and industrial applications. However, the genetic mechanisms underlying the biosynthesis, diversification, and environmental adaptation of bioactive compounds in Glycyrrhiza species have long remained unclear. Herein, we assembled a gapless telomere-to-telomere (T2T) genome of G. uralensis with resolved telomeres and centromeres and three significantly improved high-quality chromosome-level Glycyrrhiza genomes, alongside a variation map of 188 wild accessions. Population analysis revealed evolutionary divergence among species, with selection signals linked to medicinal compound pathways. We identified 4CL5 as a key gene for stress response and compound synthesis. GWAS validation highlighted the GiPHL1-Gi4CL5 module's role in licochalcone A accumulation and enhanced stress adaptation in G. inflata. This study provides the first T2T Glycyrrhiza genome and insights into medicinal compound biosynthesis and environmental adaptation.

Glycyrrhiza↗

(S)-4,5-dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid polyethers: a solution to nephrotoxicity.

Previous studies revealed that within a family of ligands the more lipophilic chelators have better iron-clearing efficiency. The larger the log P(app) value of the compound, the better the iron-clearing efficiency. What is also clear from the data is that although the relative effects of log P(app) changes are essentially the same through different families, there are differences in absolute value between families. However, there also exists a second, albeit somewhat more disturbing, relationship. In all sets of ligands, the most lipophilic chelator is always the most toxic. The current study focuses on designing ligands that balance the lipophilicity/toxicity problem while iron-clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH(3)O)-DADFT, 6] indicated that this methyl ether was a ligand with excellent iron-clearing efficiency in both rodents and primates; however, it was too toxic. On the basis of this finding, a less lipophilic, more water-soluble ligand than 6 was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE, 11], a polyether analogue, along with its ethyl and isopropyl esters. The parent polyether and its isopropyl and ethyl esters were all shown to be highly efficient iron chelators in both rodents and primates. A comparison of 11 in rodents with the desferrithiocin analogue (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT, 1] revealed the polyether to be more tolerable, achieving higher concentrations in the liver and significantly lower concentrations in the kidney. The lower renal drug levels are in keeping with the profound difference in the architectural changes seen in the kidney of rodents given 1 versus those treated with 11.

Acids↗

Polyamine-vectored iron chelators: the role of charge.

The utility of polyamines as vectors for the intracellular transport of iron chelators is further described. Consistent with earlier results with polyamine analogues, these studies underscore the importance of charge in the design of polyamine-vectored chelators. Four polyamine conjugates are synthesized, two of terephthalic acid [N(1)-(4-carboxy)benzoylspermine (7) and its methyl ester (6)] and two of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT] [(S)-4,5-dihydro-2-[2-hydroxy-4-(12-amino-5,9-diazadodecyl-oxy)phenyl]-4-methyl-4-thiazolecarboxylic acid (10) and its ethyl ester (9)]. These four molecules were evaluated in murine leukemia L1210 cells for their impact on cell proliferation (48- and 96-h IC(50) values), their ability to compete with spermidine for the polyamine transport apparatus (K(i)), and their intracellular accumulation. The data revealed that when neutral molecules (cargo fragments) were fixed to the polyamine vector, the conjugates competed well with spermidine for transport and were accumulated intracellularly to millimolar levels. However, this was not the case when the cargo fragments were negatively charged. Metabolic studies of the polyamine-vectored (S)-4'-(HO)-DADFTs in rodents indicated that not only did the expected deaminopropylation step occur, but also a surprisingly high level of oxidative deamination at the terminal primary nitrogens took place. Finally, the iron-clearing efficiency of the (S)-4'-(HO)-DADFT conjugates was determined in a bile-duct-cannulated rodent model. Attaching the ligand to a polyamine vector had a profound effect on increasing the iron-clearing efficiency of this chelator relative to its parent drug.

Animals↗

Synthesis and biological evaluation of aminopolyamines.

Exploitation of the polyamine backbone as a vector for intracellular transport of various pharmacophores has focused largely on fixing the cargo molecule to one of the nitrogens in the linear chain. This communication describes the assembly of a model aminopolyamine analogue, 6-amino-N(1),N(12)-diethylspermine, and its biological properties. This amino polyamine presents an additional site of attachment for cargo molecules, reduces cell growth, and achieves cellular concentrations that are higher than those of N(1),N(12)-diethylspermine.

Acetyltransferases↗

[The effect of gemcitabine on proliferation and telomerase activity of Tca8113 cell lines].

PURPOSE: To investigate the effect of gemcitabine on the proliferation and telomerase activity of Tca8113 cell line cells. METHODS: MTT assay, flow cytometry were used to examine the effect of gemcitabine on cell proliferation and cell cycle respectively, telomerase activity was detected with telomeric repeat amplification protocol (TRAP) and polyacrylamide gel electrophoresis (PAGE). The data were analyzed by independent samples t test and one-way ANOVA of SPSS10.0 for windows. RESULTS: Cell proliferations were significantly inhibited in these cells after exposure to gemcitabine as well as cell cycles were arrested. Furthermore, the effect was closely associated with the concentration and time of gemcitabine. The average rate of cell proliferating inhibition in group 5.0 microg/ml at 72 h was 72.2%.The number of cells in S phase was decreased,the average rate of S phase in group 5.0 microg/ml at 72 h was 18.1%,which was lower than that in group 0 microg/ml(38.5%) (t=5.801,P<0.05).Longer exposure time and higher concentration to gemcitabine, much telomerase activity was inhibited. After 72h, the A values of group 0 and 5.0 microg/ml were 1.32+/-0.12, 0.28+/-0.02, respectively (F=811.208, P<0.05). CONCLUSIONS: Gemcitabine could significantly inhibit Tca8113 proliferation and decrease its telomerase activity. Gemcitabine may be applied in clinical therapy of oral cancer.

Carcinoma, Squamous Cell↗

[Effects of arsenic trioxideon the cell apoptosis and hTERT mRNA of human tongue cancer cells].

OBJECTIVE: To study the effects and its mechanisms of arsenic trioxide (As2O3) on cell growth and human telomerase reverse transcriptase (hTERT) of human tongue cancer cells (Tca8113 cell line). METHODS: The growth inhibition rates of Tca8113 by various concentrations of As2O3 were detected by MTF method. Cell apoptosis was detected by FCM labeled with Annexin V-FITC. hTERT gene expression was detected by RT-PCR method. hTERT protein of Tca8113 cells was determined by Western blot assay. RESULTS: The results showed that As2O3 could inhibit the growth of Tca8113 effectively and apoptotic rate of Tca8113 cells was obviously increased in a dose and time-dependent manner. (83.40 +/- 7.31)% cells treated with 5 micromol/L As2O3 were inhibited on 72 hour point, the early apoptosis rate reached on 26.40% +/- 3.42% at that time. Moreover hTERT mRNA and protein were decreased depended on the dose and time of As2OC3, mRNA expressions of hTERT in test groups were greatly lower than that of control group on 72 hour point. CONCLUSION: It was suggested that As2O3 could significantly inhibit the growth of Tca8113 cells by inducing causing cell apoptosis and down-regulating the expression of hTERT mRNA gene and protein which might be one of its action mechanisms.

Apoptosis↗

[Effects of tea polyphenols on cell proliferation and hTERT of human Tca8113 cell lines].

OBJECTIVE: To investigate the effects of tea polyphenols (TP) on cell proliferation and human telomerase reverse transcriptase (hTERT). METHODS: The experiment was divided into tea polyphenols 0.100 g/L, tea polyphenols 0.050 g/L and blank control groups. The inhibitory ratio of cell proliferation was assayed with MTT, and hTERT mRNA was detected by RT-PCR, and hTERT protein analyzed by Western-blotting. The data were analyzed by one-way ANOVA and Student-Newman-Keuls of SPSS 11.0 for windows. RESULTS: Cell proliferations were significantly inhibited after exposure to TP. The proliferation inhibiting rate of TP 0.025, 0.050, 0.100, 0.200 g/L on Tca8113 cell at 72 h was 69.75% +/- 3.24%, 63.17% +/- 3.19%, 50.35% +/- 4.21% and 34.75% +/- 3.71%, respectively (F = 270.19, P < 0.05). At the end of 72 h, the hTERT mRNA expression in TP 0.100 g/L, 0.050 g/L and control group were 0.32 +/- 0.05, 0.41 +/- 0.04, 0.72 +/- 0.05, respectively (P < 0.05). The Western-blotting assay showed that hTERT protein was also decreased by tea polyphenols compared to control group. CONCLUSIONS: Tea polyphenols could inhibit the proliferation of Tca8113 cells and expression of the hTERT mRNA and protein in Tca8113 cell lines. This effect might be one of the mechanisms for anticancer function of tea polyphenols.

Carcinoma, Squamous Cell↗

[Appraisal of occupational stress and its influential factors in executive group].

OBJECTIVE: To assess occupational stress and its influential factors in executive group. METHODS: A test of occupational stress, its influential factors, was carried out with revised occupational stress inventory (OSI-R) for 263 executive group and 319 controls. RESULTS: (1) Among the 6 items of occupational role questionnaire, the scores of role overload, role insufficiency, role boundary, role ambiguity, responsibility are obviously higher in the executive group (P < 0.01). The scores of vocational strain, psychological strain, interpersonal strain and physical strain in the executive group are significantly higher (P < 0.01). The results of personal resources indicate that social support scores in executive group are superior (P < 0.05). (2) Occupational role and personal strain were positively correlated (r = 0.337, P < 0.01), both of which correlated negatively to the personal resources (r = - 0.311, P < 0.01). (4) The major influential factors of personal strain and psychological strain were: responsibility, personal resources, role boundary and working environment. The major influential factors of interpersonal strain were role ambiguity, role boundary and personal resources. The major influential factors of physical strain were personal resources, responsibility, role boundary and education. CONCLUSION: Different measure should be taken to reduce the occupational stress so as to improve the work ability of executive group.

Administrative Personnel↗

[Molecular genetic mechanism of sodium arsenite on growth and development].

OBJECTIVE: To study the effects of sodium arsenite on gene expression related to growth and development and explored the molecular mechanism of arsenic effects using gene chips. METHODS: Normal human hepatic cells were dripped on chips and then hybrided with the first strand of cDNA from hepatic cell exposed to different concentration of sodium arsenite. Gene sequence of clone differently expressed was determined and then defined which gene it was and finally those genes which associated with growth and development were identified. RESULTS: The p55 gene expression level of two experimental groups was severaly 2.21 and 2.93 times as the control group. The PL gene level of two experimental groups were 0.13 and 0.27 times as the control group, and the HOXA10 gene level was 0.22 and 0.35 times of the control group. These results indicated that sodium arsenite increase p55 gene expression, and inhibited PL and HOXA10 gene expression. CONCLUSIONS: The sodium arsenite could affect the gene expression related to growth and development and it is shown that the molecular genetic mechanism of sodium arsenite is related to growth and development.

Arsenites↗

Polyamine-iron chelator conjugate.

The current study demonstrates unequivocally that polyamines can serve as vectors for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy-4(1H)-pyridinone is assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III) and to be taken up by the polyamine transporter 1900-fold against a concentration gradient. The K(i) of the conjugate is 3.7 microM vs spermidine for the polyamine transporter. The conjugate is also at least 230 times more active in suppressing the growth of L1210 murine leukemia cells than is the parent ligand, decreases the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N (1)-acetyltransferase. However, the effect on native polyamine pools is a moderate one. These findings are in keeping with the idea that polyamines can also serve as efficient vectors for the intracellular delivery of other iron chelators.

Acetyltransferases↗

[Construction of normal human lymphocyte cDNA library].

A lymphocyte cDNA library of normal human was constructed in order to obtain specific gene and prepare lymphocyte gene chips to detect the relative genes between psychiatric diseases and immunity. The lymphocyte was abstracted from fresh normal human blood and cultured in vitro. Total RNA of lymphocyte was extracted from the cultured cells and then mRNA was extracted further. Moreover,single-strand cDNA and double-strand cDNA were synthesized in turn. The double-strand cDNAs were ligated to SalI and NotI adaptor,which were later ligated to arms of gammaZipLox. Ligated-cDNAs were packed in vitro, and then infected E. coli Y1090. Titering the phage and amplifying the library. The lymphocyte cDNA library consisted of 2.6 x 10(6) recombinants with the length of 1-5 kb and the cloning efficiency was 5 x 10(12) recombinants/g cDNA. The amplified library was 3 x 10(7) recombinants/microl in concentration and the number of bacteriophage plagues was the most suitable in density after it was diluted to 10(-6) in concentration. The constructed cDNA library of normal human lymphocyte would be helpful to further detecting target genes and preparing gene chips etc.

English Abstract↗