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Biomedical subjects

Jing Yang

Publications and source records attributed to Jing Yang.

At least 163 records · Page 9Linked to original sources

CYP2E1 mediated isoniazid-induced hepatotoxicity in rats.

AIM: To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS: Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, sAST) and histopathological examinations. Hepatic CYP2E1 activity was measured by aniline hydroxylase (ANH), and CYP2E1 mRNA expression was determined by RT-PCR. Plasma hydrazine concentration was determined by RP-HPLC. RESULTS: For a 10 d INH-treatment, hepatic CYP2E1 level was increased to 3.7-fold over the control; liver impairment appeared after 21 d treatment, while CYP2E1 and plasma hydrazine were, respectively, increased to 4.6-fold and 1.7-fold. However, in INH-RFP group for 10 d, CYP2E1 and plasma hydrazine were, respectively, decreased by 13 % and 18 % over INH group; similarly, hepatic injury is equal to INH group appeared after 21 d, and CYP2E1 was further decreased by 26 %. Correlation analysis showed that sALT had a positive correlation with plasma hydrazine and with CYP2E1 activity; CYP2E1 activity was also markedly correlated with plasma hydrazine. And compared with control, there is no difference in changes of CYP2E1 mRNA expression in INH and INH-RFP treatment for 21 d. CONCLUSION: The metabolite of INH, hydrazine, plays an important role in INH-induced hepatotoxicity in rats. The induction of CYP2E1 by hydrazine is involved in the hepatotoxicity of INH. RFP does not exacerbate INH-induced hepatotoxicity in short term, which relates to down-regulation of CYP2E1.

Alanine Transaminase↗

Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells.

BACKGROUND: In China the ginseng root began to be used in medicine over 2000 years ago. Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rg1 on the spectrum of gene expression in the endothelial cells stimulated by TNF-alpha and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rg1. METHODS: Nitric oxide (NO) production in the cultured human umbilical vein endothelial cells (HUVECs) was measured by using an NO assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rg1 in HUVECs which were activated by TNF-alpha were detected by oligonucleotide microarray analysis. RESULTS: NO production in HUVECs was decreased significantly after TNF-alpha treatment, while pretreatment with ginsenoside Rg1 enhanced NO production in TNF-alphastimulated HUVECs. Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-alphastimulated HUVECs. CONCLUSIONS: Ginsenoside Rg1 could enhance NO production and the expression of eNOS mRNA in TNF-alpha stimulated HUVECs. Ginsenoside Rg1 regulated sets of genes in endothelial cells and protected endothelial cells from TNF-alpha activation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.

Endothelial Cells↗

[The study developments about changes of methamphetamine-induced genes' transcriptions and translations].

The basic changes are to transform the levels of many genes' transcriptions and translations when methamphetamine is injected into the organism. Those genes enclose four classes: genes intermediating the damages or death of neurons,genes involving circadian rhythms of activity, genes concerning the abnormality of behaviors and some genes difficult to be classified. The transformations of the transcriptions or translations of these genes cooperate to produce many clinic syndromes of methamphetamine-addictors. Moreover, the study of these genes can provide testimonies to forensic identification.

Animals↗

[Construction and identification of anti-chymopapain scFv phage display library].

AIM: To construct phage display library of anti-chymopapain scFv. METHODS: V(H) and V(L) gene repertoires were amplified from splenocyte mRNA by RT-PCR and joined by a (Gly(4)ser)3 linker to obtain scFv genes. The scFv genes were then cloned into phagemid pFAB5C to construct phage display library. Affinity selection and ELISA were used to identify specific phage antibody to chymopapain. RESULTS: After 4 rounds of panning, high affinity scFv was obtained. CONCLUSION: Phage display library of anti-chymopapain scFv was successfully constructed, and scFv with binding ability to chymopapain was obtained.

Animals↗

[Synthesis and antitumor activity of 20-O-linked camptothecin ester derivatives].

AIM: To improve the profile of 20 (S)-camptothecin, a series of 20-O-linked camptothecin phenoxyacetic acid ester derivatives have been designed. METHODS: These derivatives were synthesized by the method of acylation. Their chemical structures were confirmed with 1HNMR, IR, MS, and HRMS. The cytotoxicities of the compounds were tested by MTT assay. The in vivo antitumor activities of these esters were evaluated against mouse liver tumor H22 in mice. RESULTS: Twelve derivatives of camptothecin ester are new compounds. CONCLUSION: In vitro and in vivo antitumor activity has indicated that some derivatives appeared significantly more effective than topotecan in the H22 mouse liver tumoral model.

Animals↗

[A study of the expression of Fas after fluid percussion brain injury in rats].

OBJECTIVE: To study the pathologic diagnosis and the injury time estimation in light closed encephalon injury. METHODS: Mice were hurt by fluid percussion, and were killed at 15, 30 min, 1, 3 , 6, 12 h, 1, 4, 7, 14 d respectively after injury. The expression of Fas-L in the cerebral cortex, thalamus, and hippocampi was detected by immunohistochemistry and the results were assessed by image analysis system. RESULTS: It is showed that the expression of Fas-L could be detected in 1 h after injury, and increased significantly in three hours, and it reached apex 12 h after injury, and decreased gradually four days after injury, and returned normal 14 days after injury. CONCLUSION: This research demonstrated that Fas-L mediated apoptosis appeared not only around brain trauma but also in the brain tissue far away from the traumatic area. It indicted that the expression of Fas-L is a useful target for diagnosis of early brain injury; the regularity of Fas-L expression could be used as one of indication to date the time of brain injury.

Animals↗

[Prokaryotic expression of an antigen gene of Trichinella spiralis and identification of the recombinant protein].

OBJECTIVE: To obtain the recombinant protein of an antigen gene Ts88 of Trichinella spiralis and identify the characteristics of the recombinant protein. METHODS: Ts88 cDNA obtained by immunoscreening the cDNA library of adult T. spiralis was subcloned into the pET-28c(+) expression vector and expressed in E. coli. Mice were immunized with the fusion protein incorporated into Freund' s adjuvant and the immune sera were collected. The titers of the Ts88 immune sera and the antigenicity of the recombinant protein were detected by ELISA and Western blotting. Immuno-fluorescence test was performed in order to confirm the distribution of Ts88 protein in the worm. RESULTS: The fragment of Ts88 gene was expressed successfully in E. coli and a highly purified fusion protein was obtained. Immunization with the recombinant protein in mice produced high titers of antibodies, which recognized some components of native antigens of soluble proteins from adult worm of T. spiralis. Western blotting analysis showed that Ts88 recombinant antigen was recognized by all the positive sera, such as the sera from infected or immunized rabbits, from infected swine and from patients of trichinosis. Immuno-fluorescence test confirmed that Ts88 protein mainly distributed in the cuticle surface of the worm. CONCLUSION: The Ts88 antigen gene from T. spiralis was successfully expressed. The recombinant protein presented antigenicity.

Animals↗

FADDdel-GFP modified mouse insulinoma cells counteract the cytotoxicity of reactive T cells.

IDDM results from pancreatic beta cell destruction by islet-reactive T cells, a process that involves beta cell apoptosis. Fas-FasL pathway plays a major role in pancreatic beta cell death. Fas-associated death domain protein (FADD), the component of the tumor necrosis factor receptor type 1 (TNFR1) and Fas signaling complexes, is involved in TNFR1- and Fas-induced apoptosis. Inhibiting the function of FADD will lead to blocking downstream apoptosis signal, which protects pancreatic beta cells from destruction by Fas-FasL pathway. In this study we constructed eukaryotic expressing vector of fusional protein FADDdel-GFP named pFADDdel-GFP. After pFADDdel-GFP was transfected into NIT, the expression of FADDdel-GFP in NIT was detected by fluorescence microscopy and the resistance of NIT transfected with pFADDdel-GFP to cytotoxicity mediated by special T cells was detected by FACS and MTT. The results showed that NIT modified by pFADDdel-GFP obviously resisted cytotoxicity mediated by special T cells. Therefore, it may be useful in the prevention or treatment of IDDM by intervening Fas-FasL pathway.

Adaptor Proteins, Signal Transducing↗

Organismal complexity, protein complexity, and gene duplicability.

Although the evolutionary significance of gene duplication has long been recognized, it remains unclear what determines gene duplicability. We find protein complexity to be an important determinant because the proportion of unduplicated genes (P) increases with the number of subunits in a protein. However, P is high (>or=65%) for both monomers and multimers in yeast, but <or=30% in human except for subunits of large multimers, implying that organismal complexity is a stronger determinant of gene duplicability than protein complexity. The same conclusion is reached from a comparison of family sizes in yeast and human.

Dimerization↗

In vivo reduction of amyloid-beta by a mutant copper transporter.

Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-beta (Abeta) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Abeta deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Abeta levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Abeta at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide.

Adenosine Triphosphatases↗

Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury.

The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.

Ammonia↗

Sulfonation of polyvinylidene difluoride resin and its application in extraction of restriction enzymes from DNA digestion solutions.

Sulfonation of polyvinylidene difluoride (PVDF) resin was achieved by incubation of the resin with sulfuric acid at a moderately high temperature. The sulfonated PVDF (SPVDF) resin was studied for its ability to extract restriction enzymes from DNA digestion solutions. The SPVDF resin was effective in adsorbing restriction enzymes such as EcoRI and BamHI and the extraction procedure was easy and simple to perform. The adsorption depended upon the amount of the resin added. We found that 1 mg of the SPVDF resin could completely remove all restriction enzyme activity routinely used in DNA digestion within 2 min after its addition. Treatment of a digestion solution with the SPVDF resin did not change the reaction solution and the same digestion buffer could be used for another digestion of the same DNA with other enzymes. We also found that, in comparison with normal PVDF, the SPVDF resin adsorbed less DNA, resulting in less loss of DNA in the extraction step. The potential application of the SPVDF resin in other procedures of molecular cloning and enzyme purification is discussed.

Absorption↗

Electron transfer reactions of redox cofactors in spinach photosystem I reaction center protein in lipid films on electrodes.

Thin film voltammetry was used to obtain direct, reversible, electron transfer between electrodes and spinach Photosystem I reaction center (PS I) in lipid films for the first time. This reaction center (RC) protein retains its native conformation in the films, and AFM showed that film structure rearranges during the first several minutes of rehydration of the film. Two well-defined chemically reversible reduction-oxidation peaks were observed for native PS I in the dimyristoylphosphatidylcholine films, and were assigned to phylloquinone, A(1) (E(m) = -0.54 V) and iron-sulfur clusters, F(A)/F(B) (E(m) = -0.19 V) by comparisons with PS I samples selectively depleted of these cofactors. Observed E(m) values may be influenced by protein-lipid interactions and electrode double-layer effects. Voltammetry was consistent with simple kinetically limited electron transfers, and analysis of reduction-oxidation peak separations gave electrochemical rate constants of 7.2 s(-)(1) for A(1) and 65 s(-)(1) for F(A)/F(B). A catalytic process was observed in which electrons were injected from PS I in films to ferredoxin in solution, mimicking in vivo electron shuttle from the terminal F(A)/F(B) cofactors to soluble ferredoxin during photosynthesis.

Catalysis↗

PP2A:B56epsilon is required for Wnt/beta-catenin signaling during embryonic development.

The Wnt/beta-catenin pathway plays important roles during embryonic development and growth control. The B56 regulatory subunit of protein phosphatase 2A (PP2A) has been implicated as a regulator of this pathway. However, this has not been investigated by loss-of-function analyses. Here we report loss-of-function analysis of PP2A:B56epsilon during early Xenopus embryogenesis. We provide direct evidence that PP2A:B56epsilon is required for Wnt/beta-catenin signaling upstream of Dishevelled and downstream of the Wnt ligand. We show that maternal PP2A:B56epsilon function is required for dorsal development, and PP2A:B56epsilon function is required later for the expression of the Wnt target gene engrailed, for subsequent midbrain-hindbrain boundary formation, and for closure of the neural tube. These data demonstrate a positive role for PP2A:B56epsilon in the Wnt pathway.

Adaptor Proteins, Signal Transducing↗

Four inteins and three group II introns encoded in a bacterial ribonucleotide reductase gene.

A bacterial ribonucleotide reductase gene was found to encode four inteins and three group II introns in the oceanic N2-fixing cyanobacterium Trichodesmium erythraeum. The 13,650-bp ribonucleotide reductase gene is divided into eight extein- or exon-coding sequences that together encode a 768-amino acid mature ribonucleotide reductase protein, with 83% of the gene sequence encoding introns and inteins. The four inteins are encoded on the second half of the gene, and each has conserved sequence motifs for a protein-splicing domain and an endonuclease domain. These four inteins, together with known inteins, define five intein insertion sites in ribonucleotide reductase homologues. Two of the insertion sites are 10 amino acids apart and next to key catalytic residues of the enzyme. Protein-splicing activities of all four inteins were demonstrated in Escherichia coli. The four inteins coexist with three group II introns encoded on the first half of the same gene, which suggests a breakdown of the presumed barrier against intron insertion in this bacterial conserved protein-coding gene.

Amino Acid Motifs↗

[Reduced resistin levels in patients with type 2 diabetes mellitus].

OBJECTIVE: To measure the serum resistin level of patients with type 2 diabetes mellitus so as to examine whether there exists a relationship between resistin, obesity and diabetes. METHODS: ELISA was used to examine the fasting serum resistin, leptin, and true insulin and those 2-hours after taking 75-g glucose in 51 untreated type 2 diabetic patients, 30 males and 21 females, and 52 sex and age-matched normal control subjects. Blood glucose, blood pressure, height, weight, waist circumstance, hip girth were measured. Body mass index (BMI), waist to hip ratio (WHR), and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: In comparison with the control, the diabetic group had higher waist-to-hip ratio (WHR) and serum insulin levels (P < 0.05), but significantly lower resistin levels both in the fasting status (23 ng/ml +/- 15 ng/ml vs 30 ng/ml +/- 18 ng/ml, P < 0.05) and 2 hours after glucose loading (22 ng/ml +/- 11 ng/ml vs 31 ng/ml +/- 15 ng/ml, P < 0.001). The leptin level was not statistically different between the two groups (P > 0.05). The resistin level 2 hours after glucose loading was not significantly different between these 2 groups. Correlation analysis demonstrated that fasting resistin level was not correlated with sex, BMI, leptin, and blood pressure, but positively correlated with QUICKI (r = 0.30, P < 0.01) and negatively correlated with blood glucose (r = -0.21, P < 0.05). CONCLUSION: The serum resistin level of patients with type 2 diabetes is reduced rather than increased in fasting status and 2 hours after glucose taking. Resistin may not be the major link between obesity and diabetes in human beings. Since human resistin level is positively correlated with insulin sensitivity, the use of term "resistin", originally for its resistance to insulin, may be somewhat premature.

Adult↗

Neural mechanisms underlying semantic and orthographic processing in Chinese-English bilinguals.

Brain activation underlying language processing in Chinese-English bilinguals was examined using fMRI in an orthographic search and a semantic classification task. In both tasks, brain areas activated by Chinese characters and English words were very similar to tasks examining Chinese reading using Chinese pinyin (an alphabetic Chinese script) and Chinese characters. However, the degree of later-alization was different, with English words (second language) causing much more right hemisphere activation than Chinese characters (native language). These differences support the hypothesis that second language usage causes more right hemisphere activation than native language usage.

Adult↗

Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects.

Townes-Brocks syndrome (TBS, OMIM #107480) is an autosomal dominant disorder that causes multiple birth defects including renal, ear, anal and limb malformations. Mutations in SALL1 have been postulated to cause TBS by haploinsufficiency; however, a mouse model carrying a sall1-null allele does not mimic the human syndrome. Since the mutations that cause TBS could express a truncated SALL1 protein containing the domain necessary for transcriptional repression but lacking the complete DNA binding domain, we hypothesized that TBS is due to dominant-negative or gain-of-function activity of a mutant protein. To test this hypothesis, we have created a mutant allele, sall1-DeltaZn2-10, that produces a truncated protein and recapitulates the abnormalities found in human TBS. Heterozygous mice mimic TBS patients by displaying high-frequency sensorineural hearing loss, renal cystic hypoplasia and wrist bone abnormalities. Homozygous sall1-DeltaZn2-10 mutant mice exhibit more severe defects than sall1-null mice including complete renal agenesis, exencephaly, limb and anal deformities. We demonstrate that truncated Sall1 mediates interaction with all Sall family members and could interfere with the normal function of all Sall proteins. These data support a model for the pathogenesis of TBS in which expression of a truncated SALL1 protein causes abnormal development of multiple organs.

Abnormalities, Multiple↗