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Haitao Zhang

Publications and source records attributed to Haitao Zhang.

At least 19 recordsLinked to original sources
PubMed2025

Ras-MAPK pathway in patients with lupus nephritis.

BACKGROUND: Pathogenic mutations in genes encoding components of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway cause RASopathy. Here, we describe five unrelated patients with SLE carrying mutations associated with RASopathy and investigate the activity of the Ras-MAPK pathway. METHODS: Pathogenic variants were identified by whole-exome/whole-genome sequencing. The activity of the Ras-MAPK pathway in peripheral blood mononuclear cells (PBMC) and kidneys was evaluated using RNA sequencing and datasets from the nephroseq database, respectively. RESULTS: Five (likely) pathogenic variants in four Ras-MAPK genes were identified, including NRAS: c.G38A: p.G13D; ARAF: c.C1435T: p.R479C; KRAS: c.T341C: p.V114A; PTPN11: c.G455A: p.R152H and NRAS: c.G34A: p.G12S. Kidney injury is the main feature, presenting with nephrotic syndrome (2/5), proteinuria and haematuria (2/5). Acute kidney injury and rapidly progressive nephritic syndrome were noted in one patient each. Other clinical features included mucocutaneous lesions (5/5), cardiac involvement (4/5) and arthralgia (3/5). Laboratory abnormalities included hypocomplementaemia (5/5), presence of antiphospholipid antibodies (4/5), decreased regulatory T cells (3/3), pancytopenia (3/5) and persistent monocytosis (2/5). Kidney biopsy revealed lupus nephritis. Most patients responded well to standard therapy, with the exception of the patient with the NRAS p.G13D mutation who died. The Ras-MAPK pathway was activated in both PBMC and kidney of patients with LN as indicated by increased expression of NRAS, KRAS, RIT1, MRAS, PPP1CB, SHOC2, SOS2 and MAP2K1, as well as decreased expression of negative regulators of the Ras-MAPK pathway, CBL, LZTR1 and NF1. CONCLUSION: Kidney involvement may be the main feature of the clinical spectrum of RASopathy. Genetic screening should be considered for patients with early onset lupus.

Humans↗
PubMed2007

Maternal cocaine administration causes an epigenetic modification of protein kinase Cepsilon gene expression in fetal rat heart.

Protein kinase Cepsilon (PKCepsilon) plays a pivotal role in cardioprotection during cardiac ischemia and reperfusion injury. Recent studies demonstrated that prenatal cocaine exposure caused a decrease in PKCepsilon expression and increased heart susceptibility to ischemic injury in adult offspring, suggesting an in utero programming of PKCepsilon gene expression pattern in the heart. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for cocaine-mediated repression of the PKCepsilon gene in the heart. Pregnant rats were administered either saline or cocaine intraperitoneally (15 mg/kg) twice daily from days 15 to 20 of gestational age, and term fetal hearts were studied. Cocaine treatment significantly decreased PKCepsilon mRNA and protein levels in the heart. CpG dinucleotides found in cAMP response element-binding protein (CREB), CREB/c-Jun1, and CREB/c-Jun2 binding sites at the proximal promoter region of the PKCepsilon gene were densely methylated and were not affected by cocaine. In contrast, methylation of CpGs in the activator protein 1 (AP-1) binding sites was low but was significantly increased by cocaine. Reporter gene assays showed that the AP-1 binding site played a strong stimulatory role of PKCepsilon gene transcription. Methylation of the AP-1 binding sites significantly decreased AP-1 binding to the PKCepsilon promoter. Supershift analyses implicated c-Jun homodimers binding to the AP-1 binding sites. Cocaine did not affect nuclear c-Jun levels or the binding of c-Jun to the unmethylated AP-1 binding sites. The results indicate a role for DNA methylation in cocaine-mediated PKCepsilon gene repression in the developing heart and suggest an epigenetic mechanism affecting this gene linked with vulnerability of ischemic injury in the heart of adult offspring.

Animals↗
PubMed2006

Augmented suppression of androgen receptor signaling by a combination of alpha-tocopheryl succinate and methylseleninic acid.

BACKGROUND: Previous reports showed that alpha-tocopheryl succinate (alphaTS) and methylseleninic acid (MSA) independently reduce the abundance of androgen receptor (AR) in prostate cancer cells. The response to MSA happens quickly, whereas the response to alphaTS takes much longer. The present study was designed to investigate whether a combination of alphaTS and MSA would produce an additive or a greater than additive effect in suppressing AR level, AR transactivation, and prostate-specific antigen (PSA). METHODS: LNCaP cells were treated with alphaTS alone for 31 hours, MSA alone for 3 hours, or alphaTS first for 28 hours and alphaTS/MSA together for the last 3 hours. AR and PSA mRNA levels were quantitated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). AR transactivation was determined by the ARE-luciferase reporter assay. Both cellular and secretory PSA was also measured by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Different doses of alphaTS were evaluated in combination with MSA. Some striking results are highlighted below for alphaTS alone, MSA alone, or alphaTS/MSA (presented in that order). AR mRNA level was depressed by 0%, 20%, or 60%, respectively; AR transactivation was inhibited by 35%, 10%, or 60%, respectively; whereas the PSA mRNA level was decreased by 40%, 60%, or 90%, respectively. Interestingly, secretory PSA was consistently reduced to a greater extent than cellular PSA. CONCLUSIONS: A combination of alphaTS/MSA produced a greater than additive effect in suppressing AR signaling compared with the single agent. Decreased AR abundance is a major factor, but not necessarily the sole factor, in diminishing the transcriptional activity of AR by alphaTS or MSA.

Androgen Receptor Antagonists↗
PubMed2006

Rice Chlorina-1 and Chlorina-9 encode ChlD and ChlI subunits of Mg-chelatase, a key enzyme for chlorophyll synthesis and chloroplast development.

Photosynthetic organisms exhibit a green color due to the accumulation of chlorophyll pigments in chloroplasts. Mg-protoporphyrin IX chelatase (Mg-chelatase) comprises three subunits (ChlH, ChlD and ChlI) and catalyzes the insertion of Mg(2+) into protoporphyrin IX, the last common intermediate precursor in both chlorophyll and heme biosyntheses, to produce Mg-protoporphyrin IX (MgProto). Chlorophyll deficiency in higher plants results in chlorina (yellowish-green) phenotype. To date, 10 chlorina (chl) mutants have been isolated in rice, but the corresponding genes have not yet been identified. Rice Chl1 and Chl9 genes were mapped to chromosome 3 and isolated by map-based cloning. A missense mutation occurred in a highly conserved amino acid of ChlD in the chl1 mutant and ChlI in the chl9 mutant. Ultrastructural analyses have revealed that the grana are poorly stacked, resulting in the underdevelopment of chloroplasts. In the seedlings fed with aminolevulinate-dipyridyl in darkness, MgProto levels in the chl1 and chl9 mutants decreased up to 25% and 31% of that in wild-type, respectively, indicating that the Mg-chelatase activity is significantly reduced, causing the eventual decrease in chlorophyll synthesis. Furthermore, Northern blot analysis indicated that the nuclear genes encoding the three subunits of Mg-chelatase and LhcpII in chl1 mutant are expressed about 2-fold higher than those in WT, but are not altered in the chl9 mutant. This result indicates that the ChlD subunit participates in negative feedback regulation of plastid-to-nucleus in the expression of nuclear genes encoding chloroplast proteins, but not the ChlI subunit.

Alleles↗
PubMed2006

Analysis of ultraviolet absorption spectrum of Chinese herbal medicine-Cortex Fraxini by double ANN.

A fast, accurate and convenient method for the simultaneous determination of multi-component in the Chinese herbal medicine was proposed by using ultraviolet absorption spectrum. In this method, dummy components were added to training sample, and a double artificial neural network (DANN) that has the function of high self-revision and self-simulation was used. Effect of other interference components could be eliminated by adjusting concentration of dummy components. Therefore, the accuracy of concentration prediction for multi-component in the complicated Chinese herbal medicine was improved. It has been realized that two effective components of Cortex Fraxini, aesculin and aesculetin, were simultaneously determined, without any separation. The predicted accuracy was 92% within the permitted relative errors. The measurement precisions of the aesculin and aesculetin were 0.37% and 1.5%, respectively.

Absorption↗
PubMed2006

Culturable actinobacteria from the marine sponge Hymeniacidon perleve: isolation and phylogenetic diversity by 16S rRNA gene-RFLP analysis.

A total of 106 actinobacteria associated with the marine sponge Hymeniacidon perleve collected from the Yellow Sea, China were isolated using eight different media. The number of species and genera of actinobacteria recovered from the different media varied significantly, underlining the importance of optimizing the isolation conditions. The phylogenetic diversity of the actinobacteria isolates was assessed using 16S rRNA gene amplification-restriction fragment length polymorphism (RFLP) analysis of the 106 strains with different morphologies. The RFLP fingerprinting of selected strains by HhaI-digestion of the 16S rRNA genes resulted in 11 different patterns. The HhaI-RFLP analysis gave good resolution for the identification of the actinobacteria isolates at the genus level. A phylogenetic analysis using 16S rRNA gene sequences revealed that the isolates belonged to seven genera of culturable actinobacteria including Actinoalloteichus, Micromonospora, Nocardia, Nocardiopsis, Pseudonocardia, Rhodococcus, and Streptomyces. The dominant genus was Streptomyces, which represented 74% of the isolates. Three of the strains identified are candidates for new species.

Actinobacteria↗
PubMed2006

Electronic structure and photocatalytic characterization of a novel photocatalyst AgAlO2.

A novel photocatalyst, AgAlO2, was prepared by cation exchange reaction and characterized by powder X-ray diffraction. The result showed AgAlO2 crystallizes in the layered orthorhombic structure with space group was Pna2(1). The energy band and electronic structures of AgAlO2 were calculated based on the crystal structure. It was found that AgAlO2 is an indirect band gap semiconductor. The valence band top mainly consists of O-2p orbitals and Ag-4d orbitals and the conduction band bottom is mainly constructed of Ag-5s5p orbitals. The band gap of AgAlO2 was estimated to be about 2.8(1) eV with UV-vis diffuse reflectance spectrometry. The photocatalytic activity of AgAlO2 was characterized by photocatalytically decomposing the dye alizarin red (AR) under visible light irradiation, and AR could be decomposed about 70% under 2 h of visible light irradiation.

Journal Article↗
PubMed2006

Tuning the properties at heterobimetallic core: mixed-ligand bismuth-rhodium paddlewheel carboxylates.

Mixed-ligand heterometallic compounds [BiRh(O2CCF3)4-x(O2CR)x] (R = But, x = 2 (cis); R = Me, Bui, x = 1) have been obtained by gas-phase reactions of bismuth(II) trifluoroacetate with the corresponding rhodium(II) carboxylate. This synthetic approach was found to be very effective for tuning the properties and introduction of chiral ligands at a heterobimetallic core.

Journal Article↗
PubMed2006

Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2.

PURPOSE: The high prevalence of osteoblastic bone metastases in prostate cancer involves the production of osteoblast-stimulating factors by prostate cancer cells. Prostate-specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serologic marker for prostate cancer. In this study, we examined the role of PSA in the induction of osteoblast differentiation. EXPERIMENTAL DESIGN: Human cDNA containing a coding region for PSA was transfected into human osteosarcoma SaOS-2 cells. SaOS-2 cells were also treated with exogenously added PSA. We evaluated changes in global gene expression using cDNA arrays and Northern blot analysis resulting from expression of PSA in human osteosarcoma SaOS-2 cells. RESULTS: SaOS-2 cells expressing PSA had markedly up-regulated expression of genes associated with osteoblast differentiation including runx-2 and osteocalcin compared with the controls. Consistent with these results, the stable clones expressing PSA showed increased mineralization and increased activity of alkaline phosphatase in vitro compared with controls, suggesting that these cells undergo osteoblast differentiation. We also found that osteoprotegerin expression was down-regulated and that the receptor activator of NF-kappaB ligand expression was up-regulated in cells expressing PSA compared with controls. CONCLUSIONS: Modulation of the expression of osteogenic genes and alteration of the balance between osteoprotegerin-receptor activator of NF-kappaB ligand by PSA suggests that PSA produced by metastatic prostate cancer cells may participate in bone remodeling in favor of the development of osteoblastic metastases in the heterogeneous mixture of osteolytic and osteoblastic lesions. These findings provide a molecular basis for understanding the high prevalence of osteoblastic bone metastases in prostate cancer.

Alkaline Phosphatase↗
PubMed2006

Neural network-based analysis of thiol proteomics data in identifying potential selenium targets.

Generation of a monomethylated selenium metabolite is critical for the anticancer activity of selenium. Because of its strong nucleophilicity, the metabolite can react directly with protein thiols to cause redox modification. Here, we report a neural network-based analysis to identify potential selenium targets. A reactive thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D gel. We constructed a dynamic model and evaluated the relative importance of proteins mediating the cellular responses to selenium. Information from this study will provide new clues to unravel mechanisms of anticancer action of selenium. High impact selenium targets could also serve as biomarkers to gauge the efficacy of selenium chemoprevention.

Antineoplastic Agents↗
PubMed2006

Analysis of protein redox modification by hypoxia.

We examined hypoxia-induced changes in global thiol proteome profile in human prostate cancer cells using a BIAM-based display method. We analyzed the kinetics of protein thiol modification by using a pattern recognition algorithm, self-organizing maps (SOM) clustering, and identified the BIAM-labeled proteins by MALDI-TOF and ESI-tandem mass spectrometry. We found 99 out of 215 of total BIAM-labeled proteins were affected by hypoxia treatment and, yet, with diverse patterns and kinetics of redox modification. Our study proved that proteomics analysis employing the BIAM-labeling method can provide valuable information pertaining to global changes in the redox status of proteins in response to hypoxia.

Apoptosis↗
PubMed2006

Actinoalloteichus hymeniacidonis sp. nov., an actinomycete isolated from the marine sponge Hymeniacidon perleve.

A polyphasic study was undertaken to establish the taxonomic status of a Gram-positive, aerobic actinomycete, strain HPA177(T), isolated from a marine sponge, Hymeniacidon perleve. The organism formed branching, non-fragmenting vegetative hyphae and produced black pigment. Chemotaxonomic characteristics were consistent with its assignment to the genus Actinoalloteichus. Analysis of the 16S rRNA gene sequence showed that strain HPA177(T) formed a robust clade with type strains of the genus Actinoalloteichus, but was distinct from them. A number of phenotypic characteristics also readily distinguished strain HPA177(T) from species of the genus Actinoalloteichus with validly published names. On the basis of the above data, it is proposed that strain HPA177(T) represents a novel species, Actinoalloteichus hymeniacidonis sp. nov. The type strain of Actinoalloteichus hymeniacidonis is HPA177(T) (=CGMCC 4.2500(T)=JCM 13436(T)).

Actinomycetales↗
PubMed2005

Synthesis and cytotoxic activity of platinum complex immobilized by branched polyethylene glycol.

Two-arm branched mPEG (monomethoxy-polyethylene glycol) with different molecular weights (M(n)=4000, 6000, 9400) was synthesized and used as carrier for immobilization of cisplatin [cis-diammine(dichloro)platinum (II), CDDP]. As a contrast, CDDP modified with linear mPEGs was also synthesized. All these polymeric drugs modified with branched mPEG are water soluble and show higher cytotoxic activity against C6 human breast cancer cells than cisplatin modified with linear mPEG with the same molecular weight. All the polymeric CDDP showed a much lower toxicity than the CDDP.

Antineoplastic Agents↗
PubMed2005

Endoplasmic reticulum stress signal mediators are targets of selenium action.

A monomethylated selenium metabolite, called methylseleninic acid (MSA), has recently been shown to cause global thiol redox modification of proteins. These changes represent a form of cellular stress due to protein misfolding or unfolding. An accumulation of aberrantly folded proteins in the endoplasmic reticulum (ER) triggers a defined set of transducers to correct the defects or commit the cells to apoptosis if the rescue effort is exhausted. Treatment of PC-3 human prostate cancer cells with MSA was found to induce a number of signature ER stress markers: (a) the survival/rescue molecules such as phosphorylated protein kinase-like ER-resident kinase (phospho-PERK), phosphorylated eukaryotic initiation factor-2alpha (phospho-eIF2alpha), glucose-regulated protein (GRP)-78, and GRP94; and (b) the apoptotic molecules such as caspase-12, caspase-7, and CAAT/enhancer binding protein homologous protein or growth arrest DNA damage-inducible gene 153 (CHOP/GADD153). Additional evidence suggested that CHOP/GADD153 might be an important transcription factor in apoptosis induction by MSA. In general, a higher concentration of MSA was required to elicit the apoptotic markers compared with the rescue markers. The apoptotic markers increased proportionally with the dose of MSA, whereas the rescue markers failed to keep pace with the increasing challenge from MSA. GRP78 is the rheostat of the ER stress transducers. In GRP78-overexpressing cells, the ability of MSA to up-regulate phospho-PERK, phospho-eIF2alpha, GRP94, caspase-12, caspase-7, and CHOP/GADD153 was significantly muted. A generous supply of GRP78 would allow cells to cope better with ER stress, thereby improving the odds for survival and negating the commitment to apoptotic death. The present study thus provides strong evidence to support an important role of ER stress response in mediating the anticancer effect of selenium.

Apoptosis↗
PubMed2005

The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump.

Extracellular pH is usually low in solid tumors, in contrast to the approximately neutral intracellular pH. V-ATPase, which overly functions in some cancers with metastatic potential, plays an important role in maintaining neutral cytosolic pH, very acidic luminal pH, and acidic extracellular pH. ATP6L, the 16 kDa subunit of proton pump V-ATPase, can provide proton hydrophilic transmembrane path. In this study, ATP6L in a human hepatocellular carcinoma cell line with highly metastatic potential (HCCLM3) was knocked down using DNA vector-based small interfering RNA (siRNA) to suppress the metastasis. The expression of ATP6L in stable siRNA transfectants, designated as si-HCCLM3 cells, was inhibited by approximately 60%. The proton secretion and the intracellular pH recovery from NH4Cl-prepulsed acidification were inhibited in si-HCCLM3 cells. The invasion of the si-HCCLM3 cells was suppressed in vitro; simultaneously, the expressions of matrix metalloproteinase-2 and gelatinase activity were reduced. In vivo, at 35th day after implantation of the si-HCCLM3 xenografts into the livers in BalB/c (nu+/nu+) mice, the size of liver tumor tissues was dramatically smaller in siRNA group than in the controlled group. The most impressing effect of ATP6L siRNA is its striking reduction of the metastatic potential of HCCLM3 cells. In control, all eight mice had the intrahepatic metastasis and six of eight the pulmonary metastasis, whereas in ATP6L siRNA-treated group, three of eight had the intrahepatic metastasis and only one of eight the pulmonary metastasis. The results suggest that the inhibition of V-ATPase function via knockdown of ATP6L expression using RNA interfering technology can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity.

Animals↗