Biomedical subjects

Jie Zhang

Publications and source records attributed to Jie Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2025

The role of the brain-bone axis in skeletal degenerative diseases and psychiatric disorders, A genome-wide pleiotropic analysis.

INTRODUCTION: Skeletal degenerative diseases and psychiatric disorders often coexist clinically. However, the genetic correlations and underlying biological mechanisms between these two types of diseases remain unclear. OBJECTIVES: To investigate the genetic correlations between skeletal degenerative diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways. METHODS: This comprehensive genome-wide pleiotropic association study utilized summary statistics from publicly available genome-wide association data. Various statistical genetic correlation methods were employed, including LDSC, HDL, PLACO, Coloc, Hyprcoloc, and Mendelian randomization (MR) analysis, along with immune cell colocalization analysis. The study aimed to identify potential shared genetic factors among three skeletal degenerative diseases (osteoarthritis, intervertebral disc degeneration, and osteoporosis) and three psychiatric disorders (schizophrenia, anxiety disorder, and major depressive disorder). RESULTS: Analyses using LDSC, HDL, and Bonferroni corrections revealed significant genetic correlations between intervertebral disc degeneration (IVDD) and anxiety disorder (ANX); fractures, IVDD, and arthritis with major depressive disorder (MDD); and arthritis with schizophrenia (SCZ). Significant genetic correlations were also observed between VDD and ANX, fractures, IVDD, hip osteoarthritis (HipOA), knee osteoarthritis (KneeOA) and MDD, and KneeOA and SCZ. Pleiotropy analysis using PLACO, MAGMA, and multitrait colocalization Hyprcoloc identified 65 pleiotropic loci, 27 shared causal loci, and 9 shared risk loci involving immune cells related to both psychiatric and bone-related diseases. Additionally, tissue-specific enrichment analysis showed that genes mapped to these loci were enriched in brain, cardiovascular, pancreatic, and other tissues. The IVW method demonstrated that MDD increased the risk of IVDD and KneeOA, while IVDD increased the risk of ANX and MDD. Conversely, SCZ was associated with a reduced risk of KneeOA. Multiple sensitivity analyses further supported a positive causal effect of IVDD on MDD. CONCLUSION: These findings suggest significant genetic correlations between skeletal degenerative diseases and psychiatric disorders, highlighting multiple shared comorbid genes and key immune cell types. Importantly, the study supports the role of the brain-bone axis in the regulation of skeletal degenerative diseases and psychiatric disorders, which could provide valuable insights for potential therapeutic targets and interventions for these conditions.

Humans↗

PubMed2024

Integrated ubiquitomics characterization of hepatocellular carcinomas.

BACKGROUND AND AIMS: Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. APPROACH AND RESULTS: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 patients with HCC. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1, and LAMA4 were highly expressed in the disease free survival-poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed cross talk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to protein kinase B-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. CONCLUSIONS: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.

Humans↗

PubMed2007

Regression models for mixed Poisson and continuous longitudinal data.

In this article we develop flexible regression models in two respects to evaluate the influence of the covariate variables on the mixed Poisson and continuous responses and to evaluate how the correlation between Poisson response and continuous response changes over time. A scenario for dealing with regression models of mixed continuous and Poisson responses when the heterogeneous variance and correlation changing over time exist is proposed. Our general approach is first to jointly build marginal model and to check whether the variance and correlation change over time via likelihood ratio test. If the variance and correlation change over time, we will do a suitable data transformation to properly evaluate the influence of the covariates on the mixed responses. The proposed methods are applied to the interstitial cystitis data base (ICDB) cohort study, and we find that the positive correlations significantly change over time, which suggests heterogeneous variances should not be ignored in modelling and inference.

China↗

PubMed2007

Facile construction of lanthanide metallomacrocycles with the bridging imidazolate and triazolate ligands and their ring expansions.

Four novel tri- or tetranuclear organolanthanide metallomacrocycles [Cp2Ln(mu-Im)(THF)3 (Cp = C5H5, Ln = Yb (1), Er (2)], [Cp2Dy(mu-Im)]4(THF)]3 x 2THF (3), and [Cp'2Yb(mu-eta1:eta2-Tz)]4 x 2THF (Cp' = CH3C5H4) (4) have been synthesized through protolysis of Cp3Ln or Cp'3Yb with imidazole or triazole, indicating that both the bridge-ligand size and the lanthanide-ion radii can be applied in the modulation of the metallomacrocycles. Further investigations on the reactivity of complexes 1, 3, and 4 toward phenyl isocyanate reveal that PhNCO inserts readily into the simple bridge Ln-N bonds of 1 and 3 to yield the corresponding insertion products [Cp2Ln(mu-eta1:eta2-OC(Im)NPh)]3 (Ln = Yb (5), Dy (6)) but cannot insert into the Ln-N bond with a mu-eta1:eta2-bonding mode in 4. The novel bridge ligand [OC(Im)NPh] can expand the numbers of the ring members from 12 to 18 in 5 or 16 to 18 in 6. The number of metal atoms in the metallacycles with the ligand [OC(Im)NPh] is independent of the lanthanide-ion size; both trinuclear lanthanide macrocycles are observed in 5 and 6. All of these new complexes have been characterized by elemental analysis and spectroscopic properties, and their structures have also been determined through X-ray single-crystal diffraction analysis.

Crystallography, X-Ray↗

PubMed2007

A nonlinear model for assessing multiple probabilistic risks: a case study in South five-island of Changdao National Nature Reserve in China.

Several methods for estimating the potential impacts caused by multiple probabilistic risks have been suggested. These existing methods mostly rely on the weight sum algorithm to address the need for integrated risk assessment. This paper develops a nonlinear model to perform such an assessment. The joint probability algorithm has been applied to the model development. An application of the developed model in South five-island of Changdao National Nature Reserve, China, combining remote sensing data and a GIS technique, provides a reasonable risk assessment. Based on the case study, we discuss the feasibility of the model. We propose that the model has the potential for use in identifying the regional primary stressor, investigating the most vulnerable habitat, and assessing the integrated impact of multiple stressors.

China↗

PubMed2007

Application of EGFP-EGF fusions to explore mechanism of endocytosis of epidermal growth factor.

AIM: To develop a simple method for monitoring protein localization of epidermal growth factor (EGF) in living cells. METHODS: Enhanced green fluorescent protein (EGFP) was used as an autofluorescent tag to label EGF ligands. SDS-PAGE and Western blot analysis were used to detect the expression of the EGFP-tagged EGF (EGFP-EGF) protein. The cell-binding and internalization activity of EGFP-EGF were analyzed by fluorescence-activated cell sorting (FACS) and confocal microscopy. RESULTS: EGFP-EGF protein was expressed in Escherichia coli and purified. A cell-binding assay demonstrated that the EGFP-EGF protein could bind efficiently to the cells expressing EGFR. The binding and internalization of EGFP-EGF can be visualized even at a very low concentration under confocal microscopy. The FACS-based assay for internalization activity indicated the accumulation of internalized EGFP-EGF over time. Furthermore, the results of the competition assay indicated its EGFR binding specificity. Using such a method, it does not need to label EGF with chemicals and avoid light in the experimental process. CONCLUSION: The fusion protein EGFP-EGF has several characters including high sensitivity, stability and convenience for manipulation, and is a powerful tool for the study of EGF endocytosis.

Binding, Competitive↗

PubMed2007

SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines.

The role of Src-family kinases (SFKs) in non-small cell lung cancer (NSCLC) has not been fully defined. Here we addressed this question by examining SFK phosphorylation in NSCLC biopsy samples and using genetic and pharmacological approaches to inhibit SFK expression and activity in cultured NSCLC cells. Immunohistochemical analysis of NSCLC biopsy samples using a Tyr416 phosphorylation-specific, pan-SFK antibody revealed staining in 123 (33%) of 370 tumors. Because c-Src is known to be both an upstream activator and downstream mediator of epidermal growth factor receptor (EGFR), we next investigated SFK phosphorylation in a panel of NSCLC cell lines, including ones that depend on EGFR for survival. The EGFR-dependent NSCLC cell lines HCC827 and H3255 had increased phosphorylation of SFKs, and treatment of these cells with an SFK inhibitor (PP1 or SKI-606) induced apoptosis. PP1 decreased phosphorylation of EGFR, ErbB2, and ErbB3 and strikingly enhanced apoptosis by gefitinib, an EGFR inhibitor. HCC827 cells transfected with c-Src short hairpin RNA exhibited diminished phosphorylation of EGFR and ErbB2 and decreased sensitivity to apoptosis by PP1 or gefitinib. We conclude that SFKs are activated in NSCLC biopsy samples, promote the survival of EGFR-dependent NSCLC cells, and should be investigated as therapeutic targets in NSCLC patients.

Aniline Compounds↗

PubMed2006

Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model.

Nicotine has a therapeutic benefit in treating Alzheimer's disease (AD). In the present study we show that nicotine decreases accumulation of beta-amyloid (Abeta) in the cortex and hippocampus of APP (V717I) transgenic mice. Nicotine prevents activation of NF-kappaB and c-Myc by inhibiting the activation of MAP kinases (MAPKs). As a result, the activity of inducible NOS and the production of NO are down-regulated. RNA interference experiments show that the above nicotine-mediated process requires alpha7 nAChR. Nicotine decreases Abeta via the activation of alpha7nAChRs through MAPK, NF-kappaB, and c-myc pathways. Nicotine also inhibits apoptosis and cell cycle progression in this mouse line. The dissected signaling pathway of nicotine-mediated neuroprotection in the present study provides a mechanistic basis for the potential development of drug targets for treating AD.

Alzheimer Disease↗

PubMed2006

Bacisubin, an antifungal protein with ribonuclease and hemagglutinating activities from Bacillus subtilis strain B-916.

An antifungal protein, with a molecular mass of 41.9 kDa, and designated as bacisubin, was isolated from a culture of Bacillus subtilis strain B-916. The isolation procedure consisted of ion exchange chromatography on DEAE-Sepharose Fast Flow, and fast protein liquid chromatography on Phenyl Sepharose 6 Fast Flow and hydroxyapatite columns. The protein was adsorbed on all three chromatographic media. Bacisubin exhibited inhibitory activity on mycelial growth in Magnaporthe grisease, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria oleracea, A. brassicae and Botrytis cinerea. The IC50 values of its antifungal activity toward the last four fungal species were 4.01 microM, 0.087 microM, 0.055 microM and 2.74 microM, respectively. Bacisubin demonstrated neither protease activity, nor protease inhibitory activity. However, it manifested ribonuclease and hemagglutinating activities.

Amino Acid Sequence↗

PubMed2006

Expression of a sorcin missense mutation in the heart modulates excitation-contraction coupling.

Sorcin is a Ca2+ binding protein implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. Structural and human genetic studies suggest that a naturally occurring sequence variant encoding L112-sorcin disrupts an E-F hand Ca2+ binding domain and may be responsible for a heritable form of hypertension and hypertrophic heart disease. We generated transgenic mice overexpressing L112-sorcin in the heart and characterized the effects on Ca2+ regulation and cardiac function both in vivo and in dissociated cardiomyocytes. Hearts of sorcin(F112L) transgenic mice were mildly dilated but ventricular function was preserved and systemic blood pressure was normal. Sorcin(F112L) myocytes were smaller than control cells and displayed complex alterations in Ca2+ regulation and contractility, including a slowed inactivation of L-type Ca2+ current, enhanced Ca2+ spark width, duration, and frequency, and increased Na+-Ca2+ exchange activity. In contrast, mice with cardiac-specific overexpression of wild-type sorcin displayed directionally opposite effects on L-type Ca2+ channel function and Ca2+ spark behavior. These data further define the role of sorcin in cardiac excitation-contraction coupling and highlight its negative regulation of SR calcium release. Our results also suggest that additional factors may be responsible for the development of cardiac hypertrophy and hypertension in humans expressing the L112-sorcin sequence variant.

Animals↗

PubMed2006

Determination of n-octanol-water partition coefficients by hollow-fiber membrane solvent microextraction coupled with HPLC.

A novel direct method has been developed for determination of n-octanol-water partition coefficients by hollow-fiber membrane solvent microextraction (HFMSME) combined with high-performance liquid chromatography (HPLC). The compound of interest is dissolved in water with sonication and a hollow fiber containing octanol inside is placed in the sample solution to perform microextraction. After microextraction the concentrations in both the aqueous and n-octanol phases are analyzed by HPLC with UV detection. The method was evaluated with ten reference compounds and shown to be suitable for determination of the partition coefficients of organic compounds accurately, cheaply, simply, and quickly. Previously unknown n-octanol-water partition coefficients have been obtained for other compounds by use of the hollow-fiber membrane solvent-microextraction technique.

1-Octanol↗

PubMed2006

Forskolin and 8-cyclopentyltheophylline synergistically facilitate the neuronal activity in the CA2 area of rat hippocampus via cAMP and non-cAMP cascades.

High level of adenosine A1 receptor-like immunoreactivity has been found in the CA2/CA3a region of adult rat hippocampus, but its roles in the neuronal activity or signal propagation in hippocampus and its intracellular cascade remain to be studied. In this study, we examined the relation between adenosine-3',5'-cyclic monophosphate (cAMP) cascade and suppression of synaptic transmission by endogenous adenosine through adenosine A1 receptor in the CA2 area. In transverse hippocampal slice, maximal electrical stimulation of the hilus region (0.6 mA) only evoked small population spikes (PSs) in the CA2 area (0.5 mV). In the presence of forskolin (20 micromol/L), a direct adenylate cyclase activator, PSs in CA2 were increased to 1.1 mV. When 8-cyclopentyltheophylline (8CPT, 2 micromol/L), an adenosine A1 receptor antagonist, was added in the presence of 20 micromol/L forskolin, PSs with an average amplitude of 4.7 mV were recorded in the CA2 area, much higher than the sum of the amplitude of PSs in the presence of forskolin and 8CPT alone. To test whether this synergistic potentiation results from the additive activation of cAMP cascade, the cAMP content in hippocampal slices was measured with enzyme immunoassay (EIA). Results showed that 8CPT did not increase the cAMP content in CA2 with or without forskolin. Co-application of forskolin and Ro 20-1724, a cAMP-specific phosphodiesterase-IV inhibitor, only increased PSs in CA2 to 1.3 mV but increased cAMP content by 4.4 times. On the other hand, co-application of 8CPT and 1, 9-dideoxyforskolin, a forskolin analog which has no effect on adenylate cyclase, did not mimic the synergistic effect of 8CPT and forskolin on PSs in CA2. These results indicate that up-regulation of adenylate cyclase activity and inhibition of adenosine A1 receptor activity synergistically facilitate the neuronal activity in the CA2 area and the effect of adenosine A1 receptor antagonist is via non-cAMP cascade. These data also suggest that acting on adenosine A1 receptors, endogenous and extragenous adenosine/adenosine A1 agonist(s) inhibit neuronal activity through different pathways.

Adenosine A1 Receptor Antagonists↗

PubMed2006

Pathological effects of the mushroom toxin alpha-amanitin on BALB/c mice.

The pathological effects of alpha-amanitin on BALB/c mice after receiving intravenous injection were evaluated by RP-HPLC and mouse genome oligonucleotide microarray. The content of alpha-amanitin in Amanita virosa was about 2833.8 microg/g dry fruiting body. The liver and kidneys showed critical pathological changes after alpha-amanitin poisoning, and sera BUN, Crea, ALT, AST, TBIL and DBIL were the sensitive markers. The compound alpha-amanitin was detected in liver and kidney tissue homogenates by RP-HPLC after 48 h. The results of mouse genome oligonucleotide microarray showed 146 genes' expression changed, which formed the alternant network. The expression of 66 genes decreased, while 80 ones increased with more than two-fold differential expression after 48 h. The compound alpha-amanitin influenced not only RNA polymerase II, but also the expression of its associated genes. The application of mouse oligo chip provided valuable data for further understanding the biological properties and molecular pathogenesis of alpha-amanitin, also might be helpful for screening the curative drug for alpha-amanitin intoxication.

Amanita↗

PubMed2006

Stereotactic cyst/ventricular-peritoneal shunting for the treatment of prepontine arachnoid cyst: case report.

BACKGROUND: Prepontine (suprasellar) arachnoid cysts are uncommon in clinical practice, so experiences in their management are limited and the best method of treatment for them remains unclear. Here we report our experience in using stereotactic cyst/ventricular-peritoneal shunting for the treatment of prepontine arachnoid cyst. CASE DESCRIPTION: A 42-year-old woman with prepontine arachnoid cyst was treated with cyst/ventricular-peritoneal shunting: the ventricular catheter was precisely inserted at a point where it could drain from the cyst and the ventricle at the same time. The postoperation CT scan showed that the cyst and the enlarged ventricle shrunk markedly. During a 1-year follow-up period, she remained symptom-free and had returned to full-time work. CONCLUSION: Stereotactic cyst/ventricular-peritoneal shunting appears to be an effective method for treating prepontine arachnoid cyst.

Adult↗

PubMed2006

A series of luminescent lanthanide-cadmium-organic frameworks with helical channels and tubes.

Lanthanide (Ln) oxides and cadmium (Cd) salts as sources of metals provided the first series of luminescent Ln-Cd-organic frameworks, [LnCd(imdc)(SO4)(H2O)3].0.5H2O (Ln = Tb, Eu, Dy, Gd, Er, Yb, Y, Nd, Pr; H3imdc = 4,5-imidazoledicarboxylic acid), in which the Ln atoms are linked by imdc ligands with skew coordination orientation, resulting in novel hetero-metallic-organic frameworks with left-/right-handed helical tubes (L1/R1) and channels (L2/R2) along the b axis.

Cadmium↗

PubMed2006

Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis.

Mammalian organogenesis results from the concerted actions of signaling pathways in progenitor cells that induce a hierarchy of regulated transcription factors critical for organ and cell type determination. Here we demonstrate that sustained Notch activity is required for the temporal maintenance of specific cohorts of proliferating progenitors, which underlies the ability to specify late-arising cell lineages during pituitary organogenesis. Conditional deletion of Rbp-J, which encodes the major mediator of the Notch pathway, leads to premature differentiation of progenitor cells, a phenotype recapitulated by loss of the basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late (Pit1) lineage into the early (corticotrope) lineage. Notch signaling is required for maintaining expression of the tissue-specific paired-like homeodomain transcription factor, Prop1, which is required for generation of the Pit1 lineage. Attenuation of Notch signaling is necessary for terminal differentiation in post-mitotic Pit1+ cells, and the Notch-repressed Pit1 target gene, Math3, is specifically required for maturation and proliferation of the GH-producing somatotrope. Thus, sustained Notch signaling in progenitor cells is required to prevent conversion of the late-arising cell lineages to early-born cell lineages, permitting specification of diverse cell types, a strategy likely to be widely used in mammalian organogenesis.

Animals↗

PubMed2006

Self-assembly of Co-based nanosheets into novel nest-shaped nanostructures: Synthesis and characterization.

We report the first observation of the formation of novel Co-based three-dimensional (3D) self-assembly hollow nanostructures, i.e., nest-shaped nanospheres composed of sheet-like particles, via reduction of cobalt salt with sodium tetrahydroboride in cetyltrimethylammonium bromide (CTAB)-cyclohexane-NH4F aqueous solutions. It was found that the cyclohexane has a significant influence on the formation of the nest-shaped Co-based nanospheres, because when the experiments are carried out in the absence of cyclohexane, only sheet-like particles are formed. NH4F plays also an important role in the formation of the hollow nanostructures because without this salt mainly solid spherical structures, composed of sheet-like particles, instead of nest-shaped structures are obtained. The nanostructures are mainly formed by Co, but also a minor amount (17%) of Co2B is present in the final compounds. The structures are characterized by X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), and field-emission scanning electron microscopy (FESEM). A possible mechanism for the formation of the novel Co-based nanostructures is proposed.

Journal Article↗

PubMed2006

Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice.

Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide (NAD) by poly(ADP-ribose) polymerase 1 (PARP-1) and degraded by poly(ADP-ribose) glycohydrolase (PARG). The aim of the present study was to examine the role of PARG in the development of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). Mice lacking the functional 110-kDa isoform of PARG (PARG(110)KO mice) were resistant to colon injury induced by DNBS. The mucosa of colon tissues showed reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Moreover, overproduction of proinflammatory factors TNF-alpha and IL-1beta and activation of cell death signaling pathway, i.e., the FAS ligand, were inhibited in these mutant mice. Finally pharmacological treatment of WT mice with GPI 16552 and 18214, two novel PARG inhibitors, showed a significant protective effect in DNBS-induced colitis. These genetic and pharmacological studies demonstrate that PARG modulates the inflammatory response and tissue injury events associated with colitis and PARG may be considered as a novel target for pharmacological intervention for the pathogenesis.

Animals↗