Biomedical subjects

Jun Zhu

Publications and source records attributed to Jun Zhu.

At least 19 recordsLinked to original sources

PubMed2026

The Znf711-Phf8 complex functions as a transcriptional rheostat essential for neutrophil development.

Neutrophil differentiation is governed by a precise transcriptional and epigenetic program. Here, we identify the zinc finger protein 711 (Znf711) and its partner, the histone demethylase PHD finger protein 8 (Phf8), as essential regulators of terminal granulopoiesis. Contrary to their established role as a transcriptional activator-co-activator pair, we found that the Znf711- Phf8 complex operates through a repressive mechanism. Znf711 promotes neutrophil maturation in a DNA-binding-independent manner by sequestering Phf8. Upon loss of Znf711, Phf8 is recruited by the growth factor independent 1 transcription repressor (Gfi1aa) to the promoter of the master regulator c/ebpα, where SUMOylated Phf8 acts as a corepressor to inhibit its transcription. Furthermore, we delineate a positive feedback loop wherein C/ebpα directly activates znf711 expression, ensuring a high level of c/ebpα at the onset of differentiation. Our findings define the Znf711-Phf8 complex as a critical transcriptional rheostat in neutrophil development.

Humans↗

PubMed2025

Synergic impact mechanisms of cover crop residue on Cd and As availability and native organic carbon mineralization in Cd and As co-contaminated paddy soil.

The synergic impacts of cover crop residue on heavy metal and metalloid availability and soil organic carbon (SOC) mineralization in contaminated paddy soil and the underlying microbial mechanism remain unclear. This study investigated the availability of cadmium (Cd) and arsenic (As) and mineralization of native SOC in paddy soil treated with 0, 0.4 %, 0.8 % and 1.2 % of δ13C-labeled cover crop residue (Astragalus sinicus L.) via 90-day incubation experiments, the related functional genes and functional microbial communities were analyzed using metagenomic binning assembly. Cover crop residue with addition rate from 0.4 % to 1.2 % significantly decreased available Cd by 56 %-85 % but increased available As by 39 %-66 % compared to the control treatment. Cover crop residue resulted in a positive priming effect on native SOC mineralization but benefited SOC sequestration. Cover crop residue increased the abundance of genes encoding iron reductase (mtrABC, pilA, omcB), sulfate reductase (sir, fpr), As(V) reductase (ArsC), organic carbon hydrolases, methanogenesis, and methylotrophy. Genomes associated with Chloroflexota and Bacteroidota encoded all these key pathways, and their abundance increased with cover crop residue application. Cover crop residue decreased soil Eh, dissolved crystalline iron oxides, enriched specific microorganisms, including Chloroflexota and Bacteroidota, and then synergistically promoted the decrease in Cd availability and the increase in As availability and native SOC mineralization in the examined paddy soil. These findings provided practical and feasible guidance for achieving both safe production and carbon sequestration in contaminated paddy fields, highlighting the requirement to cautious utilization of cover crop residue in As-contaminated paddy fileds.

Soil Pollutants↗

PubMed2025

Modulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.

With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing. NECTIN4-CAR T cells have potent anti-tumor activity even against EV resistant cells, which largely retain NECTIN4 expression, including in a post-EV biopsy cohort. Our results elucidate a therapeutically actionable mechanism that UC cells use to control NECTIN4 expression and suggest therapeutic approaches that leverage PPARγ agonists for rational combinations with NECTIN4-targeting agents in UC, as well as future potential treatment options for EV-refractory patients.

Humans↗

PubMed2023

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Animals↗

PubMed2007

Detection of minor drug-resistant populations by parallel allele-specific sequencing.

We developed a highly sensitive parallel allele-specific sequencing (PASS) assay to simultaneously analyze a large number of viral genomes and detect minor drug-resistant populations at approximately 0.1-0.01% levels. Using this assay on samples from individuals infected with human immunodeficiency viruses (HIV), we successfully detected and quantified minor populations of drug-resistant viruses and performed linkage analysis of multiple-drug resistance mutations. This assay may serve as a useful tool to study drug resistance in HIV and other infectious agents.

Anti-HIV Agents↗

PubMed2006

Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo.

MAGE-D1 is a member of the MAGE family of proteins, and functions as an adaptor that mediates multiple signaling pathways. The current study for the first time provides evidence for a role of MAGE-D1 in the negative regulation of angiogenic activity in vitro and in vivo models. Our findings showed that MAGE-D1 over-expression significantly suppressed the angiogenic key events such as endothelial cell migration and invasion, adhesion on collagen I substrate, and in vitro differentiation into tube-like structures under both normoxic and hypoxic conditions. MAGE-D1 over-expression also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. With further experiments, we revealed that MAGE-D1 over-expression disrupted actin cytoskeleton organization and lamellipodia formation, and down-regulated HIF-1-dependent gene expression in endothelial cells under hypoxic conditions. These findings demonstrate a new function of MAGE-D1 in the regulation of angiogenesis and provide new insight into the ability of MAGE-D1 to suppress the growth and angiogenic response of endothelial cells by interfering with HIF-1-dependent gene expression, and actin cytoskeleton reorganization, suggesting that MAGE-D1 might be a novel inhibitor of angiogenesis in vitro and in vivo.

Actins↗

PubMed2006

Serum-free mouse embryo cells generate a self-sustaining feedback loop for an astrocyte marker protein and respond to cytokines and bisphenol A in accordance with the subtle difference in their differentiation state.

Serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, generated a self-sustaining feedback loop for glial fibrillary acidic protein (GFAP) expression after a period of cell passages. The period required was about 150 days (30 passages). SFME and high-GFAP-expressing SFME (G-SFME) cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10 ng/ml bone morphogenetic protein 2 (BMP2) to induce differentiation and their responses to cytokine signals were analyzed. Although differentiation was significantly induced in both cell types, SFME cells showed more obvious responses to the cytokine signals. Various concentrations of bisphenol A (BPA) (0.1 pg/ml to 1 microg/ml) were added to determine its effects on cell differentiation. A completely serum-free culture was developed for effective differentiation of G-SFME cells with LIF and BMP2, and GFAP expression was significantly increased in the presence of 1-100 pg/ml BPA. These increases were attributed to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA. The data obtained in the present study revealed that the sensitivity of the cells to LIF, BMP2 and BPA could change upon cell differentiation, suggesting that the cells may possibly respond differently to cytokines and endocrine disruptors depending on subtle differences in their differentiation state.

Animals↗

PubMed2006

Temporal quorum-sensing induction regulates Vibrio cholerae biofilm architecture.

Vibrio cholerae, the pathogen that causes cholera, also survives in aqueous reservoirs, probably in the form of biofilms. Quorum sensing negatively regulates V. cholerae biofilm formation through HapR, whose expression is induced at a high cell density. In this study, we show that the concentration of the quorum-sensing signal molecule CAI-1 is higher in biofilms than in planktonic cultures. By measuring hapR expression and activity, we found that the induction of quorum sensing in biofilm-associated cells occurs earlier. We further demonstrate that the timing of hapR expression is crucial for biofilm thickness, biofilm detachment rates, and intestinal colonization efficiency. These results suggest that V. cholerae is able to regulate its biofilm architecture by temporal induction of quorum-sensing systems.

Bacterial Proteins↗

PubMed2006

A retro-Diels-Alder reaction to uncover maleimide-modified surfaces on monolayer-protected nanoparticles for reversible covalent assembly.

Maleimide-modified monolayer-protected gold nanoparticles (MPGN) are prepared from the protected furan-maleimide via the thermally reversible Diels-Adler reaction when required. These maleimide-MPGNs serve as a general platform allowing for a Diels-Alder reaction with furan-modified MPN to prepare larger 3D networks reversibly. [reaction: see text]

Journal Article↗

PubMed2006

Osmabenzenes from the reactions of a dicationic osmabenzyne complex.

Treatment of the osmabenzyne Os([triple bond]CC(SiMe(3))=C(Me)C(SiMe(3))=CH)Cl(2)(PPh(3))(2) (1) with 2,2'-bipyridine (bipy) and thallium triflate (TlOTf) produces the thermally stable dicationic osmabenzyne [Os([triple bond]CC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)](OTf)(2) (2). The dicationic osmabenzyne 2 reacts with ROH (R = H, Me) to give osmabenzene complexes [Os(=C(OR)CH=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf, in which the metallabenzene ring deviates significantly from planarity. In contrast, reaction of the dicationic complex 2 with NaBH(4) produces a cyclopentadienyl complex, presumably through the osmabenzene intermediate [Os(=CHC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf. The higher thermal stability of [Os(=C(OR)CH=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf relative to [Os(=CHC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf can be related to the stabilization effect of the OR groups on the metallacycle. A theoretical study shows that conversion of the dicationic osmabenzyne complex [Os([triple bond]CC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)](OTf)(2) to a carbene complex by reductive elimination is thermodynamically unfavorable. The theoretical study also suggests that the nonplanarity of the osmabenzenes [Os(=C(OR)CH=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf is mainly due to electronic reasons.

Journal Article↗

PubMed2006

[Expression of peroxisome proliferators-activated receptor-gamma and cyclooxygenase-2 in Helicobacter pylori infection-associated diseases and significance thereof].

OBJECTIVE: To investigate the expression of peroxisome proliferators-activated receptor-gamma (PPAR-gamma) and cyclooxygenase-2 (COX-2) in Helicobacter pylori (Hp)-associated gastric mucosal lesions and the relations among them. METHODS: Two-step immunohistochemical staining was used to detect the expression of PPAR-gamma and COX-2 proteins in the gastric biopsy specimens from 209 patients with lesions of gastric mucosa, including 75 cases of chronic superficial gastritis (CSG), 24 cases of chronic atrophic gastritis (CAG), and 90 cases of intestinal metaplasia (MI) and dysplasia (DYS), and from 20 subjects with normal gastric mucosa negative in Hp as controls. In addition, 36 CSG patients were followed up for 10 years to observe the changes of expression of PPAR-gamma and COX-2. RESULTS: (1) The expression of COX-2 protein in the glandular cells of the CSG, CAG, and IM + DYS groups were 42.7%, 45.8%, and 61.1% respectively, all significantly higher than that of the control group (20%, P < 0.01 or 0.05). The expression of COX-2 protein in the inflammatory cells of the CSG, CAG, and IM + DYS groups were 32%, 29.2%, and 36.7% respectively, all significantly higher than that of the control group (0%, all P < 0.05). (2) In the CSG and IM + DYS groups the expression levels of COX-2 in both the inflammatory and glandular cells were both significantly higher in the Hp-positive patients than in the Hp-negative patients (P < 0.05 or 0.01). (3) The expression of PPAR-gamma protein in the glandular cells of the CSG, CAG, and IM + DYS groups were 18.7%, 29.2%, and 45.6% respectively, all significantly higher than that of the control group (0%, all P < 0.01); and the expression levels of PPAR-gamma protein in the inflammatory cells of the CSG, CAG, and IM + DYS groups were 22.5%, 20.8%, and 22.2% respectively, all significantly higher than that of the control group (0%, P < 0.05 or 0.01). (4) In the CSG and IM + DYS groups the expression levels of PPAR-gamma in the inflammatory cells of the Hp-positive patients were both significantly higher than those of the Hp-negative patients (both P < 0.01); and the. expression levels of PPAR-gamma in the glandular cells of the Hp-positive patients were both significantly higher than those of the Hp-negative patients (both P < 0.01). (5) The expression level of COX-2 in the inflammatory cells of the CSG patients with a persistent Hp infection after a period of ten years was 33.3%, significantly lower than that a decade before (38.9%, P < 0.05). However, the expression level of PPAR-gamma in the inflammatory cells of the patients with a persistent Hp infection after a period of ten years was 30.6%, not significantly different from that a decade before (33.3%, P > 0.05). (6) The expression levels of COX-2 and PPAR-gamma in the glandular cells of the CSG patients with a persistent Hp infection after a period of ten years were 55.6% and 30.6% respectively, both significantly higher than those a decade before (47.2% and 22.2%, both P < 0.01). (7) In all Hp-negative disease groups the expression level of COX-2 in the inflammatory cells was not significantly correlated with the expression level of PPAR-gamma in the inflammatory cells(r = 0.006 and 0.149, P > 0.05) In the Hp-negative disease groups, the expression level of COX-2 in the glandular cells was significantly positively correlated with the expression level of PPAR-gamma in the glandular cells in the IM + DYS group (r = 0.336, P < 0.05), however, not significantly correlated with the expression level of PPAR-gamma in the glandular cells in both CAG and CSG groups (r = 0.035 and 0.126, both P > 0.05). (8) In both the inflammatory cells and glandular cells the COX-2 expression was significantly positively correlated with the PAR-gamma expression in all disease groups with Hp positivity (r = 0.348 and 0.645, P < 0.05 or 0.01). CONCLUSION: (1) Hp infection induces the overexpression of COX-2 and PPAR-gamma in the inflammatory and glandular cells within gastric mucosa, thus participating in the pathogenesis of gastric cancer (2) The expression of COX-2 induces by Hp is related to acute inflammation caused by Hp infection. In the glandular cells, significant increase of COX-2 and PPAR-gamma expression implies that along with time the expression of COX-2 and PPAR-gamma may change in advance of the morphological changes of the gastric mucosa.

Adult↗

PubMed2006

On the generalized poisson regression mixture model for mapping quantitative trait loci with count data.

Statistical methods for mapping quantitative trait loci (QTL) have been extensively studied. While most existing methods assume normal distribution of the phenotype, the normality assumption could be easily violated when phenotypes are measured in counts. One natural choice to deal with count traits is to apply the classical Poisson regression model. However, conditional on covariates, the Poisson assumption of mean-variance equality may not be valid when data are potentially under- or overdispersed. In this article, we propose an interval-mapping approach for phenotypes measured in counts. We model the effects of QTL through a generalized Poisson regression model and develop efficient likelihood-based inference procedures. This approach, implemented with the EM algorithm, allows for a genomewide scan for the existence of QTL throughout the entire genome. The performance of the proposed method is evaluated through extensive simulation studies along with comparisons with existing approaches such as the Poisson regression and the generalized estimating equation approach. An application to a rice tiller number data set is given. Our approach provides a standard procedure for mapping QTL involved in the genetic control of complex traits measured in counts.

Algorithms↗

PubMed2006

Vibrio cholerae virulence regulator-coordinated evasion of host immunity.

To successfully propagate and cause disease, pathogenic bacteria must modulate their transcriptional activities in response to pressures exerted by the host immune system, including secreted immunoglobulins such as secretory IgA (S-IgA), which can bind and agglutinate bacteria. Here, we present a previously undescribed flow cytometry-based screening method to identify bacterial genes expressed in vitro and repressed during infections of Vibrio cholerae, an aquatic Gram-negative bacterium responsible for the severe diarrheal disease cholera. We identified a type IV mannose-sensitive hemagglutinin (MSHA) pilus that is repressed specifically in vivo. We showed that bacteria that failed to turn off MSHA biosynthesis were unable to colonize the intestines of infant mice in the presence of S-IgA. We also found that V. cholerae bound S-IgA in an MSHA-dependent and mannose-sensitive fashion and that binding of S-IgA prevented bacteria from penetrating mucus barriers and attaching to the surface of epithelial cells. The ability of V. cholerae to evade the non-antigen-specific binding of S-IgA by down-regulating a surface adhesin represents a previously undescribed mechanism of immune evasion in pathogenic bacteria. In addition, we found that repression of MSHA was mediated by the key virulence transcription factor ToxT, indicating that V. cholerae is able to coordinate both virulence gene activation and repression to evade host defenses and successfully colonize intestines.

Animals↗

PubMed2006

Effects of low-molecular-weight organic ligands and phosphate on DNA adsorption by soil colloids and minerals.

Adsorption of DNA on montmorillonite, kaolinite, goethite and soil clays from an Alfisol in the presence of citrate, tartrate and phosphate was studied. A marked decrease in DNA adsorption was observed on montmorillonite and kaolinite with increasing anion concentrations from 0 to 5 mM. However, the amount of DNA adsorbed by montmorillonite and kaolinite was enhanced when ligand concentration was higher than 5 mM. In the system of soil colloids and goethite, with the increase of anion concentrations, a steady decrease was found and the ability of ligands in depressing DNA adsorption followed the sequence: phosphate > citrate > tartrate. Compared to H2O2-treated clays (inorganic clays), a sharp decrease in DNA adsorption was observed on goethite and organo-mineral complexes (organic clays) with increasing ligand concentrations. The results suggest that the influence of anions on DNA adsorption varies with the type and concentration of anion as well as the surface properties of soil components. Introduction of DNA into the system before the addition of ligands had the greatest amount of DNA adsorption on soil colloids and goethite. Organic and inorganic ligands promoted DNA adsorption on montmorillonite and kaolinite when ligands were introduced into the system before the addition of DNA. The results obtained in this study have important implications for the understanding of the persistence and fate of DNA in soil environments especially rhizosphere soil where various organic and inorganic ligands are active.

Adsorption↗

PubMed2006

Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats.

AIM: To investigate the role of IFN-gamma inducible protein -10 (IP-10) and regulated upon activation, normal T cell expressed and secreted (RANTES) protein in acute pancreatic allograft rejection in rats. METHODS: An experimental pancreas transplantation model was established using diabetic SD rats as the recipient, induced by applying streptozocin (STZ). Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group (group A, n = 24) and allograft group (group B, n = 24) in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS: In group B (allograft group), the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A (isograft group). CONCLUSION: Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.

Animals↗

PubMed2006

Low-level bisphenol A increases production of glial fibrillary acidic protein in differentiating astrocyte progenitor cells through excessive STAT3 and Smad1 activation.

The effects of bisphenol A (BPA) on the differentiation of serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, were examined. SFME cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10ng/ml bone morphogenetic protein 2 (BMP2) to increase glial fibrillary acidic protein (GFAP) expression and induce cell differentiation. Various concentrations of BPA (0.1 pg/ml-1 microg/ml) were then added to determine their effects on the cell differentiation. SFME cells were effectively differentiated by LIF and BMP2 in completely serum-free cultures. Cell proliferation following cell differentiation was not significantly affected by low-level BPA. However, GFAP expression was significantly increased in SFME cells in the presence of 1-100 pg/ml BPA. These increases were due to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA.

Air Pollutants, Occupational↗

PubMed2006

Characterization of endogenous human promyelocytic leukemia isoforms.

Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s).

Animals↗

PubMed2006

Dimerization-induced corepressor binding and relaxed DNA-binding specificity are critical for PML/RARA-induced immortalization.

The pathogenesis of acute promyelocytic leukemia involves the transcriptional repression of master genes of myeloid differentiation by the promyelocytic leukemia-retinoic acid receptor alpha (PML/RARA) oncogene. PML-enforced RARA homodimerization allows the tighter binding of corepressors, silencing RARA target genes. In addition, homodimerization dramatically extends the spectrum of DNA-binding sites of the fusion protein compared with those of normal RARA. Yet, any contribution of these two properties of PML/RARA to differentiation arrest and immortalization of primary mouse hematopoietic progenitors was unknown. We demonstrate that dimerization-induced silencing mediator of retinoid and thyroid receptors (SMRT)-enhanced binding and relaxed DNA-binding site specificity are both required for efficient immortalization. Thus, enforced RARA dimerization is critical not only for triggering transcriptional repression but also for extending the repertoire of target genes. Our studies exemplify how dimerization-induced gain of functions converts an unessential transcription factor into a dominant oncogenic protein.

Animals↗