Biomedical subjects

Zheng Zhao

Publications and source records attributed to Zheng Zhao.

7 recordsLinked to original sources

PubMed2026

SDC1+ CAFs secreting CTGF drive tumour metastasis via FGFR3 signalling in cancers.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key stromal components of the tumour microenvironment (TME) that profoundly influence tumour progression. However, CAFs exhibit pronounced phenotypic and functional heterogeneity, and whether conserved CAF subtypes with shared functional hallmarks exist across different cancer types remains unclear. OBJECTIVE: We sought to uncover universal CAF subtypes that transcend tumour origins, defining their core molecular signatures and pro-tumorigenic functions within the TME. DESIGN: We constructed a pan-cancer CAF atlas through single-cell transcriptomic analysis of 554 specimens across 14 cancer types. To validate the findings, we performed further functional analyses, including in vitro migration and invasion assays, in vivo lymphatic metastasis models and mechanistic studies focusing on candidate signalling pathways. RESULTS: We identified a conserved syndecan 1 (SDC1) + CAF subset associated with advanced tumour stage and poor outcomes. These CAFs enhanced tumour cell migration and invasion in vitro and promoted lymphatic metastasis in vivo. This effect is mediated through connective tissue growth factor (CTGF) secretion, which activates fibroblast growth factor receptor 3 (FGFR3) signalling in tumour cells to induce epithelial-mesenchymal transition (EMT). Blocking CTGF or FGFR3 signalling abrogated these effects. We also found that kruppel like factor 6 (KLF6) directly regulates CTGF in SDC1+ CAFs, establishing a complete KLF6-CTGF-FGFR3 metastatic axis. CONCLUSIONS: Our study establishes SDC1+ CAFs as a universal, metastasis-promoting CAF subset across multiple cancer types and uncovers a novel KLF6-CTGF-FGFR3 axis that drives EMT and tumour dissemination. These findings provide mechanistic insight into CAF-tumour cell crosstalk and highlight actionable stromal targets for anti-metastatic therapies across diverse malignancies.

Humans↗

PubMed2025

eccDNABase: A Comprehensive and High-Quality Database for Extrachromosomal Circular DNA.

Extrachromosomal circular DNA (eccDNA) refers to small, circular DNA molecules that originate from chromosomal sequences and are prevalent across nearly all eukaryotic organisms. In humans, eccDNAs are widely distributed in normal tissues, cancerous tissues, and body fluids, where they play important roles in tumorigenesis and are often associated with poor clinical outcomes. Given their biological and clinical significance, a well-integrated and high-quality database is essential for advancing eccDNA-related research. To address this need, we developed eccDNABase, a comprehensive and curated resource for browsing, searching, and analyzing eccDNAs across multiple species. The database systematically catalogs eccDNA-disease associations from diverse tissues and organisms. Currently, eccDNABase contains 1,875,452 eccDNA-disease associations, encompassing 8,398 ecDNA entries across nine species, 63 diseases, and healthy individuals. Each entry provides detailed information, including eccDNA ID, type, chromosomal localization, species, tissue or cell line source, disease name and Disease Ontology ID, overlap length and percentage with genes, oncogene overlap, detection method, and links to literature and source databases. Given its extensive and curated datasets, eccDNABase serves as a valuable resource for both basic and translational research, offering deeper insights into the role of eccDNA in health and disease. The database is publicly accessible at http://cgga.org.cn/eccDNABase/.

Humans↗

PubMed2006

ADAM28 participates in the regulation of tooth development.

Disintegrin and metalloprotease (ADAM) proteins are a family of membrane-anchored glycoproteins with diverse functions in fertilisation, development, neurogenesis and protein ectodomain shedding. ADAM28 is a newly discovered member of the ADAM family in humans and murine with autocatalytic activity. Recently, the authors screened ADAM28 genes from patients with congenital hypoplasia of tooth root, and studied the relationship between ADAM28 and tooth development. A polyclonal antibody (pAb) against ADAM28 was preparared, and the expression and localisation of ADAM28 were detected in tooth germ and dental mesenchymal cells. The results indicated that the prokaryotic expression vector pGEX-4T-ADAM28 was constructed successfully. Glutathione S-transferase-ADAM28 fusion protein was generated after inducement by isopropylthio-beta-d-galactoside and isolated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The purified fusion protein was used as an antigen for production of antibody. Western blot and enzyme-linked immunosorbent assay analyses verified that the antibody had a high specificity and titre. Immunohistochemistry and reverse transcriptase-polymerase chain reaction showed that ADAM28 was expressed at each stage of tooth germ development at different levels. Moreover, it was expressed in human dental follicle cells, human dental papilla cells, human dental pulp stem cells, human periodontal ligament cells and human dental cervical loop epithelial cells at transcription level. In conclusion, it is reasonable to suggest that ADAM28 may participate in tooth development and the regulation of odontogenic mesenchymal cells through progressive reciprocal inductive interactions between the epithelium and the mesenchyme.

ADAM Proteins↗

PubMed2006

Neuron-specific Enolase and myelin basic protein in cerebrospinal fluid of patients with first episode schizophrenia.

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P<0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P< 0. 05). These findings suggested that patients with schizophrenia had cerebral injury.

Adolescent↗

PubMed2006

[Effects of ADAM28 AS-ODN on proliferation and AKPase of HDFCs].

PURPOSE: To study the effects of ADAM28 antisense oligodeoxynucleotide (AS-ODN) on proliferation of human dental follicle cells (HDFCs) and activity of alkaline phosphatase (AKPase). METHODS: Cell culture, gene transfection, MTT chromatometry and enzyme kinetics methods were used to detect the possible mechanisms of ADAM28 AS-ODN on proliferation, differentiation of HDFCs and effect of the activity of AKPase. Statistical significance was assessed by multiple comparison (q test, SNK) in one-way analysis of variance (ANOVA). RESULTS: ADAM28 AS-ODN was transfected into HDFCs successfully. MTT and AKPase activity assays indicated that cell proliferation and AKPase activity of ADAM28 AS-ODN group were significantly lower than those of S-ODN and vacuity control group (P<0.01). MTT assay revealed P value between AS-ODN and S-ODN, blank control group was 0.0002, 0.0001 respectively, P<0.01; AKPase assay showed P value between AS-ODN and S-ODN, vacuity control group was 0.0007, 0.0003 respectively, P<0.01. ADAM28 AS-ODN could inhibit the proliferation and AKPase activity of HDFCs significantly. CONCLUSIONS: ADAM28 may promote proliferation and differentiation of HDFCs by participating in Notch signal pathway.

ADAM Proteins↗

PubMed2005

Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia.

Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AML1/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLN1, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF, C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We performed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML.

Acute Disease↗

PubMed2005

Agrocybin, an antifungal peptide from the edible mushroom Agrocybe cylindracea.

An antifungal peptide with a molecular mass of 9 kDa was isolated from fresh fruiting bodies of the mushroom Agrocybe cylindracea. The isolation procedure comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography by fast protein liquid chromatography (FPLC) on Mono S, and FPLC-gel filtration on a Superdex 75 column. The antifungal peptide, designated as agrocybin, was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and Mono S. Agrocybin exerted antifungal activity against several fungal species but lacked inhibitory activity against bacteria when tested up to 300 microM. The activity of HIV-1 reverse transcriptase was attenuated in the presence of agrocybin. It exhibited weaker mitogenic activity than Con A on isolated murine splenocytes, but was devoid of antiproliferative activity on Hep G2 (hepatoma) cells when tested at 110 microM.

Agaricales↗