Biomedical subjects

Jiong Wang

Publications and source records attributed to Jiong Wang.

9 recordsLinked to original sources

PubMed2026

KLK6 is Associated with a Neutrophil-Dominant Immunosuppressive Microenvironment and Epigenetic Deregulation in Lung Adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer and is associated with poor survival despite advances in targeted therapies. Kallikrein-related peptidase 6 (KLK6) has been implicated in several malignancies, but its expression pattern, clinical relevance, and biological function in LUAD remain incompletely characterized. This study aimed to evaluate KLK6 expression and its associations with prognosis, epigenetic regulation, immune infiltration, and migratory phenotypes in LUAD. METHODS: RNA-seq expression and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. KLK6 expression was analyzed in relation to clinicopathological parameters, survival outcomes, promoter methylation status (via UALCAN), and tumor-infiltrating immune cell abundance (via TIMER2.0). In vitro, KLK6 was knocked down using shRNA in A549 and H1299 LUAD cell lines. Cell migration was assessed by transwell assays, and the expression of Epithelial-Mesenchymal Transition (EMT)- and Wnt signaling-related markers was examined by qRT-PCR and Western blotting. RESULTS: KLK6 expression was significantly upregulated in LUAD tissues compared with normal lung tissues. High KLK6 expression was associated with poorer overall survival (HR = 1.52, P = 0.009) and disease-specific survival (HR = 1.55, P = 0.03). ROC analysis showed that KLK6 discriminated stage I LUAD from normal tissues with an AUC of 0.73. Promoter hypomethylation was observed in LUAD tumors and correlated with increased KLK6 expression. Immune infiltration analysis revealed that KLK6-high tumors exhibited reduced B-cell infiltration and increased neutrophil infiltration. Functional experiments demonstrated that KLK6 knockdown significantly suppressed cell migration, accompanied by increased E-cadherin and decreased N-cadherin, Vimentin, Wnt5a, and β-catenin expression. DISCUSSION: These findings suggest that KLK6 overexpression in LUAD is driven in part by promoter hypomethylation and is closely linked to a neutrophil-dominant immunosuppressive microenvironment. Furthermore, KLK6 appears to promote LUAD cell migration through EMT- and Wnt-related signaling pathways. Collectively, these multi-layered data position KLK6 as a potential driver of aggressive tumor behavior and a candidate biomarker for risk stratification. CONCLUSION: KLK6 is aberrantly overexpressed in LUAD and is associated with poor prognosis and enhanced migratory capacity. It may serve as a promising prognostic biomarker and a potential therapeutic target for LUAD.

KLK6↗

PubMed2006

Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V.

Efavirenz resistance during HIV-1 treatment failure is usually associated with the reverse transcriptase mutation K103N. L100I, V108I, or P225H can emerge after K103N and increase its level of efavirenz resistance. K103N + L100I is the most drug-resistant of the double mutants but is the least common clinically. We hypothesized that differences in replication efficiency, or fitness, influence the relative frequencies of these secondary efavirenz resistance mutations in clinical isolates. We measured fitness of each secondary mutant introduced into HIV(NL4-3), alone and in combination with K103N, using growth competition assays in H9 cells. In the absence of efavirenz, the fitness of V108I was indistinguishable from wild type. K103N, L100I, and P225H were minimally, but consistently, less fit than wild type. K103N + L100I had a greater reduction in fitness and was less fit than K103N + V108I and K103N + P225H. The fitness defect of K103N + L100I relative to K103N was completely compensated for by the addition of the nucleoside resistance mutation L74V. In the presence of efavirenz, L100I was less fit than K103N, and K103N + L100I was more fit than K103N + V108I. Our studies suggest the primary driving force behind the selection of secondary efavirenz resistance mutations is the acquisition of higher levels of drug resistance, but the specific secondary mutations to emerge are those with the least cost in terms of replication efficiency. In addition, nucleoside and NNRTI resistance mutations can interact to affect HIV replication efficiency; these interactions may influence which mutations emerge during treatment failure. These studies have important implications for the design of more durable NNRTI-nucleoside combination regimens.

Alkynes↗

PubMed2006

Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture.

Human immunodeficiency virus type 1 (HIV-1) replication efficiency or fitness, as measured in cell culture, has been postulated to correlate with clinical outcome of HIV infection, although this is still controversial. One limitation is the lack of high-throughput assays that can measure replication efficiency over multiple rounds of replication. We have developed a multiple-cycle growth competition assay to measure HIV-1 replication efficiency that uses flow cytometry to determine the relative proportions of test and reference viruses, each of which expresses a different reporter gene in place of nef. The reporter genes are expressed on the surface of infected cells and are detected by commercially available fluorescence-labeled antibodies. This method is less labor-intensive than those that require isolation and amplification of nucleic acids. The two reporter gene products are detected with similar specificity and sensitivity, and the proportion of infected cells in culture correlates with the amount of viral p24 antigen produced in the culture supernatant. HIV replication efficiencies of six different drug-resistant site-directed mutants were reproducibly quantified and were similar to those obtained with a growth competition assay in which the relative proportion of each variant was measured by sequence analysis, indicating that recombination between the pol and reporter genes was negligible. This assay also reproducibly quantified the relative fitness conferred by protease and reverse transcriptase sequences containing multiple drug resistance mutations, amplified from patient plasma. This flow cytometry-based growth competition assay offers advantages over current assays for HIV replication efficiency and should prove useful for the evaluation of patient samples in clinical trials.

Animals↗

PubMed2004

Biclustering in gene expression data by tendency.

The advent of DNA microarray technologies has revolutionized the experimental study of gene expression. Clustering is the most popular approach of analyzing gene expression data and has indeed proven to be successful in many applications. Our work focuses on discovering a subset of genes which exhibit similar expression patterns along a subset of conditions in the gene expression matrix. Specifically, we are looking for the Order Preserving clusters (OPCluster), in each of which a subset of genes induce a similar linear ordering along a subset of conditions. The pioneering work of the OPSM model[3], which enforces the strict order shared by the genes in a cluster, is included in our model as a special case. Our model is more robust than OPSM because similarly expressed conditions are allowed to form order equivalent groups and no restriction is placed on the order within a group. Guided by our model, we design and implement a deterministic algorithm, namely OPCTree, to discover OP-Clusters. Experimental study on two real datasets demonstrates the effectiveness of the algorithm in the application of tissue classification and cell cycle identification. In addition, a large percentage of OP-Clusters exhibit significant enrichment of one or more function categories, which implies that OP-Clusters indeed carry significant biological relevance.

Algorithms↗

PubMed2003

Induction of hepatitis C virus-specific humoral and cellular immune responses in mice and rhesus by artificial multiple epitopes sequence.

The investigation of antigenic epitopes in hepatitis C virus (HCV) protein suggests that a central sequence combined with multiple antigenic epitopes of HCV might be significant as a potential vaccine candidate. This artificial sequence of combined and modified multiple antigenic epitopic peptides (Hc-B2), containing three B and four T cell epitopes, was constructed and expressed in E. coli. Antigen analysis indicated that this peptide antigen was capable of interacting with anti-sera collected from hepatitis C patients infected by three genotypes of HCV from three different geographic areas of China, respectively. The immunological analysis of this peptide antigen in mice and rhesus suggested that its immunogenicity was effective. However, a complete evaluation of this peptide could not be made as an effective animal model for HCV infection (such as in the chimpanzee) was not available for this study.

Amino Acid Sequence↗

PubMed2002

An SR-protein induced by HSVI binding to cells functioning as a splicing inhibitor of viral pre-mRNA.

The interaction between a virus and its specific receptor on the membrane of the host cell mimics the physiological combination of signal ligand and its receptor, and initiates the specific signal transduction from this activated receptor to induce a relative gene response. During the investigation of the interaction between Herpes simplex virus I (HSVI) and human fibroblast via the virus binding to its receptor complex on the cellular membrane, a new gene of cellular response against the specific stimulation of HSVI binding to fibroblasts was cloned from a cDNA library established from mRNA of an early gene response. This gene encoded a protein of 14.9kDa with the structural characteristics of Arg-rich and RS repeats. The analysis of the role of this protein in the infection by HSVI indicated that this protein, expressed only in G(1)/S phase and phosphorylated, functioned as a splicing inhibitor of HSVI pre-mRNA. The details of the mechanism of this inhibition of HSVI pre-mRNA splicing is still unclear.

Amino Acid Sequence↗

PubMed2002

[The clinical significance of detection of p53 gene mutation in patients with lung cancer].

OBJECTIVE: To assess the value of detection of p53 gene mutation in bronchial biopsy and sputum samples for the diagnosis of lung cancer. METHODS: Bronchial biopsy and sputum samples were collected from 120 patients confirmed to have lung cancer and 40 patients with benign pulmonary diseases. Polymerase chain reaction-single strand conformation polymorphism-AgNOS(3) staining method (PCR-SSCP) was performed for the detection of point mutation at exon 5 - 8 of the p53 gene. RESULTS: The positive rates of p53 point mutation in the carcinomatous tissue, the para-carcinomatous tissue, the contralateral bronchial tissue and the sputum from patients with lung cancer were 60% (36/60), 17% (10/60), 5% (3/60) and 43% (26/60), respectively (P < 0.05). In patients with benign pulmonary diseases, p53 point mutation in bronchial biopsy sample was detected in only one case (5%). The positive rate for the diagnosis of lung cancer increased from 48% (cytology alone) to 68% when the detection of p53 point mutation and cytological examination for sputum samples were combined. CONCLUSIONS: Detection of p53 gene mutation with PCR-SSCP-silver stain combined with cytological examination of sputum samples can improve the diagnosis of lung cancer.

Adult↗

PubMed2000

Early Expression of Protooncogenes Induced by the Binding to Cells of Two Viruses.

The specific binding of virus to receptor is essentially the interaction of ligand and receptor. This binding is able to induce cellular primary gene response that has various regulatory function in cells. Different immediate-early gene responses could be induced with different binding virus. The different gene responses were observed as poliovirus and HSV-I bind to human diploid cells. These differences showed that early expression of protooncogenes were enhanced and/or suppressed in the primary gene responses.

Journal Article↗

PubMed1997

DiO-C(18)-(3) Mediated Cell Fusion.

DiO, a fluorescent membrane probe, induced the rapid fusion of human erythrocytes and also mediated the fusion of mouse L-929 cells (fibroblastoma) in isotonic buffer (pH7.4) at room temperature. The fusion was independent of external Ca(2+) activating cysteine proteinase. PMSF, an inhibitor of serine proteinase, had no stopping effect on the fusion. The fluorescent cell images showed the existence of binding sites characteristic of high local concentration of DiO on the cell surface. Fluorescent filaments protruding from the cells and fused pairs were also recorded. These observations may have implication for a mechanism which promotes the protrusions of plasma membrane in the course of cell fusion. Based on the membrane electrostatics an the stress of the removal of water between bilayers, we infer that microregions of shared phospholipid bilayer may be formed at the distal ends of the protrusions when they are formed together as a consequence of the local dehydration action of the fusogen.

Journal Article↗