Biomedical subjects

Tong Zhou

Publications and source records attributed to Tong Zhou.

At least 19 recordsLinked to original sources

PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗

PubMed2026

Modtector: ultra-fast modification signal mining on mapped sequencing reads.

SUMMARY: Existing tools for RNA epitranscriptomic modification and structural signal analysis are often fragmented, inefficiency, and limited to single signal types. We developed Modtector, an unified tool for extracting mutation and reverse-transcription stop signals from aligned sequencing reads. By using a "count-then-correct" strategy, Modtector reduces computational complexity and enables efficient dual-signal analysis. It achieves multi-fold speedups on large-genome and high-coverage datasets, including completing HEK293 22G data analysis in 5 minutes, and show strong scalability on single-cell datasets with speedups exceeding 50-fold. AVAILABILITY: The source code is available at GitHub (https://github.com/TongZhou2017/modtector) and Crates.io (https://crates.io/crates/modtector). The archived source-code snapshot used in this study is available at Zenodo (DOI: 10.5281/zenodo.20967747), corresponding to GitHub commit 7c60e9d. Workflow examples, datasets, and analysis scripts are available at Zenodo (DOI: 10.5281/zenodo.17316476 and 10.5281/zenodo.18523297).

Humans↗

PubMed2025

Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer.

Mitochondrial-related nuclear genes (MNGs) have shown great importance in cancer diagnosis and prognosis, but their role in gastric cancer (GC) remains unclear. GC-related transcriptome data from the gene expression omnibus and cancer genome atlas databases were analyzed to identify differentially expressed MNGs. A prognostic risk model was constructed through univariate Cox and least absolute shrinkage and selection operator regression, validated by Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve. This was followed by immune infiltration analysis, independent prognostic analysis, functional enrichment analysis, drug sensitivity analysis, drug prediction, molecular docking and construction of regulatory networks. Three prognostic genes (ATP8A2, COX15 and TARS2) were identified. The expression of TARS2 and COX15 was positively correlated with CNV, while ATP8A2 was unaffected. The risk model and nomogram, integrating risk score and clinicopathological factors, exhibited excellent predictive performance. A significant correlation was observed between prognostic genes and differential immune cells, such as T cells, B cells, and NK cells. BMS-754807, Gefitinib, JQ1, Lapatinib, and Sapitinib exhibited significant differences in sensitivity between the high-risk group and the low-risk group. The results of molecular docking showed TP8A2 has stable binding ability with cytosine, COX15 with indomethacin, and TARS2 with bisacodyl. RT-qPCR revealed downregulation of ATP8A2 and upregulation of COX15 and TARS2 in GC samples. MNGs, including ATP8A2, COX15, and TARS2, demonstrated significant associations with immune infiltration, CNV, and prognostic outcomes of GC.

Humans↗

PubMed2006

Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease.

The Artemis nuclease is required for V(D)J recombination and for repair of an as yet undefined subset of radiation-induced DNA double strand breaks. To assess the possibility that Artemis acts on oxidatively modified double strand break termini, its activity toward model DNA substrates, bearing either 3'-hydroxyl or 3'-phosphoglycolate moieties, was examined. A 3'-phosphoglycolate had little effect on Artemis-mediated trimming of long 3' overhangs (> or =9 nucleotides), which were efficiently trimmed to 4-5 nucleotides. However, 3'-phosphoglycolates on overhangs of 4-5 bases promoted Artemis-mediated removal of a single 3'-terminal nucleotide, while at least 2 nucleotides were trimmed from identical hydroxyl-terminated substrates. Artemis also efficiently removed a single nucleotide from a phosphoglycolate-terminated 3-base 3' overhang, while leaving an analogous hydroxyl-terminated overhang largely intact. Such removal was completely dependent on DNA-dependent protein kinase and ATP and was largely dependent on Ku, which markedly stimulated Artemis activity toward all 3' overhangs. Together, these data suggest that efficient Artemis-mediated cleavage of 3' overhangs requires a minimum of 2 nucleotides, or a nucleotide plus a phosphoglycolate, 3' to the cleavage site, as well as 2 unpaired nucleotides 5' to the cleavage site. Shorter 3'-phosphoglycolate-terminated overhangs and blunt ends were also processed by Artemis but much more slowly. Consistent with a role for Artemis in repair of terminally blocked double strand breaks in vivo, human cells lacking Artemis exhibited hypersensitivity to x-rays, bleomycin, and neocarzinostatin, which all induce 3'-phosphoglycolate-terminated double strand breaks.

Bleomycin↗

PubMed2006

p53-Dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts.

This study focused on the activation of cell cycle checkpoint responses in diploid human fibroblasts that were treated with cadmium chloride and the potential roles of ATM and p53 signaling pathways in cadmium-induced responses. The alkaline comet assay indicated that cadmium caused a dose-dependent increase in DNA damage. Cells that were rendered p53-defective by expression of a dominant-negative p53 allele or knockdown of p53 mRNA were more resistant to cadmium-induced inactivation of colony formation than normal and ataxia telangiectasia (AT) cells. Synchronized fibroblasts in S were more sensitive to cadmium toxicity than cells in G1, suggesting that cadmium may target some element of DNA replication. Cadmium produced a dose- and time-dependent inhibition of DNA synthesis. An immediate inhibition was associated with severe delay in progression through S phase and a delayed inhibition seen 24 h after treatment was associated with accumulation of cells in G2. AT and normal cells displayed similar patterns of inhibition of DNA synthesis and G2 delay after treatment with cadmium, while p53-defective cells displayed significantly less of the delayed inhibition of DNA synthesis and accumulation in G2 post-treatment. Total p53 protein and ser15-phosphorylated p53 were induced by cadmium in normal and AT cells. The p53 transactivation target Gadd45alpha was induced in both p53-effective and p53-defective cells after 4 h cadmium treatment, and this was associated with an acute inhibition of mitosis. Cadmium produced a very unusual pattern of toxicity in human fibroblasts, inhibiting DNA replication and inducing p53-dependent growth arrest but without induction of p21(Cip1/Waf1) or activation of Chk1.

Ataxia Telangiectasia↗

PubMed2006

Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function.

Induction of tumor cell resistance to therapeutics has been a major obstacle in cancer therapy. Targeting of the death receptors by a natural ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or agonistic monoclonal antibodies against TRAIL receptor 1 (TRAIL-R1) or TRAIL receptor 2 (TRAIL-R2) has been thought to be a promising cancer therapy. To determine whether tumor cells are able to generate a resistance to apoptosis induced by an anti-TRAIL-R2 antibody, TRA-8, we examined the apoptotic response of human breast and ovarian cancer cell lines after treatment with TRA-8. Our results show that tumor cell resistance to TRA-8 can be induced by repeated treatment of tumor cells with low, non-apoptosis-inducing doses of TRA-8. Interestingly, the induced resistance to apoptosis was not due to a global apoptotic defect in tumor cells but rather a selective defect in the TRAIL-R2 signaling pathway. Whereas TRA-8-treated tumor cells developed a selective resistance to TRAIL-R2-mediated apoptosis, the apoptotic responses induced by TRAIL, an anti-TRAIL-R1 antibody (2E12), and other apoptotic stimuli were not impaired. The expression levels of cell surface TRAIL-R2 were not altered and mutations of TRAIL-R2 were not found in the resistant cells. The induced TRA-8 resistance was due to a selective blockade at the level of the death domain and could be reversed by a wide array of chemotherapeutic agents. Proteomic analysis of death-inducing signaling complex formation during TRA-8 treatment shows that the translocation of TRAIL-R2-associated apoptotic proteins was significantly altered. Our results suggest that the prevention of tumor cell resistance to therapeutic agents that target the death receptors must be taken into consideration.

Apoptosis↗

PubMed2006

Role of complement component C5 in cerebral ischemia/reperfusion injury.

We evaluated the role of complement component C5 during the course of cerebral ischemic reperfusion injury in a rat model of middle cerebral artery occlusion (MCAO). Systemic C5 inhibition was achieved with an anti-C5 monoclonal antibody, which significantly prevented the deterioration of the motor functions by reducing cerebral lesion and edema. Our results show that activated C5 complement components played an important role in cerebral tissue inflammation resulting from ischemia/reperfusion injury.

Animals↗

PubMed2006

Survivin mutant (Surv-DD70, 71AA) disrupts the interaction of Survivin with Aurora B and causes multinucleation in HeLa cells.

Survivin is associated with Aurora B, inner centromere protein (INCENP), and borealin to form a chromosomal passenger complex that plays multiple roles during cell division. We used mutational analysis to study interaction of Survivin with Aurora B and the effect of this interaction on cell division. A Survivin mutant with the terminal domain deleted (Survivin 1-107) bound Aurora B as efficiently as Survivin wild type. This indicated that the proximal BIR domain of Survivin was responsible for Survivin binding to Aurora B. Survivin mutants (Surv-R18A, Surv-D53A, and Sur-KK78, and 79AA) all bound to Aurora B efficiently, but mutation in the conserved amino acid residues of the acidic patch on Survivin (Surv-DD70, 71AA) abolished the direct interaction of Survivin and Aurora B. The Survivin mutant (Surv-DD70, 71AA) localized diffusely in metaphase and failed to successfully accumulate in the midbody during cytokinesis. Furthermore, over-expression of the Survivin mutant (Surv-DD70, 71AA) severely disturbed cytokinesis, resulting in multinucleation in HeLa cell. This indicated that the direct interaction of Survivin and Aurora B was critical for the correct location of Survivin and the function of the Survivin complex in cell division.

Amino Acid Sequence↗

PubMed2006

Support vector machine for classification of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae based on codon composition.

BACKGROUND: Meiotic double-strand breaks occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). Hotspots and coldspots are receiving increasing attention in research into the mechanism of meiotic recombination. However, predicting hotspots and coldspots from DNA sequence information is still a challenging task. RESULTS: We present a novel method for classification of hot and cold ORFs located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using support vector machine (SVM), which relies on codon composition differences. This method has achieved a high classification accuracy of 85.0%. Since codon composition is a fusion of codon usage bias and amino acid composition signals, the ability of these two kinds of sequence attributes to discriminate hot ORFs from cold ORFs was also investigated separately. Our results indicate that neither codon usage bias nor amino acid composition taken separately performed as well as codon composition. Moreover, our SVM based method was applied to the full genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of recombination rate. We found that the performance of our method for predicting cold ORFs is not as good as that for predicting hot ORFs. Besides, we also observed a considerable correlation between meiotic recombination rate and amino acid composition of certain residues, which probably reflects the structural and functional dissimilarity between the hot and cold groups. CONCLUSION: We have introduced a SVM-based novel method to discriminate hot ORFs from cold ones. Applying codon composition as sequence attributes, we have achieved a high classification accuracy, which suggests that codon composition has strong potential to be used as sequence attributes in the prediction of hot and cold ORFs.

Algorithms↗

PubMed2006

Early removing gastrointestinal decompression and early oral feeding improve patients' rehabilitation after colorectostomy.

AIM: To evaluate the feasibility, safety, and tolerance of early removing gastrointestinal decompression and early oral feeding in the patients undergoing surgery for colorectal carcinoma. METHODS: Three hundred and sixteen patients submitted to operations associated with colorectostomy from January 2004 to September 2005 were randomized to two groups: In experimental group (n=161), the nasogastric tube was removed after the operation from 12 to 24 h and was promised immediately oral feeding; In control group (n=155), the nasogastric tube was maintained until the passage of flatus per rectum. Variables assessed included the time to first passage of flatus, the time to first passage of stool, the time elapsed postoperative stay, and postoperative complications such as anastomotic leakage, acute dilation of stomach, wound infection and dehiscense, fever, pulmonary infection and pharyngolaryngitis. RESULTS: The median and average days to the first passage of flatus (3.0+/-0.9 vs 3.6+/-1.2, P<0.001), the first passage of stool (4.1+/-1.1 vs 4.8+/-1.4, P<0.001) and the length of postoperative stay (8.4+/-3.4 vs 9.6+/-5.0, P<0.05) were shorter in the experimental group than in the control group. The postoperative complications such as anastomotic leakage (1.24% vs 2.58%), acute dilation of stomach (1.86% vs 0.06%) and wound complications (2.48% vs 1.94%) were similar in the groups, but fever (3.73% vs 9.68%, P<0.05), pulmonary infection (0.62% vs 4.52%, P<0.05) and pharyngolaryngitis (3.11% vs 23.23%, P<0.001) were much more in the control group than in the experimental group. CONCLUSION: The present study shows that application of gastrointestinal decompression after colorectostomy can not effectively reduce postoperative complications. On the contrary, it may increase the incidence rate of fever, pharyngolaryngitis and pulmonary infection. These strategies of early removing gastrointestinal decompression and early oral feeding in the patients undergoing colorectostomy are feasible and safe and associated with reduced postoperative discomfort and can accelerate the return of bowel function and improve rehabilitation.

Adult↗

PubMed2006

Computer simulations of diffusion and dynamics of short-chain polyelectrolytes.

Brownian dynamics simulations are conducted to investigate the diffusional and dynamic properties of polyelectrolytes in dilute salt-free solutions. The polyelectrolyte molecule is represented by a bead-spring chain in a primitive model. The long-range hydrodynamic and Coulomb interactions are both taken into consideration through the Ewald summations for the first time. The major finding of our simulations is that the dependence of the long-time chain diffusivity on the Coulomb interaction strength is very different from that of the Kirkwood short-time diffusivity, which simply shows a trend nearly opposite to the chain size. When ignoring the hydrodynamic interaction (HI), the coupling effect between the chain and its counterions gives rise to a noticeable increase in the long-time diffusivity at intermediate electrostatic interaction strengths. However, the incorporation of HI suppresses this effect to a degree that one can no longer discern it. Moreover, the rotational relaxation is found to show a dependence opposite to that of the gyration radius relaxation.

Computer Simulation↗

PubMed2006

Anti-P-selectin lectin-EGF domain monoclonal antibody inhibits the maturation of human immature dendritic cells.

Dendritic cells (DCs) are professional antigen-presenting cells with the ability to initiate primary T cell responses. While it is well known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DC maturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesion of P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs. Immature DCs are generated from human cord blood CD34+ hematopoietic stem/progenitor cells that were cultured in the presence of stem cell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-beta1. When stimulated with tumor necrosis factor-alpha (TNF-alpha), immature DCs differentiated into mature DCs, producing increased levels of costimulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naïve T cells. Interestingly, in contrast to mature DCs derived from TNF-alpha-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for 7 days were completely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibited production of IL-12, and inability to activate naïve T cells in vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to be a valuable tool for the study of the molecular mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated autoimmunity.

Antibodies, Monoclonal↗

PubMed2006

Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis.

OBJECTIVE: The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice. METHODS: Individual hybridomas isolated from the spleen of a 10-month-old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme-linked immunosorbent assay, Western blotting, 2-dimensional gel electrophoresis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high-throughput epitope mapping method. RESULTS: The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)-modified enolase, Ro, alpha-actin, and heat-shock proteins (HSPs) preceding peak levels of antihistone, anti-DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT-modified enolase, ATP5b, alpha-actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism. CONCLUSION: The polyreactivity of autoantibodies that target a novel class of autoantigens may enable these autoantibodies to induce erosive arthritis or glomerulonephritis either by direct pathogenic mechanisms or indirectly via Fc or immune complex deposition.

Animals↗

PubMed2006

Profiles of global gene expression in ionizing-radiation-damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence.

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40-45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1.

Cell Line↗

PubMed2006

TRAIL receptor-targeted therapy.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines. Based on its ability to induce apoptosis selectively in a wide variety of cancer cell lines and human tumor xenografts, TRAIL has been in drug development as a potential biological agent for cancer therapy. A variety of chemotherapy agents have been shown to enhance the cytotoxic effects of TRAIL. The potential benefits of TRAIL as an anticancer therapy have been further indicated by its ability to enhance the efficacy of radiotherapy. Preclinical studies have shown the potential use of agonistic monoclonal antibodies that selectively bind TRAIL death receptors for cancer therapy. This review provides an overview of TRAIL receptor-mediated apoptosis of tumor cells, with TRAIL or agonistic monoclonal antibodies only or with chemotherapy drugs. Treatment of tumor xenografts with these ligands, alone or in combination with chemotherapy or radiation, are discussed along with preliminary information about early clinical trials. Additional clinical trials with TRAIL receptor ligands in combination treatment regimens are required to determine their potential for targeted therapy of cancer.

Animals↗

PubMed2006

Valsartan inhibited the accumulation of dendritic cells in rat fibrotic renal tissue.

To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis, under influence of valsartan on DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four experimental groups were included: normal, sham, model (SNx) and the group treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12, respectively. CD1a+CD80+ DCs were assayed by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin was analyzed by immunohistochemistry or semi-quantitative RT-PCR, and the level of tubulointerstitial firosis (TIF) was scored. CD1a+CD80+ DCs were gradually increased among renal tubules, interstitium and vessels, especially in interstitium, and the number of DCs in model group at week 12 was much more than that in model groups at week 1 or 4. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin in tubulointerstitial areas and the degree of TIF was increased substantially in model group at week 12. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fibrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury.

Angiotensin II Type 2 Receptor Blockers↗

PubMed2006

DC-SIGN and immunoregulation.

Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.

Cell Adhesion Molecules↗

PubMed2006

[The association of single nucleotide P-selectin gene polymorphism with IgA nephropathy].

OBJECTIVE: IgA nephropathy is one of the most common form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin gene polymorphism and IgA nephropathy. METHODS: In this study, a comprehensive P-selectin gene survey, including entire coding region, part of regulatory region and exon-intron connection region, was performed with PCR-direct sequencing and 16 single nucleotide polymorphism (SNPs) were detected. Then 210 renal-biopsy proven sporadic IgA nephropathy cases of Chinese Han nationality and 103 normal volunteers were recruited. 9 candidate SNPs (frequency > 5%) in P-selectin gene of both the case and control groups were genotyped with direct sequencing and a case-control association study was carried out. RESULTS: It was revealed that the SNP of -825A/G in promoter region of P-selectin gene was significantly associated with IgA nephropathy. Both the frequency of AG/GG genotype (21.9% vs 34.9%, P < 0.05) and G allele (11.4% vs 18.4%, P < 0.05) were less in the IgA nephropathy cases than in the healthy controls. Those carrying the low frequency G allele (AG/GG genotype) had a protective effect on the morbidity of IgA nephropathy and the odds ratio for the IgA nephropathy patients versus controls was 0.522 with AG/GG genotype versus AA genotype. Within the IgA nephropathy group, patients with AA genotype tended to present higher level of serum creatinine and soluble P-selectin than those carrying at least one G allele (AG/GG genotype) (P < 0.05). CONCLUSION: The SNP of -825A/G in the promoter region of P-selectin gene was significantly associated with IgA nephropathy susceptibility and patient's renal function, thus suggesting the genetic effect of P-selectin gene in the pathogenesis of IgA nephropathy.

Adolescent↗