Biomedical subjects

Xinming Chen

Publications and source records attributed to Xinming Chen.

16 recordsLinked to original sources

PubMed2026

In silico analysis based on network pharmacology and biomolecular informatics to explore the mechanism of action of Erjing Pills (from Shengji Zonglu) in the treatment of leukotrichia.

This study aimed to explore the core active ingredients and potential molecular mechanisms of Erjing Pills, a prescription in the classic work of Traditional Chinese Medicine, "Shengji Zonglu," in the treatment of leukotrichia by utilizing network pharmacology and biomolecular docking techniques. The chemical components and potential targets of Chinese herbal medicines were analyzed through databases such as the Traditional Chinese Medicine Systems Pharmacology Database. The targets related to leukotrichia were collected using GeneCards. The intersection targets were obtained using RStudio. The protein-protein interaction (PPI) network map and the "drug-component-target-disease" visualization network were generated using Cytoscape and STRING to screen the core components and key targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were carried out using the Database for Annotation, Visualization and Integrated Discovery and RStudio. Finally, molecular docking verification was performed by AutoDock and PyMOL (Schrödinger LLC). The key active ingredients of Erjing Pills in the treatment of leukotrichia are β-sitosterol, quercetin, baicalein, and stigmasterol. The top 5 PPI core target proteins, in order, are AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta. The Gene Ontology enrichment analysis suggests that the biological processes mainly include responses to exogenous stimuli, membrane rafts, and DNA-binding transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes pathways involve signal pathways such as lipid and atherosclerosis, hepatitis B, Kaposi sarcoma virus infection, chemical carcinogenesis, and human cytomegalovirus infection. The molecular docking results indicate that most of the main active ingredients in Erjing Pills have relatively stable binding activities with the key targets, such as AKT serine/threonine kinase 1, interleukin 6, tumor protein p53, cysteine-aspartic acid protease 3, and interleukin 1 beta, in the PPI network. The active ingredients of Erjing Pills may interfere with the pathological process of leukotrichia by regulating key targets and signal pathways. This study provides a theoretical basis for the clinical application of Erjing Pills and indicates the direction for subsequent experimental research.

Drugs, Chinese Herbal↗

PubMed2006

Transforming growth factor-beta1 differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells.

Transforming growth factor-beta(1) (TGF-beta(1)) is not only an important fibrogenic but also immunomodulatory cytokine in the human kidney. We have recently demonstrated that TGF-beta(1) induces interleukin-8 (IL-8), macrophage chemoattractant protein-1 (MCP-1), and fibronectin production in renal proximal tubular (HK-2) cells. However, the unique dependence of IL-8, MCP-1, and fibronectin on TGF-beta(1) expression is unknown. The TGF-beta(1) gene was effectively silenced in HK-2 cells using small-interference (si) RNA. Basal secretion of IL-8 and MCP-1 decreased (both P < 0.05) but, paradoxically, fibronectin increased (P < 0.05) in TGF-beta(1)-silenced cells compared with cells transfected with nonspecific siRNA. Significant increases were observed in mRNA for the TGF-beta(2) (P < 0.05), TGF-beta(3) (P < 0.05) isoforms and pSmad2 (P < 0.05), which were reflected in protein expression. Concurrent exposure to pan-specific TGF-beta antibody reversed the observed increase in fibronectin expression, suggesting that TGF-beta(2) and TGF-beta(3) isoforms mediate the increased fibronectin expression in TGF-beta(1)-silenced cells. An increase in the DNA binding activity of activator protein-1 (AP-1; P < 0.05) was also observed in TGF-beta(1)-silenced cells. In contrast, nuclear factor-kappaB (NF-kappaB) DNA binding activity was significantly decreased (P < 0.0005). These studies demonstrate that TGF-beta(1) is a key regulator of IL-8 and MCP-1, whereas fibronectin expression is regulated by a complex interaction between the TGF-beta isoforms in the HK-2 proximal tubular cell line. Decreased expression of TGF-beta(1) reduces chemokine production in association with reduced NF-kappaB DNA binding activity, suggesting that immunomodulatory pathways in the kidney are specifically dependent on TGF-beta(1). Conversely, decreased expression of TGF-beta(1) results in increased TGF-beta(2), TGF-beta(3), AP-1, and pSmad2 that potentially mediates the observed increase in fibronectin.

Cell Line, Transformed↗

PubMed2006

Intratumor genomic heterogeneity correlates with histological grade of advanced oral squamous cell carcinoma.

To assess the difference in genetic aberration patterns among the invasive tumor front (ITF), center/superficiality and the stroma adjacent to oral squamous cell carcinoma (OSCC), we studied loss of heterozygosity (LOH) and microsatellite instability (MI) at chromosome 9p21 and 17p13 on the three regions by combining laser capture microdissection (LCM) and PCR. We studied 20 OSCC patients with TP53 on chromosome 17p13 and RPS6 on chromosome 9p21. Genomic DNA samples from the ITF, center/superficial and stromal cells adjacent to the tumor were prepared from cryosections using laser-assistant microdissection, then LOH and MI were determined. Cells at the ITF, center/superficiality and stroma showed a high frequency of LOH and MI on chromosomes 17p13 (TP53) and 9p21 (RPS6). Comparison of the patterns of allelic loss and MI encountered at the ITF, center/superficial and stromal cells revealed no concordance. The frequency of RPS6 and TP53 aberration at the epithelial compartment (both ITF and center, 64.7%, 11/17; 70.6%, 12/17) was statistically higher than the stroma (23.5%, 4/17; 43.8%, 7/16) (p<0.05). Furthermore, for the epithelial compartment, the aberrations proportions of TP53 rose from 60.0% (9/15) to 64.7% (11/17) between the center/superficial part and ITF. Also the rate of RPS6 increased from 29.4% (5/17) to 58.8% (10/17) between the center/superficial parts and ITF. The overall frequency of the two markers was statistically higher at the ITF (20/32) than the center/superficial part (15/34) (p<0.05). The current study revealed that intratumor genetic heterogeneity exists in the different histological areas of OSCCs and some particular tumor cell genotypes have correlation with histological patterns.

Adult↗

PubMed2006

Glandular odontogenic cyst in China: report of 12 cases and immunohistochemical study.

OBJECTIVE: The purpose of this study was to present 12 additional cases of glandular odontogenic cyst (GOC) in the Department of Oral Pathology, School of Stomatology, Wuhan University, People's Republic of China, and to investigate their immunohistochemical cytokeratins (CKs) expression in the epithelial components. METHODS: A total of 12 GOCs were reviewed clinically and radiographically, and immunohistologic CKs AE1, 7, 8/18, 10/13, 14, 16, 19 and 20 were performed by using a standard biotin-streptavidin immunoperoxidase technique on paraffin sections. RESULTS: The present series showed that eight occurred in males and four in females. The mean age was 37.6 years with a peak incidence occurring in the third decades (six of 12). Mandibles were more affected than maxillas (7:5), especially anterior mandible (four of seven). Radiographically, ratio multilocular to unilocular radiolucencies was 5:7 usually with well-defined borders. Histologically, cystic spaces were lined by non-keratinized stratified epithelia containing focal plaque-like or whirlpool-like thickenings; surface epithelial layer-containing eosinophilic cuboidal cells; mucous cells; and mucin pools of microcystic areas in the epithelium. Immunohistochemistry showed that epithelium of GOCs stained for CKs AE1, 7, 8/18, 10/13, 14 and 19 with slight changes in their patterns, and no reaction to CKs 16 and 20. CONCLUSIONS: Most clinical and histologic features in this study were analogous to those reported west population, although with slight difference between them. Histologically, the morphology of the epithelium strongly suggested an odontogenic origin, and CKs expression of GOC was similar to that of odontogenic epithelium, suggesting histochemically that GOC might be derived from odontogenic epithelium.

Adult↗

PubMed2006

Transcriptional profiling of the cell cycle checkpoint gene krüppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.

Krüppel-like factor 4 (KLF4; also known as gut-enriched Krüppel-like factor or GKLF) is known to exhibit checkpoint function during the G1/S and G2/M transitions of the cell cycle. The mechanism by which KLF4 exerts these effects is not fully established. Here we investigated the expression profile of KLF4 in an inducible system over a time course of 24 h. Using oligonucleotide microarrays, we determined that the fold changes relative to control in expression levels of KLF4 exhibited a time-dependent increase from 3- to 20-fold between 4 and 24 h following KLF4 induction. During this period and among a group of 473 cell cycle regulatory genes examined, 96 were positively correlated and 86 were negatively correlated to KLF4's expression profile. Examples of upregulated cell cycle genes include those encoding tumor suppressors such as MCC and FHIT, and cell cycle inhibitors such as CHES1 and CHEK1. Examples of downregulated genes include those that promote the cell cycle including several cyclins and those required for DNA replication. Unexpectedly, several groups of genes involved in macromolecular synthesis, including protein biosynthesis, transcription, and cholesterol biosynthesis, were also significantly inhibited by KLF4. Thus, KLF4 exerts a global inhibitory effect on macromolecular biosynthesis that is beyond its established role as a cell cycle inhibitor.

Cell Cycle↗

PubMed2005

Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome.

OBJECTIVE: To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands. METHODS: Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. RESULTS: The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival. CONCLUSION: The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.

Antigens, CD34↗

PubMed2005

TGF-beta1 induces IL-8 and MCP-1 through a connective tissue growth factor-independent pathway.

Transforming growth factor-beta(1) (TGF-beta(1)) functions as an important immunomodulatory cytokine in human kidney. Evidence suggests that connective tissue growth factor (CTGF) is an important downstream mediator of the profibrotic effects of TGF-beta(1). However, the role of CTGF in TGF-beta(1)-induced chemokine production remains unknown. This study was undertaken to determine whether CTGF is involved in mediating TGF-beta(1)-induced chemokine production in renal proximal tubular (HK-2) cells. Interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured. TGF-beta(1) induced an increase in IL-8 and MCP-1 (both P < 0.05) compared with control levels. CTGF was effectively silenced using small interference RNA (siRNA) in HK-2 cells. RT-PCR and real-time PCR confirmed a 94% reduction in CTGF mRNA. In the CTGF-silenced cells, TGF-beta(1)-stimulated IL-8 and MCP-1 secretion was not altered compared with control cells. Similarly, basal secretion of IL-8 and MCP-1 was not changed in CTGF-silenced cells. The direct effect of CTGF (20, 200, and 400 ng/ml) on IL-8 and MCP-1 was assessed at 24-, 48-, and 72-h time points and no stimulation was observed. Our studies further demonstrate that in the CTGF gene-silenced cells, CTGF partially mediates TGF-beta(1)-induced fibronectin and collagen IV secretion. These data suggest that TGF-beta(1) induced IL-8 and MCP-1 via CTGF-independent pathway. TGF-beta mediates both fibrosis and chemokine production in the proximal tubule of the kidney. However, CTGF plays a more specific role as a downstream mediator of TGF-beta(1)-induced fibrosis.

Base Sequence↗

PubMed2005

The renal cortical fibroblast in renal tubulointerstitial fibrosis.

Renal cortical fibroblasts have key roles in mediating intercellular communication with neighboring/infiltrating cells and extracellular matrix (ECM) and maintenance of renal tissue architecture. They express a variety of cytokines, chemokines, growth factors and cell adhesion molecules, playing an active role in paracrine and autocrine interactions and regulating both fibrogenesis and the interstitial inflammatory response. They additionally have an endocrine function in the production of epoetin. Tubulointerstitial fibrosis, the common pathological consequence of renal injury, is characterized by the accumulation of extracellular matrix largely due to excessive production in parallel with reduced degradation, and activated fibroblasts characterized by a myofibroblastic phenotype. Fibroblasts in the kidney may derive from resident fibroblasts, from the circulating fibroblast population or from haemopoetic progenitor or stromal cells derived from the bone marrow. Cells exhibiting a myofibroblastic phenotype may derive from these sources and from tubular cells undergoing epithelial to mesenchymal transformation in response to renal injury. The number of interstitial myofibroblasts correlates closely with tubulointerstitial fibrosis and progressive renal failure. Hence inhibiting myofibroblast formation may be an effective strategy in attenuating the development of renal failure in kidney disease of diverse etiology.

Animals↗

PubMed2003

Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.

We have examined the role that the transcription factor gut-enriched Krüppel-like factor (KLF4 or GKLF) plays in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase (IAP). A yeast one-hybrid screen was used to identify proteins interacting with a previously identified cis-element (IF-III) located within the human IAP gene promoter. DNA-protein interactions were determined by using EMSA. Northern blot analysis was used to study RNA expression in human colon cancer RKO cells engineered to overexpress KLF4. Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription. The yeast one-hybrid screen and EMSA identified KLF4 as binding to IF-III. RKO cells induced to overexpress KLF4 demonstrated a corresponding dose-dependent increase in IAP expression, and EMSA with nuclear extract from these cells confirmed that KLF4 binds to the IF-III element. Transient transfections revealed that KLF4 transactivated the IAP gene largely via a critical segment in the IAP promoter that includes the IF-III cis-element. Mutant KLF4 constructs failed to fully activate IAP. We have identified the enterocyte differentiation marker IAP as a KLF4 target gene. IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region.

Alkaline Phosphatase↗

PubMed2003

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity.

Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor, the expression of which is enriched in the postmitotic cells of the intestinal epithelium. KLF4 is a target gene of the tumor suppressor adenomatous polyposis coli (APC). We sought to determine the role of KLF4 in suppressing the tumorigenecity of RKO colon cancer cells, which do not express KLF4. We utilized an established system in RKO cells, in which an inducible promoter controls expression of KLF4. Four independent assays were used to assess the effects of KLF4 induction on tumor cells. We find that KLF4 overexpression reduces colony formation, cell migration and invasion, and in vivo tumorigenecity. The mechanism of action of KLF4 does not involve apoptosis. These findings, along with our previous findings that KLF4 induces G1/S arrest, suggest that KLF4 is a cell cycle checkpoint protein that can reduce tumorigenecity of colon cancer cells.

Animals↗

PubMed2003

Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.

Krüppel-like factor 4 (KLF4) is an epithelially enriched, zinc finger-containing transcription factor, the expression of which is associated with growth arrest. Constitutive expression of KLF4 inhibits G1/S transition of the cell cycle but the manner by which it accomplishes this effect is unclear. To better understand the biochemical function of KLF4, we identified its target genes using cDNA microarray analysis in an established human cell line containing inducible KLF4. RNA extracted from induced and control cells were hybridized differentially to microarray chips containing 9600 human cDNAs. In all, 84 genes with significantly increased expression and 107 genes with significantly reduced expression due to KLF4 induction were identified. The affected genes are sorted to several clusters on the basis of functional relatedness. A major cluster belongs to genes involved in cell-cycle control. Within this cluster, many up-regulated genes are inhibitors of the cell cycle and down-regulated genes are promoters of the cell cycle. Another up-regulated gene cluster includes nine keratin genes, of which seven are located in a specific region on chromosome 12. The results indicate that KLF4 is involved in the control of cell proliferation and does so by eliciting changes in expression of numerous cell-cycle regulatory genes in a concerted manner. Furthermore, KLF4 regulates expression of a group of epithelial-specific keratin genes in a manner consistent with a potential locus control region function.

Blotting, Northern↗

PubMed2003

[The effect of rehabilitation of flared root canal on the fracture resistance of root and post-core system].

OBJECTIVE: To assess the effect of rehabilitation of flared root canal on the fracture resistance of root and post-core system. METHODS: Thirty-two simulated tooth roots made of polymethyl methacrylate were divided into 4 groups, including the normal root canal group and 3 flared root canal groups. One flared root canal group was rehabilitated by light-cared composite, another group was rehabilitated by amalgam, and the third flared root conal group was not treated. Casting post and core restored every simulated tooth root. Each specimen was embedded in acrylic resin and then fixed in a special jig on the universal load-testing machine. A compressive load was applied at a 90-degree angle to the long axis of the core until fracture, at a crosshead speed of 1 mm/min; the maximum of load was recorded. RESULTS: The means of load in normal root canal group, light-cared composite rehabilitated group, amalgam rehabilitated group, not treated group were 202.92 N, 194.60 N, 146.89 N, 142.09 N. It was shown that the load of normal root canal group is significantly greater than the load of not-treated group (P < 0.01); the light-cared composite rehabilitated group is significantly stronger than the not-treated group (P < 0.01), but there is no significant difference between the light-cared composite rehabilitated group and normal root canal group, and no significant difference between the amalgam rehabilitated group and not-treated group (P > 0.05). CONCLUSION: The rehabilitation of flared root canal using suitable material not only changes the shape of root canal, but also increases the fracture resistance of root canal because of its thicker and stronger root canal wall which obviously improves the fracture resistance of post and core.

Acrylic Resins↗

PubMed2002

Kruppel-like factor 4 mediates p53-dependent G1/S cell cycle arrest in response to DNA damage.

The tumor suppressor p53 is required for the maintenance of genomic integrity following DNA damage. One mechanism by which p53 functions is to induce a block in the transition between the G(1) and S phase of the cell cycle. Previous studies indicate that the Krüppel-like factor 4 (KLF4) gene is activated following DNA damage and that such activation depends on p53. In addition, enforced expression of KLF4 causes G(1)/S arrest. The present study examines the requirement of KLF4 in mediating the p53-dependent cell cycle arrest process in response to DNA damage. We show that the G(1) population of a colon cancer cell line, HCT116, that is null for the p53 alleles (-/-) was abolished following gamma irradiation compared with cells with wild-type p53 (+/+). Conditional expression of KLF4 in irradiated HCT116 p53-/- cells restored the G(1) cell population to a level similar to that seen in irradiated HCT116 p53+/+ cells. Conversely, treatment of HCT116 p53+/+ cells with small interfering RNA (siRNA) specific for KLF4 significantly reduced the number of cells in the G(1) phase following gamma irradiation compared with the untreated control or those treated with a nonspecific siRNA. In each case the increase or decrease in KLF4 level because of conditional induction or siRNA inhibition, respectively, was accompanied by an increase or decrease in the level of p21(WAF1/CIP1). Results of our study indicate that KLF4 is an essential mediator of p53 in controlling G(1)/S progression of the cell cycle following DNA damage.

Adenoviridae↗

PubMed2002

[Proliferating activity and differentiation between peripheral cells and central cells in ameloblastoma].

OBJECTIVE: To investigate the proliferating activities and differentiation between peripheral cells and central cells in ameloblastoma. METHODS: Expressions of proliferating cell nuclear antigen (PCNA), Ki-67, CK10&13 and CK19 were detected in 43 ameloblastoma (15 follicular, 20 plexiform and 8 acanthomatous) by SP immunohistochemical methods. RESULTS: The PCNA labelling indices were significantly higher in peripheral cells (5.12% +/- 2.76%) of tumour nests or strands than in central cells (1.36% +/- 1.02%, P < 0.001). The peripheral cells of tumour nests or strands exhibited a significantly higher Ki-67 labelling index (3.63% +/- 1.80%) than central cells (1.26% +/- 0.96%, P < 0.001). The labelling indices between PCNA and Ki-67 showed a significant correlation (P < 0.01). The positive expressions of CK10&13 and CK19 were significantly higher in central cells than in peripheral cells (P < 0.01). CONCLUSIONS: The peripheral zones of tumour nests or strands are regarded as proliferating areas; there exists a significantly different differentiation between central cells and peripheral cells.

Adolescent↗

PubMed2002

[A quantitatively pathological study on malignant ameloblastomas].

OBJECTIVE: The purpose of this study was to investigate the role of nuclear morphometric parameters, DNA content and Ag-NOR count in the differentiating malignant and benign ameloblastomas. METHODS: Totally 17 cases of malignant ameloblastomas were examined by using HE, AgNOR and DNA stain methods. Morphometric parameters of cell nuclei, DNA content and AgNOR count were quantitatively studied by using an image analysis system. RESULTS: Seven parameters (area, perimeter, equal diameter, minor diameter, mean diameter, round index, axis ratio) out of ten shape factors were significantly different between malignant and benign ameloblastoma (P < 0.01). AgNOR count and DNA index in malignant ameloblastoma were significantly higher than those in benign ameloblastoma (P < 0.01). Logistic regression equation was established, according to nuclear morphormetric parameters and DNA index. CONCLUSION: Quantitative analysis of DAN content, nuclear morphmetric parameters and AgNOR count may be helpful in differentiating malignant and benign ameloblastomas.

Adolescent↗

PubMed2002

[A histological and ultrastructural study of the tidemark in human condylar cartilage].

OBJECTIVE: To study the histology and ultrastructure of the tidemark in the adult condylar cartilage and their significance. METHODS: After embedded in paraffin, 50 adult condyles were stained with HE, partly with Van-Gieson and histochemical methods, then observed by light microscope. 3 cases of the tidemark region were observed by transmission electron microscope, another 5 cases were studied by scanning electron microscope. RESULTS: In the tidemark region, there had shown the presence of the AKP and calcium, absence of the proteoglycan, abundance of the membrane-bound matrix vesicles, crystals of hydroxyapatite and lipid nodule-like substances, which were often observed in the load-bearing areas. The collagen fibrils of the noncalcified cartilage crossed the tidemark gradiently and were continuous with those of the calcified cartilage; a band of horizontal fibrils surrounded the whole tidemark region, which was wider in the load-bearing areas than that in the nonload-bearing areas and which interweaved with the gradient fibrils so as to form a net. Digested with papain, the surface of the tidemark was highly undulating, and a lot of chondrocyte lacunae were seen on the surface, which were surrounded by calcified tissues. CONCLUSIONS: In the region of the tidemark, physiological calcification takes place and is more active in the load-bearing areas; gradient and horizontal fibrils interweave with each other, which is correlated with the force on the articulation.

Adult↗