Biomedical subjects

Yipeng Wang

Publications and source records attributed to Yipeng Wang.

At least 19 recordsLinked to original sources

PubMed2026

Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.

Despite breakthrough advancements in cancer immunotherapy, significant inter-individual heterogeneity in clinical outcomes persists, bringing the regulatory roles of intrinsic host biological variables into sharp focus. Accumulating fundamental and clinical evidence indicates that age and sex play crucial roles in determining tumor susceptibility, disease progression, and the remodeling of the anti-tumor immune microenvironment. This review systematically delineates the profound impacts of the dual dimensions of age and sex on anti-tumor immune responses and immune evasion mechanisms. In the dimension of age, this article outlines the progressive functional decline of T/B lymphocytes and innate immune subsets driven by immunosenescence, and emphatically reveals how inflammaging and its associated senescence-associated secretory phenotype (SASP) orchestrate the formation of an immunosuppressive tumor microenvironment. In the dimension of sex, we deeply explore four core mechanisms comprising sex chromosome genomics (e.g., escape from X-chromosome inactivation and loss of Y chromosome), sex hormone networks, microenvironmental metabolic reprogramming, and the host gut microbiome, elucidating the molecular basis driving the disparities in innate and adaptive immunity between males and females. In summary, thoroughly deciphering the complex immune regulatory networks driven by age and sex not only helps elucidate the disparities in efficacy and toxicity observed in patients undergoing immune checkpoint inhibitors, but also provides crucial theoretical foundations and translational insights for the future development of "age-tailored" and "sex-specific" strategies in personalized immuno-oncology.

Humans↗

PubMed2006

Comparison of 1-stage versus 2-stage anterior and posterior spinal fusion for severe and rigid idiopathic scoliosis--a randomized prospective study.

STUDY DESIGN: A randomized prospective study. OBJECTIVE: To compare safety, efficacy, and cost between 1-stage and 2-stage anterior and posterior spinal fusion in treating rigid thoracic adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Retrospective study issued different outcomes comparing 1-stage with 2-stage surgical procedures in treating neuromuscular and congenital scoliosis. A randomized prospective study in AIS has rarely been reported. METHODS.: Twenty-four patients were randomly divided into 2 groups. Group A underwent a 2-stage procedure, group B a 1-stage procedure. Inclusion criteria were: (1) AIS; (2) rigid single thoracic curve, > or =90 degrees on anteroposterior and > or =60 degrees on side bending view; and (3) pulmonary function tests, vital capacity > or =500 mL or FEV1 > or =50%. Exclusion criteria were: (1) curves either <90 degrees on anteroposterior or <60 degrees on bending view; and (2) pulmonary function tests, both vital capacity <500 mL and FEV1 <50%. The mean follow up was 3.3 years (range 2-5.1). Clinical outcomes between the 2 groups were analyzed. RESULTS: A statistical t test demonstrated no significant difference in age (P = 0.299), curves on anteroposterior (P = 0.908), on bending (P = 0.905), after surgery (P = 0.699), and at last follow-up (P = 0.946). No significant difference in blood loss (P = 0.089), transfusion (P = 0.334), operation time (P = 0.172), fusion segments anterior (P = 0.161), posterior (P = 0.546), wound drainage (P = 0.557), thoraco drainage (P = 0.948), and loss of correction at follow-up (P = 0.596). However, significant differences were found in length of stay (P < 0.001), patient cost of hospitalization (P < 0.001) between 2 groups, and curve correction (P < 0.001) in each group. Perioperative complications included 1 patient each with pneumonia, pneumothorax (group A), and ileus (group B). Screw nut loosing was found in 1 patient in group B, but no curve deteriorated. No neurologic deficit occurred in either group. CONCLUSION: A comparison of 1-stage versus 2-stage fusion in treating rigid thoracic curves in AIS did not show significant differences in safety or efficacy but did demonstrate significant difference in length of stay and patient cost.

Adolescent↗

PubMed2006

Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella.

Horizontal gene transfer plays a major role in microbial evolution. However, newly acquired sequences can decrease fitness unless integrated into preexisting regulatory networks. We found that the histone-like nucleoid structuring protein (H-NS) selectively silences horizontally acquired genes by targeting sequences with GC content lower than the resident genome. Mutations in hns are lethal in Salmonella unless accompanied by compensatory mutations in other regulatory loci. Thus, H-NS provides a previously unrecognized mechanism of bacterial defense against foreign DNA, enabling the acquisition of DNA from exogenous sources while avoiding detrimental consequences from unregulated expression of newly acquired genes. Characteristic GC/AT ratios of bacterial genomes may facilitate discrimination between a cell's own DNA and foreign DNA.

Bacterial Proteins↗

PubMed2005

WebArray: an online platform for microarray data analysis.

BACKGROUND: Many cutting-edge microarray analysis tools and algorithms, including commonly used limma and affy packages in Bioconductor, need sophisticated knowledge of mathematics, statistics and computer skills for implementation. Commercially available software can provide a user-friendly interface at considerable cost. To facilitate the use of these tools for microarray data analysis on an open platform we developed an online microarray data analysis platform, WebArray, for bench biologists to utilize these tools to explore data from single/dual color microarray experiments. RESULTS: The currently implemented functions were based on limma and affy package from Bioconductor, the spacings LOESS histogram (SPLOSH) method, PCA-assisted normalization method and genome mapping method. WebArray incorporates these packages and provides a user-friendly interface for accessing a wide range of key functions of limma and others, such as spot quality weight, background correction, graphical plotting, normalization, linear modeling, empirical bayes statistical analysis, false discovery rate (FDR) estimation, chromosomal mapping for genome comparison. CONCLUSION: WebArray offers a convenient platform for bench biologists to access several cutting-edge microarray data analysis tools. The website is freely available at http://bioinformatics.skcc.org/webarray/. It runs on a Linux server with Apache and MySQL.

Algorithms↗

PubMed2005

Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs.

We generated several cell models of tauopathy in order to study the mechanisms of neurodegeneration in diseases involving abnormal changes of tau protein. N2a neuroblastoma cell lines were created that inducibly express different variants of the repeat domain of tau (tau(RD)) when exposed to doxycycline (Tet-On system). The following three constructs were chosen: (i) the repeat domain of tau that coincides with the core of Alzheimer paired helical filaments; (ii) the repeat domain with the deletion mutation DeltaK280 known from frontotemporal dementia and highly prone to spontaneous aggregation; and (iii) the repeat domain with DeltaK280 and two proline point mutations that inhibit aggregation. The comparison of wild-type, pro-aggregation, and anti-aggregation mutants shows the following. (a) Aggregation of tau(RD) is toxic to cells. (b) The degree of aggregation and toxicity depends on the propensity for beta-structure. (c) Soluble mutants of tau(RD) that cannot aggregate are not toxic. (d) Aggregation is preceded by fragmentation. (e) Fragmentation of tau(RD) in cells is initially due to a thrombin-like protease activity. (f) Phosphorylation of tau(RD) (at KXGS motifs) precedes aggregation but is not correlated with the degree of aggregation. (g) Aggregates of tau(RD) disappear when the expression is silenced, showing that aggregation is reversible. (h) Aggregation can be prevented by drugs and even pre-formed aggregates can be dissolved again by drugs. Thus, the cell models open up new insights into the relationship between the structure, expression, phosphorylation, aggregation, and toxicity of tau(RD) that can be used to test current hypotheses on tauopathy and to develop drugs that prevent the aggregation and degeneration of cells.

Alzheimer Disease↗

PubMed2005

Expression of transforming growth factor and basic fibroblast growth factor and core protein of proteoglycan in human vertebral cartilaginous endplate of adolescent idiopathic scoliosis.

STUDY DESIGN: To compare the expression of cytokines and core protein of proteoglycan in the scoliotic concave and convex cartilaginous endplate using immunohistochemical staining. OBJECTIVES: To define the possible role of transforming growth factor beta 1 (TGFbeta1), basic fibroblast growth factor (bFGF), and core protein of proteoglycan in the development of adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Changes in the endplate composition have been implicated as possible etiologic factors in the pathogenesis of adolescent idiopathic scoliosis. Cytokines have exclusive effects on cartilage. Thus comparing the expression of the cytokines and matrix on the convex and concave sides of scoliotic endplate tissues may help to understand the role of endplate tissues in the induction and/or progression of idiopathic scoliosis. METHODS: The convex and concave half of cartilage endplate was collected at the apex and end vertebrae from 12 patients. The expression of TGFbeta1, bFGF, and core protein on both sides was examined with the immunohistochemistry method, and results were analyzed with the image analysis system. RESULTS: TGFbeta1, bFGF, and core protein of proteoglycan were all expressed in the cytoplasm of chondrocytes in the cartilaginous endplate. The area density and quantity density of TGFbeta1 and bFGF on the concave side are expressed in an even significantly higher level than that on the convex side (P > or = 0.05). The expression of the core protein of proteoglycan on the convex side is higher than that on the concave side, the difference is not significant (P > 0.05). CONCLUSION: There was a significantly higher expression of TGFbeta1 and bFGF, although a lower expression of the core protein on the concave side, which suggests a possible etiological factor or a secondary change in the development of adolescent idiopathic scoliosis.

Adolescent↗

PubMed2005

Enhanced microarray performance using low complexity representations of the transcriptome.

Low abundance mRNAs are more difficult to examine using microarrays than high abundance mRNAs due to the effect of concentration on hybridization kinetics and signal-to-noise ratios. This report describes the use of low complexity representations (LCRs) of mRNA as the targets for cDNA microarrays. Individual sequences in LCRs are more highly represented than in the mRNA populations from which they are derived, leading to favorable hybridization kinetics. LCR targets permit the measurement of abundance changes that are difficult to measure using oligo(dT) priming for target synthesis. An oligo(dT)-primed target and three LCRs detect twice as many differentially regulated genes as could be detected by the oligo(dT)-primed target alone, in an experiment in which serum-starved fibroblasts responded to the reintroduction of serum. Thus, this target preparation strategy considerably increases the sensitivity of cDNA microarrays.

Cell Line↗

PubMed2005

A new operative classification of idiopathic scoliosis: a peking union medical college method.

STUDY DESIGN: A retrospective radiographic study on the type of surgically treated idiopathic scoliosis, with a prospective study on the reliability of the type-related fusion guide. OBJECTIVES: To identify and classify surgically treated idiopathic scoliosis, and define its related fusion levels by a new classification system. SUMMARY OF BACKGROUND DATA: Some classification methods for idiopathic scoliosis have been suggested. However, poor intraobserver reproducibility and interobserver reliability were experienced in these studies, and were not appropriate for guiding surgical planning. METHODS: A total of 427 surgically treated idiopathic scoliosis cases were reviewed. Preoperative and postoperative standing anteroposterior, lateral, and preoperative supine side-bending radiograph were analyzed using the Scoliosis Research Society definition of scoliosis and curve apex. The resulting classification was tested for intraobserver reliability and interobserver reliability, and by 6 surgeons. Apical frequencies were determined for each type, and prospective surgical testing of the new type and its related fusion guide was performed. RESULTS: Three major types and 13 subtypes were identified, of which the Peking Union Medical College type I accounted for 56.62%, type II 42.16%, and type III 1.22%. The interobserver reliability testing was 85% (kappa coefficient 0.832), while intraobserver reproducibility was 91% (kappa coefficient 0.898). Each type had its corresponding fusion levels. A prospective study of 152 cases was performed according to the classification. All of these cases were followed over 18 months, and no postoperative decompensation was noted. CONCLUSION: The Peking Union Medical College classification of idiopathic scoliosis is one system to combine each type with its corresponding fusion level, and it had much higher interobserver reliability and intraobserver reproducibility than the King system. Further prospectivestudies would help to clarify and expand this system.

Adolescent↗

PubMed2005

"Promoter array" studies identify cohorts of genes directly regulated by methylation, copy number change, or transcription factor binding in human cancer cells.

DNA microarrays of promoter sequences have been developed in order to identify the profile of genes bound and activated by DNA regulatory proteins such as the transcription factors c-Jun and ATF2 as well as DNA-modifying methylases. The arrays contain 3083 unique human promoter sequences from +500 to -1000 nts from the transcription start site. Cisplatin-induced DNA damage rapidly leads to specific activation of the Jun kinase pathway leading to increased phosphorylation of c-Jun and ATF2-DNA complexes at hundreds of sites within 3 hours. Using three statistical criteria, approximately 269 most commonly phosphorylated c-Jun/ATF2-DNA complexes were identified and representative cases were verified by qPCR measurement of ChIP-captured DNA. Expression was correlated at the mRNA and protein levels. The largest functional cohort was 24 genes of known DNA repair function, most of which exhibited increased protein expression indicated coordinate gene regulation. In addition, cell lines of prostate cancer exhibit stable methylation or copy number changes that reflect the alterations of the corresponding primary tumors. 504 (18.5%) promoters showed differential hybridization between immortalized control prostate epithelial and cancer cell lines. Among candidate hypermethylated genes in cancer-derived lines, eight had previously been observed in prostate cancer, and 13 were previously determined methylation targets in other cancers. The vast majority of genes that appear to be both differentially methylated and differentially regulated between prostate epithelial and cancer cell lines are novel methylation targets, including PAK6, RAD50, TLX3, PIR51, MAP2K5, INSR, FBN1, GG2-1, representing a rich new source of candidate genes to study the role of DNA methylation in prostate tumors. Earlier studies using prototype promoter arrays examine approximately 7% of the proximal regulatory sequences while the current gene regulatory events surveyed here occur on a large scale and may rapidly effect the coordinated expression of a large number of genes.

Cell Line, Tumor↗

PubMed2005

Survey of differentially methylated promoters in prostate cancer cell lines.

DNA methylation and copy number in the genomes of three immortalized prostate epithelial and five cancer cell lines (LNCaP, PC3, PC3M, PC3M-Pro4, and PC3M-LN4) were compared using a microarray-based technique. Genomic DNA is cut with a methylation-sensitive enzyme HpaII, followed by linker ligation, polymerase chain reaction (PCR) amplification, labeling, and hybridization to an array of promoter sequences. Only those parts of the genomic DNA that have unmethylated restriction sites within a few hundred base pairs generate PCR products detectable on an array. Of 2732 promoter sequences on a test array, 504 (18.5%) showed differential hybridization between immortalized prostate epithelial and cancer cell lines. Among candidate hypermethylated genes in cancer-derived lines, there were eight (CD44, CDKN1A, ESR1, PLAU, RARB, SFN, TNFRSF6, and TSPY) previously observed in prostate cancer and 13 previously known methylation targets in other cancers (ARHI, bcl-2, BRCA1, CDKN2C, GADD45A, MTAP, PGR, SLC26A4, SPARC, SYK, TJP2, UCHL1, and WIT-1). The majority of genes that appear to be both differentially methylated and differentially regulated between prostate epithelial and cancer cell lines are novel methylation targets, including PAK6, RAD50, TLX3, PIR51, MAP2K5, INSR, FBN1, and GG2-1, representing a rich new source of candidate genes used to study the role of DNA methylation in prostate tumors.

Cell Line, Tumor↗

PubMed2004

Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress.

The NH2-terminal Jun kinases (JNKs) function in diverse roles through phosphorylation and activation of AP-1 components including ATF2 and c-Jun. However, the genes that mediate these processes are poorly understood. A model phenotype characterized by rapid activation of Jun kinase and enhanced DNA repair following cisplatin treatment was examined using chromatin immunoprecipitation with antibodies against ATF2 and c-Jun or their phosphorylated forms and hybridization to promoter arrays. Following genotoxic stress, we identified 269 genes whose promoters are bound upon phosphorylation of ATF2 and c-Jun. Binding did not occur following treatment with transplatin or the JNK inhibitor SP600125 or JNK-specific siRNA. Of 89 known DNA repair genes represented on the array, 23 are specifically activated by cisplatin treatment within 3-6 hr. Thus, the genotoxic stress response occurs at least partly via activation of ATF2 and c-Jun, leading to large-scale coordinate gene expression dominated by genes of DNA repair.

Activating Transcription Factor 2↗

PubMed2004

Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells.

The abnormal aggregation of tau protein into paired helical filaments (PHFs) is one of the hallmarks of Alzheimer's disease. Aggregation takes place in the cytoplasm and could therefore be cytotoxic for neurons. To find inhibitors of PHF aggregation we screened a library of 200,000 compounds. The hits found in the PHF inhibition assay were also tested for their ability to dissolve preformed PHFs. The results were obtained using a thioflavin S fluorescence assay for the detection and quantification of tau aggregation in solution, a tryptophan fluorescence assay using tryptophan-containing mutants of tau, and confirmed by a pelleting assay and electron microscopy of the products. Here we demonstrate the feasibility of the approach with several compounds from the family of anthraquinones, including emodin, daunorubicin, adriamycin, and others. They were able to inhibit PHF formation with IC50 values of 1-5 microm and to disassemble preformed PHFs at DC50 values of 2-4 microm. The compounds had a similar activity for PHFs made from different tau isoforms and constructs. The compounds did not interfere with the stabilization of microtubules by tau. Tau-inducible neuroblastoma cells showed the formation of tau aggregates and concomitant cytotoxicity, which could be prevented by inhibitors. Thus, small molecule inhibitors could provide a basis for the development of tools for the treatment of tau pathology in AD and other tauopathies.

Alzheimer Disease↗

PubMed2004

High-throughput polyribosome fractionation.

Polyribosome sedimentation velocity centrifugation can be used to identify differential regulation of the translation of mRNAs. However, ultracentrifugation presents practical limitations on the number of sedimentation velocity gradients that can be run simultaneously. A method for sedimentation velocity analysis of polyribosomes is presented that is based on low-speed centrifugation of sucrose gradients prepared in deep 96-well plates, the advantage of which is that hundreds of polyribosome fractionations can be performed simultaneously in a tabletop centrifuge.

Cell Fractionation↗

PubMed2004

Persister cells and tolerance to antimicrobials.

Bacterial populations produce persister cells that neither grow nor die in the presence of microbicidal antibiotics. Persisters are largely responsible for high levels of biofilm tolerance to antimicrobials, but virtually nothing was known about their biology. Tolerance of Escherichia coli to ampicillin and ofloxacin was tested at different growth stages to gain insight into the nature of persisters. The number of persisters did not change in lag or early exponential phase, and increased dramatically in mid-exponential phase. Similar dynamics were observed with Pseudomonas aeruginosa (ofloxacin) and Staphylococcus aureus (ciprofloxacin and penicillin). This shows that production of persisters depends on growth stage. Maintaining a culture of E. coli at early exponential phase by reinoculation eliminated persisters. This suggests that persisters are not at a particular stage in the cell cycle, neither are they defective cells nor cells created in response to antibiotics. Our data indicate that persisters are specialized survivor cells.

Anti-Bacterial Agents↗

PubMed2004

In silico dissection of cell-type-associated patterns of gene expression in prostate cancer.

Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.

Gene Expression Profiling↗

PubMed2004

The effect of cdk-5 overexpression on tau phosphorylation and spatial memory of rat.

In Alzheimer's disease (AD), hyperphosphorylation of tau may be the underlying mechanism for the cytoskeletal abnormalities and neuronal death. It was reported that cyclin-dependent kinase5 (cdk-5) could phosphorylate tau at most AD-related epitopes in vitro. In this study, we investigated the effect of cdk-5 overexpression on tau phosphorylation and spatial memory in rat. We demonstrated that 24 h after transfection into rat hippocampus, cdk-5 was overexpressed and induced a reduced staining with antibody tau-1 and an enhanced staining with antibodies 12e8 and PHF-1, suggesting hyperphosphorylation of tau at Ser199/202, Ser262/356 and Ser396/404 sites. Additionally, the cdk-5 transfected rats showed long latency to find the hidden platform in Morris water maze compared to the control rat. 48 h after transfection, the level of cdk-5 was decreased significantly, and the latency of rats to find the hidden platform was prolonged. It implies that in vivo overexpression of cdk-5 leads to impairment of spatial memory in rat and tau hyperphosphorylation may be the underlying mechanism.

Animals↗

PubMed2003

Anterior spinal fusion with TSRH instrumentation for scoliosis.

OBJECTIVE: To introduce a new spinal internal fixation system, Texas Scottish Rite Hospital (TSRH), and to investigate its early clinical outcomes. METHODS: The preliminary clinical outcomes of 15 patients with thoracolumbar or lumbar scoliosis treated by anterior spinal fusion with TSRH instrumentation were studied retrospectively. Fourteen patients were diagnosed as idiopathic scoliosis and 1 as neuromuscular scoliosis. RESULTS: Preoperatively, the Cobb's angle on the coronal plane was 55.8 degrees (range 35 degrees to approximately 78 degrees), and 14 degrees postoperatively, with an average correction of 74.8%. The average unfused thoracical curve was 35.9 degrees preoperatively (range 26 degrees to approximately 51 degrees) and 21.8 degrees (10 degrees to approximately 42 degrees) postoperatively, with 40% correction. The sagittal curve of lumbar was kept physiologically, preoperative 27.9 degrees and postoperative 25.7 degrees respectively. The trunk shift was 13.4 mm (5 to approximately 28 mm) preoperatively and 3.5 mm (0 to approximately 7 mm) postoperatively. The averaged apic vertebra derivation was 47.8 mm (21 to approximately 69 mm) before operation and 10.8 mm (3 to approximately 20 mm) after operation. The distance of C7 to center sacrum vertical line (CSVL) was 19.5 mm (16 to approximately 42) preoperatively and 11.3 mm (0 to approximately 32 mm) postoperatively. The apical vertebra rotation was 3 degree in 15 patients preoperatively, and were improved to normal in 10 patients, 1 degree in 4 patients, and 2 degree in 1 patients postoperatively. None had neurological injury and infection. Only 1 patient complained a cool feeling in the low extremity of concave side, and the symptom vanished at 3-month followed up. CONCLUSION: If used appropriately, TSRH anterior spinal system is a good teatment for low thoracic or thoracic lumbar scoliosis.

Adolescent↗

PubMed2002

[Surgical treatment of spinal myeloma, report of 19 cases].

OBJECTIVES: To discuss the indications for surgical procedures of spinal myeloma. METHODS: A retrospective analysis was made of the data of operation results of Nineteen patients with spinal myeloma, 13 males and 6 females, with the mean age of 45.1 (range 31 approximately 52). Pain was present in all patients. Nine patients had neurological deficit. According to Frankel classification 5 cases were Frankel B, 3 cases were Frenkel C, and 1 case was Frenkel D. Fourteen cases were diagnosed before operation, and 5 cases were diagnosed by pathology after operation. Surgical procedures performed included anterior approach in 11 cases, posterior approach in 7 cases and combined approach in 1 case. RESULTS: Decrease of pain was observed in all cases after surgery. Neurological improvement was observed in 8 out of the 9 cases. Complication (alteration of intestinal flora) occurred in one case. Follow-up lasted more than 1 year except in one case with a follow-up of only 6 months. Four cases were lost of follow-up. One case was still alive during the follow-up 8 years after operation. Other cases survived for 26.5 months on average (range 16 approximately 48 months). CONCLUSION: Surgery can ensure neurological improvement and spinal stability for patients with spinal myeloma, but should be associated with adjunctive medical treatment.

Adult↗