Biomedical subjects

Jianmin Wang

Publications and source records attributed to Jianmin Wang.

At least 19 recordsLinked to original sources

PubMed2026

EZH2 Suppression Diversifies Prostate Cancer Lineage Variant Evolution and Lacks Efficacy in Inhibiting Disease Progression.

UNLABELLED: Advanced prostate cancer remains a leading cause of cancer-related death among men due to disease progression in nearly all patients on standard-of-care therapy targeting the androgen receptor. An important mechanism driving therapeutic resistance is lineage plasticity, which enables prostate cancer cells to reprogram into lineage variants no longer dependent on androgen receptor signaling. As inhibitors of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) are being evaluated clinically for the treatment of advanced prostate cancer, we investigated in this study how EZH2 affects prostate cancer lineage plasticity. Data from genetically engineered mice and human clinical samples demonstrated that genetic or pharmacologic suppression of EZH2 altered chromatin to expand active transcription factor programs. These changes in gene expression during prostate cancer progression increased the diversity of prostate cancer lineage variants that arose. EZH2 suppression did not inhibit disease progression nor therapeutic resistance in this context. These findings advance the current understanding of prostate cancer lineage plasticity and suggest that EZH2 inhibitors may be less effective in treating prostate cancer prone to lineage plasticity. SIGNIFICANCE: EZH2 suppression diversifies prostate cancer lineage plasticity, which has implications for EZH2-targeted therapies that are being evaluated for prostate cancer treatment. See related commentary by Thienger et al., p. 827.

Enhancer of Zeste Homolog 2 Protein↗

PubMed2025

An image-based protein-ligand binding representation learning framework via multi-level flexible dynamics trajectory pre-training.

MOTIVATION: Accurate prediction of protein-ligand binding (PLB) relationships plays a crucial role in drug discovery, which helps identify drugs that modulate the activity of specific targets. Traditional biological assays for measuring PLB relationships are time consuming and costly. In addition, models for predicting PLB relationships have been developed and widely used in drug discovery tasks. However, learning more accurate PLB representations is essential to meet the stringent standards required for drug discovery. RESULTS: We propose an image-based PLB representation learning framework, called ImagePLB, which equips ligand representation learner (LRL) and protein representation learner (PRL) to accept 3D multi-view ligand images and protein graphs as input, respectively, and learns rich interaction information between ligand and protein through a binding representation learner (BRL). Considering the scarcity of protein-ligand pairs, we further propose a multi-level next trajectory prediction (MLNTP) task to pre-train ImagePLB on the 4D flexible dynamics trajectory of 16 972 complexes, including ligand level, protein level, and complex level, to learn information related to trajectories. Besides, by introducing trajectory regularization (TR), we effectively alleviate the problem of high (even almost identical) feature similarity caused by adjacent trajectories. Compared with the current state-of-the-art methods, ImagePLB has achieved competitive improvements on PLB-related prediction tasks, including protein-ligand affinity and efficacy prediction tasks. This study opens the door to the image-based PLB learning paradigm. AVAILABILITY AND IMPLEMENTATION: All data and implementation details of code can be obtained from https://github.com/HongxinXiang/ImagePLB.

Ligands↗

PubMed2006

Quantifying the availability and the stability of trace cationic elements in fly ash.

For adsorption-desorption controlled leaching processes, the total leachable mass and the adsorption constant are parameters representing the availability and the stability of trace elements in solid media. With these parameters, one can predict the leaching behavior of trace elements from solids under various pH and solid-to-liquid ratio conditions. An approach was developed in this paper to determine these parameters for model elements Cu(II), Cd(II), and Ni(II) in fly ash. This approach consists of a batch equilibrium titration, a batch equilibrium leaching with and without target element addition, and mathematical modeling. Results indicated that the adsorption constant of a trace element can be determined by modeling the adsorption ratio of the added element to the system as a function of pH. Results also indicated that the trace element originally present in fly ash had similar adsorption-desorption behavior as that added externally. By modeling the batch leaching data with and without external element addition, the total leachable mass and adsorption constant of the target element can be determined simultaneously. The total leachable mass is in agreement with experimental data from 50mM EDTA extraction.

Cadmium↗

PubMed2006

Reduced folate carrier gene G80A polymorphism is associated with an increased risk of gastroesophageal cancers in a Chinese population.

Low folate intake has been associated with an increased risk of both oesophageal and gastric cancers. Reduced folate carrier (RFC1, also named SLC19A1) is an essential folate transporter and functions as a bidirectional anion exchanger, taking up folate cofactors and exporting various organic anions. A G80A polymorphism in RFC1 gene has been shown to be associated with alterations in folate and homocysteine metabolism in healthy individuals. In this study, we hypothesised that genetic variants in RFC1 may modulate risk of oesophageal cancer (EC) and gastric cancer (GC). To test this hypothesis, we evaluated the associations of the G80A polymorphism of RFC1 with EC and GC risk in a case-control study of 216 EC and 633 GC cases and 673 cancer-free controls in a Chinese population. We found that compared with the 80GG/GA genotypes in the recessive model, the variant homozygote RFC1 80AA was associated with a significantly increased risk of EC (adjusted odds ratio (OR)=1.80, 95% confidence interval (CI)=1.29-2.51), GC (adjusted OR=1.59, 95% CI=1.25-2.02) and EC and GC combined (adjusted OR=1.63, 95% CI=1.30-2.04). In the dominant model, the risk associated with RFC1 80AA was also elevated in EC (OR=1.35, 95% CI=0.91-1.99), GC (OR=1.43, 95% CI=1.07-1.91) and EC and GC combined (adjusted OR=1.40, 95% CI=1.07-1.83), compared with the 80GG genotype. The stratification analyses showed that effects of the RFC1 80AA genotype were more evident in subgroups of relatively older (60 years), female, non-smokers, and non-drinkers both in EC and GC. Although the exact biological mechanism of this association remains to be explored, our findings suggest possible involvement of RFC1 variant in the susceptibility of EC and GC. Further large and functional studies are needed to confirm our findings.

Adult↗

PubMed2006

Quantitative relationship of two viruses (MrNV and XSV) in white-tail disease of Macrobrachium rosenbergii.

Macrobrachium rosenbergii nodavirus (MrNV) and extra small virus (XSV) were purified from diseased freshwater prawns M. rosenbergii and used to infect healthy post-larvae (PL) by an immersion method. Three groups of prawns were challenged with various combined doses of MrNV and XSV. Signs of white-tail disease (WTD) were observed in Groups 1 and 2, which had been challenged with combinations containing relatively high proportions of MrNV and low proportions of XSV. By contrast there was little sign of WTD in Group 3, which had been challenged with a higher proportion of XSV than MrNV. A 2-step Taqman real-time RT-PCR was developed and applied to quantify viral copy numbers in each challenged PL. Results showed that genomic copies of both viruses were much higher in Groups 1 and 2 than they were in Group 3, indicating that MrNV plays a key role in WTD of M. rosenbergii. The linear correlation between MrNV and XSV genome copies in infected prawns demonstrated that XSV is a satellite virus, dependent on MrNV, but its role in pathogenicity of WTD remains unclear.

Animals↗

PubMed2006

Predicting metals partitioning in wastewater treatment plant influents.

Interactions of heavy metals with primary sludge particulates were investigated using batch equilibrium metal uptake experiments. Results showed that metal uptake by primary sludge is significantly affected by pH. A mathematical model was developed to describe metals partitioning as a function of pH. The metal adsorption constants were determined. Results showed that for the same metal ion, the values of metal adsorption constants for primary sludge samples collected from different locations and at different times were in the same order of magnitude. Therefore, the adsorption constants were normalized and calibrated using field data. For Ag(I), Cd(II), Co(II), Cr(III), Cu(II), Ni(II), Pb(II), and Zn(II), the calibrated values of adsorption constants (logK(S)) are, respectively, 4.4, 5.1, 3.6, 4.5, 4.6, 3.6, 6.0, and 6.0. These constants can be used to predict the metal partitioning in plant influents and metal removal in primary treatment processes.

Adsorption↗

PubMed2006

Impacts of pH and ammonia on the leaching of Cu(II) and Cd(II) from coal fly ash.

Many coal-fired power plants are implementing ammonia-based technologies to reduce NO(x) emissions. Excess ammonia in the flue gas often deposits on the coal fly ash. Ammonia can form complexes with many heavy metals and change the leaching characteristics of these metals. This research tends to develop a fundamental understanding of the ammonia impact on the leaching of some heavy metals, exemplified by Cu(II) and Cd(II), under different pH conditions. Batch results indicated that the adsorption is the main mechanism controlling Cu(II) and Cd(II) leaching, and high concentrations of ammonia (>5,000 mg/l) can increase the release of Cu(II) and Cd(II) in the alkaline pH range. Based on the chemical reactions among fly ash, ammonia, and heavy metal ion, a mathematical model was developed to quantify effects of pH and ammonia on metal adsorption. The adsorption constants (logK) of Cu(2+), Cu(OH)(+), Cu(OH)(2), and Cu(NH(3))(m)(2+) for the fly ash under investigation were respectively 6.0, 7.7, 9.6, and 2.9. For Cd(II), these constants were respectively 4.3, 6.9, 8.8, and 2.6. Metal speciation calculations indicated that the formation of less adsorbable metal-ammonia complexes decreased metal adsorption, therefore enhanced metal leaching.

Adsorption↗

PubMed2006

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma.

BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma. METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0-6), and 1.5 (0-9) respectively. CONCLUSION: A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.

Journal Article↗

PubMed2006

Long-term engraftment of p18(INK4C)-deficient hematopoietic stem cells is enhanced in the sublethally-irradiated recipients.

Non-myeloablative regimens for host conditioning have been widely used in clinical hematopoietic stem cell transplantation due to their reduced toxicity on the recipients. But a milder conditioning regimen may require a higher engrafting ability of donor stem cells in competing with endogenous stem cells. Thus, new strategies for enhancing the competitiveness of donor stem cells in non-myeloablative recipients would have important implications for current clinical stem cell transplantation. It is known that the absence of p18(INK4C) (p18) gene can enhance the self-renewal potential of hematopoietic stem cells (HSCs). We applied the approach of competitive bone marrow transplantation to evaluate the impact of p18 gene deletion on long-term engraftment of HSCs in sublethally irradiated hosts. We found that p18(-/-) HSCs had a significant advantage over wild-type HSCs during long-term engraftment in the mouse recipients that received a sub-lethal irradiation (5-Gy). The engraftment efficiency of p18(-/-) HSCs in the sub-lethally irradiated recipients was similar to that in the lethally irradiated (10-Gy) recipients. Our current study demonstrates that enhanced engraftment of donor HSCs in the absence of p18 does not strictly depend on the dose of irradiation used for host conditioning. Therefore, p18 might serve as a potential drug target for increasing the efficacy of stem cell transplant in the patients that are preconditioned with either a myeloablative or non-myeloablative regimen.

Animals↗

PubMed2006

Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers.

Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers. Fifty-three cases of non-high grade and 46 cases of high grade DCIS were selected, and representative sections from each case were stained with antibodies to these cytokeratin markers. High grade DCIS showed significantly higher rates of expression with stem and basal cell markers compared with non-high grade DCIS (p <0.05). The majority of DCIS, both high grade and non-high grade, expressed luminal cell markers (67% to 91%) and single type of cell origin marker (72% to 87%). High-grade DCIS more frequently co-expressed all three types of cell origin markers compared with non-high grade DCIS (p <0.05). In summary, a subset of high grade DCIS frequently rises from stem or/and basal cell populations; the subset is associated with poor prognosis in invasive breast carcinoma. Thus, these markers may be used to identify a potentially more aggressive subgroup of breast carcinoma at its pre-invasive stage (DCIS), and to manage it accordingly. Second, most DCIS express luminal cell markers, suggesting that malignant transformation occurs relatively late along the cell differentiation pathway, contrary to the traditional belief that most neoplasms arise from a more primitive stem cell population. Third, the majority of DCIS exclusively express one type of progenitor marker, indicating that in most incidences they may arise from a single progenitor population. Last, triple expression of all types of cell origin marker is frequently associated with high grade DCIS, suggesting that more complicated pathways are involved in these more aggressive lesions. Further studies are needed to delineate the relationships of cell origin markers in DCIS and invasive carcinoma to the clinical outcome.

Biomarkers, Tumor↗

PubMed2006

Expression patterns of ER-alpha, PR, HER-2/neu, and EGFR in different cell origin subtypes of high grade and non-high grade ductal carcinoma in situ.

We have previously reported that high grade and non-high grade ductal carcinoma in situ (DCIS) of the breast can be subdivided into 3 cell origin subtypes (luminal, basal/stem, and null), and that high grade DCIS is more frequently associated with basal/stem cell subtypes compared to non-high grade DCIS. Here we refine the relationships between these 3 subtypes and the expression patterns of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (ERFR) in 53 cases of non-high grade and 46 cases of high nuclear grade DCIS. Using a panel of antibodies to ER-alpha, PR, HER-2/neu, and EGFR, along with cytokeratin (CK) markers (CK5/6, CK8, CK14, CK17, and CK18), we found that all 3 cell origin subtypes can express ER-alpha and PR, and their expression is higher in non-high grade DCIS than in high grade DCIS; the expression of HER-2/neu is associated with luminal subtype only in non-high grade DCIS, but can be seen in all 3 subtypes in high grade DCIS; the expression of EGFR is low and is present only in luminal cell subtypes in both high and non-high grade DCIS. Basal/ stem cell and null cell subtypes occur in younger patients in non-high grade DCIS compared to high grade DCIS. In conclusion, the expression patterns of ER-alpha, PR, HER-2/neu, and EGFR are markedly different in different cell origin subtypes of both high grade and non-high grade DCIS, suggesting that cell origin subtypes as well as nuclear grade contribute to the biological and molecular heterogeneity of DCIS.

Adult↗

PubMed2006

[Genetic diversity of indigenous sheep breeds in Shandong Province based on microsatellite markers study].

By using 24 microsatellite markers, this paper studied the genetic diversity of four indigenous sheep breeds in Shandong Province. 467 alleles were detected from 164 sheep of 71 breeding groups, and the proportion of effective alleles was 49.59%. The differences of the allele number among microsatellite loci were larger than those among breeds. 123 peculiar alleles and 43 dominative alleles were found from these sheep. 89% of the microsatellite markers were not in Hardy-Weinberg, and 50% of them were neutral. All the microsattelite markers were of high polymorphic (PIC > 0.5), and the values of Shannon indexes were relatively high. The observed heterozygosities (0.454 to approximately 0.560) were significantly lower than their expected values (0.831 to approximately 0.849). It was suggested that the four indigenous sheep breeds in Shandong Province were highly genetic polymorphic but somewhat inbred. The NJ and UPGRAM dendrograms indicated that the small-tailed and large-tailed Han sheep in west Shandong were closer in genetics, and the Shandi and Wadi sheep in east Shandong were similar. The genetic distances between different sheep breeds were accordant to geographical distances.

Alleles↗

PubMed2005

Evolution of alternative splicing after gene duplication.

Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice (AS) forms than single-copy genes, and that a negative correlation exists between the mean number of AS forms and the gene family size. Interestingly, we found that the loss of alternative splicing in duplicate genes may occur shortly after the gene duplication. These results support the subfunctionization model of alternative splicing in the early stage after gene duplication. Further analysis of the alternative splicing distribution in human duplicate pairs showed the asymmetric evolution of alternative splicing after gene duplications; i.e., the AS forms between duplicates may differ dramatically. We therefore conclude that alternative splicing and gene duplication may not evolve independently. In the early stage after gene duplication, young duplicates may take over a certain amount of protein function diversity that previously was carried out by the alternative splicing mechanism. In the late stage, the gain and loss of alternative splicing seem to be independent between duplicates.

Alternative Splicing↗

PubMed2005

Separation and quantitative analysis of coumarin compounds from Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook. f by pressurized capillary electrochromatography.

A pressurized capillary electrochromatography (pCEC) method with post-column detection cell has been developed for the therapeutically important coumarins from Angelica dahurica extract. The separation of five major coumarins (xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate, byakangelicin) was optimized with respect to composition of the mobile phase, ionic strength of buffers, pH, and applied voltage. Baseline separation was achieved for the five coumarins in less than 25 min using a mobile phase of methanol-acetonitrile-phosphate buffer (pH 4.8; 15 mM) (22.5:15:62.5, v/v/v). The method showed satisfactory retention time and peak area repeatability with the first use of post-column detection cell in the pCEC instrument. Comparing to capillary high performance liquid chromatography (capillary HPLC) and conventional high performance liquid chromatography (HPLC), higher column efficiency, and shorter analysis time were achieved in pCEC. The five coumarins in the extract samples representing different stages of traditional extraction of A. dahurica were also quantitatively analyzed by pCEC. The calibration curves were linear in the range 37-129, 36-126, 12-41, 88-306, 20-69 microg/ml of the standard solutions containing the five coumarins with correlation coefficients between 0.9976 and 0.9994.

Calibration↗

PubMed2005

Identification of novel and improved antimitotic agents derived from noscapine.

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.

Animals↗

PubMed2005

Genetic variation in selenoprotein S influences inflammatory response.

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.

Adult↗

PubMed2005

A method for finding single-nucleotide polymorphisms with allele frequencies in sequences of deep coverage.

BACKGROUND: The allele frequencies of single-nucleotide polymorphisms (SNPs) are needed to select an optimal subset of common SNPs for use in association studies. Sequence-based methods for finding SNPs with allele frequencies may need to handle thousands of sequences from the same genome location (sequences of deep coverage). RESULTS: We describe a computational method for finding common SNPs with allele frequencies in single-pass sequences of deep coverage. The method enhances a widely used program named PolyBayes in several aspects. We present results from our method and PolyBayes on eighteen data sets of human expressed sequence tags (ESTs) with deep coverage. The results indicate that our method used almost all single-pass sequences in computation of the allele frequencies of SNPs. CONCLUSION: The new method is able to handle single-pass sequences of deep coverage efficiently. Our work shows that it is possible to analyze sequences of deep coverage by using pairwise alignments of the sequences with the finished genome sequence, instead of multiple sequence alignments.

Computers, Molecular↗

PubMed2005

Discovery of S-phase arresting agents derived from noscapine.

Analogues of the natural product noscapine were synthesized, and their potential as antitumor agents were examined. The discovery of a novel regio- and stereoselective O-demethylation led to the synthesis of several O-alkylated analogues that induced an unexpected S-phase arrest of mammalian cells. Compound 4a was the most potent analogue inhibiting cell proliferation at an EC(50) of 1.9 microM.

Antineoplastic Agents↗