Biomedical subjects

Zhiping Wang

Publications and source records attributed to Zhiping Wang.

12 recordsLinked to original sources

PubMed2025

Multi-omics Mendelian randomization integrating RNA-seq, eQTL and pQTL data revealed CPXM1 as a potential drug target for osteoporosis.

Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mineral density and increased fracture risk, continues to be a major global health concern. Traditional treatments for osteoporosis have limited efficacy and safety profiles, highlighting the need for novel therapeutic targets. This study integrates multi-omics data, including RNA-seq, expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data, through Mendelian randomization (MR) to identify potential drug targets for osteoporosis. By leveraging bidirectional two-sample MR analysis, we identified CPXM1 (Carboxypeptidase X, M14 family member 1) as a novel gene that is causally linked to osteoporosis risk. Through transcriptomic and proteomic validation, we demonstrate that CPXM1 was upregulated in aged bone tissues and osteoporotic conditions in both human and murine models. Gene set enrichment analysis (GSEA) revealed significant dysregulation of bone homeostasis pathways, including increased extracellular matrix degradation and suppression of osteoblast differentiation in aged mice. Furthermore, phenome-wide association studies (PheWAS) confirmed minimal off-target effects of CPXM1, reinforcing its potential as a therapeutic target. Finally, computational drug repurposing predicted several promising drug candidates, including Doxorubicin, 5-Fluorouracil, and 2-Methylcholine, which may target CPXM1 pathways for osteoporosis treatment. These findings highlight CPXM1 as a potential biomarker and therapeutic target, offering new avenues for osteoporosis therapy.

Osteoporosis↗

PubMed2007

iGibbs: improving Gibbs motif sampler for proteins by sequence clustering and iterative pattern sampling.

The motif prediction problem is to predict short, conserved subsequences that are part of a family of sequences, and it is a very important biological problem. Gibbs is one of the first successful motif algorithms and it runs very fast compared with other algorithms, and its search behavior is based on the well-studied Gibbs random sampling. However, motif prediction is a very difficult problem and Gibbs may not predict true motifs in some cases. Thus, the authors explored a possibility of improving the prediction accuracy of Gibbs while retaining its fast runtime performance. In this paper, the authors considered Gibbs only for proteins, not for DNA binding sites. The authors have developed iGibbs, an integrated motif search framework for proteins that employs two previous techniques of their own: one for guiding motif search by clustering sequences and another by pattern refinement. These two techniques are combined to a new double clustering approach to guiding motif search. The unique feature of their framework is that users do not have to specify the number of motifs to be predicted when motifs occur in different subsets of the input sequences since it automatically clusters input sequences into clusters and predict motifs from the clusters. Tests on the PROSITE database show that their framework improved the prediction accuracy of Gibbs significantly. Compared with more exhaustive search methods like MEME, iGibbs predicted motifs more accurately and runs one order of magnitude faster.

Algorithms↗

PubMed2006

In vivo CD4+ T-cell up-regulation and high dose side effects of refolded duck interleukin-2.

The recombinant duck interleukin-2 (rduIL-2) monomer was firstly isolated under nature condition, and refolded by oxidization procedure. Refolded rduIL-2 monomer induced in vitro proliferation of Con A-stimulated duck splenocytes in a sensitive and dose-dependent manner, and up-regulated in vivo the amounts of CD4+ T cells with low dose of administration. However, high doses intermittent administration resulted in sever side effects in vivo, with typical lymphocytic interstitial pneumonitis and nephritis, and lymphocytic depletion in splenic corpuscle. Our findings might be beneficial to studies of both mechanism and applications in vivo of avian IL-2.

Animals↗

PubMed2006

Heavy metal distribution in tissues and eggs of Chinese alligator (Alligator sinensis).

Chinese alligator (Alligator sinensis) is a critically endangered species endemic to China. Concentrations of heavy metals (As, Fe, Mn, Cu, Pb, Cd, Cr, Zn, and Hg) were examined in the tissues of Chinese alligators to elucidate the background distribution of these metals in the alligator body. Generally, within the body compartments, metal concentrations were high in liver, kidney, and heart, and low in pancreas and gonad. Study of heavy metal levels in the feces and eggs of Chinese alligator suggested that Chinese alligators could reduce body burden of toxic substances by excreting them to feces and/or sequestrating them into eggs to a lesser extent. In addition, to test whether eggshell or egg membrane could be used as surrogates to measure heavy metal load in egg contents, the correlation of metal concentrations between three egg compartments was determined. Of the nine elements analyzed, concentrations of iron, copper, and zinc in the shell membrane were highly correlated with the levels in egg contents, whereas no metal was significantly correlated between eggshell and egg contents. This suggested that the shell membrane could be a useful bioindicator for Fe, Cu, and Zn contaminations in the eggs of Chinese alligator. In a comparison of metal contents in the eggs of individuals from the Anhui captive population, the wild population in Anhui Province, and those of the Changxing captive population, higher Cu, Zn, and Cd levels and a lower Pb level were found in the Changxing individuals, indicative of specific pollutants in different areas. In addition, the majority of metal elements in the muscles of Chinese alligators and American alligators are in the same ranges. As a result of the data found in the eggs of the two alligator species, the Chinese alligators may be exposed to a higher level of metal pollutants. The study provided measurement of the heavy metal distribution in the endangered Chinese alligator for the first time and could serve as the background for the monitoring of possible heavy metal contaminations in the alligator habitats.

Alligators and Crocodiles↗

PubMed2006

Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation.

Like other small G proteins of the Ras superfamily, Rap1 is activated by distinct guanine nucleotide exchange factors (GEFs) in response to different signals to elicit cellular responses. Activation of Rap1 by cyclic AMP (cAMP) can occur via cAMP-dependent protein kinase A (PKA)-independent and PKA-dependent mechanisms. PKA-independent activation of Rap1 by cAMP is mediated by direct binding of cAMP to Rap1-guanine nucleotide exchange factors (Rap1-GEFs) Epac1 (exchange protein directly activated by cAMP 1) and Epac2 (Epac1 and Epac2 are also called cAMP-GEFI and -GEFII). The availability of cAMP analogues that selectively activate Epacs, but not PKA, provides a specific tool to activate Rap1. It has been argued that the inability of these analogues to regulate extracellular signal-regulated kinases (ERKs) signaling despite activating Rap1 provides evidence that Rap1 is incapable of regulating ERKs. We confirm that the PKA-independent activation of Rap1 by Epac1 activates a perinuclear pool of Rap1 and that this does not result in ERK activation. However, we demonstrate that this inability to regulate ERKs is not a property of Rap1 but is rather a property of Epacs themselves. The addition of a membrane-targeting motif to Epac1 (Epac-CAAX) relocalizes Epac1 from its normal perinuclear locale to the plasma membrane. In this new locale it is capable of activating ERKs in a Rap1- and cAMP-dependent manner. Rap1 activation by Epac-CAAX, but not wild-type Epac, triggers its association with B-Raf. Therefore, we propose that its intracellular localization prevents Epac1 from activating ERKs. C3G (Crk SH3 domain Guanine nucleotide exchanger) is a Rap1 exchanger that is targeted to the plasma membrane upon activation. We show that C3G can be localized to the plasma membrane by cAMP/PKA, as can Rap1 when activated by cAMP/PKA. Using a small interfering RNA approach, we demonstrate that C3G is required for the activation of ERKs and Rap1 by cAMP/PKA. This activation requires the GTP-dependent association of Rap1 with B-Raf. These data demonstrate that B-Raf is a physiological target of Rap1, but its utilization as a Rap1 effector is GEF specific. We propose a model that specific GEFs activate distinct pools of Rap1 that are differentially coupled to downstream effectors.

Amino Acid Motifs↗

PubMed2005

Effects of extracellular polymeric substances on aerobic granulation in sequencing batch reactors.

The effects of extracellular polymeric substances on aerobic granulation in sequencing batch reactors were investigated by evaluating the content and compositions of extracellular polymeric substances, and the relationship between extracellular polymeric substances composition and surface properties of glucose-fed aerobic granules. The results showed that extracellular polymeric substances could affect surface properties of cells, such as surface charge and hydrophobicity, enhance polymeric interaction and promote aerobic granulation. Moreover, extracellular polymeric substances were produced mainly in the exponential phase, and served as carbon and energy source in starvation phase during granulation process, thus regulating the growth of bacteria in the interior and exterior of granules, and maintaining the integrality of granules.

Aerobiosis↗

PubMed2004

[The synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3].

OBJECTIVE: To observe the synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3 in vitro. METHODS: Cell morphology, MTU, flow cytometer and immunocytochemical method were used to observe the effects of 10(-6), 10(-7), 10(-8) mol/L paclitaxel and 10(-7), 10(-8), 10(-9) mol/L gemcitabine on prostate cancer cell line PC-3 by single or synergistic administration for 48 hours in vitro. RESULTS: Gemcitabine above 10(-8) mol/L enhanced the growth suppression [suppression ratio > or = (50.8 +/- 4.2)%, P < 0.05] and apoptosis [apoptosis ratio > or = (22.9 +/- 2.3)%, P < 0.05] and down-regulation of the expression of cyclin D1 [expression ratio < or = (9.6 +/- 1.6)%, P < 0.01] induced by paclitaxel above 10(-7) mol/L in PC-3 cells. Gemcitabine changed the ratio of G2/M cell arrest induced by paclitaxel from (70.3 +/- 9.7)% to (38.2 +/- 4.2)%, and reversed the G2/M arrest partially (P < 0.01). CONCLUSION: Paclitaxel and gemcitabine can enhance the growth suppression and apoptosis induced by paclitaxel in a synergistic way. They show great potential in the treatment of androgen-independent carcinoma of the prostate.

Antimetabolites, Antineoplastic↗

PubMed2004

[Study on extraction process of the volatile oil for biyuan dropping pills].

OBJECTIVE: To determine the optimal extracting process of the volatile oil for Biyuan Dropping Pills. METHODS: Conditions for the extraction were studied by orthogonal design guided by the increasement of the volatile oil. RESULTS: The distilling time is the main factor,and the fineness of the herbal material is the second. The optimal process is as follows: crush the herbal material into coarse powder, macerate 1 hour with 9 times water and distill 4 hours. CONCLUSION: The optimized process is feasible and stable.

Analysis of Variance↗

PubMed2003

[Effect of inorganic nitrogen on CH4 oxidation in soils].

The effects of N inputs, including N fertilizer applications and atmospheric N depositions, on CH4 oxidation by soils were determined by CH4-oxidizing bacteria, N inputs and soil factors. These effects were inhibitory or stimulative, but inhibition was more popular than stimulation, and the inhibition of NH4+ was more popular than that of NO3-. Wealthy experiments in different soils and climate regions are required to monitor and evaluate how N inputs influence CH4 oxidation in soils. Generally, CH4 oxidation in soils following N inputs showed multiple inhibition patterns, i.e., immediate or direct inhibition, delayed inhibition, and absence of inhibition. Some researchers explained the inhibition mechanism through using competition between CH4 and NH4+ for the same enzyme sites, elevated threshold, salt effect and ion-exchange, and N turnover rate and N concentration. However, the inhibitory mechanism is still unclear. Therefore, inhibitory mechanism is one of the main research concerns in future.

Ammonia↗

PubMed2002

The role of superoxide anion in the regulation of epidermal growth factor or the expression and proliferation of its receptor in prostate cancer cell line PC3.

The purpose of this study was to investigate the role of superoxide anion(O2-) in the regulation of epidermal growth factor (EGF) or epidermal growth factor receptor (EGFR) expression and proliferation in the prostate cancer cell line PC3. Cell proliferation was tested by a 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay in the presence of O2-, EGF or their combination. Immunohistochemistry was carried out to assay the expression of EGF or EGFR. EGF or EGFR mRNA expression in the cells treated with O2- was examined by in situ hybridisation. The proliferation was significantly inhibited by O2- in a concentration-dependent manner ranging from 9 to 36 micromol/l nicotinamide adenine dinucleotide (NADH) combined with 2-8 micromol/l N-methylphenazonium methyl sulfate (PMS). The enhancement of proliferation induced by 5 ng/ml EGF was significantly overcome by O2-. Although O2- was not able to alter EGFR mRNA expression, O2- at the concentration of 18 micromol/l NADH and 4 micromol/l PMS reduced EGFR protein expression. O2- at the concentration of 18 micromol/l NADH and 4 micromol/l PMS can downregulate EGF and EGF mRNA expression.

Cell Line, Tumor↗

PubMed2002

Gene expression profiling of initiated epidermal cells with benign or malignant tumor fates.

High-density oligonucleotide array technology was used to search for gene expression changes that may predict or cause sporadic tumorigenesis. To reduce variation among samples, a non-transformed mouse epidermal keratinocyte clone was compared with its carcinoma-producing or papilloma-producing 7,12-dimethylbenz[a]anthracene-initiated cell derivative. The majority of the approximately 12 325 genes or expressed sequence tags (ESTs) analyzed remained unaltered reflective of the clonal nature of the model. Consistent gene expression changes among biological replicates included 69 in malignancy-prone initiated cells, 46 in papilloma-precursor initiated cells and an additional 45 with changes in both initiated cell lineages. The changes covered a broad spectrum of cellular activities, implying that multiple pathways cooperate at the initiation of carcinogenesis. There was a tendency in the malignancy-prone cells for differences in proliferation and apoptosis-related genes. The benign lineage tended toward aberrant expression of genes involved in differentiation and epidermal barrier function. Several independently confirmed gene expression changes revealed plausible effectors to bypass an activated ras protein in proliferation pathways and to compromise the wild-type p53 and other apoptosis pathways at initiation of carcinogenesis. The differential expression patterns of the initiated cells are consistent with the hypothesis that changes in gene expression at initiation may cooperate with subsequent oncogenic changes to determine malignant fate. The cloned epidermal cell lineages allowed detection of putative early cancer genes in a model that is conducive to testing their direct role in epithelial multistep carcinogenesis in vitro and in vivo.

Animals↗

PubMed2002

[Effects of global warming on productivity and soil moisture in Taihang mountain: a transplant study].

By transferring natural vegetation with soil from high elevation to low elevation, a 2 degrees C warmer condition was created. In each site, 5 different precipitation treatments were applied to test if the temperature and precipitation changes under global warming will result in a lower soil moisture condition and, therefore, feedback negatively on vegetation productivity of the Taihang Mountain. Two years' field experiment suggested that, because of the low adaptability of Arundinelia hirta under a warmer condition, its productivity decreased significantly at the end of the experiment. Productivities of grass with better adaptability such as Themeda japonica and Artemisia sacrorum did not change significantly between the two sites. Tested vegetation demonstrated a significant increase in productivity under the higher precipitation condition by showing 22% increase in productivity under 20% higher precipitation treatment. Soil moisture condition under treatments with higher precipitation was generally higher than that under treatments with lower precipitation. In the warmer site, soil moisture became higher since the beginning of the second year.

Climate↗