Publications by authors named "Xiaowei Ye"

6 Publications

  • Page 1 of 1

Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 6;190:114593. Epub 2021 May 6.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences; Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Novel inhibitors that target both the wild-type and mutant SMO are in high demand. In this study, we identified a novel Hh pathway inhibitor, pseudolaric acid B (PAB), which significantly inhibited the expression of Gli1 and its transcriptional target genes, such as cyclin D1 and N-myc, thus inhibiting the proliferation of DAOY and Ptch1 primary MB cells. Mechanistically, PAB can potentially bind to the extracellular entrance of the heptahelical transmembrane domain (TMD) of SMO, based on molecular docking and the BODIPY-cyclopamine binding assay. Further, PAB also efficiently blocked ciliogenesis, demonstrating the inhibitory effects of PAB on the Hh pathway at multiple levels. Thus, PAB may overcome drug-resistance induced by SMO mutations, which frequently occurs in clinical setting. PAB markedly suppressed tumor growth in the subcutaneous allografts of Ptch1 MB cells. Together, our results identified PAB as a potent Hh pathway inhibitor to treat Hh-dependent MB, especially cases resistant to SMO antagonists.
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May 2021

Comparative analyses of copy number variations between Bos taurus and Bos indicus.

BMC Genomics 2020 Oct 1;21(1):682. Epub 2020 Oct 1.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Background: Bos taurus and Bos indicus are two main sub-species of cattle. However, the differential copy number variations (CNVs) between them are not yet well studied.

Results: Based on the new high-quality cattle reference genome ARS-UCD1.2, we identified 13,234 non-redundant CNV regions (CNVRs) from 73 animals of 10 cattle breeds (4 Bos taurus and 6 Bos indicus), by integrating three detection strategies. While 6990 CNVRs (52.82%) were shared by Bos taurus and Bos indicus, large CNV differences were discovered between them and these differences could be used to successfully separate animals into two subspecies. We found that 2212 and 538 genes uniquely overlapped with either indicine-specific CNVRs and or taurine-specific CNVRs, respectively. Based on F, we detected 16 candidate lineage-differential CNV segments (top 0.1%) under selection, which overlapped with eight genes (CTNNA1, ENSBTAG00000004415, PKN2, BMPER, PDE1C, DNAJC18, MUSK, and PLCXD3). Moreover, we obtained 1.74 Mbp indicine-specific sequences, which could only be mapped on the Bos indicus reference genome UOA_Brahman_1. We found these sequences and their associated genes were related to heat resistance, lipid and ATP metabolic process, and muscle development under selection. We further analyzed and validated the top significant lineage-differential CNV. This CNV overlapped genes related to muscle cell differentiation, which might be generated from a retropseudogene of CTH but was deleted along Bos indicus lineage.

Conclusions: This study presents a genome wide CNV comparison between Bos taurus and Bos indicus. It supplied essential genome diversity information for understanding of adaptation and phenotype differences between the Bos taurus and Bos indicus populations.
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October 2020

PRDX1 stimulates non-small-cell lung carcinoma to proliferate via the Wnt/β-Catenin signaling.

Panminerva Med 2020 Sep 3. Epub 2020 Sep 3.

Department of Oncology, Guangdong Provincial People's Hospital's Nanhai Hospital, The Second People's Hospital Of Nanhai District, Foshan, China.

Background: Previous studies have shown that PRDX1 is upregulated in some types of malignant tumors. The role of PRDX1 in non-small-cancer lung carcinoma (NSCLC) remains unclear. This study aims to identify the role of PRDX1 in influencing in vitro biological functions of NSCLC and the molecular mechanism.

Patients And Methods: We collected 50 cases of fresh NSCLC and adjacent non-tumoral tissues for detecting differential expressions of PRDX1 by quantitative real-time polymerase chain reaction (qRT-PCR). Survival time of NSCLC patients, defined as the period from the operation to the latest follow-up or death due to recurrence or metastasis, was recorded for assessing the relationship between PRDX1 and prognosis in NSCLC. Using lentivirus transfection, PRDX1 level was downregulated in NSCLC cells. Subsequently, proliferative and apoptotic abilities, and expression levels of vital genes in the Wnt/β-Catenin signaling were examined. Finally, the significance of activated Wnt/β-Catenin signaling during PRDX1-regulated NSCLC proliferation was explored.

Results: Using GEPIA database and NSCLC tissues we collected, PRDX1 was detected to be upregulated in NSCLC samples than controls. PRDX1 level was related to tumor staging and prognosis in NSCLC. Knockdown of PRDX1 attenuated proliferative ability and stimulated apoptosis in NSCLC. Protein levels of Wnt5A was downregulated in H1299 and SPC-A1 cells with PRDX1 knockdown. Overexpression of β-Catenin enhanced proliferative ability and inhibited apoptosis in NSCLC cells with PRDX1 knockdown.

Conclusions: PRDX1 is upregulated in NSCLC samples, and linked to tumor staging and prognosis. It stimulates NSCLC to proliferate by activating the Wnt/β-Catenin signaling.
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September 2020

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Shuangbai San for Treating Primary Liver Cancer Patients With Cancer Pain.

J Pain Symptom Manage 2016 06 26;51(6):979-86. Epub 2016 Feb 26.

Department of Oncology, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China.

Context: Shuangbai San is a Chinese herb preparation used externally to treat pain. There have been few randomized controlled trials addressing the safety and usefulness of Shuangbai San, such as its effect on pain relief and quality of life (QOL) improvement.

Objectives: This study was conducted to evaluate the effect of Shuangbai San on relieving pain and improving QOL in primary liver cancer patients with cancer pain.

Methods: A total of 134 primary liver cancer patients with mild pain (numerical rating scale [NRS] ≤ 3), either locally in the liver or in the upper abdomen, were enrolled and randomly allocated to the group receiving Shuangbai San or the control group (receiving placebo). The primary outcome measures were the NRS score and QOL scales, including the QOL scale for patients with liver cancer, version 2.0 and the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30. The secondary outcome measures included the Karnofsky Performance Status score, blood indicators, and liver and kidney function before and after treatment.

Results: The NRS scores decreased more significantly in the Shuangbai San group than in the placebo group (P < 0.05) at the corresponding time points. The changes in the scores for the physical function, psychological function, and symptoms/adverse effects domains of the QOL scale for patients with liver cancer, version 2.0 and the physical, emotional, and cognitive domains of the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30 were significantly greater in the Shuangbai San group than in the placebo group (P < 0.05). The changes in the scores for the other domains were not significantly different (P > 0.05).

Conclusion: The use of Shuangbai San can relieve mild pain in liver cancer patients and improve their QOL.
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June 2016

Straightforward synthesis of the Brønsted acid hfipOSO3H and its application for the synthesis of protic ionic liquids.

Angew Chem Int Ed Engl 2014 Jun 26;53(26):6637-40. Epub 2014 May 26.

Institut für Anorganische und Analytische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg im Breisgau (Germany); Freiburger Materialforschungszentrum (FMF), Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Strasse 21, 79104 Freiburg im Breisgau (Germany); Current address: Institute of Inorganic Chemistry, Karlsruhe Institute of Technology, Engesserstrasse 15, 76131 Karlsruhe (Germany).

The easily accessible hexafluoroisopropoxysulfuric acid (1, hfipOSO3H; hfip = C(H)(CF3)2) was synthesized by the reaction of hexafluoroisopropanol and chlorosulfonic acid on the kilogram scale and isolated in 98 % yield. The calculated gas-phase acidity (GA) value of 1 is 58 kJ mol(-1) lower in ΔG° than that of sulfuric acid (GA value determined by a CCSD(T)-MP2 compound method). Considering the gas-phase dissociation constant as a measure for the intrinsic molecular acid strength, a hfipOSO3H molecule is more than ten orders of magnitude more acidic than a H2SO4 molecule. The acid is a liquid at room temperature, distillable at reduced pressure, stable for more than one year in a closed vessel, reactive towards common solvents, and decomposes above 180 °C. It is a versatile compound for further applications, such as the synthesis of ammonium- and imidazolium-based air- and moisture-stable protic ionic liquids (pILs). Among the six synthesized ionic compounds, five are pILs with melting points below 100 °C and three of them are liquids at nearly room temperature. The conductivities and viscosities of two representative ILs were investigated in terms of Walden plots, and the pILs were found to be little associated ILs, comparable to conventional aprotic ILs.
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June 2014

Toxicity, uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid (PFOS).

Aquat Toxicol 2010 Jun 6;98(2):139-47. Epub 2010 Feb 6.

Institute of Watershed Science and Environmental Ecology, Wenzhou Medical College, Wenzhou 325035, PR China.

Perfluorooctanesulphonicacid (PFOS), a persistent organic contaminant, has been widely detected in the environment, wildlife and humans, but few studies have assessed its effect on aquatic organisms. The present study evaluated the effect of PFOS on zebrafish embryos. Zebrafish embryos exhibited developmental toxicity of bent spine, uninflated swim bladder, decreased heart rate and affected spontaneous movement after exposure to various PFOS concentrations (0-8mg/L) from 6 to 120h post-fertilization (hpf). The LC(50) at 120hpf was 2.20mg/L and the EC(50) at 120hpf was 1.12mg/L. Continuous exposure to PFOS from 1 to 121hpf resulted in a steady accumulation with no evidence of elimination. PFOS induced cell death at 24hpf was consistently found in the brain, eye, and tail region of embryos. PFOS exposure induced lesions in the muscle fibers with histological examination. Behavior assessment of PFOS in zebrafish embryos elevated the basal rate of swimming after 4 days of exposure, and larvae exposed to PFOS (0.25-4mg/L) for only 1h at 6dpf swam faster with increasing PFOS concentration. Embryos/larvae exposed to 8mg/L PFOS for 24h periods from 1 to 121hpf showed the highest incidence of malformations in the 97-121hpf window. This is the first study to define uptake kinetics and to focus on behavioral consequences following PFOS exposure in zebrafish. Our results further the understanding of the toxicity of PFOS to aquatic organisms and suggest the need for additional research to identify the mode of PFOS toxicity.
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June 2010