105 results on '"Hong WX"'
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2. Metabolic engineering of the borneol and camphor degradation pathways in Pseudomonas to produce optically pure bicyclic monoterpenes.
- Author
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Hong YA, Khine AA, Lin YW, Lee PY, Hong WX, Hu A, Shih TL, and Chen HP
- Abstract
Borneol, a medicinally important bicyclic monoterpene, facilitates drug transport across mucous membranes and the blood-brain barrier. Derivatives of borneol and camphor also have numerous biomedical applications. Borneol is currently industrially synthesized via the conversion of turpentine and α-pinene. However, the major product is racemic isoborneol rather than racemic borneol. Both borneol and isoborneol are degraded by the soil bacterium Pseudomonas via a well-established degradation pathway. Two indigenous Pseudomonas strains were used to convert racemic isoborneol to other optically pure bicyclic monoterpenes here. Our results showed that deletion of the camE
2,5 gene alone from the strain TCU-HL1 genome led to the complete loss of borneol and camphor degradation ability. Knockout of both camE2,5 and bdh1 (TCU-HL1Δbdh1ΔcamE2,5 ) restored the degradation capability as the role of Bdh1 was replaced by that of Bdh2. This mutant converted racemic isoborneol into an optically pure bicyclic monoterpene, 2,5-diketocamphane, with a 45 % recovery yield. RT-qPCR results suggested that camE2,5 expression plays a pivotal role in regulating the borneol/camphor degradation cluster. While (+)-borneol, (-)-borneol and (+)-camphor can be obtained from plants for mass production purposes, (-)-camphor cannot be obtained in the same manner. P. monteilii TCU-CK1 converted racemic isoborneol into (-)-camphor and 3,6-diketocamphane, with 15 % and 10 % recovery yields, respectively. In conclusion, we report the role of camE2,5 in regulating the borneol/camphor degradation operon and biotransformation methods to produce several optically pure bicyclic monoterpenes., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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3. Molecular and Family Analyses of a Novel RHD1058G>C Allele in a Chinese RhD Population.
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Wang Y, Zhou R, Hong WX, Wang X, Zhang Z, Gu J, Wang X, Wu CL, and Shao C
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- Adult, Female, Humans, Young Adult, Alleles, China, Genotype, Phenotype, Rh-Hr Blood-Group System genetics, Asian People genetics, Blood Group Antigens
- Abstract
Background: Rh(D) phenotype in a sample from a 19-year-old female patient showed weak positivity (1+). A follow-up sample was requested to further define the Rh(D) phenotype, her Rh(D) phenotype was tested by using another reagent, Rh(D) phenotype still showed weak reactivity (1+), RhCcEe phenotype was Ccee., Methods: Seven samples from the family members of the proposita were received. The RhDCcEe phenotypes were typed by the microcolumn gel card and the unexpected antibodies were assayed by indirect anti-human globulin test (IAT). Genomic DNA was extracted from the blood sample and the novel RHD1058G>C allele was detected through an established sequence-specific primer PCR (PCR-SSP), RHD exons 1 - 10 were sequenced afterward by exon-specific amplification. The distribution of RHD1058G>C allele and RHD weak positive phenotype were investigated in the pedigrees., Results: The unexpected antibodies all were negative in the family members. The novel RHD1058G>C allele was found in the proposita, her father, and grandfather. Five family members were detected serologically with the common Rh(D)-positive phenotypes either as homozygote of RHD/RHD or heterozygote of RHD/RHd. Two family members were detected as weak D phenotypes in accordance with the genotyping results by PCR-SSP, and both of them have a D1058Ce haplotype and a dce haplotype. One member, her father, was tested common Rh(D)-positive with D1058Ce haplotype and a Dce haplotype., Conclusions: These data allow us to describe the characteristics of the weak D phenotype with a novel c.RHD-1058G>C allele, which may be partial D and increase the risk of RHD alloantibody. The novel RHD1058G>C allele was inherited in three generations in a family rather than spontaneous mutation in an individual.
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- 2024
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4. Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.
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Hu X, Cao D, Zhou Z, Wang Z, Zeng J, and Hong WX
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- Humans, DNA Copy Number Variations, T-Lymphocytes, Gene Expression Profiling, Tumor Microenvironment, Leukocytes, Mononuclear, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
Purpose: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML., Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) to analyse the PBMC microenvironment from five AML patients treated with different chemotherapy regimens and six healthy donors. We compared the cell compositions in AML patients and healthy donors, and performed gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis., Results: Using scRNA-seq technology, 91,772 high quality cells of 44,950 PBMCs from AML patients and 46,822 PBMCs from healthy donors were classified as 14 major cell clusters. Our study revealed the sub-cluster diversity of T cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), and haematopoietic stem cell progenitors (HSC-Prog) in AML patients under chemotherapy. NK cells and monocyte-DCs showed significant changes in transcription factor expression and chromosome copy number variation (CNV). We also observed significant heterogeneity in CNV and intercellular interaction networks in HSC-Prog cells., Conclusion: Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML., (© 2023. The Author(s).)
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- 2024
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5. Iridium(III) complex induces apoptosis in HeLa cells by regulating mitochondrial and PI3K/AKT signaling pathways: In vitro and in vivo experiments.
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He SF, Han WC, Shao YY, Zhang HB, Hong WX, Yang QH, Zhang YQ, He RR, and Sun J
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- Humans, Mice, Animals, HeLa Cells, Cell Line, Tumor, Proto-Oncogene Proteins c-akt metabolism, Iridium pharmacology, Phosphatidylinositol 3-Kinases metabolism, Zebrafish metabolism, Apoptosis, Mitochondria metabolism, Reactive Oxygen Species metabolism, Signal Transduction, Cell Proliferation, Coordination Complexes pharmacology, Coordination Complexes metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents metabolism
- Abstract
Cyclometalated iridium complexes with mitochondrial targeting show great potential as substitutes for platinum-based complexes because of their strong anti-cancer properties. Three novel cyclometalated iridium(III) compounds were synthesized and evaluated in five different cell lines as part of the ongoing systematic investigations of these compounds. The complexes were prepared using 4,7-dichloro-1,10-phenanthroline ligands. The cytotoxicity of complexes Ir1-Ir3 towards HeLa cells was shown to be high, with IC
50 values of 0.83±0.06, 4.73±0.11, and 4.95±0.62 μM, respectively. Complex Ir1 could be ingested by HeLa cells in 3 h and has shown high selectivity toward mitochondria. Subsequent investigations demonstrated that Ir1 triggered apoptosis in HeLa cells by augmenting the generation of reactive oxygen species (ROS), reducing the mitochondrial membrane potential, and depleting ATP levels. Furthermore, the movement of cells was significantly suppressed and the progression of the cell cycle was arrested in the G0/G1 phase following the administration of Ir1. The Western blot analysis demonstrated that the induction of apoptosis in HeLa cells by Ir1 involves the activation of the mitochondria-dependent channel and the PI3K/AKT signaling pathway. No significant cytotoxicity was observed in zebrafish embryos at concentrations less than or equal to 16 µM, e.g., survival rate and developmental abnormalities. In vivo, antitumor assay demonstrated that Ir1 suppressed tumor growth in mice. Therefore, our work shows that complex Ir1 could be a promising candidate for developing novel antitumor drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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6. A Novel RHCE*cE (c.827C>A) Allele, Containing the Single-Nucleotide Change, Encodes Altered c/E Antigens.
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Wu CL, Yi P, Tang BD, Zhang QL, Du X, Hong WX, Ou ZY, and Shao CP
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- Humans, Alleles, Rh-Hr Blood-Group System genetics, Polymorphism, Genetic, Antigens, Hepatitis B e Antigens genetics, Blood Group Antigens genetics
- Abstract
The RH blood group system is the most complex with over 50 antigens. So far over hundreds of RhCE variant alleles have been described resulting in weakened and/or partial expression of RhCE antigens [1], some variant Rh phenotypes are caused by exchange of genetic material between the RHD and RHCE genes, resulting in many hybrid genes, other phenotypes result from missense mutations. Variant alleles encode altered phenotypes with either weakened antigens, lacked antigens, or unexpected antigens. Besides, the mutation of RH blood group genes may lead to the changes of Rh antigen epitopes. RHCE gene mutations or polymorphisms may bring about altered RH antigens in quality and quantity [2]. Serologic weaknesses or discrepancies are regularly faced by blood transfusion laboratories, and molecular background explaining this feature can be precisely characterized only by the molecular biological methods.
- Published
- 2023
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7. A novel RHCE*03 with 255G > A, 538G > A, and Exon 9 of RHD in a Chinese individual encodes for altered c and E antigens.
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Wu CL, Yi P, Ruan SJ, Zhang QL, Du X, Hong WX, Ou ZY, and Shao CP
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- Humans, Alleles, Exons genetics, Gene Frequency, Genetic Variation, Phenotype, East Asian People, Rh-Hr Blood-Group System genetics
- Published
- 2023
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8. Association of variations in the Fanconi anemia complementation group and prognosis in Non-small cell lung cancer patients with Platinum-based chemotherapy.
- Author
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Mo JL, Liu JS, Xiao Q, Hong WX, Yin JY, Chen J, and Liu ZQ
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Genotype, Humans, Male, Middle Aged, Platinum therapeutic use, Polymorphism, Single Nucleotide, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Fanconi Anemia drug therapy, Fanconi Anemia genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Purpose: To explore the associations between FANC (FANCA, FANCC, FANCE, FANCF, and FANCJ) single nucleotide polymorphisms (SNPs) and prognosis of non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy., Methods: According to the inclusion criteria, we selected 395 DNA samples from NSCLC patients for genotyping and combined with clinical data for Cox regression analysis and stratification analyses to assess relationships between overall survival (OS) and progression free survival (PFS) with SNPs genotypes., Results: The results revealed that patients with FANCE rs6907678 TT genotype have a longer OS than TC and CC genotype (Additive model: P = 0.004, HR = 1.696, 95% CI = 1.186-2.425). In stratification analyses, Longer PFS is found in female, age ≤ 55 years old and non-smoking patients with FANCE rs6907678 TT genotype, and patients with TT genotypes were significantly had longer OS in male, age >55 years old, non-smoking, squamous cell carcinoma and stage IV stratification., Conclusion: Our data demonstrates that patients with FANCE rs6907678 TT genotype are contributed to better prognosis. FANCE rs6907678 may be used as a clinical biomarker for predicting the prognosis of NSCLC patients with platinum-based chemotherapy., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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9. An exploration of new methods for metabolic syndrome examination by infrared thermography and knowledge mining.
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Mi BH, Zhang WZ, Xiao YH, Hong WX, Song JL, Tu JF, Jiang BY, Ye C, and Shi GX
- Subjects
- Body Temperature, Cross-Sectional Studies, Humans, Infrared Rays, Temperature, Metabolic Syndrome diagnostic imaging, Thermography methods
- Abstract
Metabolic syndrome (MS) is a clinical syndrome with multiple metabolic disorders. As the diagnostic criteria for MS still lacking of imaging laboratory method, this study aimed to explore the differences between healthy people and MS patients through infrared thermography (IRT). However, the observation region of the IRT image is uncertain, and the research tried to solve this problem with the help of knowledge mining technology. 43 MS participants were randomly included through a cross-sectional method, and 43 healthy participants were recruited through number matching. The IRT image of each participant was segmented into the region of interest (ROI) through the preprocessing method proposed in this research, and then the ROI features were granulated by the K-means algorithm to generate the formal background, and finally, the two formal background were separately built into a knowledge graph through the knowledge mining method based on the attribute partial order structure. The baseline data shows that there is no difference in age, gender, and height between the two groups (P > 0.05). The image preprocessing method can segment the IRT image into 18 ROI. Through the K-means method, each group of data can be separately established with a 43 × 36 formal background and generated a knowledge graph. It can be found through knowledge mining and independent-samples T test that the average temperature and maximum temperature difference between the chest and face of the two groups are statistically different (P < 0.01). IRT could reflect the difference between healthy people and MS people. The measurement regions were found by the method of knowledge mining on the premise of unknown. The method proposed in this paper may add a new imaging method for MS laboratory examinations, and at the same time, through knowledge mining, it can also expand a new idea for clinical research of IRT., (© 2022. The Author(s).)
- Published
- 2022
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10. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer.
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Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, and Levy R
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- Humans, Immunologic Factors, Immunotherapy methods, Neoadjuvant Therapy methods, Tumor Microenvironment, Neoplasms therapy, Toll-Like Receptor 9
- Abstract
The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into the tumor microenvironment, eradicating simultaneous untreated sites of metastatic disease. Here we explore the application of this in situ immunotherapy to the neoadjuvant setting. Current neoadjuvant checkpoint blockade therapy is delivered systemically, resulting in off-target adverse effects. In contrast, intratumoral immunotherapy minimizes the potential for toxicities and allows for greater development of combination therapies. In two metastatic solid tumor models, neoadjuvant intratumoral immunotherapy generated a local T-cell antitumor response that then acted systemically to attack cancer throughout the body. In addition, the importance of timing between neoadjuvant immunotherapy and surgical resection was established, as well as the increased therapeutic power of adding systemic anti-PD1 antibody. The combination of local and systemic immunotherapy generated an additional survival benefit due to synergistic inhibitory effect on tumor-associated macrophages. These results provide a strong rationale for translating this neoadjuvant intratumoral immunotherapy to the clinical setting, especially in conjunction with established checkpoint inhibitors., Significance: This work demonstrates the ability of neoadjuvant intratumoral immunotherapy to target local and distant metastatic disease and consequently improve survival., (©2022 American Association for Cancer Research.)
- Published
- 2022
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11. Correlation of Human Leukocyte Antigen-E Genomic Polymorphism with Leukemia and Functional Study of Human Leukocyte Antigen-E Different Type Promoters.
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Xu YP, Sun LY, Wang SX, and Hong WX
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- Humans, Polymorphism, Genetic, Alleles, Female, Male, Genotype, Gene Frequency, Promoter Regions, Genetic genetics, Leukemia genetics, HLA-E Antigens, Histocompatibility Antigens Class I genetics
- Abstract
Human leukocyte antigen (HLA)-E is one of the least polymorphic nonclassical major histocompatibility complex (MHC) I genes; its nucleotide variability can affect immune response. In this study, we assess the correlation between HLA-E polymorphism and leukemia and further study the transcriptional activity of promoter variation at nucleotide position-26. A total of 142 healthy blood donors and 111 leukemia patients were collected. The genomic sequence of HLA-E was amplified by high-fidelity reaction system and identified by Sanger and cloning sequencing. The dual luciferase reporter gene assay was used to detect the transcription activity of promoter variation at nucleotide position-26. In the HLA-E genomic sequence results, a total of 16 alleles and 32 genotypes were detected; the HLA-E*01:01:01:06 allele had a significantly lower frequency in leukemia patients than in healthy participants ( p = 0.026 < 0.05). And the HLA-E*01:03:02:01, *01:03:02:01 genotype showed the greatest difference in frequency between the two groups of participants ( p = 0.028 < 0.05). Eight HLA-E alleles were first reported worldwide in Chinese individuals. The results of the dual luciferase reporter gene experiment showed that the transcription activity of the mutant-type promoter (HLA-E*01:01:01:06 with "T" allele at nucleotide position-26) was significantly lower compared with the wild-type promoter (HLA-E*01:01:01:01 with "G" allele at nucleotide position-26) ( p = 0.0242 < 0.05). HLA-E*01:01:01:06 allele has a protective effect against leukemia through decreasing transcription activity by "T" variation at nucleotide position-26.
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- 2022
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12. Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis.
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Liang XS, Mo JL, Hu LM, Gong CM, Liu T, Hong WX, Yin JY, Liu ZQ, and Zhou HH
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- Alleles, Asian People, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Risk Factors, Apoptosis Regulatory Proteins genetics, Breast Neoplasms genetics, Trans-Activators genetics
- Abstract
Objective: To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer., Methods: Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots., Results: Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190-1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216-1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172-1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778-0.933, P = .001)., Conclusion: The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2021
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13. Targeting translation regulators improves cancer therapy.
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Jiang SL, Mo JL, Peng J, Lei L, Yin JY, Zhou HH, Liu ZQ, and Hong WX
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- Animals, Antineoplastic Agents therapeutic use, Gene Expression Regulation, Neoplastic drug effects, Humans, Neoplasms genetics, Neoplasms metabolism, Protein Biosynthesis drug effects, Antineoplastic Agents pharmacology, Neoplasms drug therapy, Ribosomal Proteins metabolism
- Abstract
Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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14. Wounds Inhibit Tumor Growth In Vivo.
- Author
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Hu MS, Maan ZN, Leavitt T, Hong WX, Rennert RC, Marshall CD, Borrelli MR, Zhu TN, Esquivel M, Zimmermann A, McArdle A, Chung MT, Foster DS, Jones RE, Gurtner GC, Giaccia AJ, Lorenz HP, Weissman IL, and Longaker MT
- Subjects
- Animals, Female, Mice, Neoplasms complications, Ulcer complications, Wounds and Injuries complications, Neoplasms pathology, Ulcer pathology, Wounds and Injuries pathology
- Abstract
Objective: The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo., Summary of Background Data: Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo., Methods: To determine the interaction of tumors and wounds, we developed a tumor xenograft/allograft (human head and neck squamous cell carcinoma SAS/mouse breast carcinoma 4T1) wound mouse model. We examined tumor growth with varying temporospatial placement of tumors and wounds or ischemic flap. In addition, we developed a tumor/wound parabiosis model to understand the ability of tumors and wounds to recruit circulating progenitor cells., Results: Tumor growth inhibition by full thickness excisional wounds was dose-dependent, maintained by sequential wounding, and relative to distance. This effect was recapitulated by placement of an ischemic flap directly adjacent to a xenograft tumor. Using a parabiosis model, we demonstrated that a healing wound was able to recruit significantly more circulating progenitor cells than a growing tumor. Tumor inhibition by wound was unaffected by presence of an immune response in an immunocompetent model using a mammary carcinoma. Utilizing functional proteomics, we identified 100 proteins differentially expressed in tumors and wounds., Conclusion: Full thickness excisional wounds have the ability to inhibit tumor growth in vivo. Further research may provide an exact mechanism for this remarkable finding and new advances in wound healing and tumor biology., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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15. DNA sequence analysis and Jk blood group genotype-phenotype assessment.
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Liang S, Su YQ, Liang YL, Wu F, Zhang H, Shi JH, Hong WX, and Xu YP
- Abstract
Background: The Kidd (JK) blood group is critical for clinical blood transfusion. Various methods for Jk typing have been commonly used, including urea hemolysis, serological test, and genotyping. However, the application of molecular methods has so far been restricted to selected samples and not been applied to the population-scale analysis., Methods: One hundred eighty-three blood samples, containing 174 samples collected from voluntary blood donors of Chinese Han individuals, together with 3 Jk (aw+b-) and 6 Jk (a-b-) samples, were investigated by standard serology urea hemolysis test and Sanger-sequencing. Complete coverage of exons 4-11 and intron-exon borders have been sequenced., Results: We report the frequencies of three SNPs in exon 4, 7, and intron 9. Besides, sequence analysis revealed the simultaneous DNA variants of intron 7 (-68) and exon 9 (838) found in all samples, suggesting the co-inheritance of these SNPs-taking the observed SNPs frequencies into account. Further, we discuss the potential of the sequencing technique for high-resolution genotyping., Conclusions: The described sequencing method for Jk exons delivers a genotyping technique for Jk molecular characterization. According to the co-inheritance of these DNA variants in intron 7 (-68) and exon 9 (838), and their regularity linkage with Jk phenotypes, these two sites offer a potential sequencing target for rapid and far more simplified Jk typing that can supplement routine serology and urea hemolysis tests., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6504). SL reports grants from The Chinese Society of Blood Transfusion, during the conduct of the study; HZ reports grants from Shenzhen Science and technology innovation Commission, during the conduct of the study; WXH and YPX report grants from Shenzhen Municipal Health Commission, during the conduct of the study. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)
- Published
- 2020
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16. [Genotyping of Duffy Blood Group by Microchip Capillary Electrophoresis].
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Wu F, Liang S, Zhuang NB, Liang YL, Su YQ, and Hong WX
- Subjects
- Gene Frequency, Genotype, Humans, Phenotype, Duffy Blood-Group System genetics, Electrophoresis, Capillary
- Abstract
Objective: To explore a method for rapidly screening the Duffy blood group genotypes and to establish an information bank of rare blood type donors., Methods: The microfluidic capillary electrophoresis system and PCR-SSP method were used to analyze the Duffy genotype of 3 936 unrelated O-type blood donors in our center from December 2014 to September 2018. The serologic identification and typing of other blood type system phenotypes for FY
a -negative specimen were performed. The Fy (a-b-) specimen was sequenced for genotyping., Results: The phenotypes of FYa -negative specimens were consistent with the genotyping results of the microfluidic capillary electrophoresis system. The results of Duffy phenotyping in 3 936 specimens were follows: Fy (a+b-) 3 564 (90.54%), Fy(a+b+) 353 (8.97%), Fy(a-b+) 18 (0.46%), Fy (a-b-) 1 (0.03%). The gene frequency was FY*A (95.03%), FY*B (4.94%), and FY*Null (0.03%). The bank of rare blood types of 19 FYa -negative specimens was established., Conclusion: Microfluidic capillary electrophoresis system is suitable for Duffy blood group genotyping screening. It can be used to establish a bank of rare blood type, so as to solve the problem of urgent blood transfusion in patients with rare blood type, and to improve blood transfusion safety.- Published
- 2020
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17. Intratumoral Immunotherapy for Early-stage Solid Tumors.
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Hong WX, Haebe S, Lee AS, Westphalen CB, Norton JA, Jiang W, and Levy R
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- Animals, Clinical Decision-Making, Clinical Trials as Topic, Combined Modality Therapy adverse effects, Combined Modality Therapy methods, Disease Management, Humans, Immunotherapy adverse effects, Injections, Intralesional, Neoplasm Staging, Prognosis, Time-to-Treatment, Treatment Outcome, Immunotherapy methods, Neoplasms pathology, Neoplasms therapy
- Abstract
The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier-stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities. The direct injection of immune stimulating agents into the tumor primes the local tumor-specific immunity to generate a systemic, durable clinical response. Intratumoral immunotherapy is a highly active area of investigation resulting in a plethora of agents, for example, immune receptor agonists, non-oncolytic and oncolytic viral therapies, being tested in preclinical and clinical settings. Currently, more than 20 neoadjuvant clinical trials exploring distinct intratumoral immune stimulatory agents and their combinations are ongoing. Practical considerations, including appropriate timing and optimal local delivery of immune stimulatory agents play an important role in safety and efficacy of this approach. Here, we discuss promising approaches in drug delivery technologies and opportunity for combining intratumoral immunotherapy with other cancer treatments and summarize the recent preclinical and clinical evidences that highlighted its promise as a part of routine oncologic care., (©2020 American Association for Cancer Research.)
- Published
- 2020
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18. A novel HLA-E allele, HLA-E*01:03:01:05, identified in a healthy Chinese blood donor.
- Author
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Xu YP, Sun LY, and Hong WX
- Subjects
- Alleles, China, Exons genetics, Humans, Sequence Analysis, DNA, HLA-E Antigens, Asian People, Blood Donors, Histocompatibility Antigens Class I genetics
- Abstract
HLA-E*01:03:01:05 differs from E*01:01:01:01 by a single nucleotide exchange in nucleotide -33(T->C)., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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19. A novel HLA-E allele, HLA-E*01:12:01:01, identified in a healthy Chinese blood donor.
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Hong WX, Sun LY, and Xu YP
- Subjects
- Alleles, Base Sequence, China, Humans, Sequence Analysis, DNA, HLA-E Antigens, Asian People, Blood Donors, Histocompatibility Antigens Class I genetics
- Abstract
HLA-E*01:12:01:01 differs from HLA-E*01:01:01:01 by a single nucleotide in exon 5 changing 276 proline to glutamine., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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20. [Allele Frequency and Distribution of Single Nucleotide Polymorphisms in Promoter Region of Gene Encoding the Kidd Blood Group Antigens].
- Author
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Liang S, Su YQ, Liang YL, Wu F, Zhang H, and Hong WX
- Subjects
- Alleles, Blood Group Antigens, China, Gene Frequency, Genotype, Humans, Kidd Blood-Group System, Promoter Regions, Genetic, Polymorphism, Single Nucleotide
- Abstract
Objective: To study the single nucleotide polymorphisms (SNPs) in promoter region of the Jk gene and its allele frequency as well as distribution characteristics in the Chinese Han nationality population., Methods: 127 blood samples containing 8 Jk(a-b-) and 119 samples (as control) taken randomly from voluntary blood donors of Chinese Han nationality persons in Shenzhen Blood Center were collected. The Kidd phenotypes were identified by using the serologic test and urea hemolysis test; the Jk promoter, exon 1-11 region and respective flanking area were amplified and sequenced, then the sequence information was analyzed., Results: 8 Jk(a-b-) samples all carried JkB/JkB allele which belongs to 2 kind of Jk
null genotypes commonly observed in Chinese Han nationality population. 6 IVS5-1g>a and 2 896G>A were found in 8 Jk(a-b-) samples. Besides, all Jk(a-b-) samples were homozygous for JkB/JkB allele. Three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene were found and sequenceds calculation of allele and genotype frequencies showed that the result accorded with Hardy-Weinberg equilibrium, indicating that the population in this study possesses representative characteristics of the Chinese Han nationality population., Conclusion: The polymorphism of the Jk gene occurs in promoter region. This study calculates the allele frequencies of three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene, and shows their distribution characteristics in distinct Kidd phenotypes. These findings provide the basic foundation for further population genetics research.- Published
- 2020
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21. A Chinese leukemia patient, typed as HLA-E*01:01:01:11, a novel HLA-E allele.
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Sun LY, Zhang XH, Hong WX, and Xu YP
- Subjects
- Alleles, China, Histocompatibility Testing methods, Humans, Introns genetics, Leukemia blood, Polymerase Chain Reaction methods, HLA-E Antigens, Asian People genetics, Histocompatibility Antigens Class I genetics, Leukemia genetics, Polymorphism, Single Nucleotide
- Abstract
There is a single nucleotide different in intron 1 between E*01:01:01:01 and E*01:01:01:11., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
22. Characterization of the novel HLA-DQB1*06:01:22 allele by next-generation sequencing.
- Author
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Quan ZR, Zou HY, Zhong YP, Deng ZH, and Hong WX
- Subjects
- Alleles, Asian People genetics, Base Sequence, China, Exons, Histocompatibility Testing methods, Humans, Sequence Analysis, DNA methods, Blood Donors, HLA-DQ beta-Chains genetics, High-Throughput Nucleotide Sequencing, Polymorphism, Single Nucleotide
- Abstract
HLA-DQB1*06:01:22 differs from HLA-DQB1*06:01:01:01 by one nucleotide substitution in codon 189 in exon 4., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
23. Identification of HLA-A*24:02:78 by next-generation sequencing in a Chinese Han individual.
- Author
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Gao SQ, Hong WX, Deng ZH, and Quan ZR
- Subjects
- Alleles, Asian People ethnology, China ethnology, Exons, High-Throughput Nucleotide Sequencing, Humans, Asian People genetics, Blood Donors, HLA-A24 Antigen genetics
- Abstract
HLA-A*24:02:78 differs from HLA-A*24:02:01:01 in exon 3 by a single nucleotide., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
24. Macrophage Transplantation Fails to Improve Repair of Critical-Sized Calvarial Defects.
- Author
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Borrelli MR, Hu MS, Hong WX, Oliver JD, Duscher D, Longaker MT, and Lorenz HP
- Subjects
- Animals, Bone Regeneration physiology, Collagen, Cranial Sutures, Diabetes Mellitus, Experimental, Durapatite, Hydrogels, Mice, Mice, Nude, Osteogenesis physiology, Parietal Bone physiopathology, Skull surgery, Tissue Scaffolds, X-Ray Microtomography, Macrophages transplantation
- Abstract
Introduction: Over 500,000 bone grafting procedures are performed every year in the United States for neoplastic and traumatic lesions of the craniofacial skeleton, costing $585 million in medical care. Current bone grafting procedures are limited, and full-thickness critical-sized defects (CSDs) of the adult human skull thus pose a substantial reconstructive challenge for the craniofacial surgeon. Cell-based strategies have been shown to safely and efficaciously accelerate the rate of bone formation in CSDs in animals. The authors recently demonstrated that supraphysiological transplantation of macrophages seeded in pullalan-collagen composite hydrogels significantly accelerated wound healing in wild type and diabetic mice, an effect mediated in part by enhancing angiogenesis. In this study, the authors investigated the bone healing effects of macrophage transplantation into CSDs of mice., Methods: CD1 athymic nude mice (60 days of age) were anesthetized, and unilateral full-thickness critical-sized (4 mm in diameter) cranial defects were created in the right parietal bone, avoiding cranial sutures. Macrophages were isolated from FVB-L2G mice and seeded onto hydroxyapatite-poly (lactic-co-glycolic acid) (HA-PLGA) scaffolds (1.0 × 10 cells per CSD). Scaffolds were incubated for 24 hours before they were placed into the CSDs. Macrophage survival was assessed using three-dimensional in vivo imaging system (3D IVIS)/micro-CT. Micro-CT at 0, 2, 4, 6, and 8 weeks was performed to evaluate gross bone formation, which was quantified using Adobe Photoshop. Microscopic evidence of bone regeneration was assessed at 8 weeks by histology. Bone formation and macrophage survival were compared at each time point using independent samples t tests., Results: Transplantation of macrophages at supraphysiological concentration had no effect on the formation of bones in CSDs as assessed by either micro-CT data at any time point analyzed (all P > 0.05). These results were corroborated by histology. 3D IVIS/micro-CT demonstrated survival of macrophages through 8 weeks., Conclusion: Supraphysiologic delivery of macrophages to CSDs of mice had no effect on bone formation despite survival of transplanted macrophages through to 8 weeks posttransplantation. Further research into the physiological effects of macrophages on bone regeneration is needed to assess whether recapitulation of these conditions in macrophage-based therapy can promote the healing of large cranial defects.
- Published
- 2019
- Full Text
- View/download PDF
25. In a healthy Chinese blood donor, a novel allele, HLA-E*01:03:07 was detected.
- Author
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Sun LY, Xu YP, Hong WX, and Liu H
- Subjects
- 3' Untranslated Regions, China, Codon, Exons, Humans, Introns, Promoter Regions, Genetic, HLA-E Antigens, Alleles, Blood Donors, Histocompatibility Antigens Class I genetics, Polymorphism, Genetic
- Abstract
The novel HLA-E*01:03:07 allele, differs from E*01:03:01 by a single synonymous change in exon 3., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
26. Identification of HLA-A*31:150 by next-generation sequencing in a Chinese Han individual.
- Author
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Liang SZ, Quan ZR, Hong WX, and Zou HY
- Subjects
- Asian People, China, Exons, HLA-A2 Antigen genetics, HLA-B35 Antigen genetics, HLA-B52 Antigen genetics, HLA-C Antigens genetics, HLA-DQ beta-Chains genetics, HLA-DRB1 Chains genetics, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Alleles, Codon, HLA-A Antigens genetics, Polymorphism, Single Nucleotide
- Abstract
HLA-A*31:150 differs from HLA-A*31:01:02:01 in exon 2 by a single nucleotide., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
27. Kinetics of antigen-specific IgM/IgG/IgA antibody responses during Zika virus natural infection in two patients.
- Author
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Zhao LZ, Hong WX, Wang J, Yu L, Hu FY, Qiu S, Yin CB, Tang XP, Zhang LQ, Jin X, and Zhang FC
- Subjects
- Adult, Female, Humans, Male, Saliva immunology, Serum immunology, Urinalysis, Antibodies, Viral analysis, Antibody Formation, Immunoglobulin A analysis, Immunoglobulin G analysis, Immunoglobulin M analysis, Zika Virus immunology, Zika Virus Infection immunology
- Abstract
Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2019
- Full Text
- View/download PDF
28. Characterization of the novel HLA-B*15:435 allele by next-generation sequencing in a Chinese family.
- Author
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Zou HY, Zhong YP, and Hong WX
- Subjects
- Base Sequence, Exons genetics, Female, Humans, Alleles, Asian People genetics, HLA-B Antigens genetics, High-Throughput Nucleotide Sequencing
- Abstract
HLA-B*15:435 has 5 nt changes from HLA-B*15:09:01 in exon 3 and 4., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
29. Clinical significance of HLA-E genotype and surface/soluble expression levels between healthy individuals and patients with acute leukemia.
- Author
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Xu YP, Wieten L, Wang SX, Cai Y, Olieslagers T, Zhang L, He LM, Tilanus MGJ, and Hong WX
- Subjects
- Adolescent, Adult, Alleles, Case-Control Studies, Female, Gene Frequency, Healthy Volunteers, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class I metabolism, Humans, Leukemia, Myeloid, Acute immunology, Male, Middle Aged, Polymorphism, Genetic, Young Adult, HLA-E Antigens, Histocompatibility Antigens Class I genetics, Leukemia, Myeloid, Acute genetics, Tumor Escape genetics
- Abstract
Human leukocyte antigen (HLA)-E is a nonclassical HLA molecule with limited polymorphisms. Genotype frequency and expression of HLA-E were examined here for the first time in acute leukemia patients and healthy controls. The frequency of HLA-E*01:03/*01:03 individuals was significantly higher (p = .008, OR = 1.845), while the frequency of HLA-E*01:01/*01:01 individuals was much lower in the patient group (p = .002, OR = .363) than in control group. The surface expression on HLA-E*01:03/*01:03 individuals was found to be significantly higher than on HLA-E*01:01/*01:01 individuals in both of acute leukemia and control groups, but no significant difference was observed between the corresponding genotypes in two groups. However, the level of expression of soluble HLA-E is significantly higher in patients than in the control group, but there was no genotype-specific expression in either group. These findings indicate that soluble HLA-E secretion and HLA-E*01:03/*01:03 genotype that brings higher surface expression might play important roles in the mechanisms underlying tumor escape in acute leukemia.
- Published
- 2019
- Full Text
- View/download PDF
30. Genomic full-length sequence of HLA-B*15:178 was identified by full-length group-specific sequencing.
- Author
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He LM, Yang H, Xu YP, and Hong WX
- Subjects
- Base Sequence, Humans, Sequence Homology, Genomics methods, HLA-B Antigens genetics, Sequence Analysis, DNA methods, Tissue Donors
- Abstract
Genomic full-length sequence of HLA-B*15:178 was identified by a group-specific sequencing approach from China., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
31. Genomic full-length sequence of HLA-A*11:172 was identified by full-length group-specific sequencing.
- Author
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Xu YP, Yang H, and Hong WX
- Subjects
- Base Sequence, China, Humans, Genomics methods, HLA-A Antigens genetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods
- Abstract
Genomic full-length sequence of HLA-A*11:172 was identified by a group-specific sequencing approach from China., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
32. Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds.
- Author
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Hu MS, Hong WX, Januszyk M, Walmsley GG, Luan A, Maan ZN, Moshrefi S, Tevlin R, Wan DC, Gurtner GC, Longaker MT, and Lorenz HP
- Abstract
Objective: In early gestation, fetal wounds heal without fibrosis in a process resembling regeneration. Elucidating this remarkable mechanism can result in tremendous benefits to prevent scarring. Fetal mouse cutaneous wounds before embryonic day (E)18 heal without scar. Herein, we analyze expression profiles of fetal and postnatal wounds utilizing updated gene annotations and pathway analysis to further delineate between repair and regeneration. Approach: Dorsal wounds from time-dated pregnant BALB/c mouse fetuses and adult mice at various time points were collected. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was utilized to select genes with >2-fold expression differences with a false discovery rate of <2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways. Results: Our analysis identified 471 differentially expressed genes in fetal versus adult wounds following injury. Utilizing enrichment analysis of significant genes, we identified the top 20 signaling pathways that were upregulated and downregulated at 1 and 12 h after injury. At 24 h after injury, we discovered 18 signaling pathways upregulated in adult wounds and 11 pathways upregulated in fetal wounds. Innovation: These novel target genes and pathways may reveal repair mechanisms of the early fetus that promote regeneration over fibrosis. Conclusion: Our microarray analysis recognizes hundreds of possible genes as candidates for regulators of scarless versus scarring wound repair. Enrichment analysis reveals 109 signaling pathways related to fetal scarless wound healing.
- Published
- 2018
- Full Text
- View/download PDF
33. Comparative studies on DNA-binding and in vitro antitumor activity of enantiomeric ruthenium(II) complexes.
- Author
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Hong WX, Huang F, Huan T, Xu X, Han Q, Wang G, Xu H, Duan S, Duan Y, Long X, Liu Y, and Hu Z
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Binding Sites, Cattle, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, HeLa Cells, Humans, Molecular Docking Simulation, Molecular Probes, Ruthenium Compounds chemistry, Ruthenium Compounds pharmacology, Spectrometry, Fluorescence, Spectrophotometry, Ultraviolet, Stereoisomerism, Viscosity, Antineoplastic Agents metabolism, DNA metabolism, Ruthenium Compounds metabolism
- Abstract
A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)
2 PBIP]2+ {bpy=2,2'-bipyridine, PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. The systematic comparative studies between two enantiomers on their DNA binding-behaviors with calf thymus DNA (CT DNA) were carried out by viscosity measurements, spectrophotometric methods and molecular simulation technology. Additional assays were performed to explore the cytotoxicity of the ruthenium(II) enantiomers against tumor cell lines. DNA-binding studies show that both the enantiomers can bind to CT DNA via intercalative mode, and the Δ form binds to CT DNA more strongly than the Λ form does. Molecular simulation further shows that both the two enantiomers intercalate between base pairs of DNA in minor groove, and that the Δ form intercalates into DNA more deeply than the Λ form does. In addition, the cell proliferation assays show that the Δ form induces a greater cytotoxicity than the Λ form on human cervical cancer HeLa cells, which is positive correlated with the results in DNA binding studies and molecular docking, and implies that the DNA binding affinities of ruthenium(II) polypyridyl complexes might be constitute to the part of their anticancer mechanisms., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
34. Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix.
- Author
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Lee AS, Inayathullah M, Lijkwan MA, Zhao X, Sun W, Park S, Hong WX, Parekh MB, Malkovskiy AV, Lau E, Qin X, Pothineni VR, Sanchez-Freire V, Zhang WY, Kooreman NG, Ebert AD, Chan CKF, Nguyen PK, Rajadas J, and Wu JC
- Abstract
Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy.
- Published
- 2018
- Full Text
- View/download PDF
35. Embryonic skin development and repair.
- Author
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Hu MS, Borrelli MR, Hong WX, Malhotra S, Cheung ATM, Ransom RC, Rennert RC, Morrison SD, Lorenz HP, and Longaker MT
- Subjects
- Animals, Humans, Models, Biological, Regeneration, Regenerative Medicine, Tissue Engineering, Skin embryology, Skin pathology, Wound Healing
- Abstract
Fetal cutaneous wounds have the unique ability to completely regenerate wounded skin and heal without scarring. However, adult cutaneous wounds heal via a fibroproliferative response which results in the formation of a scar. Understanding the mechanism(s) of scarless wound healing leads to enormous clinical potential in facilitating an environment conducive to scarless healing in adult cutaneous wounds. This article reviews the embryonic development of the skin and outlines the structural and functional differences in adult and fetal wound healing phenotypes. A review of current developments made towards applying this clinical knowledge to promote scarless healing in adult wounds is addressed.
- Published
- 2018
- Full Text
- View/download PDF
36. An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice.
- Author
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Hu MS, Cheng J, Borrelli MR, Leavitt T, Walmsley GG, Zielins ER, Hong WX, Cheung ATM, Duscher D, Maan ZN, Irizarry DM, Stephan B, Parsa FD, Wan DC, Gurtner GC, Lorenz HP, and Longaker MT
- Abstract
Objective: Splinting full-thickness cutaneous wounds in mice has allowed for a humanized model of wound healing. Delineating the epithelial edge and assessing time to closure of these healing wounds via macroscopic visualization have remained a challenge. Approach: Double transgenic mice were created by crossbreeding K14-Cre and ROSA
mT/mG reporter mice. Full-thickness excisional wounds were created in K14-Cre/ROSAmT/mG mice ( n = 5) and imaged using both normal and fluorescent light on the day of surgery, and every other postoperative day (POD) until wound healing was complete. Ten blinded observers analyzed a series of images from a single representative healing wound, taken using normal or fluorescent light, to decide the POD when healing was complete. K14-Cre/ROSAmT/mG mice ( n = 4) were subsequently sacrificed at the four potential days of rated wound closure to accurately determine the histological point of wound closure using microscopic fluorescence imaging. Results: Average time to wound closure was rated significantly longer in the wound series images taken using normal light, compared with fluorescent light (mean POD 13.6 vs. 11.6, * p = 0.008). Fluorescence imaging of histological samples indicated that reepithelialization was complete at 12 days postwounding. Innovation: We describe a novel technique, using double transgenic mice K14-Cre/ROSAmT/mG and fluorescence imaging, to more accurately determine the healing time of wounds in mice upon macroscopic evaluation. Conclusion: The accuracy by which wound healing can be macroscopically determined in vivo in mouse models of wound healing is significantly enhanced using K14-Cre/ROSAmT/mG double transgenic mice and fluorescence imaging.- Published
- 2018
- Full Text
- View/download PDF
37. Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts.
- Author
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Hu MS, Borrelli MR, Januszyk M, Luan A, Malhotra S, Walmsley GG, Hong WX, Tevlin R, Gurtner GC, Longaker MT, and Lorenz HP
- Abstract
Objective: Fetuses early in gestation heal skin wounds without forming scars. The biological mechanisms behind this process are largely unknown. Fibroblasts, however, are cells known to be intimately involved in wound healing and scar formation. We examined fibroblasts in different stages of development to characterize differences in gene expression that may result in the switch from regenerative wound repair to repair with scarring. Approach: Fibroblasts were isolated and cultured from the back skin of BALB/c wild-type mouse fetuses at embryonic day (E)14 and E18 ( n = 10). The fibroblast total RNA was extracted, and microarray analysis was conducted using chips containing 42,000 genes. Significance analysis of microarrays was performed to identify genes with greater than twofold expression difference and a false discovery rate of less than two. Identified genes subsequently underwent enrichment analysis to detect differentially expressed pathways. Results: Two hundred seventy-five genes were differentially expressed between E14 and E18 in fetal fibroblasts. Thirty genes were significantly downregulated and 245 genes were significantly upregulated at E18 compared with E14. Ingenuity pathway analysis identified the top 20 signaling pathways differentially activated in fetal fibroblasts between the E18 and E14 time points. Innovation: To our knowledge, this work represents the first instance where differentially expressed genes and signaling pathways between fetal fibroblasts at E14 and E18 have been studied. Conclusion: The genes and pathways identified here potentially underlie the mechanism behind the transition from fetal wound healing via regeneration to wound healing by repair, and may prove to be key targets for future therapeutics.
- Published
- 2018
- Full Text
- View/download PDF
38. An investigation of methyl tert‑butyl ether‑induced cytotoxicity and protein profile in Chinese hamster ovary cells.
- Author
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Xie G, Hong WX, Zhou L, Yang X, Huang H, Wu D, Huang X, Zhu W, and Liu J
- Subjects
- Animals, CHO Cells, Catalase metabolism, Cell Death, Cell Membrane drug effects, Cell Membrane metabolism, Cell Survival drug effects, Cricetinae, Cricetulus, Electrophoresis, Gel, Two-Dimensional, Glutathione Peroxidase metabolism, L-Lactate Dehydrogenase metabolism, Lipid Peroxidation drug effects, Membrane Proteins metabolism, Oxidative Stress drug effects, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Superoxide Dismutase metabolism, Methyl Ethers pharmacology, Proteome metabolism, Proteomics
- Abstract
Methyl tert-butyl ether (MTBE) is widely used as an oxygenating agent in gasoline to reduce harmful emissions. However, previous studies have demonstrated that MTBE is a cytotoxic substance that has harmful effects in vivo and in vitro. Although remarkable progress has been made in elucidating the mechanisms underlying the MTBE‑induced reproductive toxicological effect in different cell lines, the precise mechanisms remain far from understood. The present study aimed to evaluate whether mammalian ovary cells were sensitive to MTBE exposure in vitro by assessing cell viability, lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) content and antioxidant enzyme activities. In addition, the effect of MTBE exposure on differential protein expression profiles was examined by two‑dimensional electrophoresis and matrix‑assisted laser desorption/ionization‑time of flight mass spectrometry. MTBE exposure induced significant effects on cell viability, LDH leakage, plasma membrane damage and the activity of antioxidant enzymes. In the proteomic analysis, 24 proteins were demonstrated to be significantly affected by MTBE exposure. Functional analysis indicated that these proteins were involved in catalytic activity, binding, structural molecule activity, metabolic processes, cellular processes and localization, highlighting the fact that the cytotoxic mechanisms resulting from MTBE exposure are complex and diverse. The altered expression levels of two representative proteins, heat shock protein family A (Hsp70) members 8 and 9, were further confirmed by western blot analysis. The results revealed that MTBE exposure affects protein expression in Chinese hamster ovary cells and that oxidative stress and altered protein levels constitute the mechanisms underlying MTBE‑induced cytotoxicity. These findings provided novel insights into the biochemical mechanisms involved in MTBE‑induced cytotoxicity in the reproductive system.
- Published
- 2017
- Full Text
- View/download PDF
39. Delivery of monocyte lineage cells in a biomimetic scaffold enhances tissue repair.
- Author
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Hu MS, Walmsley GG, Barnes LA, Weiskopf K, Rennert RC, Duscher D, Januszyk M, Maan ZN, Hong WX, Cheung AT, Leavitt T, Marshall CD, Ransom RC, Malhotra S, Moore AL, Rajadas J, Lorenz HP, Weissman IL, Gurtner GC, and Longaker MT
- Subjects
- Acute-Phase Proteins metabolism, Animals, Biomimetics, Cell Differentiation physiology, Diabetes Mellitus, Experimental immunology, Immunocompromised Host, Mice, Inbred Strains, Monocytes transplantation, Skin injuries, Skin Physiological Phenomena immunology, Wound Healing immunology, Diabetes Mellitus, Experimental physiopathology, Macrophages transplantation, Tissue Scaffolds, Wound Healing physiology
- Abstract
The monocyte lineage is essential to normal wound healing. Macrophage inhibition or knockout in mice results in impaired wound healing through reduced neovascularization, granulation tissue formation, and reepithelialization. Numerous studies have either depleted macrophages or reduced their activity in the context of wound healing. Here, we demonstrate that by increasing the number of macrophages or monocytes in the wound site above physiologic levels via pullulan-collagen composite dermal hydrogel scaffold delivery, the rate of wound healing can be significantly accelerated in both wild-type and diabetic mice, with no adverse effect on the quality of repair. Macrophages transplanted onto wounds differentiate into M1 and M2 phenotypes of different proportions at various time points, ultimately increasing angiogenesis. Given that monocytes can be readily isolated from peripheral blood without in vitro manipulation, these findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases.
- Published
- 2017
- Full Text
- View/download PDF
40. Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.
- Author
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Lee AS, Tang C, Hong WX, Park S, Bazalova-Carter M, Nelson G, Sanchez-Freire V, Bakerman I, Zhang W, Neofytou E, Connolly AJ, Chan CK, Graves EE, Weissman IL, Nguyen PK, and Wu JC
- Subjects
- Apoptosis radiation effects, Cell Differentiation radiation effects, Cell Proliferation radiation effects, Humans, Pluripotent Stem Cells radiation effects, Teratoma pathology, Pluripotent Stem Cells pathology, Radiation, Ionizing, Teratoma radiotherapy
- Abstract
Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 10
3 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000., (© 2017 AlphaMed Press.)- Published
- 2017
- Full Text
- View/download PDF
41. A novel HLA-E allele, HLA-E*01:01:01:06, identified in a Chinese Leukemia patient.
- Author
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Xu YP, Wang SX, and Hong WX
- Subjects
- Asian People, Base Sequence, Bone Marrow Transplantation, Exons, Gene Expression, Histocompatibility Antigens Class I immunology, Histocompatibility Testing, Humans, Introns, Leukemia immunology, Leukemia pathology, Leukemia therapy, Polymerase Chain Reaction, Sequence Alignment, Sequence Analysis, DNA, HLA-E Antigens, Alleles, Histocompatibility Antigens Class I genetics, Leukemia genetics, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Transplant Recipients
- Abstract
A novel HLA-E allele, HLA-E*01:01:01:06, was identified in a Chinese leukemia patient., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
42. Differential expression profile of membrane proteins in L-02 cells exposed to trichloroethylene.
- Author
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Hong WX, Huang A, Lin S, Yang X, Yang L, Zhou L, Huang H, Wu D, Huang X, Xu H, and Liu J
- Subjects
- Cell Line, Electrophoresis, Gel, Two-Dimensional, Humans, Liver cytology, Membrane Proteins classification, Proteome analysis, Proteome metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins analysis, Membrane Proteins metabolism, Proteome drug effects, Proteomics methods, Trichloroethylene toxicity
- Abstract
Trichloroethylene (TCE), a halogenated organic solvent widely used in industries, is known to cause severe hepatotoxicity. However, the mechanisms underlying TCE hepatotoxicity are still not well understood. It is predicted that membrane proteins are responsible for key biological functions, and recent studies have revealed that TCE exposure can induce abnormal levels of membrane proteins in body fluids and cultured cells. The aim of this study is to investigate the TCE-induced alterations of membrane proteins profiles in human hepatic L-02 liver cells. A comparative membrane proteomics analysis was performed in combination with two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. A total of 15 proteins were identified as differentially expressed (4 upregulated and 11 downregulated) between TCE-treated cells and normal controls. Among this, 14 of them are suggested as membrane-associated proteins by their transmembrane domain and/or subcellular location. Furthermore, the differential expression of β subunit of adenosine triphosphate synthase (ATP5B) and prolyl 4-hydroxylase, β polypeptide (P4HB) were verified by Western blot analysis in TCE-treated L-02 cells. Our work not only reveals the association between TCE exposure and altered expression of membrane proteins but also provides a novel strategy to discover membrane biomarkers and elucidate the potential mechanisms involving with membrane proteins response to chemical-induced toxic effect., (© The Author(s) 2015.)
- Published
- 2016
- Full Text
- View/download PDF
43. Epidemiological and Virological Characterizations of the 2014 Dengue Outbreak in Guangzhou, China.
- Author
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Zhao H, Zhang FC, Zhu Q, Wang J, Hong WX, Zhao LZ, Deng YQ, Qiu S, Zhang Y, Cai WP, Cao WC, and Qin CF
- Subjects
- Adult, Aged, Aged, 80 and over, China epidemiology, Dengue Virus classification, Dengue Virus genetics, Dengue Virus pathogenicity, Disease Outbreaks statistics & numerical data, Female, Genome, Viral genetics, Genotype, Humans, Male, Middle Aged, Molecular Epidemiology, Phylogeny, Sequence Analysis, DNA, Serogroup, Dengue epidemiology
- Abstract
Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future.
- Published
- 2016
- Full Text
- View/download PDF
44. Dengue Specific Immunoglobulin A Antibody is Present in Urine and Associated with Disease Severity.
- Author
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Zhao H, Qiu S, Hong WX, Song KY, Wang J, Yang HQ, Deng YQ, Zhu SY, Zhang FC, and Qin CF
- Subjects
- Adult, Aged, Aged, 80 and over, China, Female, Humans, Male, Middle Aged, Young Adult, Antibodies, Viral urine, Dengue immunology, Dengue pathology, Dengue Virus immunology, Immunoglobulin A urine
- Abstract
The kinetics of dengue virus (DENV)-specific IgA antibody in urine and the potential correlation with disease severity remain elusive. In this study, 262 serial urine samples from 78 laboratory-confirmed patients were assayed by a commercial immunoglobulin A (IgA) kit against DENV. All cases were classified into dengue fever (DF) and severe dengue (SD) according to the 2009 WHO/TDR guideline. The total positive rate of IgA in urine was 59%. DENV-specific IgA was detected in urine from day 2 to day 13 after the onset of illness in DF patients; While for SD patients, anti-DENV IgA could be detected till day 14. The positive rate of IgA in patients with secondary infection was higher than that in patients with primary infection. Importantly, during 4-7 days after the onset of illness, the IgA positive rate of SD patients was significantly higher than that of DF patients. Especially, the intensity of IgA signal in SD patients was obviously stronger than that in DF patient at the recovery stage. Overall, our results suggested that the existence of DENV-specific IgA antibodies in urine might be a warning sign for the severity of disease and its measurement might provide valuable guidance for proper patient management.
- Published
- 2016
- Full Text
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45. [Effect of SET deficiency on the trichloroethylene-induced alteration of cell proliferation and cell apoptosis and DNA methylation in human hepatic L-02 cells].
- Author
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Xie GS, Liu JJ, Hong WX, Zhang H, Sun Y, and Zhu WG
- Subjects
- Cell Line, Epigenesis, Genetic, Humans, Liver, Trichloroethylene, Apoptosis, Cell Proliferation, DNA Methylation, Hepatocytes
- Abstract
Objective: To compare the trichloroethylene (TCE) -induced alteration in cell proliferation, cell apoptosis, histone deacetylase activity and expression levels in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the TCE-induced effect in histone modification and the role of SET on epigenetic pathway., Methods: The L-02 cells and preestablished SET deficient cells were treated with different TCE concentrations. For the changes of cell proliferation level and apoptosis rate, The L-02 cells and SET deficiency cells without TCE treatment were served as the control group, the TCE treatment was in the concentration of 2.0 and 8.0 mmol/L for 24 h. For histone deacetylase activity and expression levels, the TCE treatment was in the concentration of 0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mmol/L for 24 h., Results: After treatment with TCE for 24 h, the cell proliferation level was significantly decreased and the apoptotic rate was significantly increased in both cell lines. When concentration of TCE were reached to 8.0 mmol/L, the difference of cell proliferation level and apoptotic rate between two groups was statistically significant (t=-4.362 for proliferation level and t=23.950 for apoptotic rate, both P<0.05). After treatment with TCE for 24 h in various concentration (0, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 mmol/L) , the activity of histone deacetylases was significantly increased in both cell lines. When the TCE concentration were high than 0.50 mmol/L, compared with control group of L-02 cells, the enzymes activity were significantly increased (F=403.26, P<0.001). When TCE concentration was reached 1.00 mmol/L, the enzyme activity is highest. Compared with control group of SET deficiency cells, the enzyme activity was significantly increased when TCE concentration was reached 1.00 mmol/L (F=44.01, P<0.001). When concentration of TCE reached 0.50 mmol/L, the difference of enzyme activity between two groups was statistically significant. For the protein expression, compared with control group of L-02 cells, TCE exposure can induced a significant increased expression level of HDAC2 in TCE-treated L-02 cells (F values were 79.99, P<0.001). But the alteration in SET deficiency cells was not significant., Conclusion: TCE exposure can induce a significant alteration on cell proliferation, apoptotic rate and, the activity and expression on histone deacetylases. SET deficiency can attenuate the TCE-induced alteration in histone modification in L-02 cells. Our results indicated that SET is involved in the mechanism of TCE-induced cytotoxicity and epigenetic regulation in L-02 cells.
- Published
- 2016
- Full Text
- View/download PDF
46. The rs5934505 single nucleotide polymorphism (SNP) is associated with low testosterone and late-onset hypogonadism, but the rs10822184 SNP is associated with overweight and obesity in a Chinese Han population: a case-control study.
- Author
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Chen YP, Nie LL, Li HG, Liu TH, Fang F, Zhao K, Yang RF, Ma XL, Kong XB, Zhang HP, Guan HT, Xia W, Hong WX, Duan S, Zeng XC, Shang XJ, Zhou YZ, Gu YQ, Wu WX, and Xiong CL
- Subjects
- Adult, Aged, Case-Control Studies, China epidemiology, Gene Frequency genetics, Health Status, Humans, Hypogonadism epidemiology, Male, Middle Aged, Obesity epidemiology, Surveys and Questionnaires, Body Weight genetics, Genetic Predisposition to Disease genetics, Hypogonadism genetics, Obesity genetics, Polymorphism, Single Nucleotide genetics, Testosterone blood
- Abstract
Low testosterone is associated with late-onset hypogonadism (LOH) and obesity. Recently, studies have shown that four single nucleotide polymorphisms (SNPs), rs12150660, rs727428, rs5934505, and rs10822184, are associated with testosterone levels in populations of European descent. Therefore, we investigated whether the SNP loci are related to low testosterone, LOH, or obesity in a Chinese Han population. Ruling out co-morbidities, DNA was prepared from 409 men (aged 40-65 years) with low serum testosterone (defined as total testosterone <11.6 nmol/L) and 1 : 1 normal controls (matched age, body mass index (BMI), and the same living area) who were selected from 6898 males. According to the same standards, 310 men with LOH and 1 : 1 normal controls were selected from 6898 males. Excluding the cases with an unreliable sequencing result, genetic analyses were performed. The minor allele frequencies of the SNP loci rs12150660, rs727428, rs5934505, and rs10822184 were 0.1%, 44.6%, 18.7%, and 38.9%, respectively. rs5934505 was associated with the serum total testosterone and calculated free testosterone (CFT) levels (p = 0.045 and p = 0.021). rs5934505 (C>T) was associated with an increased risk of low total testosterone, low CFT, and LOH and adjusted for other factors, with an odds ratio (OR) of 2.01 (1.34-3.01), 2.14 (1.42-3.20), and 1.64 (1.04-2.58). rs10822184 was significantly correlated with weight and BMI (p = 0.035 and p = 0.027). rs10822184 (T>C) was associated with an increased risk of overweight and obesity. We adjusted for other factors, with odds ratios (ORs) of 1.94 (1.36-2.78) and 1.56 (1.00-2.43). In summary, our study provided convincing evidence that rs5934505 (C>T) was associated with the risk of low testosterone and LOH in Chinese populations. We were the first to find that rs10822184 (T>C) was significantly correlated with the risk of overweight and obesity in Chinese populations. However, further large and functional studies are warranted to confirm our findings., (© 2015 American Society of Andrology and European Academy of Andrology.)
- Published
- 2016
- Full Text
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47. Proteomic profiling of occupational medicamentosa-like dermatitis induced by trichloroethylene in serum based on MALDI-TOF MS.
- Author
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Liu W, Hong WX, Zhang Y, Huang P, Yang X, Ren X, Huang H, and Liu J
- Subjects
- Adolescent, Adult, Autoimmune Diseases pathology, China, Dermatitis pathology, Dermatitis, Contact pathology, Diagnosis, Differential, Female, Humans, Male, Occupational Diseases diagnosis, Occupational Diseases pathology, Sensitivity and Specificity, Young Adult, Autoimmune Diseases diagnosis, Blood Proteins analysis, Dermatitis diagnosis, Dermatitis, Contact diagnosis, Serum chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Trichloroethylene toxicity
- Abstract
Trichloroethylene (TCE) has long been well known as a major pollutant that affects both occupational and general environments. Occupational medicamentosa-like dermatitis induced by TCE (OMLDT) is an autoimmune disease, which has become one of the critical occupational health issues in China. In this study, we analyzed 18 OMLDT patients and 29 professional TCE contact people on serum proteomic analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ClinProTools bioinformatics software. The intensities of 35 protein/peptide peaks were significantly different between TCE contact controls and OMLDT patients. A pattern of six peaks (m/z 1,450.33, 1,866.16, 3,262.39, 4,109.55, 5,064.85 and 5,956.57) were selected to construct a diagnostic model to discriminate the OMLDT patients from controls with sensitivity and specificity of both 93.8 %. Our findings provide an alternative proteomic approach to differentiate the OMLDT patients from TCE contact workers with high sensitivity and high specificity, which will be of potential value in clinical diagnosis for occupational disease.
- Published
- 2015
- Full Text
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48. Assessment of the Radiation Effects of Cardiac CT Angiography Using Protein and Genetic Biomarkers.
- Author
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Nguyen PK, Lee WH, Li YF, Hong WX, Hu S, Chan C, Liang G, Nguyen I, Ong SG, Churko J, Wang J, Altman RB, Fleischmann D, and Wu JC
- Subjects
- Aged, Aged, 80 and over, Annexin A5 analysis, Ataxia Telangiectasia Mutated Proteins analysis, Cohort Studies, DNA Repair, DNA-Binding Proteins analysis, Female, Flow Cytometry, Histones analysis, Humans, Immunohistochemistry, Male, Middle Aged, Phantoms, Imaging, Polymerase Chain Reaction, Prospective Studies, Sequence Analysis, DNA, Sequence Analysis, RNA, bcl-2-Associated X Protein analysis, Apoptosis, Biomarkers analysis, Coronary Angiography adverse effects, DNA Damage, Heart radiation effects, Tomography, X-Ray Computed adverse effects
- Abstract
Objectives: The purpose of this study was to evaluate whether radiation exposure from cardiac computed tomographic angiography (CTA) is associated with deoxyribonucleic acid (DNA) damage and whether damage leads to programmed cell death and activation of genes involved in apoptosis and DNA repair., Background: Exposure to radiation from medical imaging has become a public health concern, but whether it causes significant cell damage remains unclear., Methods: We conducted a prospective cohort study in 67 patients undergoing cardiac CTA between January 2012 and December 2013 in 2 U.S. medical centers. Median blood radiation exposure was estimated using phantom dosimetry. Biomarkers of DNA damage and apoptosis were measured by flow cytometry, whole genome sequencing, and single cell polymerase chain reaction., Results: The median dose length product was 1,535.3 mGy·cm (969.7 to 2,674.0 mGy·cm). The median radiation dose to the blood was 29.8 mSv (18.8 to 48.8 mSv). Median DNA damage increased 3.39% (1.29% to 8.04%, p < 0.0001) and median apoptosis increased 3.1-fold (interquartile range [IQR]: 1.4- to 5.1-fold, p < 0.0001) post-radiation. Whole genome sequencing revealed changes in the expression of 39 transcription factors involved in the regulation of apoptosis, cell cycle, and DNA repair. Genes involved in mediating apoptosis and DNA repair were significantly changed post-radiation, including DDB2 (1.9-fold [IQR: 1.5- to 3.0-fold], p < 0.001), XRCC4 (3.0-fold [IQR: 1.1- to 5.4-fold], p = 0.005), and BAX (1.6-fold [IQR: 0.9- to 2.6-fold], p < 0.001). Exposure to radiation was associated with DNA damage (odds ratio [OR]: 1.8 [1.2 to 2.6], p = 0.003). DNA damage was associated with apoptosis (OR: 1.9 [1.2 to 5.1], p < 0.0001) and gene activation (OR: 2.8 [1.2 to 6.2], p = 0.002)., Conclusions: Patients exposed to >7.5 mSv of radiation from cardiac CTA had evidence of DNA damage, which was associated with programmed cell death and activation of genes involved in apoptosis and DNA repair., Competing Interests: CONFLICTS OF INTERESTS None, (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
49. [Clinical significance of changes of lipid in elderly patients with hepatic schistosomiasis].
- Author
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Yang DM, Tu YP, and Hong WX
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Liver Diseases etiology, Male, Middle Aged, Schistosomiasis blood, Apolipoprotein A-I blood, Cholesterol blood, Liver Diseases blood, Schistosomiasis complications, Triglycerides blood
- Abstract
Objective: To explore the clinical significance of lipid levels including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and apolipoprotein (APOA I and APOB) of elderly patients with hepatic schistosomiasis., Methods: A total of 280 hospitalized elderly patients with hepatic schistosomiasis (198 cases of chronic liver fibrosis and 82 cases of hepatocirrhosis) were chosen as study objects, and their clinical data were collected and analyzed retrospectively. Meanwhile, the lipid levels between the patients with liver fibrosis and hepatocirrhosis, and those among the patients with A, B, C degrees of Child-pugh grading of liver function were compared., Results: Among the 280 patients, the abnormality rates of the lipid levels were 34.8%(69/198)and 100% (82/82) in the liver fibrosis group and hepatocirrhosis group respectively, and the difference between them were statistically significant (χ2 = 5.74, P < 0.05). The levels of TC, HDL-C, LDL-C, APOA I of the patients in the latter group were significantly lower than those in the former group (all P <0.05). The levels of TC, TG, HDL-C, APOA I, APOB of the patients with C degree liver function were significantly lower than those of the patients with A degree liver function, and the levels of TC, TG, HDL-C of the former were also lower than those of the patients with B degree liver function (all P <0.05)., Conclusions: The lipid levels of the elderly patients with hepatic schistosomiasis reduce obviously in the course of hepatocirrhosis, and it is correlated with the damage level of the liver. Lipid and apolipoprotein detections have certain values on the illness judgment and prognosis assessment.
- Published
- 2015
50. A mouse fetal skin model of scarless wound repair.
- Author
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Walmsley GG, Hu MS, Hong WX, Maan ZN, Lorenz HP, and Longaker MT
- Subjects
- Animals, Chorionic Gonadotropin pharmacology, Female, Horses, Humans, Male, Mice, Phenotype, Pregnancy, Regeneration physiology, Cicatrix embryology, Disease Models, Animal, Skin embryology, Wound Healing physiology
- Abstract
Early in utero, but not in postnatal life, cutaneous wounds undergo regeneration and heal without formation of a scar. Scarless fetal wound healing occurs across species but is age dependent. The transition from a scarless to scarring phenotype occurs in the third trimester of pregnancy in humans and around embryonic day 18 (E18) in mice. However, this varies with the size of the wound with larger defects generating a scar at an earlier gestational age. The emergence of lineage tracing and other genetic tools in the mouse has opened promising new avenues for investigation of fetal scarless wound healing. However, given the inherently high rates of morbidity and premature uterine contraction associated with fetal surgery, investigations of fetal scarless wound healing in vivo require a precise and reproducible surgical model. Here we detail a reliable model of fetal scarless wound healing in the dorsum of E16.5 (scarless) and E18.5 (scarring) mouse embryos.
- Published
- 2015
- Full Text
- View/download PDF
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