Publications by authors named "Yixin Yao"

45 Publications

Advances in the assessment of minimal residual disease in mantle cell lymphoma.

J Hematol Oncol 2020 09 24;13(1):127. Epub 2020 Sep 24.

Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer methods using next-generation sequencing, such as ClonoSeq, are being incorporated in clinical trials. Other techniques under evolution include CAPP-seq and anchored multiplex polymerase chain reaction-based methods. This review article aims to provide a comprehensive update on the status of minimal residual disease detection and its prognostic effect in mantle cell patients. The role of circulating tumor DNA-based minimal residual disease detection in lymphomas is also discussed.
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http://dx.doi.org/10.1186/s13045-020-00961-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513535PMC
September 2020

Quantification Analysis of 13 Organic Components and 8 Inorganic Elements in and Its Different Parts Combined with Chemical Recognition Pattern.

J Anal Methods Chem 2020 31;2020:8836184. Epub 2020 Aug 31.

Deyang Food and Drug Safety Inspection and Testing Center, Deyang 618000, China.

(Danggui, DG) is one of the most commonly prescribed traditional Chinese medicines. The organic components include phthalides and phenolic acids. Meanwhile, inorganic elements play an important role in clinical effect. DG and its different parts have different effects. There is no relevant report on the analysis of organic compounds and inorganic elements among them. Therefore, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was developed for the simultaneous determination of 13 organic components (8 phthalides and 5 phenolic acids), and 8 inorganic elements were determined by inductively coupled plasma mass spectrometry. The contents of 32 samples were analyzed by orthogonal partial least squares discrimination analysis, hierarchical cluster analysis, and least-significant difference of one-way analysis of variance. The results showed that the differences were significant among DG and its different parts. 11 difference markers (Ca, Z-ligustilide, Mg, Mn, Fe, Na, K, Cu, Zn, coniferyl ferulate, and senkyunolide A) were obtained by variable importance for the project. These difference markers were some different among DG and its different parts, especially Z-ligustilide, coniferyl ferulate, Mg, Zn, the differences were significant. This study can provide a reference for DG research.
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http://dx.doi.org/10.1155/2020/8836184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479475PMC
August 2020

Simultaneous determination of 20 bioactive components in Chuanxiong Rhizoma from different production origins in Sichuan province by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with multivariate statistical analysis.

Electrophoresis 2020 10 2;41(18-19):1606-1616. Epub 2020 Jul 2.

Deyang Food and Drug Safety Inspection and Testing Center, Deyang, P. R. China.

Chuanxiong Rhizoma is a commonly used in traditional Chinese medicine. Chuanxiong Rhizoma is widely distributed in Sichuan province, China, including the cities of Dujiangyan, Pengzhou, Meishan, Qionglai, and Shifang. However, reports on the comparisons of quality of Chuanxiong Rhizoma of different production origins are limited. Therefore, an ultra-HPLC with triple quadrupole MS method was developed for the determination of 20 bioactive components (12 aromatic acids and eight phthalides) in 36 samples from different production origins and further assessed its quality. The contents of these 20 constituents of samples were analyzed by hierarchical cluster analysis and orthogonal partial least squares discrimination analysis; the result indicated that Chuanxiong Rhizoma of different production origins had some differences. Thirteen constituents of quality difference markers were acquired by variable importance for the project. Furthermore, the sum of the contents of these quality difference markers was different from various production origins of Chuanxiong Rhizoma. Meanwhile, Z-ligustilide and senkyunolide A as main constituents of quality difference markers, the rate of various production origins of Chuanxiong Rhizoma was different. This study provides a foundation for the quality assessment of Chuanxiong Rhizoma.
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http://dx.doi.org/10.1002/elps.202000082DOI Listing
October 2020

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients.

Am J Hematol 2020 06 17;95(6):623-629. Epub 2020 Apr 17.

Department of Lymphoma and myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax-based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole-exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2-4-fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non-BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.
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http://dx.doi.org/10.1002/ajh.25796DOI Listing
June 2020

Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL.

Blood Adv 2020 03;4(6):1038-1050

Department of Lymphoma and Myeloma.

Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P = .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (<50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.
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http://dx.doi.org/10.1182/bloodadvances.2019001396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094021PMC
March 2020

Simultaneous Determination of Night Effective Constituents and Correlation Analysis of Multiconstituents and Antiplatelet Aggregation Bioactivity in Chuanxiong Rhizoma Subjected to Different Decoction Times.

J Anal Methods Chem 2019 22;2019:8970624. Epub 2019 Nov 22.

Kangmei Pharmaceutical Co., Ltd., Puning 515300, China.

Several effective constituents, such as vanillin, ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, Z-ligustilide, butylphthalide, senkyunolide A, and levistilide A, are unstable and possess mutual transformation relationships in Chuanxiong Rhizoma (CR). Traditional Chinese medicine mainly involves decoction, and the content of effective constituents and antiplatelet aggregation bioactivity (AAB) in CR may vary with different decoction time (10 min, 20 min, 30 min, 40 min, 50 min, and 60 min). Here, we showed that coniferyl ferulate and levistilide A were detected in CR material, but not in the decoction. The effective components possessed transformation and degradation in CR decoction of different times. The effective components and the strength of AAB at 10 and 20 minutes were the strongest, followed by 30-50 minutes, and 60 minutes were the weakest by analysis of SIMCA-PLS in CR decoction of different times. In the Pearson correlation analysis, there were correlations ( < 0.05) between effective components, which were ferulic acid and senkyunolide I (coefficient was 0.976), ferulic acid and senkyunolide H (coefficient was 0.972), senkyunolide I and senkyunolide H (coefficient was 0.982), senkyunolide A and butylphthalide (coefficient was 0.974), senkyunolide A and Z-ligustilide (coefficient was 0.947), and butylphthalide and Z-ligustilide (coefficient was 0.993). Effective components (ferulic acid, senkyunolide I, and senkyunolide H) and AAB were correlated and the Pearson correlation coefficients were respectively 0.965, 0.973, and 0.999. In the stepwise regression analysis, senkyunolide H and senkyunolide I were correlated with AAB ( < 0.05). Senkyunolide H (H) was positively correlated with AAB, senkyunolide I (I) was negatively correlated with AAB, and its expression was AAB = 1.187  H - 0.199  I - 0.422. These findings indicate that there are some correlations between effective components and AAB in CR.
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http://dx.doi.org/10.1155/2019/8970624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893248PMC
November 2019

How to meet your 'silent partner': tips for approaching editors at conferences.

Authors:
Yixin Yao

Genome Biol 2019 09 17;20(1):200. Epub 2019 Sep 17.

Genome Biology, BMC, Shanghai, 200040, China.

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http://dx.doi.org/10.1186/s13059-019-1820-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747742PMC
September 2019

A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity.

JCI Insight 2019 07 11;4(13). Epub 2019 Jul 11.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Ubiquitin-conjugating enzyme E2O (UBE2O) is expressed preferentially in metabolic tissues, but its role in regulating energy homeostasis has yet to be defined. Here we find that UBE2O is markedly upregulated in obese subjects with type 2 diabetes and show that whole-body disruption of Ube2o in mouse models in vivo results in improved metabolic profiles and resistance to high-fat diet-induced (HFD-induced) obesity and metabolic syndrome. With no difference in nutrient intake, Ube2o-/- mice were leaner and expended more energy than WT mice. In addition, hyperinsulinemic-euglycemic clamp studies revealed that Ube2o-/- mice were profoundly insulin sensitive. Through phenotype analysis of HFD mice with muscle-, fat-, or liver-specific knockout of Ube2o, we further identified UBE2O as an essential regulator of glucose and lipid metabolism programs in skeletal muscle, but not in adipose or liver tissue. Mechanistically, UBE2O acted as a ubiquitin ligase and targeted AMPKα2 for ubiquitin-dependent degradation in skeletal muscle; further, muscle-specific heterozygous knockout of Prkaa2 ablated UBE2O-controlled metabolic processes. These results identify the UBE2O/AMPKα2 axis as both a potent regulator of metabolic homeostasis in skeletal muscle and a therapeutic target in the treatment of diabetes and metabolic disorders.
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http://dx.doi.org/10.1172/jci.insight.128269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629239PMC
July 2019

MoS Coexisting in 1T and 2H Phases Synthesized by Common Hydrothermal Method for Hydrogen Evolution Reaction.

Nanomaterials (Basel) 2019 Jun 2;9(6). Epub 2019 Jun 2.

Key Laboratory of Eco-Textiles, Ministry of Education, Jiangnan University, Wuxi 214122, China.

Molybdenum disulfide has been one of the most studied hydrogen evolution catalyst materials in recent years, but its disadvantages, such as poor conductivity, hinder its further development. Here, we employ the common hydrothermal method, followed by an additional solvothermal method to construct an uncommon molybdenum disulfide with two crystal forms of 1T and 2H to improve catalytic properties. The low overpotential (180 mV) and small Tafel slope (88 mV/dec) all indicated that molybdenum disulfide had favorable catalytic performance for hydrogen evolution. Further conjunctions revealed that the improvement of performance was probably related to the structural changes brought about by the 1T phase and the resulting sulfur vacancies, which could be used as a reference for the further application of MoS.
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http://dx.doi.org/10.3390/nano9060844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630712PMC
June 2019

Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma.

Sci Transl Med 2019 05;11(491)

Department of Lymphoma and Myeloma, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomic analyses of clinical specimens, we show that metabolic reprogramming toward oxidative phosphorylation (OXPHOS) and glutaminolysis is associated with therapeutic resistance to the Bruton's tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma (MCL), a B cell lymphoma subtype with poor clinical outcomes. Inhibition of OXPHOS with a clinically applicable small molecule, IACS-010759, which targets complex I of the mitochondrial electron transport chain, results in marked growth inhibition in vitro and in vivo in ibrutinib-resistant patient-derived cancer models. This work suggests that targeting metabolic pathways to subvert therapeutic resistance is a clinically viable approach to treat highly refractory malignancies.
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http://dx.doi.org/10.1126/scitranslmed.aau1167DOI Listing
May 2019

Exposure to air pollution is associated with adverse cardiopulmonary health effects in international travellers.

J Travel Med 2019 Jun;26(5)

Department of Environmental Medicine, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.

Background: With the number of annual global travellers reaching 1.2 billion, many individuals encounter greater levels of air pollution when they travel abroad to megacities around the world. This study's objective was to determine if visits to cities abroad with greater levels of air pollution adversely impact cardiopulmonary health.

Methods: A total of 34 non-smoking healthy adult participants who travelled abroad to selected cities from the New York City (NYC) metropolitan area were pre-trained to measure lung function, blood pressure and heart rate (HR)/HR variability (HRV) and record symptoms before, during and after travelling abroad. Outdoor particulate matter (PM)2.5 concentrations were obtained from central monitors in each city. Associations between PM exposure concentrations and cardiopulmonary health endpoints were analysed using a mixed effects statistical design.

Results: East and South Asian cities had significantly higher PM2.5 concentrations compared with pre-travel NYC PM2.5 levels, with maximum concentrations reaching 503 μg/m3. PM exposure-related associations for lung function were statistically significant and strongest between evening Forced Expiratory Volume in the first second (FEV1) and same-day morning PM2.5 concentrations; a 10-μg/m3 increase in outdoor PM2.5 was associated with a mean decrease of 7 mL. Travel to a highly polluted city (PM2.5 > 100 μg/m3) was associated with a 209-ml reduction in evening FEV1 compared with a low polluted city (PM2.5 < 35 μg/m3). In general, participants who travelled to East and South Asian cities experienced increased respiratory symptoms/scores and changes in HR and HRV.

Conclusions: Exposure to increased levels of PM2.5 in cities abroad caused small but statistically significant acute changes in cardiopulmonary function and respiratory symptoms in healthy young adults. These data suggest that travel-related exposure to increased PM2.5 adversely impacts cardiopulmonary health, which may be particularly important for travellers with pre-existing respiratory or cardiac disease.
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http://dx.doi.org/10.1093/jtm/taz032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621915PMC
June 2019

PTEN self-regulates through USP11 via the PI3K-FOXO pathway to stabilize tumor suppression.

Nat Commun 2019 02 7;10(1):636. Epub 2019 Feb 7.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

PTEN is a lipid phosphatase that antagonizes the PI3K/AKT pathway and is recognized as a major dose-dependent tumor suppressor. The cellular mechanisms that control PTEN levels therefore offer potential routes to therapy, but these are as yet poorly defined. Here we demonstrate that PTEN plays an unexpected role in regulating its own stability through the transcriptional upregulation of the deubiquitinase USP11 by the PI3K/FOXO pathway, and further show that this feedforward mechanism is implicated in its tumor-suppressive role, as mice lacking Usp11 display increased susceptibility to PTEN-dependent tumor initiation, growth and metastasis. Notably, USP11 is downregulated in cancer patients, and correlates with PTEN expression and FOXO nuclear localization. Our findings therefore demonstrate that PTEN-PI3K-FOXO-USP11 constitute the regulatory feedforward loop that improves the stability and tumor suppressive activity of PTEN.
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http://dx.doi.org/10.1038/s41467-019-08481-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367354PMC
February 2019

Genome editing: from tools to biological insights.

Authors:
Yixin Yao

Genome Biol 2018 11 6;19(1):186. Epub 2018 Nov 6.

Genome Biology, BMC, Shanghai, 200040, China.

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http://dx.doi.org/10.1186/s13059-018-1570-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219208PMC
November 2018

Dual inhibition of PI3K signaling and histone deacetylation halts proliferation and induces lethality in mantle cell lymphoma.

Oncogene 2019 03 25;38(11):1802-1814. Epub 2018 Oct 25.

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The dysregulation of PI3K signaling has been implicated as an underlying mechanism associated with resistance to Bruton's tyrosine kinase inhibition by ibrutinib in both chronic lymphocytic leukemia and mantle cell lymphoma (MCL). Ibrutinib resistance has become a major unmet clinical need, and the development of therapeutics to overcome ibrutinib resistance will greatly improve the poor outcomes of ibrutinib-exposed MCL patients. CUDC-907 inhibits both PI3K and HDAC functionality to exert synergistic or additive effects. Therefore, the activity of CUDC-907 was examined in MCL cell lines and patient primary cells, including ibrutinib-resistant MCL cells. The efficacy of CUDC-907 was further examined in an ibrutinib-resistant MCL patient-derived xenograft (PDX) mouse model. The molecular mechanisms by which CUDC-907 dually inhibits PI3K and histone deacetylation were assessed using reverse protein array, immunoblotting, and chromatin immunoprecipitation (ChIP) coupled with sequencing. We showed evidence that CUDC-907 treatment increased histone acetylation in MCL cells. We found that CUDC-907 caused decreased proliferation and increased apoptosis in MCL in vitro and in vivo MCL models. In addition, CUDC-907 was effective in inducing lethality in ibrutinib-resistant MCL cells. Lastly, CUDC-907 treatment increased histone acetylation in MCL cells. Overall, these studies suggest that CUDC-907 may be a promising therapeutic option for relapsed or resistant MCL.
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http://dx.doi.org/10.1038/s41388-018-0550-3DOI Listing
March 2019

Rapid and Integrated Quality Assessment of Organic-Inorganic Composite Herbs by FTIR Spectroscopy-Global Chemical Fingerprints Identification and Multiple Marker Components Quantification of Indigo Naturalis ().

Molecules 2018 Oct 24;23(11). Epub 2018 Oct 24.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.

This research aimed to develop an FTIR-based method for rapid and low-cost integrated quality assessment of organic-inorganic composite herbs, which are kinds of herbs composed of both organic and inorganic active ingredients or matrix components. A two-step quality assessment route was designed and verified using the example of Indigo Naturalis (). First, the FTIR spectra were used as global chemical fingerprints to identify the true and fake samples. Next, the contents of the organic and inorganic marker components were estimated by FTIR quantification models to assess the quality of the true samples. Using the above approaches, all the 56 true samples and five fake samples of Indigo Naturalis could be identified correctly by the correlation threshold of the FTIR chemical fingerprints. Furthermore, the FTIR calibration models provided an accurate estimation of the contents of marker components with respect to HPLC and inductively coupled plasma optical emission spectrometry (ICP-OES). The coefficients of determination (R²) for the independent validation of indigo, indirubin, and calcium were 0.977, 0.983, and 0.971, respectively. Meanwhile, the mean relative errors (MRE) for the independent validation of indigo, indirubin, and calcium were 2.2%, 2.4%, and 1.8%, respectively. In conclusion, this research shows the potential of FTIR spectroscopy for the rapid and integrated quality assessment of organic-inorganic composite herbs in both chemical fingerprints identification and marker components quantification.
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http://dx.doi.org/10.3390/molecules23112743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278429PMC
October 2018

Structural characterization and biological fate of lactoferrin-loaded liposomes during simulated infant digestion.

J Sci Food Agric 2019 Apr 24;99(6):2677-2684. Epub 2019 Jan 24.

Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang, China.

Background: Limited information is concerned on the structure changes of liposomal delivery system under infant conditions. Positively charged lactoferrin (LF)-loaded liposomes, with the entrapment efficiency (EE) of 52.3 ± 6.3%, were prepared from soybean-derived phospholipids using a thin-layer dispersion method. The structure changes and digestibility of LF-loaded liposomes under infant conditions, including simulated gastric fluid (SGF) and simulated small intestinal fluid (SIF), were characterized in terms of the average particle size, zeta potential, turbidity, fourier transform infrared, transmission electron microscopy, lipolysis and protein hydrolysis.

Results: This study showed that the functional groups, favorable membrane structure and the EE of liposomes were slightly changed as a function of time when the liposome digested under SGF conditions. However, the intact bilayer structures were damaged and the EE of LF-loaded liposomes decreased to 28.5% after digestion in infant SIF.

Conclusion: These results suggested that liposomal membrane could prevent the gastric degradation and the structure of liposomes was not completely destroyed with a low concentration of pancreatin and bile salts under infant conditions. Present study provided information on the insight into the characteristics of liposomes during infant gastrointestinal digestion, which was useful for the development of microcapsule systems in infant diet. © 2018 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9435DOI Listing
April 2019

The CD20-specific engineered toxin antibody MT-3724 exhibits lethal effects against mantle cell lymphoma.

Blood Cancer J 2018 03 20;8(3):33. Epub 2018 Mar 20.

Departments of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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http://dx.doi.org/10.1038/s41408-018-0066-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861115PMC
March 2018

Self-assembly of nitrogen-doped carbon dots anchored on bacterial cellulose and their application in iron ion detection.

Carbohydr Polym 2017 Sep 30;172:93-101. Epub 2017 Apr 30.

Key Laboratory of Eco-textiles, Jiangnan University, Wuxi 214122, China. Electronic address:

Nitrogen-doped carbon dots (N-CDs) were synthesized through a facile hydrothermal method using citric acid (CA) and ethanediamine (EDA) as precursors. A green and simple fluorescence biosensor was obtained by biosynthesis of bacterial cellulose (BC)/N-CDs. As-prepared N-CDs with rich functional groups exhibited a blue emission under the excitation wavelength of 350nm. Biosynthesis of BC/N-CDs was analyzed by Digital photos, Fourier Transform Infrared (FTIR) and Transmission Electron Microscopy (TEM). The results indicated that N-CDs were successfully anchored on BC. As-prepared BC/N-CDs were applied to the detection of Fe in aqueous solution. Spectroscopic data revealed that, fluorescence materials prepared presented an sensitive response to Fe in acceptable range of 0.5-600μM and ultralow detection limit of 84nM as a fluorescence sensor. Furthermore, the results also indicate that a novel BC/N-CDs composite has great potential for the detection of Fe ions based on membrane fluorescence materials.
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http://dx.doi.org/10.1016/j.carbpol.2017.04.086DOI Listing
September 2017

Synthesis of novel nitrogen-doped carbon dots for highly selective detection of iron ion.

Nanotechnology 2017 Apr 22;28(16):165502. Epub 2017 Mar 22.

Key Laboratory of Eco-textiles, Jiangnan University, Wuxi 214122, People's Republic of China.

Herein, we report an eco-friendly and simple fluorescent nitrogen-doped carbon quantum dot (N-CQD) biosensor which was synthesized via a hydrothermal method using erhanediamine (EDA) and citric acid (CA) as precursors. The surface functionalization of N-CQDs exhibited a bright blue emission under the excitation wavelength of 350 nm. The obtained N-CQDs were characterized by atomic force microscopy (AFM), Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, and transmission electron microscopy. It was found that the surface of the CQDs was successfully functionalized. After that, as-prepared N-CQDs were further applied in Fe(III) detection. Spectroscopic data indicated that fluorescent carbon-based nanomaterials displayed a sensitive response to Fe in the range of 0.5-1000 μM as a fluorescence sensor in real environmental samples. Furthermore, the results also showed that a novel N-CQD nanomaterial could be employed as an ideal fluorescent Fe(III) probe.
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http://dx.doi.org/10.1088/1361-6528/aa6320DOI Listing
April 2017

A UBE2O-AMPKα2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy.

Cancer Cell 2017 02 2;31(2):208-224. Epub 2017 Feb 2.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

UBE2O is localized in the 17q25 locus, which is known to be amplified in human cancers, but its role in tumorigenesis remains undefined. Here we show that Ube2o deletion in MMTV-PyVT or TRAMP mice profoundly impairs tumor initiation, growth, and metastasis, while switching off the metabolic reprogramming of tumor cells. Mechanistically, UBE2O specifically targets AMPKα2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1α pathway. Notably, inactivation of AMPKα2, but not AMPKα1, abrogates the tumor attenuation caused by UBE2O loss, while treatment with rapamycin or inhibition of HIF1α ablates UBE2O-dependent tumor biology. Finally, pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPKα2, suggesting the UBE2O-AMPKα2 axis as a potential cancer therapeutic target.
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http://dx.doi.org/10.1016/j.ccell.2017.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463996PMC
February 2017

Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels.

J Cell Physiol 2016 Jul 10;231(7):1611-20. Epub 2015 Dec 10.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.

Oxygen levels range from 2% to 9% in vivo. Atmospheric O2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O2 and the effects of higher O2 on these cells are understudied. Here, we addressed this problem by culturing immortalized human bronchial epithelial (BEAS-2B) cells at ambient atmospheric, 21% O2 and lower, 10% O2. Our results show increased inflammatory response at 21% O2 but not at 10% O2. We found higher RelA binding at the NF-κB1/RelA target gene promoters as well as upregulation of several pro-inflammatory cytokines in cells cultured at 21% O2. RelA knockdown prevented the upregulation of the pro-inflammatory cytokines at 21% O2, suggesting NF-κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O2. Interestingly, unlike the 21% O2 cultured cells, exposure of 10% O2 cultured cells to H2O2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O2 levels.
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http://dx.doi.org/10.1002/jcp.25262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845657PMC
July 2016

Malignant human cell transformation of Marcellus Shale gas drilling flow back water.

Toxicol Appl Pharmacol 2015 Oct 22;288(1):121-30. Epub 2015 Jul 22.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Electronic address:

The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity and potential carcinogenic effects of these wastewaters, flow back waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed. The physicochemical nature of these samples was analyzed by inductively coupled plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray spectroscopy. A cytotoxicity study using colony formation as the endpoint was carried out to define the LC50 values of test samples using human bronchial epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to assess the carcinogenic potential of the samples. Barium and strontium were among the most abundant metals in these samples and the same metals were found to be elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for 6weeks with flow back waters produced colony formation in soft agar that was concentration dependent. In addition, flow back water-transformed BEAS-2B cells show better migration capability when compared to control cells. This study provides information needed to assess the potential health impact of post-hydraulic fracturing flow back waters from Marcellus Shale natural gas mining.
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http://dx.doi.org/10.1016/j.taap.2015.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698968PMC
October 2015

Oxidative stress alters global histone modification and DNA methylation.

Free Radic Biol Med 2015 May 3;82:22-8. Epub 2015 Feb 3.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 100016, USA. Electronic address:

The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2',7'-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H2O2 inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.
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http://dx.doi.org/10.1016/j.freeradbiomed.2015.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464695PMC
May 2015

Chromatin Memory in the Development of Human Cancers.

Gene Technol 2014 Aug;3(2):114

Department of Environmental Medicine New York University, New York, USA ; Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, Tuxedo, New York, USA.

Cancer is a complex disease with acquired genomic and epigenomic alterations that affect cell proliferation, viability and invasiveness. Almost all the epigenetic mechanisms including cytosine methylation and hydroxymethylation, chromatin remodeling and non-coding RNAs have been found associate with carcinogenesis and cancer specific expression profile. Altered histone modification as an epigenetic hallmark is frequently found in tumors. Understanding the epigenetic alterations induced by carcinogens or infectious agents may help us understand early epigenetic changes prior to the development of cancer. In this review, we focus on chromatin remodeling and the associated histone modifiers in the development of cancer; the application of these modifiers as a cancer therapy target in different clinical trial phases is also discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297643PMC
August 2014

Genomic Instability and Cancer.

Authors:
Yixin Yao Wei Dai

J Carcinog Mutagen 2014 ;5

Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, 10987, USA. ; Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, Tuxedo, New York, 10987, USA.

Genomic instability is a characteristic of most cancer cells. It is an increased tendency of genome alteration during cell division. Cancer frequently results from damage to multiple genes controlling cell division and tumor suppressors. It is known that genomic integrity is closely monitored by several surveillance mechanisms, DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. A defect in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. Posttranslational modifications of the histone tails are closely associated with regulation of the cell cycle as well as chromatin structure. Nevertheless, DNA methylation status is also related to genomic integrity. We attempt to summarize recent developments in this field and discuss the debate of driving force of tumor initiation and progression.
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http://dx.doi.org/10.4172/2157-2518.1000165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274643PMC
January 2014

Toxicogenomic effect of nickel and beyond.

Authors:
Yixin Yao Max Costa

Arch Toxicol 2014 Sep 29;88(9):1645-50. Epub 2014 Jul 29.

Department of Environmental Medicine, New York University Langone Medical Center, 57 Old Forge Road, Tuxedo, NY, 10987, USA,

Nickel is widely applied in industrial settings and Ni(II) compounds have been classified as group one human carcinogens. The molecular basis of Ni(II) carcinogenicity has proved complex, for many stress response pathways are activated and yield unexpected Ni(II)-specific toxicology profile. Ni(II)-induced toxicogenomic change has been associated with altered activity of HIF, p53, c-MYC, NFκB and iron and 2-oxoglutarate-dependent dioxygenases. Advancing high-throughput technology has indicated the toxicogenome of Ni(II) involves crosstalk between HIF, p53, c-MYC, NFκB and dioxygenases. This paper is intended to review the network of Ni(II)-induced common transcription-factor-governed pathways by discussing transcriptome alteration, its governing transcription factors and the underlying mechanism. Finally, we propose a putative target network of Ni(II) as a human carcinogen.
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http://dx.doi.org/10.1007/s00204-014-1313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134377PMC
September 2014

Cobalt and nickel stabilize stem cell transcription factor OCT4 through modulating its sumoylation and ubiquitination.

PLoS One 2014 31;9(1):e86620. Epub 2014 Jan 31.

Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America ; Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, Tuxedo, New York, United States of America.

Stem cell research can lead to the development of treatments for a wide range of ailments including diabetes, heart disease, aging, neurodegenerative diseases, spinal cord injury, and cancer. OCT4 is a master regulator of self-renewal of undifferentiated embryonic stem cells. OCT4 also plays a crucial role in reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Given known vivo reproductive toxicity of cobalt and nickel metals, we examined the effect of these metals on expression of several stem cell factors in embryonic Tera-1 cells, as well as stem cells. Cobalt and nickel induced a concentration-dependent increase of OCT4 and HIF-1α, but not NANOG or KLF4. OCT4 induced by cobalt and nickel was due primarily to protein stabilization because MG132 stabilized OCT4 in cells treated with either metals and because neither nickel nor cobalt significantly modulated its steady-state mRNA level. OCT4 stabilization by cobalt and nickel was mediated largely through reactive oxygen species (ROS) as co-treatment with ascorbic acid abolished OCT4 increase. Moreover, nickel and cobalt treatment increased sumoylation and mono-ubiquitination of OCT4 and K123 was crucial for mediating these modifications. Combined, our observations suggest that nickel and cobalt may exert their reproductive toxicity through perturbing OCT4 activity in the stem cell compartment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086620PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908935PMC
October 2014

Enhancing bone marrow regeneration by SALL4 protein.

J Hematol Oncol 2013 Nov 5;6:84. Epub 2013 Nov 5.

Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient's morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein.
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http://dx.doi.org/10.1186/1756-8722-6-84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882884PMC
November 2013