23 results on '"Jin, Mengyao"'
Search Results
2. Unraveling the triplet excited-state dynamics of Bi3+ in vacancy-ordered double perovskite Cs2SnCl6 nanocrystals
- Author
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Jin, Mengyao, Zheng, Wei, Gong, Zhongliang, Huang, Ping, Li, Renfu, Xu, Jin, Cheng, Xingwen, Zhang, Wei, and Chen, Xueyuan
- Published
- 2022
- Full Text
- View/download PDF
3. Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy
- Author
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Cao, Wei, Jin, Mengyao, Yang, Kang, Chen, Bo, Xiong, Maoming, Li, Xiang, and Cao, Guodong
- Published
- 2021
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4. C9orf72 in myeloid cells suppresses STING-induced inflammation
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McCauley, Madelyn E., O’Rourke, Jacqueline Gire, Yáñez, Alberto, Markman, Janet L., Ho, Ritchie, Wang, Xinchen, Chen, Shuang, Lall, Deepti, Jin, Mengyao, Muhammad, A. K. M. G., Bell, Shaughn, Landeros, Jesse, Valencia, Viviana, Harms, Matthew, Arditi, Moshe, Jefferies, Caroline, and Baloh, Robert H.
- Published
- 2020
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5. Functional carbon dots derived from biomass and plastic wastes.
- Author
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Kuang, Tairong, Jin, Mengyao, Lu, Xinrui, Liu, Tong, Vahabi, Henri, Gu, Zhipeng, and Gong, Xiao
- Subjects
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PLASTIC scrap , *BIOMASS , *MANUFACTURING processes , *PLASTIC scrap recycling , *CARBON , *ENVIRONMENTAL regulations - Abstract
Carbon dots (CDs) have emerged as a promising class of zero-dimensional (0D) carbon nanomaterials due to their outstanding photoluminescence and electrical properties, along with their non-toxic, non-hazardous, and biocompatible advantages. These unique properties have sparked considerable interest in their applications in various fields. The utilization of biomass and plastic wastes as carbon sources to prepare CDs has become a significant area of research interest in recent years, driven by the increasingly strict environmental regulations and the growing volume of waste generated during production processes. In this context, a comprehensive and timely review of the fabrication, structures, properties, and applications of biomass and plastic wastes-derived CDs would significantly expand this field of research. Here, we present an overview of the fabrication methods of biomass and plastic wastes-derived CDs, employing either a top-down or bottom-up strategy. Furthermore, the most recent advances in the structures and properties of these CDs are highlighted and their utilization in polymer composites derived from biomass and plastic wastes are critically reviewed and summarized. Finally, the pending challenges and prospects for future research on polymer/biomass and plastic wastes-derived CDs composites for various applications are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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6. An LC–MS/MS method for concurrent determination of nicotine metabolites and the role of CYP2A6 in nicotine metabolite-mediated oxidative stress in SVGA astrocytes
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Ande, Anusha, Earla, Ravinder, Jin, Mengyao, Silverstein, Peter S., Mitra, Ashim K., Kumar, Anil, and Kumar, Santosh
- Published
- 2012
- Full Text
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7. Unraveling the triplet excited-state dynamics of Bi3+ in vacancy-ordered double perovskite Cs2SnCl6 nanocrystals.
- Author
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Jin, Mengyao, Zheng, Wei, Gong, Zhongliang, Huang, Ping, Li, Renfu, Xu, Jin, Cheng, Xingwen, Zhang, Wei, and Chen, Xueyuan
- Abstract
Luminescent metal halides doped with ns
2 -metal ions such as 6s2 -metal Bi3+ have aroused reviving interest owing to their outstanding optical properties; however, the origin of the photoluminescence (PL) remains controversial and unclear. Herein, we report a strategy for the controlled synthesis of Bi3+ -doped vacancy-ordered double perovskite Cs2 SnCl6 nanocrystals (NCs) and unravel the triplet excited-state dynamics of Bi3+ through temperature-dependent PL and ultrafast femtosecond transient absorption spectroscopies. Owing to the aliovalent Bi3+ doping in the spatially confined zero-dimensional (0D) structure of Cs2 SnCl6 , Bi3+ ions experience an enhancive Jahn-Teller distortion in the excited state, which results in intense broadband blue PL originating from the inter-configurational3 P0,1 →1 S0 transitions of Bi3+ at 450 nm, with a large Stokes shift and a quantum yield of 35.2%. Specifically, an unusual thermal-enhanced Jahn-Teller splitting of the excitation band and a remarkable transition of the PL lifetime from ms at 10 K to µs at 300 K were observed, as solid evidence for the isolated Bi3+ emission. These findings clarify the controversy about the PL origin in ns2 -metal ion-doped lead-free luminescent metal halides, thereby paving the way for exploring their optoelectronic applications. [ABSTRACT FROM AUTHOR]- Published
- 2022
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- View/download PDF
8. A LC-MS/MS Method for Concurrent Determination of Nicotine Metabolites and Role of CYP2A6 in Nicotine Metabolism in U937 Macrophages: Implications in Oxidative Stress in HIV + Smokers
- Author
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Jin, Mengyao, Earla, Ravinder, Shah, Ankit, Earla, Rajya L., Gupte, Raeesa, Mitra, Ashim K., Kumar, Anil, and Kumar, Santosh
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- 2012
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9. Efficient Near‐Infrared Luminescence in Lanthanide‐Doped Vacancy‐Ordered Double Perovskite Cs2ZrCl6 Phosphors via Te4+ Sensitization.
- Author
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Sun, Jinyue, Zheng, Wei, Huang, Ping, Zhang, Meiran, Zhang, Wen, Deng, Zhonghua, Yu, Shaohua, Jin, Mengyao, and Chen, Xueyuan
- Subjects
LUMINESCENCE ,PHOSPHORS ,PEROVSKITE ,METAL halides ,YTTERBIUM ,LIGHT emitting diodes ,RARE earth metals - Abstract
All‐inorganic lead‐free perovskite‐derivative metal halides have shown great promise in optoelectronics, however, it remains challenging to realize efficient near‐infrared (NIR) luminescence in these materials. Herein, we report a novel strategy based on Te4+/Ln3+ (Ln=Er, Nd, and Yb) co‐doping to achieve efficient NIR luminescence in vacancy‐ordered double perovskite Cs2ZrCl6 phosphors, which are excitable by a low‐cost near‐ultraviolet light‐emitting diode (LED) chip. Through sensitization by the spin‐orbital allowed 1S0→3P1 transition of Te4+, intense and multi‐wavelength NIR luminescence originating from the 4f→4f transitions of Er3+, Nd3+, and Yb3+ was acquired, with a quantum yield of 6.1 % for the Er3+ emission. These findings provide a general approach to achieve efficient NIR emission in lead‐free metal halides through ns2‐metal and lanthanide ion co‐doping, thereby opening up a new avenue for exploring NIR‐emitting perovskite derivatives towards versatile applications such as NIR‐LEDs and bioimaging. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. Effect of Alcohol on Drug Efflux Protein and Drug Metabolic Enzymes in U937 Macrophages
- Author
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Jin, Mengyao, Arya, Priyanka, Patel, Kalpeshkumar, Singh, Bhupendra, Silverstein, Peter S., Bhat, Hari K., Kumar, Anil, and Kumar, Santosh
- Published
- 2011
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11. FHL3 Contributes to EMT and Chemotherapy Resistance Through Up-Regulation of Slug and Activation of TGF β /Smad-Independent Pathways in Gastric Cancer.
- Author
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Cao, Guodong, Li, Pengping, He, Xiaobo, Jin, Mengyao, Li, Mengying, Chen, Sihan, Xu, Xin, Sun, Qiang, Xiong, Maoming, and Chen, Bo
- Subjects
STOMACH cancer ,GLYCOGEN synthase kinase ,MITOGEN-activated protein kinases ,OVERALL survival ,PANCREATIC tumors ,CANCER chemotherapy - Abstract
Background: Gastric cancer presents high risk of metastasis and chemotherapy resistance. Hence, it is important to understand the mechanisms of gastric cancer distant metastasis and chemotherapeutic resistance. Our previous study has revealed Four and a Half LIM Domains 3 (FHL3) plays as a binding partner of Glycogen Synthase Kinase 3 Beta (GSK3 β), promoted tumor metastasis in pancreatic cancer. However, the role of FHL3 in gastric cancer still remains unclear. Methods: TCGA database and clinical samples are used for exploring the role of FHL3 in disease progression and prognosis. Oxaliplatin (OHP) resistance cell lines were established to study the role of FHL3 in chemotherapy resistance. The experiments about cell proliferation, apoptosis, and metastasis were performed to measure the chemotherapy effects of sh-FHL3 on gastric cancer cell lines and in vivo. That FHL3 changed the EMT phenotype was verified by western blot. Finally, we explored the mechanism of FHL3-mediated EMT and chemotherapy resistance. Results: mRNA and protein level of FHL3 were significantly up-regulated in gastric cancer tissues when compared with adjacent tissue. FHL3 higher expression is always accompanied with higher TNM stage and worse overall survival. FHL3 over-expressed could lead to OHP resistance. Knockdown of FHL3 slightly inhibited the cell growth, while it obviously sensitized the chemotherapy in vivo and in vitro. In addition, down-regulation of FHL3 increased the mesenchymal markers, such as Slug, Snail, Twist Family BHLH Transcription Factor 1 (Twist1), and Vimentin, while it decreased the epithelial marker E-cadherin. Cell and animal experiments also proved that down-regulation of FHL3 can decrease cancer cell metastasis. For mechanism study, FHL3 knockdown down-regulated the expression level of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Regulated Protein Kinase (ERK) pathway and Transforming Growth Factor- β (TGF β)/Phosphatidylinositol 3-Kinase (PI3K)/protein kinase B(Akt)/GSK3 β -(Ring Finger Protein 146) RNF146/ubiquitin pathway. FHL3 competitively bonded the ubiquitin complex (Slug/GSK3β/RNF146) with Slug and inhibited ubiquitination of Slug. Mesenchymal phenotype cells hold higher level of Multidrug Resistance Gene1 (MDR1), and the FHL3 knockdown reverts the MDR1 in this type cell. Conclusion: FHL3 high expression contributed to EMT and chemotherapy resistance via MAPK, and PI3K pathways were activated. FHL3 competitively bonded the ubiquitin complex with Slug, resulting in the up-regulation of Slug and leading to metastasis of gastric cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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12. An advanced 2D feature transmitted algorithm for mask defect detection.
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Zeng, Yilei, Cheng, Yi, Jin, Mengyao, and Li, Hunter
- Published
- 2023
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13. Graph-Oriented Code Transformation Approach for Register-Limited Stencils on GPUs.
- Author
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Jin, Mengyao, Fu, Haohuan, Lv, Zihong, and Yang, Guangwen
- Published
- 2016
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14. Effect of ethanol on spectral binding, inhibition, and activity of CYP3A4 with an antiretroviral drug nelfinavir
- Author
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Kumar, Santosh, Earla, Ravinder, Jin, Mengyao, Mitra, Ashim K., and Kumar, Anil
- Subjects
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ETHANOL , *CYTOCHROME P-450 , *ANTIRETROVIRAL agents , *BINDING sites , *METABOLISM , *LIQUID chromatography , *REVERSE transcriptase - Abstract
Abstract: Cytochrome P450 3A4 (CYP3A4) is the most abundant CYP enzyme in the liver and metabolizes approximately 50% of the drugs, including antiretrovirals. Although CYP3A4 induction by ethanol and impact of CYP3A4 on drug metabolism and toxicity is known, CYP3A4-ethanol physical interaction and its impact on drug binding, inhibition, or metabolism is not known. Therefore, we studied the effect of ethanol on binding and inhibition of CYP3A4 with a representative protease inhibitor, nelfinavir, followed by the effect of alcohol on nelfinavir metabolism. Our initial results showed that methanol, ethanol, isopropanol, isobutanol, and isoamyl alcohol bind in the active site of CYP3A4 and exhibit type I spectra. Among these alcohol compounds, ethanol showed the lowest K D (5.9±0.34mM), suggesting its strong binding affinity with CYP3A4. Ethanol (20mM) decreased the K D of nelfinavir by >5-fold (0.041±0.007 vs. 0.227±0.038μM). Similarly, 20mM ethanol decreased the IC 50 of nelfinavir by >3-fold (2.6±0.5 vs. 8.3±3.1μM). These results suggest that ethanol facilitates binding of nelfinavir with CYP3A4. Furthermore, we performed nelfinavir metabolism using LCMS. Although ethanol did not alter k cat, it decreased the K m of nelfinavir, suggesting a decrease in catalytic efficiency (k cat/K m). This is an important finding because alcoholism is prevalent in HIV-1-infected persons and alcohol is shown to decrease the response to antiretroviral therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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15. Comparative transcriptomics reveals osmotic and ionic stress key genes contributing to the difference in the salinity tolerance of two pak choi cultivars.
- Author
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Du, Xueling, Yu, Rugang, Shi, Changqian, Wang, Ying, Meng, Rui, Shi, Wenwen, Jin, Mengyao, Wei, Xiuqi, and Sun, Tao
- Subjects
- *
BOK choy , *SALINITY , *CULTIVARS , *TRANSCRIPTOMES , *GENES , *GENETIC engineering - Abstract
• The root transcriptomic changes of Shanghaijimaocai (tolerant to salinity) and Te'aiqing (sensitive to salinity) were first investigated. • Osmotic stress-related genes might contribute to the difference in salinity tolerance between Shanghaijimaocai and Te'aiqing. • Ionic -related genes, NHX7 , SLAH1 and ALMT13 might contribute to the difference in salinity tolerance between Shanghaijimaocai and Te'aiqing. Pak choi is an important leafy vegetable crop. Salinity is among the most harmful agents that negatively influence the pak choi yield. However, the mechanism of salinity tolerance in pak choi has not been well understood. In this study, the root transcriptomics of two cultivars differing in salinity tolerance, i.e., Shanghaijimaocai (S, tolerant to salinity) and Te'aiqing (T, sensitive to salinity), were investigated under 0 and 100 mM NaCl treatments. A total of 6765, 2454, 2451 and 5798 differentially expressed unigenes (DEUs) were identified in comparison of S 100 /S 0 , T 100 /T 0 , S 0 /T 0 and S 100 /T 100 , respectively. In Shanghaijimaocai is more sensitive to NaCl stress than Te'aiqing in terms of root transcriptomics. Based on GO and KEGG pathway analyses, the expression levels of several osmotic and ionic stress-related genes, including MP3K18 , PYL8 , PP2C15 / 16 / 49 , ARF2 , bHLH112 , bZIP43 , COL5 , CDF1/3 , ERF25/60 , HSFA6 , MYBS3 / 59 / 92 / CCA1 / PHL5 , POD21 , GOLS7 , CIPK4 / 7 / 12 , NHX7 , SLAH1 and ALMT13 , in Shanghaijimaocai were higher than those in Te'aiqing. Therefore, these genes might contribute to the difference in salinity tolerance. Moreover, the physiological shift of peroxidase activity was in accordance with the dynamic transcript profile of relevant unigenes. These findings would be useful for further functional analysis as potential targets to improve resistance to salinity stress via genetic engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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16. A real-word study: is normothermic intraoperative intraperitoneal chemotherapy impactful as we expect?
- Author
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Jin M, Cao W, Chen J, Xiong M, Cao G, and Chen B
- Abstract
Background: Patients with gastric cancer have a poor prognosis. Currently, intraperitoneal chemotherapy has been considered a therapeutic option to improve prognosis due to its appealing theoretical rationales. But there is no consensus on the choice of chemotherapeutic agents used in intraperitoneal chemotherapy for gastric cancer. The real-world efficacy of applying intraoperative chemotherapy in gastric cancer still remains undefined., Methods: Patients with gastric cancer who underwent radical gastrectomy at the Gastrointestinal Department of The First Affiliated Hospital of Anhui Medical University between 2012 and 2019 were enrolled in this study. Patients were divided into two groups based on whether they received intraperitoneal chemotherapy. The t-test (mean of two samples) was conducted to compare the difference in measurement data between the two groups, and the chi-square test was used to compare the difference in count data. Kaplan-Meier method with log-rank test was performed to analyze the overall survival of patients. Kaplan-Meier method with log-rank test was also performed in various subgroups to respectively compare the survival of patients. Multivariate Cox analysis was performed to analyze the prognosis factors of these patients., Results: A total of 1253 patients were included in the final analysis, in which 861 patients received intraperitoneal chemotherapy and 352 not received intraperitoneal chemotherapy. The clinicopathological features of the participants in the two groups were comparable. There was no significant difference between the two groups in overall survival ( P > 0.05). Consistently, no significant difference was found between the two groups in each subgroup ( P > 0.05). The multivariate Cox analysis demonstrated that only age, BMI, pathological type, TNM stage, and differentiation grade were independent risk factors of survival., Conclusion: Intraoperative intraperitoneal chemotherapy usage did not improve survival in patients with gastric cancer undergoing radical gastrectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Cao, Chen, Xiong, Cao and Chen.)
- Published
- 2023
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17. Efficient Near-Infrared Luminescence in Lanthanide-Doped Vacancy-Ordered Double Perovskite Cs 2 ZrCl 6 Phosphors via Te 4+ Sensitization.
- Author
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Sun J, Zheng W, Huang P, Zhang M, Zhang W, Deng Z, Yu S, Jin M, and Chen X
- Abstract
All-inorganic lead-free perovskite-derivative metal halides have shown great promise in optoelectronics, however, it remains challenging to realize efficient near-infrared (NIR) luminescence in these materials. Herein, we report a novel strategy based on Te
4+ /Ln3+ (Ln=Er, Nd, and Yb) co-doping to achieve efficient NIR luminescence in vacancy-ordered double perovskite Cs2 ZrCl6 phosphors, which are excitable by a low-cost near-ultraviolet light-emitting diode (LED) chip. Through sensitization by the spin-orbital allowed1 S0 →3 P1 transition of Te4+ , intense and multi-wavelength NIR luminescence originating from the 4f→4f transitions of Er3+ , Nd3+ , and Yb3+ was acquired, with a quantum yield of 6.1 % for the Er3+ emission. These findings provide a general approach to achieve efficient NIR emission in lead-free metal halides through ns2 -metal and lanthanide ion co-doping, thereby opening up a new avenue for exploring NIR-emitting perovskite derivatives towards versatile applications such as NIR-LEDs and bioimaging., (© 2022 Wiley-VCH GmbH.)- Published
- 2022
- Full Text
- View/download PDF
18. Tumor-Derived Lactate Creates a Favorable Niche for Tumor via Supplying Energy Source for Tumor and Modulating the Tumor Microenvironment.
- Author
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Jin M, Cao W, Chen B, Xiong M, and Cao G
- Abstract
Tumor evolution is influenced by events involving tumor cells and the environment in which they live, known as the tumor microenvironment (TME). TME is a functional and structural niche composed of tumor cells, endothelial cells (ECs), cancer-associated fibroblasts (CAFs), mesenchymal stromal cells (MSCs), and a subset of immune cells (macrophages, dendritic cells, natural killer cells, T cells, B cells). Otto Warburg revealed the Warburg effect in 1923, a characteristic metabolic mechanism of tumor cells that performs high glucose uptake and excessive lactate formation even in abundant oxygen. Tumor tissues excrete a large amount of lactate into the extracellular microenvironment in response to TME's hypoxic or semi-hypoxic state. High lactate concentrations in tumor biopsies have been linked to metastasis and poor clinical outcome. This indicates that the metabolite may play a role in carcinogenesis and lead to immune escape in TME. Lactate is now recognized as an essential carbon source for cellular metabolism and as a signaling molecule in TME, forming an active niche that influences tumor progression. This review summarized the advanced literature demonstrating the functional role of lactate in TME remodeling, elucidating how lactate shapes the behavior and the phenotype of both tumor cells and tumor-associated cells. We also concluded the intriguing interactions of multiple immune cells in TME. Additionally, we demonstrated how lactate functioned as a novel function factor by being used in a new histone modification, histone lysine lactylation, and to regulate gene expression in TME. Ultimately, because lactate created a favorable niche for tumor progression, we summarized potential anti-tumor strategies targeting lactate metabolism and signaling to investigate better cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin, Cao, Chen, Xiong and Cao.)
- Published
- 2022
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19. IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation.
- Author
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Smith S, Wu PW, Seo JJ, Fernando T, Jin M, Contreras J, Montano EN, Gabhann JN, Cunningham K, Widaa A, McCarthy EM, Molloy ES, Kearns G, Murphy CC, Kong W, Björkbacka H, Kornfeld H, Forbess L, Venuturupalli S, Ishimori M, Wallace D, Weisman MH, and Jefferies CA
- Subjects
- Adult, Animals, Cell Line, Disease Models, Animal, Epithelium immunology, Epithelium pathology, Female, Gene Expression Regulation immunology, Humans, Interleukin-16 immunology, Lung cytology, Lung drug effects, Lung pathology, Lupus Erythematosus, Systemic complications, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs immunology, Middle Aged, Neutrophil Infiltration immunology, Neutrophils immunology, Pneumonia chemically induced, Pneumonia pathology, Primary Cell Culture, Terpenes administration & dosage, Terpenes immunology, Interleukin-16 genetics, Lung immunology, Lupus Erythematosus, Systemic immunology, MicroRNAs metabolism, Pneumonia immunology
- Abstract
Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.
- Published
- 2018
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20. Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease.
- Author
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Crook KR, Jin M, Weeks MF, Rampersad RR, Baldi RM, Glekas AS, Shen Y, Esserman DA, Little P, Schwartz TA, and Liu P
- Subjects
- Animals, Antibody Formation immunology, Arthritis, Experimental immunology, Arthritis, Experimental pathology, Arthritis, Experimental therapy, Autoimmune Diseases pathology, Autoimmune Diseases therapy, CD4-Positive T-Lymphocytes immunology, Cell Proliferation, Dinoprostone metabolism, Female, Immunization, Interferon-gamma metabolism, Interleukin-17 metabolism, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Monocytes pathology, Myeloid Cells transplantation, Nitric Oxide Synthase Type II metabolism, Phenotype, Receptors, CCR2 deficiency, Receptors, CCR2 metabolism, Autoimmune Diseases immunology, B-Lymphocytes immunology, Myeloid Cells immunology, T-Lymphocytes immunology
- Abstract
MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in cancer and autoimmune disease. The effect of MDSCs on B cell function is not clear. Using the CIA model of autoimmune disease, we found an increase in M-MDSCs in the periphery of WT mice with CIA compared with naïve mice. These MDSCs were absent from the periphery of CCR2(-/-) mice that developed exacerbated disease. M-MDSCs, isolated from immunized mice, inhibited autologous CD4(+) T cell proliferation. The M-MDSC-mediated suppression of T cell proliferation was NO and IFN-γ dependent but IL-17 independent. Furthermore, we demonstrated for the first time that M-MDSCs from CIA mice also inhibited autologous B cell proliferation and antibody production. The suppression of B cells by M-MDSCs was dependent on the production of NO and PGE2 and required cell-cell contact. Administration of M-MDSCs rescued CCR2(-/-) mice from the exacerbated CIA phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M-MDSCs reduced autoantibody production by CCR2(-/-) and WT mice. In summary, M-MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic approach in the treatment of autoimmune arthritis., (© Society for Leukocyte Biology.)
- Published
- 2015
- Full Text
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21. Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes.
- Author
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Kumar S, Jin M, Ande A, Sinha N, Silverstein PS, and Kumar A
- Subjects
- Acquired Immunodeficiency Syndrome drug therapy, Acquired Immunodeficiency Syndrome metabolism, Drug Tolerance, HIV Infections drug therapy, HIV Infections metabolism, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, HIV-1 physiology, Humans, Isoenzymes metabolism, Liver drug effects, Liver metabolism, Protease Inhibitors therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Virus Replication, Alcohol Drinking adverse effects, Antiretroviral Therapy, Highly Active, Cytochrome P-450 CYP2E1 metabolism, Cytochrome P-450 CYP3A metabolism, HIV-1 pathogenicity, Oxidative Stress drug effects
- Abstract
Introduction: Alcohol consumption, which is highly prevalent in HIV-infected individuals, poses serious concerns in terms of rate of acquisition of HIV-1 infection, HIV-1 replication, response to highly active antiretroviral therapy (HAART) and AIDS/neuroAIDS progression. However, little is known about the mechanistic pathways by which alcohol exerts these effects, especially with respect to HIV-1 replication and the patient's response to HAART., Areas Covered: In this review, the authors discuss the effects of alcohol consumption on HIV-1 pathogenesis and its effect on HAART. They also describe the role of cytochrome P450 2E1 (CYP2E1) in alcohol-mediated oxidative stress and toxicity, and the role of CYP3A4 in the metabolism of drugs used in HAART (i.e., protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI)). Based on the most recent findings the authors discuss the role of CYP2E1 in alcohol-mediated oxidative stress in monocytes/macrophages and astrocytes, as well as the role of CYP3A4 in alcohol-PI interactions leading to altered metabolism of PI in these cells., Expert Opinion: The authors propose that alcohol and PI/NNRTI interact synergistically in monocytes/macrophages and astrocytes through the CYP pathway leading to an increase in oxidative stress and a decrease in response to HAART. Ultimately, this exacerbates HIV-1 pathogenesis and neuroAIDS.
- Published
- 2012
- Full Text
- View/download PDF
22. Ethanol-mediated regulation of cytochrome P450 2A6 expression in monocytes: role of oxidative stress-mediated PKC/MEK/Nrf2 pathway.
- Author
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Jin M, Kumar A, and Kumar S
- Subjects
- Active Transport, Cell Nucleus drug effects, Ascorbic Acid pharmacology, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2E1 metabolism, Enzyme Activation drug effects, Ethanol pharmacology, Humans, Mitogen-Activated Protein Kinase Kinases metabolism, Models, Biological, Monocytes enzymology, NF-E2-Related Factor 2 metabolism, Protein Kinase C metabolism, U937 Cells, Aryl Hydrocarbon Hydroxylases metabolism, Ethanol metabolism, Monocytes drug effects, Monocytes metabolism, Oxidative Stress drug effects, Signal Transduction drug effects
- Abstract
Cytochrome P450 2A6 (CYP2A6) is known to metabolize nicotine, the major constituent of tobacco, leading to the production of toxic metabolites and induction of oxidative stress that result in liver damage and lung cancer. Recently, we have shown that CYP2A6 is induced by ethanol and metabolizes nicotine into cotinine and other metabolites leading to generation of reactive oxygen species (ROS) in U937 monocytes. However, the mechanism by which CYP2A6 is induced by ethanol is unknown. In this study, we have examined the role of the PKC/Nrf2 pathway (protein kinase C-mediated phosphorylation and translocation of nuclear erythroid 2-related factor 2 to the nucleus) in ethanol-mediated CYP2A6 induction. Our results showed that 100 mM ethanol significantly induced CYP2A6 mRNA and protein (~150%) and increased ROS formation, and induction of gene expression and ROS were both completely blocked by treatment with either a CYP2E1 inhibitor (diallyl sulfide) or an antioxidant (vitamin C). The results suggest the role of oxidative stress in the regulation of CYP2A6 expression. Subsequently, we investigated the role of Nrf2 pathway in oxidative stress-mediated regulation of CYP2A6 expression in U937 monocytes. Our results showed that butylated hydroxyanisole, a stabilizer of nuclear Nrf2, increased CYP2A6 levels >200%. Staurosporine, an inhibitor of PKC, completely abolished ethanol-induced CYP2A6 expression. Furthermore, our results showed that a specific inhibitor of mitogen-activated protein kinase kinase (MEK) (U0126) completely abolished ethanol-mediated CYP2A6 induction and Nrf2 translocation. Overall, these results suggest that CYP2E1-mediated oxidative stress produced as a result of ethanol metabolism translocates Nrf2 into the nucleus through PKC/MEK pathway, resulting in the induction of CYP2A6 in monocytes. An increased level of CYP2A6 in monocytes is expected to further increase oxidative stress in smokers through CYP2A6-mediated nicotine metabolism. Thus, this study has clinical relevance because of the high incidence of alcohol use among smokers, especially in HIV-infected individuals.
- Published
- 2012
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23. Cytochrome P450-Mediated Phytoremediation using Transgenic Plants: A Need for Engineered Cytochrome P450 Enzymes.
- Author
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Kumar S, Jin M, and Weemhoff JL
- Abstract
There is an increasing demand for versatile and ubiquitous Cytochrome P450 (CYP) biocatalysts for biotechnology, medicine, and bioremediation. In the last decade there has been an increase in realization of the power of CYP biocatalysts for detoxification of soil and water contaminants using transgenic plants. However, the major limitations of mammalian CYP enzymes are that they require CYP reductase (CPR) for their activity, and they show relatively low activity, stability, and expression. On the other hand, bacterial CYP enzymes show limited substrate diversity and usually do not metabolize herbicides and industrial contaminants. Therefore, there has been a considerable interest for biotechnological industries and the scientific community to design CYP enzymes to improve their catalytic efficiency, stability, expression, substrate diversity, and the suitability of P450-CPR fusion enzymes. Engineered CYP enzymes have potential for transgenic plants-mediated phytoremediation of herbicides and environmental contaminants. In this review we discuss: 1) the role of CYP enzymes in phytoremediation using transgenic plants, 2) problems associated with wild-type CYP enzymes in phytoremediation, and 3) examples of engineered CYP enzymes and their potential role in transgenic plant-mediated phytoremediation.
- Published
- 2012
- Full Text
- View/download PDF
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