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Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts

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Cellular & Molecular Immunology 2022年第10期19卷 1185-1195页

作者： Ruby J.Siegel Anil K.Singh Paul M.Panipinto Farheen S.Shaikh Judy Vinh Sang U.Han H.Mark Kenney Edward M.Schwarz Cynthia S.Crowson sadik a.khuder Basil S.khuder David A.Fox Salahuddin Ahmed Department of Pharmaceutical Sciences Washington State University College of Pharmacy and Pharmaceutical SciencesSpokaneWAUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Department of Quantitative Health Sciences and Division of Rheumatology Mayo ClinicRochesterMNUSA Department of Medicine and Public Health University of ToledoToledoOHUSA Department of Pathology and Laboratory Medicine Phoenix Children’s HospitalPhoenixAZUSA Department of Medicine Division of Rheumatology and Clinical Autoimmunity Center of ExcellenceUniversity of Michigan Medical SystemAnn ArborMIUSA Division of Rheumatology University of Washington School of MedicineSeattleWAUSA

Extracellular sulfatase-2(Sulf-2)influences receptor-ligand binding and subsequent signaling by chemokines and growth factors,yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis(RA).In the present study,we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts(RASFs).Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg *** sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated~2500 genes compared to scrambled *** Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in *** blot,ELISA,and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1,VCAM1,CAD11,PDPN,CCL5,CX3CL1,CXCL10,and *** studies identified the protein kinase C-delta(PKCδ)and c-Jun N-terminal kinase(JNK)pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and *** of Sulf-2 abrogated TNF-α-induced RASF ***-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδand JNK,thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human ***,Sulf-2 expression positively correlated with the expression of TNF receptor 1,and coimmunoprecipitation assays demonstrated the binding of these two proteins,suggesting they exhibit crosstalk in TNF-α*** study identified a novel role of Sulf-2 in TNF-αsignaling and the activation of RA synoviocytes,providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.

关键词： Sulfatase-2 TNF-α Rheumatoid arthritis Synovial fibroblasts Signal transduction

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Dosimetric Effects of a Commercial Breast Board Patient Support System

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2022年第1期11卷 1-11页

作者： Eve Schodowski Austin Wilkinson sadik khuder David Pearson Department of Radiation Oncology University of Toledo Toledo USA

Aim: In prone breast treatments, a carbon fiber support device resides under the contralateral breast. Tangent beams are designed to encompass the treated breast and these often pass through the board at a shallow angle, resulting in significant attenuation. Our planners account for this attenuation by adding field-in-field dose to the deep part of the breast, through the board. Concern was raised about how accurate the treatment delivery is when the inherent uncertainties of patients’ positions are accounted for. Furthermore, transmission measurements are usually carried out perpendicular to the board, a non-clinical situation. The goal of this study is to evaluate the dosimetric effect of the board and the robustness of the plan to positional uncertainty. Materials and Methods: Twenty-two breast patients treated on a commercial prone breast board between 2017 and 2020 were selected for this retrospective study. To evaluate the board’s attenuation, we compared the plans with the board removed from the dose calculation. To quantify the robustness of this technique, we moved the beam isocenter with respect to the patient and board. Results: Our results showed that when the breast board is removed from a plan which was designed to account for the board attenuation, the average point dose increases by 7.48%, with a maximum of 22%. Comparing results with a mixed Analysis of Variance (ANOVA) and a least-square means analysis, our robustness evaluation indicates that anterior shifts at every magnitude (1 mm through 5 mm) make a significant difference in all dose statistics (D95, max, 95% prescription coverage and homogeneity index) investigated. In/out and right/left shifts resulted in an insignificant change in dose statistics. Conclusion: Prone breast boards can add significant dosimetric uncertainty into the treatment delivery process. Accounting for plan robustness in the design of the plan is highly recommended. A prone breast board design with support moved away fro

关键词： Prone Breast Treatment Breast Board Attenuating Structure Interfraction-al Set-Up Patient Support System Robustness

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hGBP-1 Expression Predicts Shorter Progression-Free Survival in Ovarian Cancers, While Contributing to Paclitaxel Resistance

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Journal of Cancer Therapy 2016年第13期7卷 994-1007页

作者： Suzan Wadi Aaron R. Tipton Jill A. Trendel sadik A. khuder Deborah J. Vestal Department of Biological Sciences University of Toledo Toledo OH USA Department of Medicine University of Toledo Toledo OH USA

Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a taxane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer.

关键词： Guanylate-Binding Protein Paclitaxel Ovarian Cancer Drug Resistance GTPase TUBB3

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Synthesis and Characterization of Schiff Base Metal Complexes Derived from Cefotaxime with 1<i>H</i>-indole-2,3-dione (Isatin) and 4-N,N-dimethyl-aminobenzaldehyde

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Open Journal of Inorganic Chemistry 2015年第4期5卷 83-101页

作者： Ahlam Jameel Abdulghani Rasha.khuder Hussain Department of Chemistry College of Science University of Baghdad Baghdad Iraq

This work involved the synthesis of two Schiff base derivatives of cefotaxime antibiotic (CFX) namely: [sodium3-(acetoxymethyl)-7-((Z)-2-(methoxyimino)-2-(2-((E)-2–oxoindolin-3-ylide-neamino) thiazol-4-yl)acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate]. (0.5) Methanol (LI) and [sodium3-(acetoxymethyl)-7-((2Z)-2-(2-(4-dimethylamino) benzylideneamino) thiazol-4-yl)-2-(methoxyimino)acetamido)-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylate]. (0.5) Methanol (LII) from the condensation reaction of the antibiotic with 1H-Indole-2,3-dione(isatin) and -N, N-dimethyl amino benzaldehyde respectively. Metal complexes of the two Schiff base ligands with Co(II), Ni(II), Cu(II), Cd(II), Pd(II) and Pt(IV) ions were prepared by reacting each ligand with the metal salts in refluxing ethanol. The chemical structures of the two ligands as well as the stereo-chemical structures and geometries of the studied metal complexes were suggested depending the results obtained from CHN and TG analysis, NMR, FTIR, and atomic absorption spectrophotometry, electronic spectra, magnetic moments and conductivity measurements. The mole ratio of the ligands to the metal ion was 1:1 with tridentate bonding behaviors of the coordinating ligands with the metal ions.

关键词： Cefotaxime Schiff Bases Metal Complexes Antibacterial Activity

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Constructive Theory of Designing Optimal Eighth-Order Derivative-Free Methods for Solving Nonlinear Equations

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American Journal of Computational Mathematics 2020年第1期10卷 100-117页

作者： Tugal Zhanlav khuder Otgondorj Renchin-Ochir Mijiddorj Institute of Mathematics and Digital Technology Mongolian Academy of Sciences Ulaanbaatar Mongolia School of Applied Sciences Mongolian University of Science and Technology Ulaanbaatar Mongolia Department of Informatics Mongolian National University of Education Ulaanbaatar Mongolia

This paper stresses the theoretical nature of constructing the optimal derivative-free iterations. We give necessary and sufficient conditions for derivative-free three-point iterations with the eighth-order of convergence. We also establish the connection of derivative-free and derivative presence three-point iterations. The use of the sufficient convergence conditions allows us to design wide class of optimal derivative-free iterations. The proposed family of iterations includes not only existing methods but also new methods with a higher order of convergence.

关键词： Multipoint Methods Derivative-Free Methods Order of Convergence

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Isolation and characterization of human polyreactive pneumococcal polysaccharide antibodies

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Open Journal of Immunology 2012年第3期2卷 98-110页

作者： Rebecca S. Thompson Noor M. Khaskhely Kristin R. Malhotra David J. Leggat Jason Mosakowski sadik khuder Gary R. McLean M. A. Julie Westerink Department of Medical Microbiology and Immunology University of Toledo Toledo USA Department of Medicine University of Toledo Toledo USA School of Human Sciences London Metropolitan University London UK

Natural antibodies serve as the body’s first line of defense against pneumococcal challenge. Polyreactive human pneumococcal polysaccharide IgG antibodies have not been extensively studied. We analyzed human polyreactive antibodies that bind multiple pneumococcal polysaccharides, including PPS14 and PPS23F. These antibodies were isolated from single pneumococcal polysaccharide specific B cells allowing for the analysis of human immunoglobulins with natively paired variable regions. Although isolated individually, these antibodies demonstrated similar characteristics. Most antibodies possessed a variable light chain with a CDR3 length made up of nine amino acids and relatively high number of flexible amino acids in combined VH/VL. While these antibodies were polyreactive and structurally alike, kinetic analysis revealed unique KD values. Variable chains are responsible for antigen recognition whereas antibody fine specificity is affected by isotype structure. To investigate the contribution of the constant region of these isotypes and their effect on antibody avidity to pneumococcal polysaccharide, the polyreactive variable regions were expressed as IgG1 or IgG2 and subjected to kinetic analysis. The IgG1 antibodies uniformly had a stronger avidity to PPS14 and PPS23F compared to IgG2. To further document the importance of the constant region in antibody avidity and fine specificity, analysis of antibody F(ab)’2 fragment binding to PPS14 and PPS23F resulted in similar KD values. These studies suggest that antigen recognition by polyreactive antibodies is determined by a conserved variable light chain CDR3 length and longer, more flexible variable heavy CDR3s when compared to pneumococcal polysaccha-ride-specific sequences while differences in specific avidities are modulated by antibody isotype.

关键词： B Cell Pneumococcal Polysaccharide Polyreactive Natural Isotype

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格林-巴利综合征住院患者的自主神经功能障碍

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中国康复 2018年第1期33卷 52-52页

作者： Anandan C khuder SA Koffman BM 何成奇(译) 不详四川大学华西医院

格林-巴利综合征（GBS）是急性神经肌肉麻痹最常见的原因.尽管自主神经功能障碍（AD）是这种疾病的一个众所周知的并发症,但很少有针对这些患者的AD表现的流行病学研究.这项调查的目的是确定GBS患者中AD的患病率.

关键词：自主神经功能障碍格林-巴利综合征住院患者神经肌肉麻痹流行病学并发症患病率 GBS

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