scholarly journals The Emerging Application of Itaconate: Promising Molecular Targets and Therapeutic Opportunities

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiaqi Lin ◽  
Jinxuan Ren ◽  
Dave Schwinn Gao ◽  
Yi Dai ◽  
Lina Yu
Keyword(s):  
Structural Characteristics ◽  
Tricarboxylic Acid Cycle ◽  
Immune Response Gene ◽  
Future Research ◽  
Response Gene ◽  
Biological Regulation ◽  
Important Intermediate ◽  
Cellular Immune ◽  
Substrate Proteins ◽  
Intermediate Metabolite

Metabolites have recently been found to be involved in significant biological regulation and changes. Itaconate, an important intermediate metabolite isolated from the tricarboxylic acid cycle, is derived from cis-aconitate decarboxylation mediated by immune response gene 1 in mitochondrial matrix. Itaconate has emerged as a key autocrine regulatory component involved in the development and progression of inflammation and immunity. It could directly modify cysteine sites on functional substrate proteins which related to inflammasome, signal transduction, transcription, and cell death. Itaconate can be a connector among immunity, metabolism, and inflammation, which is of great significance for further understanding the mechanism of cellular immune metabolism. And it could be the potential choice for the treatment of inflammation and immune-related diseases. This study is a systematic review of the potential mechanisms of metabolite associated with different pathology conditions. We briefly summarize the structural characteristics and classical pathways of itaconate and its derivatives, with special emphasis on its promising role in future clinical application, in order to provide theoretical basis for future research and treatment intervention.

Lack of immune response gene control for induction of epitope-specific suppression by TGAL antigen

Nature ◽  
1982 ◽  
Vol 295 (5847) ◽  
pp. 329-331 ◽  
Author(s):  
Leonore A. Herzenberg ◽  
Takeshi Tokuhisa ◽  
Kyoko Hayakawa ◽  
Leonard A. Herzenberg
Keyword(s):  
Immune Response ◽  
Immune Response Gene ◽  
Gene Control ◽  
Response Gene ◽  
Specific Suppression

Immune response gene polymorphisms in tuberculosis

2015 ◽  
Vol 62 (4) ◽  
pp. 633-640 ◽  
Author(s):  
Marek Fol ◽  
Magdalena Druszczynska ◽  
Marcin Wlodarczyk ◽  
Elzbieta Ograczyk ◽  
Wieslawa Rudnicka
Keyword(s):  
Immune Response ◽  
Gene Polymorphisms ◽  
Immune Response Gene ◽  
Response Gene

scholarly journals Insights into Ebola Virus VP35 and VP24 Interferon Inhibitory Functions and their Initial Exploitation as Drug Targets

2019 ◽  
Vol 19 (4) ◽  
pp. 362-374 ◽  
Author(s):  
Elisa Fanunza ◽  
Aldo Frau ◽  
Angela Corona ◽  
Enzo Tramontano
Keyword(s):  
Drug Development ◽  
Drug Targets ◽  
Cellular Response ◽  
Ebola Virus ◽  
Virus Disease ◽  
Structural Characteristics ◽  
Inhibitory Function ◽  
The Family ◽  
Effective Shield ◽  
Cellular Immune

Upon viral infection, the interferon (IFN) system triggers potent antiviral mechanisms limiting viral growth and spread. Hence, to sustain their infection, viruses evolved efficient counteracting strategies to evade IFN control. Ebola virus (EBOV), member of the family Filoviridae, is one of the most virulent and deadly pathogen ever faced by humans. The etiological agent of the Ebola Virus Disease (EVD), EBOV can be undoubtedly considered the perfect example of a powerful inhibitor of the host organism immune response activation. Particularly, the efficacious suppression of the IFN cascade contributes to disease progression and severity. Among the EBOVencoded proteins, the Viral Proteins 35 (VP35) and 24 (VP24) are responsible for the EBOV extreme virulence, representing the core of such inhibitory function through which EBOV determines its very effective shield to the cellular immune defenses. VP35 inhibits the activation of the cascade leading to IFN production, while VP24 inhibits the activation of the IFN-stimulated genes. A number of studies demonstrated that both VP35 and VP24 is validated target for drug development. Insights into the structural characteristics of VP35 and VP24 domains revealed crucial pockets exploitable for drug development. Considered the lack of therapy for EVD, restoring the immune activation is a promising approach for drug development. In the present review, we summarize the importance of VP35 and VP24 proteins in counteracting the host IFN cellular response and discuss their potential as druggable viral targets as a promising approach toward attenuation of EBOV virulence.

The Future

1992 ◽  
Author(s):  
John A. Tossell ◽  
David J. Vaughan
Keyword(s):  
Ab Initio ◽  
Quantum Chemical ◽  
Force Fields ◽  
Structural Characteristics ◽  
Future Research ◽  
Quantum Mechanical ◽  
Bond Lengths ◽  
Hartree Fock ◽  
Qualitative Level ◽  
Dynamics Simulations

In this final chapter, an attempt is made to provide an overview of the capabilities of quantum-mechanical methods at the present time, and to highlight the needs for future development and possible future applications of these methods, particularly in areas related to mineral structures, energetics, and spectroscopy. There is also a brief account of some new areas of application, specific directions for future research, and possible developments in the perception and use of quantum-mechanical approaches. The book ends with an epilog on the overall role of “theoretical geochemistry” in the earth and environmental sciences. The local structural characteristics of minerals such as Mg2SiO4, which contain only main-group elements, are reasonably well reproduced by ab initio Hartree-Fock-Roothaan (SCF) cluster calculations at the mediumbasis- set level. Calculations incorporating configuration interaction will inevitably follow and probably lead to somewhat better agreement with experiment. The most pressing needs in this area of study are for the development of systematic procedures for cluster selection and embedding, for a greater understanding of the results at a qualitative level, and for more widespread efficient application of the quantum-chemical results currently available. In the last area, substantial progress has already been made by Lasaga and Gibbs (1987), Sanders et al. (1984), Tsuneyuki et al. (1988), and others, who have used ab initio calculations to generate theoretical force fields which can then be used in molecular-dynamics simulations. If the characteristics of the resultant force fields can be understood at a first-principles level, then it may be possible to understand details of the simulated structures at the same level. Unfortunately, as regards a greater qualitative understanding of the quantum-mechanical calculations, little progress has been made. Rather old qualitative theories describe some aspects of bond-angle variation (Tossell, 1986), but no general model to interpret variations in bond lengths has been developed within either chemistry or geochemistry beyond the model of additive atomic (Slater) or ionic (Shannon and Prewitt) radii. Indeed, global theories of bond-length variations within an ab initio framework seem to be nonexistent. Nonetheless, quantum-chemical studies have shown the presence of intriguing systematics in bond lengths (Gibbs et al., 1987), which had been already noted empirically.

scholarly journals Limited Dynamic Range of Immune Response Gene Expression Observed in Healthy Blood Donors Using RT-PCR

2006 ◽  
Vol 12 (7-8) ◽  
pp. 185-195 ◽  
Author(s):  
Kevin McLoughlin ◽  
Ken Turteltaub ◽  
Danute Bankaitis-Davis ◽  
Richard Gerren ◽  
Lisa Siconolfi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Donors ◽  
Dynamic Range ◽  
Immune Response Gene ◽  
Rt Pcr ◽  
Response Gene

scholarly journals Thymus dictates major histocompatibility complex (MHC) specificity and immune response gene phenotype of class II MHC-restricted T cells but not of class I MHC-restricted T cells.

1984 ◽  
Vol 160 (6) ◽  
pp. 1752-1766 ◽  
Author(s):  
W M Kast ◽  
L P de Waal ◽  
C J Melief
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Sendai Virus ◽  
Immune Response Gene ◽  
Response Gene ◽  
Class I Mhc ◽  
Ctl Response ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

Athymic H-2b nude mice received grafts from C57BL/6 (Sendai virus and H-Y antigen cytotoxic T lymphocyte [CTL] responder type), bm1 (H-2Kb mutant, Sendai CTL nonresponder type), or bm12 (H-21-A mutant, H-Y CTL nonresponder type) neonates. In observations of the CTL response to H-Y, both recipients and thymus donors were female. All types of thymus engraftment resulted in mature H-2b splenic T lymphocyte surface phenotype in nude hosts. T cell immunocompetence (as measured by major histocompatibility complex [MHC] CTL responses to allogeneic cells) was restored, and induced nonresponsiveness to the MHC determinants of the engrafted thymus in the nude host. The CTL reaction to Sendai virus in both responder type C57BL/6 and nonresponder type bm1 neonatal thymuses allowed maturation of Sendai-specific, H-2Kb-restricted CTL. For the CTL reaction to H-Y, only responder type C57BL/6 thymuses restored the CTL response, whereas this was not achieved with thymuses from nonresponder type bm12 neonatal females. Results of double thymus (B6 and bm12) engraftment excluded the possibility that this latter effect was caused by suppression. In addition, athymic bm1 mice were engrafted with thymuses from either B6 (Sendai CTL responder type) or syngeneic bm1 neonates (Sendai CTL nonresponder type). Again, both types of neonate thymuses restored T cell competence as measured by MHC/CTL responses to allogeneic cells. However, neither responder B6 nor nonresponder bm1 neonate thymus grafts allowed maturation of Sendai-specific CTL. In conclusion, the thymus dictates MHC specificity and immune response gene phenotype of T cells restricted to class II MHC molecules but not of T cells restricted to class I MHC molecules.

scholarly journals Effect of Temperature on Plant Resistance to Arthropod Pests

2020 ◽  
Vol 49 (3) ◽  
pp. 537-545
Author(s):  
James R Nechols ◽  
Ashley R Hough ◽  
David C Margolies ◽  
John R Ruberson ◽  
Brian P McCornack ◽  
...  
Keyword(s):  
Plant Resistance ◽  
Indirect Effects ◽  
Host Plants ◽  
Structural Characteristics ◽  
Effect Of Temperature ◽  
Future Research ◽  
Experimental Approaches ◽  
Arthropod Pests ◽  
Effects Of Temperature ◽  
Effective Use

Abstract Temperature has a strong influence on the development, survival, and fecundity of herbivorous arthropods, and it plays a key role in regulating the growth and development of their host plants. In addition, temperature affects the production of plant secondary chemicals as well as structural characteristics used for defense against herbivores. Thus, temperature has potentially important implications for host plant resistance. Because temperature directly impacts arthropod pests, both positively and negatively, distinguishing direct effects from indirect effects mediated through host plants poses a challenge for researchers and practitioners. A more comprehensive understanding of how temperature affects plant resistance specifically, and arthropod pests in general, would lead to better predictions of pest populations, and more effective use of plant resistance as a management tactic. Therefore, the goals of this paper are to 1) review and update knowledge about temperature effects on plant resistance, 2) evaluate alternative experimental approaches for separating direct from plant-mediated indirect effects of temperature on pests, including benefits and limitations of each approach, and 3) offer recommendations for future research.

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