4) Novel Insight into Obesity Disease-Development of Treatment Employing the Modulation of Intracellular Stress Response Pathways

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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NMR and LC-MS-Based Metabolomics to Study Osmotic Stress in Lignan-Deficient Flax

Molecules ◽

10.3390/molecules26030767 ◽

2021 ◽

Vol 26 (3) ◽

pp. 767

Author(s):

Kamar Hamade ◽

Ophélie Fliniaux ◽

Jean-Xavier Fontaine ◽

Roland Molinié ◽

Elvis Otogo Nnang ◽

...

Keyword(s):

Stress Response ◽

Osmotic Stress ◽

Biosynthetic Pathway ◽

Potential Role ◽

Plant Secondary Metabolites ◽

Wild Type ◽

Osmotic Stress Response ◽

Transgenic Flax ◽

Insight Into

Lignans, phenolic plant secondary metabolites, are derived from the phenylpropanoid biosynthetic pathway. Although, being investigated for their health benefits in terms of antioxidant, antitumor, anti-inflammatory and antiviral properties, the role of these molecules in plants remains incompletely elucidated; a potential role in stress response mechanisms has been, however, proposed. In this study, a non-targeted metabolomic analysis of the roots, stems, and leaves of wild-type and PLR1-RNAi transgenic flax, devoid of (+) secoisolariciresinol diglucoside ((+) SDG)—the main flaxseed lignan, was performed using 1H-NMR and LC-MS, in order to obtain further insight into the involvement of lignan in the response of plant to osmotic stress. Results showed that wild-type and lignan-deficient flax plants have different metabolic responses after being exposed to osmotic stress conditions, but they both showed the capacity to induce an adaptive response to osmotic stress. These findings suggest the indirect involvement of lignans in osmotic stress response.

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Individuals at risk for developing rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

10.1101/2021.02.03.429590 ◽

2021 ◽

Author(s):

Mihnea R. Mangalea ◽

David Paez-Espino ◽

Kristopher Kieft ◽

Anushila Chatterjee ◽

Jennifer A. Seifert ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

At Risk ◽

Autoimmune Disease ◽

Intestinal Microbiota ◽

Disease Development ◽

Metabolic Potential ◽

Metabolic Genes ◽

Auxiliary Metabolic Genes ◽

Citrullinated Protein ◽

Insight Into

SUMMARYRheumatoid arthritis (RA) is an autoimmune disease characterized in seropositive individuals by the presence of anti-cyclic citrullinated protein (CCP) antibodies. RA is linked to the intestinal microbiota, yet the association of microbes with CCP serology and their contribution to RA is unclear. We describe intestinal phage communities of individuals at risk for developing RA, with or without anti-CCP antibodies, whose first degree relatives have been diagnosed with RA. We show that at-risk individuals harbor intestinal phage compositions that diverge based on CCP serology, are dominated by Lachnospiraceae phages, and originate from disparate ecosystems. These phages encode unique repertoires of auxiliary metabolic genes (AMGs) which associate with anti-CCP status, suggesting that these phages directly influence the metabolic and immunomodulatory capability of the microbiota. This work sets the stage for the use of phages as preclinical biomarkers and provides insight into a possible microbial-based causation of RA disease development.

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Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia

eLife ◽

10.7554/elife.37673 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 24

Author(s):

Cheng Wang ◽

Zhijia Tan ◽

Ben Niu ◽

Kwok Yeung Tsang ◽

Andrew Tai ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Stress Response ◽

Cell Fate ◽

Therapeutic Strategy ◽

Chondrocyte Differentiation ◽

Integrated Stress Response ◽

Stress Response Pathway ◽

Skeletal Disorders ◽

The Impact ◽

Insight Into

The integrated stress response (ISR) is activated by diverse forms of cellular stress, including endoplasmic reticulum (ER) stress, and is associated with diseases. However, the molecular mechanism(s) whereby the ISR impacts on differentiation is incompletely understood. Here, we exploited a mouse model of Metaphyseal Chondrodysplasia type Schmid (MCDS) to provide insight into the impact of the ISR on cell fate. We show the protein kinase RNA-like ER kinase (PERK) pathway that mediates preferential synthesis of ATF4 and CHOP, dominates in causing dysplasia by reverting chondrocyte differentiation via ATF4-directed transactivation of Sox9. Chondrocyte survival is enabled, cell autonomously, by CHOP and dual CHOP-ATF4 transactivation of Fgf21. Treatment of mutant mice with a chemical inhibitor of PERK signaling prevents the differentiation defects and ameliorates chondrodysplasia. By preventing aberrant differentiation, titrated inhibition of the ISR emerges as a rationale therapeutic strategy for stress-induced skeletal disorders.

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Identification and Characterization of the Heat-Induced Plastidial Stress Granules Reveal New Insight Into Arabidopsis Stress Response

Frontiers in Plant Science ◽

10.3389/fpls.2020.595792 ◽

2020 ◽

Vol 11 ◽

Author(s):

Monika Chodasiewicz ◽

Ewelina Maria Sokolowska ◽

Anna C. Nelson-Dittrich ◽

Aleksandra Masiuk ◽

Juan Camilo Moreno Beltran ◽

...

Keyword(s):

Stress Response ◽

Stress Granules ◽

Identification And Characterization ◽

Insight Into

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A new insight into the role of intracellular nickel levels for the stress response, surface properties and twitching motility by Haemophilus influenzae

Metallomics ◽

10.1039/c4mt00245h ◽

2015 ◽

Vol 7 (4) ◽

pp. 650-661 ◽

Cited By ~ 1

Author(s):

Alexandra Tikhomirova ◽

Donald Jiang ◽

Stephen P. Kidd

Keyword(s):

Stress Response ◽

Haemophilus Influenzae ◽

Response Surface ◽

Surface Properties ◽

Twitching Motility ◽

Insight Into

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MP034CLARIFY THE INTRACELLULAR STRESS RESPONSE IN EARLY-STAGE ALPORT SYNDROME AND ESTABLISH AN EVALUATION SYSTEM FOR INTRACELLULAR REGULATION OF COL4A5

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfw182.04 ◽

2016 ◽

Vol 31 (suppl_1) ◽

pp. i354-i354

Author(s):

Kohei Omachi ◽

Misato Kamura ◽

Keisuke Teramoto ◽

Haruka Kojima ◽

Mary Ann Suico ◽

...

Keyword(s):

Stress Response ◽

Evaluation System ◽

Alport Syndrome ◽

Early Stage ◽

Intracellular Regulation ◽

Intracellular Stress Response

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Ceramides as Key Players in Cellular Stress Response

Physiology ◽

10.1152/physiologyonline.2000.15.1.11 ◽

2000 ◽

Vol 15 (1) ◽

pp. 11-15 ◽

Cited By ~ 1

Author(s):

Josef Pfeilschifter ◽

Andrea Huwiler

Keyword(s):

Stress Response ◽

Cell Growth ◽

Second Messengers ◽

Cellular Stress Response ◽

Therapeutic Approaches ◽

Cell Responses ◽

Key Players ◽

Sense And Respond ◽

Insight Into ◽

Novel Therapeutic

The recent discovery of sphingolipid-derived second messengers that regulate fundamental cell responses such as cell growth and apoptosis has provided insight into the way cells sense and respond to stressful stimuli. This will help the understanding of the pathogenesis of stress-related diseases and eventually offer novel therapeutic approaches.

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