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Toxic stress syndrome

Guannan Chen, Juan Wei, Xin Lyu
The anti-oxidant stress of the body is mainly mediated by the transcription factor nuclear factor-erythroid 2 related factor 2 (Nrf2). Nrf2 can promote cell protective gene expression. Nrf2 plays an important role in regulating the oxidative stress, the metabolism of toxic substances, the inflammation, the apoptosis, and the physiological functions of cells. Multiple studies have shown that the activation of Nrf2 alleviates oxidative stress and inflammation, plays an important role in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and is expected to be potential targets for the prevention and treatment of ALI/ARDS...
March 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Zhen-Yu Yao, Wen-Bin Chen, Shan-Shan Shao, Shi-Zhan Ma, Chong-Bo Yang, Meng-Zhu Li, Jia-Jun Zhao, Ling Gao
Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells...
2018: Journal of Zhejiang University. Science. B
Ray Kreienkamp, Simona Graziano, Nuria Coll-Bonfill, Gonzalo Bedia-Diaz, Emily Cybulla, Alessandro Vindigni, Dale Dorsett, Nard Kubben, Luis Francisco Zirnberger Batista, Susana Gonzalo
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by a truncated lamin A protein (progerin) that drives cellular and organismal decline. HGPS patient-derived fibroblasts accumulate genomic instability, but its underlying mechanisms and contribution to disease remain poorly understood. Here, we show that progerin-induced replication stress (RS) drives genomic instability by eliciting replication fork (RF) stalling and nuclease-mediated degradation. Rampant RS is accompanied by upregulation of the cGAS/STING cytosolic DNA sensing pathway and activation of a robust STAT1-regulated interferon (IFN)-like response...
February 20, 2018: Cell Reports
Seyoung Lee, Dong Jun Park, Jihee Yoon, Seung Hyuck Bang, Yang-Hoon Kim, Jiho Min
Formaldehyde is a toxic compound due to its ability to react with proteins, nucleic acids and lipids and is the primary cause of nasopharyngeal cancer and sick building syndrome (SBS). Aldehyde dehydrogenases (ALDHs) are able to oxidize aldehyde substrates and maintain cellular homeostasis by metabolic reactions in prokaryotic and eukaryotic cells. ALDHs catalyze the conversions of various aldehydes to carboxylic acids using NAD or NADP as a cofactor. In this study, we designed a method for using aldehyde dehydrogenase 6 (ALD6) from recombinant Saccharomyces cerevisiae to reduce formaldehyde...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Yong Gang Tian, Jian Zhang
Prolonged exposure to hyperoxia results in acute lung injury (ALI). Pulmonary damage caused by oxygen toxicity occurs due to the generation of reactive oxygen species and subsequent formation of more potent oxidants. The present study demonstrated that sirtuin 3 (SIRT3) may attenuate hyperoxia‑induced ALI due to its potential antioxidative effect. In the present study, a hyperoxia‑induced acute lung injury mouse model, reverse transcription‑quantitative polymerase chain reaction, western blotting, retroviral mediated gene over‑expression and knockdown assays revealed that the expression of SIRT3 in the lung tissue of mice with hyperoxia‑induced ALI was decreased and overexpression of SIRT3 may significantly reduce hyperoxia‑induced ALI, as reflected by decreases in protein concentration, infiltrated neutrophils in bronchoalveolar lavage (BAL) fluid and wet/dry ratio of lung tissues...
January 22, 2018: Molecular Medicine Reports
Michael Hultström, Mediha Becirovic-Agic, Sofia Jönsson
Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and urine production caused by a number of different diseases. It is associated with renal tissue damage. This tissue damage can cause tubular atrophy and interstitial fibrosis that leads to nephron loss and progression of chronic kidney disease (CKD). This review describes the in-common mechanisms behind tissue damage in AKI caused by different underlying diseases. Comparing six high-quality microarray studies of renal gene expression after AKI in disease models (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant hypertension, rhabdomyolysis, and cisplatin toxicity) identified 5,254 differentially expressed genes in at least one of the AKI models; 66% of genes were found only in one model, showing that there are unique features to AKI depending on the underlying disease...
March 1, 2018: Physiological Genomics
F Haczeyni, K S Bell-Anderson, G C Farrell
Adipose tissue plays a significant role in whole body energy homeostasis. Obesity-associated diabetes, fatty liver and metabolic syndrome are closely linked to adipose stress and dysfunction. Genetic predisposition, overeating and physical inactivity influence the expansion of adipose tissues. Under conditions of constant energy surplus, adipocytes become hypertrophic and adipose tissues undergo hyperplasia so as to increase their lipid storage capacity, thereby keeping circulating blood glucose and fatty acids below toxic levels...
December 15, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Katelyn M Green, M Rebecca Glineburg, Michael G Kearse, Brittany N Flores, Alexander E Linsalata, Stephen J Fedak, Aaron C Goldstrohm, Sami J Barmada, Peter K Todd
Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G4 C2 repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome...
December 8, 2017: Nature Communications
Gaëlle Naert, Valentine Ferré, Emeline Keller, Amy Slender, Dorota Gibbins, Elizabeth Mc Fisher, Victor Lj Tybulewicz, Tangui Maurice
RATIONALE: The prevalence of Alzheimer's disease is increased in people with Down syndrome. The pathology appears much earlier than in the general population, suggesting a predisposition to develop Alzheimer's disease. Down syndrome results from trisomy of human chromosome 21, leading to overexpression of possible Alzheimer's disease candidate genes, such as amyloid precursor protein gene. To better understand how the Down syndrome context results in increased vulnerability to Alzheimer's disease, we analysed amyloid-β [25-35] peptide toxicity in the Tc1 mouse model of Down syndrome, in which ~75% of protein coding genes are functionally trisomic but, importantly, not amyloid precursor protein...
February 2018: Journal of Psychopharmacology
Alfonso Rubio-Navarro, Maria Dolores Sanchez-Niño, Melania Guerrero-Hue, Cristina García-Caballero, Eduardo Gutiérrez, Claudia Yuste, Ángel Sevillano, Manuel Praga, Javier Egea, Elena Román, Pablo Cannata, Rosa Ortega, Isabel Cortegano, Belén de Andrés, María Luisa Gaspar, Susana Cadenas, Alberto Ortiz, Jesús Egido, Juan Antonio Moreno
Recurrent and massive intravascular haemolysis induces proteinuria, glomerulosclerosis, and progressive impairment of renal function, suggesting podocyte injury. However, the effects of haemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway, and altered podocyte morphology, with decreased expression of the slit diaphragm proteins nephrin and synaptopodin...
March 2018: Journal of Pathology
Eitan Fibach, Eliezer A Rachmilewitz
While most common symptom of impairment of iron homeostasis is iron deficiency anemia, some hematological disorders are associated with iron overload (IO). These disorders are related mainly to chronic severe hemolytic anemia, where red blood cells (RBC) or their precursors are destroyed prematurely (hemolyzed), leading to anemia that cannot be compensated by increased production of new RBC. In such cases, IO is mainly due to repeated RBC transfusions and/or increased uptake of iron in the gastrointestinal tract...
December 2017: La Presse Médicale
Atsuko Miyagi, Sayaka Kitano, Yutaka Oono, Yoshihiro Hase, Issay Narumi, Masatoshi Yamaguchi, Hirofumi Uchimiya, Maki Kawai-Yamada
Some Rumex species such as sorrel are edible as baby leaf salad greens. On the other hand, Rumex plants accumulate soluble oxalate, a toxic metabolite which causes serious diseases such as renal syndrome. We attempted to produce low-oxalate plants of R. obtusifolius, a perennial weed which has higher vitamin C and amino acid content and higher tolerance to stress than many other Rumex species. Ion beams are ionising radiation with high linear energy transfer that causes a wide spectrum of mutations. Thus, in the present study we evaluated the effects of ion beams on oxalate and other primary metabolites in leaves of R...
January 2018: Plant Physiology and Biochemistry: PPB
Aristidis S Charonis, Marek Michalak, Jody Groenendyk, Luis B Agellon
Starting from 1994, every 2 years, an international workshop is organized focused on calreticulin and other endoplasmic reticulum chaperones. In 2017, the workshop took place at Delphi Greece. Participants from North and South America, Europe, Asia and Australia presented their recent data and discussed them extensively with their colleagues. Presentations dealt with structural aspects of calreticulin and calnexin, the role of Ca2+ in cellular signalling and in autophagy, the endoplasmic reticulum stress and the unfolded protein response, the role of calreticulin in immune responses...
December 2017: Journal of Cellular and Molecular Medicine
Donna L Mendrick, Anna Mae Diehl, Lisa S Topor, Rodney R Dietert, Yvonne Will, Michele A La Merrill, Sebastien Bouret, Vijayalaskshmi Varma, Kenneth L Hastings, Thaddeus T Schug, Susan G Emeigh Hart, Florence G Burleson
Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting was convened to raise awareness of metabolic syndrome and its associated diseases and serve as a melting pot with scientists of multiple disciplines (e.g., toxicologists, clinicians, regulators) so as to spur research and understanding of this condition. The criteria for metabolic syndrome include obesity, dyslipidemia (low HDL and/or elevated triglycerides), elevated blood pressure, and alterations in glucose metabolism...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Achintya Mitra, Tapas Kumar Sur, Sachhidananda Upadhyay, Dipankar Bhattacharyya, Jayram Hazra
BACKGROUND: Swarna Jibanti scientifically known as Coelogyne cristata Lindley (Orchidaceae), an orchid mentioned in Ayurvedic medicine is used to promote healthy life span. OBJECTIVE: The present work was planned to study the efficacy of hydro-alcoholic extract of pseudobulbs of C.cristata (CCE) to assess its role on chronic fatigue syndrome (CFS) induced behavioural and biochemical changes in aged Wistar rats compared to Panax ginseng (PG), a prototype anti-stress agent...
November 1, 2017: Journal of Ayurveda and Integrative Medicine
Chong Li, Jennifer M Brazill, Sha Liu, Christofer Bello, Yi Zhu, Marie Morimoto, Lauren Cascio, Rini Pauly, Zoraida Diaz-Perez, May Christine V Malicdan, Hongbo Wang, Luigi Boccuto, Charles E Schwartz, William A Gahl, Cornelius F Boerkoel, R Grace Zhai
Polyamines are tightly regulated polycations that are essential for life. Loss-of-function mutations in spermine synthase (SMS), a polyamine biosynthesis enzyme, cause Snyder-Robinson syndrome (SRS), an X-linked intellectual disability syndrome; however, little is known about the neuropathogenesis of the disease. Here we show that loss of dSms in Drosophila recapitulates the pathological polyamine imbalance of SRS and causes survival defects and synaptic degeneration. SMS deficiency leads to excessive spermidine catabolism, which generates toxic metabolites that cause lysosomal defects and oxidative stress...
November 2, 2017: Nature Communications
Juliane Gust, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, David Myerson, Luis F Gonzalez-Cuyar, Cecilia Yeung, W Conrad Liles, Mark Wurfel, Jose A Lopez, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Tahsin Özpolat, Kathleen R Fink, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability...
December 2017: Cancer Discovery
Isa Dietrich, Gustavo Arruda Braga, Fernanda Gomes de Melo, Ana Carolina Calmon da Costa Silva Silva
PURPOSE OF REVIEW: This article reviewed very recent papers (2016) discussing or bringing clinical evidences of the possible common pathways leading to diabetic foot syndrome (DFS) and increased mortality rates. RECENT FINDINGS: Diabetic patients with diabetic foot syndrome have a mortality rate greater than twofold when compared with non-ulcerated diabetics. In addition, the 5-year mortality rate following amputation is estimated at 39-68%, a life expectancy comparable to aggressive types of cancer or advanced congestive heart failure...
October 2, 2017: Current Atherosclerosis Reports
Gregory Hall, Shinichiro Kurosawa, Deborah J Stearns-Kurosawa
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells...
September 19, 2017: Toxins
Shams Y-Hassan, Per Tornvall
Takotsubo syndrome is a recently recognized acute cardiac disease entity with a clinical presentation resembling that of an acute coronary syndrome. The typical takotsubo syndrome patient has a unique circumferential left (bi-) ventricular contraction abnormality profile that extends beyond a coronary artery supply territory and appears to follow the anatomical cardiac sympathetic innervation. The syndrome predominantly affects postmenopausal women and is often preceded by emotional or physical stress. Patients with predisposing factors such as malignancy and other chronic comorbidities are more prone to suffer from takotsubo syndrome...
February 2018: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
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