The adipokine sFRP4 induces insulin resistance and lipogenesis in the liver
Publication date: Available online 20 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tina Hörbelt, Birgit Knebel, Pia Fahlbusch, David Barbosa, Daniella Herzfeld de Wiza, Frederique Van de Velde, Yves Van Nieuwenhove, Bruno Lapauw, G. Hege Thoresen, Hadi Al-Hasani, Dirk Müller-Wieland, D. Margriet Ouwens, Jorg KotzkaAbstractSecreted frizzled-related protein (sFRP) 4 is an adipokine with increased expression in white adipose tissue from obese subjects with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Yet, it is unknown whether sFRP4 action contributes ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 21, 2019 Category: Molecular Biology Source Type: research

Global glycosphingolipid analysis in urine and plasma of female Fabry disease patients
Publication date: Available online 15 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Wendy Heywood, Ivan Doykov, Justyna Spiewak, Jenny Hallqvist, Kevin Mills, Albina NowakAbstractFabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase-A, which results in accumulation of the glycosphingolipid (GSL) globotriaosylceramide (Gb3). Gb3 and globotriaosylsphingosine (lyso-Gb3) levels in plasma and urine are used routinely for diagnosis and treatment monitoring. FD female patients are problematic to diagnose and to predict when to begin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 16, 2019 Category: Molecular Biology Source Type: research

Critical role of the endogenous renin-angiotensin system in maintaining self-renewal and regeneration potential of epidermal stem cells
Publication date: Available online 16 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xuan Liao, Jing Xiao, Sheng-Hong Li, Li-Ling Xiao, Biao Cheng, Xiao-Bing Fu, Taixing Cui, Hong-Wei LiuAbstractA tightly controlled activity of renin-angiotensin system (RAS) including renin, angiotensin-converting enzymes (ACEs), and angiotensin II (Ang II) receptors is critical not only for maintaining systemic hemodynamics and blood volume but also for controlling cell proliferation, differentiation, and tissue remodeling in target organs. ACE inhibitors or Ang II receptor type 1 (AT1R) blocke...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 16, 2019 Category: Molecular Biology Source Type: research

The molecular tweezer CLR01 reduces aggregated, pathologic, and seeding-competent α-synuclein in experimental multiple system atrophy
Publication date: Available online 16 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marcos Herrera-Vaquero, Danielle Bouquio, Martin Kallab, Karl Biggs, Gayatri Nair, Jessica Ochoa, Antonio Heras-Garvin, Christian Heid, Inesa Hadrovic, Werner Poewe, Gregor K. Wenning, Frank-Gerrit Klärner, Thomas Schrader, Gal Bitan, Nadia StefanovaAbstractMultiple system atrophy (MSA) is a fatal, adult-onset neurodegenerative disorder that has no cure and very limited treatment options. MSA is characterized by deposition of fibrillar α-synuclein (α-syn) in glial cytoplasmic in...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 16, 2019 Category: Molecular Biology Source Type: research

The good side of inflammation: Staphylococcus aureus proteins SpA and Sbi contribute to proper abscess formation and wound healing during skin and soft tissue infections
Publication date: Available online 9 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cintia D. Gonzalez, Camila Ledo, Eliana Cela, Inés Stella, Chunliang Xu, Diego S. Ojeda, Paul S. Frenette, Marisa I. GómezAbstractStaphylococcus aureus is the most prominent cause of skin and soft tissue infections (SSTI) worldwide. Mortality associated with invasive SSTI is a major threat to public health considering the incidence of antibiotic resistant isolates in particular methicillin resistant S. aureus both in the hospital (HA-MRSA) and in the community (CA-MRSA). To overcome...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 10, 2019 Category: Molecular Biology Source Type: research

Cardiomyocyte targeted overexpression of IGF1 during detraining restores compromised cardiac condition via mTORC2 mediated switching of PKCδ to PKCα
In conclusion, this is the first report to unravel the intricate molecular mechanism of switching a physiologically hypertrophied heart to a pathologically hypertrophied heart during exercise withdrawal. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 10, 2019 Category: Molecular Biology Source Type: research

Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1
The objective of this study is to investigate whether ethanol exposure can induce apoptosis in NCCs by inhibiting epithelial-mesenchymal transition (EMT) and whether SFN can prevent ethanol-induced apoptosis by epigenetically modulating the expression of Snail1, a key transcriptional factor that promotes EMT. We found that ethanol exposure resulted in a significant increase in apoptosis in NCCs. Co-treatment with SFN significantly reduced ethanol-induced apoptosis. Treatment with SFN also dramatically diminished ethanol-induced changes in the expression of E-cadherin and vimentin, and restored EMT in ethanol-exposed NCCs. ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 8, 2019 Category: Molecular Biology Source Type: research

The regulation of NDRG2 expression during ATLL development after HTLV-1 infection
Publication date: Available online 8 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tomonaga Ichikawa, Shingo Nakahata, Masahiro Fujii, Hidekatsu Iha, Kazuya Shimoda, Kazuhiro MorishitaAbstractN-myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor that is frequently downregulated in adult T-cell leukemia/lymphoma (ATLL) and functions to negatively regulate several cellular signaling pathways as PP2A recruiter. To clarify the molecular mechanisms of suppression of NDRG2 expression, we initially determined the expression pattern of NDRG2 in various types of T-ce...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 8, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 9Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 6, 2019 Category: Molecular Biology Source Type: research

Neural regeneration therapies for Alzheimer's and Parkinson's disease-related disorders
Publication date: Available online 2 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Arubala P. Reddy, Janani Ravichandran, Nurgul Carcaci-SalliAbstractNeurodegenerative diseases are devastating mental illnesses without a cure. Alzheimer's disease (AD) characterized by memory loss, multiple cognitive impairments, and changes in personality and behavior. Although tremendous progress has made in understanding the basic biology in disease processes in AD and PD, we still do not have early detectable biomarkers for these diseases. Just in the United States alone, federal and nonfeder...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 3, 2019 Category: Molecular Biology Source Type: research

Exacerbated intestinal inflammation in P2Y6 deficient mice is associated with Th17 activation
Publication date: Available online 2 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mabrouka Salem, Mohammed Amine el-Azreq, Julie Pelletier, Bernard Robaye, Fawzi Aoudjit, Sévigny JeanAbstractExtracellular nucleotides are released as constitutive danger signals by various cell types and activate nucleotide (P2) receptors such as P2Y6 receptor. P2Y6 activation on monocytes induces the secretion of the chemokine CXCL8 which may propagate intestinal inflammation. Also, P2Y6 expression is increased in infiltrating T cells of Crohn's disease patients. As inflammatory bowel di...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 3, 2019 Category: Molecular Biology Source Type: research

Peli1 induction impairs cardiac microvascular endothelium through Hsp90 dissociation from IRE1α
This study aims to investigate whether Peli1 in endothelial cells promotes diabetes-induced cardiac microvascular injury through activating IRE1α. Here we found that Peli1 was markedly up-regulated in cardiac endothelial cells of both diabetic mice and in AGEs-treated cardiac microvascular endothelial cells (CMECs). Peli1 deficiency in endothelial cells significantly alleviated diabetes-induced cardiac microvascular permeability, promoted microvascular regeneration, and suppressed apoptosis, accompanied by the attenuation of adverse cardiac remodeling. Furthermore, Peli1 deletion in CMECs ameliorated AGEs-induced dam...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 29, 2019 Category: Molecular Biology Source Type: research

Oleic acid increases the transcriptional activity of FoxO1 by promoting its nuclear translocation and β-catenin binding in pancreatic β-cells
Publication date: Available online 27 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Magdalena Jazurek-Ciesiolka, Justyna Janikiewicz, Pawel Dobrzyn, Anna Dziewulska, Kamil Kozinski, Agnieszka DobrzynAbstractIn the setting of metabolic overload, chronic elevations of free fatty acids in blood and tissues are associated with pancreatic β-cell lipotoxicity and failure. Ultimately, obesity combined with insulin resistance increases the dysfunctional demand of β-cells and contributes to the development of type 2 diabetes. Forkhead box O1 (FoxO1) is a potent transcriptional...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 28, 2019 Category: Molecular Biology Source Type: research

Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP
Publication date: Available online 26 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Wang Peilin, Teng Songsong, Zhuang Chengyu, Cui Zhi, Ma Chunhui, Yu Yinxian, Zhou Lei, Mao Min, Wang Zongyi, Yang Mengkai, Xu Jing, Zhang Tao, Wang Zhuoying, Yin Fei, Yi ChengqingAbstractAging drives the accumulation of senescent cells (SnCs) by secreting factors that cause the senescence-associated secretory phenotype (SASP), including stem cells in the bone marrow, which contribute to aging-related bone degradation. Osteoarthritis (OA) is a serious chronic injury disease, and increasing age is...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 27, 2019 Category: Molecular Biology Source Type: research

FMO3 and its metabolite TMAO contribute to the formation of gallstones
In this study, we found that high plasma TMAO levels were positively associated with the presence of gallstone disease in humans. We further found increased hepatic FMO3 expression and elevated plasma TMAO level in a gallstone-susceptible strain of mice C57BL/6 J fed a lithogenic diet (LD), but not in a gallstone-resistant strain of mice AKR/J. Dietary supplementation of TMAO or its precursor choline increased hepatic FMO3 expression and plasma TMAO levels and induced hepatic canalicular cholesterol transporters ATP binding cassette (Abc) g5 and g8 expression in mice. Up-regulation of ABCG5 and ABCG8 expression was obser...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 27, 2019 Category: Molecular Biology Source Type: research

Dihomo-γ-linolenic acid inhibits several key cellular processes associated with atherosclerosis
This study provides novel insights into the molecular mechanisms underlying the anti-atherogenic actions of DGLA and supports further assessments on its protective effects on plaque regression in vivo and in human trials. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 22, 2019 Category: Molecular Biology Source Type: research

BRG1 regulates endothelial-derived IL-33 to promote ischemia-reperfusion induced renal injury and fibrosis in mice
In conclusion, we propose that BRG1 may contribute to ischemia-reperfusion induced renal injury and fibrosis by promoting IL-33 transcription in endothelial cells. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 20, 2019 Category: Molecular Biology Source Type: research

De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia
Publication date: Available online 20 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Luis A. Cea, Elisa Balboa, Aníbal A. Vargas, Carlos Puebla, María C. Brañes, Rosalba Escamilla, Tomás Regueira, Juan C. SáezAbstractEndotoxemia caused by bacterial lipopolysaccharides (LPSs) leads to severe skeletal muscular deterioration, starting with higher membrane permeability and decline in resting membrane potential (RMP). However, the molecular mechanism of such changes remains unclear. Here, we evaluated the possible involvement of connexin43- and conn...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 20, 2019 Category: Molecular Biology Source Type: research

Applying modern Omic technologies to the Neuronal Ceroid Lipofuscinoses
Publication date: Available online 15 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Rachel A. Kline, Thomas M. Wishart, Kevin Mills, Wendy E. HeywoodAbstractThe Neuronal Ceroid Lipofuscinoses are a group of severe and progressive neurodegenerative disorders, which generally present during childhood. With new treatments emerging on the horizon, there is a growing need to understand the specific disease mechanisms as well as identify prospective biomarkers for use to stratify patients and monitor treatment. The use of Omics technologies to NCLs has the potential to address this n...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 15, 2019 Category: Molecular Biology Source Type: research

Liver disease predominates in a mouse model for mild human Zellweger spectrum disorder
We report a hypomorphic ZSD mouse model, which is homozygous for Pex1-c.2531G>A (p.G844D), the equivalent of the most common pathogenic variant found in ZSD, and which predominantly presents with liver disease. After introducing the PEX1-G844D allele by knock-in, we characterized homozygous PEX1-G844D mice for survival, biochemical parameters, including peroxisomal and mitochondrial functions, organ histology, and developmental parameters. The first 20 post-natal days (P20) were critical for survival of homozygous PEX1-G844D mice (~20% survival rate). Lethality was likely due to a combination of cholestatic liver proble...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 15, 2019 Category: Molecular Biology Source Type: research

EGR1 promotes the cartilage degeneration and hypertrophy by activating the Krüppel-like factor 5 and β-catenin signaling
In this study,we observed abnormally high EGR1 expression in the articular cartilage of patients with osteoarthritis. We also found significantly high EGR1 expression in the articular cartilage of mice with destabilized medial meniscus (DMM)-induced osteoarthritis and 20-month-old mice. In vitro experiments indicated that IL-1β could significantly enhance EGR1 expression in primary mouse chondrocytes. EGR1 over-expression in chondrocytes using adenovirus could inhibit COl2A1 expression and enhance MMP9 and MMP13 expression. And silencing EGR1, using RNAi, had the opposite effects. Moreover, EGR1 over-expression acce...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 13, 2019 Category: Molecular Biology Source Type: research

Dihimo-γ-linolenic acid inhibits several key cellular processes associated with atherosclerosis
This study provides novel insights into the molecular mechanisms underlying the anti-atherogenic actions of DGLA and supports further assessments on its protective effects on plaque regression in vivo and in human trials. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 13, 2019 Category: Molecular Biology Source Type: research

Stem cell therapy in heart failure: Where do we stand today?
This article is part of a Special Issue entitled: Stem Cells and Their Applications to Human Diseases edited by Hemachandra Reddy. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 11, 2019 Category: Molecular Biology Source Type: research

Human steroid sulfatase enhances aerobic glycolysis through induction of HIF1α and glycolytic enzymes
In conclusion, we suggest that STS may induce aerobic glycolysis through enhancing HIF1α expression. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 11, 2019 Category: Molecular Biology Source Type: research

Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis
ConclusionNR attenuated HSC activation, leading to reduced liver fibrosis in a diet-induced mouse model of liver fibrosis. The data suggest that NR may be developed as a potential preventative for human liver fibrosis. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 11, 2019 Category: Molecular Biology Source Type: research

Protein arginine methyltranferase-1 induces ER stress and epithelial-mesenchymal transition in renal tubular epithelial cells and contributes to diabetic nephropathy
ConclusionsBy activating ER stress, PRMT1 essentially regulates the apoptosis and EMT of PTECs in response to diabetic milieu. Thus, targeting PRMT1 may alleviate both tissue injury and renal fibrosis, and thus benefit the treatment of DN. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 11, 2019 Category: Molecular Biology Source Type: research

Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury
Publication date: Available online 11 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Coral García-Pastor, Rafael Blázquez-Serra, Ricardo J. Bosch, Francisco J. Lucio Cazaña, Ana B. Fernández-MartínezAbstractThe therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX-2)/int...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 11, 2019 Category: Molecular Biology Source Type: research

The metastasis suppressor, NDRG1, differentially modulates the endoplasmic reticulum stress response
Publication date: Available online 11 April 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): A.M. Merlot, G.M. Porter, S. Sahni, E.G. Lim, P. Peres, D.R. RichardsonAbstractThe metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), is a stress response protein that is involved in the inhibition of multiple oncogenic signaling pathways. Initial studies have linked NDRG1 and the endoplasmic reticulum (ER) stress response. Considering this, we extensively examined the mechanism by which NDRG1 regulates the ER stress response in pancreatic and colon cancer cells. We also examined...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 10, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 8Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 10, 2019 Category: Molecular Biology Source Type: research

Novel MicroRNA-455-3p and its protective effects against abnormal APP processing and amyloid beta toxicity in Alzheimer's disease
Publication date: Available online 8 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Subodh Kumar, Arubala P. Reddy, Xiangling Yin, P. Hemachandra ReddyAbstractThe purpose of our study is to understand the protective role of miR-455-3p against abnormal amyloid precursor protein (APP) processing, amyloid beta (Aβ) formation, defective mitochondrial biogenesis/dynamics and synaptic damage in AD progression. In-silico analysis of miR-455-3p has identified the APP gene as a putative target. Using mutant APP cells, miR-455-3p construct, biochemical and molecular assays, immunoflu...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 8, 2019 Category: Molecular Biology Source Type: research

l-Carnitine prevents oxidative stress in striatum of glutaryl-CoA dehydrogenase deficient mice submitted to lysine overload
In this study, we evaluated L-car and glutarylcarnitine levels, the lipid and protein damage, reactive oxygen species (ROS) production and antioxidant enzymes activities in striatum of Gcdh−/− and wild-type (WT) mice. We also determined the effect of the L-car treatment on these parameters. Thirty-day-old Gcdh−/− and WT mice were fed a normal chow (0.9% Lys) or submitted to a high Lys diet (4.7%) for 72 h. Additionally, these animals were administered with three intraperitoneal injections of saline or L-car in different times. Gcdh−/− mice were deficient in L-car and presented a higher...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 8, 2019 Category: Molecular Biology Source Type: research

Human placental GLUT1 glucose transporter expression and the fetal insulin-like growth factor axis in pregnancies complicated by diabetes
In this report we asked whether changes in GLUT1 expression and glucose transport activity in diabetic pregnancies were associated with alterations in the fetal IGF axis. Cord blood samples and paired syncytial microvillous and basal membranes were isolated from normal term pregnancies and pregnancies characterized by gestational diabetes type A2 (GDM A2) and pre-existing insulin-dependent diabetes mellitus (IDDM). Circulating IGF-I, basal membrane GLUT1 expression and glucose transporter activity were correlated with birth weight, but only in control, not diabetic groups. Basal membrane GLUT1 and transporter activity were...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 6, 2019 Category: Molecular Biology Source Type: research

The Smad3-miR-29b/miR-29c axis mediates the protective effect of macrophage migration inhibitory factor against cardiac fibrosis
Publication date: Available online 6 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jing-nan Liang, Xiao Zou, Xian-hong Fang, Jin-dong Xu, Zhen Xiao, Jie-ning Zhu, Hui Li, Jing Yang, Ni Zeng, Shu-jing Yuan, Rong Pan, Yong-heng Fu, Ming Zhang, Jian-fang Luo, Sheng Wang, Zhi-xin ShanAbstractAlthough macrophage migration inhibitory factor (MIF) is known to have antioxidant property, the role of MIF in cardiac fibrosis has not been well understood. We found that MIF was markedly increased in angiotension II (Ang-II)-infused mouse myocardium. Myocardial function was impaired and card...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 6, 2019 Category: Molecular Biology Source Type: research

5-Lipoxagenase deficiency attenuates L-NAME-induced hypertension and vascular remodeling
ConclusionL-NAME may activate the 5-LO/LT pathway in immune cells, such as neutrophils, and promote the products of 5-LO metabolites, including LTB4 and CysLTs, which aggravate vascular remodeling in hypertension. 5-LO deficiency may protect against hypertension and vascular remodeling by reducing levels of 5-LO downstream inflammatory metabolites.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 3, 2019 Category: Molecular Biology Source Type: research

LncRNA GAS5 regulates vascular smooth muscle cell cycle arrest and apoptosis via p53 pathway
Publication date: Available online 2 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Rui Tang, Xiaohan Mei, Yung-Chun Wang, Xiao-Bing Cui, Gui Zhang, Wenjing Li, Shi-You ChenAbstractVascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 2, 2019 Category: Molecular Biology Source Type: research

CD74 knockout attenuates alcohol intake-induced cardiac dysfunction through AMPK-Skp2-mediated regulation of autophagy
This study examined the potential role of CD74 in binge drinking-induced cardiac contractile dysfunction. WT and CD74 knockout mice were exposed to ethanol (3 g/kg/d, i.p., for 3 days). Echocardiography, cardiomyocyte function, histological staining and autophagy signaling including AMPK, mTOR, and AMPK downstream signals Skp2 and Sirt1 were evaluated. Our results revealed that ethanol challenge overtly compromised echocardiographic, cardiomyocyte contractile, intracellular Ca2+ and ultrastructural properties along with overt apoptosis, inflammation (elevated MIF, IL-1β and IL-6) and mitochondrial O2– production (p 
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - June 2, 2019 Category: Molecular Biology Source Type: research

Argonaute-2 is associated to brown adipose tissue activation
Publication date: Available online 30 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Estelle Roger, Olivier Dumortier, Didier F. Pisani, Nadine Gautier, Emmanuel Van Obberghen, Charlotte HinaultAbstractMicroRNAs (miRNAs) are important modulators of thermogenic brown adipose tissue (BAT). They have been involved in its differentiation and hence its functioning. While different regulators of the miRNA machinery have been shown to be essential for BAT differentiation, little is known about their implication in BAT activation. The aim of this work was to evaluate the role of AGO2, th...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 30, 2019 Category: Molecular Biology Source Type: research

Impact of hyperinsulinemia and hyperglycemia on valvular interstitial cells – A link between aortic heart valve degeneration and type 2 diabetes
Publication date: Available online 30 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jessica I. Selig, D. Margriet Ouwens, Silja Raschke, G. Hege Thoresen, Jens W. Fischer, Artur Lichtenberg, Payam Akhyari, Mareike BarthAbstractType 2 diabetes is a known risk factor for cardiovascular diseases and is associated with an increased risk to develop aortic heart valve degeneration. Nevertheless, molecular mechanisms leading to the pathogenesis of valve degeneration in the context of diabetes are still not clear. Hence, we hypothesized that classical key factors of type 2 diabetes, hyp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 30, 2019 Category: Molecular Biology Source Type: research

Altered maternal metabolism during mild gestational hyperglycemia as a predictor of adverse perinatal outcomes: A comprehensive analysis
This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnorm...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 30, 2019 Category: Molecular Biology Source Type: research

16- Overview of advances in educational and social supports for young persons with NCL disorders
Publication date: Available online 30 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Bengt Elmerskog, Anne-Grethe Tøssebro, Rebecca Atkinson, Svein Rokne, Barbara Cole, Adam Ockelford, Heather R. AdamsAbstractVision loss, dementia, and motor and speech declines all impact the educational experience of individuals with Batten disease and can adversely impact effective learning. There are as yet limited data to support evidence-based approaches to meeting the educational needs of affected individuals. This paper provides an overview of recent work to evaluate and address edu...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 30, 2019 Category: Molecular Biology Source Type: research

Mutations of GADD45G in rabbits cause cleft lip by the disorder of proliferation, apoptosis and epithelial-mesenchymal transition (EMT)
Publication date: Available online 29 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Yi Lu, Mingming Liang, Quanjun Zhang, Zhiquan Liu, Yuning Song, Liangxue Lai, Zhanjun LiAbstractThe cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects in humans. Genome-wide association studies (GWAS) have been widely used for identifying candidate genes, and different genes or chromosomal regions have shown strong evidence for the presence of causal genes in CL/P. To date, two independent GWAS have identified GADD45G as influencing risk for CL/P. However, ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 30, 2019 Category: Molecular Biology Source Type: research

Impaired renal organic anion transport 1 (SLC22A6) and its regulation following acute myocardial infarction and reperfusion injury in rats
This study examined and identified the effect of AMI-induced AKI on organic anion transporter 1 (Oat1) and Oat3 transport using clinical setting of pre-renal AKI in vivo. Cardiac ischaemia (CI) and cardiac ischaemia and reperfusion (CIR) were induced in rats by 30-min left anterior descending coronary artery occlusion and 30-min occlusion followed by 120-min reperfusion, respectively. Renal hemodynamic parameters, mitochondrial function and Oat1/Oat3 expression and function were determined along with biochemical markers. Results showed that CI markedly reduced renal blood flow and pressure by approximately 40%, while these...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 22, 2019 Category: Molecular Biology Source Type: research

IDH2 deficiency exacerbates acetaminophen hepatotoxicity in mice via mitochondrial dysfunction-induced apoptosis
In conclusion, IDH2 deficiency leads to a fundamental shortage of GSH that increases susceptibility to ROS generation and oxidative stress. This leads to excessive mitochondrial dysfunction and ER stress induction in response to APAP administration. Our study provides further evidence that IDH2 has a protective role against APAP-induced liver injury and emphasizes the importance of the elaborate linkages and functions of the antioxidant system in liver health.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 21, 2019 Category: Molecular Biology Source Type: research

Warburg-like effect is a hallmark of complex I assembly defects
Publication date: Available online 20 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Valerie Desquiret-Dumas, Geraldine Leman, Celine Wetterwald, Stephanie Chupin, Anaïs Lebert, Salim Khiati, Morgane Le Mao, Guillaume Geffroy, Mariame Selma Kane, Arnaud Chevrollier, David Goudenege, Cedric Gadras, Lydie Tessier, Magalie Barth, Stephanie Leruez, Patrizia Amati-Bonneau, Daniel Henrion, Dominique Bonneau, Vincent Procaccio, Pascal ReynierAbstractDue to its pivotal role in NADH oxidation and ATP synthesis, mitochondrial complex I (CI) emerged as a crucial regulator of cellular m...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 21, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 7Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 18, 2019 Category: Molecular Biology Source Type: research

Post-translational modifications in brain health and disease
Publication date: Available online 15 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sónia C. Correia, Cristina Carvalho, Susana Cardoso, Paula I. Moreira (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 16, 2019 Category: Molecular Biology Source Type: research

Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin
In this study, we demonstrate that hemin-induced ferroptosis in platelets is mediated through ROS-driven proteasome activity and inflammasome activation, which were mitigated by Melatonin (MLT). Although inflammasome activation is linked with pyroptosis, it is still not clear whether ferroptosis is associated with inflammasome activation. Our study for the first time demonstrates an association of platelet activation/ferroptosis with proteasome activity and inflammasome activation. Although, high-throughput screening has recognized ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent ferroptosis inhibitors, having an...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 16, 2019 Category: Molecular Biology Source Type: research

Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation
Publication date: Available online 16 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Junyu Lai, Manqing Ge, Sikui Shen, Tao Jin, Kunjie Wang, Qiang Wei, Hong Li, Jianzhong AiAbstractChronic cystitis is characterized by the hyperplasia and fibrosis of the bladder wall as well as attenuated compliance of the bladder. To further unravel its underlying molecular mechanism, the role of NFκB-JMJD3 signaling pathway in cystitis induced bladder fibrosis was investigated. Jmjd3 and Col1/3 expression was detected in a cystitis mouse model that was developed by intraperitoneal injecti...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 16, 2019 Category: Molecular Biology Source Type: research

Activated NF-κB/Nrf2 and Wnt/β-catenin pathways are associated with lipid metabolism in CKD patients with microalbuminuria and macroalbuminuria
This study first demonstrates the association of plasma inflammation, oxidative stress, Wnt/β-catenin and lipid metabolism in CKD patients with microalbuminuria and macroalbuminuria.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 16, 2019 Category: Molecular Biology Source Type: research

Mitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury
Publication date: Available online 14 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mingjie Yang, Becky S. Linn, Yingmei Zhang, Jun RenAbstractIschemia-reperfusion injury (IR injury), produced by initial interruption and subsequent restoration of organ blood flow, is an important clinical dilemma accompanied by various cardiac reperfusion strategies following acute myocardial infarction (AMI). Although the restored blood flow is necessary for oxygen and nutrient supply, reperfusion often results in pathological sequelae leading to elevated ischemic damage. Among various theories...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - May 16, 2019 Category: Molecular Biology Source Type: research