Pharmacologic IL-6Rα inhibition in cholangiocarcinoma promotes cancer cell growth and survival
Publication date: Available online 9 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Florian Kleinegger, Eva Hofer, Christina Wodlej, Nicole Golob-Schwarzl, Anna Maria Birkl-Toeglhofer, Alexander Stallinger, Johannes Petzold, Anna Orlova, Stefanie Krassnig, Robert Reihs, Tobias Niedrist, Harald Mangge, Young Nyun Park, Michael Thalhammer, Ariane Aigelsreiter, Sigurd Lax, Christoph Garbers, Peter Fickert, Stefan Rose-John, Richard MorigglAbstractBiliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 11, 2018 Category: Molecular Biology Source Type: research

Acute pancreatic beta cell apoptosis by IL-1β is responsible for postburn hyperglycemia: Evidence from humans and mice
ConclusionsOur findings reveal a novel mechanism of acute hyperglycemia postburn in which impaired insulin secretory capacity mediated by IL-1β leads to acute hyperglycemia. These data suggest that targeting IL-1β to restore endogenous insulin secretory function may be a novel glycemic control strategy to improve outcomes for burn patients.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 11, 2018 Category: Molecular Biology Source Type: research

Cause or casualty: The role of mitochondrial DNA in aging and age-associated disease
Publication date: Available online 9 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): E. Sandra Chocron, Erin Munkácsy, Andrew M. PickeringAbstractThe mitochondrial genome (mtDNA) represents a tiny fraction of the whole genome, comprising just 16.6 kilobases encoding 37 genes involved in oxidative phosphorylation and the mitochondrial translation machinery. Despite its small size, much interest has developed in recent years regarding the role of mtDNA as a determinant of both aging and age-associated diseases. A number of studies have presented compelling evidence for...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 11, 2018 Category: Molecular Biology Source Type: research

Corrigendum to “A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration” [Biochim. Biophys. Acta 1863 (2017) 801–809]
Publication date: Available online 10 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Víctor López del Amo, Martina Palomino-Schätzlein, Marta Seco-Cervera, José Luis García-Giménez, Federico Vicente Pallardó, Antonio Pineda-Lucena, Máximo Ibo Galindo (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 11, 2018 Category: Molecular Biology Source Type: research

Treg cells depletion is a mechanism that drives microvascular dysfunction in mice with established hypertension
ConclusionsThe present study suggests that Treg cells survival is regulated by autophagy. Also, Treg cells as a cellular therapy aimed at rescuing the microvascular function through an autophagy-dependent mechanism and independently of arterial blood pressure lowering effects. Because our mouse model of established hypertension mimics the clinical situation, our results have the potential for new therapeutic approaches that involve the manipulation of Treg cells and autophagy to overcome established hypertension-induced cardiovascular complications. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 9, 2018 Category: Molecular Biology Source Type: research

Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling
Publication date: Available online 7 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Taylor Richards, Kavindiya Modarage, Charlotte Dean, Aidan McCarthy-Boxer, Helen Hilton, Chris Esapa, Jill Norman, Patricia Wilson, Paraskevi GoggolidouAbstractAutosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for n...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 8, 2018 Category: Molecular Biology Source Type: research

SCUBE1-enhanced bone morphogenetic protein signaling protects against renal ischemia-reperfusion injury
In this study, we first showed that I/R-induced SCUBE1 was expressed in proximal tubular cells, which coincided with the expression of renoprotective BMP7. Molecular and biochemical analyses revealed that SCUBE1 directly binds to BMP7 and its receptors, functioning as a BMP co-receptor to promote BMP7 signaling. Furthermore, we used a new Scube1 deletion (Δ2) mouse strain to further elucidate the renal pathophysiological function of SCUBE1 after I/R injury. As compared with wild-type littermates, Δ2 mice showed severe renal histopathologic features (extensive loss of brush border, tubular necrosis, and tubular ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 8, 2018 Category: Molecular Biology Source Type: research

Diminished O-GlcNAcylation in Alzheimer's disease is strongly correlated with mitochondrial anomalies
Publication date: Available online 6 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tiffany S. Pinho, Sónia C. Correia, George Perry, António Francisco Ambrósio, Paula I. MoreiraAbstractUncover the initial cause(s) underlying Alzheimer's disease (AD) pathology is imperative for the development of new therapeutic interventions to counteract AD-related symptomatology and neuropathology in a timely manner. The early stages of AD are characterized by a brain hypometabolic state as denoted by faulty glucose uptake and utilization and abnormal mitochondrial fu...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 8, 2018 Category: Molecular Biology Source Type: research

Ferutinin directs dental pulp-derived stem cells towards the osteogenic lineage by epigenetically regulating canonical Wnt signaling
This study was undertaken to develop a potential stem cell therapy for osteoporosis. We have isolated and expanded human dental pulp-derived stem cells (DPSCs), characterized them, and confirmed their multipotential differentiation abilities. Stem cells often remain quiescent and require activation to differentiate and function. Herein, we show that ferutinin activates DPSCs by modulating the Wnt/β-catenin signaling pathway and key osteoblast-secreted proteins osteocalcin and collagen 1A1 both mRNA and protein levels. To confirm that ferutinin modulates the Wnt pathway, we inhibited glycogen synthase kinase 3 (GSK3) a...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 8, 2018 Category: Molecular Biology Source Type: research

Post-translational modifications of Parkinson's disease-related proteins: Phosphorylation, SUMOylation and ubiquitination
Publication date: Available online 6 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Stella C. Junqueira, Eduarda G.Z. Centeno, Kevin A. Wilkinson, Helena CimarostiAbstractParkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the nigrostriatal pathway. The etiology of PD remains unclear and most cases are sporadic, however genetic mutations in more than 20 proteins have been shown to cause inherited forms of PD. Many of these proteins are linked to mitochondrial function, defects in which are a central characteristic of PD. ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2018 Category: Molecular Biology Source Type: research

KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer
Publication date: Available online 4 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Zhongyin Yang, Chen Li, Chao Yan, Jianfang Li, Min Yan, Bingya Liu, Zhenggang Zhu, Yingli Wu, Qinlong GuAbstractThe kinesin family member 14 (KIF14) is a potential oncogene and is involved in the metastasis of various cancers. Nevertheless, its function in gastric cancer (GC) remains poorly defined. The expression of KIF14 was examined in GC cell lines and a clinical cohort of GC specimens by qPCR, western blotting and immunohistochemistry (IHC) staining. The relationship between KIF14 expres...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 4, 2018 Category: Molecular Biology Source Type: research

Paternal hyperglycemia induces transgenerational inheritance of susceptibility to hepatic steatosis in rats involving altered methylation on Pparα promoter
ConclusionsPaternal hyperglycemia may induce epigenetic modification of Ppara in offspring's liver, probably through interaction with SP1 binding, causing impaired lipid metabolism. Our investigation may have implications for the understanding of father-offspring interactions with the potential to account for metabolic syndromes.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 4, 2018 Category: Molecular Biology Source Type: research

Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes
Publication date: Available online 2 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Aditya Sharma, Chandan K. Maurya, Deepti Arha, Amit K. Rai, Sushmita Singh, Salil Varshney, Jonathan D. Schertzer, Akhilesh K. TamrakarAbstractChronic inflammation contributes to obesity mediated metabolic disturbances, including insulin resistance. Obesity is associated with altered microbial load in metabolic tissues that can contribute to metabolic inflammation. Different bacterial components such as, LPS, peptidoglycans have been shown to underpin metabolic disturbances through interactio...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 3, 2018 Category: Molecular Biology Source Type: research

Deficiency of the mitochondrial sulfide regulator ETHE1 disturbs cell growth, glutathione level and causes proteome alterations outside mitochondria
Publication date: Available online 2 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Navid Sahebekhtiari, Paula Fernandez-Guerra, Zahra Nochi, Jasper Carlsen, Peter Bross, Johan PalmfeldtAbstractThe mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of well-described clinical symptoms of the disease, detailed cellular and molecular characterization is still ambiguous. Cellular redox regulation has been desc...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 3, 2018 Category: Molecular Biology Source Type: research

Metabolomics of Ndufs4−/− skeletal muscle: Adaptive mechanisms converge at the ubiquinone-cycle
We report a respective 48 and 34 discriminatory metabolites between Ndufs4−/− and WT white quadriceps and soleus muscles, among which the most prominent alterations indicate the involvement of the glycerol-3-phosphate shuttle, electron transfer flavoprotein system, CII, and proline cycle in fueling the Q cycle. By restoring the electron flux to CIII via the Q cycle, these adaptive mechanisms could maintain adequate oxidative ATP production, despite CI deficiency. Taken together, our results shed light on the underlying pathogenic mechanisms of CI dysfunction in skeletal muscle. Upon further investigation, these...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 1, 2018 Category: Molecular Biology Source Type: research

Cofactors revisited – Predicting the impact of flavoprotein-related diseases on a genome scale
Publication date: Available online 29 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Agnieszka B. Wegrzyn, Sarah Stolle, Rienk A. Rienksma, Vítor A.P. Martins dos Santos, Barbara M. Bakker, Maria Suarez-DiezAbstractFlavin adenine dinucleotide (FAD) and its precursor flavin mononucleotide (FMN) are redox cofactors that are required for the activity of more than hundred human enzymes. Mutations in the genes encoding these proteins cause severe phenotypes, including a lack of energy supply and accumulation of toxic intermediates. Ideally, patients should be diagnosed befo...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

Post-translational modifications in MeHg-induced neurotoxicity
Publication date: Available online 29 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tao Ke, Filipe Marques Gonçalves, Cinara Ludvig Gonçalves, Alessandra Antunes dos Santos, João B.T. Rocha, Marcelo Farina, Anatoly Skalny, Aristidis Tsatsakis, Aaron B. Bowman, Michael AschnerAbstractMercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular me...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice
Publication date: Available online 30 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Chunling Yuan, Xiaoli Guo, Qifan Zhou, Fangyu Du, Wei Jiang, Xiaoyu Zhou, Peng Liu, Tianyan Chi, Xuefei Ji, Jinheng Gao, Chengwen Chen, Hongli Lang, Jia Xu, Danyang Liu, Yang Yang, Shimeng Qiu, Xing Tang, Guoliang Chen, Libo ZouAbstractThe pathogenesis of Alzheimer's disease (AD) is complex, though the clinical failures of anti-AD candidates targeting Aβ production (such as β- and γ-secretase inhibitors) make people suspect the Aβ hypothesis, in which the neurotoxicity of...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity
In this study, we identify histone methyltransferase mixed-lineage leukemia protein 3 (MLL3) as a critical regulator of PD-L1 in prostate cancer cells. MLL3 and PD-L1 were highly expressed in the metastatic cancer tissues, compared to the primary cancer tissues. Furthermore, their expressions were highly correlated in the cancer tissues in the databases of TCGA and Xiangya Hospital. We found that MLL3 bound to the enhancer of PD-L1. Depletion of MLL3 decreased the binding level of H3K4me1 in the enhancer of PD-L1 and Pol II Ser-5p in the promoter of PD-L1. Importantly, MLL3 depletion impaired the mouse xenograft growth and...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL-1β production upon intravascular hemolysis
Publication date: Available online 30 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Benard Bogonko Nyakundi, Andrea Tóth, Enikő Balogh, Béla Nagy, Judit Erdei, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória JeneyAbstractDamage associated molecular patterns (DAMPs) are released form red blood cells (RBCs) during intravascular hemolysis (IVH). Extracellular heme, with its pro-oxidant, pro-inflammatory and cytotoxic effects, is sensed by innate immune cells through pattern recognition receptors such as toll-like receptor 4 and nucleotide-b...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

A FBN1 3′UTR mutation variant is associated with endoplasmic reticulum stress in aortic aneurysm in Marfan syndrome
In conclusion, we here identify a 3′UTR mutation of FBN1 in MFS patients, whose molecular mechanism suggest the involvement of the ER stress response in the formation of the aortic aneurysm. Our results emphasise the importance of mutations in non-coding regions and their resulting molecular mechanisms in the development of connective tissue diseases with impact on the cardiovascular system. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research

SREBP-2 aggravates breast cancer associated osteolysis by promoting osteoclastogenesis and breast cancer metastasis
In this study, we demonstrated that important roles sterol regulatory element-binding protein 2 (SREBP-2) play in osteoclast formation a function, and in breast cancer metastasis. SREBP-2 expression was found to be induced during the early stages of osteoclast formation under the control of the RANKL/cAMP-response element binding protein (CREB) signaling cascade. SREBP-2 is subsequently translocated into the nucleus where it participates with other transcriptional factors to induce the expression of NFATc1 required for mature osteoclast formation. Additionally, SREBP-2 was also found to be highly expressed in breast cancer...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2018 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 12Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 27, 2018 Category: Molecular Biology Source Type: research

The role of obesity in inflammatory bowel disease
Publication date: January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 1Author(s): Roxane Kreuter, Miriam W.ell, Golo Ahlenstiel, Lionel HebbardAbstractIn just over a generation overweight and obesity has become a worldwide health concern. The ramifications for this on future health care costs and longevity are consequent, whilst increased adiposity is a harbinger for diabetes, kidney and bone failure, and cancer. An area of intense interest where the role of adiposity is avidly discussed is in inflammatory bowel disease (IBD), which presents mainly as Crohn's disease (CD...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 23, 2018 Category: Molecular Biology Source Type: research

The impact of histone post-translational modifications in neurodegenerative diseases
Publication date: Available online 20 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Samantha N. Cobos, Seth A. Bennett, Mariana P. TorrenteAbstractEvery year, neurodegenerative disorders take more than 5000 lives in the US alone. Cures have not yet been found for many of the multitude of neuropathies. The majority of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) cases have no known genetic basis. Thus, it is evident that contemporary genetic approaches have failed to explain the etiology or etiologies of ALS/FTD and PD. Recen...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 21, 2018 Category: Molecular Biology Source Type: research

Nr5a1-Cre-mediated Tspo conditional knockout mice with low growth rate and prediabetes symptoms – A mouse model of stress diabetes
Publication date: Available online 18 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jinjiang Fan, Enrico Campioli, Vassilios PapadopoulosAbstractTranslocator protein (TSPO) is a high-affinity cholesterol- and drug-binding mitochondrial protein. Nuclear receptor subfamily 5 group A member 1 or steroidogenic factor 1 (Nr5a1)-Cre mice were previously used to generate steroidogenic cell-specific Tspo gene conditional knockout (cKO) mice. TSPO-depleted homozygotes showed no response to adrenocorticotropic hormone (ACTH) in stimulating adrenal cortex corticosterone production but ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 19, 2018 Category: Molecular Biology Source Type: research

Methylglyoxal accumulation de-regulates HoxA5 expression, thereby impairing angiogenesis in glyoxalase 1 knock-down mouse aortic endothelial cells
This study demonstrates, for the first time, that MGO accumulation increases the antiangiogenic factor HoxA5 via NF-ĸB-p65, thereby impairing the angiogenic ability of endothelial cells.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 19, 2018 Category: Molecular Biology Source Type: research

Role of autophagy in inherited metabolic and endocrine myopathies
Publication date: Available online 18 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ying Tan, Yan Gong, Maolong Dong, Zhaohui Pei, Jun RenAbstractThe prevalence of cardiometabolic disease has reached an exponential rate of rise over the last decades owing to high fat/high caloric diet intake and satiety life style. Although the presence of dyslipidemia, insulin resistance, hypertension and obesity mainly contributes to the increased incidence of cardiometabolic diseases, population-based, clinical and genetic studies have revealed a rather important role for inherited myopat...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 19, 2018 Category: Molecular Biology Source Type: research

The role of mitochondria in sepsis-induced cardiomyopathy
Publication date: Available online 17 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Giacomo Stanzani, Michael R. Duchen, Mervyn SingerAbstractSepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial dysfunction, often termed sepsis-induced cardiomyopathy, is a frequent complication and is associated with worse outcomes. Numerous mechanisms contribute to sepsis-induced cardiomyopathy and a growing body of evidence suggests that bioenergetic and metabolic derangements play a central role in its development; howev...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 18, 2018 Category: Molecular Biology Source Type: research

Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls
Publication date: Available online 17 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sina Saari, Geovana S. Garcia, Katharina Bremer, Marina M. Chioda, Ana Andjelković, Paul V. Debes, Mikko Nikinmaa, Marten Szibor, Eric Dufour, Pierre Rustin, Marcos T. Oliveira, Howard T. JacobsAbstractThe alternative respiratory chain (aRC), comprising the alternative NADH dehydrogenases (NDX) and quinone oxidases (AOX), is found in microbes, fungi and plants, where it buffers stresses arising from restrictions on electron flow in the oxidative phosphorylation system. The aRC enzymes are al...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 18, 2018 Category: Molecular Biology Source Type: research

Corrigendum to “Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation” [Biochim. Biophys. Acta, 1862 (2016) 1182–1190]
Publication date: Available online 16 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): F. Bonacina, S.S. Barbieri, L. Cutuli, P. Amadi, A. Don, M. Sironi, S. Tartari, A. Mantovani, B. Bottazzi, C. Garlanda, E. Tremoli, A.L. Catapano, G.D. Norata (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 17, 2018 Category: Molecular Biology Source Type: research

mTOR inhibitor INK128 attenuates systemic lupus erythematosus by regulating inflammation-induced CD11b+Gr1+ cells
In conclusion, CD11b+Gr1+ cells increased in the early stages of the lupus progression and mTOR pathway was critical for CD11b+Gr1+ cells in lupus development, suggesting the changes of inflammation-induced CD11b+Gr1+ cells initate lupus development. We also provide evidence for the first time that INK128, a second generation mTOR inhibitor, has a good therapeutic action on lupus development by regulating CD11b+Gr1+ cells. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 16, 2018 Category: Molecular Biology Source Type: research

Epigenetic upregulation and functional role of the mitochondrial aspartate/glutamate carrier isoform 1 in hepatocellular carcinoma
Publication date: Available online 12 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Vittoria Infantino, Francesco Dituri, Paolo Convertini, Anna Santarsiero, Ferdinando Palmieri, Simona Todisco, Serena Mancarella, Gianluigi Giannelli, Vito IacobazziAbstractMetabolic reprogramming is a common hallmark of cancer cells. Although some biochemical features have been clarified, there is still much to learn about cancer cell metabolism and its regulation. Aspartate-glutamate carrier isoform 1 (AGC1), encoded by SLC25A12 gene, catalyzes an exchange between intramitochondrial asparta...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 13, 2018 Category: Molecular Biology Source Type: research

Phosphorylation of NHERF1 S279 and S301 differentially regulates breast cancer cell phenotype and metastatic organotropism
Publication date: Available online 13 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Maria Raffaella Greco, Emeline Bon, Rosa Rubino, Lorenzo Guerra, Manuel Bernabe-Garcia, Stefania Cannone, Maria-Luisa Cayuela, Loredana Ciaccia, Séverine Marionneau-Lambot, Thibauld Oullier, Gaëlle Fromont, Roseline Guibon, Sébastien Roger, Stephan Joel Reshkin, Rosa Angela CardoneAbstractMetastatic cancer cells are highly plastic for the expression of different tumor phenotype hallmarks and organotropism. This plasticity is highly regulated but the dynamics of the signalin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 13, 2018 Category: Molecular Biology Source Type: research

Microglial overexpression of fALS-linked mutant SOD1 induces SOD1 processing impairment, activation and neurotoxicity and is counteracted by the autophagy inducer trehalose
Publication date: Available online 10 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Francesca Massenzio, Emiliano Peña-Altamira, Sabrina Petralla, Marco Virgili, Giampaolo Zuccheri, Andrea Miti, Elisabetta Polazzi, Ilaria Mengoni, Deborah Piffaretti, Barbara MontiAbstractAmyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Mutations in the gene encoding copper/zinc superoxide dismutase-1 (SOD1) are responsible for most familiar cases, but the role of mutant SOD1 protein dysfunction in non-cell autonomous neurodegeneration, especially in relation to mic...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 11, 2018 Category: Molecular Biology Source Type: research

YM155 sensitizes non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitors through the mechanism of autophagy induction
In this study, we showed that YM155 markedly enhanced the sensitivity of erlotinib to EGFR-TKI resistant NSCLC cell lines H1650 (EGFR exon 19 deletion and PTEN loss) and A549 (EGFR wild type and KRAS mutation) through inducing autophagy-dependent apoptosis and autophagic cell death. The effects of YM155 combined with erlotinib on apoptosis and autophagy inductions were more obvious than those of YM155 in combination with survivin knockdown by siRNA transfection, suggesting that YM155 induced autophagy and apoptosis in the NSCLC cells partially depend on survivin downregulation. Meanwhile, we found that the AKT/mTOR pathway...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 11, 2018 Category: Molecular Biology Source Type: research

Aldehyde dehydrogenase 2 deficiency promotes atherosclerotic plaque instability through accelerating mitochondrial ROS-mediated vascular smooth muscle cell senescence
This study was designed to examine the effect of ALDH2 deficiency on cholesterol diet-induced atherosclerotic plaque progression and plaque vulnerability in atherosclerosis-prone ApoE knockout (ApoE−/−) mice with a focus on foam cell formation in macrophages and senescence of vascular smooth muscle cells (VSMCs). Serum lipid profile, plaque progression, and plaque vulnerability were examined in ApoE−/− and ALDH2/ApoE double knockout (ALDH2−/−ApoE−/−) mice after high-cholesterol diet intake for 8 weeks. ALDH2 deficiency increased the serum levels of triglycerides while it de...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 11, 2018 Category: Molecular Biology Source Type: research

Post-translational histone modifications and their interaction with sex influence normal brain development and elaboration of neuropsychiatric disorders
Publication date: Available online 10 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): G. Singh, V. Singh, J.S. SchneiderAbstractSex differences in the risk for and expression of various brain disorders have been known for some time. Yet, the molecular underpinnings of these sex differences as well as how sex modifies normal brain development are still poorly understood. It has recently become known that epigenetic mechanisms play an essential role in establishing and maintaining sex differences in neurodevelopment and disease susceptibility. Epigenetic mechanisms such as post-...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 10, 2018 Category: Molecular Biology Source Type: research

Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice
Publication date: Available online 6 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Natalia Presa, Robin D. Clugston, Susanne Lingrell, Samuel E. Kelly, Alfred H. Merrill, Sayantan Jana, Zamaneh Kassiri, Antonio Gómez-Muñoz, Dennis E. Vance, Rene L. Jacobs, Jelske N. van der VeenAbstractPhosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver. Pemt−/− mice are protected from high-fat diet (HFD)-induced obesity and insulin resistance, but develop severe non-alcoholic fa...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 7, 2018 Category: Molecular Biology Source Type: research

Endoplasmic reticulum stress induces inverse regulations of major functions in portal myofibroblasts during liver fibrosis progression
In conclusion, PMF develop ER stress as they expand with the progression of fibrosis, which further increases their proangiogenic activity, but also inhibits their proliferation and migration. This phenotypic switch may restrict PMF expansion while they support angiogenesis. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Differential expression of tumor-associated genes and altered gut microbiome with decreased Akkermansia muciniphila confer a tumor-preventive microenvironment in intestinal epithelial Pten-deficient mice
Publication date: Available online 4 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cody Howe, Su Jin Kim, Jonathon Mitchell, Eunok Im, Yong Sung Kim, You Sun Kim, Sang Hoon RheeAbstractPhosphatase and tensin homolog (Pten) antagonizes PI3K-Akt signaling; therefore, Pten impairment causes tumorigenesis. However, the correlation between Pten deficiency and colon cancer has remained elusive due to numerous opposite observations. To study this correlation, we examined whether Pten deficiency in intestinal epithelial cells (IECs) induces tumorigenesis.With mucosal biopsies of hum...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Intracellular cholesterol accumulation and coenzyme Q10 deficiency in Familial Hypercholesterolemia
Publication date: Available online 5 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Juan M. Suárez-Rivero, Mario de la Mata, Ana Delgado Pavón, Marina Villanueva-Paz, Suleva Povea-Cabello, David Cotán, Mónica Álvarez-Córdoba, Irene Villalón-García, Patricia Ybot-González, Joaquín J. Salas, Ovidio Muñiz, Mario D. Cordero, José A. Sánchez-AlcázarAbstractFamilial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Dysregulated Txnip-ROS-Wnt axis contributes to the impaired ischemic heart repair in diabetic mice
Publication date: Available online 24 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mingzhi Shen, Danna Bai, Bei Liu, Xiaozhao Lu, Rongrong Hou, Chao Zeng, Na Li, Zhenhong Fu, Congye Li, Ling Tao, Haichang Wang, Tao YinAbstractHyperglycemia-induced impairment of angiogenesis contributes to the unfavorable prognosis of myocardial ischemia in long-standing diabetes mellitus. The underlying mechanism remains largely unknown and therapeutic strategies thereby limited. In the present study, we investigated the possible involvement of thioredoxin-interacting protein (TXNIP) and ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Dietary nitrate's effects on exercise performance in heart failure with reduced ejection fraction (HFrEF)
Publication date: Available online 24 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Vinaya Mulkareddy, Susan B. Racette, Andrew R. Coggan, Linda R. PetersonAbstractHeart failure with reduced ejection fraction (HFrEF) is a deadly and disabling disease. A key derangement contributing to impaired exercise performance in HFrEF is decreased nitric oxide (NO) bioavailability. Scientists recently discovered the inorganic nitrate pathway for increasing NO. This has advantages over organic nitrates and NO synthase production of NO. Small studies using beetroot juice as a source of ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Application of Magnetic Resonance Spectroscopy in metabolic research
Publication date: Available online 24 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Tineke van de Weijer, Vera B. Schrauwen-HinderlingAbstractThe etiology of metabolic disease in humans is far from understood, and even though potential pathways are identified in animal models and cell studies, it is often difficult to determine their relevance in humans, as the possibilities of tissue sampling are limited. The application of non-invasive imaging techniques can provide essential metabolic information and this mini review focuses on the opportunities of Magnetic Resonance Sp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Interplay between NAD+ and acetyl‑CoA metabolism in ischemia-induced mitochondrial pathophysiology
Publication date: Available online 24 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Nina Klimova, Aaron Long, Susana Scafidi, Tibor KristianAbstractBrain injury caused by ischemic insult due to significant reduction or interruption in cerebral blood flow leads to disruption of practically all cellular metabolic pathways. This triggers a complex stress response followed by overstimulation of downstream enzymatic pathways due to massive activation of post-translational modifications (PTM). Mitochondria are one of the most sensitive organelle to ischemic conditions. They beco...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Hypoxia-inducible factor 1 signalling, metabolism and its therapeutic potential in cardiovascular disease
Publication date: Available online 25 September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Maria da Luz Sousa Fialho, Amira H. Abd Jamil, George A. Stannard, Lisa C. HeatherAbstractCardiovascular disease (CVD) accounts for the largest number of deaths worldwide, necessitating the development of novel treatments and prevention strategies. Given the huge energy demands placed on the heart, it is not surprising that changes in energy metabolism play a key role in the development of cardiac dysfunction in CVD. A reduction in oxygen delivery to the heart, hypoxia, is sensed and respon...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy
Publication date: Available online 1 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Rosa Fernandes, Sofia D. Viana, Sara Nunes, Flávio ReisAbstractThe increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiot...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

TLR4 triggered complex inflammation in human pancreatic islets
Publication date: Available online 1 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Wei He, Osmond Rebello, Rocco Savino, Rosa Terracciano, Carole Schuster-Klein, Beatrice Guardiola, Kathrin MaedlerAbstractType 2 Diabetes (T2D) is strongly associated with obesity and inflammation. Toll-like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its ligands and downstream products increased systemically in T2D and in at-risk individuals. Detailed mechanisms of the complex proinflammatory response in pancreatic islets remain unknown.In isolated human islets LPS induced I...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

Asthma alleviates obesity in males through regulating metabolism and energy expenditure
Publication date: Available online 2 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xiaomin Song, Bolun Li, Haoran Wang, Xuan Zou, Ran Gao, Wei Zhang, Ting Shu, Hongmei Zhao, Bin Liu, Jing WangAbstractMany epidemiological studies suggested a correlation between obesity and asthma. However, little is known about the molecular details explaining this correlation. Here, we show that asthma decreased body weight of asthmatic male mice fed with high fat diet via increasing energy expenditure and insulin sensitivity. The increase of energy expenditure was mainly due to upregulation...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research