PKC λ/ι regulates Th17 differentiation and house dust mite-induced allergic airway inflammation
In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associa...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 3, 2018 Category: Molecular Biology Source Type: research

The role of AdipoR1 and AdipoR2 in liver fibrosis
Publication date: March 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 3 Author(s): Badr Alzahrani, Tristan Iseli, Mehdi Ramezani-Moghadam, Vikki Ho, Miriam W.ell, Eun Jin Sun, Liang Qiao, Jacob George, Lionel W. Hebbard Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model o...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2017 Category: Molecular Biology Source Type: research

Febrile temperature reprograms by redox-mediated signaling the mitochondrial metabolic phenotype in monocyte-derived dendritic cells
In this study we asked if challenging human monocyte-derived dendritic cells with a relatively short-time thermal shock in the fever-range, typically observed in humans, caused alterations in the mitochondrial oxidative metabolism. We found that following hyperthermic stress (3h exposure at 39°C) TNF-α-releasing dendritic cells undergo rewiring of the oxidative metabolism hallmarked by decrease of the mitochondrial respiratory activity and of the oxidative phosphorylation and increase of lactate production. Moreover, enhanced production of reactive oxygen and nitrogen species and accumulation of mitochondrial Ca2...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2017 Category: Molecular Biology Source Type: research

AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs
In conclusion, AMD3100 treatment attenuated pulmonary angiogenesis in CBDL rats and prevented the development of HPS via reductions in pulmonary c-kit+ cells and inhibition of the prosurvival signals. Our study provides new insights in HPS treatment. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2017 Category: Molecular Biology Source Type: research

Factor VII deficiency: Unveiling the cellular and molecular mechanisms underlying three model alterations of the enzyme catalytic domain
Publication date: March 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 3 Author(s): Maria Eugenia Chollet, Elisabeth Andersen, Ellen Skarpen, Christiane F. Myklebust, Christian Koehler, Jens Preben Morth, Ampaiwan Chuansumrit, Mirko Pinotti, Francesco Bernardi, Bernd Thiede, Per Morten Sandset, Grethe Skretting Activated factor (F) VII is a vitamin K-dependent glycoprotein that initiates blood coagulation upon interaction with tissue factor. FVII deficiency is the most common of the rare congenital bleeding disorders. While the mutational pattern has been extensively chara...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2017 Category: Molecular Biology Source Type: research

Cholesterol ester hydrolase inhibitors reduce the production of synaptotoxic amyloid- β oligomers
Publication date: March 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 3 Author(s): Harriet McHale-Owen, Clive Bate The production of amyloid-β (Aβ) is the key factor driving pathogenesis in Alzheimer's disease (AD). Increasing concentrations of Aβ within the brain cause synapse degeneration and the dementia that is characteristic of AD. Here the factors that affect the release of disease-relevant forms Aβ were studied in a cell model. 7PA2 cells expressing the human amyloid precursor protein released soluble Aβ oligomers that caused synapse damage...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 20, 2017 Category: Molecular Biology Source Type: research

New perspectives for pharmacological chaperoning treatment in methylmalonic aciduria cblB type
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): S. Brasil, A. Briso-Montiano, A. Gámez, J. Underhaug, M.I. Flydal, L. Desviat, B. Merinero, M. Ugarte, A. Martinez, B. Pérez (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 16, 2017 Category: Molecular Biology Source Type: research

Activation of the EPOR- β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Alessandra Bitto, Natasha Irrera, Gabriele Pizzino, Giovanni Pallio, Federica Mannino, Mario Vaccaro, Vincenzo Arcoraci, Federica Aliquò, Letteria Minutoli, Michele R. Colonna, Maria Rosaria Galeano, Michael Brines, Chiara De Ponte, Massimo Collino, Francesco Squadrito, Domenica Altavilla Diabetes is characterized by poor wound healing which currently lacks an efficacious treatment. The innate repair receptor (IRR) is a master regulator of tissue protection and repair which is exp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 13, 2017 Category: Molecular Biology Source Type: research

Mitochondrial pore opening and loss of Ca2+ exchanger NCLX levels occur after frataxin depletion
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): R. Purroy, E. Britti, F. Delaspre, J. Tamarit, J. Ros Frataxin-deficient neonatal rat cardiomyocytes and dorsal root ganglia neurons have been used as cell models of Friedreich ataxia. In previous work we show that frataxin depletion resulted in mitochondrial swelling and lipid droplet accumulation in cardiomyocytes, and compromised DRG neurons survival. Now, we show that these cells display reduced levels of the mitochondrial calcium transporter NCLX that can be restored by calcium-chel...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 9, 2017 Category: Molecular Biology Source Type: research

Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Pasquale Agosti, Carlo Sabbà, Antonio Mazzocca Despite the reducing incidence of chronic hepatitis infections, an unexpected increasing incidence of hepatocellular carcinoma (HCC) has being occurred. This may be explained by the increasing number of HCCs developing on steatosis (NAFLD) and steatohepatitis (NASH), related to metabolic risk factors (i.e. diabetes mellitus type II, obesity, metabolic syndrome), which are becoming emerging risk factors for HCC. This led to a growing s...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 8, 2017 Category: Molecular Biology Source Type: research

Metabolomic markers of fatigue: Association between circulating metabolome and fatigue in women with chronic widespread pain
Conclusion The results of this agnostic metabolomics screening show that fatigue is metabolically distinct from CWP, and is associated with a decrease in circulating levels of EPA. Our panel of circulating metabolites provides the starting point for a diagnostic test for fatigue in CWP. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 7, 2017 Category: Molecular Biology Source Type: research

Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Miguel A. Velazquez, Bhavwanti Sheth, Stephanie J. Smith, Judith J. Eckert, Clive Osmond, Tom P. Fleming Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to e...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 6, 2017 Category: Molecular Biology Source Type: research

TGF- β synergizes with ML264 to block IL-1β-induced matrix degradation mediated by Krüppel-like factor 5 in the nucleus pulposus
In this study, we revealed that KLF5 is involved in IL-1β activated NF-kB cascade by enhancing both p65 phosphorylation and p65 acetylation. Moreover, the catabolic effect of KLF5 can be abolished by transforming growth factor-β (TGF-β) via promoting the proteasomal degradation of KLF5. Therefore, a KLF5 inhibitor ML264 was further proved to synergize with TGF-β to attenuate IL-1β-induced intervertebral disc degeneration. These results indicate the critical role of KLF5 in regulating intervertebral disc metabolism and suggest KLF5 inhibitor such as ML264 as potential compound for treatment of degen...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 6, 2017 Category: Molecular Biology Source Type: research

Melatonin protects diabetic heart against ischemia-reperfusion injury, role of membrane receptor-dependent cGMP-PKG activation
This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG. Streptozotocin-induced diabetic Sprague-Dawley rats and high-glucose medium-incubated H9c2 cardiomyoblasts were utilized to determine the effects of melatonin against MI/R injury. Melatonin treatment preserved cardiac function and reduced oxidative damage and apoptosis. Additionally, melatonin increased intracellular cGMP level, PKGIα expression, p-VASP/VASP ratio and further modulated myocardial Nrf-2-HO-1 and MAPK sig...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 6, 2017 Category: Molecular Biology Source Type: research

TGF- β-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Huanan Li, Huimin Cai, Jia Deng, Xiaolong Tu, Yanyan Sun, Zhen Huang, Zhi Ding, Lei Dong, Jiangning Chen, Yuhui Zang, Junfeng Zhang TGF-β signaling plays a principal role in renal fibrosis, but the precise mechanisms and the downstream factors are still largely unknown. Sox9 exhibits diverse roles in regulating the production of extracellular matrix proteins. Here we found that Sox9 was induced by TGF-β in the kidney fibroblast and acted as an important downstream mediator of T...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 6, 2017 Category: Molecular Biology Source Type: research

N-acetylcysteine effects on a murine model of chronic critical limb ischemia
In conclusion, NAC treatment decreases oxidative damage and inflammation, and modulates oxygen consumption under hypoxic conditions in a model of chronic limb ischemia. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 6, 2017 Category: Molecular Biology Source Type: research

Altered TGF- β endocytic trafficking contributes to the increased signaling in Marfan syndrome
We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased c...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 1, 2017 Category: Molecular Biology Source Type: research

Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral ischemia: Possible benefits for stroke-induced inflammation control
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Ping Sun, Mar Hernandez-Guillamón, Mireia Campos-Martorell, Alba Simats, Joan Montaner, Mercedes Unzeta, Montse Solé Beyond cholesterol reduction, statins mediate their beneficial effects on stroke patients through pleiotropic actions. They have shown anti-inflammatory properties by a number of different mechanisms, including the inhibition of NF-κB transcriptional activity and the consequent increase and release of adhesion molecules. We have studied simvastatin's ef...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 29, 2017 Category: Molecular Biology Source Type: research

CDK5-mediated phosphorylation of Sirt2 contributes to depressive-like behavior induced by social defeat stress
This study highlights that inhibiting CDK5-dependent phosphorylation of Sirt2 at serine residues 368 and 372 by myristoylated membrane-permeabilising peptide (Sirt2-p), rather than using non-specific sirtuin inhibitors, may be a novel strategy for treating depression. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 27, 2017 Category: Molecular Biology Source Type: research

Membrane cholesterol depletion in cortical neurons highlights altered NMDA receptor functionality in a mouse model of amyotrophic lateral sclerosis
In this study, performed on the widely used G93A mouse model of ALS, we have shown an equal content of total membrane cholesterol in Control and G93A cortical cultures. Moreover, by electrophysiological studies, we have recorded NMDA- and AMPA-evoked currents which were not significantly different between the two neuronal populations. To study the role of membrane cholesterol on glutamate receptor functionality, we have analysed NMDA and AMPA receptors following cholesterol membrane depletion by methyl-β-cyclodextrin (MβCD). Interestingly, MβCD chronic treatment has provoked a significant reduction of NMDA-e...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 25, 2017 Category: Molecular Biology Source Type: research

Human umbilical vein endothelium-derived exosomes play a role in foetoplacental endothelial dysfunction in gestational diabetes mellitus
In conclusion foetoplacental endothelial-released exosomes play a role in the maintenance of a GDM phenotype in HUVECs. It is suggested that Ex N and Ex GDM cargo are different with differential effects in cells from normal or GDM pregnancies. This phenomenon could contribute to the understanding of mechanisms behind foetoplacental endothelial dysfunction in GDM pregnancies. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 25, 2017 Category: Molecular Biology Source Type: research

Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Xihong Zhou, Liuqin He, Shengnan Zuo, Yumei Zhang, Dan Wan, Ciming Long, Pan Huang, Xin Wu, Canrong Wu, Gang Liu, Yulong Yin Serine deficiency has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Whether serine supplementation has any beneficial effects on the prevention of NAFLD remains unknown. The present study was conducted to investigate the effects of serine supplementation on hepatic oxidative stress and steatosis and its related mechanisms. Forty male C57B...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 24, 2017 Category: Molecular Biology Source Type: research

Corrigendum to ‘CD95-mediated apoptosis in Burkitt's lymphoma B-cells is associated with Pim-1 down-regulation’[Biochimica et Biophysica Acta 1863/1 (2017) 239–252]
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Sabine Matou-Nasri, Zaki Rabhan, Haya Albuayjan, Hamad Al-Eidi, Wesam Bin Yahya, Abdelkareem Al Abdulrahman, Nasser Almobadel, Mona Alsubeai, Saleh Al Ghamdi, Ahmed Alaskar, Mohammed AlBalwi, Mohsen Alzahrani, Ibrahim Alabdulkareem (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 23, 2017 Category: Molecular Biology Source Type: research

Site-specific effects of apolipoprotein E expression on diet-induced obesity and white adipose tissue metabolic activation
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Aikaterini Hatziri, Christina Kalogeropoulou, Eva Xepapadaki, Eleni Birli, Eleni A. Karavia, Eugenia Papakosta, Serafoula Filou, Caterina Constantinou, Kyriakos E. Kypreos Apolipoprotein E (APOE) has been strongly implicated in the development of diet induced obesity. In the present study, we investigated the contribution of brain and peripherally expressed human apolipoprotein E3 (APOE3), the most common human isoform, to diet induced obesity. In our studies APOE3 knock-in (Apoe3 knock-...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 22, 2017 Category: Molecular Biology Source Type: research

Characterization of three novel pathogenic SLC40A1 mutations and genotype/phenotype correlations in 7 Italian families with type 4 hereditary hemochromatosis
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Silvia Majore, Maria Carmela Bonaccorsi di Patti, Michele Valiante, Fabio Polticelli, Andrea Cortese, Sabrina Di Bartolomeo, Carmelilia De Bernardo, Marianna De Muro, Fiorella Faienza, Francesca Clementina Radio, Paola Grammatico, Giovanni Musci Mutations of SLC40A1 encoding ferroportin (Fpn), the unique cellular iron exporter, severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations....
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 21, 2017 Category: Molecular Biology Source Type: research

PAKs in the brain: Function and dysfunction
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Laura Civiero, Elisa Greggio p21-Activated kinases (PAKs) comprise a family of proteins covering a central role in signal transduction. They are downstream effectors of Rho GTPases and can affect a variety of processes in different cell types and tissues by remodeling the cytoskeleton and by promoting gene transcription and cell survival. Given the relevance of cytoskeletal organization in neuronal development as well as synaptic function and the importance of pro-survival signals in con...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 18, 2017 Category: Molecular Biology Source Type: research

Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a rodent model of oestrogen deficiency
This study established that systemic oestrogen deficiency mediates parallel structural changes in both the claw (primarily keratin) and bone proteins (primarily collagen). This strengthens the hypothesis that nail keratin can act as a surrogate marker of bone protein status where systemic processes induce changes. Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2017 Category: Molecular Biology Source Type: research

CCR6 promotes tumor angiogenesis via the AKT/NF- κB/VEGF pathway in colorectal cancer
In conclusion, CCR6 facilitates tumor angiogenesis via the AKT/NF-κB/VEGF pathway in colorectal cancer. CCR6 inhibition may be a novel option for anti-vascular treatment in CRC. Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2017 Category: Molecular Biology Source Type: research

Regulatory crosstalk between KLF5, miR-29a and Fbw7/CDC4 cooperatively promotes atherosclerotic development
In conclusion, our data are the first to reveal that the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2017 Category: Molecular Biology Source Type: research

Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Rishi K. Somvanshi, Amrit Jhajj, Michael Heer, Ujendra Kumar The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington's Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptoph...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2017 Category: Molecular Biology Source Type: research

Disruption of AT-hook 1 domain in MeCP2 protein caused behavioral abnormality in mice
In this study, we generated a mouse line carrying deletion of eight conserved amino acids in AT-hook 1 domain by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. Mecp2 ΔAT-hook1/y mutant male mice exhibited low locomotor activity, motor incoordination and cognitive deficit. In addition, these mutant mice exhibited increased anxiety. Moreover, pain insensitivity was noted in the mutant males. However, the social interactions were unaffected in AT-hook 1 mutant mice. Thinner CA1 region of the hippocampus was observed in the mutant mice. On the molecular basis, Western blot analysis sh...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 15, 2017 Category: Molecular Biology Source Type: research

Histone methyltransferase G9a modulates hepatic insulin signaling via regulating HMGA1
Publication date: February 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 2 Author(s): Weili Xue, Jin Huang, Hong Chen, Yu Zhang, Xiuqin Zhu, Jianshuang Li, Wenquan Zhang, Yangmian Yuan, Yan Wang, Ling Zheng, Kun Huang Hepatic insulin sensitivity is critical for glucose homeostasis, and insulin resistance is a fundamental syndrome found in various metabolic disorders, including obesity and type 2 diabetes. Despite considerable studies on the mechanisms of hepatic insulin resistance, the link between epigenetic regulation and the development of insulin resistance remains el...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 14, 2017 Category: Molecular Biology Source Type: research

The therapeutic value of protein (de)nitrosylation in experimental septic shock
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Patrícia O. Benedet, Angela C.O. Menegatti, Muryel C. Gonçalves, Hernán Terenzi, Jamil Assreuy Cardiovascular dysfunction and organ damage are hallmarks of sepsis and septic shock. Protein S-nitrosylation by nitric oxide has been described as an important modifier of protein function. We studied whether protein nitrosylation/denitrosylation would impact positively in hemodynamic parameters of septic rats. Polymicrobial sepsis was induced by cecal ligation and puncture...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

Increased intraocular pressure alters the cellular distribution of HuR protein in retinal ganglion cells – A possible sign of endogenous neuroprotection failure
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Adrian Smedowski, Xiaonan Liu, Lucia Podracka, Saeed Akhtar, Anna Trzeciecka, Marita Pietrucha-Dutczak, Joanna Lewin-Kowalik, Arto Urtti, Marika Ruponen, Kai Kaarniranta, Markku Varjosalo, Marialaura Amadio The RNA-binding protein, HuR, modulates mRNA processing and gene expression of several stress response proteins i.e. Hsp70 and p53 that have been postulated to be involved in the pathogenesis of glaucoma, a chronic optic neuropathy leading to irreversible blindness. We evaluated HuR pr...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

Chronic hyperammonemia alters in opposite ways membrane expression of GluA1 and GluA2 AMPA receptor subunits in cerebellum. Molecular mechanisms involved
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Andrea Cabrera-Pastor, Lucas Taoro-González, Esperanza López-Merino, Ferran Celma, Marta Llansola, Vicente Felipo Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its phosphorylation. T...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Wen-Chung Liu, Chih-Wei Wu, You-Lin Tain, Mu-Hui Fu, Chun-Ying Hung, I-Chun Chen, Lee-Wei Chen, Kay L.H. Wu Diet-associated insulin resistance (IR) is intimately correlated with the progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has been applied to enhance insulin sensitivity. With limited permeability to blood-brain-barrier, it is unclear that whether oral PIO available...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease
In conclusion, our results suggest that a hypothalamic metabolism abnormality may comprise a potential indicator for the early-diagnosis and monitoring of amyloid pathology progression. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

The extent of pyroptosis varies in different stages of apical periodontitis
In conclusion, caspase-1 and pyroptosis contributed to AP inflammation and lesion and pyroptosis extent was in line with AP progression. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

TOP2A induces malignant character of pancreatic cancer through activating β-catenin signaling pathway
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Yao-fei Pei, Xi-min Yin, Xi-qiang Liu It has been reported that Topoisomerase II alpha (TOP2A) could induce tumor development and progression in many cancer types. Herein, through analysis of different independent cohorts, we found TOP2A was up-regulated in pancreatic cancer as compared with non-tumor tissues. Moreover, the up-regulation of TOP2A was significantly correlated with tumor metastasis and shorter survival in patients with pancreatic cancer. Knockdown of TOP2A in pancreatic can...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 6, 2017 Category: Molecular Biology Source Type: research

Long non-coding RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by competitively binding miR-200c
This study showed that the lncRNA-ATB promoted EMT by acting as a miR-200c sponge. miR-200c was identified by miRNA array as a potential target of lncRNA-ATB and verified by dual luciferase reporter gene together with RNA pull-down assays. Moreover, our findings demonstrated that lncRNA-ATB is abundantly expressed during EMT of lung epithelial cells, which contributes to decreased levels of miR-200c. miR-200c targeted ZEB1 to relief silicosis by blocking EMT in vivo and in vitro. The results also suggested M2 macrophages secreted transforming growth factor-β1 (TGF-β1) to induce EMT process by activating lncRNA-AT...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 5, 2017 Category: Molecular Biology Source Type: research

Epigenetic regulation of astrocyte function in Neuroinflammation and Neurodegeneration
Publication date: Available online 4 November 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Matthew Neal, Jason R. Richardson Epigenetic mechanisms control various functions throughout the body, from cell fate determination in development to immune responses and inflammation. Neuroinflammation is one of the prime contributors to the initiation and progression of neurodegeneration in a variety of diseases, including Alzheimer's and Parkinson's diseases. Because astrocytes are the largest population of glial cells, they represent an important regulator of CNS function, both in healt...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 5, 2017 Category: Molecular Biology Source Type: research

Predicting and analyzing early wake-up associated gene expressions by integrating GWAS and eQTL studies
This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 4, 2017 Category: Molecular Biology Source Type: research

PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p
Publication date: Available online 3 November 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): R. Brea, O. Motiño, D. Francés, C. García-Monzón, J. Vargas, M. Fernández-Velasco, L. Boscá, M. Casado, P. Martín-Sanz, N. Agra MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still l...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 4, 2017 Category: Molecular Biology Source Type: research

Molecular mechanisms of cardiac pathology in diabetes – Experimental insights
This article is part of a Special Issue entitled: Cardiac Adaptations to Obesity, Diabetes and Insulin Resistance: Novel Targets and Therapies, edited by Dr. Jan Glatz, Professor Jason Dyck and Dr. Christine Des Rosiers. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 4, 2017 Category: Molecular Biology Source Type: research

Zac1/GPR39 phosphorylating CaMK-II contributes to the distinct roles of Pax3 and Pax7 in myogenic progression
This study will help the better understanding of the molecular mechanism of Pax3 and Pax7 in the regulation of myogenic progression and muscle fiber types, laying the providing suitable targets for the treatment of muscle diseases. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - November 3, 2017 Category: Molecular Biology Source Type: research

Parkinson's disease-associated pathogenic VPS35 mutation causes complex I deficits
In this study, we aimed to determine whether pathogenic VPS35 mutation impacts the activity of complex I and its underlying mechanism. Indeed, VPS35 D620N mutation led to decreased enzymatic activity and respiratory defects in complex I and II in patient fibroblasts. While no changes in the expression of the complex I and II subunits were noted, the level of assembled complex I and II as well as the supercomplex was significantly reduced in D620N fibroblasts. Importantly, inhibition of mitochondrial fission rescued the contents of assembled complexes as well as the functional defects in complex I and II. Overall, these res...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 24, 2017 Category: Molecular Biology Source Type: research

Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling
Publication date: November 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1863, Issue 11 Author(s): Zhenhua Ren, Xin Wang, Fanmuyi Yang, Mei Xu, Jacqueline A. Frank, Haiping Wang, Siying Wang, Zun-ji Ke, Jia Luo Ethanol exposure during development causes fetal alcohol spectrum disorders (FASD). A large body of evidence shows that ethanol produces multiple abnormalities in the developing central nervous system (CNS), such as smaller brain size, reduced volume of cerebral white matter, permanent loss of neurons, and alterations in synaptogenesis and myelinogenesis. The effects of ethano...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 24, 2017 Category: Molecular Biology Source Type: research

Arachidonic acid sex-dependently affects obesity through linking gut microbiota-driven inflammation to hypothalamus-adipose-liver axis
Publication date: November 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1863, Issue 11 Author(s): Pan Zhuang, Qiyang Shou, Yanhua Lu, Guangfa Wang, Jieni Qiu, Jun Wang, Lilin He, Jingnan Chen, Jingjing Jiao, Yu Zhang Unraveling the role of dietary lipids is beneficial to treat obesity and metabolic dysfunction. Nonetheless, how dietary lipids affect existing obesity remains unknown. Arachidonic acid (AA), a derivative of linoleic acid, is one of the crucial n-6 fatty acids. The aim of this study was to investigate whether AA affects obesity through associating microbiota-driven infl...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 24, 2017 Category: Molecular Biology Source Type: research

Hepatic mitochondrial bioenergetics in aged C57BL/6 mice exhibit delayed recovery from severe burn injury
Publication date: November 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1863, Issue 11 Author(s): Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Marc G. Jeschke Severe burn injuries initiate a cascade of downstream events, culminating in multiple organ dysfunction, sepsis, and even death. The elderly are in particular vulnerable to such outcomes, due primarily to a scarcity of knowledge on trauma progression at the biomolecular level in this population. Mitochondria, the cellular powerhouses, have been increasingly scrutinized recently for their ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 24, 2017 Category: Molecular Biology Source Type: research

Integrated approach reveals diet, APOE genotype and sex affect immune response in APP mice
Publication date: January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 1 Author(s): Kyong Nyon Nam, Cody M. Wolfe, Nicholas F. Fitz, Florent Letronne, Emilie L. Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 23, 2017 Category: Molecular Biology Source Type: research