Early intervention with breast milk mesenchymal stem cells attenuates the development of diabetic-induced testicular dysfunction via hypothalamic Kisspeptin/Kiss1r-GnRH/GnIH system in male rats
This study was an attempt to explore the potential effect of breast milk mesenchymal stem cells (Br-MSCs) as a therapeutic tool for diabetic induced reproductive dysfunction at molecular level. Forty-five adult male Sprague Dawely rats were divided into 3 groups (n = 15); control group, diabetic group, and Br-MSCs treated diabetic group. The homing ability of Br-MSCs in diabetic treated rat testicles was confirmed via semi-quantitative RT- PCR analysis of a human specific Gapdh mRNA expression level. Our result showed that type1 diabetic rats exerted an elevation in blood glucose level and a reduction in body weight, f...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

TIPE1 accelerates atherogenesis by inducing endothelial dysfunction in response to oxidative stress
In this study, we demonstrated that TIPE1 promoted atherogenesis by inducing endothelial dysfunction. When human umbilical vein endothelial cells (HUVECs) were exposed to oxidative stress, the level of TIPE1 was significantly up-regulated, and the ROS generation markedly increased in TIPE1 over-expressing HUVECs. As a result, the growth of HUVECs was inhibited, and the apoptosis was enhanced. However, the cell contact ability between HUVECs and THP-1 cells were augmented due to the up-regulation of adhesion molecules such as E-selectin and ICAM-1 induced by TIPE1 overexpression. Importantly, ApoE−/− mice inject...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

Plasma based targeted metabolomic analysis reveals alterations of phosphatidylcholines and oxidative stress markers in guinea pig model of allergic asthma
Publication date: Available online 29 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Martin Kertys, Marian Grendar, Petra Kosutova, Daniela Mokra, Juraj MokryAbstractBronchial asthma is one of the most common, chronic respiratory diseases, characterized by reversible airway obstruction, eosinophil and Th2 infiltration, airway hyperresponsiveness and airway remodelling; with many cells and mediators involved. Metabolomics is a relatively new field in “omics” sciences enabling the identification of metabolome for better diagnostics and studying of diseases phenotype...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

The imbalance between dynamic and stable microtubules underlies neurodegeneration induced by 2,5-hexanedione
In conclusion, by showing the imbalance between dynamic and stable microtubules in hydrocarbon-induced parkinsonism, our data support the crucial role of microtubule defects in triggering neurodegeneration. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

N-terminal tau truncation in the pathogenesis of Alzheimer's disease (AD): Developing a novel diagnostic and therapeutic approach
Publication date: Available online 29 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): G. Amadoro, V. Latina, V. Corsetti, P. CalissanoAbstractTau truncation occurs at early stages during the development of human Alzheimer's disease (AD) and other tauopathy dementias. Tau cleavage, particularly in its N-terminal projection domain, is able to drive per se neurodegeneration, regardless of its pro-aggregative pathway(s) and in fragment(s)-dependent way. In this short review, we highlight the pathological relevance of the 20-22 kDa NH2-truncated tau fragment which is endowed with...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

Fasting reveals largely intact systemic lipid mobilization mechanisms in respiratory chain complex III deficient mice
Publication date: Available online 29 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Nikica Tomašić, Heike Kotarsky, Rejane de Oliveira Figueiredo, Eva Hansson, Matthias Mörgelin, Ivan Tomašić, Jukka Kallijärvi, Eskil Elmér, Matti Jauhiainen, Erik A. Eklund, Vineta FellmanAbstractMice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystroph...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 29, 2019 Category: Molecular Biology Source Type: research

Eicosanoid pathway on host resistance and inflammation during Mycobacterium tuberculosis infection is comprised by LTB4 reduction but not PGE2 increment
Publication date: Available online 28 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Carlos Arterio Sorgi, Elyara Maria Soares, Rogério Silva Rosada, Claudia Silva Bitencourt, Karina Furlani Zoccal, Priscilla Aparecida Tartari Pereira, Caroline Fontanari, Izaíra Brandão, Ana Paula Masson, Simone Gusmão Ramos, Célio Lopes Silva, Fabiani Gai Frantz, Lúcia Helena FaccioliAbstractThe functions of eicosanoids, a family of potent biologically active lipid mediators, are not restricted to inflammatory responses and they also act as mediators...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 28, 2019 Category: Molecular Biology Source Type: research

Icariin protects human nucleus pulposus cells from hydrogen peroxide-induced mitochondria-mediated apoptosis by activating nuclear factor erythroid 2-related factor 2
In this study, the mechanisms underlying its protection against hydrogen peroxide (H2O2)-induced oxidative stress injury were investigated. In vitro, we demonstrated that icariin inhibits H2O2-induced mitochondria-mediated apoptosis. It upregulates oxidative stress mediators, i.e., reactive oxygen species, and downregulates mitochondrial membrane potential. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a key factor involved in the regulation of the endogenous defense system. It was proved that icariin could activate the Nrf-2 signaling pathway, upregulate the protein expression of nuclear respiratory factor-1 and ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 28, 2019 Category: Molecular Biology Source Type: research

A lactate-induced Snail/STAT3 pathway drives GPR81 expression in lung cancer cells
Publication date: Available online 28 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Qiang Xie, Zhanzhan Zhu, Yuanpeng He, Zhijian Zhang, Yao Zhang, Yixuan Wang, Jincheng Luo, Tianchou Peng, Feng Cheng, Jiguang Gao, Yuxiang Cao, Huijun Wei, Zhihao WuAbstractHighly expressed G protein-coupled receptor 81 (GPR81), a receptor for lactate, is emerging as a critical regulator of tumor growth and metastasis. However, the mechanistic basis for its highly expression in cancer cells remains elusive. Here we report that tumor-derived lactate transcriptionally regulates GPR81 expression...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 28, 2019 Category: Molecular Biology Source Type: research

Differential metabolic and multi-tissue Transcriptomic responses to fructose consumption among genetically diverse mice
We report that fructose has strain-specific effects, involving tissue-specific gene regulatory cascades in hypothalamus, liver, and white adipose tissues. DBA mice showed the largest numbers of genes associated with adiposity, congruent with their highest susceptibility to adiposity gain and glucose intolerance across the three tissues. In contrast, B6 and FVB mainly exhibited cholesterol phenotypes, accompanying the largest number of adipose genes correlating with total cholesterol in B6, and liver genes correlating with LDL in FVB mice. Tissue-specific network modeling predicted strain-and tissue-specific regulators such...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 26, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 12Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 25, 2019 Category: Molecular Biology Source Type: research

Cellular models of batten disease
Publication date: Available online 23 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Christopher J. Minnis, Christopher D. Thornton, Lorna M. FitzPatrick, Tristan R. McKayAbstractThe Neuronal Ceroid Lipofuscinoses (NCL), otherwise known as Batten disease, are a group of neurodegenerative diseases caused by mutations in 13 known genes. All except one NCL is autosomal recessive in inheritance, with similar aetiology and characterised by the accumulation of autofluorescent storage material in the lysosomes of cells. Age of onset and rate of progression vary between the NCLs. The...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 25, 2019 Category: Molecular Biology Source Type: research

Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity
Publication date: Available online 23 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): V. Arroyo-Jousse, A. Jaramillo, E. Castaño-Moreno, M. Lépez, K. Carrasco-Negüe, P. CasanelloAbstractMaternal pregestational obesity is a well-known risk factor for offspring obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes. The mechanisms by which maternal obesity can induce alterations in fetal and later neonatal metabolism are not fully elucidated due to its complexity and multifactorial causes. Two adipokines, leptin and adiponectin, are involved i...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 23, 2019 Category: Molecular Biology Source Type: research

Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity
This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the l...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 22, 2019 Category: Molecular Biology Source Type: research

RAD6B is a major mediator of triple negative breast cancer cisplatin resistance: Regulation of translesion synthesis/Fanconi anemia crosstalk and BRCA1 independence
Publication date: Available online 19 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Brittany Haynes, Ambikai Gajan, Pratima Nangia-Makker, Malathy P. ShekharAbstractTriple negative breast cancer (TNBC) is an aggressive breast cancer subtype with few therapy options besides chemotherapy. Although platinum-based drugs have shown initial activity in BRCA1-mutated TNBCs, chemoresistance remains a challenge. Here we show that RAD6B (UBE2B), a principal mediator of translesion synthesis (TLS), is overexpressed in BRCA1 wild-type and mutant TNBCs, and RAD6B overexpression correlate...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 20, 2019 Category: Molecular Biology Source Type: research

Painful interactions: Microbial compounds and visceral pain
Publication date: Available online 18 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): I.A.M. van Thiel, S. Botschuijver, W.J. de Jonge, J. SeppenAbstractVisceral pain, characterized by abdominal discomfort, originates from organs in the abdominal cavity and is a characteristic symptom in patients suffering from irritable bowel syndrome, vulvodynia or interstitial cystitis. Most organs in which visceral pain originates are in contact with the external milieu and continuously exposed to microbes. In order to maintain homeostasis and prevent infections, the immune- and nervous sy...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 19, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 11Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 15, 2019 Category: Molecular Biology Source Type: research

Publisher's note
Publication date: 1 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 11Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 15, 2019 Category: Molecular Biology Source Type: research

O-GlcNAcylation of RAF1 increases its stabilization and induces the renal fibrosis
Publication date: Available online 12 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Du Feng, Li Sheng-Dong, Wu Tong, Du Zhen-XianAbstractEpithelial-mesenchymal transition (EMT) is considered to be one of the most important mechanisms for the progression of renal interstitial fibrosis (RIF). Recently the relationship between post-translational modifications and EMT has been reported. O-GlcNAcylation, one of the key post-translational modifications, was rarely mentioned about its role in EMT, especially in EMT during the process of RIF. The current study aimed to determine w...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 13, 2019 Category: Molecular Biology Source Type: research

Pharmacological approaches to tackle NCLs
Publication date: Available online 12 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Kauss Valerjans, Dambrova Maija, Medina Diego LuisAbstractNeuronal ceroid lipofuscinoses, also collectively known as Batten disease, are a group of rare monogenic disorders caused by mutations in at least 13 different genes. They are characterized by the accumulation of lysosomal storage material and progressive neurological deterioration with dementia, epilepsy, retinopathy, motor disturbances, and early death [1]. Although the identification of disease-causing genes provides an important ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 13, 2019 Category: Molecular Biology Source Type: research

Downregulation of hepatic stem cell factor by Vivo-Morpholino treatment inhibits mast cell migration and decreases biliary damage/senescence and liver fibrosis in Mdr2−/− mice
ConclusionCholangiocytes secrete increased levels of SCF inducing MC migration, contributing to biliary damage/hepatic fibrosis. Targeting MC infiltration may be an option to ameliorate PSC progression. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 13, 2019 Category: Molecular Biology Source Type: research

Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus
In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 10, 2019 Category: Molecular Biology Source Type: research

Inactivation of FAM20B causes cell fate changes in annulus fibrosus of mouse intervertebral disc and disc defects via the alterations of TGF-β and MAPK signaling pathways
In this study, we created Fam20B conditional knockout (cKO) mice in which FAM20B was inactivated in type I collagen-expressing cells, the main type of cells in the outer AF of IVD. The cKO mice showed severe spine deformity and remarkable IVD defects associated with AF malformation. The AF of cKO mice had a lower level of chondroitin sulfate and heparan sulfate, and the outer AF cells lost their normal fibroblast-like morphology and acquired chondrocyte phenotypes, expressing a higher level of Sox 9 and type II collagen along with a reduced level of type I collagen. The level of phospho-Smad 2 and phospho-Smad 3, and that ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 10, 2019 Category: Molecular Biology Source Type: research

Chronic inhibition of chemokine receptor CXCR2 attenuates cardiac remodeling and dysfunction in spontaneously hypertensive rats
Publication date: Available online 5 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Yun-Long Zhang, Chi Geng, Jie Yang, Jiao Fang, Xiao Yan, Pang-Bo Li, Lei-Xin Zou, Chen Chen, Shu-Bin Guo, Hui-Hua Li, Ying LiuAbstractSystem hypertension is a major risk factor for cardiac hypertrophy and heart failure. Our recent findings reveal that the ablation or inhibition of C-X-C chemokine receptor (CXCR) 2 blocks this process in mice; however, it is not clear whether the pharmacological inhibition of CXCR2 attenuates hypertension and subsequent cardiac remodeling in spontaneously hyp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 6, 2019 Category: Molecular Biology Source Type: research

mTORC1 inhibition attenuates necroptosis through RIP1 inhibition-mediated TFEB activation
Publication date: Available online 6 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Koki Abe, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Tatsuya Sato, Hidemichi Kouzu, Kei Nakata, Wataru Ohwada, Yukishige Kimura, Hirohito Sugawara, Satoru Shibata, Yusuke Igaki, Shoya Ino, Tetsuji MiuraAbstractAccumulating evidence indicates that necroptosis contributes to cardiovascular diseases. We recently reported suppression of autophagy by necroptotic signals in cardiomyocytes and protective action of rapamycin. Here we examined the mechanism by which mTORC1 inhibition ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - September 6, 2019 Category: Molecular Biology Source Type: research

Type 1 diabetes induces cognitive dysfunction in rats associated with alterations of the gut microbiome and metabolomes in serum and hippocampus
In this study, therefore, we investigated changes in the gut microbiome and metabolome in serum and hippocampus between advanced-stage T1D (AST1D) rats with cognitive decline and age-matched controls (AMC), and explored the possible mechanism of the gut-microbiota-metabolite axis in T1D-induced cognitive dysfunction. The results demonstrated that AST1D rats possessed peculiar metabolic phenotypes in serum and hippocampus relative to AMC rats, as characterized by decreases in tricarboxylic acid (TCA) cycle and amino acid and choline metabolism as well as disturbances in glutamate/GABA-glutamine cycle and astrocyte-neuron me...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 29, 2019 Category: Molecular Biology Source Type: research

Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis
Publication date: Available online 29 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Deepika Awasthi, Sheela Nagarkoti, Samreen Sadaf, Tulika Chandra, Sachin Kumar, Madhu DikshitAbstractNeutrophil extracellular traps (NETs) play a pivotal role in the innate immune defense, as well as in the pathophysiology of various inflammatory disease conditions. Two major types of NETosis have been described - NOX-dependent and independent. The present study was undertaken to assess metabolic requirements of NETs formation by using PMA and A23187 as the inducers of NOX-dependent and NOX-in...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 29, 2019 Category: Molecular Biology Source Type: research

G-MDSC-derived exosomes attenuate collagen-induced arthritis by impairing Th1 and Th17 cell responses
Publication date: Available online 27 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Dongwei Zhu, Jie Tian, Xinyu Wu, Min Li, Xinyi Tang, Ke Rui, Hongye Guo, Jie Ma, Huaxi Xu, Shengjun WangAbstractThe therapeutic effect of myeloid-derived suppressor cells (MDSCs) in mice with collagen-induced arthritis (CIA) remains controversial. We analyzed the role of exosomes derived from granulocytic MDSCs (G-MDSCs) in CIA and explored the potential mechanism underlying the immunosuppressive effect. In CIA mice, G-MDSC-derived exosomes (G-exo) efficiently reduced the mean arthritis index,...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 29, 2019 Category: Molecular Biology Source Type: research

Heparan sulfate proteoglycans: The sweet side of development turns sour in mucopolysaccharidoses
Publication date: Available online 26 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Valeria De Pasquale, Luigi Michele PavoneAbstractHeparan sulfate proteoglycans (HSPGs) are complex carbohydrate-modified proteins ubiquitously expressed on cell surfaces, extracellular matrix and basement membrane of mammalian tissues. Beside to serve as structural constituents, they regulate multiple cellular activities. A critical involvement of HSPGs in development has been established, and perturbations of HSPG-dependent pathways are associated with many human diseases. Recent evidence sug...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 28, 2019 Category: Molecular Biology Source Type: research

Multi-omics studies in cellular models of methylmalonic acidemia and propionic acidemia reveal dysregulation of serine metabolism
ConclusionWe identified abnormal serine metabolism as a novel area of cellular dysfunction in MMA and PA, thus introducing a potential new target for therapeutic investigation. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 25, 2019 Category: Molecular Biology Source Type: research

Identification of novel TGF-β regulated genes with pro-migratory roles
In this study, we performed RNA-sequencing analysis of MCF10A cells and identified 1166 genes that were upregulated and 861 genes that were downregulated by TGF-β. Gene set enrichment analysis revealed that focal adhesion and metabolic pathways were the top enriched pathways of the up- and downregulated genes, respectively. Genes in these pathways also possess significant predictive value for renal cancers. Moreover, we confirmed that TGF-β induced expression of MICAL1 and 2, and the histone demethylase, KDM7A, and revealed their regulatory roles on TGF-β-induced cell migration. We also show a critical effec...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 23, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 10Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 23, 2019 Category: Molecular Biology Source Type: research

Characterization of the C584R variant in the mtDNA depletion syndrome gene FBXL4, reveals a novel role for FBXL4 as a regulator of mitochondrial fusion
We report two siblings, from consanguineous parents, harbouring a previously uncharacterized homozygous variant in FBXL4 (c.1750 T > C; p.Cys584Arg). Both patients presented with encephalomyopathy, lactic acidosis and cardiac hypertrophy, which are reported features of FBXL4 impairment. Remarkably, dichloroacetate (DCA) administration to the younger sibling improved metabolic acidosis and reversed cardiac hypertrophy. Characterization of FBXL4 patient fibroblasts revealed severe bioenergetic defects, mtDNA depletion, fragmentation of mitochondrial networks, and abnormalities in mtDNA nucleoids. These phenotypes, o...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 22, 2019 Category: Molecular Biology Source Type: research

Enhanced differentiation of human dopaminergic neuronal cell model for preclinical translational research in Parkinson's disease
Publication date: Available online 20 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Dilshan S. Harischandra, Dharmin Rokad, Shivani Ghaisas, Saurabh Verma, Alan Robertson, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G. KanthasamyAbstractHuman-derived neuronal cell lines are progressively being utilized in understanding neurobiology and preclinical translational research as they are biologically more relevant than rodent-derived cells lines. The Lund human mesencephalic (LUHMES) cell line comprises human neuronal cells that can be differentiated to post-mito...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 22, 2019 Category: Molecular Biology Source Type: research

Placental structure in gestational diabetes mellitus
This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 22, 2019 Category: Molecular Biology Source Type: research

Neutrophil gelatinase-associated lipocalin (NGAL) is localised to the primary cilium in renal tubular epithelial cells - A novel source of urinary biomarkers of renal injury
ConclusionThe accumulation of NGAL in supernatants in vitro and in the urine of CAN patients was concurrent with loss of Arl13b, a specific ciliary protein. The findings of this study propose that increased NGAL urinary concentrations are directly linked to deciliation of the renal epithelial cells as a result of injury. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 16, 2019 Category: Molecular Biology Source Type: research

Cross-talk between guanidinoacetate neurotoxicity, memory and possible neuroprotective role of creatine
This study helps to elucidate the protective effects of creatine against the damage caused by GAA. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis
This study, tested improvement in glycemic control by Ad36 and delay in onset of cognitive decline in APPswe transgenic mice (Tg2576 line), a model of genetic predisposition to impaired glycemic control and AD. Three-month old APPswe mice were divided into Ad36 infected (Ad36) or mock infected (control) groups and baseline glycemic control measured by glucose tolerance test (GTT) prior to infection. Changes in glycemic control were determined 10- and 24-week post infection. Serum insulin was also measured during GTT. Cognition was determined by Y-maze test, while motor coordination and skill acquisition by rotarod test. Gl...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Role of endothelin receptor type A on catecholamine regulation in the olfactory bulb of DOCA-salt hypertensive rats: Hemodynamic implications
Publication date: Available online 6 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): María J. Guil, Mercedes I. Schöller, Luis R. Cassinotti, Vinicia C. Biancardi, Soledad Pitra, Liliana G. Bianciotti, Javier E. Stern, Marcelo S. VattaAbstractIncreasing evidence shows that the olfactory bulb is involved in blood pressure regulation in health and disease. Enhanced noradrenergic transmission in the olfactory bulb was reported in hypertension. Given that endothelins modulate catecholamines and are involved in the pathogenesis of hypertension, in the present study we so...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Vibrational spectroscopy-based quantification of liver steatosis
In conclusion, our work demonstrates the easy-to-use method that can be applied in laboratory routine as a beneficial alternative to the established ORO staining. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Structure-toxicity relationships of saturated and unsaturated free fatty acids for elucidating the lipotoxic effects in human EndoC-βH1 beta-cells
Publication date: Available online 6 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): T. Plötz, A.S. von Hanstein, B. Krümmel, A. Laporte, I. Mehmeti, S. LenzenAbstractLipotoxicity has been considered a major cause for beta-cell dysfunction in type 2 diabetes mellitus. However, the underlying mechanisms are still unclear. To achieve a better understanding of the toxicity a wide range of structurally different free fatty acids (FFAs) has been analyzed in human EndoC-βH1 beta-cells.Exposure of human EndoC-βH1 beta-cells to physiological saturated and monounsatu...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Simvastatin induces autophagic flux to restore cerulein-impaired phagosome-lysosome fusion in acute pancreatitis
ConclusionOur findings reveal the novel role of simvastatin in enhancing autophagic flux to prevent pancreatic cell injury and pancreatitis.Graphical abstractModel representing the protective effects of simvastatin in cerulein-induced acute pancreatitis in mice. Cerulein induced mitophagy, however, the fusion of autophagosomes and lysosomes is impaired causing accumulation of autophagosomes and mtDNA release in extracellular environment. Simvastatin restored the fusion resulting in formation of functional autolysosomes resulted in cargo clearance including dysfunctional mitochondria (red). Simvastatin-induced mitophagy als...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Inhibition of peripheral serotonin synthesis by LP533401 and disturbances in calciotropic hormones attenuated excessive osteoblastogenesis with simultaneous improvement of bone mineral status in 5/6 nephrectomized rats
In conclusion, the inhibition of GDS synthesis resulted in the mitigation of osteoblastogenesis observed in CKD, which translated into improvement of bone mineral status. This study provides key mechanistic insights into how modification of GDS-dependent molecular pathway affects bone mineral status in CKD and lays the groundwork for translating the role of functional serotonin signaling in the origin of impaired bone mineral status in patients with CKD. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 7, 2019 Category: Molecular Biology Source Type: research

Elimination of KLK5 inhibits early skin tumorigenesis by reducing epidermal proteolysis and reinforcing epidermal microstructure
Publication date: Available online 2 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Georgios Pampalakis, Eleni Zingkou, Lucas Kaklamanis, Magda Spella, Georgios T. Stathopoulos, Georgia SotiropoulouAbstractEpidermal desquamation involves a finely-tuned proteolytic cascade ensuring the regulated cleavage of desmosomes that releases old stratum corneum outermost layers. Although the roles of desmosomes in normal physiology are well-established, their putative involvement in cancer remains unexplored. The KLK5 protease is thought of having fundamental roles in epidermal proteolys...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 3, 2019 Category: Molecular Biology Source Type: research

Tetrahydrobiopterin enhances mitochondrial biogenesis and cardiac contractility via stimulation of PGC1α signaling
Publication date: Available online 3 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Hyoung Kyu Kim, Jouhyun Jeon, In-Sung Song, Hae Jin Heo, Seung Hun Jeong, Le Thanh Long, Vu Thi Thu, Tae Hee Ko, Min Kim, Nari Kim, Sung Ryul Lee, Jae-Seong Yang, Mi Seon Kang, Jung-Mo Ahn, Je-Yoel Cho, Kyung Soo Ko, Byoung Doo Rhee, Bernd Nilius, Nam-Chul Ha, Ippei ShimizuAbstractTetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous target in cardiovascular diseases. Although it is involved in cardiovascular metabolism and mitochondrial biology, its mechanisms of action are un...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 3, 2019 Category: Molecular Biology Source Type: research

IDH2 deficiency impairs cutaneous wound healing via ROS-dependent apoptosis
Publication date: Available online 31 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sung Hwan Kim, Jeen-Woo ParkAbstractDermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue that play a pivotal role in cutaneous wound healing by synthesizing fibronectin (a component of the extracellular matrix), secreting angiogenesis factors, and generating strong contractile forces. In wound healing, low concentrations of reactive oxygen species (ROS) are essential in combating invading microorganisms and in cell-survival signaling. However, excessi...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 1, 2019 Category: Molecular Biology Source Type: research

Role of heme oxygenase 1 and human chorionic gonadotropin in pregnancy associated diseases
Publication date: Available online 31 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Victoria Gallardo, Marcelo González, Fernando Toledo, Luis SobreviaAbstractHeme oxygenase (HO) is the enzyme that catalyses heme breakdown to biliverdin, carbon monoxide, and ferrous ion. Biliverdin is rapidly converted to bilirubin by biliverdin reductase. HO-1, the inducible HO isoenzyme, is involved in placental development. HO-1 decreases the oxidative stress and promotes an immune tolerant microenvironment at the foetomaternal interface. This isozyme also regulates angiogenesis and v...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 1, 2019 Category: Molecular Biology Source Type: research

Adseverin modulates morphology and invasive function of MCF7 cells
Publication date: Available online 29 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): J. Tanic, Y. Wang, W. Lee, N.M. Coelho, M. Glogauer, C.A. McCullochAbstractAdseverin (Ads) is a Ca2+-dependent actin-capping and severing protein that is highly expressed in gastric, prostate and bladder cancer cells. Currently it is unknown whether Ads contributes to the subcortical actin remodeling associated with the formation of cell extensions and matrix invasion in cancer. We compared cell extension formation and matrix degradation in Ads wildtype and Ads-null MCF7 breast cancer cells gene...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 30, 2019 Category: Molecular Biology Source Type: research

Low fluid shear stress conditions contribute to activation of cerebral cavernous malformation signalling pathways
Publication date: Available online 29 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jia Li, Yang Zhao, Paul Coleman, Jinbiao Chen, Ka Ka Ting, Jaesung Peter Choi, Xiangjian Zheng, Mathew A. Vadas, Jennifer R. GambleAbstractCerebral cavernous malformations (CCMs) are vascular malformations that cause hemorrhagic stroke. CCMs can arise from loss-of-function mutations in any one of CCM1 (KRIT1), CCM2 or CCM3 (PDCD10). Despite the mutation being in all endothelial cells the CCM lesions develop primarily in the regions with low fluid shear stress (FSS). Here we investigated the role...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 30, 2019 Category: Molecular Biology Source Type: research

Salubrinal enhances eIF2α phosphorylation and improves fertility in a mouse model of classic galactosemia
Publication date: Available online 27 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): B. Balakrishnan, A. Siddiqi, J. Mella, A. Lupo, E. Li, J. Hollien, J. Johnson, K. LaiAbstractLoss of galactose-1 phosphate uridylyltransferase (GALT) activity in humans results in Classic Galactosemia, and the GalT-deficient (GalT−/−) mouse mimics the patient condition. GalT−/− ovaries display elevated endoplasmic reticulum (ER) stress marker, BiP, and downregulated canonical phosphatidylinositol 3-kinase (Pi3k)/protein kinase B (Akt) growth/pro-survival signaling. Number...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 28, 2019 Category: Molecular Biology Source Type: research