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https://www.readbyqxmd.com/read/28646617/melanoma-associated-grm3-variants-dysregulate-melanosome-trafficking-and-camp-signaling
#1
Ana Neto, Craig J Ceol
Large-scale sequencing studies have revealed several genes that are recurrently mutated in melanomas. To annotate the melanoma genome we have expressed tumor-associated variants of these genes in zebrafish and characterized their effects on melanocyte development and function. Here, we describe expression of tumor-associated variants of the recurrently-mutated metabotropic glutamate receptor 3 (GRM3) gene. Unlike wild-type GRM3, tumor-associated GRM3 variants disrupted trafficking of melanosomes, causing their aggregation in the cell body...
June 24, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28646613/novel-tmc8-splice-site-mutation-in-epidermodysplasia-verruciformis-and-review-of-hpv-infections-in-patients-with-the-disease
#2
E Imahorn, Z Yüksel, I Spoerri, G Gürel, C Imhof, Z N Saraçoğlu, A E Koku Aksu, P L Rady, S K Tyring, W Kempf, P H Itin, B Burger
BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described EV patients. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families...
June 24, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28646530/pirfenidone-reduces-subchondral-bone-loss-and-fibrosis-after-murine-knee-cartilage-injury
#3
Deva D Chan, Jun Li, Wei Luo, Dan N Predescu, Brian J Cole, Anna Plaas
Pirfenidone is an anti-inflammatory and anti-fibrotic drug that has shown efficacy in lung and kidney fibrosis. Because inflammation and fibrosis have been linked to the progression of osteoarthritis, we investigated the effects of oral Pirfenidone in a mouse model of cartilage injury, which results in chronic inflammation and joint-wide fibrosis in mice that lack hyaluronan synthase 1 (Has1(-/-) ) in comparison to wild-type. Femoral cartilage was surgically injured in wild-type and Has1(-/-) mice, and Pirfenidone was administered in food starting after 3 days...
June 23, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28646223/regular-exercise-participation-improves-genomic-stability-in-diabetic-patients-an-exploratory-study-to-analyse-telomere-length-and-dna-damage
#4
Ivan Dimauro, Antonella Sgura, Monica Pittaluga, Fiorenza Magi, Cristina Fantini, Rosa Mancinelli, Antonio Sgadari, Stefania Fulle, Daniela Caporossi
Physical activity has been demonstrated to be effective in the prevention and treatment of different chronic conditions, including type 2 diabetes (T2D). In particular, several studies highlighted how the beneficial effects of physical activity may be related to the stability of the DNA molecule, such as longer telomeric ends. Here we analyze the effect of exercise training on telomere length, spontaneous and H2O2-induced DNA damage, as well as the apoptosis level in leukocytes from untrained or trained T2D patients vs...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646201/comprehensive-investigation-of-temporal-and-autism-associated-cell-type-composition-dependent-and-independent-gene-expression-changes-in-human-brains
#5
Qianhui Yu, Zhisong He
The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed. The substantial transcriptome alteration in neural disorders like autism has also been observed and is thought to be important for the pathology. While the cell type composition is known to be variable in brains, it remains unclear how it contributes to the temporal and pathological transcriptome changes in brains. Here, we applied a transcriptome deconvolution procedure to an age series RNA-seq dataset of healthy and autism samples, to quantify the contribution of cell type composition in shaping the temporal and autism pathological transcriptome in human brains...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646197/upregulate-kif4a-enhances-proliferation-invasion-of-hepatocellular-carcinoma-and-indicates-poor-prognosis-across-human-cancer-types
#6
Guojun Hou, Chuanpeng Dong, Zihui Dong, Gang Liu, Huilin Xu, Lei Chen, Lei Liu, Hongyang Wang, Weiping Zhou
Hepatocellular carcinoma (HCC) is one of the most aggressive and heterogeneous cancers worldwide. Herein, we demonstrate KIF4A (Chromosome-associated kinesin KIF4A) as a potential biomarker, is up-regulated in most samples of HCC. The expression level of KIF4A in tumor tissue is significantly associated with the survival time, and a significant correlation between KIF4A expression and clinical information stage, metastasis and tumor dimension was observed. We further measured the proliferation and migration ability of two HCC cell lines, HCC-LM3 and PLC/PRF/5, following KIF4A-siRNA transfection...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646076/transcriptomic-and-proteomic-profiling-provides-insight-into-mesangial-cell-function-in-iga-nephropathy
#7
Peidi Liu, Emelie Lassén, Viji Nair, Celine C Berthier, Miyuki Suguro, Carina Sihlbom, Matthias Kretzler, Christer Betsholtz, Börje Haraldsson, Wenjun Ju, Kerstin Ebefors, Jenny Nyström
IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22)...
June 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28646043/an-efficient-flp-based-toolkit-for-spatiotemporal-control-of-gene-expression-in-caenorhabditis-elegans
#8
Celia María Muñoz-Jiménez, Cristina Ayuso, Agnieszka Dobrzynska, Antonio Torres, Patricia de la Cruz Ruiz, Peter Askjaer
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To increase the utility of the FLP system in C. elegans we have generated a series of single-copy transgenic strains that stably express an optimized version of FLP in specific tissues or by heat induction...
June 23, 2017: Genetics
https://www.readbyqxmd.com/read/28646039/monocyte-adhesion-migration-and-extracellular-matrix-breakdown-is-regulated-by-integrin-%C3%AE-v%C3%AE-3-in-mycobacterium-tuberculosis-infection
#9
Sara Brilha, Riccardo Wysoczanski, Ashley M Whittington, Jon S Friedland, Joanna C Porter
In tuberculosis (TB), the innate inflammatory immune response drives tissue destruction, morbidity, and mortality. Monocytes secrete matrix metalloproteinases (MMPs), which have key roles in local tissue destruction and cavitation. We hypothesized that integrin signaling might regulate monocyte MMP secretion in pulmonary TB during cell adhesion to the extracellular matrix (ECM). Adhesion to type I collagen and fibronectin by Mycobacterium tuberculosis-stimulated monocytes increased MMP-1 gene expression by 2...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645700/antagonistic-regulation-of-spermatogonial-differentiation-in-zebrafish-danio-rerio-by-igf3-and-amh
#10
R D V S Morais, D Crespo, R H Nóbrega, M S Lemos, H J G van de Kant, L R de França, R Male, J Bogerd, R W Schulz
Fsh-mediated regulation of zebrafish spermatogenesis includes modulating the expression of testicular growth factors. Here, we study if and how two Sertoli cell-derived Fsh-responsive growth factors, anti-Müllerian hormone (Amh; inhibiting steroidogenesis and germ cell differentiation) and insulin-like growth factor 3 (Igf3; stimulating germ cell differentiation), cooperate in regulating spermatogonial development. In dose response and time course experiments with primary testis tissue cultures, Fsh up-regulated igf3 transcript levels and down-regulated amh transcript levels; igf3 transcript levels were more rapidly up-regulated and responded to lower Fsh concentrations than were required to decrease amh mRNA levels...
June 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28645613/regulation-of-testicular-steroidogenesis-by-foxa3-via-transcriptional-modulation-of-er%C3%AE-signaling-in-type-2-diabetes-mellitus-t2dm
#11
Yong Zhao, Hong-Xin Li, Ke Wang, Bin-Yuan Yan, Wei Li
Although both insulin and estrogen receptor α (ERα) are known to exert inhibitory effects on testicular steroidogenesis, it remains unknown whether these pathways regulate testosterone (T) production under certain pathological conditions [e.g., type 2 diabetes mellitus (T2DM)] in a coordinated manner. Here, we found that the expression of forkhead box protein A3 (Foxa3), an essential transcriptional regulator engaged in adipogenesis and energy metabolism, was significantly down-regulated in the Leydig cells (LCs) from T-deficient T2DM mice...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645612/il-1%C3%AE-induced-methylation-of-the-estrogen-receptor-er%C3%AE-gene-correlates-with-emt-and-chemoresistance-in-breast-cancer-cells
#12
Aura M Jiménez-Garduño, Mónica G Mendoza-Rodríguez, Daniel Urrutia-Cabrera, María C Domínguez-Robles, Eloy A Pérez-Yépez, Jorge Tonatiuh Ayala-Sumuano, Isaura Meza
Inflammation has been recently acknowledged as a key participant in the physiopathology of oncogenesis and tumor progression. The inflammatory cytokine IL-1β has been reported to induce the expression of markers associated with malignancy in breast cancerous cells through Epithelial-Mesenchymal Transition (EMT). Aggressive breast cancer tumors classified as Triple Negative do not respond to hormonal treatment because they lack three crucial receptors, one of which is the estrogen receptor alpha (ERα). Expression of ERα is then considered a good prognostic marker for tamoxifen treatment of this type of cancer, as the binding of this drug to the receptor blocks the transcriptional activity of the latter...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645582/improved-pfastbac%C3%A2-donor-plasmid-vectors-for-higher-protein-production-using-the-bac-to-bac%C3%A2-baculovirus-expression-vector-system
#13
Hui Shang, Tyler A Garretson, C M Senthil Kumar, Robert F Dieter, Xiao-Wen Cheng
The Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-based Bac-to-Bac(®) expression system consists of a bacmid and five pFastBac™ donor transfer vectors. It has been widely used for eukaryotic gene expression in insect cells to elucidate gene function in biotechnology laboratories. The pFastBac™ vectors contain a 50bp AcMNPV polyhedrin (polh) promoter and a 127bp SV40 polyadenylation (pA) signal for cloning a gene of interest into the bacmid, resulting in unsolved lower gene expression levels than the wild type (wt) AcMNPV in insect cells...
June 20, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28645527/inhibition-of-17beta-hydroxysteroid-dehydrogenase-type-7-modulates-breast-cancer-protein-profile-and-enhances-apoptosis-by-down-regulating-grp78
#14
Xiao-Qiang Wang, Juliette A Aka, Tang Li, Dan Xu, Charles J Doillon, Sheng-Xiang Lin
17beta-hydroxysteroid dehydrogenase type 7 (17β-HSD7) promotes breast cancer cell growth via dual-catalytic activity by modulating estradiol and DHT. Here, we clarified the expression pattern of 17β-HSD7 in postmenopausal luminal A type breast cancer with The Cancer Genome Atlas (TCGA) cohort. The impact of 17β-HSD7 inhibition on the proteome of MCF-7 cells was investigated and on cell apoptosis was revealed. MCF-7 cells were treated with an efficient inhibitor of 17β-HSD7 or with vehicle, and a differential proteomics study was performed using two-dimensional (2D) gel electrophoresis followed by mass spectrometry and ingenuity pathway analysis (IPA)...
June 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28645512/the-rna-seq-analysis-suggests-a-potential-multi-component-complement-system-in-oyster-crassostrea-gigas
#15
Lingling Wang, Huan Zhang, Leilei Wang, Daoxiang Zhang, Zhao Lv, Zhaoqun Liu, Weilin Wang, Zhi Zhou, Limei Qiu, Hao Wang, Jun Li, Linsheng Song
The complement system is one of the major effector mechanisms of immune system, playing essential roles in both the innate and adaptive immune responses. In the present study, the counterparts of vertebrate complement components were identified by screening the sequenced genome of Crassostrea gigas, resulting in the identification of 792 gene models containing complement-related domains. The transcriptome of haemocytes at 6, 12 and 24 h post lipopolysaccharides (LPS) stimulation showed differential expression of 77 C1q domain containing proteins, 53 C-type lectins and 42 fibrinogen-related proteins...
June 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28645477/the-overexpression-of-cpr-and-p450-3a4-in-pancreatic-cancer-cells-changes-the-metabolic-profile-and-increases-the-cytotoxicity-and-pro-apoptotic-activity-of-acridine-antitumor-agent-c-1748
#16
Barbara Borowa-Mazgaj, Anna Mróz, Ewa Augustin, Ewa Paluszkiewicz, Zofia Mazerska
Drug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and AsPC-1, differing in expression levels of commonly mutated genes for this cancer type, to C-1748 treatment and (ii) the role of P450 3A4 isoenzyme and cytochrome P450 reductase (CPR) in the modulation of this response...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28645315/role-of-inhibitors-of-serine-peptidases-in-protecting-leishmania-donovani-against-the-hydrolytic-peptidases-of-sand-fly-midgut
#17
Sudha Verma, Sushmita Das, Abhishek Mandal, Md Yousuf Ansari, Sujata Kumari, Rani Mansuri, Ajay Kumar, Ruby Singh, Savita Saini, Kumar Abhishek, Vijay Kumar, Ganesh Chandra Sahoo, Pradeep Das
BACKGROUND: In vector-borne diseases such as leishmaniasis, the sand fly midgut is considered to be an important site for vector-parasite interaction. Digestive enzymes including serine peptidases such as trypsin and chymotrypsin, which are secreted in the midgut are one of the obstacles for Leishmania in establishing a successful infection. The presence of some natural inhibitors of serine peptidases (ISPs) has recently been reported in Leishmania. In the present study, we deciphered the role of these ISPs in the survival of Leishmania donovani in the hostile sand fly midgut environment...
June 23, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28645305/high-expression-of-collagen-triple-helix-repeat-containing-1-cthrc1-facilitates-progression-of-oesophageal-squamous-cell-carcinoma-through-mapk-mek-erk-fra-1-activation
#18
Chunni Wang, Zitong Li, Fei Shao, Xueying Yang, Xiaoli Feng, Susheng Shi, Yibo Gao, Jie He
BACKGROUND: Oesophageal cancer is one of the most common malignancies worldwide,and oesophageal squamous cell carcinoma (ESCC) is the predominant histological type both globally and in China. Collagen triple helix repeat containing 1 (CTHRC1) has been found to be upregulated in ESCC. However, its role in tumourigenesis and progression of ESCC remains unclear. METHODS: Using our previous ESCC mRNA profiling data, we screened upregulated genes to identify those required for proliferation...
June 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28645300/bacterial-ghosts-as-adjuvants-mechanisms-and-potential
#19
REVIEW
Irshad A Hajam, Pervaiz A Dar, Gayeon Won, John Hwa Lee
Bacterial ghosts (BG) are empty cell envelopes derived from Gram-negative bacteria. They contain many innate immunostimulatory agonists, and are potent activators of a broad range of cell types involved in innate and adaptive immunity. Several considerable studies have demonstrated the effectiveness of BG as adjuvants as well as their ability to induce proinflammatory cytokine production by a range of immune and non-immune cell types. These proinflammatory cytokines trigger a generalized recruitment of T and B lymphocytes to lymph nodes that maximize the chances of encounter with their cognate antigen, and subsequent elicitation of potent immune responses...
June 24, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28645297/interleukin-1-receptor-type-1-is-overexpressed-in-neurons-but-not-in-glial-cells-within-the-rat-superficial-spinal-dorsal-horn-in-complete-freund-adjuvant-induced-inflammatory-pain
#20
Krisztina Holló, László Ducza, Zoltán Hegyi, Klaudia Dócs, Krisztina Hegedűs, Erzsébet Bakk, Ildikó Papp, Gréta Kis, Zoltán Mészár, Zsuzsanna Bardóczi, Miklós Antal
BACKGROUND: All known biological functions of the pro-inflammatory cytokine interleukin-1β (IL-1β) are mediated by type 1 interleukin receptor (IL-1R1). IL-1β-IL-1R1 signaling modulates various neuronal functions including spinal pain processing. Although the role of IL-1β in pain processing is generally accepted, there is a discussion in the literature whether IL-1β exerts its effect on spinal pain processing by activating neuronal or glial IL-1R1. To contribute to this debate, here we investigated the expression and cellular distribution of IL-1R1 in the superficial spinal dorsal horn in control animals and also in inflammatory pain...
June 23, 2017: Journal of Neuroinflammation
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