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https://www.readbyqxmd.com/read/29342010/the-ever-expanding-saga-of-the-proprotein-convertases-and-their-roles-in-body-homeostasis-emphasis-on-novel-proprotein-convertase-subtilisin-kexin-number-9-functions-and-regulation
#1
Nabil G Seidah, Michel Chrétien, Majambu Mbikay
PURPOSE OF REVIEW: The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis...
January 15, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29341930/activation-of-estrogen-receptor-beta-er%C3%AE-regulates-the-expression-of-n-cadherin-e-cadherin-and-%C3%AE-catenin-in-androgen-independent-prostate-cancer-cells
#2
Rafael de Souza Silva, Ana Paola G Lombardi, Deborah Simão de Souza, Carolina M Vicente, Catarina S Porto
The aim of the present study was to investigate the impact of the activation of estrogen receptors on expression and localization of N-cadherin, E-cadherin and non-phosphorylated β-catenin in androgen-independent prostate cancer cells (PC-3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A). Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145 cells. E-cadherin was detected only in DU-145 cells and β-catenin was detected in all cells studied. N-cadherin and β-catenin were located preferentially in the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells...
January 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29341830/pregnancy-related-hormones-progesterone-and-human-chorionic-gonadotrophin-upregulate-expression-of-maternal-plasma-gelsolin
#3
Renu Garg, Nagesh Peddada, Kunzes Dolma, Neeraj Khatri, Ashish Ashish
Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating actin filaments, is an upcoming novel biomarker. Its level changes in multiple disease and injury conditions, attributable mainly to its consumption during actin clearance, the endogenous regulation of its expression, however, remains elusive as well as unexplored. Here, we are reporting first isolation of the promoter region of pGSN gene and investigation of its transcriptional regulation during pregnancy (a natural process associated with a well programmed injury course of parturition)...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29341224/comparative-rna-seq-transcriptome-analysis-on-silica-induced-pulmonary-inflammation-and-fibrosis-in-mice-silicosis-model
#4
Jiayi Chen, Yuqin Yao, Xiaolan Su, Ying Shi, Xuejiao Song, Linshen Xie, Jia You, Liantian Tian, Luo Yang, Aiping Fang, Jingyuan Xiong
Silicosis is a long-established public health issue in developing countries due to increasingly serious air pollution and poorly implemented occupational safety regulation. Inhalation of silica triggers cytotoxicity, oxidative stress, pulmonary inflammation and eventually silicosis. Current understanding in the pathogenesis and mechanism of silicosis is limited, and no effective cure is clinically available once silicosis is developed. A number of studies were conducted to investigate silica-induced alternate gene expressions in pulmonary cells...
January 16, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29339716/to-explore-the-mechanism-of-the-grm4-gene-in-osteosarcoma-by-rna-sequencing-and-bioinformatics-approach
#5
Yunguo Pang, Jinmin Zhao, Mitra Fowdur, Yun Liu, Hao Wu, Maolin He
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics...
January 17, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29339659/fc%C3%AE-r-ros-ck2%C3%AE-is-the-key-inducer-of-nf-%C3%AE%C2%BAb-activation-in-a-murine-model-of-asthma
#6
June-Mo Kim, Hae-Kyoung Kim, Yoo-Na Im, Yun-Soo Bae, Suhn-Young Im, Hern-Ku Lee
BACKGROUND: The transcription factor nuclear factor (NF)-κB plays a pivotal role in the development of allergic airway inflammation. However, the mechanism of NF-κB activation in asthma remains to be elucidated. METHODS: CK2α activation was assessed by CK2α phosphorylation and protein expression. Airway levels of histamine and cytokines were determined by ELISA. We used 2 (active and passive) forms of allergic pulmonary inflammation models. In the active form, the animals were immunized with ovalbumin (OVA) intraperitoneally, followed by an airway challenge with OVA...
January 17, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29339535/functional-changes-of-ampa-responses-in-human-induced-pluripotent-stem-cell-derived-neural-progenitors-in-fragile-x-syndrome
#7
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339504/complement-pathway-gene-activation-and-rising-circulating-immune-complexes-characterize-early-disease-in-hiv-associated-tuberculosis
#8
Hanif Esmail, Rachel P Lai, Maia Lesosky, Katalin A Wilkinson, Christine M Graham, Stuart Horswell, Anna K Coussens, Clifton E Barry, Anne O'Garra, Robert J Wilkinson
The transition between latent and active tuberculosis (TB) occurs before symptom onset. Better understanding of the early events in subclinical disease will facilitate the development of diagnostics and interventions that improve TB control. This is particularly relevant in the context of HIV-1 coinfection where progression of TB is more likely. In a recent study using [18F]-fluoro-2-deoxy-d-glucose positron emission/computed tomography (FDG-PET/CT) on 35 asymptomatic, HIV-1-infected adults, we identified 10 participants with radiographic evidence of subclinical disease, significantly more likely to progress than the 25 participants without...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339500/regulation-of-the-stability-of-rgf1-receptor-by-the-ubiquitin-specific-proteases-ubp12-ubp13-is-critical-for-root-meristem-maintenance
#9
Zhichao An, Yuliang Liu, Yang Ou, Jia Li, Baowen Zhang, Daye Sun, Yu Sun, Wenqiang Tang
ROOT MERISTEM GROWTH FACTOR (RGF) 1 is an important peptide hormone that regulates root growth. Upon binding to its receptor, RGFR1, RGF1 regulates the expression of two transcription factors, PLETHORA 1 and 2 (PLT1/2), to influence root meristem development. Here, we show that the ubiquitin-specific proteases UBP12 and UBP13 are positive regulators of root meristem development and that UBP13 interacts directly with RGF1 receptor (RGFR1) and its close homolog RGFR2. The ubp12,13 double-mutant root is completely insensitive to exogenous applied RGF1...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339496/thymic-stromal-lymphopoietin-drives-the-development-of-il-13-th2-cells
#10
Sotaro Ochiai, Ferdinand Jagot, Ryan L Kyle, Evelyn Hyde, Ruby F White, Melanie Prout, Alfonso J Schmidt, Hidehiro Yamane, Olivier Lamiable, Graham Le Gros, Franca Ronchese
T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339455/high-n-acetyltransferase-1-nat1-expression-is-associated-with-estrogen-receptor-expression-in-breast-tumors-but-is-not-under-direct-regulation-by-estradiol-17beta-diol-or-dihydrotestosterone-in-breast-cancer-cells
#11
Xiaoyan Zhang, Samantha M Carlisle, Mark A Doll, Robert C G Martin, J Christopher States, Carolyn M Klinge, David W Hein
N-acetyltransferase 1 (NAT1) is an enzyme which metabolizes carcinogens suggesting a potential role in breast carcinogenesis. High NAT1 expression in breast tumors is associated with estrogen receptor α (ERα+) and the luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ERα/ESR1 compared to normal breast tissue. There was a strong correlation between NATb promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in tumors was not due to adipocytes as evidenced by low PLIN expression...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29339448/development-of-intestinal-m-cells-and-follicle-associated-epithelium-is-regulated-by-traf6-mediated-nf-%C3%AE%C2%BAb-signaling
#12
Takashi Kanaya, Sayuri Sakakibara, Toshi Jinnohara, Masami Hachisuka, Naoko Tachibana, Shinya Hidano, Takashi Kobayashi, Shunsuke Kimura, Toshihiko Iwanaga, Tomoo Nakagawa, Tatsuro Katsuno, Naoya Kato, Taishin Akiyama, Toshiro Sato, Ifor R Williams, Hiroshi Ohno
M cells are located in the follicle-associated epithelium (FAE) that covers Peyer's patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell-associated molecules but is not sufficient to complete M cell differentiation...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339435/corrected-and-republished-from-the-cop9-signalosome-interacts-with-and-regulates-interferon-regulatory-factor-5-protein-stability
#13
Justyna Korczeniewska, Betsy J Barnes
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability...
February 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339402/canonical-notch-signaling-is-dispensible-for-adult-steady-state-and-stress-myelo-erythropoiesis
#14
Sara Duarte, Petter S Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl, Sten Eirik W Jacobsen
While an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29339073/the-human-gcom1-complex-gene-interacts-with-the-nmda-receptor-and-internexin-alpha
#15
Raymond S Roginski, Chi W Lau, Phillip P Santoiemma, Sara J Weaver, Peicheng Du, Patricia Soteropoulos, Jay Yang
The known functions of the human GCOM1 complex hub gene include transcription elongation and the intercalated disk of cardiac myocytes. However, in all likelihood, the gene's most interesting, and thus far least understood, roles will be found in the central nervous system. To investigate the functions of the GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel, 105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H) screens...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#16
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29338785/benefits-of-vce-003-2-a-cannabigerol-quinone-derivative-against-inflammation-driven-neuronal-deterioration-in-experimental-parkinson-s-disease-possible-involvement-of-different-binding-sites-at-the-ppar%C3%AE-receptor
#17
Concepción García, María Gómez-Cañas, Sonia Burgaz, Belén Palomares, Yolanda Gómez-Gálvez, Cristina Palomo-Garo, Sara Campo, Joel Ferrer-Hernández, Carolina Pavicic, Carmen Navarrete, M Luz Bellido, Moisés García-Arencibia, M Ruth Pazos, Eduardo Muñoz, Javier Fernández-Ruiz
BACKGROUND: Neuroprotection with cannabinoids in Parkinson's disease (PD) has been afforded predominantly with antioxidant or anti-inflammatory cannabinoids. In the present study, we investigated the anti-inflammatory and neuroprotective properties of VCE-003.2, a quinone derivative of the non-psychotrophic phytocannabinoid cannabigerol (CBG), which may derive its activity at the peroxisome proliferator-activated receptor-γ (PPARγ). The compound is also an antioxidant. METHODS: We evaluated VCE-003...
January 16, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29338742/m2-polarized-tumor-associated-macrophages-facilitated-migration-and-epithelial-mesenchymal-transition-of-hcc-cells-via-the-tlr4-stat3-signaling-pathway
#18
Rong-Rong Yao, Jing-Huan Li, Rui Zhang, Rong-Xin Chen, Yan-Hong Wang
BACKGROUND: M2-polarized macrophages are tumor-associated-macrophages (TAMs), which are important contents of tumor-infiltrating immune cells. Toll-like receptor 4 (TLR4) is a molecular biomarker of tumor aggressiveness and poor prognosis. Toll-like receptors (TLRs) have important roles in the immune system and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized macrophages...
January 16, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29338737/transcriptome-profiling-of-whitefly-guts-in-response-to-tomato-yellow-leaf-curl-virus-infection
#19
Liang Geng, Li-Xin Qian, Ruo-Xuan Shao, Yin-Quan Liu, Shu-Sheng Liu, Xiao-Wei Wang
BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide, and over 75% of them are transmitted from infected to healthy plants by insect vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the largest and most economically important group of plant viruses, transmitted by the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves complex insect-virus interactions, whereas the molecular mechanisms of these interactions remain ambiguous...
January 16, 2018: Virology Journal
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#20
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
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