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https://www.readbyqxmd.com/read/29668110/phenylbutyl-isoselenocyanate-induces-reactive-oxygen-species-to-inhibit-androgen-receptor-and-to-initiate-p53-mediated-apoptosis-in-lncap-prostate-cancer-cells
#1
Wei Wu, Deepkamal Karelia, Kartick Pramanik, Shantu G Amin, Arun K Sharma, Cheng Jiang, Junxuan Lu
Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNCaP prostate cancer cells with ISC-4 and examined their apoptosis responses, and interrogated the signaling mechanisms through pharmacological and siRNA knockdown approaches. Our results show that ISC-4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation...
April 18, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29667913/ubiquitin-c-terminal-hydrolase-l1-deletion-is-associated-with-urinary-%C3%AE-klotho-deficiency-and-perturbed-phosphate-homeostasis
#2
Naomi C Boisvert, Chet E Holterman, Alexey Gutsol, Josee Coulombe, Wanling Pan, R Todd Alexander, Douglas A Gray, Chris R Kennedy
Loss of ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1-/- mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels were similar to wild type levels...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667908/the-macula-densa-prorenin-receptor-is-essential-in-renin-release-and-blood-pressure-control
#3
Anne D M Riquier-Brison, Arnold Sipos, Ágnes Prókai, Sarah L Vargas, Ildiko Toma, Elliott J Meer, Karie G Villanueva, Jennifer C M Chen, Georgina Gyarmati, Christopher Yih, Elaine Tang, Bahram Nadim, Sujith Pendekanti, Ingrid M Garrelds, Genevieve Nguyen, A H Jan Danser, Janos Peti-Peterdi
The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS), however recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667863/leo-kanner-and-autism-a-75-year-perspective
#4
James Harris
In 1943, Leo Kanner published the first systematic description of early infantile autism. He concluded that this was a neurodevelopmental disorder and that 'these children have come into the world with an innate inability to form the usual, biologically provided contact with people'. Moreover, his astute descriptions of parental behavior in his first publications were prescient and underlie later recognition of the importance of genetics. Our understanding has grown over the ensuing years with revisions in diagnostic classification, recognition of the broader autism phenotype in families, appreciation of the importance of developmental models, advances in genetic methodology, better understanding of the relationship to intellectual deficits, recognition of syndromic autism in neurogenetic sydromes, advances in neuroimaging, and advances in animal models, both mutant mouse models and transgenic non human primate models...
April 18, 2018: International Review of Psychiatry
https://www.readbyqxmd.com/read/29667751/suz12-is-a-novel-putative-oncogene-promoting-tumorigenesis-in-head-and-neck-squamous-cell-carcinoma
#5
Yaping Wu, Huijun Hu, Wei Zhang, Zhongwu Li, Pengfei Diao, Dongmiao Wang, Wei Zhang, Yanling Wang, Jianrong Yang, Jie Cheng
The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC patient cohorts...
April 18, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29667749/effect-of-lysm-macrophage-depletion-on-lung-pathology-in-mice-with-chronic-bronchitis
#6
Yogesh Saini, Brandon W Lewis, Dongfang Yu, Hong Dang, Alessandra Livraghi-Butrico, Fabio Del Piero, Wanda K O'Neal, Richard C Boucher
Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29667742/genetic-association-and-expression-analyses-of-the-phosphatidylinositol-4-phosphate-5-kinase-pip5k1c-gene-in-alcohol-use-disorder-relevance-for-pain-signaling-and-alcohol-use
#7
Ji Soo Lee, Jill L Sorcher, Allison D Rosen, Ruslan Damadzic, Hui Sun, Melanie Schwandt, Markus Heilig, John Kelly, Kelsey L Mauro, Audrey Luo, Daniel Rosoff, Christine Muench, Jeesun Jung, Zachary A Kaminsky, Falk W Lohoff
BACKGROUND: The gene encoding Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. METHODS: We conducted a case-control association study of genetic variants in PIP5K1C...
April 18, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29667532/human-osteoblast-derived-extracellular-matrix-with-high-homology-to-bone-proteome-is-osteopromotive
#8
Marta Baroncelli, Bram C J van der Eerden, Siddharth Chatterji, Enrique Rull Trinidad, Yik Y Kan, Marijke Koedam, Ingmar A J van Hengel, Rodrigo D A M Alves, Lidy E Fratila-Apachitei, Jeroen A A Demmers, Jeroen van de Peppel, Johannes Ptm van Leeuwen
Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is crucial to accelerate bone formation. In this context, the use of extracellular matrix (ECM) as natural 3D-framework mimicking in vivo tissue architecture is of interest. The aim of this study was to generate a devitalized human osteogenic MSC-derived ECM and to investigate its impact on MSC osteogenic differentiation to improve MSC properties in bone regeneration. The devitalized ECM significantly enhanced MSC adhesion and proliferation...
April 18, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29667327/novel-west-syndrome-candidate-genes-in-a-chinese-cohort
#9
Jing Peng, Ying Wang, Fang He, Chen Chen, Li-Wen Wu, Li-Fen Yang, Yu-Ping Ma, Wen Zhang, Zi-Qing Shi, Chao Chen, Kun Xia, Hui Guo, Fei Yin, Nan Pang
AIMS: West syndrome (WS) is a classic form of early infantile epileptic encephalopathy (EIEE) characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on electroencephalography. Genetic defects play a critical role in the pathology of WS, and 54 EIEE genes have been identified till date. This study was designed to uncover new candidate genes for West syndrome. METHODS: In this study, we recruited 56 Chinese families with WS of unknown etiology...
April 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29667227/effects-of-knockout-of-the-receptor-for-advanced-glycation-end-products-on-bone-mineral-density-and-synovitis-in-mice-with-intra-articular-fractures
#10
Dongrim Seol, Yuki Tochigi, Ashley M Bogner, Ino Song, Douglas C Fredericks, Gail L Kurriger, Sonja M Smith, Jessica E Goetz, Joseph A Buckwalter, James A Martin
Our group employed the mouse closed intra-articular fracture (IAF) model to test the hypothesis that the innate immune system plays a role in initiating synovitis and post-traumatic osteoarthritis (PTOA) in fractured joints. A transgenic strategy featuring knockout of the receptor for advanced glycation end-products (RAGE -/- ) was pursued. The 42 and 84 mJ impacts used to create fractures were in the range previously reported to cause PTOA at 60 days post-fracture. MicroCT (µCT) was used to assess fracture patterns and epiphyseal and metaphyseal bone loss at 30 and 60 days post-fracture...
April 17, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29667135/optimising-intratumoral-treatment-of-head-and-neck-squamous-cell-carcinoma-models-with-the-diterpene-ester-tigilanol-tiglate
#11
Catherine M E Barnett, Natasa Broit, Pei-Yi Yap, Jason K Cullen, Peter G Parsons, Benedict J Panizza, Glen M Boyle
The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment...
April 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29667130/beneficial-effects-of-the-calcium-channel-blocker-ctk-01512-2-in-a-mouse-model-of-multiple-sclerosis
#12
Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29667129/elevation-of-mmp-9-levels-promotes-epileptogenesis-after-traumatic-brain-injury
#13
Barbara Pijet, Marzena Stefaniuk, Agnieszka Kostrzewska-Ksiezyk, Photini-Effie Tsilibary, Athina Tzinia, Leszek Kaczmarek
Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that often develops secondary to traumatic brain injury (TBI) that is caused by an external mechanical force. Recent evidence shows that the brain extracellular matrix plays a major role in the remodeling of neuronal connections after injury. One of the proteases that is presumably responsible for this process is matrix metalloproteinase-9 (MMP-9). The levels of MMP-9 are elevated in rodent brain tissue and human blood samples after TBI. However, no studies have described the influence of MMP-9 on the development of PTE...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29667067/a-first-in-class-inhibitor-mln4924-pevonedistat-induces-cell-cycle-arrest-senescence-and-apoptosis-in-human-renal-cell-carcinoma-by-suppressing-ube2m-dependent-neddylation-modification
#14
Bo Xu, Yuyou Deng, Ran Bi, Haoran Guo, Chang Shu, Neelam Kumari Shah, Junliang Chang, Guanchen Liu, Yujun Du, Wei Wei, Chunxi Wang
PURPOSE: MLN4924 is a second-generation inhibitor that targets ubiquitin-proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29667006/establishment-and-characterization-of-a-c57bl-6-mouse-model-of-bone-metastasis-of-breast-cancer
#15
Toru Hiraga, Tadashi Ninomiya
Bone is one of the most common sites of metastasis in patients with advanced breast cancer; however, the mechanisms of bone metastasis remain to be fully elucidated. Animal models are essential research tools for investigating the mechanisms of diseases and drug actions. To date, there have only been a few reports in which C57BL/6 mice were used for the study of bone metastases of breast cancer. In the current study, we found that intracardiac inoculation of C57BL/6 mouse-derived parental E0771 breast cancer cells (E0771/Pa) frequently lead to bone metastases in C57BL/6 mice within 2 weeks...
April 17, 2018: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29667003/chemical-genomics-reveals-inhibition-of-breast-cancer-lung-metastasis-by-ponatinib-via-c-jun
#16
Wei Shao, Shasha Li, Lu Li, Kequan Lin, Xinhong Liu, Haiyan Wang, Huili Wang, Dong Wang
Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS2 ) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models...
April 17, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29666981/an-early-life-mucosal-insult-temporarily-decreases-acute-oxazolone-induced-inflammation-in-mice
#17
Katja M Bendtsen, Peter Tougaard, Axel K Hansen
Inflammatory priming of immune cells in early life may optimize the response to a subsequent inflammatory challenge later in life. To prime the immune cells in the gut in vivo through a short inflammatory insult, we administered a low dose of dextran sulfate sodium (DSS) to 5-weeks-old BALB/c mice in the drinking water. We hypothesized that DSS-primed mice would show decreased inflammation and difference in immunological profiling, when subjected to presensitizing and oxazolone-induced colitis by rectal instillation at 9 weeks compared to non-DSS-primed control mice...
April 18, 2018: Inflammation
https://www.readbyqxmd.com/read/29666943/the-gtn-patch-a-simple-and-effective-new-approach-to-cardioprotection
#18
Derek M Yellon, Zhenhe He, Rayomand Khambata, Amrita Ahluwalia, Sean M Davidson
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI. Although nitric oxide is central to many cardioprotective strategies currently undergoing investigation, cardioprotection from the delivery of nitrates/nitrites has been inconsistently observed. The route of administration appears to be a critical variable. The glyceryl trinitrate (GTN) patch is commonly used as a simple and practical means of delivering nitric oxide to patients with ischaemic heart disease, but whether acute cardioprotection can be achieved by application of a GTN patch has not been investigated before...
April 17, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29666796/plc%C3%AE-induced-ca-2-oscillations-in-mouse-eggs-involve-a-positive-feedback-cycle-of-ca-2-induced-insp-3-formation-from-cytoplasmic-pip-2
#19
Jessica R Sanders, Bethany Ashley, Anna Moon, Thomas E Woolley, Karl Swann
Egg activation at fertilization in mammalian eggs is caused by a series of transient increases in the cytosolic free Ca2+ concentration, referred to as Ca2+ oscillations. It is widely accepted that these Ca2+ oscillations are initiated by a sperm derived phospholipase C isoform, PLCζ that hydrolyses its substrate PIP2 to produce the Ca2+ releasing messenger InsP3 . However, it is not clear whether PLCζ induced InsP3 formation is periodic or monotonic, and whether the PIP2 source for generating InsP3 from PLCζ is in the plasma membrane or the cytoplasm...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29666587/cardioprotective-effects-of-qishenyiqi-dripping-pills-on-transverse-aortic-constriction-induced-heart-failure-in-mice
#20
Guoran Ruan, Haojin Ren, Chi Zhang, Xiaogang Zhu, Chao Xu, Liyue Wang
QiShenYiQi dripping pills (QSYQ), a traditional Chinese medicine, are commonly used to treat coronary heart disease, and QSYQ was recently approved as a complementary treatment for ischemic heart failure in China. However, only few studies reported on whether QSYQ exerts a protective effect on heart failure induced by pressure overload. In this study, we explored the role of QSYQ in a mouse model of heart failure induced by transverse aortic constriction (TAC). Twenty-eight C57BL/6J mice were divided into four groups: Sham + NS group, Sham + QSYQ group, TAC + NS group, and TAC + QSYQ group...
2018: Frontiers in Physiology
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