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https://www.readbyqxmd.com/read/27915449/common-variants-in-cldn14-are-associated-with-differential-excretion-of-magnesium-over-calcium-in-urine
#1
REVIEW
Tanguy Corre, Eric Olinger, Sarah E Harris, Michela Traglia, Sheila Ulivi, Stefania Lenarduzzi, Hendrica Belge, Sonia Youhanna, Natsuko Tokonami, Olivier Bonny, Pascal Houillier, Ozren Polasek, Ian J Deary, John M Starr, Daniela Toniolo, Paolo Gasparini, Peter Vollenweider, Caroline Hayward, Murielle Bochud, Olivier Devuyst
The nature and importance of genetic factors regulating the differential handling of Ca(2+) and Mg(2+) by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2...
December 3, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27915273/altered-mirna-expression-in-high-fat-diet-induced-prostate-cancer-progression
#2
Taketoshi Nara, Shintaro Narita, Huang Mingguo, Toshiaki Yoshioka, Atsushi Koizumi, Kazuyuki Numakura, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array...
December 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27915244/antifungal-activity-in-vitro-and-in-vivo-of-a-salmon-protamine-peptide-and-its-derived-cyclic-peptide-against-candida-albicans
#3
Jun-Ichi Nagao, Tamaki Cho, Makoto Mitarai, Keishi Iohara, Kazumi Hayama, Shigeru Abe, Yoshihiko Tanaka
Protamine peptides (PP) derived from salmon are 14-mer consisting of 10 arginine residues. We investigated the in vitro and in vivo antifungal activity of PP against Candida albicans PP showed the concentration-dependent dual mode of action; fungicidal activity and inhibitory activity of hyphal development in vitro. At lethal concentration of PP, intracellular accumulation of PP was energy-dependent but independent of endocytosis that resulted in ATP efflux and the generation of reactive oxygen species in the cells...
December 2, 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27915183/search-for-new-potential-anticonvulsants-with-anxiolytic-and-antidepressant-properties-among-derivatives-of-4-4-diphenylpyrrolidin-2-one
#4
Katarzyna Malawska, Aleksandra Rak, Beata Gryzło, Kinga Sałat, Małgorzata Michałowska, Elżbieta Żmudzka, Krzysztof Lodarski, Barbara Malawska, Katarzyna Kulig
BACKGROUND: The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. METHODS: The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction...
September 22, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27915171/progress-in-the-development-of-%C3%AE-lactams-as-n-acylethanolamine-acid-amidase-naaa-inhibitors-synthesis-and-sar-study-of-new-potent-n-o-substituted-derivatives
#5
R Petracca, S Ponzano, S M Bertozzi, O Sasso, D Piomelli, T Bandiera, F Bertozzi
The anti-inflammatory effects resulting from raising the levels of palmitoylethanolamide (PEA), an endogenous bioactive lipid, led to envisage N-Acylethanolamine Acid Amidase (NAAA), the cysteine hydrolase mainly responsible for PEA degradation, as an attractive target for small molecule inhibitors. Previous work in our group identified serine-derived β-lactams as potent and systemically active inhibitors of NAAA activity. Aiming to expand the SAR study around this class of compounds, we investigated the effect of the substitution on the endocyclic nitrogen by designing and synthesizing a series of N-substituted β-lactams...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27915139/impairment-of-fetal-hematopoietic-stem-cell-function-in-the-absence-of-fancd2
#6
Sakiko Suzuki, Ronny R Racine, Nathan A Manalo, Sharon B Cantor, Glen D Raffel
Fanconi Anemia (FA), results from mutations in genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests hematopoietic defects originate in utero which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of E14...
November 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27915055/identification-of-human-udp-glucuronosyltransferase-isoforms-involved-in-the-isofraxidin-glucuronidation-and-assessment-of-the-species-differences-of-the-reaction
#7
Fanxing Meng, Yan Li, Guiyuan He, Guangbo Ge, Shumin Liu
Isofraxidin, 7-Hydroxy-6.8-dimethoxy-2H-1-benzopyran-2-one, is a major active component of Acanthopanax senticosus, which has been used as Acanthopanax (Ciwujia) injection to treat cardiovascular and cerebrovascular diseases in China for more than thirty years. The purpose of this study was to identify the roles of human UDP-glucuronosyltransferases (UGTs) in isofraxidin glucuronidation in the liver and intestinal microsomes and to reveal the potential species differences by comparing the liver microsomal glucuronidation from different experimental animals...
November 30, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27915049/csn1201-a-subunit-of-the-cop9-signalosome-regulates-the-virulence-in-cryptococcus-neoformans-infection
#8
Yibin Fan, Xiaohua Tao, Weili Pan, Wei Fang, Youming Huang, Mingyan Jia
The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence...
November 30, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27915044/a-novel-aldosterone-synthase-inhibitor-ameliorates-mortality-in-pressure-overload-mice-with-heart-failure
#9
Shinji Furuzono, Masaki Meguro, Satoru Miyauchi, Shinichi Inoue, Tsuyoshi Homma, Keisuke Yamada, Yoh-Ichi Tagawa, Futoshi Nara, Takahiro Nagayama
It has been elucidated that mineralocorticoid receptor antagonists reduce mortality in patients with congestive heart failure and post-acute myocardial infarction. A direct inhibition of aldosterone synthase (CYP11B2) is also expected to have therapeutic benefits equal in quality to mineralocorticoid receptor antagonists in terms of reducing mineralocorticoid receptor signaling. Therefore, we have screened our chemical libraries and identified a novel and potent aldosterone synthase inhibitor, 2,2,2-trifluoro-1-{4-[(4-fluorophenyl)amino]pyrimidin-5-y}-1-[1-(methylsulfonyl)piperidin-4-yl]ethanol (compound 1), by lead optimization...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27915007/effect-of-the-oral-administration-of-nanoencapsulated-quercetin-on-a-mouse-model-of-alzheimer-s-disease
#10
Lina Clara Gayoso E Almendra Ibiapina, Elena Puerta, José Eduardo Suárez-Santiago, Nereide Stela Santos-Magalhães, Maria J Ramirez, Juan M Irache
Quercetin has been identified as a promising compound with a neuroprotective potential against age-related neurodegenerative diseases such as Alzheimer's disease (AD). Nevertheless, the clinical application of quercetin is hampered by its low oral bioavailability. The aim of this work was to evaluate the capability of nanoencapsulated quercetin in zein nanoparticles (NPQ), that significantly improves the oral absorption and bioavailability of the flavonoid, as potential oral treatment for AD. For this purpose, SAMP8 mice were orally treated for two months with either NPQ (25mg/kg every 48hours) or a solution of quercetin (Q; 25mg/kg daily)...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27915005/development-and-characterisation-of-disulfiram-loaded-plga-nanoparticles-for-the-treatment-of-non-small-cell-lung-cancer
#11
Mohammad Najlah, Zahima Ahmed, Mohammed Iqbal, Zhipeng Wang, Patrica Tawari, Weiguang Wang, Christopher McConville
Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4 minutes) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27914985/combination-therapy-with-doxorubicin-loaded-galactosylated-poly-ethyleneglycol-lithocholic-acid-to-suppress-the-tumor-growth-in-an-orthotopic-mouse-model-of-liver-cancer
#12
Bijay Singh, Yoonjeong Jang, Sushila Maharjan, Hyeon-Jeong Kim, Ah Young Lee, Sanghwa Kim, Nomundelger Gankhuyag, Myeon-Sik Yang, Yun-Jaie Choi, Myung-Haing Cho, Chong-Su Cho
Despite advances in technology, neither conventional anti-cancer drugs nor current nanoparticle (NP) drugs have gained substantial success in cancer treatment. While conventional chemotherapy drugs have several limitations such as low potency, poor in vivo stability and limited bioavailability, non-specific targeting of NP drugs diminishes their potency at actual target sites. In addition, the development of drug resistance to anti-cancer drugs is another challenging problem. To overcome these limitations, we aimed to develop a polymer-drug conjugate, which functions as an active NP drug and drug carrier both, to deliver a chemotherapeutic drug for combination therapy...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27914948/triazolopyridine-ethers-as-potent-orally-active-mglu2-positive-allosteric-modulators-for-treating-schizophrenia
#13
Mendi A Higgins, Lawrence R Marcin, F Christopher Zusi, Robert Gentles, Min Ding, Bradley C Pearce, Amy Easton, Walter A Kostich, Matthew A Seager, Clotilde Bourin, Linda J Bristow, Kim A Johnson, Regina Miller, John Hogan, Valerie Whiterock, Michael Gulianello, Meredith Ferrante, Yanling Huang, Adam Hendricson, Andrew Alt, John E Macor, Joanne J Bronson
Triazolopyridine ethers with mGlu2 positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10mg/kg (p...
November 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27914827/inhibition-of-long-non-coding-rna-igf2as-protects-apoptosis-and-neuronal-loss-in-anesthetic-damaged-mouse-neural-stem-cell-derived-neurons
#14
Chengwei Song, Chengjun Song, Kui Chen, Xiangdong Zhang
BACKGROUND: In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells. METHODS: Murine E18.5 brain-derived neural stem cells were cultured in vitro. During neural differentiation stage, ketamine-induced gene expression changes of IGF2 and IGF2AS were recorded by qRT-PCR...
November 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27914809/actein-enhances-trail-effects-on-suppressing-gastric-cancer-progression-by-activating-p53-caspase-3-signaling
#15
Zhi-Chao Yang, Ji Ma
Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#16
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914708/generation-and-phenotypic-analysis-of-mice-lacking-all-urea-transporters
#17
Tao Jiang, Yingjie Li, Anita T Layton, Weiling Wang, Yi Sun, Min Li, Hong Zhou, Baoxue Yang
Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914527/prophylactic-effects-of-alkaloids-from-ba-lotus-seeds-on-l-nna-induced-hypertension-in-mice
#18
Peng Sun, Kai Zhu, Cun Wang, Wei-Wei Liu, De-Guang Peng, Xin Zhao
Alkaloids from Ba lotus seeds (ABLS) are a kind of important functional compounds in lotus seeds. The present study was designed to determine its hypertension prophylactic effects in the L-NNA-induced mouse hypertension model. The mice were treated with ABLS, the serum and tissues levels of NO, MDA, ET-1, VEGF, and CGRP were determined using the experimental kits, the mRNA levels of various genes in the heart muscle and blood vessel tissues were further determined by RT-PCR assay. ABLS could reduce the systolic blood pressure (SBP), mean blood pressure (MBP), and diastolic blood pressure (DBP), compared to that of the model control group...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27914463/study-of-immunomodulatory-effects-of-extracellular-hsp70-in-a-mouse-model-of-allergic-airway-inflammation
#19
M A Shevchenko, N I Troyanova, E A Servuli, E L Bolkhovitina, A S Fedorina, A M Sapozhnikov
Immunostimulatory properties of extracellular heat shock proteins 70 kDa (HSP70) became interesting for investigators a long time ago. However, in recent years a series of works showing a significant relation of the immunostimulating effects of recombinant HSP70 to contamination of the protein samples with bacterial endotoxins (lipopolysaccharide, LPS) has been published. The authors showed that intensive elimination of LPS from the protein samples resulted in inversion of immunostimulating effects of HSP70 to immunosuppressive activity of the protein...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914457/tumor-necrosis-factor-and-lymphotoxin-in-regulation-of-intestinal-inflammation
#20
REVIEW
E O Gubernatorova, A V Tumanov
Ulcerative colitis and Crohn's disease are the major forms of inflammatory bowel disease. Cytokines of the tumor necrosis factor (TNF) family play an important role in the regulation of intestinal inflammation. In this review, we discuss the function of key cytokines of this family - TNF and lymphotoxin (LT) - in mucosal healing, IgA production, and in control of innate lymphoid cells (ILCs), novel regulators of mucosal homeostasis in the gut. TNF plays a central role in the pathogenesis of inflammatory bowel diseases (IBD)...
November 2016: Biochemistry. Biokhimii︠a︡
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