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https://www.readbyqxmd.com/read/29045497/ceftriaxone-and-n-acetylcysteine-induced-brain-tolerance-to-ischemia-influence-on-glutamate-levels-in-focal-cerebral-ischemia
#1
Weronika Krzyżanowska, Bartosz Pomierny, Beata Bystrowska, Lucyna Pomierny-Chamioło, Małgorzata Filip, Bogusława Budziszewska, Joanna Pera
One of the major players in the pathophysiology of cerebral ischemia is disrupted homeostasis of glutamatergic neurotransmission, resulting in elevated extracellular glutamate (Glu) concentrations and excitotoxicity-related cell death. In the brain, Glu concentrations are regulated by Glu transporters, including Glu transporter-1 (GLT-1) and cystine/Glu antiporter (system xc-). Modulation of these transporters by administration of ceftriaxone (CEF, 200 mg/kg, i.p.) or N-acetylcysteine (NAC, 150 mg/kg, i.p.) for 5 days before focal cerebral ischemia may induce brain tolerance to ischemia by significantly limiting stroke-related damage and normalizing Glu concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/29038345/administering-xct-inhibitors-based-on-circadian-clock-improves-antitumor-effects
#2
Fumiyasu Okazaki, Naoya Matsunaga, Kengo Hamamura, Kayoko Suzuki, Takaharu Nakao, Hiroyuki Okazaki, Masahiko Kutsukake, Shiro Fukumori, Yasuhiro Tsuji, Hideto To
Clock genes encoding transcription factors that regulate circadian rhythms may inform chrono-modulated chemotherapy, where time-dependent dose alterations might affect drug efficacy and reduce side effects. For example, inhibiting the essential cystine transporter xCT with sulfasalazine induces growth arrest in cancer cells. Although the anticancer effects of sulfasalazine have been studied extensively, its effects on transcriptional control of xCT expression have not been studied. Here we show that sulfasalazine administration during the period of increased xCT expression improves its anticancer effects, and that the Clock gene itself induces xCT expression and regulates its circadian rhythm...
October 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/29038291/cystine-uptake-through-the-cystine-glutamate-antiporter-xct-triggers-glioblastoma-cell-death-under-glucose-deprivation
#3
Takeo Goji, Kazuhiko Takahara, Manabu Negishi, Hironori Katoh
Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species (ROS). However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation (i.e. in high glucose dependence), which rapidly induces cell death...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29033965/novel-alleles-of-two-tightly-linked-genes-encoding-polygalacturonase-inhibiting-proteins-vrpgip1-and-vrpgip2-associated-with-the-br-locus-that-confer-bruchid-callosobruchus-spp-resistance-to-mungbean-vigna-radiata-accession-v2709
#4
Anochar Kaewwongwal, Jingbin Chen, Prakit Somta, Alisa Kongjaimun, Tarika Yimram, Xin Chen, Peerasak Srinives
Nearly all mungbean cultivars are completely susceptible to seed bruchids (Callosobruchus chinensis and Callosobruchus maculatus). Breeding bruchid-resistant mungbean is a major goal in mungbean breeding programs. Recently, we demonstrated in mungbean (Vigna radiata) accession V2802 that VrPGIP2, which encodes a polygalacturonase inhibiting protein (PGIP), is the Br locus responsible for resistance to C. chinensis and C. maculatus. In this study, mapping in mungbean accession V2709 using a BC11F2 population of 355 individuals revealed that a single major quantitative trait locus, which controlled resistance to both C...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29033832/cyclotides-isolated-from-an-ipecac-root-extract-antagonize-the-corticotropin-releasing-factor-type-1-receptor
#5
Mohsen Fahradpour, Peter Keov, Carlotta Tognola, Estela Perez-Santamarina, Peter J McCormick, Alireza Ghassempour, Christian W Gruber
Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants' uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28994534/-a-new-styrene-dimer-derivative-from-litsea-greenmaniana
#6
Ya-Nan Wang, Ling-Yan Wang, Yu-Hong Qu, Ming Jiang, Yu-Zhuo Wu, Rui Li, Bo-Lin Qiu, Su-Juan Wang, Sheng Lin
A new styrene dimer derivative has been isolated from the branch of Litsea greenmaniana by column chromatography over silica gel and Sephadex LH-20, as well as semi-preparative HPLC. Its structure was identified by spectroscopic data analysis (MS, UV, IR, 1D and 2D NMR) as (E)-2,4-bis(p-hydroxyphenyl)-2-butenol, named as listeanol. At a concentration of 1×10-5 mol•L⁻¹, compound 1 was inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), antioxidant activity in Fe²⁺-cystine-induced rat liver microsomal lipid peroxidation, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B)...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28987048/-the-application-of-n-acetylcysteine-in-optimization-of-specific-pharmacological-therapies
#7
REVIEW
Iga Hołyńska-Iwan, Marcin Wróblewski, Dorota Olszewska-Słonina, Tomasz Tyrakowski
Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28985506/nrf2-is-a-major-target-of-arf-in-p53-independent-tumor-suppression
#8
Delin Chen, Omid Tavana, Bo Chu, Luke Erber, Yue Chen, Richard Baer, Wei Gu
Although ARF can suppress tumor growth by activating p53 function, the mechanisms by which it suppresses tumor growth independently of p53 are not well understood. Here, we identified ARF as a key regulator of nuclear factor E2-related factor 2 (NRF2) through complex purification. ARF inhibits the ability of NRF2 to transcriptionally activate its target genes, including SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS)-induced ferroptosis. As a consequence, ARF expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28984551/chitinimonas-lacunae-sp-nov-isolated-from-artificial-pond-in-korea
#9
Dong Jin Yang, Hyun Seok Choi, Jin-Kyung Hong
A gram-negative, rod shaped bacterium designated as strain H2(T) was isolated from an artificial pond in Korea. The strain H2(T) was able to grow aerobically and anaerobically with optimal growth occurring at 30 °C and pH 7.0 under aerobic conditions. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain H2(T) belonged to the genus Chitinimonas of the family Burkholderiaceae. Phylogenetic similarity calculated from 16S rRNA gene sequences of strain H2(T) and valid species belongs to the genus Chitinimonas ranged from 93...
October 6, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28983406/mutation-analysis-of-the-ctns-gene-in-iranian-patients-with-infantile-nephropathic-cystinosis-identification-of-two-novel-mutations
#10
Forough Sadeghipour, Mitra Basiratnia, Ali Derakhshan, Majid Fardaei
Nephropathic cystinosis is an inherited lysosomal transport disorder caused by mutations in the CTNS gene that encodes for a lysosomal membrane transporter, cystinosin. Dysfunction in this protein leads to cystine accumulation in the cells of different organs. The accumulation of cystine in the kidneys becomes apparent with renal tubular Fanconi syndrome between 6 and 12 months of age and leads to renal failure in the first decade of life. The aim of this study was to analyze the CTNS mutations in 20 Iranian patients, from 20 unrelated families, all of whom were afflicted with infantile nephropathic cystinosis...
2017: Human Genome Variation
https://www.readbyqxmd.com/read/28981107/targeting-redox-homeostasis-in-rhabdomyosarcoma-cells-gsh-depleting-agents-enhance-auranofin-induced-cell-death
#11
Karoline Johanna Habermann, Leon Grünewald, Sjoerd van Wijk, Simone Fulda
Rhabdomyosarcoma (RMS) cells have recently been reported to be sensitive to oxidative stress. Therefore, we investigated whether concomitant inhibition of the two main antioxidant defense pathways, that is, the thioredoxin (TRX) and the glutathione (GSH) systems, presents a new strategy to trigger cell death in RMS. In this study, we discover that GSH-depleting agents, i.e. γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine (BSO) or the cystine/glutamate antiporter inhibitor erastin (ERA), synergize with thioredoxin reductase (TrxR) inhibitor auranofin (AUR) to induce cell death in RMS cells...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980090/isolated-sulfite-oxidase-deficiency
#12
Helena Claerhout, Peter Witters, Luc Régal, Katrien Jansen, Marie-Rose Van Hoestenberghe, Jeroen Breckpot, Pieter Vermeersch
Isolated sulfite oxidase deficiency (ISOD) is a life-threatening, autosomal recessive disease characterized by severe neurological impairment. As no long-term effective treatment is available, distinction from other treatable diseases, such as molybdenum cofactor deficiency (MoCD) type A, should be made. We reviewed 47 patients (45 previously reported in the literature). Cases were reviewed for consanguinity, sex, age at onset, death, clinical findings (including spasticity, seizures, psychomotor retardation, feeding difficulties, ectopia lentis, microcephaly), laboratory findings [urinary sulfite, S-sulfocysteine (in plasma and urine), plasma cystine, total homocysteine, uric acid, and oxypurines in urine] and radiological findings (including cerebral/cerebellar atrophy, cystic white matter changes, ventriculomegaly)...
October 4, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28978047/restoring-microenvironmental-redox-and-ph-homeostasis-inhibits-neoplastic-cell-growth-and-migration-therapeutic-efficacy-of-esomeprazole-plus-sulfasalazine-on-3-mca-induced-sarcoma
#13
Enrica Balza, Patrizia Castellani, Paola Sanchez Moreno, Patrizia Piccioli, Iria Medraño-Fernandez, Claudia Semino, Anna Rubartelli
Neoplastic cells live in a stressful context and survive thanks to their ability to overcome stress. Thus, tumor cell responses to stress are potential therapeutic targets. We selected two such responses in melanoma and sarcoma cells: the xc- antioxidant system, that opposes oxidative stress, and surface v-ATPases that counteract the low pHi by extruding protons, and targeted them with the xc- blocker sulfasalazine and the proton pump inhibitor esomeprazole. Sulfasalazine inhibited the cystine/cysteine redox cycle and esomeprazole decreased pHi while increasing pHe in tumor cell lines...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974116/decreased-reproductive-performance-in-xct-knockout-male-mice
#14
Shinji Hamashima, Takujiro Homma, Sho Kobayashi, Naoki Ishii, Toshihiro Kurahashi, Ren Watanabe, Naoko Kimura, Hideyo Sato, Junichi Fujii
Sulfoxidation occurs in protamines that are enriched in cysteine and supplies chromatin for packaging. The extracellular fluid contains higher levels of oxidized cysteine (cystine), and some cells utilize system xc(-), a cystine transporter in which xCT is the main protein component, to fulfill the need for cysteine. We hypothesized that system xc(-) might ensure the supply of cysteine needed for spermatogenesis. The reproductive ability of xCT(-/-) male mice at 6- to 18-weeks of age appeared to be lower than xCT(+/+) male mice...
October 4, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28959851/-changes-in-amino-acid-profiling-in-spontaneously-hypertensive-rats-and-regulatory-effect-of-extract-from-coreopsis-tinctoria
#15
Xiao-Li Ma, Li-Na Ma, Xin-Min Mao, Yu-Jie Zhang, Yi Lan
To compare the amino acid metabolic profiling in urine of spontaneously hypertensive rats (SHR) and normal Wistar rats, and investigate the regulatory effect of extract from Coreopsis tinctoria on blood pressure and amino acid metabolic profiling in SHR. Right aged SHR and Wistar rats were housed to fit the new environment for 2 weeks. After that, their systolic pressure(SBP), diastolic pressure(DBP) were measured and urine was collected. Amino acids profiles for SHR and Wistar rats were acquired by using AQC precolumn derivatization HPLC-fluorescence method, and then partial least squares discriminant analysis(PLS-DA) was applied to facilitate differentiation and determine metabolic differences between collected samples from two groups of rats...
February 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28956014/development-of-a-primary-microglia-screening-assay-and-its-use-to-characterize-inhibition-of-system-xc-by-erastin-and-its-analogs
#16
Mariana Figuera-Losada, Ajit G Thomas, Marigo Stathis, Brent R Stockwell, Camilo Rojas, Barbara S Slusher
The inflammatory response in the central nervous system involves activated microglia. Under normal conditions they remove damaged neurons by phagocytosis. On the other hand, neurodegenerative diseases are thought to involve chronic microglia activation resulting in release of excess glutamate, proinflammatory cytokines and reactive oxygen species, leading to neuronal death. System xC(-) cystine/glutamate antiporter (SXC), a sodium independent heterodimeric transporter found in microglia and astrocytes in the CNS, imports cystine into the cell and exports glutamate...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28952007/rapid-kv-switching-single-source-dual-energy-ct-ex-vivo-renal-calculi-characterization-using-a-multiparametric-approach-refining-parameters-on-an-expanded-dataset
#17
J Scott Kriegshauser, Robert G Paden, Miao He, Mitchell R Humphreys, Steven I Zell, Yinlin Fu, Teresa Wu, Mark D Sugi, Alvin C Silva
PURPOSE: We aimed to determine the best algorithms for renal stone composition characterization using rapid kV-switching single-source dual-energy computed tomography (rsDECT) and a multiparametric approach after dataset expansion and refinement of variables. METHODS: rsDECT scans (80 and 140 kVp) were performed on 38 ex vivo 5- to 10-mm renal stones composed of uric acid (UA; n = 21), struvite (STR; n = 5), cystine (CYS; n = 5), and calcium oxalate monohydrate (COM; n = 7)...
September 26, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28950840/diagnostic-challenge-in-a-patient-with-nephropathic-juvenile-cystinosis-a-case-report
#18
Satomi Higashi, Natsuki Matsunoshita, Masako Otani, Etsuro Tokuhiro, Kandai Nozu, Shuichi Ito
BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis...
September 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28945133/dual-energy-computed-tomography-of-canine-uroliths
#19
Stephanie G Nykamp
OBJECTIVE To determine whether dual-energy CT (DECT) could accurately differentiate the composition of common canine uroliths in a phantom model. SAMPLE 30 canine uroliths with pure compositions. PROCEDURES Each urolith was composed of ≥ 70% struvite (n = 10), urate (8), cystine (5), calcium oxalate (4), or brushite (3) as determined by standard laboratory methods performed at the Canadian Veterinary Urolith Centre. Uroliths were suspended in an agar phantom, and DECT was performed at low (80 kV) and high (140 kV) energies...
October 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28944744/progress-in-the-formulation-and-delivery-of-somatostatin-analogs-for-acromegaly
#20
Sarinj Fattah, David J Brayden
A 14 amino acid cystin bridge containing neuropeptide was discovered in 1973 and designated as growth hormone-inhibiting hormone, in other words, somatostatin. Its discovery led to the synthesis of three analogs which were licensed for the treatment of acromegaly: octreotide, lanreotide and pasireotide. Somatostatin analogs are currently approved only as either subcutaneous or intramuscular long-acting injections. We examine the challenges that must be overcome to create oral formulations of somatostatin analogs and examine selected clinical trial data...
October 2017: Therapeutic Delivery
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