Animals

The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whetherMoringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke.M. oleiferaleaves extract at doses of 100, 200 and 400 mg·kg−1was orally given to male Wistar rats (300–350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of ext...

Recently, substances possessing antioxidant can prevent cataractogenesis of diabetic cataract. Therefore, this study was carried out to determine the anticataract effect ofZea maysL. (purple waxy corn), a flavonoids rich plant, in experimental diabetic cataract. Enucleated rat lenses were incubated in artificial aqueous humor containing 55 mM glucose with various concentrations ofZea maysL. (purple waxy corn) ranging between 2, 10, and 50 mg/mL at room temperature for 72 h. At the end of the incubation period, the evaluation of lens opacification, MDA level, and the activities of SOD, CAT, GPx, and AR in lens were performed. The results showed that both medium and high doses of extract decreased lens opacity together with the decreased MDA level. In addition, medium dose of extract increased GPx activity while the high dose decreased AR activity. No other significant changes were observed. The purple waxy corn seeds extract is the potential candidate to protect against diabetic cata...

The application of plasmonic-enhanced Raman imaging of cancer cells and drug delivery is gaining momentum. Here, we propose a new theranostic strategy based on an efficient plasmonic-tunable Raman/Fourier transform infrared (FTIR) spectroscopy imaging, to simultaneously evaluate the anticancer drug scattering cellular imaging and the Raman scattering molecular vibration signals in living cells. This technique allows to monitoring the drug release throughout the cell cycle and in vivo biodistribution and biocompatibility with low dose drug therapy (200 μg/mL) and low toxicity effect. This system can directly track in real-time the delivery and release of an anticancer drug (mitoxantrone, MTX) from gold nanostars in single living cells and in mice (healthy and lung cancer mice models), revealing a strong accumulation in the heart of healthy mice 5 min after administration and infiltration in the tumor site of lung cancer mice 5 h after systemic injection. This in vivo SERS detection m...

Gold nanobeacons can be used as a powerful tool for cancer theranostics. Here, we proposed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold nanoparticle and only emit light following conjugation to the Kras target owing to reorganization and opening of the nanobeacons, thus increasing the distance between the dye and the quencher. The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascula...

Multidrug resistance (MDR) in cancer cells is a substantial limitation to the success of chemotherapy. Here, we describe facile means to overcome resistance by silencing the multidrug resistance protein 1 (MRP1), before chemotherapeutic drug delivery in vivo with a single local application. Our platform contains hydrogel embedded with dark-gold nanoparticles modified with 5-fluorouracil (5-FU)-intercalated nanobeacons that serve as an ON/OFF molecular nanoswitch triggered by the increased MRP1 expression within the tumor tissue microenvironment. This nanoswitch can sense and overcome MDR prior to local drug release. The nanobeacons comprise a 5-FU intercalated DNA hairpin, which is labeled with a near-infrared (NIR) dye and a dark-quencher. The nanobeacons are designed to open and release the intercalated drug only upon hybridization of the DNA hairpin to a complementary target, an event that restores fluorescence emission due to nanobeacons conformational reorganization. Despite th...

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [(64)Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [(64)Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [(18)F]FDG-PET, discriminated IPA from a general increase in metabolic acti...

Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Maximum binding (mean ± SD) of [(57)Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding o...

Background— Evaluation of novel cellular therapies in large-animal models and patients is currently hampered by the lack of imaging approaches that allow for long-term monitoring of viable transplanted cells. In this study, sodium iodide symporter (NIS) transgene imaging was evaluated as an approach to follow in vivo survival, engraftment, and distribution of human-induced pluripotent stem cell (hiPSC) derivatives in a pig model of myocardial infarction. Methods and Results— Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NIS pos -hiPSCs) were established. Iodide uptake, efflux, and viability of NIS pos -hiPSCs were assessed in vitro. Ten (±2) days after induction of myocardial infarction by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NIS pos -hiPSCs guided by 3-dimensional NOGA mapping was performed. Dual-isotope single photon emission computed tomographic/computed tomographic imaging was applied w...

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans.

Significance Appropriate homeostatic regulation of catecholamines (dopamine, norepinephrine) is important for the maintenance of normal brain function and mental state. The dysregulation of dopamine systems has been correlated with a hyperactive phenotype and social abnormalities, which are frequently observed in patients with psychiatric disorders. In this report, we found that IRBIT regulates catecholamine homeostasis by binding to calcium calmodulin-dependent kinase II alpha and subsequently controlling tyrosine hydroxylase phosphorylation. In addition, mice lacking IRBIT present with increased locomotor activity and social abnormalities. Our finding provides new insight into the homeostatic regulation of catecholamines.

Chronic stress is associated with anxiety and depressive disorders, and can cause weight gain. Ca(2+)-dependent activator protein for secretion 2 (CAPS2) is involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body weight, reduced glucose-induced insulin release, and abnormal psychiatric behaviors. We chronically administered the stress hormone corticosterone (CORT), which induces anxiety/depressive-like behavior and normally increases plasma insulin levels, via the drinking water for 10 weeks, and we examined the stress response in KO mice. Chronic CORT exposure inhibited stress-induced serum CORT elevation in wild-type (WT) mice, but not in KO mice. Poor weight gain in CORT-treated animals was observed until week 6 in WT mice, but persisted for the entire duration of the experiment in KO mice, although there is no difference in drug*genotype interaction. Among KO mice, food consumption was unchanged, while water consumption was higher, over the duration of the e...

In research and development studies for human and veterinary medicine, relevant comparators for interpreting clinical pathology results are matched with concurrent control animals. However, reference intervals (RI) provide a comparator database and important aids for interpreting clinical pathology data, especially in laboratory beagle dogs. Furthermore, RI incorporate biologic variation, which includes analytical, intraindividual, and interindividual variation. No studies to date have established RI and studied the effect of biologic variation on hematologic variables in a large group of laboratory dogs. The purpose of this retrospective study was to establish hematologic RI for laboratory beagles according to international recommendations and estimate the effect of biologic variation in routinely measured hematologic analytes by using the databank at a pharmaceutical center. Blood specimens from 340 healthy beagles (age, 9 to 36 mo) were evaluated by using a flow-cytometry-based hematology analyzer. RI and their 90% confidence intervals were established by using a nonparametric method. Effects of sex, age, and weight were investigated. Weight had no effect on any analyte. RBC, Hgb, Hct, MCV, MCH, RBC distribution width, and platelet count increased with age, whereas WBC count decreased. The only clinically relevant effect of sex was observed for platelets, which were lower in male beagles than in female and warranted 2 different RI. The calculated index of individuality showed that population-based RI were appropriate for almost all hematologic analytes, as might be expected for a homogeneous group of laboratory beagles.