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Glioblastoma (GBM) is one of the most widespread and lethal types of cancer. However, there are currently no drugs or therapeutic strategies that can completely cure GBM. Doramectin (DRM) has a broad range of activities against endoparasites and ectoparasites, and is extensively used in livestock. In the present study, the effect of DRM on the induction of autophagy in U87 and C6 GBM and glioma cell lines, as well as the mechanism of autophagy, were examined. First, transmission electron microscopy, plasmid transfection and western blot analysis demonstrated that DRM could induce autophagy in U87 and C6 cells in vitro . Next, MTT and colony formation assays revealed that DRM‑induced autophagy prevented U87 and C6 cell viability and colony formation ratio. In addition, DRM‑induced autophagy promoted U87 and C6 cell apoptosis, as indicated by DAPI analysis and flow cytometry. Furthermore, transcriptome analysis demonstrated that DRM modulated a number of genes and pathways involved in autophagy. In a nude mouse xenograft model, immunohistochemical staining and the TUNEL assay demonstrated that the effect of DRM on the tumor was consistent with that in vivo . These data indicated that DRM induced autophagy mainly by blocking the PI3K/AKT/mTOR signaling pathway in GBM cells. DRM‑induced autophagy promoted the inhibition of GBM cell proliferation and apoptosis in vitro and in vivo . The present study suggested that DRM may be an effective drug for the treatment of GBM.

Burn injury leads to mitochondrial dysfunction and autophagy, also known as mitophagy. The alleviation of mitochondrial damage may be a potential method for the treatment of burn injury and complications. In this animal study, we analyzed the expression of mitochondrial damage- and mitophagy-related factors, specifically PINK1 and PRKN. The results showed mitochondria damage in the skin; compared with the normal control group, genes involved in the mitochondrial damage, such as Nrf-1, UQCRC2, CYC1, and NDUFA9, as well as in the mitophagy, including PINK1, PRKN, MFN1, and USP30, were differentially expressed. Furthermore, PINK1 interacted with PRKN and participated in mitophagy in the skin. In conclusion, our data reveal more about the mechanism underlying mitophagy in burns, providing a potential clinical treatment., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

<b>Background and Objective:</b> Chitosan has many functional properties and biological activities. This work aimed to prepare and characterize Chitosan Nanoparticles (CN). Then, evaluate the hypolipidemic and antioxidant effect of CN in rats. Incorporate CN in camel yogurt and evaluation of yogurt properties. <b>Materials and Methods:</b> Chitosan Nanoparticles (CN) were prepared and analyzed for the size, zeta potential and poly Polydispersity Index (PDI). Total 24 rats were divided into 4 groups, the negative control group was fed on the basal diet and the positive control group was fed on a High-Fat Diet (HFD), the group I and II were fed on the HFD+(CC) or (CN). The feeding period was 6 weeks. Prepared and Characterization stirred camel yogurt fortified by CN. <b>Results:</b> CN the size was 27.20 nm, ζ-potential+38.78. After the feeding period for CN and CC groups were a decrease in body weight, serum lipid profile and liver function in both tested groups and an increase in HDL-cholesterol and an increase in antioxidants in the CN group more than that in the CC group was observed. mRNA expression with qPCR for hepatic PPARγ, HL, GSS and CYP2E1 genes was performed to investigate the alterations in their levels after CN treatment on the liver of rats fed with HFD. <b>Conclusion:</b> CN possesses the ability to improve the impairment of lipid metabolism as strongly associated with gene expressions related to lipogenesis and oxidative stress. Also, the addition of 2% CN to camel yogurt gave sensory acceptable and microbiological quality.

Insulin receptor substrate (IRS)-2, along with IRS-1, is a key signaling molecule that mediates the action of insulin and insulin-like growth factor (IGF)-I. The activated insulin and IGF-I receptors phosphorylate IRSs on tyrosine residues, leading to the activation of downstream signaling pathways and the induction of various physiological functions of insulin and IGF-I. Studies using IRS-2 knockout (KO) mice showed that the deletion of IRS-2 causes type 2 diabetes due to peripheral insulin resistance and impaired β-cell function. However, little is known about the roles of IRS-2 in other animal models. Here, we created IRS-2 KO rats to elucidate the physiological functions of IRS-2 in rats. The body weights of IRS-2 KO rats at birth were lower compared with those of their WT littermates. The postnatal growth of both male and female IRS-2 KO rats was also suppressed. Compared with male WT rats, the glucose and insulin tolerance of male IRS-2 KO rats were slightly enhanced, whereas a similar difference was not observed between female WT and IRS-2 KO rats. Besides the modestly increased insulin sensitivity, male IRS-2 KO rats displayed the enhanced insulin-induced activation of the mTOR complex 1 pathway in the liver compared with WT rats. Taken together, these results indicate that in rats, IRS-2 plays important roles in the regulation of growth but is not essential for the glucose-lowering effects of insulin., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest., (© 2020 Toyoshima et al.)

Pidan, as the preserved duck egg, is a traditional alkaline-pickled food in China. Previous studies have suggested preserved egg white has an anti-inflammatory effect, though the mechanism of action was unclear. In this work, the difference of peptides distribution in the digestive products was identified from those of duck egg. The effects of preserved egg diet on the modulation of gut microbiota as well as the alteration in fecal metabolites were further investigated. Minor variations of gut microbiota in phylum level were observed between preserved and fresh duck egg diet groups, even though, preserved egg diet intake attributed to increases in the relative abundance of Prevotella and Phascolarctobacterium (p < 0.05), while Ruminococcaceae and Allobaculum were quantitatively decreased (p < 0.05). In terms of metabolites, the contents of acetic acid (p < 0.01) and propionic acid (p < 0.05) were significantly increased in the preserved egg diet group. It was speculated that the preserved egg diet might alter the proportion of short-chain fatty acids (SCFAs) in the gut of rats by modulating specific intestinal bacteria, and subsequently play an active role in anti-inflammatory effects. Compared to the fresh egg group, the bacterial produced SCFAs of preserved egg group were increased in abundance (p < 0.05), which may have potential anti-obesity and anti-inflammatory effects. The results provide a novel insight into the relationship between preserved egg intake, gut microbiota and potential positive effects on host health., (Copyright © 2020 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Providing an alternative to pyrethroids, organophosphates, and carbamates, the neonicotinoids are now the most widely used insecticides in the world. They are water soluble and relatively stable in soil and water which allows for run-off through surface waters and thus potentially impacting aquatic species and environments.While the mammalian metabolism of neonicotinoids has been studied extensively, there is a lack of understanding of their metabolism in fish species. The current study constitutes the first report of the metabolism of imidacloprid (IMI) and acetamiprid (AC) in rainbow trout.Formation of respective metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was conserved across orders of biological organization in both microsomal and liver slice assays.Michaelis-Menten kinetics were determined for the microsomal conversion of IMI to 5-hydroxy-imidacloprid in rainbow trout (Km = 79.2 µM; Vmax = 0.75 pmole/min/mg) and rat (Km = 158.7 µM; Vmax = 38.4 pmole/min/mg). Kinetics for the microsomal demethylation of AC to N-desmethyl-acetamiprid were determined in the rat (Km = 70.9 µM; Vmax = 10 pmoles/min/mg). N-desmethyl-acetamiprid was found in detectable but below quantifiable levels across the range of test concentrations which precluded a calculation of kinetic rate constants in rainbow trout (RBT).Ultimately, the formation of the metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was conserved across RBT and rat species.

Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

Effect of fonio-moringa seed meal (FMSM)-based complementary food in Wistar rats was assessed in a 28 days balanced study. Seventy, 21-day-old Wistar rats were allotted to seven groups in a completely randomized design. Infant weaning foods (IWFs) 1, 2, 3, 4, and 5 had 0%, 5%, 10%, 15%, and 20% FMSM inclusion levels, respectively, while two commercial IWFs purchased were coded CFT and CFC. The water absorption capacity, swelling power, and the pasting properties, except peak time varied (p < .05) among the IWFs. Rats fed on IWFs 3 and 4 had comparable weight gain with those fed on the commercial foods. The heart and kidney relative weights were influenced (p < .05), while villus length (duodenum) of the rats were significant (p < .05). The blood indices were not significant, but the alanine aminotransferase and cholesterol levels ranged 15.65-32.25 µ/dl and 75.75-94.55 mg/100 ml, respectively. Incorporation of 10% FMSM is recommended in IWFs. PRACTICAL APPLICATIONS: The need to reduce hunger and starvation among the less-privileged people in society is becoming increasingly important. Specifically, many infants, preschool and school children are often not having access to nutritive foods that will enhance their mental alertness. The commercial IWFs on sale in Nigeria are in most cases high in prices and consequently out of the reach of the populace. Fonio is a starchy grain with an important potential not only as a survival food but as a compliment for standard diets. Also, moringa seed is known to be of nutritional value. Most infant formulae are based on maize and soybean and it is hoped that the incorporation of FMSM in the infant weaning formula will help to increase the nutritive value and stem the cost of IWFs., (© 2019 Wiley Periodicals, Inc.)

It is known that copper (Cu) is highly accumulated in several organs in the perinatal period, suggesting changes in Cu metabolism with development, although the precise mechanisms are still unclear. To elucidate the mechanisms underlying Cu accumulation in the organs of neonatal rats, we performed speciation analysis using high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry. In the neonatal rat liver immediately after birth, the Cu concentration was elevated 10-fold compared to that in the juvenile rat liver. Most of the accumulated Cu was bound to metallothionein, although Cu in Cu, zinc-superoxide dismutase (SOD) was reduced. Contrary to the hepatic Cu accumulation, the serum Cu concentrations in the neonatal rats were low due to the decreased amount of Cu bound to ceruloplasmin. The mRNA expression of antioxidant protein 1 (Atox1), a Cu chaperone that transports Cu to Atp7b, remained low up to two weeks after birth. These results suggest that Cu accumulation in the neonatal rat liver is caused by the low expression of Atox1, and the accumulation is useful to distribute Cu to Cu-containing anti-oxidative enzymes (e.g., SOD and Atox1) after respiration starts.

Background: Methionine is an essential sulfur-containing amino acid. To elucidate the influence of l-methionine on activation of the nuclear factor erythroid 2-related factor 2-antioxidant responsive element (Nrf2-ARE) antioxidant pathway to stimulate the endogenous antioxidant activity for depressing reactive oxygen species (ROS)-derived oxidative stress, male Wistar rats were orally administered l-methionine daily for 14 days., Results: With the intake of l-methionine, Nrf2 was activated by l-methionine through depressing Keap1 and Cul3, resulting in upregulation of ARE-driven antioxidant expression (glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modulatory subunit, glutathione synthase (GS), catalase (CAT), superoxide dismutase (SOD), heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx)) with increasing l-methionine availability. Upon activation of Nrf2, glutathione synthesis was increased through upregulated expression of methionine adenosyltransferase, S-adenosylhomocysteine hydrolase, cystathionine β-synthase, cystathionine γ-lyse, glutamate cysteine ligase (GCL) and GS, while hepatic expressions of methionine sulfoxide reductases (MsrA, MsrB2, MsrB3) and hepatic enzyme activities (CAT, SOD, GCL, GR, GST, GPx) were uniformly stimulated with increasing consumption of l-methionine. As a result, hepatic content of ROS and MDA were effectively reduced by l-methionine intake., Conclusion: The present study demonstrates that methionine availability plays a critical role in activation of the Nrf2-ARE pathway to induce an endogenous antioxidant response for depressing ROS-derived oxidative stress, which is primarily attributed to the stimulation of methionine sulfoxide reductase expression and glutathione synthesis. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) have an important role in lifestyle-related diseases. To evaluate species differences, we compared LPL and HTGL activities in different animal models of lifestyle-related diseases using the same assay kit. Normal animals (JW rabbits, ICR mice, and SD rats), a hypercholesterolemic animal model (WHHLMI rabbits), and obese animal models (KK-A y mice and Zucker fatty rats) fed standard chow were used in this study. Plasma was prepared before and after an intravenous injection of heparin sodium under fasting and feeding. LPL and HTGL activities were measured with the LPL/HTGL activity assay kit (Immuno-Biological Laboratories) using an auto-analyzer. Only in mice, high HTGL activity was observed in pre-heparin plasma. In normal animals, LPL and HTGL activities were high in ICR mice and SD rats but low in JW rabbits. Compared to normal animals, LPL activity was high in Zucker fatty rats and WHHLMI rabbits at both fasting and feeding, while LPL activity after feeding was low in KK-A y mice. HTGL activity was higher in fasted and fed WHHLMI rabbits and fasted Zucker fatty rats, but was lower in fed KK-A y mice. Gender difference was observed in HTGL activity in SD rats and LPL activity in WHHLMI rabbits but not in ICR mice. In conclusion, this simple assay method was effective for measuring LPL and HTGL activities of experimental animals, and the activities are highly regulated depending on animal species, animal models, feeding/fasting conditions and genders.

Major urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.

Background: Nuclear factor-kB is highly activated in cardiovascular disorders. However, few articles have targeted at the role of nuclear factor-kB inhibitor in heart failure., Aims: To evaluate the effects of nuclear factor-kB inhibitor pyrrolidine dithiocarbamate on cardiocyte apoptosis and cardiac function in a rat heart failure model., Study Design: Animal experiment., Methods: A stable and reproducible rat heart failure model (n=64) was prepared by injecting homologous microthrombotic particles into the left ventricle of Sprague–Dawley rats while obstructing the ascending aorta to produce coronary microembolization. Rats with heart failure were randomized into untreated (HFu) and pyrrolidine dithiocarbamate-treated (HFp) groups; the latter received an intraperitoneal injection of pyrrolidine dithiocarbamate (100 mg/kg/day) 1 h prior to surgery as well as on postoperative days 1-7. The sham group comprised 32 Sprague–Dawley rats. Eight rats from each group were sacrificed on days 1, 3, 7, and 14 postoperatively. Masson’s trichrome staining was used to determine the micro-fibrotic area to indicate the severity of myocardial loss. Terminal transferase uridine triphosphate nick end labeling staining was used to detect apoptotic cardiomyocytes. Echocardiography and hemodynamics were performed to evaluate left ventricular function., Results: Rats with heart failure exhibited pathological changes evidenced by patchy myocardial fibrosis, remarkably elevated severity of myocardial loss, and persistently reduced left ventricular function. At the end of the study, compared with the HFu group, myocardial infarct size was reduced by 28% (p=0.001), cardiocyte apoptosis was suppressed (7.17%±1.47% vs 2.83%±0.75%, p<0.001), cardiac function parameters such as left ventricular ejection fraction (80%±4% vs 61%±6%), left ventricular + dP/dt max (4828±289 vs 2918±76 mmHg.s −1 ), left ventricular - dP/dt max (4398±269 vs 2481±365 mmHg.s −1 ), and left ventricular systolic pressure (126±13 vs 100±10 mmHg) were significantly increased, and left ventricular end-diastolic pressure was reduced (18±2 vs 13±1 mmHg) (p<0.001, for all) in the HFu group., Conclusion: Our rat model can adequately mimic heart failure via coronary vessel embolization. Moreover, pyrrolidine dithiocarbamate treatment can reduce cardiocyte apoptosis and improve cardiac function, which may be beneficial for patients with heart failure secondary to myocardial infarction.

During epigenetic reprogramming germ cells activate alternative mechanisms to maintain the repression retrotransposons. This mechanism involves the recruitment of genome defence proteins such as MAEL, PIWIL4 and TDRD9, which associate with piRNAs and promote Line-1 silencing. MAEL, PIWIL4 and TDRD9 form the piP-bodies, which organization and dynamics vary according to the stage of germ cell epigenetic reprogramming. Although these data have been well documented in mice, it is not known how this mechanism operates in the rat. Thus, the aim of this study was to describe the distribution and interaction of MAEL, PIWIL4, TDRD9 and DAZL during rat germ cell development and check whether specific localization of these proteins is related to the distribution of Line-1 aggregates. Rat embryo gonads at 15 days post-conception (dpc), 16dpc and 19dpc were submitted to MAEL, PIWIL4, TDRD9 and DAZL immunolabelling. The gonads of 19dpc embryos were submitted to the double-labelling of MAEL/DAZL, TDRD9/MAEL and PIWIL4/MAEL. The 19dpc gonads were submitted to co-immunoprecipitation assays and fluorescent in situ hybridization for Line-1 detection. MAEL and TDRD9 showed very similar localization at all ages, whereas DAZL and PIWIL4 showed specific distribution, with PIWIL4 showing shuttling from the nucleus to the cytoplasm by the end epigenetic reprogramming. In quiescent 19dpc gonocytes all proteins colocalized in a nuage adjacent to the nucleus. DAZL interacts with PIWIL4 and MAEL, suggesting that DAZL acts with these proteins to repress Line-1. TDRD9, however, does not interact with DAZL or MAEL despite their colocalization. Line-1 aggregates were detected predominantly in the nuclear periphery, although did not show homogeneous distribution as observed for the nuage. In conclusion, the nuage in quiescent rat gonocytes show a very distinguished organization that might be related to the organization of Line-1 clusters and describe the association of DAZL with proteins responsible for Line-1 repression., Competing Interests: The authors have declared that no competing interests exist.

Cocoa is rich in polyphenols and methylxanthines, and it has been reported that its consumption, among other properties, has beneficial effects on metabolism. This study aimed to investigate the role of theobromine in cocoa's metabolic properties in healthy rats. In addition to morphometric measurements, biochemical markers of lipids and glucose metabolism and gene expression of molecules related to immune cells in adipose and hepatic tissues were assessed after 7 or 18 days of diet. Additionally, a metabolomic analysis was carried out at day 7. This study revealed the presence of six discriminant metabolites in plasma due to the diets. Moreover, the results showed that theobromine is the main responsible factor for cocoa's effects on body weight gain as well as on lipid and glucose metabolism. The effects on body weight and lipids appeared as early as after 7 days of diet, whereas those affecting glucose metabolism required a longer intervention.

The nutritional performance and antioxidant profile of sprouted sorghum-based weaning diets were evaluated in weaning wistar rats. Rats were fed basal diet, unroasted germinated sorghum-based diet, roasted germinated sorghum-based diet, or a commercial weaning feed (nutrend) for 28 days. Energy, carbohydrate, crude protein, lipids, crude fiber, and ash contents of the sorghum-based diets compared significantly with FAO/WHO recommendations. Contrastingly, moisture content of the germinated sorghum-based diet was higher than the recommendation. Weight gain, feed efficiency ratio, protein efficiency ratio, net protein utilization, biological value, and digestibility of unroasted germinated sorghum-based diet-fed rats compared significantly with Nutrend. Roasted germinated sorghum-based diet produced differential effects on these indices. The unroasted germinated sorghum-based diet significantly raised the antioxidant enzymes in the rat liver and kidney. Overall, evidence from the study indicates that unroasted germinated sorghum-based diet improves the nutritional performance and the antioxidants of weaning rats compared to the roasted germinated sorghum-based diet. PRACTICAL APPLICATIONS: The provision of nutritionally adequate food from local sources during the weaning period of infants continues to be a major source of concern in developing countries. The formulated unroasted sprouted sorghum-based diet can be adapted and used as weaning food. Furthermore, the diet can be processed and developed into a weaning food., (© 2019 Wiley Periodicals, Inc.)

1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is the main pathway of selexipag metabolism, irrespective of species. Some interspecies differences were evident for both compounds in terms of both metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower than that of selexipag in all three species. 2. The metabolism of selexipag was also studied in bile-duct-cannulated rats and dogs after a single oral and intravenous dose of [ 14 C]selexipag. MRE-269 acyl glucuronide was found in both rat and dog bile. Internal acyl migration reactions of MRE-269 glucuronide were identified in an experiment with the synthetic standard MRE-6001. 3. MRE-269 was the major component in the faeces of rats and dogs. In ex vivo study using rat and dog faeces, selexipag hydrolysis to MRE-269 by the intestinal microflora is considered to be a contributory factor in rats and dogs. 4. A taurine conjugate of MRE-269 was identified in rat bile sample. Overall, selexipag was eliminated via multiple routes in animals, including hydrolysis, oxidative metabolism, conjugation, intestinal deconjugation, and gut flora metabolism.

In eukaryotes, almost all RNA species are processed at their 3' ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'., (© 2018 The Authors.)

This study compared the effects of casein, soy protein (SP), red (RMP), and white meat (WMP) proteins on growth and metabolism of young rats. Compared to casein, the ratio of daily feed intake to daily body weight gain of rats was not changed by meat protein but reduced by SP by 93.3% ( P < 0.05). Feeding RMP and WMP reduced the liver total cholesterol (TC) contents by 24.3% and 17.8%, respectively ( P < 0.05). Only RMP increased plasma HDL-cholesterol concentrations (by 12.7%, P < 0.05), whereas SP increased plasma triacylglycerol, TC, and LDL-cholesterol concentrations by 23.7%, 19.5%, and 61.5%, respectively ( P < 0.05). Plasma essential and total amino acid concentrations were increased by WMP (by 18.8% and 12.4%, P < 0.05) but reduced by SP (by 28.3% and 37.7%, P < 0.05). Twenty-five liver proteins were differentially expressed in response to different protein sources. Therefore, meat proteins were beneficial for growth and metabolism of young rats compared to casein and SP.

In this work, the effects of different sources of meat protein on liver metabolic enzymes were investigated. Rats were fed for 90 days with semisynthetic diets in which casein was fully replaced by isolated soybean, fish, chicken, pork, or beef proteins. Then, liver proteomics was performed using iTRAQ and LC-ESI-MS/MS. The results indicated that intake of meat protein diets significantly reduced the protein levels of CYP450s, GSTs, UGTs, and SULTs compared to those of the casein and soybean protein diet groups. The total antioxidant capacity and lipid peroxidation values did not differ between four meat protein diet groups and the casein diet group. However, GSH activity in the fish, chicken, and beef protein groups was significantly higher than those of the casein and soybean protein groups. The beef protein diet significantly upregulated the expression of immune-related proteins. The Keap1-Nrf2-ARE signaling pathway was suggested to involve the diet-mediated regulation of biotransformation, inflammation, and redox status.

Starches resistant to mammalian digestion are present in foods and pass to the large bowel, where they may be degraded and fermented by the microbiota. Increases in relative abundances of bifidobacteria (blooms) have been reported in rats whose diet was supplemented with Hi-Maize resistant starch. We determined that the bifidobacterial species present in the rat cecum under these circumstances mostly belonged to Bifidobacterium animalis However, cultures of B. animalis isolated from the rats failed to degrade Hi-Maize starch to any extent. In contrast, Bifidobacterium pseudolongum also detected in the rat microbiota had high starch-degrading ability. Transcriptional comparisons showed increased expression of a type 1 pullulanase, alpha-amylase, and glycogen debranching enzyme by B. pseudolongum when cultured in medium containing Hi-Maize starch. Maltose was released into the culture medium, and B. animalis cultures had shorter doubling times in maltose medium than did B. pseudolongum Thus, B. pseudolongum , which was present at a consistently low abundance in the microbiota, but which has extensive enzymatic capacity to degrade resistant starch, showed the attributes of a keystone species associated with the bifidobacterial bloom. IMPORTANCE This study addresses the microbiology and function of a natural ecosystem (the rat gut) using DNA-based observations and in vitro experimentation. The microbial community of the large bowel of animals, including humans, has been studied extensively through the use of high-throughput DNA sequencing methods and advanced bioinformatics analysis. These studies reveal the compositions and genetic capacities of microbiotas but not the intricacies of how microbial communities function. Our work, combining DNA sequence analysis and laboratory experiments with cultured strains of bacteria, revealed that the increased abundance of bifidobacteria in the rat gut, induced by feeding indigestible starch, involved a species that cannot itself degrade the starch ( Bifidobacterium animalis ) but cohabits with a species that can ( Bifidobacterium pseudolongum ). B. pseudolongum has the characteristics of a keystone species in the community because it had low abundance but high ability to perform a critical function, the hydrolysis of resistant starch., (Copyright © 2018 American Society for Microbiology.)

Probing previously unknown neuropeptides and/or peptide hormones is essential for our understanding of the regulation of energy homeostasis in the brain. We recently performed a cDNA subtractive screening of the chicken hypothalamus, which contained one of the feeding and energy metabolic centers. We found a gene encoding a novel protein of 182 amino acid residues, including one putative small secretory protein of 80 amino acid residues. The C-terminal amino acids of the small protein were Gly-Leu-NH 2 , and as a result, the small protein was termed neurosecretory protein GL (NPGL). Subcutaneous and intracerebroventricular infusions of NPGL increased body mass gain in chicks, suggesting a central role for this protein in regulating growth and energy homeostasis. A database search revealed that the Npgl gene is conserved in vertebrates, including mice and rats. This review summarizes the advances in the characterization, localization, and biological action of NPGL, in birds and rodents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Human, mouse, and zebrafish ovarian cancer G protein-coupled receptors (OGR1s) are activated by both metals and extracellular protons. In the present study, we examined whether pig, rat, chicken, and Xenopus OGR1 homologs could sense and be activated by protons and metals. We found that all homologs stimulated serum response element (SRE)-driven promoter activities when they are stimulated by protons. On the other hand, metals differentially activated the homologs. The results using chimeric receptors of human and zebrafish OGR1s indicate that the specificity of the metal-induced activation lies in the extracellular region. These results suggest that protons are an evolutionally conserved agonist of OGR1. However, the types of metals that activated the receptor differed among the homologs.

The objective of this work was to identify the nutritional and physiological effects of commercial soy and whey protein preparations. Wistar rats were fed with soy (S), whey (W), or casein (C) preparations as the sole dietary protein source. The nitrogen balance, body composition, changes in caecal microbiota, mucosal and bacterial enzyme activities, and allergenic potential of the preparations were analysed. The whey diet elicited greater skeletal muscle anabolism than the soy diet. Rats from the S group had the lowest values of body weight, fat, and lean mass gain. Compared to casein, soy and whey preparations decreased the protein efficiency ratio, increased N in the urine, and triggered the reduction of ammonia levels in the caecum. Changes in β-glucuronidase and β-galactosidase activities in the small intestine, caecum, and colon between experimental groups were observed. Significant differences were noted in the total counts of anaerobic bacteria and sulphite reducing bacteria during soy and whey treatments. This probably affected the short chain fatty acid level in caecal digesta resulting in the lowest propionic acid and total putrefactive short chain fatty acid levels during S treatment. Generally, whey preparations are a good choice for rapid bodybuilding (skeletal muscles), whereas soy preparations are more helpful during mass reduction.

Weaning is an essential and important event for infants and rodent animals, and the dietary supplementation plays a crucial role in regulating the composition and function of gut microbiota in the initial period after weaning. In this study, we investigated the potential effects of two probiotics along with three polysaccharides (PP) in weaned rats. Male SD rats, 21 days of age, were divided into two groups: one group was administered with PP for four weeks and the other was not. Body weight, food intake, gut epithelial barrier function, digestive enzyme activities, and the composition and function of gut microbiota were analyzed. The dietary PP increased the body weight and food intake, promoted gut epithelial barrier integrity, and elevated the activities of digestive enzymes. Moreover, the microbial community structure was different between the two groups. At the genus level, Bifidobacterium, Lactobacillus, and Allobaculum were significantly increased, whereas Anaerostipes, Enterococcus, and Parabacteroides were observably reduced. Furthermore, PP significantly increased amino acid metabolism, energy metabolism, and SCFA-related metabolism. This study shows that synbiotics containing probiotics (L. acidophilus NCFM and B. lactis Bi-07) in combination with polysaccharides (LBP, PCPs, and Lentinan) can modulate the composition of gut microbiota, stimulate the maturation of gut microbiota biological function, and promote the growth performance in weaned rats.

Objectives The aim of this report is to describe the identification of a novel vitamin D metabolite, a C-3, alpha-epimer of 25-hydroxycholecalciferol (3-epi-25(OH)D 3 ), in serum and plasma extracts of cat blood and compare its abundance in cat, dog and rat serum to 25-hydroxycholecalciferol (25(OH)D 3 ), a conventional marker of vitamin D status. Methods Serum 25(OH)D 3 and 3-epi-25(OH)D 3 concentrations were measured in healthy cohorts of cats (n = 8), dogs (n = 8) and rats (n = 17) using validated reverse and normal-phase high-performance liquid chromatography methods. The methods were verified using liquid chromatography tandem mass spectrophotometry. Dietary intake and dietary concentrations of vitamin D were also measured for evaluation of species differences and effect of dietary change on vitamin D metabolite concentrations. Differences between cat serum and plasma metabolite concentrations were determined. Results Detectable concentrations of 3-epi-25(OH)D 3 were observed in all cats and rats. No 3-epi-25(OH)D 3 was detected in dogs, where our limit of detection was 5 ng/ml. There were significant differences ( P <0.05) in serum concentrations of 25(OH)D 3 and 3-epi-25(OH)D 3 among species, with cats having the greatest concentrations of both metabolites. Serum and plasma results were not significantly different. A diet change, which resulted in an increase in vitamin D intake among the cats, affected serum concentration with an increase ( P = 0.004) in 3-epi-25(OH)D 3 but no significant change in 25(OH)D 3 . Conclusions and relevance Serum and plasma of cats contain 3-epi-25(OH)D 3 in varied and extraordinary concentrations, much greater than in rats and certainly than that of dogs, a species for which the metabolite was not detected. Importantly, this finding indicates a C-3 epimerization pathway is quantitatively significant for vitamin D metabolism in domestic cats, making 3-epi-25(OH)D 3 assays essential for the evaluation of vitamin D status in cats and positioning the cat as a novel model for study of this pathway.

Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Arsenic (As) is ubiquitously present in the environment. The toxicity of As is related to its forms. This study was designed to compare the translocation and transformation of four As species from soil to rice, and metabolism in rats for four arsenic species. A set of 26550 data was obtained from pot experiments of rice plants grown in soil fortified with four As species, and 4050 data were obtained from rat experiments in which 81 rats were administered with the four As species. The total As in grain from the methyl arsenate fortified soil was 6.1, 4.9, and 5.2 times that from As(III), As(V), and dimethyl arsenate fortified soil, respectively. The total As in husk was 1.2-7.8 times greater than that in grain. After oral administration of each As species to rats, 83-96% was accumulatively excreted via feces and urine, while 0.1-16% was detected in blood. The translocation, transformation, and metabolism of different forms of arsenic vary greatly.

Sox2-expressing stem/progenitor cells in the anterior lobe of the pituitary gland form two types of micro-environments (niches): the marginal cell layer and dense cell clusters in the parenchyma. In relation to the mechanism of regulation of niches, juxtacrine signaling via ephrin and its receptor Eph is known to play important roles in various niches. The ephrin and Eph families are divided into two subclasses to create ephrin/Eph signaling in co-operation with confined partners. Recently, we reported that ephrin-B2 localizes specifically to both pituitary niches. However, the Ephs interacting with ephrin-B2 in these pituitary niches have not yet been identified. Therefore, the present study aims to identify the Ephs interacting with ephrin-B2 and the cells that produce them in the rat pituitary gland. In situ hybridization and immunohistochemistry demonstrated cell type-specific localization of candidate interacting partners for ephrin-B2, including EphA4 in cells located in the posterior lobe, EphB1 in gonadotropes, EphB2 in corticotropes, EphB3 in stem/progenitor cells and EphB4 in endothelial cells in the adult pituitary gland. In particular, double-immunohistochemistry showed cis-interactions between EphB3 and ephrin-B2 in the apical cell membranes of stem/progenitor cell niches throughout life and trans-interactions between EphB2 produced by corticotropes and ephrin-B2 located in the basolateral cell membranes of stem/progenitor cells in the early postnatal pituitary gland. These data indicate that ephrin-B2 plays a role in pituitary stem/progenitor cell niches by selective interaction with EphB3 in cis and EphB2 in trans.

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E -16 ). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Grape pomace (GP), the residue of grapes after wine making, is rich in dietary polyphenols and fiber, and it has potential to serve as a functional food ingredient to improve health. However, high polyphenol diets have also been reported to inhibit the growth of young animals and cause liver necrosis. This study investigated the effect of diets containing different amounts of GP on the growth performance and blood lipid profile by using a young rat model. Twenty female Sprague-Dawley rats of age 7 weeks were randomly divided into four groups that were fed AIN-93G diets that were modified by substituting 0%, 10%, 20%, and 30% of carbohydrate with GP for 10 weeks (the diets, thus, obtained contained 0%, 6.9%, 13.8%, and 20.7% of GP). The group fed original AIN-93G (0% GP) was used as control. Feed consumption, body weight, length, and height were recorded weekly. Blood samples were taken biweekly to analyze plasma lipid profile. At the end of the feeding period, the rats were fasted overnight and euthanized by exsanguination under anesthesia. Livers, hearts, and kidneys were collected, and their weights were recorded. Results show that the diet containing a maximum of 20.7% of GP did not influence the body weights, lengths, and heights of rats. As the GP content increased, the blood triglyceride and very low-density lipoproteins (VLDL) decreased, the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased slightly but were statistically significant, and total cholesterol remained constant. In conclusion, GP in the AIN-93G diet did not influence the growth performance of young rats, but it exhibited both positive and negative effects on the blood lipid profile.

In the present study, the effects of sex, age, nutritional status, and habitat use on hair and internal tissue concentrations of some trace metals (Zn, Cu, Ni, Pb and Cd) in brown rat (Rattus norvegicus) and great gerbil (Rhombomys opimus) from Aran-O-Bidgol City in Central Iran were investigated. Five sampling stations in different land-uses were selected for the study. Concentrations of Cd and Pb in liver and whole body concentration as well as concentration of Zn in hair of male rats were significantly higher than females. A significantly higher concentration was only observed for Pb in kidney of male gerbils than females. In numerous cases, age had significantly negative correlations with concentration of metals in different tissues of both species, and was only significantly (and positively) correlated with the concentration of Cd in kidney and Zn in liver of gerbils. This finding may indicate that the early neonatal age is a critical period for metals accumulation. The relationships between nutritional status and metal concentrations for both species were negative, which can be ascribed to the weight-specific metabolic rate that cause to a relatively low uptake of metals per unit of body weight. No significant differences were observed for soil metals concentrations in different sites. So, this suggests that the influence of life history, microhabitat use and foraging behavior did significantly influence on inter and intra specific variation of metals concentration in small mammals. Our observations suggest that hair cannot be used alone for monitoring exposure of metals., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The gating properties of the inositol 1, 4, 5-trisphosphate (IP 3 ) receptor (IP 3 R) are determined by the binding and unbinding capability of Ca 2+ ions and IP 3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP 3 R (Oo-IP 3 R1), type-3 IP 3 R (Oo-IP 3 R3) and Spodoptera frugiperda IP 3 R (Sf-IP 3 R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP 3 Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model. By comparing the fitting parameter distributions of three IP 3 Rs, we suggest that the three types of IP 3 Rs have the similar open sensitivity in responding to IP 3 . The Oo-IP 3 R3 channel is easy to open in responding to low Ca 2+ concentration, while Sf-IP 3 R channel is easily inhibited in responding to high Ca 2+ concentration. We also show that the IP 3 binding rate is not a sensitive parameter for stationary gating dynamics for three IP 3 Rs, but the inhibitory Ca 2+ binding/unbinding rates are sensitive parameters for gating dynamics for both Oo-IP 3 R1 and Oo-IP 3 R3 channels. Such differences may be important in generating the spatially and temporally complex Ca 2+ oscillations in cells. Our study also demonstrates that the immune algorithm can be applied for model parameter searching in biological systems.

It has been hypothesized that herbivores host tannin-degrading bacteria (TDB) to overcome the toxic challenges posed by plant tannins. While TDB have been isolated from the guts of numerous mammals, their functional significance to their hosts has never been explicitly tested. We introduced TDB into lab rats, which do not host TDB, and measured host performance on tannin-rich diets. We first isolated three species of TDB, Escherichia coli, Bacillus subtilis and Enterococcus faecalis, from the guts of the desert woodrat (Neotoma lepida), which regularly feeds on tannin-rich plants. Then, we inoculated isolated TDB, as well as full woodrat microbial communities into laboratory rats. A control group was inoculated with sterilized woodrat faeces. Recipient lab rats were fed increasing concentrations of tannic acid, and we monitored tannic acid intake, body mass and liver damage as measured by serum alanine aminotransferase activity. Lab rats given TDB as isolates or full communities exhibited increased tannic acid intake, higher maintenance of body mass and lower indicators of liver damage compared with control animals. These differences were maintained when the trial was repeated after 6 weeks of feeding on tannin-free diets. Our results are the first to demonstrate that TDB significantly increase host performance on tannin-rich diets., (© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: In spite of intensive use of bromadiolone, rodent control was inefficient on a farm infested by rats in Zaragoza, Spain. While metabolic resistance was previously described in this rodent species, the observation of a target resistance to antivitamin K rodenticides had been poorly documented in Rattus rattus., Results: From rats trapped on the farm, cytochrome b and Vkorc1 genes were amplified by PCR and sequenced in order to identify species and detect potential Vkorc1 mutations. VKORC1-deduced amino acid sequences were thus expressed in Pichia pastoris, and inhibition constants towards various rodenticides were determined. The ten rats trapped on the farm were all identified as R. rattus. They were found to be homozygous for the g.74A>T nucleotide replacement in exon 1 of the Vkorc1 gene, leading to p.Y25F mutation. This mutation led to increased apparent inhibition constants towards various rodenticides, probably caused by a partial loss of helical structure of TM4., Conclusion: The p.Y25F mutation detected in the Vkorc1 gene in R. rattus trapped on the Spanish farm is associated with the resistance phenotype to bromadiolone that has been observed. It is the first evidence of target resistance to antivitamin K anticoagulants in R. rattus., (© 2015 Society of Chemical Industry.)

Secreted mucins constitute a crucial part of the gel that protects respiratory and digestive epithelia, being MUC2/Muc2 the predominant gel-forming mucin of the intestine while MUC5AC/Muc5ac is one of the gel-forming mucins most expressed at the airways. In this study, we have analyzed Muc2 and Muc5ac during rat development by using immunohistochemistry, Western blotting and RT-PCR. We demonstrated that rat Muc2 was expressed in fetal intestinal goblet cells of surface epithelium of villi and developing Lieberkühn crypts. In neonates and adults, Muc2 was expressed at luminal goblet cells of small and large intestine and at gastric mucous and glandular cells. Muc5ac protein was observed in embryonic gastric and lung samples; expression increased during development and postnatal and adult life. After birth, a low reaction was detected at the tracheal surface epithelium and glands, which increased in adults., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI-58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19 d) and young adulthood (3 mo). Female rats (28 d old, n = 9/group) were fed control (CON, AIN93G, 7% soybean oil) or HFD (AIN93G, 20% lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19 d) and 3 mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3 mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3 mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3 mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI-58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood.

The Brazilian federal government Agency for Health Surveillance detected pesticide residues in fresh food available for consumers all over the country. The current study investigated the effects of a mixture of some of those pesticides (dichlorvos, dicofol, dieldrin, endosulfan, and permethrin) on the reproductive system of Sprague-Dawley (SD), Wistar (WT), and Lewis (LEW) rats. Female rats from each strain were randomized into three experimental groups and were fed a control diet or diets added with pesticides mixture at their respective no-observed-effect level (NOEL)/no-observed-adverse-effect level (NOAEL) (low dose) (mg/kg/d): dichlorvos (0.23), dicofol (0.5), dieldrin (0.025), endosulfan (0.7), permethrin (5), or lowest-observed-effect level (LOEL)/lowest-effect level (LEL)/ lowest-observed-adverse-effect level (LOAEL) (toxically effective dose) (mg/kg/d): dichlorvos (2.3), dicofol (2.1), dieldrin (0.05), endosulfan (3.8), and permethrin (25) as reported in the literature. Euthanasia was performed between wk 10 and 12, during the estrous stage. Decreased body weights gain (SD and WT) and increased liver weights (SD, WT, and LEW) were observed in each strain fed the pesticides mixture at the higher levels. At that dose level, rat strains also varied in their responses regarding the estrous cycle, hormonal levels, and number of developing ovarian follicles. The studied mixture of pesticides was found to interfere with the female reproductive system when individual pesticides were mixed above a certain level, indicating a threshold exists for each of the strains studied.

In addition to having selective potency against the molecular target(s), a compound must be able to reach its intended site of action in vivo in sufficient quantity and for the appropriate duration of time to exert a biological effect. The fate of a compound after in vivo administration depends upon its absorption, distribution, metabolism, and excretion (ADME), as well as its target residence time. The concentration of the compound in the blood, plasma, and other tissues represents the sum of all of these processes. Described in this unit are protocols for administering a compound by various routes to rats and for collecting the appropriate samples to determine the pharmacokinetics profile. The basic terms used in pharmacokinetics studies are defined, and representative examples are given to illustrate important variables to consider., (Copyright © 2014 John Wiley & Sons, Inc.)

The mammalian habenulae consist of medial (MHb) and lateral (LHb) nuclear complexes. Especially the LHb has received much interest because it has been recognized as the potential center of an "anti-reward system." Subnuclear organization and connectivity of the LHb are well known. In contrast, criteria to classify habenular neurons into distinct groups with potentially different biological functions are missing, most likely as a result of the lack of appropriate marker proteins. Actually, a huge amount of data concerning the localization of more than 20,000 mouse protein genes is provided in the Allen Brain Atlas. Unfortunately, the immediate use of this information is prohibited by the fact that the subnuclear organization of the habenular complexes in mouse is not known so far. The present report, therefore, uses topographic, structural, and cytochemical information from the rat to recognize corresponding areas within the mouse habenulae. Taking advantage of the fact that the Klüver-Barrera technique allows simultaneous observation of neuronal cell bodies and myelinated fibers, we were able to correlate subnuclear areas in the mouse habenula to subnuclei, which had been rigorously identified by several criteria in the rat. Our data suggest that the topographic localization of habenular subnuclei is rather similar between mouse and rat and that they may be homologous in these two species. Consequently, our data may allow using the Allen Brain Atlas as a source of basal information, which should be helpful to select candidate molecular markers for functionally different neurons in the mouse and potentially in higher mammalian species., (© 2014 Wiley Periodicals, Inc.)

Whole prey diets encourage species-typical behaviors making them popular in the zoo and home setting for captive exotic and domestic felids, respectively. We evaluated macronutrient, mineral, and long-chain fatty acid composition of 20 whole prey items: mice (1-2, 10-13, 21-25, 30-40, and 150-180 days of age); rats (1-4, 10-13, 21-25, 33-42, and >60 days of age); rabbits (still born, 30-45 days, >65 days with skin, and >65 days of age with skin removed); chicken (1-3 days of age, ground adult); duck (ground adult); and quail (1-3, 21-40, and >60 days of age). Composition of whole prey was highly variable (15-40% DM, 34-75% CP, 10-60% fat, and 8-18% ash). A majority of whole prey samples (15/20) had at least one mineral or fatty acid below AAFCO [] or NRC [] minimum recommended concentrations for domestic cats (K, Na, Cl, Mg, Cu, Mn, and/or Zn; total fat, linolenic acid, arachidonic acid and/or EPA and DHA). These data identify potential nutrient deficiencies allowing for alterations in dietary formulation prior to long-term feeding., (© 2014 Wiley Periodicals, Inc.)

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Background: Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats., Methods: An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed., Results: Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p<0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined., Conclusions: Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy effects on biochemical parameters but in line with OECD regulation. Gelam honey may have potential in controlling weight gain and triglyceride levels in female rats compared to Acacia honey. SD rats have some effect on biochemical parameters, an exploration of which would make for intriguing analysis.

The aim of this study was to evaluate the influence of diets with different types of fibres on Ca bioavailability and metabolic parameters in growing Wistar rats. Twenty four male Wistar rats were fed with 3 different diets: control (C), polydextrose (PD), and extruded whole maize (M) during a 60 day period. Apparent Ca absorption percentage (%Ca Abs), total skeleton bone mineral content (t BMC), total bone mineral density (t BMD), femur (F), spine (S) and tibia (T) BMD, cecum weight, and pH were evaluated. Malondialdehyde (MDA) and lipid (TG and cholesterol) contents in serum and liver were also evaluated. The results showed that rats fed with M and PD had the same cecum weight, but higher than that of C (1.53 ± 0.02 vs. 0.94 ± 0.01). There was moderate acidification of the cecal content in rats fed with M compared to C (pH 5.93 vs. 6.98) and the fecal weight was 1.06 ± 0.02, 3.07 ± 0.03 and 4.81 ± 0.05 for PD, M and C, respectively. There were significant differences in %Ca Abs between PD and C (87.57 ± 1.20 vs. 71.10 ± 1.11). The PD group had the highest values of F-BMD, S-BMD, and T-BMD, but there were no differences between M and C groups. Regarding lipids, there was a significant lowering effect in the M liver triglycerides content. Moreover, liver MDA levels significantly decreased with M and PD diets. The consumption of PD and grain fibres can exert some beneficial gastrointestinal effects such as lowering of the pH, hepatic TG and MDA content related to fibre colon fermentation.

The thermal energetics of rodents from cool, wet tropical highlands are poorly known. Metabolic rate, body temperature and thermal conductance were measured in the moss-forest rat, Rattus niobe (Rodentia), a small murid endemic to the highlands of New Guinea. These data were evaluated in the context of the variation observed in the genus Rattus and among tropical murids. In 7 adult R. niobe, basal metabolic rate (BMR) averaged 53.6±6.6mLO2h(-1), or 103% of the value predicted for a body mass of 42.3±5.8g. Compared to other species of Rattus, R. niobe combines a low body temperature (35.5±0.6°C) and a moderately low minimal wet thermal conductance cmin (5.88±0.7mLO2h(-1)°C(-1), 95% of predicted) with a small size, all of which lead to reduced energy expenditure in a constantly cool environment. The correlations of mean annual rainfall and temperature, altitude and body mass with BMR, body temperature and cmin were analyzed comparatively among tropical Muridae. Neither BMR, nor cmin or body temperature correlated with ambient temperature or altitude. Some of the factors which promote high BMR in higher latitude habitats, such as seasonal exposure to very low temperature and short reproductive season, are lacking in wet montane tropical forests. BMR increased with rainfall, confirming a pattern observed among other assemblages of mammals. This correlation was due to the low BMR of several desert adapted murids, while R. niobe and other species from wet habitats had a moderate BMR., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Piceatannol (trans-3,3',4,5'-tetrahydroxystilbene), a natural analogue of resveratrol, has multiple biological functions. Nevertheless, piceatannol's biological fate is yet to be determined. In this study, we evaluated the absorption and metabolism of piceatannol in rats. Furthermore, the area under the plasma concentration curves (AUC) and metabolic pathway of piceatannol were compared with those of resveratrol. We determined the plasma concentrations of piceatannol, resveratrol, and their respective metabolites following their intragastric administration. Resveratrol metabolites were only conjugates, whereas piceatannol metabolites were piceatannol conjugates, O-methyl piceatannol, and its conjugates. The AUC for piceatannol, resveratrol, and their metabolites increased in a dose-dependent manner (90-360 μmol/kg). The AUC for total piceatannol was less than that for total resveratrol, whereas the AUC for piceatannol (8.6 μmol·h/L) after piceatannol and resveratrol coadministration was 2.1 times greater than that for resveratrol (4.1 μmol·h/L). The greater AUC for piceatannol was a result of its higher metabolic stability.

Glycation starts from nonenzymatic amino-carbonyl reaction that binds carbonyl group of reducing sugars to the amino group of amino acids. Glycation leads to further complex reactions to form advanced glycation end products (AGE). Because AGE are implicated in the gradual development of diabetic complications, tissue accumulation of AGE has been widely examined in various tissues of rats. Avian species are known to have high body temperature and blood glucose concentration compared with mammals. Although these characteristics enabled chickens to be used as experimental models for diabetes mellitus, the information of AGE accumulation in various tissues of chickens has not been limited so far. In the present study, therefore, the radioactive AGE prepared by reacting (14)C-glucose and amino acids were intravenously administrated, and comparison of tissue accumulation of (14)C-labeled AGE was made between chickens and rats. At 30 min after administration, tissues (18-20) were collected, and the radioactivity incorporated into tissues was determined. High levels of radioactivity per gram of tissue in the liver and kidney were observed in both rats and chickens. In chickens but not rats, a large amount of (14)C-labeled AGE incorporated into 1 g of spleen was observed, and the specific accumulation of AGE in the avian spleen might have a particular role in immune response in avian species.