Receptor Protein Content Research Articles

Adrenalectomy improves MSG-induced obesity in rats by increasing UCP-1 levels in interscapular brown adipose tissue

The administration of monosodium glutamate (MSG) to neonates has been shown to result in hypothalamic damage and development of metabolic syndrome. The objective of this study was to investigate whether bilateral adrenalectomy (ADX) could alter sympathetic activity in adult MSG rats, with the potential to contribute to the improvement of metabolic syndrome by interfering with intermediary metabolism. Following a period of 99 days, the rats that received the control treatment and MSG were subjected to bilateral adrenalectomy (ADX). The following experimental groups were established, and designated as follows: CTL-SHAM, CTL-ADX, MSG-SHAM, and MSG-ADX. The subjects were 109 and 110 days-old at the time of the experiment. The assessment included murinometric and biochemical parameters, an intravenous glucose tolerance test (IVGTT), sympathetic nerve activity in interscapular brown adipose tissue (iBAT), and protein content of β3-adrenergic receptor (β3-ADR) and uncoupling protein 1 (UCP-1). The MSG rats presented metabolic syndrome, which was associated with lower sympathetic activity and a decreased content of the β3-adrenergic receptor when compared to the controls in iBAT. We can conclude that the lower β3-adrenergic receptor contributed to the maintenance of obesity in the MSG rats model. Although it has an adverse effect on the glucose tolerance of CTL-ADX animals, the typical features of metabolic syndrome in adult MSG rats were mitigated by ADX. These effects included an enhancement of UCP-1 in iBAT, a reduction in fat accumulation, and an improvement in glycemia, thereby contributing to an improvement in metabolic syndrome.

The effects of social loss and isolation on partner odor investigation and dopamine and oxytocin receptor expression in female prairie voles.

In humans, grief is characterized by intense sadness, intrusive thoughts of the deceased, and intense longing for reunion with the deceased. Human fMRI studies show hyperactivity in emotional pain and motivational centers of the brain when an individual is reminded of a deceased attachment figure, but the molecular underpinnings of these changes in activity are unknown. Prairie voles (Microtus ochrogaster), which establish lifelong social bonds between breeding pairs, also display distress and motivational shifts during periods of prolonged social loss, providing a model to investigate these behavioral and molecular changes at a mechanistic level. Here, a novel odor preference test was used to assess social vs non-social odor investigation, and a sucrose preference test was used to assess non-social, reward-driven motivation. Females that lost a male partner investigated partner- and food-associated cues significantly more than females that lost a female cagemate or remained intact with a male partner. However, females experiencing the loss of a male partner did not change investigation of stranger-associated cues. Western blotting revealed significant increases of dopamine receptor type 1 (DRD1) and oxytocin receptor protein content in specific brain regions in response to the loss of distinct social relationships. Such effects included an increase in DRD1 in the medial preoptic area of the hypothalamus (mPOA) in females experiencing loss of a male partner compared to all other conditions. Pharmacological antagonism of DRD1 in the mPOA blocked the loss-associated increase of investigation of the partner odor but did not affect investigation of food or stranger odors. This reveals a novel dopamine-mediated mechanism for partner-seeking behavior during periods of partner loss in female prairie voles.

Serum 25-hydroxyvitamin D, vitamin D receptor, and vitamin D binding protein concentrations in dogs with acute pancreatitis compared to healthy control dogs.

Previous studies have documented vitamin D imbalance in dogs with acute pancreatitis (AP), but no studies have investigated serum vitamin D receptor (VDR) and vitamin D-binding protein (VDBP) concentrations. Compare serum 25-hydroxyvitamin D (25[OH]D), VDR, and VDBP concentrations in healthy dogs and dogs with AP and identify correlations between these concentrations with ionized calcium, C-reactive protein (CRP), and canine-specific pancreatic lipase (Spec cPL) concentrations. Twenty-two dogs with AP and 20 healthy control dogs. Prospective cross-sectional study. Serum 25(OH)D concentrations were measured using a chemiluminescence immunoassay, and VDR and VDBP concentrations were measured using a ELISA kit designed for dogs. Serum concentrations of 25(OH)D were lower in dogs with AP (mean ± SD, 66.1 ± 39.2 ng/mL) than in controls (96.8 ± 30.4 ng/mL; P = .01), and VDR concentrations were lower in dogs with AP (5.3 ± 3.5 ng/mL) than in controls (7.4 ± 2.5 ng/mL; P = .03). No difference was observed in serum VDBP concentrations between the groups. Serum VDR concentrations differed between survivors (median [interquartile range] = 6.6 [4.3-8.2] ng/mL) and nonsurvivors (2.7 [0.5-3.5] ng/mL; P = .01). Negative correlations were observed among serum VDR, CRP (rs = -0.55), and Spec cPL (rs = -0.47) concentrations in dogs with AP. Dogs with AP had lower serum 25(OH)D and VDR concentrations than controls. Additionally, our study suggests a potential role of VDR expression in the inflammatory process of AP in dogs.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury

To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

Efficacy of iron-folic acid treatment for reducing anemia prevalence and improving iron status in women of reproductive age: A one-year longitudinal study.

Anemia control has hitherto been through prophylaxis with weekly iron folic acid (IFA) in Indian women of reproductive age (WRA). Recently, a more precise approach has been proposed, that uses a 'screen and treat with IFA' approach for anemic WRA, combined with continued prophylactic IFA in non-anemic WRA. The efficacy of this approach was assessed in Indian WRA, along with changes in iron status biomarkers. Young WRA (n=470), aged 17-21y, were screened for their venous blood hemoglobin (Hb) and treated with IFA for 90 days according to their grade of anemia, or if non-anemic, administered prophylactic IFA, per Indian policy guidelines, and then followed-up for an additional 9-months. Their Hb, plasma ferritin (PF), transferrin receptor, hepcidin and C-reactive protein concentrations were measured at baseline, during treatment and further follow-up. Anemia was diagnosed using Hb (<12g/dL) and iron deficiency (ID) using PF (<15μg/L) cut-offs after adjustment for inflammation. Co-existence of anemia and ID was labelled iron deficiency anemia (IDA). At baseline, in the whole group anemia, ID and IDA prevalence was 69.6%, 68.7% and 62.4%, respectively. At 90 days, IFA treatment or prophylaxis significantly reduced anemia by 40 percentage points (pp), from 69.6% at baseline to 29.8%; ID by 47.3 pp, and IDA by 48 pp. Moreover, significant treatment effects persisted at 365 days of follow-up. The 'screen and treat with IFA' approach is efficacious in reducing the prevalence of anemia in general among WRA, with persistent and significant effects after 9 months of follow-up. CTRI No:2019/02/017806, http://ctri.nic.in/.

Altered cerebrovascular regulation in low birthweight swine

Full-term low birthweight (LBW) offspring exhibit peripheral vascular dysfunction in the postnatal period; however, whether such impairments extend to the cerebrovasculature remains to be elucidated. We used a swine model to test the hypothesis that LBW offspring would exhibit cerebrovascular dysfunction at later stages of life. Offspring from 14 sows were identified as normal birthweight (NBW) or LBW and were assessed at 28 (similar to end of infancy) and 56 (similar to childhood) days of age. LBW swine had lower absolute brain mass, but demonstrated evidence of brain sparing (increased brain mass scaled to body mass) at 56 days of age. The cerebral pulsatility index, based on transcranial Doppler, was increased in LBW swine. Moreover, arterial myography of isolated cerebral arteries revealed impaired vasoreactivity to bradykinin and reduced contribution of nitric oxide (NO) to vasorelaxation in the LBW swine. Immunoblotting demonstrated a lower ratio of phosphorylated-to-total endothelial NO synthase in LBW offspring. This impairment in NO signaling was greater at 28 vs. 56 days of age. Vasomotor responses to sodium nitroprusside (NO-donor) were unaltered, while Leu31, Pro34 neuropeptide Y-induced vasoconstriction was enhanced in LBW swine. Increases in total Y1 receptor protein content in the LBW group were not significant. In summary, LBW offspring displayed signs of cerebrovascular dysfunction at 28 and 56 days of age, evidenced by altered cerebral hemodynamics (reflective of increased impedance) coupled with endothelial dysfunction and altered vasomotor control. Overall, the data reveal that normal variance in birthweight of full-term offspring can influence cerebrovascular function later in life.

Morphological and molecular effects of overexpressed GH on mice mammary gland

Growth Hormone (GH) plays crucial roles in mammary gland development and growth, and its upregulation has been associated with breast cancer promotion and/or progression. To ascertain how high GH levels could promote mammary tissue oncogenic transformation, morphological characteristics and the expression of receptors involved in mammary growth, development and cancer, and of mitogenic mediators were analyzed in the mammary gland of virgin adult transgenic mice that overexpress GH.Whole mounting and histologic analysis evidenced that transgenic mice exhibit increased epithelial ductal elongation and enlarged ducts along with deficient branching and reduced number of alveolar structures compared to wild type mice. The number of differentiated alveolar structures was diminished in transgenic mice while the amount of terminal end buds (TEBs) did not differ between both groups of mice. GH, insulin-like growth factor 1 (IGF1) and GH receptor mRNA levels were augmented in GH-overexpressing mice breast tissue, as well as IGF1 receptor protein content. However, GH receptor protein levels were decreased in transgenic mice. Fundamental receptors for breast growth and development like progesterone receptor and epidermal growth factor receptor were also increased in mammary tissue from transgenic animals. In turn, the levels of the proliferation marker Ki67, cFOS and Cyclin D1 were increased in GH-overexpressing mice, while cJUN expression was decreased and cMYC did not vary.In conclusion, prolonged exposure to high GH levels induces morphological and molecular alterations in the mammary gland that affects its normal development. While these effects would not be tumorigenic per se, they might predispose to oncogenic transformation.

Neonatal programming with sex hormones: Effect on expression of dopamine D1 receptor and neurotransmitters release in nucleus accumbens in adult male and female rats

Steroid sex hormones produce physiological effects in reproductive and non-reproductive tissues, such as the brain. In the brain, sex hormones receptors are expressed in cortical, limbic and midbrain areas modulating memory, arousal, fear and motivation between other behaviors. One neurotransmitters system regulated by sex hormones is dopamine (DA), where during adulthood, sex hormones promote neurophysiological and behavioral effects on DA systems such as tuberoinfundibular (prolactin secretion), nigrostriatal (motor circuit regulation) and mesocorticolimbic (driving of motivated behavior). However, the long-term effects induced by neonatal exposure to sex hormones on DA release induced by D1 receptor activation and its expression in nucleus accumbens (NAcc) have not been fully studied. To answer this question, neurochemical, cellular and molecular techniques were used. The data show sex differences in NAcc DA extracellular levels induced by D1 receptor activation and protein content of this receptor in male and female control rats. In addition, neonatal programming with a single dose of TP increases the NAcc protein content of D1 receptors of adult male and female rats. Our results show new evidence related with sex differences that could explain the dependence to drug of abuse in males and females, which may be associated with increased reinforcing effects of drugs of abuse.

Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

Characterisation of the types of anaemia prevalent among children and adolescents aged 1–19 years in India: a population-based study

Anaemia is a serious public health concern in India. However, national estimates for its prevalence are not available for the 5-14 years age group, nor are estimates available for the types of anaemia among children and adolescents (1-19 years). We aimed to assess the prevalence of anaemia among children and adolescents in India and to categorise types of anaemia on the basis of micronutrient deficiencies. We assessed the prevalence of anaemia among children (1-4 years and 5-9 years) and adolescents (10-19 years) using nationally representative data from the Comprehensive National Nutrition Survey. Anaemia was classified on the basis of age and sex-specific WHO cutoffs and serum ferritin, soluble transferrin receptor, folate, cyanocobalamin, and C-reactive protein concentrations as iron deficiency anaemia, folate or vitamin B12 deficiency anaemia, dimorphic anaemia (iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), anaemia of other causes (anaemia not classified as iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), and anaemia of inflammation. We included 26 765 children (11 624 aged 1-4 years and 15 141 aged 5-9 years) and 14 669 adolescents. In the weighted sample, anaemia prevalence was 40·5% (4553 of 11 233) among 1-4 year-olds, 23·4% (3439 of 14 664) among 5-9 year-olds, and 28·4% (4064 of 14 300) among adolescents. Among 2862 children aged 1-4 years, iron deficiency anaemia (1045 [36·5%]) was the most prevalent type, followed by anaemia of other causes (702 [24·5%]), folate or vitamin B12 deficiency anaemia (542 [18·9%]), dimorphic anaemia (387 [13·5%]), and anaemia of inflammation (186 [6·5%]). Among 2261 children aged 5-9 years, anaemia of other causes was the most common (986 [43·6%]), followed by folate or vitamin B12 deficiency anaemia (558 [24·6%]), iron deficiency anaemia (353 [15·6%]), dimorphic anaemia (242 [10·7%]), and anaemia of inflammation (122 [5·4%]). 861 (31·4%) of 2740 adolescents had anaemia of other causes, 703 (25·6%) had folate or vitamin B12 deficiency anaemia, 584 (21·3%) had iron deficiency anaemia, 498 (18·2%) and dimorphic anaemia, and 94 (3·4%) had anaemia of inflammation. Iron deficiency anaemia is the most common form of anaemia among younger children and anaemia of other causes among 5-9-year-old children and adolescents. Folate or vitamin B12 deficiency anaemia accounts for more than a third of anaemia prevalence. Anaemia prevention efforts should focus on strengthening the existing iron and folate supplementation programmes and prevention of folate or vitamin B12 deficiency anaemia. The Mittal Foundation.

Gene and protein expression of exercise pressor reflex‐related molecular receptors in dorsal root ganglion of spontaneous‐hypertensive and normotensive rats

BACKGROUNDThe exercise pressor reflex (EPR), mediated by mechano‐ and metabosensitive skeletal muscle afferent feedback, is exaggerated in spontaneously hypertensive rats. This cardiovascular reflex dysfunction could be the result of disease‐related abnormalities in the expression and/or sensitivity of molecular receptors located on the terminal end of these muscle afferents, altered central integration of muscle afferent feedback, and/or altered end‐organ responsiveness to a given sympathetic activity.PURPOSETo examine dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized to be significant determinants of the EPR in control (CTRL) and spontaneous hypertensive rats (SHR).METHODSTwelve lumbar DRGs (6 left, 6 right) were harvested from each of the ten CTRL (mean arterial blood pressure (MAP): 99 ± 2 mmHg) and the ten SHR (MAP: 146 ± 3 mmHg) male rats. DRGs from the right side were quickly frozen for later extraction and RNA sequencing. All mRNA values were normalized to transcripts per million (TPM). DRGs from the left were quickly frozen and later assessed for protein expression by Western Blot. All protein was normalized to GAPDH. Analyses were focused on the transient receptor potential cation channel 1 (TRPV1), acid‐sensing ion channel 3 (ASIC3), purinergic receptor 2X3 (P2X3), and prostaglandin E2 receptor 4 (EP4).RESULTSmRNA content was similar between SHR and CTRL animals (TRPV1: 113 ± 9 TPM vs 110 ± 13 TPM; ASIC3: 39 ± 9 vs 44 ± 7; P2X3: 246 ± 16 vs 246 ± 26; EP4: 10 ± 1 vs 9 ± 1, respectively; all P &gt; 0.18). In contrast, SHR animals demonstrated a greater protein expression for all receptors measured compared to CTRL animals (TRPV1: 1.47 ± 0.20% vs 0.86 ± 0.06%; ASIC3: 1.36 ± 0.09 vs 0.77 ± 0.07; P2X3: 1.49 ± 0.11 vs 1.18 ± 0.11; EP4: 1.36 ± 0.21 vs 1.11 ± 0.13; all P &lt; 0.01).CONCLUSIONIn the face of an equivalent mRNA content in the SHR and CRTL DRG, the substantially greater receptor protein content in the SHR supports the potential for a dysregulated expression of muscle receptor protein in the hypertensive rats. Furthermore, these findings suggest an abnormally increased content of EPR‐related molecular receptors as a potential mechanism contributing to the exaggerated EPR which characterizes these animals.Support or Funding InformationHL‐116579This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of orexin-A on firing activity of gastric distension-sensitive neurons in the basomedial amygdala and food intake in diet-induced obese rats

Objective To investigate the effects of orexin-A on firing activity of gastric distension-sensitive (GD) neurons in the basomedial amygdala (BMA) and food intake in diet-indaced obese rats. Methods Healthy male Wistar rats were selected, and the diet-induced obesity (DIO) rat model and diet-induced resistant (DR) rat model were established by high-fat diet. The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons.The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization.The mRNA expression and protein expression of orexin-1 receptor (OX-1R) and μ opioid receptor were detected by real-time PCR and Elisa, respectively. Results After microinjection of orexin-A into the BMA, the firing frequency of GD-sensitive neurons in the normal rats was significantly increased (GD-E: (78.3±6.9)%, GD-I: (55.5±4.7)%, P<0.01), and this effect was completely blocked by OX-1R receptor antagonist SB334867, and naloxone partially blocked the discharge-promoting effect of orexin-A; Compared with the normal rats, the firing frequency of GD-sensitive neurons in the DIO(GD-E: (91.6±7.1)%, GD-I: (67.9±8.1)%) and DR(GD-E: (87.9±6.8)%, GD-I: (69.2±5.8)%)rats was significantly increased after BMA injection of orexin-A (P<0.05). After administration of orexin-A into the BMA, food intake of the normal rats, DIO rats and DR rats ((2.38±0.34) g, (3.75±0.32) g, (4.01±0.38) g, respectively) was significantly increased (P<0.01), and the food intake of DR and DIO rats were significantly higher than that of normal rats (P<0.05). After BMA was injected with naloxone, the food intake of rats was inhibited, and the food intake of the DIO rats was significantly lower than that of the DR rats (P<0.05), food intake of the DR rats was significantly lower than that of the normal rats (P<0.05). The results of real-time PCR showed that the mRNA levels of OX-1R in DIO and DR rats were( 5.85±0.45 )and (6.03±0.42) were higher than that of normal rats, and the difference was significant (P<0.05); and mRNA levels of μ-opioid receptors in DIO and DR rats((4.51±0.42) and (8.31±0.41)times) were higher than those in normal rats (P<0.05). The results of Elisa showed that the protein levels of OX-1R in DIO ((2.98±0.28) ng/μl) and DR rats ((3.05±0.31) ng/μl) were higher than those in normal rats ((1.53±0.31)ng/μl, P<0.05). The content of μ-opioid receptor protein in DR rats ((4.21±0.35)ng/μl) was higher than that of DIO rats ((2.77±0.27) ng/μl), and higher than that of normal rats((1.48±0.32) ng/μl), the difference was significant (P<0.05). Conclusion BMA orexin-A promotes the spontaneous discharge of GD-sensitive neurons and food intake in normal rats, DIO rats and DR rats, μ-opioid receptors may be involved in the regulation of this process. Key words: Orexin-A; Food intake; Gastric distension-sensitive neurons; Diet-induced obesity rat; Amygdala

Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders to Resistance Exercise Training: Current Perspectives and Future Research Directions.

Numerous reports suggest there are low and high skeletal muscle hypertrophic responders following weeks to months of structured resistance exercise training (referred to as low and high responders herein). Specifically, divergent alterations in muscle fiber cross sectional area (fCSA), vastus lateralis thickness, and whole body lean tissue mass have been shown to occur in high versus low responders. Differential responses in ribosome biogenesis and subsequent protein synthetic rates during training seemingly explain some of this individual variation in humans, and mechanistic in vitro and rodent studies provide further evidence that ribosome biogenesis is critical for muscle hypertrophy. High responders may experience a greater increase in satellite cell proliferation during training versus low responders. This phenomenon could serve to maintain an adequate myonuclear domain size or assist in extracellular remodeling to support myofiber growth. High responders may also express a muscle microRNA profile during training that enhances insulin-like growth factor-1 (IGF-1) mRNA expression, although more studies are needed to better validate this mechanism. Higher intramuscular androgen receptor protein content has been reported in high versus low responders following training, and this mechanism may enhance the hypertrophic effects of testosterone during training. While high responders likely possess “good genetics,” such evidence has been confined to single gene candidates which typically share marginal variance with hypertrophic outcomes following training (e.g., different myostatin and IGF-1 alleles). Limited evidence also suggests pre-training muscle fiber type composition and self-reported dietary habits (e.g., calorie and protein intake) do not differ between high versus low responders. Only a handful of studies have examined muscle biomarkers that are differentially expressed between low versus high responders. Thus, other molecular and physiological variables which could potentially affect the skeletal muscle hypertrophic response to resistance exercise training are also discussed including rDNA copy number, extracellular matrix and connective tissue properties, the inflammatory response to training, and mitochondrial as well as vascular characteristics.

The association between airway eosinophilic inflammation and IL-33 in stable non-atopic COPD

BackgroundInterleukin(IL)-33 is an epithelial alarmin important for eosinophil maturation, activation and survival. The aim of this study was to examine the association between IL-33, its receptor expression and airway eosinophilic inflammation in non-atopic COPD.MethodsIL-33 concentrations were measured in exhaled breath condensate (EBC) collected from healthy non-smokers, asthmatics and non-atopic COPD subjects using ELISA. Serum and sputum samples were collected from healthy non-smokers, healthy smokers and non-atopic COPD patients. Based on sputum eosinophil count, COPD subjects were divided into subgroups with airway eosinophilic inflammation (sputum eosinophils > 3%) or without (sputum eosinophils ≤3%). IL-33 and soluble form of IL-33 receptor (sST2) protein concentrations were measured in serum and sputum supernatants using ELISA. ST2 mRNA expression was measured in peripheral mononuclear cells and sputum cells by qPCR. Hemopoietic progenitor cells (HPC) expressing ST2 and intracellular IL-5 were enumerated in blood and induced sputum by means of flow cytometry.ResultsIL-33 levels in EBC were increased in COPD patients to a similar extent as in asthma and correlated with blood eosinophil count. Furthermore, serum and sputum IL-33 levels were higher in COPD subjects with sputum eosinophilia than in those with a sputum eosinophil count ≤3% (p < 0.001 for both). ST2 mRNA was overexpressed in sputum cells obtained from COPD patients with airway eosinophilic inflammation compared to those without sputum eosinophilia (p < 0.01). Similarly, ST2 + IL-5+ HPC numbers were increased in the sputum of COPD patients with airway eosinophilia (p < 0.001).ConclusionsOur results indicate that IL-33 is involved in the development of eosinophilic airway inflammation in non-atopic COPD patients.

Subclinical inflammation affects iron and vitamin A but not zinc status assessment in Senegalese children and Cambodian children and women - ERRATUM.

OBJECTIVE To assess the impact of the acute-phase response (APR) during inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of micronutrient status in populations. DESIGN Ferritin (FER), soluble transferrin receptor (TfR), retinol-binding protein (RBP), Zn, α1-acid glycoprotein and C-reactive protein concentrations were measured. Correction factors (CF) for each biomarker were calculated as the ratio for groups at different stages of inflammation v. the reference group without inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n 2471); Cambodian women of reproductive age (n 2117). RESULTS TfR was higher during the incubation phase (CF=1·17) and lower during early and late convalescence (CF=0·87 and 0·78). FER was higher during all phases (CF=0·83, 0·48 and 0·65, respectively). RBP was higher during incubation (CF=0·88) and lower during early convalescence (CF=1·21). No effect of inflammation on Zn status was found. CONCLUSIONS Inflammation led to overestimation of Fe status and underestimation of vitamin A status. The response of the biomarker for vitamin A status to inflammation depended on the vitamin A status of the populations. Surprisingly, the assessment of Zn status was hardly affected by inflammation. Different phases of the APR had opposite effects on the assessment of Fe status using TfR. More research is needed to define the correct methods to adjust for inflammation in nutritional studies.

Cardiac μ-opioid receptor contributes to opioid-induced cardioprotection in chronic heart failure

BackgroundThe therapeutic potential of cardiac μ-opioid receptors in ischaemia-reperfusion (I/R) injury during opioid-modulating diseases, such as heart failure, is unknown. We aimed to explore the changes of cardiac μ-opioid receptor expression during heart failure, and its role in opioid-induced cardioprotection. MethodsRats received doxorubicin (DOX) or were subjected to coronary artery ligation to induce heart failure, or received normal saline (NS) as control. Hearts from NS or DOX rats were isolated and subjected to myocardial ischaemia and reperfusion in an in vitro perfusion system. The opioid [D-Ala,2N-MePhe,4 Gly-ol]-enkephalin (DAMGO), with a high μ-opioid receptor specificity, morphine, and remifentanil were administrated before I/R with or without opioid receptor antagonists, or an extracellular signal-regulated kinase (ERK) inhibitor. ResultsCardiac μ-opioid receptor mRNA concentrations were 3.2 times elevated in DOX-treated rats compared with NS rats, while cardiac μ-opioid receptor protein concentrations showed 6.1- and 3.5-fold increases in DOX-treated and post-infarcted rats, respectively. DAMGO reduced I/R-caused infarct size, expressed as the ratio of area at risk, from 0.50 (0.04) to 0.25 (0.03) in failing rat hearts, but had no effect on infarct size in control hearts. DAMGO promoted phosphorylation of ERK and glycogen synthase kinase (GSK)-3β only in failing hearts. DAMGO-mediated cardioprotection was blocked by an ERK inhibitor. The μ-opioid receptor antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) prevented morphine- and remifentanil-induced cardioprotection and phosphorylation of ERK and GSK-3β in failing hearts. In contrast, δ- and κ-opioid receptor selective antagonists were less potent than CTOP in the failing hearts. ConclusionsCardiac μ-opioid receptors were substantially up-regulated during heart failure, which increased DAMGO-induced cardioprotection against I/R injury.

Beneficial effects of thyroid hormone on adipose inflammation and insulin sensitivity of obese Wistar rats.

Thyroid hormones play an important role in glucose metabolism and there is evidence of increased prevalence of thyroid dysfunction in obese and diabetic patients. This study aimed at evaluating the thyroid function and the effects of the triiodothyronine (T3) treatment on glycemia control, insulin sensitivity and subclinical inflammation in cafeteria‐diet‐induced obesity in rats. Obesity was induced in male Wistar rats by offering a cafeteria diet and a subset of the obese rats was treated with T3 (1.5 μg per 100 g of body weight) for a 28‐day period. The pituitary‐thyroid axis was evaluated by molecular and biochemical parameters. Cytokine content was measured in the serum as well as in the mesenteric and epididymal white adipose tissue. Obese rats exhibited impairment of glycemia control, increased content of inflammatory cytokines in mesenteric white adipose tissue, decreased serum thyrotropin (TSH) concentration and increased sodium/iodide symporter (NIS) and TSH receptor (TSHR) protein content in thyroid gland. T3 treatment improved insulin sensitivity, glucose tolerance, and reduced inflammatory cytokine content in mesenteric white adipose tissue. In the thyroid gland NIS, TSHR, and thyroperoxidase (TPO) content were reduced while thyroglobulin (TG) content was increased by T3. The thyrotrophic response to negative feedback exerted by T3 was preserved in obese rats. The present data reinforce the beneficial effects of T3 treatment of obese rats on the improvement of insulin sensitivity and on the negative modulation of inflammatory cytokine expression in adipose tissue. Moreover, we have evidenced that the pituitary‐thyroid axis is affected in obese rats, as illustrated by the impaired TSH secretion.

Subclinical inflammation affects iron and vitamin A but not zinc status assessment in Senegalese children and Cambodian children and women.

To assess the impact of the acute-phase response (APR) during inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of micronutrient status in populations. Ferritin (FER), soluble transferrin receptor (TfR), retinol-binding protein (RBP), Zn, α1-acid glycoprotein and C-reactive protein concentrations were measured. Correction factors (CF) for each biomarker were calculated as the ratio for groups at different stages of inflammation v. the reference group without inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n 2471); Cambodian women of reproductive age (n 2117). TfR was higher during the incubation phase (CF=1·17) and lower during early and late convalescence (CF=0·87 and 0·78). FER was higher during all phases (CF=0·83, 0·48 and 0·65, respectively). RBP was higher during incubation (CF=0·88) and lower during early convalescence (CF=1·21). No effect of inflammation on Zn status was found. Inflammation led to overestimation of Fe status and underestimation of vitamin A status. The response of the biomarker for vitamin A status to inflammation depended on the vitamin A status of the populations. Surprisingly, the assessment of Zn status was hardly affected by inflammation. Different phases of the APR had opposite effects on the assessment of Fe status using TfR. More research is needed to define the correct methods to adjust for inflammation in nutritional studies.

Effects of Ginkgo biloba leaf extract on local renin-angiotensin system through TLR4/NF-κB pathway in cardiac myocyte.

The present study investigated the effects of Ginkgo biloba leaf extract (GBE50) on lipopolysaccharide (LPS) induced Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its effects on angiotensinogen (ATG) and AT1a receptor, so as to explore the mechanism of GBE50 in prevention and treatment of left ventricular remodeling. In vitro cultured neonatal rat ventricular myocytes (NRVMs) were divided into 4 groups including i) control group: DMEM medium; ii) LPS group: iii) LPS + GBE50 group; iv) LPS + caffeic acid phenethyl ester (CAPE, specific inhibitor of NF-κB) group. Nuclear translocation of NF-κB p65 was detected by immunocytochemical method after intervention for 24 h. Expression of TLR4, ATG, AT1a receptors and β-myosin heavy chain (β-MHC) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein content of cardiomyocytes was measured by Coomassie Brilliant Blue method. Under LPS stimulation, expression level of TLR4 mRNA in NRVMs was significantly increased (P<0.01), nuclear translocation of NF-κB p65 was increased, expression levels of ATG, AT1a receptor and β-MHC mRNA and the protein content in cells were also increased significantly (P<0.01). GBE50 and CAPE significantly inhibited nuclear translocation of NF-κB p65. GBE50 and CAPE treatments also reduced the increased mRNA levels of TLR4, ATG, AT1a receptor and β-MHC and protein content in cell caused by LPS stimulation. We concluded that, GBE50 can inhibit the activation of local renin-angiotensin system by inhibiting the activation of TLR4/NF-κB and TLR4/NF-κB, signaling pathway inhibition may be one of the mechanisms of the role of Ginkgo biloba leaf extract in preventing myocardial remodeling.

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey

BackgroundZinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12–36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency.MethodsWe used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α1-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 μg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency.ResultsWhole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 μmol/mol and 40 μmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, μmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%–53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%.ConclusionsIn young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened.Trial registrationClinicalTrials.gov NCT02073149 (25 February 2014).