Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

Effects of inorganic copper injection in beef cows at late gestation on fetal and postnatal growth, hematology and immune function of their progeny.

To determine if Cu injection during late gestation can affect fetal and postnatal growth, hematology and immune function of progeny, 70 multiparous pregnant Angus cows, at 219 ± 15 d of gestation, were ranked by BW and BCS and randomly assigned to one of two treatments: Cu + (n = 35) in total 160 mg of Cu were administered subcutaneously in two moments (80 mg per moment) at 64 ± 15 d and 54 ± 15 d prepartum; and Cu- (n = 35), in total of 16 ml of sterile NaCl solution (9 g / l) were administered subcutaneously in two moments (8 ml per moment) at 64 ± 15 d and 54 ± 15 d prepartum. Calves from both treatments were weaned at 260 ± 15 d of age, male calves were separated from female calves and stockered on natural pastures until 690 ± 15 d of age, then placed into a feedlot for 104 d before slaughter. At the beginning of the experiment, cows Cu serum concentration was similar (P = 0.34) between treatments and these reflected a severe Cu deficiency (Cu + = 24.2 ± 1.5 µg/dl; Cu- = 22.2 ± 1.4 µg/dl). At calving, Cu serum concentration was greater (P < 0.01) in Cu + cows than Cu- cows. Copper serum concentration in calves from Cu + cows was greater at birth (P = 0.02) and 75 ± 15 d of age (P < 0.01) and tended (P = 0.07) to be greater at 160 ± 15 d of age compared to calves from Cu- cows. Calf BW at birth did not differ (P > 0.10) between treatments, however, calf BW adjusted at 75 d of age tended to be greater (P = 0.10) in calves from Cu + cows compared to calves from Cu- cows. Calf ADG from birth to 75 d of age was greater (P = 0.04) in calves from Cu + cows compared to calves from Cu- cows. Calf hematological parameters and titers of neutralizing antibodies against BHV-1 after primary and secondary vaccination against respiratory diseases did not differ (P > 0.10) between treatments. During finishing period, steers BW, 12th rib fat thickness and LM area were not affected (P > 0.10) by treatments. In summary, inorganic Cu injection during late gestation in Cu deficient beef cows allows to increase Cu serum concentration in calves from birth to 160 d of age. This event was associated with an increase in ADG and a tendency to increase BW during the first 75 days of life. After 75 days of age, any effect on the offspring performance was not observed.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Dietary Supplementation of Astaxanthin Improved the Growth Performance, Antioxidant Ability and Immune Response of Juvenile Largemouth Bass (Micropterus salmoides) Fed High-Fat Diet.

High-fat diet (HFD) usually induces oxidative stress and astaxanthin is regarded as an excellent anti-oxidant. An 8-week feeding trial was conducted to investigate the effects of dietary astaxanthin supplementation on growth performance, lipid metabolism, antioxidant ability, and immune response of juvenile largemouth bass (Micropterus salmoides) fed HFD. Four diets were formulated: the control diet (10.87% lipid, C), high-fat diet (18.08% lipid, HF), and HF diet supplemented with 75 and 150 mg kg-1 astaxanthin (HFA1 and HFA2, respectively). Dietary supplementation of astaxanthin improved the growth of fish fed HFD, also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD, while having no effect on body fat. Malondialdehyde content and superoxide dismutase activity were increased in fish fed HFD, astaxanthin supplementation in HFD decreased the oxidative stress of fish. The supplementation of astaxanthin in HFD also reduced the mRNA levels of Caspase 3, Caspase 9, BAD, and IL15. These results suggested that dietary astaxanthin supplementation in HFD improved the growth performance, antioxidant ability and immune response of largemouth bass.

Effect of a commercial product containing canthaxanthin for in ovo feeding to broiler embryos on hatchability, chick quality, oxidation status, and performance.

In ovo feeding has been indicated to improve hatchability, newly hatched chick quality, and broiler performance. The aim of this study was to investigate the effect of in ovo feeding of a commercial canthaxanthin product (CCX) containing lignosulphonate, corn starch, canthaxanthin, dextrin (yellow), and ethoxyquin through assessing incubation results, newly hatched quality and oxidation status and broiler performance at 1 to 14 d of age. A total of 780 egg were distributed in a randomized complete block design with 5 treatments (levels of CCX: 0.0, 0.35, 0.45, 0.55, and 0.65 mg/0.5 mL of sterilized and distilled water) and 156 eggs per treatment. The blocking factor was setters. At 17.5 d of embryo development, in ovo injected treatments were applied, using a manual needle. The in ovo feeding of CCX resulted in lower hatching rates (P < 0.05) and a longer hatching window (P < 0.05) as compared with noninjected CCX treatment. The CCX injection did not affect the bursa and spleen percentage of newly hatched chick (P > 0.05). In addition, a higher percentage of chicks with poor physical quality score (<71.0 points) was obtained among the chicks from eggs injected with 0.55 and 0.65 mg of CCX (P < 0.05). There were higher total proteins and catalase activity in the livers of the chicks injected with CCX. Broiler chicks in the control group (0.0 mg of CCX) presented higher BW and BW gain during 1 to 7 and 7 to 14 d of after hatch (P < 0.05). The viability (%) of chicks at 1 to 14 d of after hatch decreased with inoculation greater than 0.45 mg of CCX in ovo (P < 0.05). Although the CCX shown an improvement in oxidation status of chicks, the hatchability and performance of broilers decreased. We concluded that a commercial CCX is not recommended for injection in ovo, and furthers studies should carried out to elucidate the use of pure canthaxanthin.

Effects of taurine on growth performance, antioxidant capacity, and lipid metabolism in broiler chickens.

To investigate the effects of dietary taurine supplementation on growth performance, antioxidant status, and lipid metabolism in broilers, 384 male broilers (Arbor Acres, 1 D of age) were randomly allocated into 4 groups with 8 replicates of 8 birds. Dietary treatments were supplemented with taurine at the level of 0.00, 2.50, 5.00, and 7.50 g/kg of the diet (denoted as CON, TAU1, TAU2, TAU3, respectively). The BW gain from 1 to 21 D and from 22 to 42 D were all increased linearly (linear, P < 0.001) by taurine supplementation. Throughout the trial period, the highest BW gain and favorable gain-to-feed ratio were observed in the TAU2 group. Taurine supplementation increased the antioxidant enzyme activities and decreased (linear, P < 0.001) the content of malondialdehyde in both serum and the liver of broilers and alleviated oxidative damage through enhancing (P < 0.05) the hepatic genes expression of nuclear factor erythroid-2-related factor 2 (NRF2), glutathione peroxidase (GPX), and heme oxygenase-1 (HO-1). Correspondingly, in serum, the activities of hepatic lipase and total lipase were decreased linearly and quadratically (linear and quadratic, P < 0.001) with the increasing inclusion of taurine in the diet. Meanwhile, in serum, the content of triglycerides was significantly decreased (P < 0.05), and except for TAU3, the total cholesterol content was also significantly decreased (P < 0.05) by taurine supplementation. In addition, the hepatic content of triglycerides was significantly decreased (P < 0.05) in the TAU1 and TAU2 groups. Compared with the CON group, the hepatic genes expression of adenosine monophosphate-activated protein kinase alpha (AMPKα), silent 1, (SIRT1) and carnitine palmitoyltransferase 1 (CPT-1) were all increased (P < 0.05), and sterol regulatory element-binding protein-1 (SREBP-1) expression was decreased (P < 0.05) in the TAU2 group. These results indicated that taurine supplementation improved the growth performance, antioxidant capacity, and lipid metabolism of broilers.

Effects of graded levels of dietary squalene supplementation on the growth performance, plasma biochemical parameters, antioxidant capacity, and meat quality in broiler chickens.

This study was conducted to evaluate the effects of dietary squalene supplementation on the growth performance, plasma biochemical indices, antioxidant status, and meat quality in broilers. Two hundred and forty 0-day-old male chicks were allocated into 5 groups of 6 replicates and were fed a basal diet supplemented with 0 (Control group), 250, 500, 1,000, or 2,000 mg/kg squalene for 42 d. Dietary squalene supplementation linearly increased weight gain and feed efficiency of broilers during the grower and overall periods (P < 0.05). Squalene linearly decreased 21-d malondialdehyde (MDA) level and 42-d glutathione peroxidase (GSH-Px) activity, and both linearly and quadratically decreased 42-d MDA level in plasma (P < 0.05). In contrast, squalene linearly increased plasma reduced form of glutathione (GSH) level on 21 and 42 d and superoxide dismutase activity on 42 d (P < 0.05). Squalene supplementation linearly decreased 21-d MDA accumulation but linearly increased GSH level on 21 d and 42 d and both linearly and quadratically increased 21-d GSH-Px activity in liver (P < 0.05). Supplementing squalene linearly increased pH value at 48 h and linearly decreased lightness at 48 h and 24-h drip loss of breast muscle (P < 0.05). The lightness at 24 h and cooking loss of breast muscle were both linearly and quadratically reduced by squalene (P < 0.05). Dietary squalene administration linearly decreased MDA accumulation but linearly increased GSH level and GSH-Px activity of breast muscle (P < 0.05). Compared with the control group, aforementioned growth performance, antioxidant-related parameters (except 42-d GSH-Px in plasma and breast and hepatic GSH), and meat quality were improved by squalene when its level was 1,000 and 2,000 mg/kg (P < 0.05), with their results being similar between these 2 groups (P > 0.05). It was concluded that squalene administration especially at a level of 1,000 mg/kg can improve growth performance, antioxidant status, and meat quality in broilers, providing insights into its application as a potential feed additive in broiler production.

The effects of different doses of curcumin compound on growth performance, antioxidant status, and gut health of broiler chickens challenged with Eimeria species.

Supplementation of broiler diets with feed additives such as chemotherapeutic drugs and antibiotics has side effects, meat residues, and antibiotics resistance complications. Plant-derived natural compounds could be safe and easy substitutes for chemical additives. One of the natural compounds is curcumin, the extract from herbal plant Curcuma longa, known for its antioxidant and antimicrobial properties which may be effective in reducing coccidia infection in poultry. The objective of this study was to evaluate the effects of curcumin on Eimeria challenged (C) and nonchallenged (NC) Cobb 500 broilers. A total of 360 12-day-old male chicks were housed in 36 cages in a completely randomized design with 6 replicates per treatment of 10 birds each cage. The six corn-soybean meal-based treatment diets were fed from day 12 to 20 to C and NC birds in 3-by-two factorial arrangement: nonchallenged control (NCC), NC + 100 mg/kg curcumin, NC + 200 mg/kg curcumin, challenged control (CC), C + 100 mg/kg curcumin, and C + 200 mg/kg curcumin. Broilers in C groups were inoculated orally with 50,000 oocysts of Eimeria maxima, 50,000 oocysts of Eimeria tenella, and 250,000 oocysts of Eimeria acervulina on day 14. The intestinal permeability (day 19), growth performance parameters, and intestinal lesion scoring were measured and recorded on day 20. The means were subjected to two-way ANOVA, and main factors effect and their interactions were considered. The growth performance and permeability were higher (P < 0.001) in the NC and C groups, respectively. However, no interaction was observed between curcumin dose and cocci challenge on both of these parameters. Results from lesion scores and oocyst shedding showed reduction (P < 0.050) in birds fed C + 200 mg/kg curcumin compared with those fed C + 100 mg/kg curcumin or CC. Curcumin treatment showed higher production of GSH (P = 0.002) and total glutathione (GSH+2GSSG) (P = 0.002) but lower GSH/GSSG ratio (P < 0.001) than the NCC group. Curcumin exhibited some positive responses on antioxidant capacity, lesion score, and oocyst shedding in the present study, suggesting that curcumin alone or a combination with other feed additives could be a dietary strategy to improve gut health in broilers.

Effects of pantothenic acid on growth performance and antioxidant status of growing male white Pekin ducks.

An experiment was conducted to investigate the effects of dietary pantothenic acid levels on growth performance, carcass traits, pantothenic acid status, and antioxidant status of male white Pekin ducks from 15 to 42 D of age and to evaluate the requirement of this vitamin for growing ducks. Different levels pantothenic acid (0, 2, 4, 6, 8, and 10 mg/kg) were supplemented to a corn-soy isolate protein basal diet to produce 6 dietary treatments with different analyzed total pantothenic acid levels (4.52, 6.44, 8.37, 9.88, 12.32, and 14.61 mg/kg). A total of 240 15-day-old male white Pekin ducks were allotted to 6 dietary treatments with 8 replicate pens of 5 birds per pen. At 42 D of age, growth performance, carcass traits, tissue pantothenic acid concentrations, and antioxidant status of white Pekin ducks were examined. Significant effects of dietary pantothenic acid on BW, average daily weight gain (ADG), plasma, and liver pantothenic acid concentrations were observed (P < 0.05) but not carcass traits. The growing ducks fed the basal diet without pantothenic acid supplementation had the lowest BW, ADG, plasma, and liver pantothenic acid content among all ducks (P < 0.05). In addition, the ducks fed the basal diet without pantothenic acid supplementation showed the lowest antioxidant capacity indicated by greatest plasma malondialdehyde content and lowest liver total antioxidant capacity (P < 0.05). And, these criteria responded linearly as dietary pantothenic acid levels increased (P < 0.05). These results indicated that dietary pantothenic acid supplementation improved growth performance and antioxidant status of the growing ducks. In accordance with the broken-line model, the pantothenic acid requirements (based on dietary total pantothenic acid) of male white Pekin ducks from 15 to 42 D of age for BW, ADG, and plasma and liver pantothenic acid contents were 10.18, 10.27, 12.06, and 10.79 mg/kg, respectively.

Dietary supplementation with oregano essential oil and monensin in combination is antagonistic to growth performance of yearling Holstein bulls.

Our previous work indicated that feeding oregano essential oil (OEO) in combination with monensin (MON) may not be mutually beneficial to dairy calf growth performance. To evaluate this observation further, a 240-d long-term growth experiment was conducted using 12 young growing Holstein bulls using a 2 × 2 factorial treatment arrangement. Main factors were OEO and MON arranged in 4 individual treatments: (1) ration fed without OEO or MON (control), (2) OEO fed at 26 mg/kg of dry matter (DM), (3) MON fed at 25 mg/kg of DM, and (4) OEO and MON fed in combination (OEO+MON). Holstein bulls were 70 d of age and similar in body weight (BW; 93.3 ± 4.54 kg) and individually fed for 240 d. The targeted feeding rates of OEO and MON were blended into 200 g of concentrate and top dressed each morning to a corn stalklage-based ration. Body weights, frame measurements, and blood samples were collected monthly. Interactions of OEO by MON were detected for BW, BW gain, average daily gain, and a trend for feed conversion. Bulls fed OEO or MON demonstrated greater final BW (368, 385, 381, and 358 kg for control, OEO, MON, and OEO+MON, respectively), and BW gains (278, 292, 285, and 265 kg) and average daily gain (1.16, 1.22, 1.19, 1.11 kg/d) were greatest for bulls fed OEO or MON compared with bulls fed OEO+MON; bulls fed the control were intermediate and similar to bulls fed MON. Intake of DM was greater for bulls fed OEO (6.55, 6.99, 6.60, and 6.42 kg/d) compared with bulls fed remaining treatments. Frame growth gain measurements for heart girth, abdominal girth, withers height, body length, and cannon bone circumference were similar for bulls fed all treatments. Serum triglyceride (0.23, 0.25, 0.28, and 0.24 mmol/L) concentrations were greater for bulls fed MON compared with bulls fed the control and OEO+MON, and bulls fed OEO were intermediate and similar. Cholesterol (2.06, 2.29, 2.20, and 2.07 mmol/L) concentrations were greater for bulls fed OEO compared with bulls fed the control and OEO+MON, and bulls fed MON were intermediate and similar. Serum antioxidant measurements were similar for bulls fed all treatments. Serum IgA, IgG, and IgM concentrations were similar for bulls fed all treatments. Feeding OEO or MON separately can improve growth performance of growing Holstein bulls. We do not know why the combination of OEO and MON is antagonistic to growth performance of Holstein bulls. However, these technologies should not be fed in combination to growing dairy cattle.

Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease.

OBJECTIVE: To compare growth in children with intestinal failure-associated liver disease (IFALD) who received a fish oil intravenous lipid emulsion (FOLE) to those who received a soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: This multisite, retrospective study pair-matched FOLE (n = 82) to SOLE recipients (n = 41) using baseline serum direct bilirubin levels and postmenstrual age. Study subjects received open-label FOLE (1 g/kg/day) until IFALD resolved or parenteral nutrition was stopped. Historical control subjects received SOLE (up to 3 g/kg/day). Growth measures (changes in body weight, height/length, and head circumference), prealbumin, triglycerides, and glucose were compared between groups over time using the Wilcoxon rank-sum test. RESULTS: Although changes in all of the growth measures were similar for both groups (P > .05), FOLE recipients demonstrated an overall improved growth trajectory. After 28 weeks, FOLE recipients had a mean body weight within a z score range of -1 to 1 indicating age-appropriate growth. FOLE recipients consistently had higher prealbumin, lower triglyceride, and more normal glucose concentrations over time compared with SOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had similar growth and fewer metabolic abnormalities compared with those who received SOLE. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy.

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = -0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 µg per kilogram of body weight (8 patients in cohort 1), 7.5 µg per kilogram (8 patients in cohort 2), 15.0 µg per kilogram (10 patients in cohort 3), or 30.0 µg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 µg per kilogram and then to 15.0 µg per kilogram, and in cohort 2, the dose was increased to 15.0 µg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months. RESULTS: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 µg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 µg per kilogram for up to 42 months. CONCLUSIONS: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).

Effects of berberine on the growth performance, antioxidative capacity and immune response to lipopolysaccharide challenge in broilers.

This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response-related genes in lipopolysaccharide (LPS)-challenged broilers. We assigned 120 one-day-old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T-SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS-induced decreases in the mRNA expression of nuclear factor-kappa B (NF-κB), TNF-α, IL-1ß, inducible nitrite synthase and cyclooxygenase-2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF-κB signalling and the expression of inflammatory mediators.

Antibiotic Treatment in the First Week of Life Impacts the Growth Trajectory in the First Year of Life in Term Infants.

OBJECTIVE: Antibiotic treatment in early life appears to increase the risk for childhood overweight and obesity. So far, the association between antibiotics administrated specifically during the first week of life and growth has not been studied. Therefore, we studied the association between growth and antibiotics, given in the first week of life and antibiotic courses later in the first year of life. METHOD: A prospective observational birth cohort of 436 term infants with 151 receiving broad-spectrum antibiotics for suspected neonatal infection (AB+), and 285 healthy controls (AB-) was followed during their first year. Weight, height, and additional antibiotic courses were collected monthly. A generalized-additive-mixed-effects model was used to fit the growth data. Growth curve estimation was controlled for differences in sex, gestational age, delivery mode, exclusive breast-feeding, tobacco exposure, presence of siblings, and additional antibiotic courses. RESULTS: Weight-for-age and length-for-age increase was lower in AB+ compared with AB- (P < 0.0001), resulting in a lower weight and length increase 6.26 kg (standard error [SE] 0.07 kg) and 25.4 cm (SE 0.27 cm) versus 6.47 kg (SE 0.06 kg) and 26.4 cm (SE 0.21 cm) (P < 0.05 and P < 0.005, respectively) in the first year of life. Approximately 30% of the children in both groups received additional antibiotic course(s) in their first year, whereafter additional weight gain of 76 g per course was observed (P = 0.0285). CONCLUSIONS: Decreased growth was observed after antibiotics in the first week of life, whereas increased growth was observed after later antibiotic course(s) in term born infants in the first year of life. Therefore, timing of antibiotics may determine the association with growth.

Anti-tumor effects of resveratrol on malignant melanoma is associated with promoter demethylation of RUNX3 gene.

The natural phytoalexin resveratrol (RES) has exhibited excellent anti-tumor effects on a variety of tumors including malignant melanoma. However, its specific mechanism of anti-melanoma needs to be further explored. It has been reported, that the expression of tumor suppressor gene RUNX3 was lost or substantially decreased in melanoma. Whether RES exerts its anti-tumor effect by regulating the expression of RUNX3 gene in melanoma is worthy of study. In the present study, we found the RUNX3 promoter is hypermethylated and the expression of RUNX3 mRNA and protein are absent in melanoma cells B16F10. After intervention with RES, promoter hypermethylation of RUNX3 in B16F10 cells could be significantly decreased and mRNA and protein expression of it was upregulated in a dose-dependent manner. We further investigated the effects of RES on B16F10 xenograft models. The intervention of RES and treatment of melanoma positive drug dacarbazine (DTIC) both could significantly inhibit tumor growth in xenograft mice, but only RES could upregulate the expression of RUNX3 mRNA and protein in peripheral blood and tumor tissues. Therefore, the upregulation of mRNA and protein expression of RUNX3 resulting from promoter demethylation might be one of the mechanisms of RES inhibiting melanoma. This research has revealed a novel mechanism for RES against melanoma from the epigenetic perspective, which is helpful to improve the understanding of the anti-tumor mechanism of RES and provide new insights for the treatment of melanoma.

Influence of AIDS antiretroviral therapy on the growth pattern / Influência da terapia antirretroviral para a AIDS no padrão de crescimento

Abstract Objectives: Human immunodeficiency virus infection can result in the early impairment of anthropometric indicators in children and adolescents. However, combined antiretroviral therapy has improved, in addition to the immune response and viral infection, the weight and height development in infected individuals. Therefore, the objective was to evaluate the effect of combined antiretroviral on the growth development of human immunodeficiency virus infected children and adolescents. Source of data: A systematic review was performed. In the study, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) strategy was used as the eligibility criterion. The MEDLINE-PubMed and LILACS databases were searched using these descriptors: HIV, children, growth, antiretroviral therapy. The objective was defined by the population, intervention, comparison/control, and outcome (PICO) technique. Inclusion and exclusion criteria were applied for study selection. Synthesis of data: Of the 549 studies indexed in MEDLINE-PubMed and LILACS, 73 were read in full, and 44 were included in the review (33 showed a positive impact of combined antiretroviral therapy on weight/height development, ten on weight gain, and one on height gain in children and adolescents infected with human immunodeficiency virus). However, the increase in growth was not enough to normalize the height of infected children when compared to children of the same age and gender without human immunodeficiency virus infection. Conclusions: Combined antiretroviral therapy, which is known to play a role in the improvement of viral and immunological markers, may influence in the weight and height development in children infected with human immunodeficiency virus. The earlier the infection diagnosis and, concomitantly, of malnutrition and the start of combined antiretroviral therapy, the lower the growth impairment when compared to healthy children.

Resumo Objetivos: A infecção pelo vírus da imunodeficiência humana pode comprometer, precocemente, os indicadores antropométricos de crianças e adolescentes. No entanto, a terapia antirretroviral combinada tem melhorado, além da resposta imunológica e da infecção viral, o ganho pôndero-estatural dos infectados. Dessa forma, nosso objetivo foi avaliar o efeito da terapia antirretroviral combinada no crescimento, de crianças e adolescentes, infectadas pelo vírus da imunodeficiência humana. Fonte dos dados: Foi realizada uma revisão sistemática. No estudo, adotou-se como critério de elegibilidade dos artigos, a estratégia PRISMA (preferred reporting items for systematic reviews and meta-analyses). Foram consultadas as bases de dados MEDLINE-PubMed e LILACS pelos descritores: HIV (vírus da imunodeficiência humana), children, growth, antiretroviral therapy. O objetivo foi definido pela estratégia PICO (population, intervention, comparison/control, outcome). Critérios de inclusão e exclusão foram aplicados na seleção dos estudos. Síntese dos dados: Dos 549 estudos indexados no MEDLINE-PubMed e LILACS, 73 foram lidos na íntegra - 44 incluídos na revisão (33 demonstraram impacto positivo da terapia antirretroviral combinada no ganho pôndero-estatural, dez no ganho de peso e um no de estatura, em crianças e adolescentes, infectados com vírus da imunodeficiência humana). No entanto, o incremento no crescimento não foi o suficiente para normalizar a estatura de crianças infectadas, quando comparado com crianças da mesma idade e sexo, sem infecção pelo vírus da imunodeficiência humana. Conclusões: A terapia antirretroviral combinada que, conhecidamente, atua na melhora de marcadores virais e imunológicos, pode influenciar no ganho pôndero-estatural de crianças infectadas com vírus da imunodeficiência humana. Quanto mais precoce o diagnóstico da infecção e, concomitante, desnutrição e início da terapia antirretroviral combinada, menores serão os prejuízos no crescimento, quando comparado às crianças saudáveis.

The association between antibiotics in the first year of life and child growth trajectory.

BACKGROUND: Antibiotics are frequently prescribed to children, and may be an environmental influence that contributes to the increasing prevalence of childhood obesity. The aim of this study was to examine the effect of antibiotic use in the first year of life on child growth trajectories from birth to age 6 years including significant covariates. METHODS: Data from 586 children in the Infant Feeding Practices II (IFPS II) and 6 year follow-up study (6YFU) were included. Antibiotic exposures, weight and height measurements were collected from birth through the first 12 months, and then again at 6 years. Linear mixed effects growth modeling, controlling for exclusive breastfeeding, socio-demographic factors, smoking during pregnancy, gestational diabetes, and maternal pre-pregnancy weight status, was used to examine the association between antibiotic exposure and child growth trajectories through age 6 years. RESULTS: The majority of infants (60.58%) did not receive any antibiotics; 33.79% received 1-2 courses and 5.63% received 3 or more antibiotic courses during the first year. In the unadjusted model, children with 1-2 antibiotic exposures had a 0.17 (SE 0.08) higher rate of change in BMI z-score (BMIz) than children without any antibiotics, and children with ≥3 exposures had a 0.42 (SE 0.16) higher rate of change in BMIz (p = 0.009). Growth trajectory over time for those who had ≥3 antibiotics was greater than those without any antibiotics (p = 0.002). CONCLUSIONS: Efforts to guide the judicious use of antibiotics should continue, particularly in the first year of life.

Long-term Growth in Congenital Adrenal Hyperplasia.

OBJECTIVES: To retrospectively assess growth of children with congenital adrenal hyperplasia (CAH) with special reference to puberty and to assess longitudinal growth and final height of subset of children with CAH. METHODS: A retrospective analysis of 30 children (14 boys) with classic CAH (11 salt wasters, 19 simple virilisers) followed up for a mean duration of 9.9 ± 2.4 y (Study period December 2002 through December 2016) was performed. Height Z scores, target height Z scores, height velocities and laboratory parameters were analysed. RESULTS: Children were treated with hydrocortisone in a mean dose of 15.7 ± 3.3 mg/m2/d. Mean 17-hydroxy progesterone in boys and girls were 10.8 ± 6.7 ng/ml and 11.3 ± 9.3 ng/ml respectively. Fifteen children (7 boys) developed central precocious puberty at mean age of 7.6 ± 1.8 y and 13 were treated with GnRH analogues for 3.5 y. Of all patients, 18 (10 girls, 8 boys) reached final height at a mean age of 14.2 ± 1.6 y. Mean final height achieved was 158.0 ± 8.5 cm in boys [target height (TH) -165.5 ± 3.8 cm] and in girls it was 149.9 ± 6.7 cm [target height (TH) 154.7 ± 6.4 cm]. Final height standard deviation scores (SDS) for boys and girls were - 2.06 ± 1.1 (TH-SDS -1.06 ± 0.5) and - 1.47 ± 1.1 (TH-SDS -0.56 ± 1.2) respectively and were not significantly different from target height Z scores (p > 0.05). Growth velocity was attenuated during pubertal years. CONCLUSIONS: Monitoring growth and puberty in children with CAH is critical for optimizing final height.

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. RESULTS: The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. CONCLUSIONS: In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).