Improvac immunocastration affects the development of thigh muscles but not pectoral muscles in male chickens.

Improvac has been tentatively used to immune-castrate roosters. The aim of this study was to investigate whether Improvac affected skeletal muscle development in chickens. The muscle fiber type and size and the expression levels of genes related to muscle development in pectoral and thigh muscles were examined at 5, 9, and 14 wk of age in the control, early, late, and early + late Improvac-treated groups. Immunocastration with Improvac affected the development of thigh muscles and the expression of MYH1B, MSTN, and SM. The cross-sectional area in the early group was significantly larger than in the control group at the 14th week (P < 0.01). At the fifth week, the expression levels of MYH1B, MYOD, and MSTN in the early group were significantly higher than those in the control group (P < 0.05), and at the ninth week, the expression level of SM1 in the control group was significantly lower than that in early and late groups (P < 0.05). Immunocastration did not affect pectoral muscle development or the expression of genes related to muscle development.

Improvac induces immunocastration by affecting testosterone levels and disrupting spermatogenesis in male broiler chickens.

Immunocastration (vaccination against Gonadotropin-releasing hormone (GnRH)) has been regarded as a friendly substitution to physical castration in animals. To date, a few studies have reported the use of Improvac for immunocastration in boar and one study in broiler chickens; however, there is an apparent dearth of scientific evidence regarding the application of Improvac for immunocastration in birds. In the present study, we evaluated the effects of Improvac-based immunocastration on testosterone levels and spermatogenesis in broiler chickens and the effects of Improvac on the expression of genes related to testosterone biosynthesis and metabolism as well as spermatogenesis. The birds were randomly divided into 4 groups (n = 30 each): Control group (non-immunized), Early group (immunized with Improvac at week 3), Late group (immunized with Improvac at week 6), and Early + Late group (immunized with Improvac at weeks 3 and 6). Immunization with Improvac significantly improved the average daily gain compared to the Control group. Of note, following Improvac vaccination, the reproductive efficiency was significantly decreased in male broiler chickens. Furthermore, parameters such as the serum testosterone concentration, spermatogenesis, and the expression levels of genes related to testosterone metabolism (Cyp17A1, Cyp19, HSD3B1, and HSD17B3) and spermatogenesis (Cyclin A1 and Cyclin A2) were significantly reduced in the immunized groups compared to the Control group. Taken together, these findings reveal that immunization against GnRH can be achieved, at least partially, in male broiler chickens. The results of our study also support the hypothesis of using Improvac as an alternative solution to caponization, with considerably improved animal welfare.

The upregulation of pro-inflammatory cytokines in the rabbit uterus under the lipopolysaccaride-induced reversible immunoresponse state.

The reproductive organs are more likely to develop gram-negative bacterial infection than other internal organs because of direct access to the body surface. The objective of this study was (1) to provide a suitable intravenous injection dose of lipopolysaccharides (LPS) instead of gram-negative bacterial infection in order to induce a reversible immunoresponse state and (2) to examine the expression levels of pro-inflammatory cytokines in the uterus of rabbits while in an immunoresponse state. Two series of experiments were performed to accomplish these objectives. In the first series, 20 healthy New Zealand White female rabbits were divided into 5 homogeneous groups (n=4), and intravenously injected with 0, 0.5, 1, 2, or 4mg/kg body weight (BW) of LPS derived from Escherichia coli dissolved in 2ml of sterile saline (LPS carrier). The control group received only saline. The concentrations of IL-1ß, IL-6, and TNF-α in serum and the white blood cell count changed with time after LPS stimulation, and certain doses of LPS led to the death of some rabbits. The results suggested that a dose of 0.5mg/kg of LPS induced a reversible immunoresponse state. In the second series, 4 rabbits were not injected (0h), 16 rabbits were injected with 0.5mg/kg LPS, and 16 rabbits in the control group were injected with 2ml of sterile saline. Tissues of the uterine horn, uterine body, and cervix from the 36 rabbits were collected at 0, 1.5, 3, 6, and 12h (n=4) postinjection for examination of the expression levels of IL-1ß, IL-6, and TNF-α by quantitative real-time PCR (qRT-PCR). The results suggested that 0.5mg/kg of LPS upregulated the expression levels of IL-1ß, IL-6 and TNF-α in the uterine body and uterine horn, and IL-6 in the cervix. In conclusion, the expression levels of IL-1ß, IL-6 and TNF-α were upregulated in the uterus of rabbits under the reversible immunoresponse state induced by 0.5mg/kg of LPS-injection.

Synergistic targeted therapy for acute promyelocytic leukaemia: a model of translational research in human cancer.

Acute promyelocytic leukaemia (APL), the M3 subtype of acute myeloid leukaemia, was once a lethal disease, yet nowadays the majority of patients with APL can be successfully cured by molecularly targeted therapy. This dramatic improvement in the survival rate is an example of the advantage of modern medicine. APL is characterized by a balanced reciprocal chromosomal translocation fusing the promyelocytic leukaemia (PML) gene on chromosome 15 with the retinoic acid receptor α (RARα) gene on chromosome 17. It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARα fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Here, we provide an insight into the pathogenesis of APL and the mechanisms underlying the respective roles of ATRA and ATO. In addition, treatments that lead to more effective differentiation and apoptosis of APL cells, including leukaemia-initiating cells, and more thorough eradication of the disease will be discussed. Moreover, as a model of translational research, the development of a cure for APL has followed a bidirectional approach of 'bench to bedside' and 'bedside to bench', which can serve as a valuable example for the diagnosis and treatment of other malignancies.

Effects of dietary betaine supplementation subjected to heat stress on milk performances and physiology indices in dairy cow.

This study aimed to determine whether feeding betaine to cows elevates their production performance during summer heat stress. Thirty-two lactating Holstein cows were randomly divided into 4 groups: the control group, which received a total mixed ration (TMR), and 3 experimental groups that received TMR blended with 10 g/day (group I), 15 g/day (group II), and 20 g/day (group III) betaine for 8 weeks. Milk and blood were sampled throughout the experimental period. The average maximum and minimum air temperatures were 28.3 and 24.1°C, respectively. The average temperature-humidity index was 78.6 units. The results showed that feeding betaine to cows increased feed intake, milk yield, milk lactose, milk protein, plasma cortisol, glutathione peroxidase, superoxide dismutase, and malondialdehyde levels (P<0.05); however, it caused HSP70 levels to decrease (P<0.05). The milk performance of group II was significantly affected. These results indicate that supplementing betaine to the diet of dairy cows increases their milk performance and improves their antioxidant capacity; these processes help relieve the cow from heat stress. In conclusion, supplementing dairy cows with 15 g/day betaine generated the most positive influence on performance and productivity, and hence caused the greatest reduction in heat stress.

First live offspring born in superovulated sika deer (Cervus nippon) after embryo vitrification.

The rapid growth in sika deer (Cervus nippon) farming and interest in their conservation is an impetus for development of embryo transfer (ET) procedures. However, a paucity of research has prevented widespread application of ET in this species. The objective of the present study was to establish a multiple ovulation and ET procedure with both fresh and vitrified embryos in sika deer. Multiparous weaned hinds (N = 18) were used as embryo donors during the reproductive season of 2008 at a local breeding farm in China. Estrus was synchronized in donors and recipients (N = 38) by inserting a controlled internal drug release for 12 days (insertion = Day 0). Superovulation was induced with a total of 320 mg of NIH-FSH-P1 (Folltropin-V; Bioniche, Belleville, ON, Canada) given as 40 mg im every 12 h from the afternoon of Day 9 to the morning of Day 13. After estrus was detected, donors were artificially inseminated using a transcervical technique. The embryo recovery rate was 76.8% (63/82), including 1.6% (1/63), 77.8% (49/63), and 1.6% (1/63) blastocysts, morula, and eight-cell embryos, respectively. After transfer of fresh and vitrified embryos, pregnancy rates were 85.7% and 61.6% and birth rates were 64.3% and 53.9% (P > 0.05). In conclusion, we developed a satisfactory multiple ovulation and ET procedure in farmed sika deer using vitrified embryos.

L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs.

The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.

Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.