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Ascites syndrome (AS) is one of the most noticeable metabolic disorders in broiler chickens. In the present study, histopathology, immunohistochemistry, quantitative real-time PCR and Western blot were performed to investigate the influence of metabolic functions on the development of AS. Pathological examination of cardiac tissues of AS broilers revealed loosely arranged myocardial fibers, blurred plasma membrane boundaries, interstitial edema, and congestion. Levels of glycolysis were analyzed in cardiac tissue samples based on the expression of major rate-limiting enzymes in the related pathway. The results showed that the mRNA levels of PFK and PKM were significantly increased 2.19-fold and 3.82-fold vs. the control group in AS group (P<0.05), respectively. IHC results showed increased protein levels of PFK1, p-PFK2 and PKM2, which were in accordance with the changes in the levels of mRNA. Then, the Western blot analysis demonstrated that the expression percentage of PFK1, p-PFK2 and p-PKM2 were increased by 48.71, 45.41 and 67.14% than healthy broilers (P<0.01). The results indicated that the acidic intermediate products induced by the activation of glycolytic pathway might trigger fluid accumulation in the abdominal cavity of broilers with AS. [ABSTRACT FROM AUTHOR]

Florfenicol (FLO) is one of the most popular antibacterial drugs used in veterinary clinics and aquaculture. The drug was found to decrease the hatchability of eggs laid by treated hens in veterinary clinics and research work. However, the pathological changes in developing embryos and their cardiovascular system and the mechanism underlying FLO-induced embryonic death remain unclear. In the present study, fertilized eggs laid by hens treated with a therapeutic dose of FLO were collected and incubated. Results showed that FLO exposure repressed embryonic development and induced early embryonic death. As a result, FLO decreased the hatchability and increased the proportion of weak chicks. Moreover, FLO exposure led to embryonic lethality and inhibited the development of chick embryos as characterized by decreased weights, lagging distribution of Hamburger–Hamilton stages, and dysplastic eyes. Pathological examination indicated that FLO exposure affected the normal development of the heart in 4.5-day-old chick embryos, as characterized by shorter transverse cardiac diameter, disordered arrangement of trabecular muscles in ventricles, and reduced thickness of ventricular walls. Furthermore, FLO decreased blood vascular densities and downregulated the expression levels of key angiogenesis-related genes, including the vascular endothelial growth factor and fibroblast growth factor, in the yolk sac membrane. These findings indicated that FLO exposure restricted vascular development during early embryonic development. In summary, our data suggest that the restricted growth and abnormal cardiovascular development may be responsible for FLO-induced early embryonic death. Thus, these findings can be useful for guiding the proper use of FLO and in laying a foundation for further studies on the mechanism of FLO-induced embryonic toxicity. [ABSTRACT FROM AUTHOR]

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.). [ABSTRACT FROM AUTHOR]