Molybdenum (Mo) is an essential trace element for animals and human beings. However, the negative effects on rumen function and distribution of trace elements in tissues induced by excessive Mo have not been well understood. Therefore, the purpose of present study was to investigate the impact of Mo on rumen microbiota, distribution of trace elements in various organs, and hematological parameters of goats. A total of 36 goats were randomly distributed into three groups with equal number and low-Mo and high-Mo groups were orally administered ammonium molybdate at 15 and 45 mg · Mo · kg · BW respectively, while the control group received corresponding quantitative deionized water. The results showed that the total number of ciliate and protozoa protein concentration decreased significantly (P < 0.01) on days 25 and 50. Concentrations of ammonia nitrogen and bacterial protein were significantly higher (P < 0.05) in low-Mo group, while they were lower (P < 0.05) in high-Mo group than the control group on days 25 and 50. In addition, Mo accumulated in serum and all detected tissues. Copper (Cu) and zinc (Zn) contents significantly decreased (P < 0.05) in hair and serum on days 25 and 50, while Cu contents increased (P < 0.05) and the change of Zn contents were not obvious (P > 0.05) in other tissues on days 25 and 50. Besides, there was no obvious variation in iron (Fe) contents during whole experiment period (P > 0.05). Furthermore, excessive Mo content had no significant effect on red blood cell (RBC) counts and hemoglobin (HGB) concentration (P > 0.05) on days 25 and 50, while white blood cell (WBC) counts increased significantly (P < 0.05) on day 50. These results indicated that excessive Mo content could impact the balance of ruminal microorganisms and interfere with the absorption and distribution of Mo and Cu mainly.
This investigation was conducted to study the effects of tanshinone IIA (TIIA) on pulmonary arterial hypertension (PAH) in broilers. Two-hundred newly hatched Arbor Acre commercial broilers were randomly divided into 3 groups. All groups, with the exception of the control group (tap water), were given NaCl water (0.3%) starting on the d 15, and broilers in the protected group were fed a diet supplemented with TIIA (2.5 g/kg) starting on the d 15. On d 28, 35, 42, and 49, the ratio of the right ventricular weight to the total ventricular weight (RV: TV) and the values of other biochemical indicators for each group chickens were determined. The concentrations of interleukin-6 (IL-6), interleukin-1β (IL-1β), nuclear factor kappa (NF-κB), and P38 (a mitogen-activated protein kinase) were measured using enzyme-linked immune sorbent assays (ELISA). The results showed that the proportion of chickens in the diseased group with an RV:TV ratio in the range of 0.250 to 0.299 (10%) was significantly higher (25 to 30%) compared to that of the other groups (P < 0.05), and the proportion in all chickens was 28%. In addition, the IL-6, IL-1β, NF-κB, and P38 protein concentrations were higher in the diseased group, whereas there were no differences between the control group and the protected group. Moreover, the measurements of body weight, liver function, kidney function and electrolytes showed significant differences between the diseased group and the other groups. These findings suggest that tanshinone IIA may protect broilers from PAH, which is an important piece of information for the poultry industry.
BackgroundWe investigated the efficacy and mechanism of the anti-KIR immunotherapy lirilumab and anti-PD-L1 immunotherapy avelumab on natural killer (NK) cell activity against HPV+ cervical cancer.MethodsNK cell-mediated lysis of autologous biopsy-derived malignant cervical squamous cells and normal cervical squamous cells were measured by europium-release cytotoxicity assays. Cytokine and granzyme B release were measured by ELISPOT effector-cell-based assays and ELISA. Murine cervical cancer tumor models were constructed to assess implanted tumor volumes over time and intratumoral immune cell infiltration. Receptor-crosslinking and plate-immobilized antibody stimulation studies, with or without p65 and Vav1 silencing, were used to investigate NF-κB pathway disinhibition in NK cells.ResultsLirilumab and avelumab each enhanced NK cell disinhibition and NK cell-mediated lysis of autologous cervical cancer cells in vitro while reducing HPV+ tumor volumes and increasing intratumoral NK cell infiltration and cytolysis in vivo. Moreover, lirilumab and avelumab each promoted NK cell NF-κB disinhibition as well as stimulated cytokine and granzyme B expression in a NF-κB-dependent manner. Lirilumab+avelumab enhanced all aforementioned effects compared to either monotherapy. Vav1 silencing eliminated disinhibition of NF-κB signaling by lirilumab and avelumab, indicating their disinhibiting effects are Vav1-dependent.ConclusionsThis study supports a novel approach to enhancing NK cell lysis against HPV+ cervical cancer cells through combining lirilumab and avelumab.
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