ABSTRACT
Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.
Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.
ABSTRACT
Avibacterium paragallinarum is the pathogen that causes infectious coryza, a highly contagious respiratory disease that brings a serious threat to chickens. Heme utilization systems play an important role in bacterial adversity adaptation and pathogenicity, and our previous report found the presence of heme utilization (HutZ) in Av. paragallinarum. However, little is known about the function of HutZ in Av. paragallinarum. In this study, the HutZ mutant strain of Av. paragallinarum was successfully developed and identified by PCR and western blot analysis. Mutation of HutZ significantly retards bacterial growth under reduced iron conditions, indicating the regulatory role of HutZ on growth and iron acquisition. Notably, the HutZ mutant strain had slower growth than the wild-type strain when heme was provided as the sole source of iron; thus, HutZ is crucial for heme utilization in Av. paragallinarum. Moreover, the HutZ mutant strain exhibited a markedly compromised tolerance to acid stress compared to the wild-type strain. Pathogenicity analysis showed that mutation of HutZ significantly weakened the ability of bacteria to invade and reproduce in host macrophage cells in vitro. Furthermore, the HutZ mutation could significantly decrease the bacterial virulence in chickens, which displayed lower morbidity and milder clinical symptoms. Hence, this is the first study to demonstrate in-depth the essential roles of HutZ on iron homeostasis and pathogenesis of Av. paragallinarum, which provides novel insight into advances of new prophylactic vaccines against this kind of bacteria.ImportanceHeme utilization (HutZ) protein has been characterized as an important heme-degrading enzyme that is critical for the cleavage of heme to biliverdin via verdoheme and can release iron to be used by bacteria. The interaction between HutZ and Av. paragallinarum is still unknown. Here, we unraveled the role of HutZ on the growth, iron acquisition, heme utilization, and resistance to acidic stress in Av. paragallinarum. We also uncovered the importance of HutZ for the success of Av. paragallinarum infection and provided new clues to the pathogenesis strategies of this organism. This work constitutes a relevant step toward an understanding of the role of HutZ protein as a master virulence factor. Therefore, this study is of great importance for understanding the mechanisms underlying Av. paragallinarum virulence and may contribute to therapeutic applications.
