Exposure Assessment
Ted W. Simon in Environmental Risk Assessment, 2019
With regard to short-term concentration, air is most variable of all exposure media. In addition, single or short-term exposures to chemicals in air may produce very different effects from repeated exposures. Toxicity factors for inhaled chemicals are developed in units of concentration—reference concentrations are generally found in units of mg/m3, and inhalation unit risk concentrations are generally found in units of per μg/m3, or reciprocal air concentration. In addition, single or short-term exposures to chemicals in air may produce very different effects from repeated exposures. Hence, it is important to understand the time scale of the toxic effect when selecting the exposure duration. In many cases, a receptor will spend time in two or more microenvironments, with different concentrations in each. EPA defines a microenvironment in terms of the chemical concentration therein, but also points out that these microenvironments include homes, schools, vehicles, restaurants, or the outdoors.90
Husbandry
Donna J. Clemons, Jennifer L. Seeman in The Laboratory GUINEA PIG, 2016
Good husbandry is an essential component of a quality animal care program. Husbandry factors not only greatly influence the health and well-being of the research guinea pig, but also have the potential to affect the outcome of current and future research studies. Good husbandry programs/practices take into account not only the immediate surroundings of the guinea pigs (microenvironment), but also the larger environment of the room and facility (macroenvironment). The microenvironment includes aspects such as type of caging system, bedding, in-cage temperature and humidity, intensity of lighting in the cage, noise, cagemates, feed, and novel manipulative items; whereas the macroenvironment includes room design, location of cage in the room and on the cage rack, room temperature and humidity, room illumination, noise, and animal care personnel. It is apparent that many of these factors are intertwined and affect both the micro- and macroenvironments of the research guinea pig.
Nutrition and the Risk of Common Forms of Cancer
David Heber, Zhaoping Li in Primary Care Nutrition, 2017
However, the tumor microenvironment is also an integral, essential part of tumorigenesis (Figure 18.2). In fact, the microenvironment often mediates and amplifies the influence of nutritional and environmental risk factors. Therefore, it is necessary to consider not just the biology of the cancer cell but also the influence of the surrounding tumor microenvironment. The stromal, inflammatory, and endothelial cells have crucial roles in the developing tumor and might account for different tumor risk even in the presence of the same amount of dividing stem cells (Baker 2015). Chronic inflammation is linked to carcinogenesis (de Visser et al. 2006; Noonan et al. 2008). Immune, endothelial, and stromal cells in the microenvironment that normally maintain homeostasis can act to promote transformed cell survival and replication. The microenvironment can be a primary factor in determining whether stem cells after a transformation event will continue to grow and become a cancer or remain as a microhyperplasia or even be cleared by the immune system. Epigenetics, which defines changes due to methylation or histone acetylation affecting gene expression while the DNA base sequence remains constant, can be modified by nutritional factors. Epigenetics also appears to play a key role in permitting a mutated cell to become a tumor or remain in an indolent state (Burgio and Migliore 2015). Therefore, bad luck may be prevented by protecting the tumor microenvironment, curbing inflammation, or stimulating antitumor adaptive immune responses, as can be seen from the recent success of immune blockade anticancer drugs (Pardoll 2012).
Time-dependently Appeared Microenvironmental Changes and Mechanism after Cartilage or Joint Damage and the Influences on Cartilage Regeneration
Published in Organogenesis, 2021
Danyang Yue, Lin Du, Bingbing Zhang, Huan Wu, Qiong Yang, Min Wang, Jun Pan
A “seed and soil theory” is raised by Stephen Paget in 1880, which implies that the initiation and progression of disease such as cancer focus not only on the cell itself, “the seed,” but also on “the soil,” in which it derives its nutrients, oxygen, and signals for growth and development.3 The importance of microenvironment is postulated thereafter. This review combs the time-dependently appeared microenvironmental changes and their mechanism following cartilage or joint damages, and the influences of one microenvironmental change on relative tissues, cells, cytokines, and other microenvironments as well as their interplays, focusing on MSCs for their promise in cartilage regeneration, which is summarized in Figure 1. We conclude that systematic studies for the timing and correlations of various microenvironmental changes and time-dependently rebuilding the multiple normal microenvironments of damaged joint may be the key to cartilage regeneration.
Recent advances in drug delivery systems for enhancing drug penetration into tumors
Published in Drug Delivery, 2020
Bin He, Xin Sui, Bing Yu, Song Wang, Youqing Shen, Hailin Cong
The cellular microenvironment consists of the intercellular substances of a cell, the cytoplasm of the cell itself, and the external environment of other cells around it (Allavena et al., 2008). Tumors and their environments are both interdependent and mutually reinforcing, while also being antagonistic and resisting each other. This is of great importance not only for understanding the occurrence, development, and metastasis of tumors, but also for their diagnosis, prevention, and prognosis of patients. Compared with normal tissues, tumor tissue has an anomalous vasculature, rigid extracellular matrix, exhibit hypoxia, a weakly acid pH, and immunosuppressive conditions (Overchuk & Zheng, 2018; Zhou et al., 2020). Microenvironment of tumor tissue plays an important role in the entry of nano-drugs into tumor cells. The concentration of tumor-associated fibroblasts (TAF) in tumor microenvironments is very high. They secrete extracellular matrix consisting of collagen, laminin, and fibrin (Xing et al., 2010). Nano-drugs must pass through this ‘barrier’ to enter the tumor cells. In addition, the microenvironment also contains fibroblasts (Kalluri & Zeisberg, 2006), immune cells (Galon et al., 2006), vascular endothelial cells (Palmer et al., 1988), stellate cells, and other cells, which affect the efficacy of nano-drugs. Therefore, researchers utilize the characteristics of tumor tissue microenvironment to design carriers with the aim of improving the anti-tumor effect.
All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway
Published in Immunological Investigations, 2023
Ya-nan Zhu, Xiao-li Gu, Lin-yuan Wang, Ning Guan, Chen-guang Li
In summary, our data show that the combination of ATRA and IL-4 activates the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages. This indicates that ATRA can play a significant role in the regulation of macrophage activity. From this perspective, ATRA has great potential as a drug to treat M2 macrophage-associated diseases such as immune thrombocytopenia, Leishmaniasis and wound healing (Feng et al. 2017; Lee et al. 2016; Vellozo et al. 2017). However, despite the key results reported in this study, there are some limitations. This study only utilized an in vitro experimental system. On the other hand, the in vivo microenvironment is complex and variable, with many factors acting synergistically and dynamically. Therefore, further in vivo experiments can help us obtain more evidence to safely translate preclinical findings into clinical trials and reliable therapies.
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