Inflammation is believed to play a role in uterine cervical remodeling and infection-induced preterm labor. One of the distinct features of remodeling uterine cervix is presence of prominent vascular events, such as angiogenesis, vasodilation, and vascular permeability. Although the functional significance of these features is not yet clear, we know that in most tissue types, vascular remodeling is intricately intertwined with inflammation. Since vascular endothelial growth factor (VEGF) is the major architect of vascular remodeling, we sought to examine and elucidate the potential relationship between VEGF and inflammation in the uterine cervix of non-pregnant mice. The animals used were divided into 4 treatment groups: A) negative control (vehicle only), B) positive control (lipopolysaccharide, LPS), C) recombinant VEGF-164 protein, and D) LPS + VEGF blocker (n = 3). After the appropriate treatments, the uterine cervices were harvested and analyzed using real-time PCR and confocal fluorescence microscopy. Results showed that exogenous VEGF upregulates expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNAs, whereas VEGF blocker partially diminishes the LPS-induced expression of pro-inflammatory factors compared to the positive control group. We conclude that a positive feed-forward relationship likely exists between VEGF and inflammation in the uterine cervix, thus implicating VEGF in inflammation-induced preterm labor.Inflammation is believed to play a role in uterine cervical remodeling and infection-induced preterm labor. During the course of pregnancy, the remodeling uterine cervix is, among other events, characterized by distinct vascular changes, notably, angiogenesis, vasodilation, and vascular permeability (7,(26)(27)(28). Although the functional significance of these changes during uterine cervical remodeling and at birth is, as yet, unclear, we know that vascular remodeling and inflammation are intricately intertwined (4). For instance, three of the five cardinal signs of inflammation are dependent on vascular changes, i.e., redness and heat are dependent on angiogenesis and vasodilation, whereas swelling or edema is dependent on leaky vessels or vascular permeability (33). More importantly, and of relevance to the present study, is the fact that uterine cervical remodeling and the birth process are generally considered inflammatory-like responses (25), in part, due to accumulation of immune cells and expansion of the vascular network in the uterine and uterine cervical tissues. The extent of tissue infiltration by different immune cells varies over the course of pregnancy, during and after birth (4). Data from non-human primate model studies showing successful blockade of infection-induced preterm labor using toll-like receptor 4 antagonists appear to support the role of in-

Hydrospires are internal structures in blastoids that primarily served a respiratory function. Historically, hydrospires have been modeled as passive-flow respiratory structures with a vertical orientation. This project constructed virtual 3D models of blastoids from legacy acetate peel collections at the Naturalis Museum in the Netherlands. Computational fluid dynamic (CFD) simulations of the blastoid models reconstructed in living position indicated that hydrospires likely were oriented horizontally when the blastoid was in feeding mode in current velocities>0.5 cm/s to 10 cm/s. In this range of current velocities, passive water flow through the hydrospires did not produce conditions optimized for efficient gas exchange. However, optimal water flow through the hydrospires could be achieved if the excurrent velocity of water exiting the hydrospire through the spiracle was approximately one-half the velocity of ambient environmental currents. Maintaining such a ratio in the dynamic current systems in which blastoids lived suggests that cilia-driven active water flow through the hydrospires is a better model for optimizing respiratory effectiveness.

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1b, IL-6, TNF-a, but up-regulation of the antiinflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

Cervical remodeling (CR) entails a physiological inflammatory response that can be induced by inflammatory agents, such as lipopolysaccharide (LPS), and inflammation is closely associated with vascular remodeling. Recently, we showed that LPS‐induced inflammation up‐regulates mRNA levels of vascular endothelial growth factor (VEGF) and its receptors, KDR and Flt‐1. Here, we sought to investigate whether VEGF can modulate inflammation by characterizing the expression pattern of pro‐inflammatory factors in VEGF‐treated mice using real time PCR. Our data revealed that VEGF up‐regulates a group of pro‐inflammatory factors in the cervix, including IL‐6. Collectively, our studies show a possible existence of a positive feed forward loop between inflammatory and vascular factors in the remodeling cervix.Grant Funding Source: Appalachian State University

No abstract