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-

Increased homogeneity of agricultural landscapes in the last century has led to a loss of biodiversity and ecosystem services. However, management practices such as wildflower borders offer supplementary resources to many beneficial arthropods. There is evidence that these borders can increase beneficial arthropod abundance, including natural enemies of many pests. However, this increase in local habitat diversity can also have effects on pest populations, and these effects are not well-studied. In this study, we investigated how wildflower borders affect both natural enemies and pests within an adjacent strawberry crop. Significantly more predators were captured in strawberry plantings with wildflower borders versus plantings without wildflowers, but this effect depended on sampling method. Overall, herbivore populations were lower in plots with a wildflower border; however, responses to wildflower borders varied across specific pest groups. Densities of Lygus lineolaris (Tarnished Plant Bug), a generalist pest, increased significantly in plots that had a border, while Stelidota geminata (Strawberry Sap Beetle) decreased in strawberry fields with a wildflower border. These results suggest that wildflower borders may support the control of some pest insects; however, if the pest is a generalist and can utilize the resources of the wildflower patch, their populations may increase within the crop.

Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA. Significance: Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.

Thirty-three patients with locally advanced epidermoid cancer of the mouth were investigated by means of the potential tumor doubling time prior to each of four weekly infusions of methotrexate. The agent used to induce metaphase arrest was vincristine sulphate 2 mg intravenous push and the methotrexate was given in a dose of 100 mg/M2 body surface. In twenty-one patients the investigation was completed. It was found that in those patients where the P.T.D.T. was maintained at its original level there was a greater than 50% reduction in the size of the lesion, whereas when the P.T.D.T. became greatly prolonged there was no such reduction. It is suggested that the P.T.D.T. provides a simple same day method of evaluating one parameter in the cell kinetics of accessible tumors and that this information can be used to individualize chemotherapy schedules.

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