Natural polyphenols with previously demonstrated anticancer potential, epigallocatechin gallate (EGCG), tannic acid, curcumin, and theaflavin, were encased into gelatin-based 200 nm nanoparticles consisting of a soft gel-like interior with or without a surrounding LbL shell of polyelectrolytes (polystyrene sulfonate/polyallylamine hydrochloride, polyglutamic acid/poly-l-lysine, dextran sulfate/protamine sulfate, carboxymethyl cellulose/gelatin, type A) assembled using the layer-by-layer technique. The characteristics of polyphenol loading and factors affecting their release from the nanocapsules were investigated. Nanoparticle-encapsulated EGCG retained its biological activity and blocked hepatocyte growth factor (HGF)-induced intracellular signaling in the breast cancer cell line MBA-MD-231 as potently as free EGCG.

Acidic extracellular pH (pHe) is a common feature of the tumor microenvironment and has been implicated in tumor invasion through the induction of protease secretion. Since lysosomes constitute the major storehouse of cellular proteases, the trafficking of lysosomes to the cell periphery may be required in order to secrete proteases. We demonstrate that a pHe of 6.4-6.8 induced the trafficking of lysosomes to membrane protrusions in the cell periphery. This trafficking event depended upon the PI3K pathway, the GTPase RhoA and sodium-proton exchange activity, resulting in lysosomal exocytosis. Acidic pHe induced a cytoplasmic acidification (although cytoplasmic acidification was not sufficient for acidic pHe-induced lysosome trafficking and exocytosis) and inhibition of NHE activity with the amiloride derivative, EIPA or the anti-diabetic agent troglitazone prevented lysosome trafficking to the cell periphery. Interestingly, using the more specific NHE1 and NHE3 inhibitors, cariporide and s3226 respectively, we show that multiple NHE isoforms are involved in acidic pHe-induced lysosome trafficking and exocytosis. Moreover, in cells expressing NHE1 shRNA, although basal NHE activity was decreased, lysosomes still underwent acidic pHe-induced trafficking, suggesting compensation by other NHE family members. Together these data implicate proton exchangers, especially NHE1 and NHE3, in acidic pHe-induced lysosome trafficking and exocytosis.

Summary Soil has a considerable effect on human health, whether those effects are positive or negative, direct or indirect. Soil is an important source of nutrients in our food supply and medicines such as antibiotics. However, nutrient imbalances and the presence of human pathogens in the soil biological community can cause negative effects on health. There are also many locations where various elements or chemical compounds are found in soil at toxic levels because of either natural conditions or anthropogenic activities. The soils of urban environments have received increased attention in the last few years, and they too pose a number of human health questions and challenges. Concepts such as soil security may provide a framework within which issues on soil and human health can be investigated using interdisciplinary and transdisciplinary approaches. It will take the contributions of experts in several different scientific, medical and social science fields to address fully soil and human health issues. Although much progress was made in understanding links between soil and human health over the last century, there is still much that we do not know about the complex interactions between them. Therefore, there is still a considerable need for research in this important area. Highlights Soil is important to human health. Effects can be positive or negative, direct or indirect. Advances have been made in recent years. Inter‐ and trans‐disciplinary research is needed.

Soil influences human health in a variety of ways, with human health being linked to the health of the soil. Historically, emphasis has been placed on the negative impacts that soils have on human health, including exposures to toxins and pathogenic organisms or the problems created by growing crops in nutrient-deficient soils. However, there are a number of positive ways that soils enhance human health, from food production and nutrient supply to the supply of medications and enhancement of the immune system. It is increasingly recognized that the soil is an ecosystem with a myriad of interconnected parts, each influencing the other, and when all necessary parts are present and functioning (ie, the soil is healthy), human health also benefits. Despite the advances that have been made, there are still many areas that need additional investigation. We do not have a good understanding of how chemical mixtures in the environment influence human health, and chemical mixtures in soil are the rule, not the exception. We also have sparse information on how most chemicals react within the chemically and biologically active soil ecosystem, and what those reactions mean for human health. There is a need to better integrate soil ecology and agronomic crop production with human health, food/nutrition science, and genetics to enhance bacterial and fungal sequencing capabilities, metagenomics, and the subsequent analysis and interpretation. While considerable work has focused on soil microbiology, the macroorganisms have received much less attention regarding links to human health and need considerable attention. Finally, there is a pressing need to effectively communicate soil and human health connections to our broader society, as people cannot act on information they do not have. Multidisciplinary teams of researchers, including scientists, social scientists, and others, will be essential to move all these issues forward.

SummaryHepatocyte growth factor (HGF) is found in tumor microenvironments, and interaction with its tyrosine kinase receptor Met triggers cell invasion and metastasis. It was previously shown that acidic extracellular pH stimulated peripheral lysosome trafficking, resulting in increased cathepsin B secretion and tumor cell invasion, which was dependent upon sodium-proton exchanger (NHE) activity. We now demonstrate that HGF induced the trafficking of lysosomes to the cell periphery, independent of HGF-induced epithelialmesenchymal transition. HGF-induced anterograde lysosome trafficking depended upon the PI3K pathway, microtubules and RhoA, resulting in increased cathepsin B secretion and invasion by the cells. HGF-induced NHE activity via increased net acid production, and inhibition of NHE activity with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), or a combination of the NHE1-specific drug cariporide and the NHE3-specific drug s3226 prevented HGF-induced anterograde trafficking and induced retrograde trafficking in HGFoverexpressing cells. EIPA treatment reduced cathepsin B secretion and HGF-induced invasion by the tumor cells. Lysosomes were located more peripherally in Rab7-shRNA-expressing cells and these cells were more invasive than control cells. Overexpression of the Rab7 effector protein, RILP, resulted in a juxtanuclear location of lysosomes and reduced HGF-induced invasion. Together, these results suggest that the location of lysosomes is an inherently important aspect of invasion by tumor cells.