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.
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.
There are clear connections between ecosystem services (ES) and human health, as well as between soils and human health. However, studies to date have not investigated links between soil ES and human ...health. Viewing the relationship between soils and human health through the ES lens reveals that soil ES such as the provisioning of shelter, clothing, and fuel have been overlooked in the soil and human health literature. Shelter is important to human health because it provides protection against inclement weather, temperature extremes, and other potential threats. Clothing provides a more consistent micro-environment around the skin and also provides protection from ultraviolet radiation and some parasites. Fuel allows us to warm shelters, providing refuge from cold temperatures, and cook food, which reduces disease. The materials supplied by soils in support of these functions are often done so in a more environmentally responsible way than is the case with many modern building and clothing materials or with fossil fuels. However, it is important to realize that sustainable management practices are critical in order to achieve environmentally responsible production of these products. Future studies need to investigate the links between these overlooked soil ES and human health.
Display omitted
•Shelter, clothing, and fuel are important to human health.•These are ecosystem services that can be supplied by soil.•They have been overlooked in soil and human health studies.•Modern methods of obtaining these are energy and resource intensive.•Sustainable practices can supply these from soil in an environmentally responsible way.
Invasion and subsequent metastasis is the major cause of death from most cancers including prostate cancer. Herein we report on the potential tumor suppressive properties of Rab7, a GTPase that ...regulates trafficking of lysosomes. The movement of lysosomes to the cell surface in response to environmental cues increases the secretion of proteinases and cell invasion. We determined that Troglitazone and other members of the Thiazolidinedione family inhibit cell-surface directed lysosome trafficking and cathepsin B secretion through a Rab7-dependent mechanism. Moreover, Rab7 shRNA expressing cells were found to be more invasive in vitro and in vivo. Increased invasiveness was accompanied by elevated expression of the c-Met receptor and prolonged downstream signaling, thereby supporting a role for Rab7 as a mediator of signaling down-regulation. Taken together, these results suggested that Rab7 acts as a negative regulator of prostate tumor growth and invasion, providing further evidence for its potential as a tumor suppressor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tumor invasion through a basement membrane is one of the earliest steps in metastasis, and growth factors, such as Epidermal Growth Factor (EGF) and Hepatocyte Growth Factor (HGF), stimulate this ...process in a majority of solid tumors. Basement membrane breakdown is one of the hallmarks of invasion; therefore, tumor cells secrete a variety of proteases to aid in this process, including lysosomal proteases. Previous studies demonstrated that peripheral lysosome distribution coincides with the release of lysosomal cathepsins.
Immunofluorescence microscopy, western blot, and 2D and 3D cell culture techniques were performed to evaluate the effects of EGF on lysosome trafficking and cell motility and invasion.
EGF-mediated lysosome trafficking, protease secretion, and invasion is regulated by the activity of p38 mitogen activated protein kinase (MAPK) and sodium hydrogen exchangers (NHEs). Interestingly, EGF stimulates anterograde lysosome trafficking through a different mechanism than previously reported for HGF, suggesting that there are redundant signaling pathways that control lysosome positioning and trafficking in tumor cells.
These data suggest that EGF stimulation induces peripheral (anterograde) lysosome trafficking, which is critical for EGF-mediated invasion and protease release, through the activation of p38 MAPK and NHEs. Taken together, this report demonstrates that anterograde lysosome trafficking is necessary for EGF-mediated tumor invasion and begins to characterize the molecular mechanisms required for EGF-stimulated lysosome trafficking.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Connecting the public with soil to improve human health Brevik, Eric C.; Steffan, Joshua J.; Rodrigo‐Comino, Jesús ...
European journal of soil science,
July 2019, 2019-07-00, 20190701, Letnik:
70, Številka:
4
Journal Article
Recenzirano
Despite the definite links between soil and human health, it is likely that most people do not think about soil when considering human health. There is a disconnect between most people in our modern ...society and soil, and when people notice soil it is often in a negative context. People care for things that matter to them, and creating a more positive public image of soil could improve human health by leading to better treatment and understanding of the soil resource. There are a number of concepts that may be able to connect people to the soil, including terroir, soil health and soil security. While terroir originally established a connection between those who appreciate wine and the soils that produce those wines, the concept has been expanded to many additional products. It might be possible to provide a terroir link to human health benefits if they can be shown to be characteristic of a given soil environment. The concept of soil health has caught on with many farmers, policymakers, scientists and the general public, thus providing another possible approach to improve peoples’ connection with soil. Soil security is a recent concept that has been advanced as a way to take advantage of the connection that concepts such as energy, food and water security have made with policymakers. Therefore, we advocate a concerted effort to investigate terroir, soil health and soil security as concepts to improve overall human health. Soil health and soil security might have the most promise, and some social marketing campaigns that include soil health are ongoing.
Highlights
Soil is important to human health.
A disconnect exists between the urban population and soil.
Education about soil can rebuild these connections.
Concepts such as terroir, soil health or soil security might help make connections.
Soil ecosystems contain and support the greatest amount of biodiversity on the planet. A majority of this diversity is made up of microorganisms, most of which are beneficial for humans. However, ...some of these organisms are considered human pathogens. In light of the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak, one may ponder the origin of the next pandemic and if soil may represent a source of pathogens with pandemic potential. This review focuses on several bacterial, fungal, and viral pathogens that can result in human infection due to direct interaction with the soil. Moreover, the current status of knowledge regarding SARS-CoV-2 survival in and transmission from soil is reviewed.
Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non-small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the ...clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines.
NSCLC cell lines with variable sensitivity to the EGFR antagonist erlotinib were studied. Cell growth was evaluated using proliferation and colony formation assays. Kinase activation was assessed via Western blot analysis. Experiments were conducted with EGCG, the EGFR antagonist erlotinib, and the c-Met inhibitor SU11274. The antagonists were also tested in a xenograft model using SCID mice.
EGCG inhibited cell proliferation in erlotinib-sensitive and -resistant cell lines, including those with c-Met overexpression, and acquired resistance to erlotinib. The combination of erlotinib and EGCG resulted in greater inhibition of cell proliferation and colony formation than either agent alone. EGCG also completely inhibited ligand-induced c-Met phosphorylation and partially inhibited EGFR phosphorylation. The triple combination of EGCG/erlotinib/SU11274 resulted in a greater inhibition of proliferation than EGCG with erlotinib. Finally, the combination of EGCG and erlotinib significantly slowed the growth rate of H460 xenografts.
EGCG is a potent inhibitor of cell proliferation, independent of EGFR inhibition, in several NSCLC cell lines, including those resistant to both EGFR kinase inhibitors and those overexpressing c-Met. Therefore, EGCG might be a useful agent to study as an adjunct to other anticancer agents.
Emerging evidence suggests that the SAM pointed domain containing ETS transcription factor (SPDEF) plays a significant role in tumorigenesis in prostate, breast, colon, and ovarian cancer. However, ...there are no in vivo studies with respect to the role of SPDEF in tumor metastasis. The present study examined the effects of SPDEF on tumor cell metastasis using prostate tumor cells as a model. Utilizing two experimental metastasis models, we demonstrate that SPDEF inhibits cell migration and invasion in vitro and acts a tumor metastasis suppressor in vivo. Using stable expression of SPDEF in PC3-Luc cells and shRNA-mediated knockdown of SPDEF in LNCaP-Luc cells, we demonstrate for the first time that SPDEF diminished the ability of disseminated tumors cells to survive at secondary sites and establish micrometastases. These effects on tumor metastasis were not a result of the effect of SPDEF on cell growth as SPDEF expression had no effect on cell growth in vitro or subcutaneous tumor xenograft-growth in vivo. Transcriptional analysis of several genes associated with tumor metastasis, invasion, and the epithelial-mesenchymal transition demonstrated that SPDEF expression selectively down-regulated MMP9 and MMP13 in prostate cancer cells. Further analysis indicated that forced MMP9 or MMP13 expression rescued the invasive phenotype in SPDEF expressing PC3 cells in vitro, suggesting that the effects of SPDEF on tumor invasion are mediated, in part, through the suppression of MMP9 and MMP13 expression. These results demonstrate for the first time, in any system, that SPDEF functions as a tumor metastasis suppressor in vivo.
Background: Role of SPDEF in tumor biology remains hotly debated.
Results: SPDEF suppressed tumor metastasis in part by modulating MMP9 and MMP13.
Conclusion: SPDEF may be a modifiable therapeutic target in prostate tumors.
Significance: This is the first study directly implicating SPDEF as a tumor metastasis suppressor, in any system, in vivo.
Prostate cancer (PCa) presents a significant health challenge in men, with a substantial number of deaths attributed to metastatic castration resistant PCa (mCRPC). Moreover, African American men ...experience disproportionately high mortality rates due to PCa. This study delves into the pivotal role of SPDEF, a prostate specific Ets transcription factor, and its regulation by DNA methylation in the context of PCa progression.
We performed Epigenetic reprogramming using daily treatment with non-toxic dose of 5Aza-2-deoxycytidine (5Aza-dC) for two weeks to assess its impact on PDEF expression in prostate cancer cells. Next, we conducted functional studies on reprogrammed cells, including cell migration (wound-healing assay), invasion (Boyden-Chamber test), and proliferation (MTT assay) to comprehensively evaluate the consequences of altered PDEF expression. We used bisulfite sequencing (BSP) to examine DNA methylation at SPDEF promoter. Simultaneously, we utilized siRNA-mediated targeting of key DNMTs (DNMT1, DNMT3A, and DNMT3B) to elucidate their specific role in regulating PDEF. We measured mRNA and protein expressions using qRT-PCR and immune-blotting techniques, respectively.
In this report, we observed that: a) there is a gradual decrease in SPDEF expression with a concomitant increase in methylated CpG sites within the SPDEF gene during prostate cancer progression from lower to higher Gleason grade; b) Expression of DNMT's (DNMT1, 3a and 3b) is increased during prostate cancer progression, and there is an inverse correlation between SPDEF and DNMT expression; c) SPDEF levels are decreased in RC77/T, a line of PCa cells from African American origin similar to PC3 and DU145 cells (CRPC cells), as compared to LNCaP cells , a line of androgen dependent cells,; d) the 5' CpG island of SPDEF gene are hypermethylated in SPDEF-negative CRPC ( PC3, DU145 and RC77/T) cell lines but the same regions are hypomethylated in SPDEF-positive castrate sensitive (LNCaP) cell line ; (e) expression of SPDEF in PCa cells lacking SPDEF decreases cell migration and invasion, but has no significant effect on cell proliferation, and; (f) treatment with the demethylating agent, 5-aza-2'-deoxycytidine, or silencing of the DNMT's by siRNA, partially restores SPDEF expression in SPDEF-negative PCa cell lines, and decreases cell migration and invasion.
These results indicate hypermethylation is a prevalent mechanism for decreasing SPDEF expression during prostate cancer progression. The data demonstrate that loss of SPDEF expression in prostate cancer cells, a critical step in cellular plasticity, results from a potentially reversible process of aberrant DNA methylation. These studies suggest DMNT activity as a potential therapeutic vulnerability that can be exploited for limiting cellular plasticity, tumor progression, and therapy resistance in prostate cancer.
PDF
