Evolution of the global phosphorus cycle.

The macronutrient phosphorus is thought to limit primary productivity in the oceans on geological timescales. Although there has been a sustained effort to reconstruct the dynamics of the phosphorus cycle over the past 3.5 billion years, it remains uncertain whether phosphorus limitation persisted throughout Earth's history and therefore whether the phosphorus cycle has consistently modulated biospheric productivity and ocean-atmosphere oxygen levels over time. Here we present a compilation of phosphorus abundances in marine sedimentary rocks spanning the past 3.5 billion years. We find evidence for relatively low authigenic phosphorus burial in shallow marine environments until about 800 to 700 million years ago. Our interpretation of the database leads us to propose that limited marginal phosphorus burial before that time was linked to phosphorus biolimitation, resulting in elemental stoichiometries in primary producers that diverged strongly from the Redfield ratio (the atomic ratio of carbon, nitrogen and phosphorus found in phytoplankton). We place our phosphorus record in a quantitative biogeochemical model framework and find that a combination of enhanced phosphorus scavenging in anoxic, iron-rich oceans and a nutrient-based bistability in atmospheric oxygen levels could have resulted in a stable low-oxygen world. The combination of these factors may explain the protracted oxygenation of Earth's surface over the last 3.5 billion years of Earth history. However, our analysis also suggests that a fundamental shift in the phosphorus cycle may have occurred during the late Proterozoic eon (between 800 and 635 million years ago), coincident with a previously inferred shift in marine redox states, severe perturbations to Earth's climate system, and the emergence of animals.

Earliest land plants created modern levels of atmospheric oxygen.

The progressive oxygenation of the Earth's atmosphere was pivotal to the evolution of life, but the puzzle of when and how atmospheric oxygen (O2) first approached modern levels (∼21%) remains unresolved. Redox proxy data indicate the deep oceans were oxygenated during 435-392 Ma, and the appearance of fossil charcoal indicates O2 >15-17% by 420-400 Ma. However, existing models have failed to predict oxygenation at this time. Here we show that the earliest plants, which colonized the land surface from ∼470 Ma onward, were responsible for this mid-Paleozoic oxygenation event, through greatly increasing global organic carbon burial-the net long-term source of O2 We use a trait-based ecophysiological model to predict that cryptogamic vegetation cover could have achieved ∼30% of today's global terrestrial net primary productivity by ∼445 Ma. Data from modern bryophytes suggests this plentiful early plant material had a much higher molar C:P ratio (∼2,000) than marine biomass (∼100), such that a given weathering flux of phosphorus could support more organic carbon burial. Furthermore, recent experiments suggest that early plants selectively increased the flux of phosphorus (relative to alkalinity) weathered from rocks. Combining these effects in a model of long-term biogeochemical cycling, we reproduce a sustained +2‰ increase in the carbonate carbon isotope (δ(13)C) record by ∼445 Ma, and predict a corresponding rise in O2 to present levels by 420-400 Ma, consistent with geochemical data. This oxygen rise represents a permanent shift in regulatory regime to one where fire-mediated negative feedbacks stabilize high O2 levels.

Shikonin Inhibits Inflammatory Cytokine Production in Human Periodontal Ligament Cells.

Shikonin, which is derived from Lithospermum erythrorhizon, a herb used in traditional medicine, has long been considered to be a useful treatment for various diseases in traditional oriental medicine. Shikonin has recently been reported to have several pharmacological properties, e.g., it has anti-microbial, anti-tumor, and anti-inflammatory effects. The aim of this study was to examine whether shikonin is able to influence the production of interleukin (IL)-6, IL-8, and/or chemokine C-C motif ligand (CCL)20, which contribute to the pathogenesis of periodontal disease, in human periodontal ligament cells (HPDLC). The production levels of IL-6, IL-8, and CCL20 in HPDLC were determined using an ELISA. Western blot analysis was used to detect nuclear factor kappa B (NF-κB) pathway activation in HPDLC. Shikonin prevented IL-1ß- or tumor necrosis factor (TNF)-α-mediated IL-6, IL-8, and CCL20 production in HPDLC. Moreover, we found that shikonin suppressed the phosphorylation and degradation of inhibitor of kappa B-alpha (IκB-α) in IL-1ß- or TNF-α-stimulated HPDLC. These findings suggest that shikonin could have direct beneficial effects against periodontal disease by reducing IL-6, IL-8, and CCL20 production in periodontal lesions.

Genipin inhibits MMP-1 and MMP-3 release from TNF-a-stimulated human periodontal ligament cells.

Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of inflammatory diseases in traditional oriental medicine. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify matrix metalloproteinase (MMP)-1 and MMP-3, which are related to the destruction of periodontal tissues in periodontal lesion, expression in tumor necrosis factor (TNF)-α-stimulated human periodontal ligament cells (HPDLCs). Genipin prevented TNF-α-mediated MMP-1 and MMP-3 productions in HPDLCs. Moreover, genipin could suppress not only extracellular signal-regulated kinase (ERK) and Jun-N-terminal kinase (JNK) phosphorylations but also AMP-activated protein kinase (AMPK) phosphorylation in TNF-α-stimulated HPDLCs. Inhibitors of ERK and AMPK could inhibit both MMP-1 and MMP-3 productions. Moreover, we revealed the ERK inhibitor suppressed AMPK phosphorylation in TNF-α-stimulated HPDLCs. These data provide a new mechanism through which genipin could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion.

Genipin inhibits IL-1ß-induced CCL20 and IL-6 production from human periodontal ligament cells.

BACKGROUND/AIMS: Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various diseases in traditional oriental medicine. Genipin has been used as a blue colorant in food industry. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify CCL20 and IL-6, which are related to bone resorption in periodontal disease, expression in human periodontal ligament cells (HPDLCs). METHODS: CCL20 and IL-6 productions from HPDLCs were determined by ELISA. Western blot analysis was used for the detection of signal transduction molecules expressions in HPDLCs. RESULTS: Genipin prevented IL-1ß-mediated CCL20 and IL-6 production in HPDLCs. Moreover, genipin could suppress nuclear factor kappa B (NF-κB) p65, extracellular signalregulated kinase (ERK) and MAPK/ERK kinase (MEK) phosphorylations in IL-1ß-stimulated HPDLCs. NF-κB inhibitor and ERK inhibitor significantly inhibited IL-6 and CCL20 productions from IL-1ß-stimulated HPDLCs. CONCLUSIONS: These data provide a novel mechanism through which genipin could be used to provide direct benefits in periodontal disease to inhibit IL-6 and CCL20 productions in periodontal lesions.

Black tea polyphenol inhibits CXCL10 production in oncostatin M-stimulated human gingival fibroblasts.

CXC chemokine ligand 10 (CXCL10) plays an important role in the infiltration of Th1 cells and thus in the exacerbation of periodontal disease. Theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, has some beneficial effects but the effect of TFDG on CXCL10 production from human gingival fibroblasts (HGFs) is uncertain. In this study, we investigated the mechanisms by which TFDG may inhibit oncostatin M (OSM)-induced CXCL10 production in human gingival fibroblasts. TFDG prevented OSM-mediated CXCL10 production by HGFs in a dose dependent manner. TFDG significantly inhibited OSM-induced phosphorylation of c-Jun N terminal kinase (JNK), protein kinase B (Akt) (Ser473) that are related to CXCL10 production from OSM-stimulated HGFs. In addition, TFDG suppressed OSM receptor (OSMR) ß expression on HGFs. These data provide a novel mechanism where the black tea flavonoid, theaflavin, could provide direct benefits in periodontal disease.

Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts.

IL-6 is well recognized to be a potent bone resorptive agent and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, and theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, have multiple beneficial effects, but the effects of catechins and theaflavins on IL-6 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG, ECG, and TFDG inhibit tumor necrosis factor superfamily 14 (TNFSF14)-induced IL-6 production in HGFs. We detected TNFSF14 mRNA expression in human diseased periodontal tissues. TNFSF14 increased IL-6 production in HGFs in a concentration-dependent manner. EGCG, ECG, and TFDG prevented TNFSF14-mediated IL-6 production in HGFs. EGCG, ECG, and TFDG prevented TNFSF14-induced extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB activation in HGFs. Inhibitors of ERK, JNK, and nuclear factor-kappaB decreased TNFSF14-induced IL-6 production. In addition, EGCG, ECG, and TFDG attenuated TNFSF14 receptor expression on HGFs. These data provide a novel mechanism through which the green tea and black tea polyphenols could be used to provide direct benefits in periodontal disease.