Network pharmacology analysis of the renal protective effects of bracken (Pteridium aquilinum) using experimental data obtained in an avian (quail) hyperuricemia model.

OBJECTIVE: To investigate the nephroprotective potential of orally administered bracken Pteridium aquilinum extract against renal damage in quails, induced by a high-purine diet, to form a foundation for subsequent clinical studies and applications. MATERIALS AND METHODS: A mass spectrometry analysis was conducted on the pteridophyte subjected to steam explosion. Network pharmacological methods were then utilized to pinpoint shared targets and pathways, which suggested that Pteridium aquilinum has a capability to counteract renal injury. A total of 48 specific-pathogen-free (SPF) "Difaku" quails were selected and segregated into six distinct groups. The control group received a standard diet, whereas the other groups were fed a high-purine diet. Beginning on day 14, each group was subjected to designated therapeutic measures. The study continued for 40 days, after which relevant biological markers were assessed. RESULTS: Active compound peaks from the steam-exploded Pteridium aquilinum were isolated. Subsequently, 101 targets and several pathways associated with renoprotective effects were discerned, indicating that the Pteridium aquilinum achieves its nephroprotective function through comprehensive regulatory mechanisms. The high-purine diet successfully induced hyperuricemia in the quails, resulting in renal impairment. Following intervention with varied Pteridium aquilinum dosages, renal protective outcomes were evident, though xanthine oxidase activity remained unaffected. Histological analyses demonstrated a notable decrease in renal lesion dimensions post-intervention. CONCLUSION: The steam-exploded bracken Pteridium aquilinum may provide nephroprotective benefits against hyperuricemia-induced renal damage in quails through comprehensive regulatory processes. This highlights the Pteridium aquilinum's potential as an innovative nephroprotective therapeutic and dietary solution, presenting a promising avenue for hyperuricemia and renal damage treatment and prevention.

Recovery of upland acid grasslands after successful Pteridium aquilinum control: Long-term effectiveness of cutting, repeated herbicide treatment and bruising.

There is a clear need for the development of management strategies to control dominant, perennial weeds and restore semi-natural communities and an important part of this is to know how long control treatments take to be effective and how long they last after treatments stop. Here, we report the results from a 17-year long experiment where we compared the effects of five control treatments on dense Pteridium aquilinum (L. Kuhn) relative to an untreated experimental-control in Derbyshire, UK. The experiment was run in two phases. In Phase 1 (2005-2012) we controlled the P. aquilinum by cutting and bruising, both twice and thrice annually, and a herbicide treatment (asulam in year 1, followed by annual spot-re-treatment of all emergent fronds). In Phase 2 (2012-2021) all treatments were stopped, and the vegetation was allowed to develop naturally. Between 2005 and 2021 we monitored P. aquilinum performance annually and full plant species composition at intervals. Here, we concentrate on analysing the Phase 2 data where we used regression approaches to model individual species responses through time and unconstrained ordination to compare treatment effects on the entire species composition over both Phases. Remote sensing was also used to assess edge invasion in 2018. At the end of Phase 1, a good reduction of P. aquilinum and restoration of acid-grassland was achieved for the asulam and cutting treatments, but not for bruising. In Phase 2, P. aquilinum increased through time in all treated plots but the asulam and cutting ones maintained a much lower P. aquilinum performance for nine years on all measures assessed. There was a reduction in species richness and richness fluctuations, especially in graminoid species. However, multivariate analysis showed that the asulam and cutting treatments were stationed some distance from the untreated and bruising treatments with no apparent sign of reversions suggesting an Alternative Stable State had been created, at least over this nine-year period. P. aquilinum reinvasion was mainly from plot edges. The use of repeated P. aquilinum control treatments, either through an initial asulam spray with annual follow-up spot-spraying or cutting twice or thrice annually for eight years gave good P. aquilinum control and helped restore an acid-grassland community. Edge reinvasion was detected, and it is recommended that either whole-patch control be implemented or treatments should be continued around patch edges.

Bracken fern does not diminish arbuscular mycorrhizal fungus inoculum potential in tropical deforested areas.

Tropical montane forests are threatened by uncontrolled fire events because of agricultural expansion. Consequently, deforested areas frequently are dominated by the bracken fern, Pteridium spp., for long periods, and forest regeneration is limited. Despite considerable research on bracken-dominated ecosystems, little is known about the relationship between bracken mycorrhizal fungi and tree seedlings. Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with terrestrial plants, providing nutrients and protection against pathogens and promoting seedling growth and establishment. Therefore, AMF inoculum have high potential for forest restoration programs. Here, we compare the species diversity of AMF spores, root colonization, and seedling growth of Clusia trochiformis 1 year after the addition of different liquefied root inocula: forest conspecific, forest heterospecific, and from Pteridium rhizomes. Thirteen morphospecies of arbuscular mycorrhizal fungi were identified on the roots of C. trochiformis, and Glomus spp. were the most abundant in all treatments. No differences were observed in spore species richness and diversity among treatments, but spore density was the highest subsequent to the Pteridium inoculum. There was no significant difference in mycorrhizal root colonization and seedling growth of C. trochiformis among inoculated treatments. We found a positive relation between root colonization and total biomass. This study shows that the AMF communities in bracken areas and forests present similar characteristics and that the bracken fern does not limit AMF inoculum potential, favouring seedling growth of Clusia.

The Norsesquiterpene Glycoside Ptaquiloside as a Poisonous, Carcinogenic Component of Certain Ferns.

Previous studies related to the ptaquiloside molecule, a carcinogenic secondary metabolite known from the world of ferns, are summarised. Ptaquiloside (PTA) belongs to the group of norsesquiterpenes of the illudane type. The name illudane refers to the fungal taxa from which the first representatives of the molecular group were identified. Ptaquiloside occurs mainly in Pteridium fern species, although it is also known in other fern taxa. The species of the genus Pteridium are common, frequent invasive species on all continents, and PTA is formed in smaller or larger amounts in all organs of the affected species. The effects of PTA and of their derivatives on animals and humans are of great toxicological significance. Its basic chemical property is that the molecule can be transformed. First, with the loss of sugar moiety, ptaquilosine is formed, and then, under certain conditions, a dienone derivative (pteridienone) may arise. The latter can alkylate (through its cyclopropane groups) certain molecules, including DNA, in animal or human organisms. In this case, DNA adducts are formed, which can later have a carcinogenic effect through point mutations. The scope of the PTA is interdisciplinary in nature since, for example, molecules from plant biomass can enter the body of animals or humans in several ways (directly and indirectly). Due to its physico-chemical properties (excellent water solubility), PTA can get from the plant into the soil and then into different water layers. PTA molecules that enter the soil, but mainly water, undergo degradation (hydrolytic) processes, so it is very important to clarify the toxicological conditions of a given ecosystem and to estimate the possible risks caused by PTA. The toxicoses and diseases of the animal world (mainly for ruminant farm animals) caused by PTA are briefly described. The intake of PTA-containing plants as a feed source causes not only various syndromes but can also enter the milk (and meat) of animals. In connection with the toxicological safety of the food chain, it is important to investigate the transport of carcinogenic PTA metabolites between organisms in a reassuring manner and in detail. This is a global, interdisciplinary task. The present review aims to contribute to this.

An Efficient Method for the Isolation of Toxins from Pteridium aquilinum and Evaluation of Ptaquiloside Against Cancer and Non-cancer Cells.

The common fern, bracken (Pteridium aquilinum), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside ( 1: ), although other toxins are present including the cyanogenic glycoside, prunasin ( 2: ). Here, we report an improved and relatively "green" process for the isolation of 1: and 2: from fresh bracken fronds and the evaluation of 1: for cytotoxicity against several cancer cell lines. The results indicate that 1: displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1: is expected to facilitate further exploration of its pharmacological properties.

Limited hydraulic adjustments drive the acclimation response of Pteridium aquilinum to variable light.

BACKGROUND AND AIMS: The success of invasive plants can be attributed to many traits including the ability to adapt to variable environmental conditions. Whether by adaptation, acclimation or phenotypic plasticity, these plants often increase their resource-use efficiency and, consequently, their fitness. The goal of this study was to examine the hydraulic and eco-physiological attributes of sun and shade populations of Pteridium aquilinum, a weedy fern, to determine whether the presence of vessels and other hydraulic attributes affects its success under a variety of light conditions. METHODS: Hydraulic traits such as cavitation resistance, hydraulic conductivity, photosynthesis and water potential at turgor loss point were measured on fronds from sun and shade populations. Anatomical and structural traits such as conduit diameter and length, stomatal density and vein density were also recorded. Diurnal measures of leaf water potential and stomatal conductance complement these data. KEY RESULTS: Gas exchange was nearly double in the sun plants, as was water-use efficiency, leaf-specific conductivity, and stomatal and vein density. This was largely achieved by a decrease in leaf area, coupled with higher xylem content. There was no significant difference in petiole cavitation resistance between the sun and shade leaves, nor in xylem-specific conductivity. Hydraulic conduit diameters were nearly equivalent in the two leaf types. CONCLUSIONS: Shifts in leaf area and xylem content allow P. aquilinum to occupy habitats with full sun, and to adjust its physiology accordingly. High rates of photosynthesis explain in part the success of this fern in disturbed habitats, although no change was observed in intrinsic xylem qualities such as cavitation resistance or conduit length. This suggests that P. aquilinum is constrained by its fundamental body plan, in contrast to seed plants, which show greater capacity for hydraulic adjustment.

Fiddlehead Fern Poisoning: A Case Report.

Outdoor enthusiasts are at a high risk of poisonous side effects after ingestion of wild and raw edible fiddlehead ferns, such as the ostrich fern (Matteuccia struthiopteris) and bracken (Pteridium genus) species, in the United States and Canada. The acute onset of nonlethal side effects manifests with gastrointestinal signs and symptoms and can last from 24 h up to 3 d. This case report is the first to outline the presentation of ingestion of a wild fiddlehead plant in the Carrabassett Valley in Maine, as well as the supportive management for this concerning and self-limiting illness.

A novel optimization approach incorporating non-stomatal limitations predicts stomatal behaviour in species from six plant functional types.

The primary function of stomata is to minimize plant water loss while maintaining CO2 assimilation. Stomatal water loss incurs an indirect cost to photosynthesis in the form of non-stomatal limitations (NSL) via reduced carboxylation capacity (CAP) and/or mesophyll conductance (MES). Two optimal formulations for stomatal conductance (gs) arise from the assumption of each type of NSL. In reality, both NSL could coexist, but one may prevail for a given leaf ontogenetic stage or plant functional type, depending on leaf morphology. We tested the suitability of two gs formulations (CAP versus MES) on species from six plant functional types (C4 crop, C3 grass, fern, conifer, evergreen, and deciduous angiosperm trees). MES and CAP parameters (the latter proportional to the marginal water cost to carbon gain) decreased with water availability only in deciduous angiosperm trees, while there were no clear differences between leaf ontogenetic stages. Both CAP and MES formulations fit our data in most cases, particularly under low water availability. For ferns, stomata appeared to operate optimally only when subjected to water stress. Overall, the CAP formulation provided a better fit across all species, suggesting that sub-daily stomatal responses minimize NSL by reducing carboxylation capacity predominantly, regardless of leaf morphology and ontogenetic stage.

Worldwide relationships in the fern genus Pteridium (bracken) based on nuclear genome markers.

PREMISE: Spore-bearing plants are capable of dispersing very long distances. However, it is not known if gene flow can prevent genetic divergence in widely distributed taxa. Here we address this issue, and examine systematic relationships at a global geographic scale for the fern genus Pteridium. METHODS: We sampled plants from 100 localities worldwide, and generated nucleotide data from four nuclear genes and two plastid regions. We also examined 2801 single nucleotide polymorphisms detected by a restriction site-associated DNA approach. RESULTS: We found evidence for two distinct diploid species and two allotetraploids between them. The "northern" species (Pteridium aquilinum) has distinct groups at the continental scale (Europe, Asia, Africa, and North America). The northern European subspecies pinetorum appears to involve admixture among all of these. A sample from the Hawaiian Islands contained elements of both North American and Asian P. aquilinum. The "southern" species, P. esculentum, shows little genetic differentiation between South American and Australian samples. Components of African genotypes are detected on all continents. CONCLUSIONS: We find evidence of distinct continental-scale genetic differentiation in Pteridium. However, on top of this is a clear signal of recent hybridization. Thus, spore-bearing plants are clearly capable of extensive long-distance gene flow; yet appear to have differentiated genetically at the continental scale. Either gene flow in the past was at a reduced level, or vicariance is possible even in the face of long-distance gene flow.

Experimental warming advances phenology of groundlayer plants at the boreal-temperate forest ecotone.

PREMISE OF THE STUDY: Changes to plant phenology have been linked to warmer temperatures caused by climate change. Despite the importance of the groundlayer to community and forest dynamics, few warming experiments have focused on herbaceous plant and shrub phenology. METHODS: Using a field study in Minnesota, United States, we investigated phenological responses of 16 species to warming over five growing seasons (2009-2013) at two sites, under two canopy covers, and in three levels of simultaneous above- and belowground warming: ambient temperature, ambient +1.7°C and ambient +3.4°C. We tested whether warming led to earlier phenology throughout the growing season and whether responses varied among species and years and depended on canopy cover. KEY RESULTS: Warming extended the growing season between 11-30 days, primarily through earlier leaf unfolding. Leaf senescence was delayed for about half of the species. Warming advanced flowering across species, especially those flowering in August, with modest impacts on fruit maturation for two species. Importantly, warming caused more than half of the species to either converge or diverge phenologically in relation to each other, suggesting that future warmed climate conditions will alter phenological relationships of the groundlayer. Warm springs elicited a stronger advance of leaf unfolding compared to cool spring years. Several species advanced leaf unfolding (in response to warming) more in the closed canopy compared to the open. CONCLUSIONS: Climate warming will extend the growing season of groundlayer species in the boreal-temperate forest ecotone and alter the synchrony of their phenology.

Change to ecosystem properties through changing the dominant species: Impact of Pteridium aquilinum-control and heathland restoration treatments on selected soil properties.

It is well known that soils are influenced by the plant species that grow in them. Here we consider the effects of management-induced changes to plant communities and their soils during restoration within a 20-year manipulative experiment where the aim was to change a late-successional community dominated by the weed, Pteridium aquilinum, to an earlier-successional grass-heath one. The ecological restoration treatments altered the above- and below-ground components of the community substantially. Untreated plots maintained a dense Pteridium cover with little understory vegetation, cutting treatments produce significant reductions of Pteridium, whereas herbicide (asulam) produced significant immediate reductions in Pteridium but regressed towards the untreated plots within 10 years. Thereafter, all asulam-treated plots were re-treated in year 11, and then were spot-sprayed annually. Both cutting and asulam treatments reduced frond density to almost zero and resulted in a grass-heath vegetation. There was also a massive change in biomass distribution, untreated plots had a large above-ground biomass/necromass that was much reduced where Pteridium was controlled. Below-ground in treated plots, there was a replacement of the substantive Pteridium rhizome mass with a much greater root mass of other species. The combined effects of Pteridium-control and restoration treatment, reduced soil total C and N as and available P concentrations, but increased soil pH and available N. Soil biological activity was also affected with a reduction in soil N mineralization rate, but an increased soil-root respiration. Multivariate analysis showed a clear trend along a pH/organic matter gradient, with movement along it correlated to management intensity from the untreated plots with low pH/high organic matter and treated plots with to a higher pH/lower organic matter in the sequence asulam treatment, cut once per year to cut twice per year. The role that these changed soil conditions might have in restricting Pteridium recovery are discussed.

Pterosin B has multiple targets in gluconeogenic programs, including coenzyme Q in RORα-SRC2 signaling.

Hepatic gluconeogenic programs are regulated by a variety of signaling cascades. Glucagon-cAMP signaling is the main initiator of the gluconeogenic programs, including glucose-6-phosphatase catalytic subunit (G6pc) gene expression. Pterosin B, an ingredient in Pteridium aquilinum, inhibits salt-inducible kinase 3 signaling that represses cAMP-response element-binding protein regulated transcription coactivator 2, an inducer of gluconeogenic programs. As the results, pterosin B promotes G6pc expression even in the absence of cAMP. In this work, however, we noticed that once cAMP signaling was initiated, pterosin B became a strong repressor of G6pc expression. The search for associated transcription factors for pterosin B actions revealed that retinoic acid receptor-related orphan receptor alpha-steroid receptor coactivator 2 (RORα-SRC2) complex on the G6pc promoter was the target. Meanwhile, pterosin B impaired the oxidation-reduction cycle of coenzyme Q in mitochondrial oxidative phosphorylation (OXPHOS); and antimycin A, an inhibitor of coenzyme Q: cytochrome c-oxidoreductase (termed mitochondrial complex III), also mimicked pterosin B actions on RORα-SRC2 signaling. Although other respiratory toxins (rotenone and oligomycin) also suppressed G6pc expression accompanied by lowered ATP levels following the activation of AMP-activated kinase, minimal or no effect of these other toxins on RORα-SRC2 activity was observed. These results suggested that individual components in OXPHOS differentially linked to different transcriptional machineries for hepatic gluconeogenic programs, and the RORα-SRC2 complex acted as a sensor for oxidation-reduction cycle of coenzyme Q and regulated G6Pc expression. This was a site disrupted by pterosin B in gluconeogenic programs.

Fern-synthesized nanoparticles in the fight against malaria: LC/MS analysis of Pteridium aquilinum leaf extract and biosynthesis of silver nanoparticles with high mosquitocidal and antiplasmodial activity.

Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum strains resistant to chloroquine. There is an urgent need to investigate new and effective sources of antimalarial drugs. This research proposed a novel method of fern-mediated synthesis of silver nanoparticles (AgNP) using a cheap plant extract of Pteridium aquilinum, acting as a reducing and capping agent. AgNP were characterized by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Phytochemical analysis of P. aquilinum leaf extract revealed the presence of phenols, alkaloids, tannins, flavonoids, proteins, carbohydrates, saponins, glycosides, steroids, and triterpenoids. LC/MS analysis identified at least 19 compounds, namely pterosin, hydroquinone, hydroxy-acetophenone, hydroxy-cinnamic acid, 5, 7-dihydroxy-4-methyl coumarin, trans-cinnamic acid, apiole, quercetin 3-glucoside, hydroxy-L-proline, hypaphorine, khellol glucoside, umbelliferose, violaxanthin, ergotamine tartrate, palmatine chloride, deacylgymnemic acid, methyl laurate, and palmitoyl acetate. In DPPH scavenging assays, the IC50 value of the P. aquilinum leaf extract was 10.04 µg/ml, while IC50 of BHT and rutin were 7.93 and 6.35 µg/ml. In mosquitocidal assays, LC50 of P. aquilinum leaf extract against Anopheles stephensi larvae and pupae were 220.44 ppm (larva I), 254.12 ppm (II), 302.32 ppm (III), 395.12 ppm (IV), and 502.20 ppm (pupa). LC50 of P. aquilinum-synthesized AgNP were 7.48 ppm (I), 10.68 ppm (II), 13.77 ppm (III), 18.45 ppm (IV), and 31.51 ppm (pupa). In the field, the application of P. aquilinum extract and AgNP (10 × LC50) led to 100 % larval reduction after 72 h. Both the P. aquilinum extract and AgNP reduced longevity and fecundity of An. stephensi adults. Smoke toxicity experiments conducted against An. stephensi adults showed that P. aquilinum leaf-, stem-, and root-based coils evoked mortality rates comparable to the permethrin-based positive control (57, 50, 41, and 49 %, respectively). Furthermore, the antiplasmodial activity of P. aquilinum leaf extract and green-synthesized AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 of P. aquilinum were 62.04 µg/ml (CQ-s) and 71.16 µg/ml (CQ-r); P. aquilinum-synthesized AgNP achieved IC50 of 78.12 µg/ml (CQ-s) and 88.34 µg/ml (CQ-r). Overall, our results highlighted that fern-synthesized AgNP could be candidated as a new tool against chloroquine-resistant P. falciparum and different developmental instars of its primary vector An. stephensi. Further research on nanosynthesis routed by the LC/MS-identified constituents is ongoing.

Palynological analysis of Dennstaedtiaceae taxa from the Paranaense Phytogeographic Province that produce Trilete spores II: Microlepia speluncae and Pteridium arachnoideum.

The spore morphology and wall ultrastructure of Microlepia speluncae and Pteridium arachnoideum from the Paranaense Province were analyzed with LM, SEM and TEM and a comparative analysis was carried out. In both species the spores are covered by a three-dimensional network of threads branched and fused, tangentially arranged to the surface, and some free-end threads are also seen. The species were differentiated by morphology and the frequency of threads fusion and the networks distribution on the surface of the spores. In both species the exospore is two-layered in section, both layers are traversed by single or branched channels. The perispore is three-layered in section: the inner layer is adhered to the exospore, the middle layer is formed of a three-dimensional network of threads and the outer layer is discontinuous. The perispore ultrastructure of Microlepia speluncae was interpreted as formed of helical subunits displayed around a central channel. The spore morphology and perispore ultrastructure allow differentiating Microlepia from Pteridium but also to the other Dennstaedtiaceae genera that grow in the Paranaense Province. The results obtained allow establishing relationships that let us recognize different groups and gave a new reference to get a better knowledge of the family.

Ptaquiloside in Irish Bracken Ferns and Receiving Waters, with Implications for Land Managers.

Ptaquiloside, along with other natural phytotoxins, is receiving increased attention from scientists and land use managers. There is an urgent need to increase empirical evidence to understand the scale of phytotoxin mobilisation and potential to enter into the environment. In this study the risk of ptaquiloside to drinking water was assessed by quantifying ptaquiloside in the receiving waters at three drinking water abstraction sites across Ireland and in bracken fronds surrounding the abstraction sites. We also investigated the impact of different management regimes (spraying, cutting and rolling) on ptaquiloside concentrations at plot-scale in six locations in Northern Ireland, UK. Ptaquiloside concentrations were determined using recent advances in the use of LC-MS for the detection and quantification of ptaquiloside. The results indicate that ptaquiloside is present in bracken stands surrounding drinking water abstractions in Ireland, and ptaquiloside concentrations were also observed in the receiving waters. Furthermore, spraying was found to be the most effective bracken management regime observed in terms of reducing ptaquiloside load. Increased awareness is vital on the implications of managing land with extensive bracken stands.

Rapid response of leaf photosynthesis in two fern species Pteridium aquilinum and Thelypteris dentata to changes in CO2 measured by tunable diode laser absorption spectroscopy.

We investigated stomatal conductance (g(s)) and mesophyll conductance (g(m)) in response to atmospheric CO2 concentration [CO2] in two primitive land plants, the fern species Pteridium aquilinum and Thelypteris dentata, using the concurrent measurement of leaf gas exchange and carbon isotope discrimination. [CO2] was initially decreased from 400 to 200 µmol mol(-1), and then increased from 200 to 700 µmol mol(-1), and finally decreased from 700 to 400 µmol mol(-1). Analysis by tunable diode laser absorption spectroscopy (TDLAS) revealed a rapid and continuous response in g m within a few minutes. In most cases, both ferns showed rapid and significant responses of g m to changes in [CO2]. The largest changes (quote % decrease) were obtained when [CO2] was decreased from 400 to 200 µmol mol(-1). This is in contrast to angiosperms where an increase in g(m) is commonly observed at low [CO2]. Similarly, fern species observed little or no response of g(s) to changes in [CO2] whereas, a concomitant decline of g(m) and g(s) with [CO2] is often reported in angiosperms. Together, these results suggest that regulation of g(m) to [CO2] may differ between angiosperms and ferns.

Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis.

Land management of bracken needs to account for bracken carcinogens--a case study from Britain.

Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management. The ptaquiloside content in fronds ranged between 50 and 5790 µg/g corresponding to a ptaquiloside load in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was also found in the underground rhizome system (11-657 µg/g) and in decaying litter (0.1-5.8 µg/g). The amount of ptaquiloside present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore be based on actual and site specific determinations of the ptaquiloside content. Care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust.

Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard.

Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned.

Ptaquiloside-induced early-stage urothelial lesions show increased cell proliferation and intact ß-catenin and E-cadherin expression.

Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on ptaquiloside has focused on the late, malignant, lesions, so the early changes of ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and ß-catenin). Two exposed animals died during the work. Six ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and ß-catenin expression. Early-stage ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression.