Background and purpose:
Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti‐cancer agents, have recently been reported to exhibit ...potent anti‐inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS‐275, two HDACi currently undergoing clinical investigations for various oncological indications.
Experimental approach:
The anti‐rheumatic effects of SAHA and MS‐275 were assessed in both mouse and rat collagen induced arthritis (CIA) models.
Key results:
SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA‐induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS‐275 displayed dramatic anti‐rheumatic activities. In prophylactic intervention, high doses of MS‐275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS‐275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS‐275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS‐275 was also confirmed through its capacity to decrease serum IL‐6 and IL‐1β levels in the CIA induced mouse model. The anti‐rheumatic activity of MS‐275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice.
Conclusion and implication:
This study strongly supported HDACi as an innovative therapeutic strategy for RA.
British Journal of Pharmacology (2007) 150, 862–872. doi:10.1038/sj.bjp.0707165
Abstract Background Primary liver malignancy is the leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) representing the majority. Combined ...HCC-CC, in contrast, accounts for less than 5% of these liver cancers and has not been clearly characterized by imaging, making diagnosis and management difficult. Materials and Methods This retrospective study investigated 32 patients with early-stage combined HCC-CC tumor who underwent hepatectomy (n = 24) or liver transplantation (n = 8). Preoperative imaging and pathologic reports were retrospectively reviewed and correlated. Survival and recurrence rates were then analyzed. Results Twelve patients with more than 50% CC component showed typical CC enhancement, whereas 17 patients with less than 50% CC component exhibited typical HCC enhancement. Those with equivocal imaging findings resulted near equal tumor component. The majority demonstrated either heterogeneous or peripheral enhancement. Considering the major tumor component, 66% of the images were consistent with histopathology. The over-all 3-year recurrent rate was 59%, with a mean time to recurrence of about 7 months. The 3-year survival rate of combined tumor after hepatectomy was 76% and after transplant was 75%, regardless of major tumor component. However, patients with more than 50% CC component showed a decrease in 3-year survival rate to 50% when transplantation was performed. Conclusion The overall survival rate for combined tumor after either hepatectomy or transplantation seems to be satisfactory but carries a high risk of recurrent when compared to pure HCC. On the other hand, a major CC component tumor after transplantation is associated with poor survival outcome; thus, liver transplantation has no role and is not a good management option.
Various hypotheses have been proposed regarding the origin of the plant pathogen Phytophthora cinnamomi. P. cinnamomi is a devastating, highly invasive soilborne pathogen associated with epidemics of ...agricultural, horticultural and forest plantations and native ecosystems worldwide. We conducted a phylogeographic analysis of populations of this pathogen sampled in Asia, Australia, Europe, southern and northern Africa, South America, and North America. Based on genotyping‐by‐sequencing, we observed the highest genotypic diversity in Taiwan and Vietnam, followed by Australia and South Africa. Mating type ratios were in equal proportions in Asia as expected for a sexual population. Simulations based on the index of association suggest a partially sexual, semi‐clonal mode of reproduction for the Taiwanese and Vietnamese populations while populations outside of Asia are clonal. Ancestral area reconstruction provides new evidence supporting Taiwan as the ancestral area, given our sample, indicating that this region might be near or at the centre of origin for this pathogen as speculated previously. The Australian and South African populations appear to be a secondary centre of diversity following migration from Taiwan or Vietnam. Our work also identified two panglobal, clonal lineages PcG1‐A2 and PcG2‐A2 of A2 mating type found on all continents. Further surveys of natural forests across Southeast Asia are needed to definitively locate the actual centre of origin of this important plant pathogen.
Fusarium wilt is a serious disease of the date palm Phoenix canariensis, caused by Fusarium oxysporum f. sp. canariensis (Foc). A previous study that characterized and compared the genetic diversity ...of the Australian Foc population with international strains suggested that the Australian population may have had an independent evolutionary origin. The current study compared the species phylogeny of the Australian and international populations and determined that Foc is not monophyletic, separating into three supported lineages across the two phylogenetic species of the Fusarium oxysporum species complex. This confirms an independent evolutionary origin for Foc in Australia. However, phylogenetic analysis of the putative pathogenicity genes Secreted In Xylem (SIX) did not reveal any separation of the Australian and international Foc strains. Furthermore, there was very low SIX sequence diversity within Foc. Horizontal gene transfer is argued to be the most parsimonious explanation for the incongruence between the species and SIX gene phylogenies.
Seed fungal endophytes play an important beneficial role in the formation of the seedling mycobiome and contribute to plant establishment, but can also occur as latent pathogens and saprotrophs. ...Current knowledge on the function and diversity of seed fungal endophytes has been gained through studies in agricultural systems whilst knowledge from natural systems is relatively less. We used two co-occurring species from the genus Banksia from four sites in Australia's Sydney Basin Bioregion to investigate the abundance and diversity of seed fungal endophyte communities present in natural ecosystem hosts. Based on results from culturing and DNA sequence analysis of multiple loci, we found that Banksia seeds house a diverse range of fungal endophyte species, that when assigned to functional guilds belonged to multiple trophic modes. Thirty-one of the fungal taxa identified had not been previously reported as endophytes. Amongst the 58 Operational Taxonomic Units identified, Leotiomycetes and Sordariomycetes were the dominant classes and Banksiamyces (Leotiomycetes) and Penicillium (Sordariomycetes) the dominant genera, with many of the species isolated recorded in the literature as having a limited distribution. The two Banksias shared few fungal endophyte species, which were not always present across all study sites. We revealed a 'hidden diversity' within seeds of Banksia from natural ecosystems and provided insights into the influence host species can have on the seed mycobiome.
Off-road vehicles are potential vectors for the spread of destructive plant pathogens such as
Phytophthora cinnamomi
. However, the retention of
Phytophthora
species in soil on vehicles used off-road ...does not appear to have been assessed empirically. We sampled soil from 22 off-road vehicles used in conservation management in New South Wales and tested samples for the presence of
Phytophthora
species. Two species (
P. cryptogea
and
P.
aff.
alticola
) were detected from three vehicles. Two of these three vehicles were regarded as being clean externally and had not been used off-road for more than one week.
Phytophthora
species can therefore survive in small amounts of soil on vehicles for extended periods, potentially facilitating the spread of these destructive pathogens. Cleaning is required of management vehicles entering areas of high conservation value vegetation to minimise the risk of spreading
Phytophthora
species. However, research is needed to find the most effective methods for removing soil.
Among the most economically relevant and environmentally devastating diseases globally are those caused by Phytophthora species. In Australia, production losses in agriculture and forestry results ...from several well-known cosmopolitan Phytophthora species and infestation of natural ecosystems by Phytophthora cinnamomi have caused irretrievable loss to biodiversity, especially in proteaceous dominated heathlands. For this review, all available records of Phytophthora in Australia were collated and curated, resulting in a database of 7 869 records, of which 2 957 have associated molecular data. Australian databases hold records for 99 species, of which 20 are undescribed. Eight species have no records linked to molecular data, and their presence in Australia is considered doubtful. The 99 species reside in 10 of the 12 clades recognised within the complete phylogeny of Phytophthora . The review includes discussion on each of these species’ status and additional information provided for another 29 species of concern. The first species reported in Australia in 1900 was Phytophthora infestans. By 2000, 27 species were known, predominantly from agriculture. The significant increase in species reported in the subsequent 20 years has coincided with extensive surveys in natural ecosystems coupled with molecular taxonomy and the recognition of numerous new phylogenetically distinct but morphologically similar species. Routine and targeted surveys within Australian natural ecosystems have resulted in the description of 27 species since 2009. Due to the new species descriptions over the last 20 years, many older records have been reclassified based on molecular identification. The distribution of records is skewed toward regions with considerable activity in high productivity agriculture, horticulture and forestry, and native vegetation at risk from P. cinnamomi . Native and exotic hosts of different Phytophthora species are found throughout the phylogeny; however, species from clades 1, 7 and 8 are more likely to be associated with exotic hosts. One of the most difficult challenges to overcome when establishing a pest status is a lack of reliable data on the current state of a species in any given country or location. The database compiled here for Australia and the information provided for each species overcomes this challenge. This review will aid federal and state governments in risk assessments and trade negotiations by providing a comprehensive resource on the current status of Phytophthora species in Australia.
The Fusarium oxysporum species complex (FOSC) causes disease in plants and animals, but is also widely dispersed in natural ecosystems without evidence of disease. The present study screened a ...population representing natural ecosystems across the Australian continent for the putative effector genes pisatin demethylase 1 (PDA1), pectate lyase (pelD), secreted gene expression (SGE1) and secreted in xylem (SIX). The genes pelD and SGE1 were prevalent in the natural isolates, PDA1 was present at an intermediate level, whereas SIX genes were detected at low levels. Phylogenies of these putative effector genes were compared to the EF‐1α species phylogeny to determine the likely modes of gene transmission: vertical gene transfer (VGT) and horizontal gene transfer (HGT). There was evidence of both modes of gene transmission within the F. oxysporum isolates. PDA1, pelD and SGE1 were likely to be only vertically inherited, whereas the SIX genes had evidence for both VGT and HGT. The phylogenetic relationships of SIX genes in isolates from natural ecosystems and formae speciales from agro‐ecosystems were also established. These findings have important implications for the evolution of effectors in the FOSC.
A survey of the endophytic fungi in fronds of Livistona chinensis was carried out in Hong Kong. The endophyte
assemblages identified using morphological characters consisted of 16 named species and ...19 ‘morphospecies’, the
latter grouped based on cultural morphology and growth rates. Arrangement of taxa into morphospecies does not
reflect species phylogeny, and therefore selected morphospecies were further identified based on ribosomal DNA
(rDNA) sequence analysis. The 5.8S gene and flanking internal transcribed spacers (ITS1 and ITS2) regions of
rDNA from 19 representative morphospecies were amplified by the polymerase chain reaction and sequenced.
Phylogenetic analysis based on 5.8S gene sequences showed that these morphospecies were filamentous
Ascomycota, belonging in the Loculoascomycetes and Pyrenomycetes. Further identification was conducted by
means of sequence comparison and phylogenetic analysis of both the ITS and 5.8S regions. Results showed that
MS704 belonged to the genus Diaporthe and its anamorph Phomopsis of the Valsaceae. MS594 was inferred to be
Mycosphaerella and its anamorph Cladosporium of the Mycosphaerellaceae. MS339, MS366, MS370, MS395,
MS1033, MS1083 and MS1092 were placed in the genus Xylaria of the Xylariaceae. MS194, MS375 and MS1028
were close to the Clypeosphaeriaceae. MS191 and MS316 were closely related to the Pleosporaceae within the
Dothideales. The other 5 morphospecies, MS786, MS1043, MS1065, MS1076 and MS1095, probably belong in
the Xylariales. The value of using DNA sequence analysis in the identification of endophytes is discussed.
Diseases in natural and agricultural systems have been linked to species of the Oomycete genus
Phytophthora
, around the world. Direct detection of the pathogen requires sampling of soil or plant ...material, which can be expensive, difficult to obtain and error-prone. As an alternative, reflectance spectroscopy provides a potential indirect method for detecting symptoms of infection by
P. cinnamomi
. Here we evaluate the use of reflectance spectroscopy to detect physiological changes associated with infection in host plants using spectral indices designed to quantify changes in plant pigments (pigment indices), leaf water content (water indices) and fluorescence (fluorescence indices). Two grasses and two tree species with different susceptibilities to
P. cinnamomi
were inoculated and/or exposed to water stress in a glasshouse experiment. Inoculated plants were detected using pigment and fluorescence indices, which also had the capacity to separate inoculated plants from water stressed uninoculated plants. While inoculation may have caused an opposing spectral response to water stress in some indices, plants that were both water stressed and inoculated then demonstrated an intermediate response. Water stress was detected using the water indices in all four species, and spectroscopic changes associated with inoculation were often greater in the susceptible species. Our results indicate that reflectance spectroscopy at the leaf scale detects the effects of
P. cinnamomi
infection in native vegetation. Extending these results has the potential to improve early detection of disease in natural vegetation and avoiding manual sampling, thus improving management of the disease.
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