Translocation of Fungicides and Their Efficacy in Controlling Phellinus noxius, the Cause of Brown Root Rot Disease.

Brown root rot disease (BRRD), caused by Phellinus noxius, is an important tree disease in tropical and subtropical areas. To improve chemical control of BRRD and deter emergence of fungicide resistance in P. noxius, this study investigated control efficacies and systemic activities of fungicides with different modes of action. Fourteen fungicides with 11 different modes of action were tested for inhibitory effects in vitro on 39 P. noxius isolates from Taiwan, Hong Kong, Malaysia, Australia, and Pacific Islands. Cyproconazole, epoxiconazole, and tebuconazole (Fungicide Resistance Action Committee [FRAC] 3, target-site G1) inhibited colony growth of P. noxius by 99.9 to 100% at 10 ppm and 97.7 to 99.8% at 1 ppm. The other effective fungicide was cyprodinil + fludioxonil (FRAC 9 + 12, target-site D1 + E2), which showed growth inhibition of 96.9% at 10 ppm and 88.6% at 1 ppm. Acropetal translocation of six selected fungicides was evaluated in bishop wood (Bischofia javanica) seedlings by immersion of the root tips in each fungicide at 100 ppm, followed by liquid or gas chromatography tandem mass spectrometry analyses of consecutive segments of root, stem, and leaf tissues at 7 and 21 days posttreatment. Bidirectional translocation of the fungicides was also evaluated by stem injection of fungicide stock solutions. Cyproconazole and tebuconazole were the most readily absorbed by roots and efficiently transported acropetally. Greenhouse experiments suggested that cyproconazole, tebuconazole, and epoxiconazole have a slightly higher potential for controlling BRRD than mepronil, prochloraz, and cyprodinil + fludioxonil. Because all tested fungicides lacked basipetal translocation, soil drenching should be considered instead of trunk injection for their use in BRRD control.

Two new species of Fulvifomes (Basidiomycota, Hymenochaetaceae) on threatened or near threatened tree species in Japan.

We describe two new species of Fulvifomes based on morphological observations and phylogenetic investigations. Both species were identified as Phellinus rimosus by former mycologists, but both are morphologically distinct from authenticated specimen of P. rimosus. Fulvifomes boninensis is characterized by perennial basidiomata, a sulcate pileus surface becoming rimose, lack of a distinct crust on the pileus surface, subdimitic hyphal system in the context, and ellipsoid basidiospores. This species is endemic to the Bonin Islands, Japan, and is specific to the host Morus boninensis, a red-listed tree species. Fulvifomes imazekii is characterized by perennial basidiomata, sulcate and velutinous pileus surface, lack of a crust on the pileus surface, dimitic hyphal system in the context, and broadly ellipsoid basidiospores. This species is specific to Berchemiella berchemiaefolia, and is known only from Mt. Yokogura-yama, in Kochi Prefecture, Japan. Fulvifomes boninensis and F. imazekii are considered threatened, because of their high host specificity each with a threatened tree species as well as the limited distribution of the former and the extremely small number of "mature individuals" of the latter. The following new combinations were also proposed: Fulvifomes aulaxinus, F. pappianus, and F. tepperi.

Tertiary lymphoid structures in the primary tumor site of patients with cancer-associated myositis: A case-control study.

Objective: To investigate histologic features of immunological components in the primary tumor site of patients with cancer-associated myositis (CAM) by focusing on tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs), which play major roles in antitumor immunity. Methods: Cancer-associated myositis patients were selected from the single-center idiopathic inflammatory myopathy cohort based on the availability of primary tumor specimens obtained before the introduction of immunomodulatory agents. Control cancer subjects without CAM were selected from the cancer tissue repository at a ratio of 1:2 matched for demographics and cancer characteristics of CAM cases. A series of immunohistochemical analyses was conducted using sequential tumor sections. TLS was defined as an ectopic lymphoid-like structure composed of DC-LAMP+ mature dendritic cells, CD23+ follicular dendritic cells (FDCs) and PNAd+ high endothelial venules. TLS distribution was classified into the tumor center, invasive margin, and peritumoral area. Results: Six CAM patients and 12 matched non-CAM controls were eligible for the study. There was no apparent difference in the density or distribution of TILs between the groups. TLSs were found in 3 CAM patients (50%) and 4 non-CAM controls (33%). TLSs were exclusively located at the tumor center or invasive margin in CAM cases but were mainly found in the peritumoral area in non-CAM controls. FDCs and class-switched B cells colocalized with follicular helper T cells were abundantly found in the germinal center-like area of TLSs from CAM patients compared with those from non-CAM controls. Conclusion: The adaptive immune response within TLSs in the primary tumor site might contribute to the pathogenic process of CAM.

Utility of Ultrasonography in Assessing Periaortitis Associated with Retroperitoneal Fibrosis: A Case Report.

Periaortitis is a rare vascular manifestation and is often associated with retroperitoneal fibrosis. Herein, we describe a case of periaortitis accompanied by retroperitoneal fibrosis in a patient who developed acute kidney insufficiency due to bilateral ureteral stenosis. Ultrasonography at presentation detected thickness of the outer layer of the bilateral common iliac artery and right internal and external iliac arteries, consistent with periaortitis. Moreover, follow-up ultrasound images revealed subsiding of the thickness of the arterial wall in response to treatment with corticosteroids. Because of its noninvasiveness and handiness, ultrasonography has become popular for the assessment of large vessels in clinical practice, particularly monitoring for affected lesions. Computed tomography, magnetic resonance imaging, and positron emission tomography are currently used for the diagnosis and monitoring of periaortitis, but in this case, ultrasonography was utilized in the diagnosis and monitoring of periaortitis as a supportive imaging modality, as the use of contrast agents was contraindicated because of renal insufficiency.

Updates on genetics in systemic sclerosis.

Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.

Spatial distribution of 137Cs concentrations in mushrooms (Boletus hiratsukae) and their relationship with soil exchangeable cation contents.

The activity concentrations of radiocesium (137Cs) in wild mushrooms are reported to vary according to species, genus or ecological types. In addition, the concentration fluctuates among the same species collected within the same area. Therefore, we investigated whether the 137Cs concentration of wild mushrooms would be (1) spatially biased, or (2) influenced by the 137Cs or exchangeable potassium concentrations in the soils below. We set two survey plots 300 m apart in a Himalayan cedar forest in Tsukuba, Japan, where ca. 30 kBq/m2 of 137Cs was deposited after the Fukushima Nuclear Power Plant accident. From these plots, we collected fruit-bodies (fungal structures for spore production) of co-occurring Boletus hiratsukae, a mycorrhizal species, as well as from the soil below. The mean 137Cs concentrations in the fruit-bodies were significantly different between the two plots, but no difference was observed in the soil 137Cs concentration between the plots. Significant spatial autocorrelation was observed in the 137Cs concentration in the organic layer for both sites, but no significant spatial autocorrelation was observed in the 137Cs of fruit-bodies. Therefore, the variation in the 137Cs concentrations of co-occurred B. hiratsukae was not explained by spatial bias or radioactivity in the below soil. In contrast, the exchangeable potassium concentration in the soil was negatively correlated with the 137Cs in the fruit-bodies. Our results suggest that the 137Cs absorption of wild mushrooms would be suppressed by the competitive effect of exchangeable potassium in the surrounding soils.

Endothelial cells and endothelial progenitor cells in the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive fibrosis, microvasculopathy, and autoimmunity. Endothelial cell (EC) injury and subsequent endothelial cell dysfunction is believed to be an initial event that eventually leads to a vicious pathogenic cycle. This process is further enhanced by defective angiogenesis and vasculogenesis, as the vascular repair machinery does not work properly. Endothelial progenitor cells (EPCs) are functionally and quantitatively insufficient to recover the endothelium in SSc patients. The dysfunctional ECs and EPCs not only trigger the formation of typical vascular lesions, such as progressive intimal fibrosis in small arteries and the loss of capillaries, but also promote a series of inflammatory and profibrotic processes, such as endothelial-mesenchymal transition and recruitment and accumulation of monocytic EPCs with profibrotic properties. These processes together contribute to the accumulation of extracellular matrix in the affected tissue. This review features current insights into the roles of ECs and EPCs in the pathogenesis of SSc.

Four Pristionchus species associated with two mass-occurring Parafontaria laminata populations.

Phoretic nematodes associated with two mass-occurring populations of the millipede Parafontaria laminata were examined, focusing on Pristionchus spp. The nematodes that propagated on dissected millipedes were genotyped using the D2-D3 expansion segments of the 28S ribosomal RNA gene. Four Pristionchus spp. were detected: P. degawai, P. laevicollis, P. fukushimae, and P. entomophagus. Of the four, P. degawai dominated and it was isolated from more than 90% of the millipedes examined. The haplotypes of partial sequences of mitochondrial cytochrome oxidase subunit I examined for Pristionchus spp. and P. degawai showed high haplotype diversity.

Important cytological findings for distinction between follicular variant and conventional papillary thyroid carcinoma, including noninvasive follicular thyroid tumors with papillary-like nuclear features.

We studied cytological specimens of conventional papillary thyroid carcinoma (PTC), follicular variant papillary thyroid carcinoma (FVPTC), and noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) (formerly noninvasive FVPTC) to identify useful cytological parameters for their differentiation. Cytological findings of invasive FVPTC and NIFTP were very similar to each other but differed from those of conventional PTC. Intranuclear cytoplasmic inclusions, true papillary cell clusters, monolayered cell sheets, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background were the observed characteristic features of conventional PTC. Microfollicular cell clusters and dense globules of colloids were characteristic features of invasive FVPTC and NIFTP. Scoring the eight parameters (intranuclear cytoplasmic inclusions, nuclear grooves, powdery chromatin, true papillary cell clusters, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background) readily distinguished NIFTP from conventional PTC, but could not distinguish NIFTP from invasive FVPTC. The average total score of NIFTP, invasive FVPTC, and conventional PTC were 2.60 ± 0.55, 2.63 ± 0.62, and 4.57 ± 0.99, respectively. The difference between conventional PTC and NIFTP or invasive FVPTC was statistically significant (p < 0.001, Student's t-test). Individuals with more than three of the identified parameters likely harbor conventional PTC, rather than NIFTP. In this way, 87.5% (112/128) of conventional PTCs could be differentiated from NIFTP, and definitively diagnosed as malignant by cytology.

Comparative and population genomic landscape of Phellinus noxius: A hypervariable fungus causing root rot in trees.

The order Hymenochaetales of white rot fungi contain some of the most aggressive wood decayers causing tree deaths around the world. Despite their ecological importance and the impact of diseases they cause, little is known about the evolution and transmission patterns of these pathogens. Here, we sequenced and undertook comparative genomic analyses of Hymenochaetales genomes using brown root rot fungus Phellinus noxius, wood-decomposing fungus Phellinus lamaensis, laminated root rot fungus Phellinus sulphurascens and trunk pathogen Porodaedalea pini. Many gene families of lignin-degrading enzymes were identified from these fungi, reflecting their ability as white rot fungi. Comparing against distant fungi highlighted the expansion of 1,3-beta-glucan synthases in P. noxius, which may account for its fast-growing attribute. We identified 13 linkage groups conserved within Agaricomycetes, suggesting the evolution of stable karyotypes. We determined that P. noxius has a bipolar heterothallic mating system, with unusual highly expanded ~60 kb A locus as a result of accumulating gene transposition. We investigated the population genomics of 60 P. noxius isolates across multiple islands of the Asia Pacific region. Whole-genome sequencing showed this multinucleate species contains abundant poly-allelic single nucleotide polymorphisms with atypical allele frequencies. Different patterns of intra-isolate polymorphism reflect mono-/heterokaryotic states which are both prevalent in nature. We have shown two genetically separated lineages with one spanning across many islands despite the geographical barriers. Both populations possess extraordinary genetic diversity and show contrasting evolutionary scenarios. These results provide a framework to further investigate the genetic basis underlying the fitness and virulence of white rot fungi.

Insights into the phylogeny of Northern Hemisphere Armillaria: Neighbor-net and Bayesian analyses of translation elongation factor 1-α gene sequences.

Armillaria possesses several intriguing characteristics that have inspired wide interest in understanding phylogenetic relationships within and among species of this genus. Nuclear ribosomal DNA sequence-based analyses of Armillaria provide only limited information for phylogenetic studies among widely divergent taxa. More recent studies have shown that translation elongation factor 1-α (tef1) sequences are highly informative for phylogenetic analysis of Armillaria species within diverse global regions. This study used Neighbor-net and coalescence-based Bayesian analyses to examine phylogenetic relationships of newly determined and existing tef1 sequences derived from diverse Armillaria species from across the Northern Hemisphere, with Southern Hemisphere Armillaria species included for reference. Based on the Bayesian analysis of tef1 sequences, Armillaria species from the Northern Hemisphere are generally contained within the following four superclades, which are named according to the specific epithet of the most frequently cited species within the superclade: (i) Socialis/Tabescens (exannulate) superclade including Eurasian A. ectypa, North American A. socialis (A. tabescens), and Eurasian A. socialis (A. tabescens) clades; (ii) Mellea superclade including undescribed annulate North American Armillaria sp. (Mexico) and four separate clades of A. mellea (Europe and Iran, eastern Asia, and two groups from North America); (iii) Gallica superclade including Armillaria Nag E (Japan), multiple clades of A. gallica (Asia and Europe), A. calvescens (eastern North America), A. cepistipes (North America), A. altimontana (western USA), A. nabsnona (North America and Japan), and at least two A. gallica clades (North America); and (iv) Solidipes/Ostoyae superclade including two A. solidipes/ostoyae clades (North America), A. gemina (eastern USA), A. solidipes/ostoyae (Eurasia), A. cepistipes (Europe and Japan), A. sinapina (North America and Japan), and A. borealis (Eurasia) clade 2. Of note is that A. borealis (Eurasia) clade 1 appears basal to the Solidipes/Ostoyae and Gallica superclades. The Neighbor-net analysis showed similar phylogenetic relationships. This study further demonstrates the utility of tef1 for global phylogenetic studies of Armillaria species and provides critical insights into multiple taxonomic issues that warrant further study.

Genetic Differentiation and Spatial Structure of Phellinus noxius, the Causal Agent of Brown Root Rot of Woody Plants in Japan.

Phellinus noxius is a pathogenic fungus that causes brown root rot disease in a variety of tree species. This fungus is distributed in tropical and sub-tropical regions of Southeast and East Asia, Oceania, Australia, Central America and Africa. In Japan, it was first discovered on Ishigaki Island in Okinawa Prefecture in 1988; since then, it has been found on several of the Ryukyu Islands. Recently, this fungus was identified from the Ogasawara (Bonin) Islands, where it has killed trees, including rare endemic tree species. For effective control or quarantine methods, it is important to clarify whether the Japanese populations of P. noxius are indigenous to the area or if they have been introduced from other areas. We developed 20 microsatellite markers from genome assembly of P. noxius and genotyped 128 isolates from 12 of the Ryukyu Islands and 3 of the Ogasawara Islands. All isolates had unique genotypes, indicating that basidiospore infection is a primary dissemination method for the formation of new disease foci. Genetic structure analyses strongly supported genetic differentiation between the Ryukyu populations and the Ogasawara populations of P. noxius. High polymorphism of microsatellite loci suggests that Japanese populations are indigenous or were introduced a very long time ago. We discuss differences in invasion patterns between the Ryukyu Islands and the Ogasawara Islands.

Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a multi-organ fibrotic disease that affects the skin and various internal organs. Therapeutic strategies for tissue fibrosis have not been established; however, aberrantly activated fibroblasts in affected lesions are key targets for modulating fibrosis. Recently, increased intracellular cyclic GMP (cGMP) levels were demonstrated to improve fibrosis levels in various diseases. The purpose of this study was to assess the anti-fibrotic properties of cGMP in cultured fibroblasts from patients with SSc. The phosphodiesterase (PDE) 5 inhibitor sildenafil increased the intracellular cGMP levels in skin fibroblasts in a dose-dependent manner. Sildenafil treatment also significantly decreased the expression of several pro-fibrotic factors that were upregulated by TGF-ß1 treatment in SSc skin fibroblasts. These inhibitory effects occurred via non-canonical TGF-ß signaling. Our findings revealed that sildenafil might be a novel strategy to treat tissue fibrosis and vasculopathy in SSc.

Paper-Based Textbooks with Audio Support for Print-Disabled Students.

Utilizing invisible 2-dimensional codes and digital audio players with a 2-dimensional code scanner, we developed paper-based textbooks with audio support for students with print disabilities, called "multimodal textbooks." Multimodal textbooks can be read with the combination of the two modes: "reading printed text" and "listening to the speech of the text from a digital audio player with a 2-dimensional code scanner." Since multimodal textbooks look the same as regular textbooks and the price of a digital audio player is reasonable (about 30 euro), we think multimodal textbooks are suitable for students with print disabilities in ordinary classrooms.

In situ observation of a hydrogel-glass interface during sliding friction.

Direct observation of hydrogel contact with a solid surface in water is indispensable for understanding the friction, lubrication, and adhesion of hydrogels under water. However, this is a difficult task since the refractive index of hydrogels is very close to that of water. In this paper, we present a novel method to in situ observe the macroscopic contact of hydrogels with a solid surface based on the principle of critical refraction. This method was applied to investigate the sliding friction of a polyacrylamide (PAAm) hydrogel with glass by using a strain-controlled parallel-plate rheometer. The study revealed that when the compressive pressure is not very high, the hydrogel forms a heterogeneous contact with the glass, and a macro-scale water drop is trapped at the soft interface. The pre-trapped water spreads over the interface to decrease the contact area with the increase in sliding velocity, which dramatically reduces the friction of the hydrogel. The study also revealed that this heterogeneous contact is the reason for the poor reproducibility of hydrogel friction that has been often observed in previous studies. Under the condition of homogeneous full contact, the molecular origin of hydrogel friction in water is discussed. This study highlights the importance of direct interfacial observation to reveal the friction mechanism of hydrogels.

Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease.

OBJECTIVE: PM and DM are often complicated by interstitial lung disease (ILD). In this study we aimed to evaluate various serum cytokines in patients with PM/DM with ILD so as to clarify the differences in pathophysiology between anti-melanoma differentiation-associated gene 5 antibody-associated ILD (anti-MDA5-ILD) and anti-aminoacyl tRNA synthetase antibody-associated ILD (anti-ARS-ILD). METHODS: We evaluated the serum cytokine profiles of 38 patients with PM/DM and compared the cytokine profiles of the non-ILD and ILD subsets as well as the anti-MDA5-ILD and anti-ARS-ILD subsets. RESULTS: The myositis intention-to-treat activity index score, which indicates whole disease activity, significantly correlated with serum IL-6, IL-8, TNF-α and IP-10. These cytokine levels were significantly higher in the ILD subset than the non-ILD subset and were lower in the ILD subset following treatment. By multivariate analysis, TNF-α was the most significant cytokine [P = 0.0006, odds ratio (OR) 1.4, CI 1.1, 2.2] associated with PM/DM with ILD. IL-8 levels were significantly higher in anti-MDA5-ILD than in anti-ARS-ILD, although IL-6, TNF-α and IP-10 levels were high in both subsets. IL-8 was the most significant cytokine (P = 0.0006, OR 1.5, CI 1.1, 3.0) associated with anti-MDA5-ILD by multivariate analysis. Moreover, the ratio of IL-4 to IFN-γ was lower in anti-MDA5-ILD than in anti-ARS-ILD. CONCLUSION: IL-6, IL-8, TNF-α and IP-10 are associated with global disease activity in PM/DM. These cytokine levels were high, especially in the ILD subset. Serum IL-8 levels and the balance between IL-4 and IFN-γ may contribute to the differences in pathophysiology between anti-ARS-ILD and anti-MDA5-ILD.

The host ranges of conifer-associated Tricholoma matsutake, Fagaceae-associated T. bakamatsutake and T. fulvocastaneum are wider in vitro than in nature.

Tricholoma matsutake is the most commercially important edible mushroom in pine forests in Japan. Tricholoma bakamatsutake and T. fulvocastaneum, species closely related to T. matsutake, occur in Fagaceae forests. We examined ectomycorrhizal (EM) formation by these Tricholoma species by in vitro synthesis among seven strains (two of T. matsutake, four of T. bakamatsutake, one of T. fulvocastaneum) and axenic plants of pine (Pinus densiflora) and oak (Quercus serrata, Q. phillyraeoides). All strains, except for one of T. matsutake, formed EM associations with both pine and oak. Plant growth and mycelial development were differently affected by EM formation depending on the plant-fungus combination.

Taxonomy and phylogenetic position of Fomitiporia torreyae, a causal agent of trunk rot on Sanbu-sugi, a cultivar of Japanese cedar (Cryptomeria japonica) in Japan.

Trunk rot poses a substantial threat to Sanbu-sugi, one of the most economically important cultivars of Japanese cedar (Cryptomeria japonica). The etiology of this disease, including its main agents, is incompletely known. This trunk rot was attributed to Fomitiporia (Phellinus) hartigii or F. (Phellinus) punctata. Here we phylogenetically analyzed DNA sequences of four markers from a set of strains isolated from trunk-rot symptoms and recovered a single, monophyletic clade, indicating that a single taxon is involved. This clade was identified as Fomitiporia torreyae, a species described from eastern China. This analysis also proved that trunk rot and/or dieback of other conifers and broadleaf trees, including Sawara cypress (Chamaecyparis pisifera), Japanese umbrella pine (Sciadopitys verticillata) and Japanese pear (Pyrus pyrifolia var. culta), were caused by the same species. The phylogenetic approach to Fomitiporia revealed that the F. torreyae clade was closely related to F. bannaensis but clearly distinct from F. punctata, which originally was thought to be the cause of trunk rot in Sanbu-sugi. Fomitiporia torreyae is redescribed on the basis of more than 40 specimens from multiple hosts from Japan and China. Fomitiporia juniperina comb. nov. is proposed.

Clinical manifestations of Adult-onset Still's disease presenting with erosive arthritis: Association with low levels of ferritin and Interleukin-18.

Objective: Adult-onset Still's disease (AOSD) is a clinical entity with heterogeneous etiology. We have encountered patients with AOSD who had severe polyarthritis and who fulfilled the classification criteria for rheumatoid arthritis (RA); however, most patients with AOSD typically exhibit mild arthritis. In this study, we proposed two clinical subsets of AOSD and investigated the clinically significant characteristics of the two subtypes. Methods: We retrospectively analyzed 71 consecutive patients with AOSD. We reviewed the medical records of all patients who were followed up for more than 2 years. We classified all the patients with AOSD into the following 2 subsets: an RA subtype for patients who met the criteria for RA according to the American College of Rheumatology and a non-RA subtype for patients who did not meet the criteria for RA. Results: Our results indicated that the non-RA subtype was accompanied by severe inflammatory complications, including pleuritis and hemophagocytic syndrome. In addition, the serum ferritin and serum IL-18 levels were significantly higher in patients with the non-RA subtype than in those with the RA subtype. Interestingly, only 1 patient with the RA subtype had anti-CCP antibodies, and 1 non-RA subtype patient had rheumatoid factor. These findings distinguish these patients from patients with true RA. Conclusions: There were two subsets of patients with AOSD in the examined population. Patients with high levels of IL-18 or ferritin presented with severe systemic inflammatory disorders (the non-RA subtype), and patients with low levels of IL-18 or ferritin developed severe arthritis (RA subtype).

Ghrelin attenuates collagen production in lesional fibroblasts from patients with systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by thickening of the skin and tissue fibrosis of the internal organs. Ghrelin is primarily described as a gut hormone, and many studies currently indicate that ghrelin has protective effects in different organs, including the heart, pancreas, lung and liver, resulting from its anti-fibrotic properties. We found decreased levels of ghrelin in the plasma from patients with SSc compared with those from healthy controls. In skin fibroblast cultures, recombinant ghrelin diminished the production of collagen type I. In addition, the mRNA levels of COL1A2 and TGFB genes were significantly decreased by the stimulation of ghrelin. We showed that ghrelin may exert anti-fibrotic effects in the skin fibroblasts from patients with SSc. Because the plasma levels of ghrelin are low in SSc, the administration of ghrelin could be a new strategy for the treatment of SSc.