Phenotypic and genomic adaptations to the extremely high elevation in plateau zokor (Myospalax baileyi).

The evolutionary outcomes of high elevation adaptation have been extensively described. However, whether widely distributed high elevation endemic animals adopt uniform mechanisms during adaptation to different elevational environments remains unknown, especially with respect to extreme high elevation environments. To explore this, we analysed the phenotypic and genomic data of seven populations of plateau zokor (Myospalax baileyi) along elevations ranging from 2,700 to 4,300 m. Based on whole-genome sequencing data and demographic reconstruction of the evolutionary history, we show that two populations of plateau zokor living at elevations exceeding 3,700 m diverged from other populations nearly 10,000 years ago. Further, phenotypic comparisons reveal stress-dependent adaptation, as two populations living at elevations exceeding 3,700 m have elevated ratios of heart mass to body mass relative to other populations, and the highest population (4,300 m) displays alterations in erythrocytes. Correspondingly, genomic analysis of selective sweeps indicates that positive selection might contribute to the observed phenotypic alterations in these two extremely high elevation populations, with the adaptive cardiovascular phenotypes of both populations possibly evolving under the functional constrains of their common ancestral population. Taken together, phenotypic and genomic evidence demonstrates that heterogeneous stressors impact adaptations to extreme elevations and reveals stress-dependent and genetically constrained adaptation to hypoxia, collectively providing new insights into the high elevation adaptation.

The distinct role and regulatory mechanism of IL-17 and IFN-γ in the initiation and development of plaque vs guttate psoriasis.

BACKGROUND: Few studies have explored the differences of immunopathogenesis in plaque vs guttate psoriasis, especially on the inhibitory role of regulatory T cells (Tregs) on IL-17/ IFN-γ production and the impact of CD4+T cells on keratinocytes. OBJECTIVE: To investigate the percentage and inhibitory function of CD4+CD25highTreg and differential expressions of IL-17/ IFN-γ in plaque vs guttate psoriasis, and the effects of CD4+T cells on the proliferation of keratinocytes. METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with the plaque and guttate psoriasis. The percentage of CD4+CD25high Tregs, IL-17/IFN-γ- producing CD4+ or CD8+T cells, and apoptosis and cell cycle of Hacat cells were determined by flow cytometry. The level of IFN-γ in supernatants was analyzed by ELISA. RESULTS: The percentage of CD4+CD25highTregs in plaque psoriasis was significantly increased, and they can inhibit IFN-γ production from CD4+CD25- effector T cells. The percentage of CD8+IFN-γ+cells was also significantly increased in plaque psoriasis, and these cells positively correlated with disease severity. The percentage of CD4+CD25highTregs was decreased and CD4+IFN-γ+/IFN-γ+IL-17+ cells were predominantly increased in guttate psoriasis. CD4+T cells from guttate psoriasis induce apoptosis of keratinocytes while they promote the proliferation of keratinocytes in plaque psoriasis by decreasing late apoptosis and increasing the percentage of G1 phase. CONCLUSION: There was considerable discrepancy of the phenotype and function of T cells between plaque vs guttate psoriasis. IFN-γ and IL-17 from CD4+T cells play a crucial role in guttate psoriasis, however, IFN-γ and IL-17 from CD8+T cells are more important in the immunopathogenesis of plaque psoriasis.

Bioguided Fraction and Isolation of the Antitumor Components from Phyllanthus niruri L.

Phyllanthus niruri L., a well-known medicinal plant, has been used as a folk antitumor remedy in the worldwide scale. However, the antitumor components in P. niruri have not been reported. In order to verify the antitumor components of P. niruri and the plants which have the high content of these components, we isolated the antitumor components with bioguided fraction and isolation, by different chromatographic methods from the ethyl acetate fraction of P. niruri., and identified them as ethyl brevifolincarboxylate and corilagin by 1H-NMR, 13C-NMR, 2D-NMR, and mass spectrometric analyses. Cell cytotoxicity assays showed that corilagin has broad-spectrum antitumor activity, a better antitumor potential, and lower toxicity in normal cells. Besides, the coefficient of drug interaction (CDI) of 10 µM corilagin and 20 µM cDDP reached up to 0.77, which means corilagin can promote the antitumor activity of cDDP. Furthermore, by the extensive screening among 10 species of plants reported to contain corilagin, we found that Dimocarpus longan Lour. has the maximum content of corilagin. In conclusion, corilagin is the major active antitumor composition in P. niruri. L. on HCC cells and has high content in D. longan.

[Research on Assessment Methods of Spectrum Data Quality of Core Scan].

Core scan is the instrument used for core spectrum and pictures detection that has been developed in recent years. Cores' data can be digitized with this equipment, then automatic core catalog can be achieved, which provides basis for geological research, mineral deposit study and peripheral deposit prospecting. Meanwhile, an online database of cores can be established by the means of core digitalization to solve the cost problem caused by core preservation and share resources. Quality of core data measurement directly affects the mineral identification, reliability of parameter inversion results. Therefore it's very important to quasi-manage the assessment of data quality with the instrument before cores' spectrum testing services. Combined with the independent R&D of CSD350A type core scan, and on the basis of spectroscopy basic theory, spectrum analysis methods, core spectrum analysis requirements, key issues such as data quality assessment methods, evaluation criteria and target parameters has been discussed in depth, and comprehensive assessment of independent R&D of core scan has been conducted, which indicates the reliability and validity of spectrum measurements of the instrument. Experimental tests show that the methods including test parameters and items can perfectly response the measurements of reflectance spectrum, wavelength accuracy, repeatability and signal to noise ratio with the instrument. Thus the quality of core scan data can be evaluated correctly, and the foundation of data quality for commercial services can be provided. In the case of the current lack of relevant assessment criteria, the method this study proposes for the assessment has great value in the work of core spectrum measurements.

Clinical analysis and etiology of porokeratosis.

The present study was performed in order to define the clinical manifestations of porokeratosis, with particular emphasis on genital porokeratosis. A total of 55 cases of porokeratosis were retrospectively reviewed between 2000 and 2007 from Huashan Hospital (Shanghai, China). Out of 55 cases, there were 22 cases of porokeratosis of Mibelli, 17 cases of disseminated superficial actinic porokeratosis (DSAP), 15 cases of disseminated superficial porokeratosis and one case of linear porokeratosis. The ratio of males to females was 39:16. Among them, 12 cases had a family history of porokeratosis. During the five-year follow-up period, no malignant transformation was observed and no further aggravation of lesions was detected. The results indicated that the initial region of DSAP in the Chinese population may differ from Caucasians. In combination with other studies, the present study found that genital porokeratosis in the Chinese population is often associated with pruritus. Since no recurrence was observed in cases treated with surgical excision, it was suggested that surgical excision is a viable treatment strategy and should be used for porokeratotic lesions if possible. In addition, regular follow-ups are required, since the aggravation of porokeratosis may cause the development of malignancy transformation.

Compound K-induced apoptosis of human hepatocellular carcinoma MHCC97-H cells in vitro.

An intestinal bacterial metabolite of ginseng protopanaxadiol saponin, 20-O-(ß-D-glucopyranosyl)-20(S)-protopanaxadiol (compound K), has been reported to induce apoptosis in a variety of cancer cells. However, the precise mechanisms induced by compound K in human hepatocellular carcinoma (HCC) cells remain unclear. In order to examine possible apoptotic mechanisms, we investigated the anticancer effect of compound K in MHCC97-H. MTT assay showed that compound K inhibited the proliferation of MHCC97-H cells with a relatively low toxicity in normal hepatoma cells. Cell cycle progression and cell staining showed an increase in apoptotic sub-G1 fraction. Treatment of MHCC97-H with compound K also induced a reduction in mitochondrial membrane potential (Δψm) and DNA damage. Further study showed that compound K upregulated Fas, FasL, Bax/Bcl-2 ratio and downregulated pro-caspase-9, pro-caspase-3 in a dose-dependent manner, and it also inhibited Akt phosphorylation. These results suggest that compound K significantly inhibits cell proliferation and induces apoptosis in MHCC97-H cells through Fas- and mitochondria-mediated caspase-dependent pathways in human HCC cells.

Orchid fleck virus: an unclassified bipartite, negative-sense RNA plant virus.

Orchid fleck virus (OFV) causes chlorotic or necrotic spots in many orchid species. Its particle morphology and cytopathic effects are similar to those of nucleorhabdoviruses. Although OFV shares clear sequence similarities with rhabdoviruses, its taxonomic status is undetermined because its negative-sense RNA genome is bipartite. This review presents a general overview of classical and contemporary findings about etiology, serology, epidemiology, pathology, molecular biology, detection and prevention methods of orchid fleck virus. Because of the characteristics of OFV and viruses of the Rhabdoviridae and Mononegavirales, it is proposed that a new genus of negative-sense RNA plant viruses outside of the Mononegavirales be established with orchid fleck virus as the type species.

Dysregulation of miRNA146a versus IRAK1 induces IL-17 persistence in the psoriatic skin lesions.

Psoriasis is a common chronic inflammatory skin disorder with dysregulation of miRNAs. The expression pattern of miR-146a and target gene IRAK1 in lesions and PBMCs of plaque psoriasis remains unclear. In our study, we found the expression of miR-146a was up-regulated both in lesions and PBMCs of psoriatic patients, and positively correlated with IL-17 expression, whereas the target gene IRAK1 expression was expressed differentially in lesions and peripheral blood. Inability of miR-146a inhibiting target gene IRAK1 may contribute to the persistent inflammation in lesions of psoriasis.

In vivo reflectance confocal microscopy of extramammary Paget disease: diagnostic evaluation and surgical management.

BACKGROUND: Extramammary Paget disease (EMPD) is a diagnostic challenge. In vivo reflectance confocal microscopy (RCM) has been reported to be useful for in vivo skin tumor evaluation. It may also assist in the surgical management of EMPD lesions. OBJECTIVE: We sought to describe confocal features of EMPD and correlate them with histopathologic findings. The potential of RCM to map the lesions for subsequent surgical management was also investigated. METHODS: A total of 23 lesions from 14 recruited patients were evaluated by RCM and histopathologic examination. RCM was used to delineate preoperative surgical margins in two patients. RESULTS: Erythematous, hyperpigmented, and hypopigmented lesions were evaluated by RCM and results were confirmed by histopathologic examination. Paget cells were observed throughout the epidermis. Typical Paget cells on RCM were characterized by a mild bright nucleus and dark cytoplasm, frequently twice the size of keratinocytes or larger. At the dermoepidermal junction, tumor nests were seen as dark glandular structures. A high density of dendritic cells was observed in pigmented lesions and a low density in erythematous lesions. Dilated vessels and inflammatory cells were seen in pigmented and erythematous lesions. Paget cells within the epidermis and nest structures at the dermoepidermal junction were seen in most lesions. These two features were useful for delineating the margins. Histologic examination corroborated the surgical margins found by RCM. LIMITATIONS: The sensitivity and specificity of these diagnostic features have not been fully studied, and differential diagnostic features require exploration. CONCLUSION: Features correlating well to histopathology are observed on the RCM of EMPD lesions. RCM may be used as an auxiliary diagnostic tool for the diagnosis and management of EMPD.

The application of ZnO luminescent nanoparticles in labeling mice.

Photoluminescent ZnO@polymer core-shell nanoparticles were used in mouse imaging through intradermal injections and intravenous injections, and the results proved that such ZnO fluorescence probes are nontoxic to live mice and have great potential in in vivo applications.

In vivo reflectance confocal microscopy for the differential diagnosis between vitiligo and nevus depigmentosus.

BACKGROUND: Nevus depigmentosus (ND) is frequently confused with vitiligo. Differential diagnosis can be difficult. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique for real-time en face imaging of the superficial layers of the skin down to the superficial dermis with cellular level resolution close to conventional histopathology. In this study, we tried to use this new technology to study the features of the distribution of pigment cells of these two hypopigmentation disorders and then concluded the differential features. METHODS: Sixty vitiligo patients and 62 ND patients were enrolled in the study. Three points in each patient (lesional, margin of the lesions and adjacent non- lesional points) were examined with RCM. The gray value of image was quantified using software, and we calculated the relative gray value. RESULTS: The RCM image feature was different between vitiligo and ND patients. The differential diagnosis was made based on the following four RCM features: complete absence of pigment cells; the distribution of pigment cells; the margins; and the relative gray value. CONCLUSION: RCM can be used as an auxiliary diagnostic tool for the differential diagnosis between vitiligo and ND.

Suction blister epidermal grafting using a modified suction method in the treatment of stable vitiligo: a retrospective study.

BACKGROUND: Of various surgical therapies used for the replenishment of melanocytes in recalcitrant and stable vitiligo, suction blister epidermal grafting (SBEG) is one of the simplest and most effective methods. OBJECTIVE: To evaluate the effectiveness and potential complications of SBEG in the treatment of stable vitiligo through the use of a modified dermis-epidermis separator designed by the authors. MATERIALS AND METHODS: One thousand one hundred people with stable vitiligo unresponsive to other medical treatments were treated with SBEG therapy. The negative pressure generated by the dermis-epidermis separator raised blisters at recipient and donor sites. Repigmentation was assessed 6 months after epidermis transplantation. RESULTS: Complete repigmentation was observed in 227 patients (20.6%), and excellent repigmentation (>50%) was observed in 568 (51.6%)-a success rate of 72.3%. No superficial scarring was observed at the grafted or donor sites, and no serious complications were encountered. CONCLUSION: SBEG is an established, simple, and effective treatment for resistant and stable vitiligo. Patients suffer few complications and are receptive to this type of therapy.

[Wide-range fiber spectral instrument covering].

To meet the requirements of outdoor field mineral analysis and remote sensing ground verification spectral analysis, the wide-range fiber spectral instrument covering 400 nm-2 500 nm was developed. The present article illustrates the design of the optical, mechanical and electrical parts of the instrument. The optical system utilizes grating horizontal-reflecting light route to implement the full coverage of the spectrum. Three line-array sensors are intercrossed in three directions on the spectrum surface to sense different spectrum ranges. CPLD device generates the sampling and driving temporal logic signals to the three line-array photoelectrical devices. Fourteen bits high speed AD converts the analog signals into digital ones. USB 2.0 is used for communication. The final results demonstrate that while implementing the measurement of wide spectrum, the instrument is improved in size, spectrum resolving power, signal quality and measuring speed. Ideal spectrum data were acquired.

Type I pityriasis rubra pilaris: upregulation of tumor necrosis factor alpha and response to adalimumab therapy.

BACKGROUND: pityriasis rubra pilaris (PRP) has unknown etiology and is often refractory to conventional therapies. OBJECTIVE: to document a PRP patient's response to adalimumab therapy and to highlight the potential role of tumor necrosis factor (TNF) in the development of PRP skin lesions. METHODS: a patient received adalimumab therapy at standard dosing intervals. In addition, the messenger ribonucleic acid (mRNA) of TNF in the lesional and perilesional normal skin was quantified in two patients with PRP. RESULTS: the patient responded to adalimumab therapy and achieved clinical remission by 4 months. There was a significant elevation of TNF mRNA in the lesional skin of PRP. CONCLUSION: TNF upregulation is detected in PRP lesional skin, consistent with the observed clinical efficacy of TNF blockade for the treatment of PRP.

Reassessment of microarray expression data of porokeratosis by quantitative real-time polymerase chain reaction.

BACKGROUND: Porokeratosis (PK) is a heterogeneous group of keratinization disorders that exhibit similarities with psoriasis at both the clinical and molecular levels. METHODS: The transcript levels of keratin (KRT) 6A, 16, 17, S100A7, A8, A9, p53 and three candidate genes (i.e. SART3, SSH1 and ARPC3) were reassessed in pairwise lesional and uninvolved skin from nine patients with PK by real-time quantitative polymerase chain reaction (RTQ-PCR). RESULTS: The results of RTQ-PCR confirmed that KRT6A, 16, S100A7, A8 and A9 (p = 0.008) were mostly up-regulated in the lesional skin when compared with uninvolved skin. Different from the microarray data, there was no significant difference observed in KRT17 expression patterns between lesional and normal-appearing skin (p = 0.066). No statistical difference was observed in p53 and three candidate genes' expression patterns between lesional and uninvolved skin. CONCLUSIONS: In the present study, 9 of the 10 gene expression measured by RTQ-PCR in PK were statistically comparable to microarray data. KRT6A was identified as specific biomarker for porokeratotic keratinocytes, as it was the most significantly up-regulated gene in the nine patient samples.

[Inhibitory effect of ginseng saponin IH901 on proliferation and metastasis of ECV304 cell line and its molecular mechanism].

This study aims to investigate the inhibitory effect on proliferation and metastasis of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH901) on ECV304 cell line. MTT assay was used to examine the effect of cell proliferation inhibition and the adhesive ability of ECV304 cells to artificial basement membrane. Morphology of cell apoptosis was observed with phase contrast microscope. Apoptosis rate and cell cycle were detected by flow cytometry (FCM). Cell migration was measured by wound healing assay. ELISA kit was used to detect VEGF and bFGF. Caspases were detected by Western blotting. Results indicated that ginseng saponin IH901 can downregulate the expression of growth promoting protein VEGF and bFGF, and upregulate pro apoptosis protein cleaved caspase-9 and cleaved caspase-3. The increase in the apoptotic sub-G1 fraction is in a dose-dependent manner, and cell cycle arrests in the G0/G1 phase was detected by FCM. Morphological examination of IH901-treated samples showed cells with chromatin condensation, cell shrinkage, and all typical characteristics of apoptotic cells. Therefore, IH901 dramatically suppresses cell proliferation and adhesion and migration of ECV304 cell line.

Expression of pigment epithelium-derived factor in human melanocytes and malignant melanoma cells and tissues: Is loss of pigment epithelium-derived factor associated with melanoma?

BACKGROUND: Pigment epithelium-derived factor (PEDF) was first isolated from the medium conditioned by human fetal retinal pigment epithelial cells and has been detected in a broad range of human fetal and adult tissues. Recent studies have indicated that PEDF activity is inhibitory to angiogenesis. OBJECTIVE: To study the expression and distribution of pigment epithelium-derived factor (PEDF) in human melanocytes, malignant melanoma cells and tissues. RESULTS: PEDF was expressed in human melanocytes. The expression of PEDF protein diminished in the following orders healthy skin, pigmented nevus and human malignant melanoma (p < 0.001). Both the expression of PEDF mRNA and protein was much lower or almost absent in the malignant melanoma cell line A375 than that in human melanocytes (p < 0.001). METHODS: The expression and distribution of PEDF in human healthy skin, pigmented nevus and malignant melanoma were studied. The expression of PEDF mRNA in human melanocytes and malignant melanoma cell line A375 was measured by reverse transcription polymerase chain reaction (RT-PCR) and PEDF protein was detected by immunohistochemical method and Western blotting analysis. CONCLUSION: The lack of PEDF expression may contribute to the pathogenesis of malignant melanoma.

Evaluation of 308-nm monochromatic excimer light in the treatment of psoriasis vulgaris and palmoplantar psoriasis.

BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of 308-nm monochromatic excimer light (MEL) in the treatment of psoriasis vulgaris and palmoplantar psoriasis. METHODS: Thirty-five patients with psoriasis vulgaris and 15 patients with palmoplantar psoriasis were recruited for this study. Thirty patients with psoriasis vulgaris completed a total of 16 treatments with 308-nm MEL twice a week, and 15 patients palmoplantar psoriasis completed 25 treatments administered once weekly. The clinical response to therapy and adverse effects were recorded. RESULTS: Patients with psoriasis vulgaris (n=30) showed a 74.6% improvement in the mean psoriasis area and severity index score after a total of 16 MEL treatments (2 x /week) with 36.7% of the patients (n=11) achieving clearance. Patients with palmoplantar psoriasis (n=15) showed a 52.5% improvement in the mean severity index score after a total of 25 MEL treatments (1 x /week) with only one patient (6.7%) achieving clearance. The MEL therapy was well tolerated with a low incidence of side effects, which included pruritus, erythema and blister formation. CONCLUSION: The 308-nm MEL can be utilized as an effective and safe treatment modality for patients with mild-to-moderate psoriasis vulgaris and palmoplantar psoriasis.

Gene expression profiling of porokeratosis.

BACKGROUND: Porokeratosis (PK) represents a heterogeneous group of disorders of keratinization and has a wide variety of clinical manifestations. PK may exhibit similarities with psoriasis at both clinical and molecular levels. The genetic basis and pathogenesis for PK remain elusive. METHODS: We studied the transcriptional profiles of three pairwise lesional and uninvolved skin biopsies from patients with different subtypes of PK using the Illumina BeadArray platform. RESULTS: A total of 37 upregulated genes were identified in our study, including wound-induced keratins, S100 calcium-binding protein genes involved in epidermal differentiation, as well as genes involved in mediating intercellular communication and the immune response. To our knowledge, this is the first study that characterizes the immune profile of PK lesions. CONCLUSIONS: Here, we report that keratinocytes (KCs)-harboring lesions have activated and overexpressed wound-induced keratin genes, which appear to be coregulated with other genes involved in mediating epidermal differentiation, intercellular communication and immunity. This study, from the perspective of gene profiling, supports that gene misregulation in PK mimics that of psoriasis. Our data indicate that the genes implicated in the T-cell-mediated immune response pathway and activation of KCs play a key role in the pathogenesis of PK.