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Abstract: Angiosarcoma is a rare, highly aggressive malignant tumor originating from endothelial cells that line the lumen of blood or lymphatic vessels. The molecular mechanisms of scalp and face angiosarcoma still need to be elucidated. This study aimed to investigate the expression of phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphorylated mitogen-activated kinase-like protein (pMAPK), and tumor protein p53 (TP53) in scalp and face angiosarcoma and to assess tumor tissue apoptosis.The expression and intracellular distribution of PTEN, PIK3CA, pMAPK, and TP53 proteins in 21 specimens of human scalp and face angiosarcoma and 16 specimens of human benign hemangioma were evaluated using immunohistochemistry. Tumor cell apoptosis was assessed by terminal deoxyribonucleotide transferase-mediated dUTP nick end-labeling staining.Significantly lower PTEN but higher PIK3CA, pMAPK, and TP53 immunostaining were detected in the angiosarcoma specimens than in the benign hemangioma specimens(P < .01). The angiosarcoma tissues exhibited significantly higher apoptosis indices than the benign hemangioma tissues (P < .01). The positive expression rates of PIK3CA, pMAPK, and TP53 were correlated with the degree of tumor differentiation in the human scalp and face angiosarcoma.The PI3K, MAPK, and TP53 pathways might be involved in angiosarcoma tumorigenesis in humans and may serve as therapeutic targets for the effective treatment of this malignancy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Radioresistance is the main reason for the failure of radiotherapy in non-small-cell lung cancer (NSCLC); however, the molecular mechanism of radioresistance is still unclear., Methods: An RNA-Seq assay was used to screen differentially expressed long non-coding RNAs (lncRNAs) and genes in irradiation-resistant NSCLC cells. RT-PCR and Western blotting assays were performed to analyze the expressions of lncRNAs and genes. The chromosome conformation capture (3C) assay was performed to measure chromatin interactions. Cell cytotoxicity, cell apoptosis, sphere formation and Transwell assays were performed to assess cellular function., Results: In this study, it was found that LINC01224 increased during the induction of radioresistance in NSCLC cells. LINC01224 was located within the enhancer of ZNF91, and LINC01224 could affect the transcription of ZNF91 by regulating the long-range interactions between the ZNF91 enhancer and promoter. Moreover, upregulation of LINC01224 and ZNF91 could promote irradiation resistance by regulating the stem cell-like properties of NSCLC cells. In addition, high expression levels of LINC01224 and ZNF91 in tissue samples were associated with radioresistance in NSCLC patients., Conclusion: Our findings demonstrated that LINC01224/ZNF91 drove radioresistance regulation by promoting the stem cell-like properties in NSCLC., Competing Interests: The authors declare that they have no competing interests., (© 2021 Fu et al.)

Background: Candida auris is an emerging pathogen associated with outbreaks in clinical settings. Isolates of the pathogen have been geographically clustered into four clades with high intra-clade clonality. Pathogenicity varies among the clades, highlighting the importance of understanding these differences., Objectives: To examine the physiological and biochemical properties of each clade of C. auris to improve our understanding of the fungus., Methods: Optimal growth temperatures of four strains from three clades, East Asia, South Asia and South Africa, were explored. Moreover, assimilation and antifungal susceptibility properties of 22 C. auris strains from the three clades were studied., Results: The optimal growth temperatures of all strains were 35-37 °C. Assimilation testing demonstrated that the commercial API ID 32 C system can be used to reliably identify C. auris based on the biochemical properties of the yeast. Notably, C. auris can be uniquely differentiated from commonly clinical fungi by its ability to assimilate raffinose and inability to utilize D-xylose, suggesting a useful simple screening tool. The antifungal susceptibility results revealed that all strains are resistant against fluconazole (minimal inhibitory concentration (MIC) 4 to > 64 µg/mL) and miconazole (MIC 8 to > 16 µg/mL), with strains from the Japanese lineage showing relatively lower MIC values (1-4 µg/mL). Conversely, itraconazole, voriconazole, amphotericin B, micafungin and caspofungin were active against most of the tested strains. On the clade level, East Asian strains generally showed lower MICs against azoles comparing to the other clades, while they displayed MICs against flucytosine higher than those of strains from South Africa and South Asia clades., Conclusion: Our data suggest a simple identification approach of C. auris based on its physiological and biochemical properties and highlight aspects of C. auris population from various clades.

Nosocomial infections, also known as hospital-acquired infections, pose a serious challenge to healthcare professionals globally during the Coronavirus disease 2019 (COVID‑19) pandemic. Nosocomial infection of COVID‑19 directly impacts the quality of life of patients, as well as results in extra expenditure to hospitals. It has been shown that COVID‑19 is more likely to transmit via close, unprotected contact with infected patients. Additionally, current preventative and containment measures tend to overlook asymptomatic individuals and superspreading events. Since the mode of transmission and real origin of COVID‑19 in hospitals has not been fully elucidated yet, minimizing nosocomial infection in hospitals remains a difficult but urgent task for healthcare professionals. Healthcare professionals globally should form an alliance against nosocomial COVID‑19 infections. The fight against COVID‑19 may provide valuable lessons for the future prevention and control of nosocomial infections. The present review will discuss some of the key strategies to prevent and control hospital‑based nosocomial COVID‑19 infections.

Ethanol-soluble proteins, including prolamins, are one of the most important seed proteins in rice ( Oryza sativa L.). However, little is known about the proteomic profile of ethanol-soluble protein fraction extracted from rice grain. In this work, the differential profile of ethanol-soluble proteins extracted by 2-chloroethanol and ethanol has been documented. Proteome analysis utilizing LC-MS/MS identified a total of 64 unique proteins in the 2-chloroethanol extract of rice seeds. The majority of these proteins had low molecular weight ranging from 10 to 25 kD and isoelectric point (pI) in mid-acidic (pH 5-pH 7) and mid-basic (pH 7-pH 9) ranges. Database searches combined with transmembrane domain (TMD) analysis revealed that >70% of identified proteins were hydrophobic, i.e., had at least one TMD. Gene ontology classification and enrichment analysis showed that the identified proteins were involved in13 types of biological processes, 5 types of cell components, and 17 types of molecular functions. These results were significant based on the hyper p-value of <0.05. The most frequent categories of biological processes, cell components, and molecular functions were, respectively, type I hypersensitivity, extracellular space and extracellular region, and serine-type endopeptidase inhibitor activity. Interestingly, in addition to seed storage proteins such as prolamins and glutelins, certain allergen proteins, protease inhibitors, and lipid transfer proteins were identified in the extracts. Together, the collected data provide novel insights into the protein profile of 2-chloroethanol extract of rice seeds., Competing Interests: The authors have declared no conflict of interest., (© 2020 The Authors.)

Purpose: Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC., Experimental Design: The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1 was verified. Various in vitro and in vivo experiments were performed to investigate the interaction between THAP9-AS1 and YAP signaling., Results: We demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. THAP9-AS1 promotes PDAC cells growth both in vitro and in vivo . THAP9-AS1 exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of THAP9-AS1 knockdown. Inversely, YAP knockdown diminished the effects of THAP9-AS1 overexpression. THAP9-AS1 acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, THAP9-AS1 binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes THAP9-AS1 transcription to form a feed-forward circuit. Importantly, THAP9-AS1 level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC., Conclusions: Our findings indicate that THAP9-AS1 plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates THAP9-AS1 transcription. THAP9-AS1 /YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment., (©2019 American Association for Cancer Research.)

Background: HGF/MET has been found to be associated with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of HGF/MET involved in regulating the metastasis of NSCLC remain unclear., Methods: The effect of HGF/MET and FOSL2 on cell migration and invasion were assessed by transwell and scratch assays. HGF/MET-induced phosphorylation and upregulation of FOSL2 was analyzed by RT-PCR and Western blotting. Regulatory effects of FOSL2 on SNAI2 transcription were detected by chromatin immunoprecipitation (ChIP) and dual-Luciferase reporter assays. The correlations of FOSL2 expression with clinical outcomes were assessed in 56 NSCLC patients., Results: HGF/MET induced the phosphorylation and upregulation of FOSL2 by ERK1/2 kinase, FOSL2 promoted the transcription of SNAI2 by binding with the SNAI2 promoter, and SNAI2 subsequently promoted the epithelial-mesenchymal transition (EMT), invasion, and migration of NSCLC cells. According to the clinical correlation analysis in NSCLC, high expression of FOSL2 correlated with advanced tumor stage and metastasis., Conclusion: Our studies propose that the regulatory mechanisms of the HGF/MET-induced cascade pathway is mediated by FOSL2 in NSCLC metastasis and suggested that FOSL2 could potentially be employed as a prognostic biomarker and potential therapeutic target of NSCLC metastasis., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Yin et al.)

Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1). To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity. P4HA1 has two glycosylation sites, Asn (N) 113 and N259. Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC. N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion. Downregulation of Stt3b and Magt1 reduces N259 glycans on P4HA1. In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues. Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites. These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.

Sphingosine-1-phosphate receptor 1 (S1PR1) is abnormally expressed in a variety of tumors. However, the clinical implications and biological roles of S1PR1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we have focused on ESCC, and analyzed the expression of S1PR1 in human specimens at various histological grades of ESCC and the role of S1PR1 in Eca109 cells. Using human ESCC tissue microarray and immunohistochemistry, we found S1PR1 protein mainly located in the cytoplasm of cancer cells and normal esophageal mucosal epithelial cells, and small amounts in the plasma membrane. The levels of cytoplasmic S1PR1 in ESCC tissues were significantly higher than those in adjacent non-cancerous tissues. Cytoplasmic S1PR1 exhibited higher expression in ESCC tissues with poor differentiation than those with well differentiation. Conversely, the positive expression of plasma membrane S1PR1 was correlated with well differentiation. Kaplan-Meier survival analysis showed that patients with positive membrane S1PR1 expression tended to have longer survival time. Univariate and multivariate Cox regression analysis revealed that membrane S1PR1 expression was an independent prognostic factor for ESCC patients. Furthermore, overexpression of cytoplasmic S1PR1 promoted Eca109 cells from G1 phase to S phase and plasma membrane S1PR1 as the opposite, which may be associated with p21. Cytoplasmic S1PR1 signaling also promoted Eca109 cells migration. Our findings demonstrate that cytoplasmic S1PR1 plays an important role in the malignant behavior of human ESCC and may serve as a new target for ESCC therapy., Competing Interests: None., (IJCEP Copyright © 2017.)

Chilling stress is an important constraint for maize seedling establishment in the field. To examine the role of salicylic acid (SA) and hydrogen peroxide (H 2 O 2 ) in response to chilling stress, we investigated the effects of seed priming with SA, H 2 O 2 , and SA+H 2 O 2 combination on maize resistance under chilling stress (13°C). Priming with SA, H 2 O 2 , and especially SA+H 2 O 2 shortened seed germination time and enhanced seed vigor and seedling growth as compared with hydropriming and non-priming treatments under low temperature. Meanwhile, SA+H 2 O 2 priming notably increased the endogenous H 2 O 2 and SA content, antioxidant enzymes activities and their corresponding genes ZmPAL, ZmSOD4, ZmAPX2, ZmCAT2 , and ZmGR expression levels. The α-amylase activity was enhanced to mobilize starch to supply metabolites such as soluble sugar and energy for seed germination under chilling stress. In addition, the SA+H 2 O 2 combination positively up-regulated expressions of gibberellic acid (GA) biosynthesis genes ZmGA20ox1 and ZmGA3ox2 , and down-regulated GA catabolism gene ZmGA2ox1 expression; while it promoted GA signaling transduction genes expressions of ZmGID1 and ZmGID2 and decreased the level of seed germination inhibitor gene ZmRGL2 . The abscisic acid (ABA) catabolism gene ZmCYP707A2 and the expressions of ZmCPK11 and ZmSnRK2.1 encoding response receptors in ABA signaling pathway were all up-regulated. These results strongly suggested that priming with SA and H 2 O 2 synergistically promoted hormones metabolism and signal transduction, and enhanced energy supply and antioxidant enzymes activities under chilling stress, which were closely relevant with chilling injury alleviation and chilling-tolerance improvement in maize seed. Highlights: Seed germination and seedling growth were significantly improved under chilling stress by priming with SA+H 2 O 2 combination, which was closely relevant with the change of reactive oxygen species, metabolites and energy supply, hormones metabolism and regulation.

The purpose of this study was to validate a method for determine the glomerular filtration rate (GFR) in healthy cynomolgus monkeys by using iohexol. Eighteen healthy cynomolgus macaque monkeys (age, 4 to 6 y [mean, 5 y]; weight, 2 to 6 kg [mean, 4 kg]) were randomly entered into 3 different doses groups (3 male and 3 female macaques per group) of 30, 60, 90 mg I/kg to receive an intravenous bolus injection of iohexol. Serum iohexol concentrations were determined by using liquid chromatography–tandem mass spectrometry, and clearance rate were determined by using WinNonlin software. The GFR value (mean ± SD) of each dose group was 2.50 ± 0.321, 2.65 ± 0.529, and 2.75 ± 0.385 mL/min/kg. These values did not differ significantly between dose levels or sexes. Iohexol clearance is a simple, precise method that is suitable for the determination of GFR in cynomolgus monkeys., (Copyright 2017 by the American Association for Laboratory Animal Science)

Increasing evidence indicates that long non-coding RNAs (lncRNAs) can act as crucial regulators of tumor progression. In the present study, UXT-AS1 was found to be significantly upregulated in colorectal cancer (CRC) and high expression levels of UXT-AS1 were significantly associated with poor prognosis in CRC patients. In addition, upregulation of UXT-AS1 resulted in inhibition of cell apoptosis and the promotion of cell proliferation. Moreover, by regulating the alternative splicing of UXT, upregulation of UXT-AS1 decreased the UXT1 transcript which promoted cell apoptosis and increased the UXT2 transcript which promoted cell proliferation. Thus, aberrant high expression of UXT-AS1 can promote CRC progression by changing the alternative splicing of UXT from the UXT1 transcript to the UXT2 transcript. In conclusion, our findings suggest that the regulation of CRC progression is by UXT-AS1-induced alternative splicing of UXT, and the expression level of UXT-AS1 may be a potential prognostic biomarker and therapy target in CRC patients.

Both nerve growth factor (NGF) and heme oxygenases-1 (HO-1) promotes neuron survival from cerebral ischemic lesions. NGF protects neurons from oxygen-glucose deprivation (OGD), and HO-1 expression can be induced by some growth factors like NGF. This work attempted to identify the contribution of HO-1 on the neuroprotection role of NGF in OGD model, which is an injury simulation of ischemic neuron in vitro. The viability of cortical neurons cells treated with OGD restored significantly by pretreatment with NGF in a dose dependent manner. Moreover, NGF provided obvious protective effects against OGD-induced neurons apoptosis. It identified that NGF could prevent apoptosis and ROS (reactive oxygen species) accumulation in the primary cortical neurons exposed to OGD. NGF could up-regulate the expression level of HO-1, and then afford neuroprotection against OGD insult. In addition, we found that MEK/ERK pathway participated NGF-induced over-expression of HO-1, and was involved in the transcriptional activity or neuroprotection effect of NGF., (Copyright © 2017. Published by Elsevier B.V.)

An N-heterocyclic carbene (NHC) catalyzed dihalomethylenation of enals is described. It is a rare example of merging NHC catalysis with single-electron chemistry, a challenging topic with limited previous success. The versatile carbon-centered trihalomethyl radicals have been demonstrated, for the first time, to be compatible with an NHC-bound intermediate, thus leading to efficient and regioselective intermolecular C-C bond formation. The mild process provides straightforward access to unsaturated δ,δ-dihalo esters., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Iron overload plays a key role in brain injury after intracerebral hemorrhage (ICH). We explored the roles of ferric iron chelator-deferiprone (DFP)-and ferrous iron chelator-clioquinol (CQ)-in ICH rats through the outcomes, iron deposits, reactive oxygen species (ROS), brain water content, and related iron transporters. One hundred eight Sprague-Dawley rats received intra-striatal infusions of 0.5 U of type IV collagenase to establish ICH models. The rats were randomly assigned to the sham, vehicle, DFP, and CQ groups. We evaluated the outcomes, iron levels, brain water content, and ROS; meanwhile, immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were utilized to determine ferritin, transferrin, transferrin receptor, divalent metal transport 1 (DMT1), and ferroportin at 48 and 72 h, 7 and 14 days after surgery. Our results showed ICH induced iron overload, brain edema, ROS formation, and neurological deficits. Both iron chelators decreased iron levels; CQ improved the neurological outcome, attenuated brain edema, and ROS production. DFP reduced iron contents but not brain water content and ROS generation. DFP failed to improve the outcome. ICH initiated endogenous iron chelators and transporters, both exogenous iron chelators enhanced expression of transferrin and transferrin receptor. CQ enhanced expression of ferroportin but not DMT1, while DFP enhanced expression of DMT1 but not ferroportin. Ferrous iron contributed to brain injury, and binding ferrous iron can modestly improve outcome after ICH in rats. The exogenous ferrous iron chelator possibly functioned via endogenous ferrous iron transporters on ICH. Therefore, ferrous iron may be a promising target for ICH in future.

This study aimed to determine the effects of different concentrations of soluble beta-amyloid 25-35 (Aβ25-35) on cell viability, calcium overload, and PI3K-p85 expression in cultured cortical rat neurons. Primary cultured cerebral cortical neurons of newborn rats were divided randomly into six groups. Five groups were treated with soluble Aβ25-35 at concentrations of 10nmol/L, 100nmol/L, 1μmol/L, 10μmol/L, or 30μmol/L. Cell Counting Kit-8 staining was used to measure cell viability, laser-scanning confocal imaging was used to detect changes in intracellular free calcium concentration, and western blot assay was used to measure neuronal PI3K-p85 expression. Soluble Aβ25-35 was found to reduce cell viability and induce calcium overload in primary cultured rat cerebral cortical neurons, in a concentration-dependent manner. At certain concentrations, soluble Aβ25-35 also increased neuronal PI3K-p85 expression. These findings reveal that soluble Aβ25-35 reduces the viability of cultured cerebral cortical rat neurons. The neurotoxicity mechanism may involve calcium overload and disruption of insulin signal transduction pathways., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Ferrous iron is a major source inducing oxidative stress after intracerebral hemorrhage (ICH). Divalent metal transporter1 (DMT1) is the important and well-known plasma membrane transport protein which was proved to be involved in the transport of free ferrous iron in mammals. Ferroportin 1 (FPN1) is the unique exporter of ferrous iron from mammalian cells. The role of DMT1 and FPN1 in brain after ICH is still not elucidated. Therefore, we measure the expression of DMT1 and FPN1, to explore the correlations between ferrous iron and its specific transporters after ICH., Methods: Ninety-six Sprague-Dawley rats received intra-striatal infusions of 0.5 U type IV collagenase to establish ICH model. Ferrous iron content in brain was determined using Turnbull's method. DMT1 and FPN1 expression were examined by immunohistochemical staining and Real-Time quantitative polymerase chain reaction (RT-PCR). With the use of confocal laser microscopy, we determined the colocalization of DMT1 and FPN1 at 1, 3, 7 and 14 days after ICH., Results: Ferrous iron deposition was shown in the perihematomal zone as early as 1 day after ICH; it reached a peak after 7 days and was not elevated within 14 days following ICH. The expression of the DMT1 upregulated and reached to peak at day 7 after ICH. FPN1 reached a plateau at 3 days post-ICH. Expression levels of DMT1 and FPN1 were in parallel with ferrous iron deposition. There was a positive correlation between FPN1 and DMT1. DMT1 mainly localized in the cytoplasm of glias and neurons. FPN1 were mostly distributed on the membrane of endothelial cells and glias. Confocal microscope showed that DMT1 colocalized with FPN1., Conclusions: DMT1 and FPN1 are positively influenced by ferrous iron status in brain after ICH. DMT1 and FPN1 attenuate iron overload after ICH via increasing transmembrane iron export.

In this article, the total syntheses of antimalarial compound decursivine and its biologically inactive sibling serotobenine are presented. The biomimetic synthesis of (±)-serotobenine was investigated first, but failed. During the subsequent investigation of other synthetic routes, we discovered a new cascade Witkop photocyclization/elimination/addition sequence, which enabled the expedient synthesis of not only racemic decursivine and serotobenine, but also enantiopure (+)- and (-)-decursivine and a variety of their analogues. The present syntheses represent the shortest pathway for the total synthesis of decursivine and serotobenine to date. Moreover, the newly developed cascade sequence for the total synthesis of decursivine does not need any protecting steps. The scope and the reaction mechanism of the cascade sequence were also studied. A rational mechanism for the cascade sequence is proposed, which is consistent with the previous studies and our current experimental results., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme catabolism and iron production, its role in intracerebral hemorrhage (ICH) is controversial. The study was to investigate correlations between brain oxidative injury and HO-1 after experimental ICH., Method: Sprague-Dawley rats received intra-striatal infusions of 100 μl autologous whole blood as ICH models. HO-1 were examined by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analysis. Brain oxidative stress was quantitated by malondialdehyde (MDA); antioxidation were measured by copper-zinc superoxide dismutase (Cu/Zn-SOD) activity using RT-PCR assay., Results: The expression of the HO-1 upregulated and reached its peak at days 3 and 7 after ICH (P < 0.01). There was a significant increase of MDA and a top at 3-day post-ICH (P < 0.01); Cu/Zn-SOD was upregulated post-ICH and reached the top at day 7 (P < 0.001); HO-1 was correlated significantly with brain MDA content at days 7 and 14 following ICH (r = 0.435-0.501, P < 0.001) but there is no definite correlation between them on 1 to 3 days (P > 0.05); conversely, HO-1 was correlated significantly with Cu/Zn-SOD on 1 to 3 days after ICH (r = 0.433-0.621, P < 0.001) but there is no definite correlation between them at days 7 and 14 (P > 0.05)., Conclusions: HO-1 has both antioxidant and prooxidant properties in ICH. The early upregulation of HO-1 possibly fit with the events and be protective against oxidative stress, whereas its overexpression in the late stages may result in its dysfunction and be toxic. So it should be prudent to intervene ICH with the inhibitor/activator of HO-1.

A highly stereocontrolled and efficient total synthesis of (-)-stephanotic acid methyl ester and (-)-celogentin C was accomplished in longest linear 14 steps (4.6% overall yield) and in 20 steps (1.6% overall yield) from l-tryptophan, respectively. Highlights of the synthesis include a tandem asymmetric Michael addition/bromination/azidation strategy for a ready access to the leucine-tryptophan moiety (Leu-Trp linkage) and an oxidative coupling reaction to form the indole-imidazole linkage.

Marine dinoflagellates of the genus Prorocentrum are famous for the production of okadaic acid (OA) and its analogues. This review covers first the source, chemistry and bioactivity of polyketides from Prorocentrum species. Then recent advances in the studies of biosynthetic origin of OA and its analogues are included. Moreover, the pharmacophore for the selective inhibition of OA to protein phosphatases types 1 (PP1) and 2A (PP2A) is highlighted.

Histiocytoses are a heterogeneous group of disorders that are characterized by the proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: class I, Langerhans cell disease; class II, non-Langerhans cell histiocytic disease without features of malignancy; and class III, malignant histiocytic disorders. Although the disorders in classes I and II usually have a benign appearance on histology and are commonly non-aggressive and self-healing, some can cause debilitating or even fatal outcomes. Such cases beg the question: what stimulates aggressive behavior of a classically benign disease? New molecular information may now provide insight into the driving force behind many of the aggressive histiocytoses. In this article, we review Langerhans cell disease and seven aggressive histiocytoses that can involve skin, discuss histologic features that may forecast a poor prognosis, and discuss the molecular findings that help to explain the pathophysiology of these aggressive histiocytic disorders.

To obtain experimental evidence on the therapeutic efficacy of essential oils in aromatherapy for inflammatory diseases, we examined the effects of geranium oil on carrageenan-induced and collagen II-induced inflammation in mice, to assess acute and chronic anti-inflammatory activities of the oil. Single intraperitoneal injection of 5 mu L of geranium oil clearly suppressed the carrageenan-induced footpaw edema and increase in tissue myeloperoxidase activity, and repeated administration of the oil suppressed collagen-induced arthritis. These results revealed that geranium oil suppressed both acute and chronic inflammatory responses in mice.

Background: Epidermodysplasia verruciformis (EV) is a rare disorder characterized by widespread flat and common verrucae. From 25% to 50% of EV cases are inherited, usually with an autosomal recessive pattern. An X-linked inheritance has also been reported. Many EV patients have a cellular immunity defect. HIV-associated lesions have been found to contain HPV-5, HPV-8, and HPV-20., Objective: We describe two HIV-positive Hispanic maternal half brothers who presented with asymptomatic polyangular papules and plaques on the face, trunk, and extremities and which first appeared 4-5 years prior. The histopathology is consistent with EV. HPV-8 was detected by in situ hybridization. The patients were treated with topical imiquimod for two months without improvement., Conclusion: To our knowledge, this is the first reported case of epidermodysplasia verruciformis in HIV-positive pediatric patients.

The effects of picolinic acid (PLA), a product of tryptophan catabolism, on anti- Candida activity of neutrophils were studied. Casein-induced peritoneal neutrophils of C3H/He mice partially inhibited mycelial growth of Candida albicans when cultured with C. albicans for 16 h in vitro. The growth inhibition of Candida was augmented by a combination of neutrophils and more than 4 mM picolinic acid. Especially in the presence of 200 U/ml murine interferon-gamma (IFN-gamma), 2 mM picolinic acid augmented the anti- Candida activity of neutrophils. The physiological significance of the augmenting effects of picolinic acid is discussed.

This is the second reported patient with systemic juvenile xanthogranuloma (JXG) to die with liver failure. The infant was born with multiple skin lesions and mild hepatomegaly. Direct hyperbilirubinemia was noted on the 2nd day of life, followed by progressive hepatomegaly, cholestasis, and death at 29 days of age. At autopsy, nodular tumor infiltrates of JXG were present throughout the liver, as well as in skin, abdominal lymph nodes, spleen, and pancreas.

Objective: To investigate the change of gene expression after the interactions of human peripheral blood mononuclear cell (PBMC) and porcine endothelial cell., Methods: Human PBMC were co-cultured with porcine vascular endothelial cell line PIEC for 18 h. The mixed un-co-cultured PBMC and PIEC were used as controls. The cDNAs of both groups were prepared and subtracted by suppression subtractive hybridization (SSH). The up-regulated cDNAs were cloned into pGEM-T Easy vector to be sequenced. Nucleic acid homology searches were performed using the BLAST program., Results: A subtracted cDNA library was obtained through SSH and cloning, which included about 300 clones corresponding to up-regulated genes. We randomly selected 24 of these clones for sequencing tests and analysis of homology in the GenBank. Four of the 24 clones were part of known human genes, 8 were known porcines expressed sequence tag (EST), and 9 held similar homology with known human genes. Three clones were not matched., Conclusion: Many genes are up-regulated after the interaction of human PBMC and porcine endothelial cell.

Objective: To investigate the relation of Jak3 constitutive activation and acute lymphoblastic leukemia(ALL)., Methods: NALM-6 cells were treated with varying concentrations of AG490, a Jak3 inhibitor. Apoptosis and proliferation of NALM-6 cells were tested by flow cytometry (FCM) analysis and MTT assay., Results: With the exception of AG490 5 mumol/L, the AG490 10, 15, 20 mumol/L induced a strong apoptotic response in NALM-6 cells by FCM analysis(P < 0.05) and significantly inhibited the proliferation of NALM-6 cells by MTT assay(P < 0.05). All of the effects were dose-dependent., Conclusion: Jak3 inhibitor AG490 can inhibit proliferation and induce apoptosis in NALM-6 cells, and Jak3 activation is associated with pre-B ALL.