Longibramides A–E,Peptaibols Isolated from a Mushroom Derived Fungus Trichoderma longibrachiatum Rifai DMG-3-1-1

Five new peptaibols, longibramides A–E ( 1 – 5 ) with 11 amino acid residues, were isolated from a fungus Trichoderma longibrachiatum Rifai DMG-3-1-1, which was isolated from a mushroom Clitocybe nebularis (Batsch) P. Kumm collected from coniferous forest in the subboreal area of northeast China. The structures of longibramides A–E were determined by their spectroscopic data (NMR and MS-MS spectra), their absolute configurations were determined by X-ray diffractions and Marfey's analyses. The X-ray diffractions of longibramides A, B, and the similar CD spectra of A–E showed that they all had α-helix conformations. Longibramides B and E showed moderate cytotoxicities against BV2 and MCF-7 cells and also showed some inhibitory effects against methicillin-resistant Staphylococcus aureus MRSA T144. L-trans-Hyp was not commonly found in natural peptaibols, which was the 6^th or 10^th amino acid residue in longibramides C–E. The X-ray diffractions of longibramides A and B afforded the accuracy conformations of their secondary structures, which maybe help to interpret the structure-activity relationships of the family of peptaibols in the future.     

Psychobiotic Potential of Gamma-Aminobutyric Acid–Producing Marine Enterococcus faecium SH9 from Marine Shrimp

Probiotics and Antimicrobial Proteins - Psychobiotics are a novel class of probiotics with potential to confer mental wellness via production of neuroactive compounds such as gamma-aminobutyric...     

Anti-Barnacle Activities of Isothiocyanates Derived from β-Citronellol and Their Structure–Activity Relationships

Antifouling agents with low toxicity are in high demand for sustaining marine industries and the environment. This study aimed to synthesize 15 isothiocyanates derived from β-citronellol and evaluate their antifouling activities and toxicities against cypris larvae of the barnacle Amphibalanus amphitrite. The synthesized isothiocyanates exhibited effective antifouling activities (EC₅₀=0.10–3.33 μg mL⁻¹) with high therapeutic ratios (LC₅₀/EC₅₀ >30). Four isothiocyanates with an amide or isocyano group showed great potential as effective antifouling agents (EC₅₀=0.10–0.32 μg mL⁻¹, LC₅₀/EC₅₀=104–833). The enantiomers of the isothiocyanates only slightly differed in their antifouling activities. These results may serve as a basis for further research and development of β-citronellol-derived isothiocyanates as effective low-toxic antifouling agents. To the best of our knowledge, this study is the first to report the antifouling activities of isothiocyanates derived from accessible natural products.     

Gynostemosides A–E,megastigmane glycosides from Gynostemma pentaphyllum

Megastigmane glycosides (1–5) together with seven (6–12) related known compounds were isolated from the whole plants of Gynostemma pentaphyllum. The structures were elucidated by means of spectroscopic methods, including 2D NMR, HR-ESIMS, and circular dichroism (CD), as well as chemical transformations to be (3R, 4R, 5S, 6S, 7E)-3,4,6-trihydroxymegastigmane-7-en-9-one-3-O-β-d-glucopyranoside (gynostemoside A, 1), (3S, 4S, 5R, 6R, 7E, 9R)-3,4,6,9-tetrahydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside B, 2), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-9-O-β-d-glucopyranoside (gynostemoside C, 3), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside D, 4), and (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-4-O-β-d-glucopyranoside (gynostemoside E, 5), respectively.     

β-Resorcylic Acid Derivatives,with Their Phytotoxic Activities,from the Endophytic Fungus Lasiodiplodia theobromae in the Mangrove Plant Xylocarpus granatum

Nine new β-resorcylic acid derivatives, (15S)-de-O-methyllasiodiplodin ( 1 ), (13S,15S)-13-hydroxy-de-O-methyllasiodiplodin ( 2 ), (14S,15S)-14-hydroxy-de-O-methyllasiodiplodin ( 3 ), (13R,14S,15S)-13,14-dihydroxy-de-O-methyllasiodiplodin ( 4 ), ethyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate ( 5 ), ethyl 2,4-dihydroxy-6-(8-hydroxyheptyl)benzoate ( 6 ), ethyl 2,4-dihydroxy-6-(4-methoxycarbonylbutyl)benzoate ( 7 ), 3-(2-ethoxycarbonyl-3,5-dihydroxyphenyl)propionic acid ( 8 ), and isobutyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate ( 9 ), together with a known ethyl 2,4-dihydroxy-6-(8-oxononyl)benzoate ( 10 ) were obtained from Lasiodiplodia theobromae GC-22. The structures of these compounds were elucidated by extensive spectroscopic analyses. Compounds 1 , 3 , and 6 showed growth inhibitory effects against Digitaria ciliaris. Conversely, treatment with compounds 5 , 6 , 7 , 9 , and 10 stimulated elongation activity toward the root of Lactuca sativa. These data expand the repertoire of new β-resorcylic acid derivatives that may function as lead compounds in the synthesis of new agrochemical agents.     

Stachybotrysams A–E,prenylated isoindolinone derivatives with anti-HIV activity from the fungus Stachybotrys chartarum

Four new farnesylated isoindolinone derivatives, named stachybotrysams A–D (2–5), and one new farnesyl-cyclized analogue, named stachybotrysam E (6), as well as one known congener (1), were isolated from the filamentous fungus Stachybotrys chartarum CGMCC 3.5365. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and by comparison with reported data. Compounds 2–4 exhibited significant HIV-inhibitory activity with IC₅₀ values of 9.3, 1.0, and 9.6 μM, respectively.     

Tumstatin,a Matrikine Derived from Collagen Type IVα3, is Elevated in Serum from Patients with Non–Small Cell Lung Cancer

OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tumstatin as a diagnostic biomarker of lung disorders. METHODS: A monoclonal antibody was raised against the neo-epitope tumstatin. A novel competitive enzyme-linked immunosorbent assay for detection of tumstatin (TUM), was developed and technically characterized. Levels of TUM were measured in serum of patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and non–small cell lung cancer (NSCLC) belonging to two cohorts. RESULTS: The developed TUM enzyme-linked immunosorbent assay (ELISA) was technically robust. In cohort 1, levels of TUM were significantly higher in NSCLC compared to healthy controls, IPF, and COPD (P = 0.007, P = 0.03 and P = 0.001, respectively). The area under the receiver operating characteristics (AUROC) for separation of patients with NSCLC from healthy controls was 0.97, for separation of NSCLC and IPF patients was 0.98, and for separation of NSCLC and COPD patients was 1.0. In cohort 2, levels of TUM were also significantly higher in patients with NSCLC compared to healthy controls (P = 0.002), and the AUROC for separation of NSCLC and healthy controls was 0.73. CONCLUSIONS: We developed a technically robust competitive ELISA targeting the fragment tumstatin. The level of TUM in circulation was significantly higher in patients with NSCLC compared to patients with IPF, COPD and healthy controls. The assay provided high diagnostic accuracy in separating NSCLC patients from other lung disorders and from healthy controls.     

Soymorphins,Novel μ Opioid Peptides Derived from Soy β-Conglycinin β-Subunit,Have Anxiolytic Activities

Based on the amino acid sequence YPFV found in the soy β-conglycinin β-subunit, which is common to an opioid peptide human β-casomorphin-4, peptides YPFVV, YPFVVN, and YPFVVNA were synthesized according to their primary structure. On guinea pig ileum (GPI) assay, they showed opioid activity (IC₅₀ = 6.0, 9.2 and 13 μM respectively) more potent than human β-casomorphins, and were named soymorphins-5, -6, and -7, respectively. Their opioid activities on mouse vas deferens (MVD) assay were less potent than on GPI assay, suggesting that they are selective for the μ opioid receptor. Human β-casomorphin-4 and soymorphin-5 were released from the soy 7S fraction (β-conglycinin) by the action of gastrointestinal proteases. Soymorphins-5, -6, and -7 had anxiolytic activities after oral administration at doses of 10–30 mg/kg in the elevated plus-maze test in mice.     

Bioactive Peptides from Marine Ascidians and Future Drug Development–A Review

Marine ascidians are considered as one of the richest sources of bioactive compounds. The extraction and utilization of marine peptides have been attracted much attention owing to their potential health benefits. Most of the bioactive compounds from marine ascidians are already in different phases of the clinical and preclinical pipeline. They can be used in different functional and nutraceutical values due to their antineoplastic, antihypertensive, antioxidant, and antimicrobial properties. The screening in vivo and in vitro bioassays are coupled to the purification process for the exploration of its biological interest which is of great value. The growing significance to study marine natural products results from the discovery of novel pharmacological tools including potent anticancer drugs and other drugs are in clinical/pre-clinical trials. The present review highlights the recent research progress in marine ascidians’ peptides and its prospects for the future pharmaceutical development.     

Amenyunnaosides A–C,Three New Neolignans Isolated from Amentotaxus yunnanensis and Their Anti-inflammatory Activities

Phytochemical study on the leaves of Amentotaxus yunnanensis led to the isolation of seventeen phenolic compounds including sixteen neolignans and lignans, and one flavone glycoside. Three among the isolates were previously unreported neolignans and named as amenyunnaosides A–C, respectively. Their structures were elucidated by extensive analyses of HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The isolated neolignans potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC₅₀ values ranging from 11.05 to 44.07 μM, compared to that of the positive control compound, dexamethasone, IC₅₀ value of 16.93 μM. Additionally, amenyunnaoside A dose-dependently reduced production of IL-6 and COX-2 but did not effect to that of TNF-α at concentrations of 0.8, 4, and 20 μM.     

Hyposterolactone A,a 3α-Hydroxy Steroidal Lactone from the Deep-Sea-Derived Fungus Hypocrea sp. ZEN14

Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A ( 1 ) and 25 known secondary metabolites ( 2 – 26 ). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC₅₀ values of 1.4 μM and 6.7 μM, respectively.     

Myrothins A–F from Endophytic Fungus Myrothecium sp. BS-31 Harbored in Panax notoginseng

Endophytic fungi play important roles for host's stress tolerance including invasion by pathogenic microbes. Small molecules are common weapons in the microbe–microbe interactions. Panax notoginseng is a widely used traditional Chinese medicinal plant and harbors many endophytes, some exert functions against pathogens. Here, we report six new compounds named myrothins A–F ( 1 – 6 ) produced by Myrothecium sp. BS-31, an endophyte isolated from P. notoginseng, and their antifungal activities against pathogenic fungi causing host root-rot disease. Their structures were elucidated with analysis of spectroscopic data including 1D and 2D NMR, HR-ESI-MS. Myrothins B ( 2 ) and E ( 5 ) showed the weak activity against Fusarium oxysporum and Phoma herbarum, and myrothins F ( 6 ) showed weak activity against F. oxysporum.     

Callicarpanes A–L,Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima

Twelve new clerodane diterpenoids named callicarpanes A–L ( 1 – 12 ), together with eight known compounds ( 13 – 20 ), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1 , 3 , 5 , 9 , 10 , 12 , 15 , 16 , and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC₅₀ against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 μM. Further study revealed that compound 10 repressed IL-1β secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.     

Pestalofones A–E,bioactive cyclohexanone derivatives from the plant endophytic fungus Pestalotiopsis fici

Pestalofones A–E (1–5), five new cyclohexanone derivatives, have been isolated from cultures of the plant endophytic fungus Pestalotiopsis fici, along with the known compounds, isosulochrin (6), isosulochrin dehydrate (7), and iso-A82775C (8). The structures of 1–5 were determined by NMR spectroscopy, and the absolute configuration of 1 was assigned using the modified Mosher method. Compounds 1, 2, and 5 displayed inhibitory effects on HIV-1 replication in C8166 cells, whereas 3 and 5 showed significant antifungal activity against Aspergillus fumigatus.     

A Transcriptional Signature of Fatigue Derived from Patients with Primary Sj?gren’s Syndrome

Background

Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.

Methods

Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren’s Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W).

Results

Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively.

Conclusions

Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.     

Bistachybotrysins A–C,three phenylspirodrimane dimers with cytotoxicity from Stachybotrys chartarum

Bistachybotrysins A–C (1–3), three phenylspirodrimane dimers representing an unusual [6,6,7,6]-tetracyclic skeleton with a central 2,10-dioxabicyclo[4.3.1]decan-7-ol core fused with two phenyl units, were isolated from a fungal strain, Stachybotrys chartarum CGMCC 3.5365. The structures of 1–3 were elucidated through extensive spectroscopic data analysis, including Mo₂(AcO)₄-induced and calculated electronic circular dichroism (ECD). 1 and 2 exhibited potent cytotoxicity against four human tumor cell lines with IC₅₀ values in the range of 2.8–7.5?μM. Furthermore, a possible biogenesis for 1–3 is proposed.     

Calofolic acids A–F,chromanones from the bark of Calophyllum scriblitifolium with vasorelaxation activity

Vasorelaxation activity guided separation of the methanol extract of Calophyllum scriblitifolium bark led to the isolation of 6 chromanones (calofolic acids A–F, 1–6). Their structures were elucidated by 1D and 2D NMR spectroscopy, and their absolute configurations were investigated by a combination of CD spectroscopy and DFT calculation. All isolated chromanones showed dose-dependent vasorelaxation activity on isolated rat aorta.     

A U-Box E3 Ubiquitin Ligase,PUB20, Interacts with the Arabidopsis G-Protein β Subunit,AGB1

An Arabidopsis U-box E3 ubiquitin ligase Plant U-box 20 (PUB20; alternatively called AtCMPG1) was identified as a possible interactor of the Arabidopsis G-protein β subunit, AGB1, by yeast two-hybrid screening. A bimolecular fluorescence complementation (BiFC) assay showed that PUB20 interacted with AGB1 in the nuclei and the cytosol. The expression levels of PUB20 and its closest homolog, PUB21 were stable under many conditions. GUS driven by the PUB20 promoter was active in anthers, pollen, premature seeds and receptacles and GUS driven by the PUB21 promoter was active in anthers and funiculi. PUB20 was found to have autoubiquitination activity in vitro.     

Hyperpatulols A–I,spirocyclic acylphloroglucinol derivatives with anti-migration activities from the flowers of Hypericum patulum

Nine new spirocyclic acylphloroglucinol derivatives, hyperpatulols A–I (1–9), were characterized from the flowers of Hypericum patulum. Their structures were elucidated by the basic analysis of the obtained spectroscopic data, and their absolute configurations were assigned by both the electronic circular dichroism (ECD) exciton chirality method and ECD calculation. The evaluation of their anti-migration effects on U2-OS human osteosarcoma cells showed that compound 4 exhibited moderate inhibitory activity in a dose-dependent manner. Further pharmacological studies revealed that 4 could regulate the expression of the proteins Vimentin and E-cadherin.