A new secondary metabolite from the marine-derived fungus Phomopsis lithocarpus FS508.

Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities.

Cytotoxic meroterpenoids from the marine sponge Dactylospongia elegans.

Three new sesquiterpene quinones/hydroquinones, 20-demethoxy-20-isopentylaminodactyloquinone D (1), 20-demethoxy-20-isobutylaminodactyloquinone D (2), and 19-methoxy-dictyoceratin-A (3), and five known related compounds (4-8) were isolated from the marine sponge Dactylospongia elegans. Their structures were elucidated by spectroscopic analysis, ECD calculation, single-crystal X-ray diffraction, and comparison with the literature. Compounds 3 and 5-8 exhibited activities against the human cancer cell lines DU145, SW1990, Huh7, and PANC-1 with IC50 values ranging from 2.33 to 37.85 µM.

Surgical treatment ofpatients with severe non-flail chest rib fractures.

BACKGROUND: Many patients have inadequate long-term analgesia, respiratory distress, and hypoxemia due to a long-standing substantial smoking history or the presence of primary pulmonary diseases; analgesic treatment is not valid in these patients. Even if the imaging findings of rib fractures are relatively mild, rib fractures may cause severe position limitation, respiratory distress, and hypoxemia. AIM: To investigate the curative effect of surgical treatment for patients with severe non-flail chest rib fractures. METHODS: A total of 78 patients from our hospital with severe noncontinuous thoracic rib fractures from September 2016 to September 2018 were enrolled in our study. Thirty-nine patients underwent surgical treatment, and 39 underwent conservative treatment. The surgical treatment group received surgery performed with titanium plates, and the screws were inserted with open reduction and internal fixation. The conservative treatment group received analgesia and symptomatic treatment. The pain scores at 72 h, 1 wk, 2 wk, 4 wk, 6 wk, 3 mo, and 6 mo were compared, and the SF-36 quality of life scores were compared atthe 3rd and 6th months. RESULTS: Pain relief in the surgical group was significantly better than that in the conservative group at each time point (72 h, 1 wk, 2 wk, 4 wk, 6 wk, 3 mo, and 6 mo after surgery, P < 0.001). ( The SF-36 scores were significantly higher in the surgical group than in the conservative group at 1 mo and 6 mo (P < 0.05). CONCLUSION: Patients with severe non-flail chest rib fractures have a better quality of life following surgical treatment than following conservative treatment, and surgical treatment is also useful for relieving pain. We should pay more attention to the physiological functions and clinical manifestations of patients with severe rib fractures. In patients with non-flail chest rib fractures, surgical treatment is feasible and effective.

Eutypellacytosporins A-D, Meroterpenoids from the Arctic Fungus Eutypella sp. D-1.

The Arctic fungus Eutypella sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (1-4), along with the known biogenetically related compound cytosporin D (5). The structures of the new compounds were elucidated by their detailed spectroscopic analysis and modified Mosher's method. Compounds 1-4 may be formed by the 12,32-ester linkage of two moieties, cytosporin D (5) and decipienolide A or B. All isolated compounds, except 5, showed weak cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cell lines with IC50 values ranging from 4.9 to 17.1 µM.

MicroRNA-422a functions as a tumor suppressor in non-small cell lung cancer through SULF2-mediated TGF-ß/SMAD signaling pathway.

MicroRNAs (miRNAs) have been demonstrated to participate in a variety of human cancers by functioning as post-transcriptional regulators of oncogenes or antioncogenes including non-small cell lung cancer (NSCLC). The aim of the current study was to identify the role of miR-422a in NSCLC via sulfatase 2 (SULF2) to further elucidate the mechanism of NSCLC. Initially, the expression of miR-422a and SULF2 was determined in NSCLC tissues and cells. The role of miR-422a in NSCLC was identified in relation with a miR-422a mimic or inhibitor, siRNA against SULF2 and TGF-ß1. The regulatory effects of miR-422a were examined following detection of the related epithelial mesenchymal transition (EMT)-related genes, and the apoptosis-related genes and evaluation of their cellular biological functions. The expression pattern of miR-422a, SULF2, and the TGF-ß/SMAD pathway-related genes was detected to elucidate the mechanism by which miR-422a influences the progression of NSCLC. Finally, xenograft tumors in nude mice were observed for tumorigenicity evaluation purposes. Our results showed that miR-422a was poorly expressed while SULF2 was highly expressed in NSCLC. Dual luciferase reporter gene assay further verified that miR-422a targeted SULF2. Altogether, this study demonstrated that miR-422a downregulated SULF2 to inhibit the TGF-ß/SMAD pathway. NSCLC cell proliferation, migration, invasion, colony formation, EMT and tumorigenesis were all inhibited while apoptosis was promoted upon restoration of miR-422a or silencing of SULF2. However, the activation of the TGF-ß/SMAD pathway was determined to reverse the tumor-suppressive effects of si-SULF2. miR-422a restoration, which ultimately inhibited the progression of NSCLC by suppressing the TGF-ß/SMAD pathway via SULF2.

Bioactive metabolites from the Arctic fungus Nectria sp. B-13.

Two new cyclohexanone derivatives, nectriatones A-B (1-2), and one new natural product, nectriatone C (3), together with three known phenolic sesquiterpene derivatives (4-6), were isolated from the culture of Nectria sp. B-13 obtained from high-latitude soil of the Arctic. The structures of all compounds were unambiguously elucidated by extensive spectroscopic analysis, as well as by comparison with the literature. These compounds were evaluated in cytotoxic and antibacterial activities. Compounds 1-6 showed cytotoxicities against SW1990, HCT-116, MCF-7, and K562 cells, with IC50 values in the range of 0.43 to 42.64 µM. Only compound 4 exhibited antibacterial activity against Escherichisa coli, Bacillus subtilis, and Staphylococcus aureus (MIC 4.0, 2.0, and 4.0 µg/ml, respectively).

Eutypellenoids A⁻C, New Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D-1.

Three new pimarane diterpenes, eutypellenoids A⁻C (1⁻3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1⁻3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 µg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candidaparapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 µg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 µM.

Libertellenones O-S and Eutypellenones A and B, Pimarane Diterpene Derivatives from the Arctic Fungus Eutypella sp. D-1.

Seven new pimarane-type diterpene derivatives, libertellenones O-S (1-5) and eutypellenones A and B (6 and 7), together with two known compounds (8 and 9), were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures were elucidated from spectroscopic data, as well as experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 1-5 possess a cyclopropyl-fused pimarane diterpene moiety, whereas compounds 6 and 7 share an unusual cyclobutyl-fused pimarane diterpene skeleton. Compounds 1-9 exhibited cytotoxicities against HeLa, MCF-7, HCT-116, PANC-1, and SW1990 cells, with IC50 values in the range of 0.3 to 29.4 µM. Compounds 6 and 7 could dose-dependently inhibit the activity of NF-κB and exhibited significantly inhibitory effects on nitric oxide production induced by lipopolysaccharide.

Biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9.

The biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2), and lecaniside C (3). The chemical structures of these metabolites were elucidated based on extensive spectral data, including 2D NMR and HRMS. The hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these metabolites were observed in the present study. In the in vitro assays, compound 1 displayed a little PTP1B inhibitory activity.

Using a new plateau hyperbaric chamber to alleviate high altitude hypoxia: Rabbit and human studies.

OBJECTIVES: To validate the effects of the new plateau hyperbaric chamber on alleviating high altitude hypoxia on Mount Kun Lun. METHODS: A prospective, controlled study of rabbits and adult volunteers was conducted at altitudes of 355, 2880 and 4532m. We obtained arterial blood samples from rabbits and volunteers before and after hyperbaric treatment. The respiratory rate, heart rate, and blood pressure (BP) of adult volunteers were monitored during hyperbaric treatment. RESULTS: The mean PaO2 levels of experimental group rabbits and volunteers increased significantly after 60min of hyperbaric treatment at 350, 2880 and 4532m. The mean PaCO2 and pH levels of rabbits were not significant different before and after hyperbaric treatment at each altitude. The mean PaCO2 and pH levels were not significant different at 355m in the human study. However, at 2880 and 4532m, pH fell with increasing PaCO2 levels in humans before and after hyperbaric treatment. CONCLUSIONS: The new multiplace plateau hyperbaric chamber may be used to alleviate plateau hypoxia by increasing patient PaO2. However, its value in treating AMS must be confirmed in field conditions.

A new sesquiterpene lactone from fungus Eutypella sp. D-1.

We isolated and identified a new sesquiterpene lactone which we named eut-Guaiane sesquiterpene (1), along with four cytochalasins from the fungus Eutypella sp. derived from the soil of high latitude of Arctic. The new structure was determined by spectroscopic studies such as 1D and 2D NMR and MS analyses, while the known compounds were identified by comparison of the NMR data with those in literatures. New compound 1 exhibited strong antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Besides, it showed a little cytotoxicity against SGC7901 cell line.

Development and preliminary test of a new plateau hyperbaric chamber.

OBJECTIVE: The objective of this study is to validate the performance, define its limits, and provide details on a new plateau hyperbaric chamber at 355-, 2880-, and 4532-m high altitude. METHODS: A new multiplace plateau hyperbaric chamber was designed to satisfy the needed of patients who have acute mountain sickness. Tests were conducted inside the chamber at 355-, 2880-, and 4532-m high altitude. The safely and conveniences of the new plateau hyperbaric chamber were estimated. RESULTS: Minimum pressures of the main compartment can reach up to 0.029, 0.022, and 0.02 MPa at 355-, 2880-, and 4532-m high altitude. During pressurization, there was no leak of air around the chamber. The time lag of pressure equilibration between main and buffer compartment varies from 30.3±2.01 to 200.5±5.44 seconds and between buffer compartment and ambient pressure varies from 60.2±4.13 to 215.9±6.76 seconds. CONCLUSIONS: The chamber can be applicated for acute mountain sickness treatment safety and convenience. However, further experience about animals and human within the chamber is needed to improve the hardware and establish conditions of effective utilization of this equipment in the high altitude.

Silencing profilin-1 inhibits gastric cancer progression via integrin ß1/focal adhesion kinase pathway modulation.

AIM: To investigate the role of profilin-1 (PFN1) in gastric cancer and the underlying mechanisms. METHODS: Immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect PFN1 expression in clinical gastric carcinoma and adjacent tissues, and the association of PFN1 expression with patient clinicopathological characteristics was analyzed. PFN1 was knocked down to investigate the role of this protein in cell proliferation and metastasis in the SGC-7901 cell line. To explore the underlying mechanisms, the expression of integrin ß1 and the activity of focal adhesion kinase (FAK) and the downstream proteins extracellular-regulated kinase (ERK)1/2, P38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) were measured through Western blot or qRT-PCR analysis. Fibronectin (FN), a ligand of integrin ß1, was used to verify the correlation between alterations in the integrin ß1/FAK pathway and changes in tumor cell aggressiveness upon PFN1 perturbation. RESULTS: Immunohistochemical, Western blot and qRT-PCR analyses revealed that PFN1 expression was higher at both the protein and mRNA levels in gastric carcinoma tissues compared with the adjacent tissues. In addition, high PFN1 expression (53/75, 70.4%) was correlated with tumor infiltration, lymph node metastasis and TNM stage in gastric cancer, but not with gender, age, location, tumor size, or histological differentiation. In vitro experiments showed that PFN1 knockdown inhibited the proliferation of SGC-7901 cells through the induction G0/G1 arrest. Silencing PFN1 inhibited cell migration and invasion and down-regulated the expression of matrix metalloproteinase (MMP)-2 and MMP9. Moreover, silencing PFN1 reduced the expression of integrin ß1 at the protein level and inhibited the activity of FAK, and the downstream effectors ERK1/2, P38MAPK, PI3K, AKT and mTOR. FN-promoted cell proliferation and metastasis via the integrin ß1/FAK pathway was ameliorated by PFN1 silencing. CONCLUSION: These findings suggest that PFN1 plays a critical role in gastric carcinoma progression, and these effects are likely mediated through the integrin ß1/FAK pathway.

Traditional Chinese medicine--sea urchin.

The sea urchin is an ancient, common, seafloor-dwelling marine invertebrate that belongs to the phylum Echinodermata. There are multiple species of sea urchin with resources that are widely distributed in China, where they were used in ancient times as Traditional Chinese Medicine for treating a variety of diseases. At present, it is known that the shell, spine and gonad of the sea urchin have many medicinal values determined through modern research. In this paper, we summarized the major chemical constituents and medicinal value of the sea urchin.

Bioactive tyrosine-derived cytochalasins from fungus Eutypella sp. D-1.

Three new cytochalasins Z24 , Z25 , Z26 (1-3, resp.) and one known compound, scoparasin B (4), were isolated from the fungus Eutypella sp. D-1 isolated from the soil of high latitude of the Arctic. The structures of 1-3 were elucidated from spectroscopic data (NMR, MS). These compounds were evaluated for cytotoxic activities against several human tumor cell lines. Among them, compound 1 exhibited moderate cytotoxicity toward human breast cancer MCF-7 cell line with IC50 of 9.33 µM.

A new aromatic glycoside from Glehnia littoralis.

A new aromatic glycoside (1) was isolated from the roots of Glehnia littoralis Fr. Schmidtex Miq. Its structure was elucidated as vanillic acid 1-O-[ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside] ester mainly by analysing the NMR and MS spectral data. In the in vitro assays, compound 1 displayed some TNF-α secretion inhibitory activity.

Glycosylation of the sodium channel ß4 subunit is developmentally regulated and involves in neuritic degeneration.

Aberrant protein glycosylation plays major roles in neurodegenerative diseases, including Parkinson's disease (PD). Glycoproteomics showed that the glycosylation of sodium channel ß4 was significantly increased in human brain tissue. ß4-specific antibodies reacted in immunoblot assays with the 35- and 38-kDa bands from the membrane fractions isolated from neonatal PD transgenic mice but only with the 35-kDa band of the neonatal wild-type mice. The size of the 38-kDa immunoreactive protein is in close agreement with previously reported, suggesting heavy glycosylation of this protein in adult wild-type and neonatal PD transgenic brain tissues. However, the neonatal wild-type mice membrane fractions only contained the 35-kDa immunoreactive protein, and the additional 38-kDa band was not shown until postnatal day 7. Enzymatic deglycosylation of the membrane preparations only converted the 38-kDa band into a faster migrating protein, which was consistent with heavy glycosylation of this protein. The glycosylated state of ß4 was developmentally regulated and was altered in disease state. Neurite outgrowth assay demonstrated that overexpression of deglycosylated mutant ß4-MUT accelerated neurite extension and increased the number of filopodia-like protrusions, when compared with ß4-WT and the vector. These results suggest that extensive glycosylation of ß4 subunit play roles in morphological changes, and the altered glycosylation may be involved in the pathogenesis of PD.

Disorders in angiogenesis and redox pathways are main factors contributing to the progression of rheumatoid arthritis: a comparative proteomics study.

OBJECTIVE: To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in fibroblast-like synoviocytes (FLS) from patients with RA with that in FLS from normal subjects, using proteomics analysis. METHODS: Proteins extracted from primary cultures of FLS obtained from 50 patients with RA and 10 normal subjects were analyzed by automated 2-dimensional nano-electrospray ionization liquid chromatography tandem mass spectometry. Differentially expressed proteins were screened by 2-sample t-test (P < 0.05) and fold change (>1.5), based on the bioinformatics analysis. The expression of vasculature development-related proteins (Thy-1, connective tissue growth factor [CTGF], and thrombospondin 1 [TSP-1]) and redox-related proteins (superoxide dismutase 2 [SOD2]) in synovial tissue was confirmed by real-time polymerase chain reaction and Western blotting. The effect of Thy-1 and CTGF knockdown on Thy-1, CTGF, TSP-1, and vascular endothelial growth factor (VEGF) was analyzed by RNA interference experiments. RESULTS: According to the criteria of having >1 unique peptide per protein present and a false discovery rate of ≤5%, 1,060 proteins were identified from patients with RA, and 1,292 proteins were identified from normal subjects, from which 100 differentially expressed proteins were screened out from the RA proteins. Of these, 46 proteins were up-regulated, and the remaining 54 proteins were down-regulated. Gene ontology and pathway analyses showed that 6 vasculature development-related proteins were up-regulated, including Thy-1, CTGF, and TSP-1, while 11 redox-related proteins were down-regulated, including SOD2. The results were consistent with those obtained using mass spectrometry. Thy-1, VEGF, CTGF, and TSP-1 were down-regulated after Thy-1 knockdown, and VEGF and CTGF were down-regulated after CTGF knockdown. Recombinant human CTGF could enhance proliferation and Transwell migration of human umbilical vein endothelial cells. CONCLUSION: Up-regulation of vasculature development-related proteins and down-regulation of redox-related proteins in FLS are predominant factors that may contribute to the pathogenesis of RA.