Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

Investigation on toxicity mechanism of halogenated aromatic disinfection by-products to zebrafish based on molecular docking and QSAR model.

Halogenated aromatic disinfection by-products (DBPs) are a new type of DBPs that have been detected in various water bodies. Previous studies have shown that most of them can induce in vivo toxicity in aquatic organisms. In this study, in order to further investigate the toxic effects and mechanisms of aromatic DBPs, the toxicity and ecological risks of 10 halogenated aromatic DBPs were assessed using the model organism zebrafish. It was found that the toxicity of DBPs was related to the number, type, and position of halogen and the type of substituent, and the 24 h-toxicity value of DBPs in this experiment could replace their 96 h-toxicity value to reduce the test time and save the test cost. Halogenated phenol and halogenated nitrophenol were more toxic, but the current ecological risks of DBPs were relatively low. In addition, the toxicity mechanism of DBPs was analyzed based on molecular docking and quantitative structure-activity relationship (QSAR) models. The molecular docking results showed that all 10 DBPs could bind to zebrafish's catalase (CAT), cytochrome P450 (CYP450), p53, and acetylcholinesterase (AChE), thereby affecting their normal life activities. QSAR models indicated that the toxicity of halogenated aromatic DBPs to zebrafish mainly depended on their hydrophobicity (log D), the interaction with CAT (ECAT), and hydrogen bonding acidity (A).

Increased expression of LINC00323 correlates with tumor progression and poor prognosis of gastric cancer.

BACKGROUD/AIMS: LINC00323 is a novel lncRNA which has reported to play an important role in the development and recurrence in several cancers. However, the expression and predictive value of LINC00323 in gastric cancer (GC) remain mysterious. METHODS: LINC00323 expression in GC tissues and adjacent normal tissues was evaluated by quantitative reverse-transcription PCR (qRT-PCR). The relationship between LINC00323 expression and clinicopathological features and patients' survival were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: LINC00323 expression were found to be significantly increased in GC tissues. High expression of LINC00323 exerted a pro-tumor effect in the late stage of GC development. Kaplan-Meier analysis showed that patients with high LINC00323 were associated with poor overall survival (OS) and progression-free survival (PFS). Moreover, the combination of TNM stage and drinking status better identified GC patient outcome than those of TNM stage alone. CONCLUSIONS: Our data showed that LINC00323 overexpression might serve as a novel independent prognostic factor for survival of GC patients, suggesting LINC00323 was a potential biomarker and therapeutic target for GC.

Two unusual novel iridoid glycosides from Cornus officinalis fruit and their biological activities.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

Three new ursane-type triterpenoids from Rosmarinus officinalis and their biological activities.

Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3ß-hydroxyurs-12-en-20, 28-olide (2) and 3ß-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 µg·mL-1.

New polymerized sesquiterpene lactones from Ainsliaea yunnanensis and their activity evaluation.

Two new dimeric and trimeric sesquiterpene lactones (1-2), and nine known sesquiterpene lactones (3-11) were isolated from the EtOAc phase of the ethanolic extract of Ainsliaea yunnanensis. Their structures were identified by NMR, IR and HR-ESIMS spectroscopic methods, and compound 1 was confirmed by single crystal X-ray diffraction experiment. All the compounds were tested for their cytotoxic, anti-microbial and anti-inflammatory activities. Compounds 1, 2, 3, 5, 7, 9 and 11 showed very significant selective cytotoxic activities on MDA-MB-468, PANC-1, HEPG2 or A549 cells. Compounds 6 and 11 showed very significant inhibiting effect on Epicoccum sp. (CPCC 400307), Fusarium solani (CPCC 800013) or Bacillus subtilis. Meanwhile, compounds 6 and 7 can inhibit the NLRP3 inflammasome's activation at the concentration of 10 µM.

Secoiridoid glycosides from the fruits of Cornus officinalis.

Five new secoiridoid glycosides, cornusphenosides E-I (1-5), were isolated and characterized from an active fraction of ethanol extract of the fruits of Cornus officinalis. Their structures were determined by extensive spectroscopic data analysis, including 2 D NMR and HRESIMS experiments. In the preliminary assay, compound 5 (when evaluated at 10 µM) showed the neuroprotective effect against H2O2-induced SH-SY5Y cell damage.

Norursane-type triterpenoids from Rosmarinus officinalis and their anti-inflammatory activity evaluation.

Five norursane-type triterpenoids, including three novel of 3ß-28-norursa-12,17,19,21-tetraene-3-ol (1), 3ß-28-norursa-12,20(30)-dien-3-ol (2) and 3ß-28-norursa-12,16,20(30)-triene-3-ol (3), as well as two known 3ß-28-norursa-17,19,21-trien-3-ol (4) and 3ß-28-norursa-12-ene-3-ol (5) were isolated from the ethyl acetate dissolved fraction of the ethanol extract from Rosmarinus officinalis. Their structures were elucidated by HR-ESI-MS, IR, 1D- and 2D-NMR spectroscopic methods. Compounds 1-5 exhibited significant inhibitory effect on NO production in LPS-activated RAW264.7 cells, and compounds 2, 3 and 5 shown better anti-inflammatory activity.

Chemical characterization of a PD-1/PD-L1 inhibitory activity fraction of the ethanol extract from Gymnadenia conopsea.

Searching for PD-1/PD-L1 inhibitor from medicinal plants has become a potential method to discover small molecular cancer immunotherapy drugs. Using PD-1/PD-L1 inhibitory activity assay in vitro, a bioactive fraction was obtained from the ethanol extract of Gymnadenia conopsea. A sensitive UPLC-HRMS/MS method was established for the rapid screening and identification of compositions from bioactive fraction. Based on the characteristic fragmentation patterns of standards analysis and extracted ion chromatogram (EIC) method, 46 compounds were rapidly screened and identified (including 35 succinic acid ester glycosides and 11 other compounds), among which 17 compounds were tentatively identified as new compounds.

Rapid Characterizaiton of Chemical Constituents of the Tubers of Gymnadenia conopsea by UPLC-Orbitrap-MS/MS Analysis.

Gymnadenia conopsea R. Br. is a traditional Tibetan medicinal plant that grows at altitudes above 3000 m, which is used to treat neurasthenia, asthma, coughs, and chronic hepatitis. However, a comprehensive configuration of the chemical profile of this plant has not been reported because of the complexity of its chemical constituents. In this study, a rapid and precise method based on ultra-high performance liquid chromatography (UPLC) combined with an Orbitrap mass spectrometer (UPLC-Orbitrap-MS/MS) was established in both positive- and negative-ion modes to rapidly identify various chemical components in the tubers of G. conopsea for the first time. Finally, a total of 91 compounds, including 17 succinic acid ester glycosides, 9 stilbenes, 6 phenanthrenes, 19 alkaloids, 11 terpenoids and steroids, 20 phenolic acid derivatives, and 9 others, were identified in the tubers of G. conopsea based on the accurate mass within 3 ppm error. Furthermore, many alkaloids, phenolic acid derivates, and terpenes were reported from G. conopsea for the first time. This rapid method provides an important scientific basis for further study on the cultivation, clinical application, and functional food of G. conopsea.

Polyhydroxylated sterols from Monascus purpureus-fermented rice.

Using a cell-based cytotoxicity assay, two new polyhydroxylated sterols, 16(S),22(S)-epoxy-3ß,5α,6ß,20(R),23(R),25-hexahydroxy-7-ergostene and 3ß,7ß,8α,25-tetrahydroxy-5,22E-ergostadiene were isolated from the ethyl acetate portion of the ethanolic extract of Monascus purpureus. Their structures were elucidated by spectroscopic analysis and in comparison with those reported in the literature. Both compounds showed cytotoxic activity against the lung adenocarcinoma (A549) with IC50 values of 12.6 and 18.5 µM, exhibited moderate activities against human ovarian cancer (A2780), with IC50 values of 8.8 and 9.4 µM.

Taraxastane-type triterpenoids from the medicinal and edible plant Cirsium setosum.

Guided by TNF-α secretion inhibitory activity assay, four taraxastane-type triterpenoids, including two new ones, 22-oxo-20-taraxasten-3ß, 30-diol (1) and 22α-hydroxy-20-taraxasten-30ß, 30-triol (2), have been obtained from an active fraction of the petroleum ether-soluble extract of the the medicinal and edible plant Cirsium setosum. Their structures were elucidated by spectroscopic data and CD data analysis. In the TNF-α secretion inhibitory activity assay, compounds 1 and 2 were active with the IC50 of 2.6 and 3.8 µmol·L-1, respectively. In addition, compounds 1 and 2 showed moderately selective cytotoxicity against the human ovarian cancer (A2780) and colon cancer (HCT-8) cell lines.

New Iridoid Derivatives from the Fruits of Cornus officinalis and Their Neuroprotective Activities.

Three previously undescribed iridoids, cornusfurals A⁻C, were isolated from the ethanolic extracts of fruits of Cornus officinalis. Their structures were elucidated by spectroscopic methods, including one-dimensional and two-dimensional nuclear magnetic resonance, ultraviolet spectroscopy, infrared spectroscopy, and mass spectrometry. The neuroprotective activity was evaluated by measuring corticosterone-induced damage in PC12 cells. The results showed that cornusfural B decreased corticosterone-induced PC12 cell damage compared with that in model cells.

Iridoid glycosides from the fruits of Cornus officinalis.

Four new iridoid glycosides named cornusphenosides A-D (1-4) were isolated from an ethanol extract of the fruits of Cornus officinalis (shan zhu yu). The structures of these compounds were elucidated on the basis of spectroscopic data (UV, IR, HRESIMS, and 1D and 2D NMR) and chemical evidence. The neuroprotective effects of compounds 1-4 were also assessed in vitro.

Novel Natural Products from Extremophilic Fungi.

Extremophilic fungi have been found to develop unique defences to survive extremes of pressure, temperature, salinity, desiccation, and pH, leading to the biosynthesis of novel natural products with diverse biological activities. The present review focuses on new extremophilic fungal natural products published from 2005 to 2017, highlighting the chemical structures and their biological potential.

Four new monacolin analogs from Monascus purpureus-fermented rice.

Four new monacolin analogs, monacolin T (1), monacolin U (2) 6a-O-methyl-4,6-dihydromonacolin L (3), and 6a-O-ethyl-4,6-dihydromonacolin L (4) were isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures were determined by a combination of 1D, 2D NMR experiments (1H-1HCOSY, HSQC, HMBC, and ROESY), and mass spectrometry. In vitro cytotoxic assay, all compounds were inactive at the concentration of 10 µM.

Synthesis of Reabsorption-Suppressed Type-II/Type-I ZnSe/CdS/ZnS Core/Shell Quantum Dots and Their Application for Immunosorbent Assay.

We report a phosphine-free one-pot method to synthesize ZnSe/CdS/ZnS core-shell quantum dots (QDs) with composite type-II/type-I structures and consequent reabsorption suppression properties. The as-synthesized QDs possess high efficient red emission (with quantum yield of 82%) and high optical stability. Compared to type-I QDs, the ZnSe/CdS/ZnS QDs show larger Stokes shift and lower reabsorption which can reduce the emission loss and improve the level of fluorescence output. The ZnSe/CdS/ZnS QDs are used as fluorescent labels to exploit their application in fluorescence-linked immunosorbent assay (FLISA) for the first time in the detection of C-reactive protein (CRP) with a limit of detection (LOD) of 0.85 ng/mL, which is more sensitive than that of CdSe/ZnS type-I QDs based FLISA (1.00 ng/mL). The results indicate that the ZnSe/CdS/ZnS type-II/type-I QDs may be good candidates for applications in biomedical information detection.

Four new taraxastane-type triterpenoic acids from Cirsium setosum.

Four new taraxastane-type triterpenoids acids 3ß,22α-dihydroxy-20-taraxasten-30-oic acid (1), 3ß-hydroxy-22-oxo-20-taraxasten-30-oic acid (2), 3-oxo-22α-hydroxy-20- taraxasten-30-oic acid (3), and 3ß,19ß-dihydroxy-20-taraxasten-30-oic acid (4) were isolated and characterized from Cirsium setosum (Willd.) MB. Their structures were determined by the combination of 1D and 2D NMR experiments ((1)H-(1)HCOSY, HSQC, HMBC and ROESY) and mass spectrometry. Compound 2 exhibited potent selective cytotoxicity against human ovarian cancer cell line A2780 with an IC50 value of 3.9 µM.

[Effects of Forsythia suspensa Volatile Oil Loaded Nanomicellar on Transdermal and Transmucosal Drug Delivery of Phillyrin in Vitro].

Objective: To prepare all components loaded liquid preparation of Forsythia suspensa( ACLL) by the technology of nanomicellar solubilization,and to investigate the effects of Forsythia suspensa volatile oil loaded nanomicellar on the transdermal and transmucosal drug delivery of phillyrin. Methods: The volatile oil and hydrosoluble components of Forsythia suspensa were obtained by double extraction synchronously,and the major components of volatile oil were determined by GC-MS. Then the ACLL prepared by the volatile oil was added to the aqueous solution in the form of nanomicellar. The characteristics of ACLL were evaluated by the TEM,PCS and CLSM. The amount of phillyrin( PN) was determined by HPLC system. The side-by-side diffusion cell was used to investigate the effects of Forsythia suspense volatile oil loaded nanomicellar on the PN transdermal and transmucosal drug delivery, with the hydrosoluble components loaded liquid( HCLL) used as control group. Results: The Forsythia suspense volatile oil was slight yellowish and transparent liquid with a fragrant odor,the major components as follows ß-pinene( 49. 01%),α-pinene( 15. 78%), ß-ocimene( 13. 79%),linalool( 5. 91%), α-thujene( 2. 07%), ß-geranene( 1. 91%),terpinolene( 1. 84%),etc. The Forsythia suspense volatile oil loaded nanomicellar had a closed spherical shape as the TEM and CLSM images appeared. The calculated mean size was 193. 3 nm,the Zeta potential values of- 83. 8 m V. During the whole experiment, the ACLL resulted in a remarkable enhancement of PN transdermal and transmucosal absorption compared with HCLL. At 7. 0 h, the accumulated permeation amount of PN from the ACLL was 2. 04 and 1. 16 folds than that of HCLL for transdermal and transmucosal absorption,respectively. Conclusion: The permeability of PN is obviously enhanced by Forsythia suspense volatile oil loaded nanomicellar for transdermal and transmucosal absorption, these results elucidate the advantages and the mechanism of pharmacological action of all components of traditional Chinese medicine.

[Diagnostic value and influencing factors for amplitude-integrated EEG in brain injury in preterm infants].

OBJECTIVE: To study the diagnostic value and influencing factors for amplitude-integrated EEG (aEEG) in brain injury in preterm infants. METHODS: One hundred and sixteen preterm infants with a gestational age (GA) between 27 weeks and 36(+6) weeks were enrolled as subjects. The aEEG scores of all preterm infants were obtained within 6 hours after birth. According to the diagnostic results, the 116 preterm infants were divided into two groups: brain injury (n=63) and non-brain injury (n=53). The risk factors for brain injury were evaluated using logistic regression analysis. According to the aEEG results, the 116 preterm infants were divided into two groups: normal aEEG (n=58) and abnormal aEEG (n=58). The influencing factors for aEEG results in preterm infants were determined using univariate analysis. RESULTS: The brain injury group had a significantly higher rate of abnormal aEEG than the non-brain injury group (83% vs 11%; P<0.05). The infants in the brain injury group from two different GA subgroups (27-33(+6) weeks and 34-36(+6) weeks) had significantly lower aEEG scores than the non-brain injury group from corresponding GA subgroups (P<0.01). Logistic regression analysis showed that low GA (<32 weeks), low birth weight (<1 500 g), abnormal placenta, fetal membranes, and umbilical cord, and hypertension during pregnancy were high-risk factors for brain injury (P<0.05). There were significant differences in GA, birth weight, abnormal placenta, fetal membranes, and umbilical cord, and hypertension during pregnancy between the normal and abnormal aEEG groups (P<0.05). CONCLUSIONS: The risk factors for brain injury are consistent with the influencing factors for aEEG results in preterm infants, suggesting that aEEG contributes to the early diagnosis of brain injury.