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.

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.

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.

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.

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.

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.

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.

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.

Penehyclidine hydrochloride decreases pulmonary microvascular permeability by upregulating beta arrestins in a murine cecal ligation and puncture model.

BACKGROUND: Penehyclidine hydrochloride (PHC) is a new anticholinergic drug, which has been shown to have a good curative effect for sepsis. Beta arrestins have been demonstrated to play important roles in sepsis. This study is to investigate the effects of PHC on pulmonary microvascular permeability and on expressions of beta arrestins in lung injury induced by the cecal ligation and puncture (CLP) procedure. MATERIALS AND METHODS: Thirty healthy female mice were randomly divided into three groups (n = 10 each): sham operation group (control group), CLP group (CLP group), and PHC 0.45 mg/kg group (PHC group). In the PHC group, mice were given an intraperitoneal injection of PHC 0.45 mg/kg 1 h before surgery. Mice in the other two groups received an intraperitoneal injection of the same volume of normal saline. At 12 h after surgery, serum and bronchoalveolar lavage fluid were collected to examine lung permeability index. The lung tissue samples were collected to examine expressions of myosin light chain kinase (MLCK), vascular endothelial-cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), NF-κB, and beta arrestins. RESULTS: Compared with the control group, pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions were significantly increased, whereas VE-cadherin and beta-arrestin protein expressions were obviously decreased in CLP group. Furthermore, compared with the CLP group, PHC group markedly decreased pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions, and increased expressions of VE-cadherin and beta arrestins. CONCLUSIONS: This study suggests that in the CLP-induced lung injury model, PHC could reduce pulmonary microvascular permeability by upregulating expressions of beta arrestins.

[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.

Cytotoxic monacolin analogs from Monascus purpureus-fermented rice.

Two new monacolin analogs, monacolins O (1) and P (2), along with three known analogs, have been isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures and absolute configurations were elucidated by spectroscopic methods, especially 2D NMR and CD spectral analyses as well as chemical method. Both 1 and 2 were tested against five tumor cell lines, and compound 1 exhibited selective cytotoxic activity against A2780 and A549 cell lines, with IC50 values of 3.7 and 8.0 µM, respectively.

[GC-MS analysis of low polar components from Ainsliaea yunnanensis].

OBJECTIVE: To analyze the chemical constituents of low polar components from ethanol extract of Ainsliaea yunnanensis. METHODS: The air-dried stems and leaves of Ainsliaea yunnanensis were extracted with ethanol using ultrasonic extration. After removal of solvent under reduced pressure, the residue was suspended in H2O, and then partitioned sequentially with petroleum ether, EtOAc and n-BuOH, respectively. Then the petroleum ether fraction was chromatographed on normal phase silica gels eluting with a gradient increasing Me2 CO in petroleum ether. Then the components of low polarity were separated from the petroleum ether-Me2CO(50:1 - 20: 1) fraction and identified by GC-MS, and the relative contents of the components were determined with area percentage method. RESULTS: 50 constituents were identified from the low polar components of Ainsliaea yunnanensis. CONCLUSION: The research provides a theoretical basis for the study of chemical constituents and pharmaceutical activities of Ainsliaea yunnanensis.

[Triterpene compounds of Ainsliaea yunnanensis].

The compounds of Ainsliaea yunnanensis were isolated and purified by various kinds of column chromatography methods and their structures were determined by spectroscopic data analysis. Twelve compounds were obtained from the petroleum ether of ethanolic extract of A. yunnanensis and elucidated as bauerenyl acetate (1), bauerenol (2), alpha-amyrin (3), psi-taraxasterol (4), beta-amyrin (5), echinocystic acid (6), multiflorenol (7), 3beta-hydroxy-olean-18-ene germanicol (8), 3beta-hexadecanoyl-12-oleanen-11-one (9), fernenol (10), fern-7-en-3beta-ol (11), and lupeol (12). All compounds were isolated from this genus for the first time except compound 1, 3, 5 and 10, and they were all isolated from this plant for the first time.

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.

Structure elucidation and NMR assignments of an unusual aromatic monacolin analog from Monascus purpureus-fermented rice.

One unusual aromatic monacolin analog, aromonacolin A (1), was isolated from the ethanolic extract of Monascus purpureus-fermented rice. Its structure was elucidated by extensive spectroscopic (HRESIMS, (1)H NMR, (13)C NMR, HSQC, HMBC, and NOESY) and chemical methods. The absolute configuration of the C-6 secondary alcohol was deduced via the circular dichroism data of the in situ formed [Rh(2)(OCOCF(3))(4)] complex.

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.

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.