Five new limonoids isolated from Walsura robusta.

Five new toosendanin limonoids with highly oxidative furan ring walsurobustones A-D (1-4), and one new furan ring degraded limonoid walsurobustone E (5) together with one known compound toonapubesic acid B (6) were isolated from the leaves of Walsura robusta. Their structures were elucidated by NMR and MS data. Especially, the absolute configuration of toonapubesic acid B (6) was confirmed by X-ray diffraction study. Compounds 1-6 exhibited good cytotoxicity against the cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480.

[Design and application of a new magnetic joint for electroacupuncture instrument].

Combined with the material characteristics of acupuncture needle, new connection technology and injection moulding technology, and through mechanical test, a new type of magnetic joint for electroacupuncture instrument, with regular appearance and simple manufacturing process, is developed, which can be connected with acupuncture needle in close range. This joint is composed of the inner magnet joint and the outer joint protective sleeve. The new conductive adhesive is used to simplify the manufacturing process. Its advantages include connection with acupuncture needle by magnetic force, being convenient to store when idle and easy to switch to the working state, and quick disconnection in case of emergency. This joint is connected safely and firmly with acupuncture needle by magnetic force, which shortens the operation time, improves the working efficiency, and effectively solves the problems existing in the crocodile clip connector.

Role of autophagy in LPS­induced inflammation in INS­1 cells.

Inflammation has been implicated in the pathogenesis of type 2 diabetes (T2D), which is a progressive disease characterized by pancreatic ß­cell dysfunction and apoptosis with consequential insufficient insulin secretion. Autophagy is necessary to maintain the structure, mass and function of pancreatic ß­cells. The present study investigated the crosstalk between autophagy and inflammasome activation in T2D. INS­1 cells were stimulated with lipopolysaccharide. Apoptosis and reactive oxygen species (ROS) formation were measured using flow cytometry, and cell proliferation was measured using Cell Counting Kit­8 solution. Autophagy was assayed using western blotting and transmission electron microscopy. The expression levels of interleukin­1ß (IL­1ß) and caspase­1 were detected by western blotting. The results demonstrated that inhibiting autophagy using 3­methyladenine (3­MA) promoted INS­1 cell apoptosis. This response was correlated with an increase in ROS production and the inflammatory response, including IL­1ß maturation and caspase­1 activation. Furthermore, when ROS were inhibited using N­acetyl­L­cysteine, inflammation was decreased. These results demonstrated that inhibition of autophagy enhanced inflammatory injury via the ROS­mediated activation of the Nod­like receptor pyrin domain­containing protein 3 inflammasome. Autophagy may have a protective effect by mitigating inflammation in T2D, which may provide a novel approach for T2D treatment.

Development and validation of an individualized diagnostic signature in thyroid cancer.

New molecular signatures are needed to improve the diagnosis of thyroid cancer (TC) and avoid unnecessary surgeries. In this study, we aimed to develop a robust and individualized diagnostic signature in TC. Gene expression profiles of tumor and nontumor samples were from 13 microarray datasets of Gene Expression Omnibus (GEO) database and one RNA-sequencing dataset of The Cancer Genome Atlas (TCGA). A total of 1246 samples were divided into a training set (N = 435), a test set (N = 247), and one independent validation set (N = 564). In the training set, 115 most frequent differentially expressed genes (DEGs) among the included datasets were used to construct 6555 gene pairs, and 19 significant pairs were detected to further construct the diagnostic signature by a penalized generalized linear model. The signature showed a good diagnostic ability for TC in the training set (area under receiver operating characteristic curve (AUC) = 0.976), test set (AUC = 0.960), and TCGA dataset (AUC = 0.979). Subgroup analyses showed consistent results when considering the type of nontumor samples and microarray platforms. When compared with two existing molecular signatures in the diagnosis of thyroid nodules, the signature (AUC = 0.933) also showed a higher diagnostic ability (AUC = 0.886 for a 7-gene signature and AUC = 0.892 for a 10-gene signature). In conclusion, our study developed and validated an individualized diagnostic signature in TC. Large-scale prospective studies were needed to further validate its diagnostic ability.

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1.

The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health problem and novel therapeutic strategies are required to prevent and treat T2DM. It has been demonstrated that resveratrol (RSV) may prevent T2DM by targeting Sirtuin type 1 (SIRT1), indicating that SIRT1 may be a novel therapeutic target for T2DM prevention. In the present study, a T2DM rat model was established by administering a high fat diet and streptozotocin (STZ) injections. Measurements of blood glucose and insulin confirmed successful establishment of the T2DM model. RSV was used to treat rats with STZ-induced T2DM and the results indicated that RSV reversed the STZ-induced downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, SIRT1 and forkhead box protein O 3a. Furthermore, RSV modulated the activity of superoxide dismutase and malondialdehyde, which are associated with oxidative stress. In vitro, cells from the insulinoma cell line clone 1E were pretreated with palmitic acid (PA) to simulate a high fat environment. The results of reverse transcription-quantitative polymerase chain reaction indicated that PA suppressed the expression of SIRT1 in a dose- and time-dependent manner. Furthermore, PA modulated the expression of mitochondrial biogenesis-associated, lipid metabolism-associated and ß-cell-associated genes, whereas RSV treatment ameliorated the PA-induced changes in the expression of these genes via SIRT1. The results of the present study suggest that RSV participates in the prevention of T2DM by regulating the expression of mitochondrial genes associated with biogenesis, lipid metabolism and ß-cells via SIRT1. The results of the current study provide an insight into the mechanisms by which SIRT1 inhibits T2DM and may be used as a basis for future studies.

Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS­1 cells.

Type 2 diabetes is a chronic inflammatory disease. Autophagy, the dynamic process of lysosomal degradation of damaged organelles and proteins, may protect ß­cells from destruction by inflammation in type 2 diabetes. The present study investigated the role of autophagy, inflammation and endoplasmic reticulum (ER) stress in type 2 diabetes. INS­1 cells were incubated with lipopolysaccharide. The chemical chaperone 4­phenylbutyric acid was used to inhibit ER stress, and 3­methyadenine (3­MA) was used to inhibit autophagy. Apoptosis was detected by flow cytometry and cell proliferation using Cell Counting kit­8 solution. Light chain­3B, interleukin (IL) 1ß, caspase­1 and C/EBP homologous protein production were assessed by western blotting, and rat activating transcription factor 4 and rat binding immunoglobulin heavy chain protein gene expression were determined by real­time reverse transcription­polymerase chain reaction. The results showed that inhibiting autophagy with 3­MA unexpectedly contributed to cell death in ß­cells. This response was associated with an increase in inflammatory cytokines, including IL1ß and caspase­1. Inhibiting ER stress with 4­phenylbutyric acid led to a decrease in cell apoptosis. These results showed that autophagy may have a protective effect by reducing inflammatory cytokines in ß­cells. In addition, the inositol­requiring enzyme 1 pathway mediated the ER stress associated with autophagy and inflammatory cytokines (IL1ß and caspase­1). Therefore, inflammatory cytokines may be critical signalling nodes, which are associated with ER stress­mediated ß­cell death.

Myritonines A-C, Alkaloids from Myrioneuron tonkinensis Based on a Novel Hexacyclic Skeleton.

Myritonines A-C (1-3), three new alkaloids bearing an unprecedented heterohexacyclic skeleton, were isolated from Myrioneuron tonkinensis. Their structures were determined by a combination of spectroscopic data and single-crystal X-ray diffraction analysis. Compound 3 represents the first Myrioneuron alkaloid featuring a unique trans-decahydroquinoline motif and was also found to possess a rare cyano functionality. Compounds 1 and 2 showed inhibition against the hepatitis C virus in vitro.

[Spatial-temporal process and characteristics of vegetation recovery after Wenchuan earthquake: A case study in Longxi River basin of Dujiangyan, China.] / 汶川地震区灾后植被恢复时空过程及特征­­ä»¥éƒ½æ±Ÿå °é¾™æºªæ²³æµåŸŸä¸ºä¾‹.

Quantitative evaluation on the vegetation recovery after the earthquake is of great scienti-fic significance for local ecological system rebuilding and regional social-economic sustainable deve-lopment. By taking the Longxi River Basin in Dujiangyan of Sichuan Province as an example, and employing the MODIS-NDVI time-series data, this paper illustrated the dynamic changes of the ve-getation cover rates in Longxi River basin before and after the 5.12 Wenchuan Earthquake by using Landsat data, and then time-space characters of the recovery rates of the damaged vegetation was quantified structurally by referring the factors of river-system and terrain. The results showed that the recovery of impaired vegetation coverage worked well from a holistic point of view, but the response of vegetation coverage to earthquake disaster showed a lagging-phenomenon. The recovery rate of damaged vegetation was significantly correlated to its distance to surrounding river systems, elevation, slope degree, and slope aspect. This finding could provide technical supports for decision-makers to intervene the recovering process after earthquake.

Alkaloids with Different Carbon Units from Myrioneuron faberi.

Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7.

Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes

Autophagy is a kind of cell biological process that maintains the cell’s energy level under nutrient-poor conditions, regulates the turnover of abnormal or aged proteins, and disposes of dysfunctional organelles. The autophagy system is activated as a novel signaling pathway in response to endoplasmic reticulum stress (ER stress)-induced insulin resistance (IR). Defective autophagy may be closely related to insulin resistance. There are at least three mechanistically distinct arms of ER stress that regulate the expression of key genes which not only function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids, and lipids. ER stress-stimulated insulin resistance is mediated by the autophagy-dependent process. In settings of chronic ER stress, the associated autophagy may contribute to pathophysiological processes involved in a number of prevalent diseases, including diabetes. Whether autophagy plays a protective or harmful role in diabetes awaits further analysis. In this review, we will summarize the current knowledge about the emerging role of autophagy in ER stress-induced insulin resistance. Strategies to take advantage of the potential protective effect of autophagy remain important in the overall treatment of insulin resistance and type 2 diabetes

Cytotoxic indole alkaloids from the fruits of Melodinus cochinchinensis.

Eight indole alkaloids, melosines A-H, together with 13 known alkaloids, were isolated from the fruits of Melodinus cochinchinensis. The structure elucidation of isolated secondary metabolites was based on comprehensive spectroscopic data analysis. Melosine B showed moderate cytotoxic activity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values ranging from 1.6 to 8.1µM.

Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes.

Autophagy is a kind of cell biological process that maintains the cell's energy level under nutrient-poor conditions, regulates the turnover of abnormal or aged proteins, and disposes of dysfunctional organelles. The autophagy system is activated as a novel signaling pathway in response to endoplasmic reticulum stress (ER stress)-induced insulin resistance (IR). Defective autophagy may be closely related to insulin resistance. There are at least three mechanistically distinct arms of ER stress that regulate the expression of key genes which not only function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids, and lipids. ER stress-stimulated insulin resistance is mediated by the autophagy-dependent process. In settings of chronic ER stress, the associated autophagy may contribute to pathophysiological processes involved in a number of prevalent diseases, including diabetes. Whether autophagy plays a protective or harmful role in diabetes awaits further analysis. In this review, we will summarize the current knowledge about the emerging role of autophagy in ER stress-induced insulin resistance. Strategies to take advantage of the potential protective effect of autophagy remain important in the overall treatment of insulin resistance and type 2 diabetes.

Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes.

Type 2 diabetes is a chronic inflammatory disease. A number of studies have clearly demonstrated that cytokines such as interleukin 1ß (IL1ß) contribute to pancreatic inflammation, leading to impaired glucose homeostasis and diabetic disease. There are findings which suggest that islet ß-cells can secrete cytokines and cause inflammatory responses. In this process, thioredoxin-interacting protein (TXNIP) is induced by endoplasmic reticulum (ER) stress, which further demonstrates a potential role for ER stress in innate immunity via activation of the NOD-like receptor (NLRP) 3/caspase1 inflammasome and in diabetes pathogenesis via the release of cytokines. Recent developments have also revealed a crucial role for the autophagy pathway during ER stress and inflammation. Autophagy is an intracellular catabolic system that not only plays a crucial role in maintaining the normal islet architecture and intracellular insulin content but also represents a form of programmed cell death. In this review, we focus on the roles of autophagy, inflammation, and ER stress in type 2 diabetes but, above all, on the connections among these factors.

Cyclohexane-fused octahydroquinolizine alkaloids from Myrioneuron faberi with activity against hepatitis C virus.

Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1-4). (±)-ß-Myrifabral A (1) and (±)-α-myrifabral A (2) formed an inseparable mixture of anomers (cluster A), as did (±)-ß-myrifabral B (3) and (±)-α-myrifabral B (4) (cluster B). Their structures were determined by X-ray diffraction and NMR analysis. Compounds 1-4 possessed novel cyclohexane-fused octahydroquinolizine skeletons and represent the first quinolizidine alkaloids from the genus Myrioneuron. The epimers of cluster A (1 and 2) were modified and separated. In vitro, clusters A and B and their derivatives inhibited replication of hepatitis C virus (HCV, IC50 0.9 to 4.7 µM) with cytotoxicity lower than that of telaprevir.

Antimicrobial Constituents of the Mature Carpels of Manglietiastrum sinicum.

Seven new compounds, including a eupodienone-type lignan (1), a dibenzocyclooctadiene-type lignan (2), three tetrahydrofuran-type lignans (3-5), and two 1-phenylbutyl benzoates (6, 7), together with six known compounds, were isolated from the mature carpels of Manglietiastrum sinicum. The structures of new compounds 1-7 were defined by spectroscopic techniques, and the absolute configuration of manglisin A (1) was determined by X-ray crystallography. Compounds 1-4 exhibited moderate antimicrobial activities (MIC values: 0.016-0.14 µM) against Staphylococcus aureus, MRSA 82(#), MRSA 92(#), MRSA 98(#), and MRSA 331(#). Compounds 2 and 3 showed weak cytotoxic activity against five human tumor cell lines.

Myrifabine, the first dimeric Myrioneuron alkaloid from Myrioneuron faberi.

One Myrioneuron alkaloid, myrifabine (1), the first example of a dimer with 12 chiral centers embraced in a decacyclic novel skeleton, was isolated from Myrioneuron faberi . Its structure was elucidated by spectroscopic data and single-crystal X-ray diffraction. The antimicrobial and cytotoxic activities of 1 were evaluated in vitro.

New steroids and sesquiterpene from Turraea pubescens.

Four new compounds, including three new steroids (1-3) and one new sesquiterpene (6), and two new natural products (4-5), as well as three known steroids (7-9) were isolated from the twigs of Turraea pubescens. Compounds 3-5 are C22 steroids isolated from the Meliaceae family for the first time. Their structures were elucidated by extensive NMR and MS analyses. Compound 1 exhibited inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cells with an IC50 value of 11.5 µM.

A new Amaryllidaceae alkaloid from the bulbs of Lycoris radiata.

AIM: To study the Amaryllidaceae alkaloids of the bulbs of Lycoris radiata. METHODS: The chemical constituents were isolated and purified by various chromatographic techniques, and the chemical structures were elucidated on the basis of spectroscopic methods. In addition, the antiviral activities of alkaloids 1-10 were evaluated using flu virus A. RESULTS: One new homolycorine-type alkaloid 2α-methoxy-6-O-ethyloduline (1), together with nine known alkaloids 2α-methoxy-6-O-methyloduline (2), trispherine (3), 8-O-demethylhomolycorine (4), homolycorine (5), 9-O-demethylhomolycorine (6), oduline (7), lycorenine (8), 6α-O-methyllycorenine (9) and O-ethyllycorenine (10) were obtained. CONCLUSION: Alkaloid 1 is a new compound, and 1-3 were major alkaloids in this plant. Alkaloids 1-3 showed weak antiviral activities against flu virus A with IC50 values of 2.06, 0.69, and 2.71 µg·mL-1 and CC50 values of 14.37, 4.79, and 80.12 µg·mL-1, respectively.

Bioactive limonoid and triterpenoid constituents of Turraea pubescens.

Eleven new limonoids, turrapubins A-K (1-11), and three new triterpenoids (12-14), along with 14 known compounds, were isolated from the twigs of Turraea pubescens. The structures of 1-14 were elucidated on the basis of NMR and MS analysis. Compounds 12, 16, 18, and 19 exhibited inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. In addition, compounds 2, 11, 18, and 26 exhibited inhibitory activities against brine shrimp larvae (Artemia salina) at 100 ppm with the corrected mortality ranging from 81.7% to 100%.

Daphmacromines K-O, alkaloids from Daphniphyllum macropodum.

Five new yuzurimine-type Daphniphyllum alkaloids, daphmacromines K-O (1-5), were isolated from the leaves and stems of Daphniphyllum macropodum. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. Daphmacromine O (5) showed moderate cytotoxic activity against brine shrimp.