Gas-assisted phototherapy for cancer treatment.

Phototherapies, mainly including photodynamic and photothermal therapy, have made considerable strides in the field of cancer treatment. With the aid of phototherapeutic agents, reactive oxygen species (ROS) or heat are generated under light irradiation to selectively damage cancer cells. However, sole-modality phototherapy faces certain drawbacks, such as limited penetration of phototherapeutic agents into tumor tissues, inefficient ROS generation due to hypoxia, treatment-induced inflammation and resistance of tumor to treatment (e.g., high levels of antioxidants, expression of heat shock protein). Gas therapy, an emerging therapy approach that damages cancer cells by improving the level of certain gas at the tumor site, shows potential to overcome the challenges associated with phototherapies. In addition, with the rapid development of nanotechnology, gas-assisted phototherapy based on nanomedicines has emerged as a promising strategy to enhance the treatment efficacy. This review summarizes recent advances in gas-assisted phototherapy and discusses the prospects and challenges of this strategy in cancer phototherapy.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

Anti-Quenching NIR-II J-Aggregates of Benzo[c]thiophene Fluorophore for Highly Efficient Bioimaging and Phototheranostics.

Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.

Highly oxygenated chemical constitutes and rearranged derivatives with neurotrophic activity from Ganoderma cochlear.

ETHNOPHARMACOLOGICAL RELEVANCE: The morphological characteristics of Ganoderma cochlear (Blume & T. Nees) Bres were identical to G. sinsense J.D. Zhao, L.W. Hsu & X.Q. Zhang, however, with the fungus stipe lying in the back of the pileus. Fruiting bodies and spores of G. cochear have been traditionally used for smoothing, sleeping improvement, memory impairment, anti-aging, and prolonging life. Alzheimer's disease (AD) is a chromic progressive neurodegenerative disorder associated with loss of memory and cognition. Hallmarks of AD include aging, amyloid-ß plaques, neurofibrillary tangles, neuron loss, neuronal degeneration, network disruption, cognitive dysfunction, inflammation and oxidation stress. In this study, norlanostanoids from G. cochear are identified as potential neurotrophic chemists related to the memory impairment usage to slow down pathogenetic process and restore neural circuits for AD. AIM OF STUDY: Chemical and biological investigations in this study uncovered the potential constituents related to the traditional usage of G. cochlear. MATERIALS AND METHODS: The extract of the mushrooms was purified using various column chromatography techniques and high-performance liquid chromatography (HPLC). The structures of the isolates were elucidated by combination of spectral, and single crystal X-ray diffraction analysis. The neurotrophic activity was evaluated by the differentiation state of PC12 cells, and the dose-dependent and time-dependant expression of growth-associated protein (GAP-43) was analyzed by western blotting. RESULTS: Ganorbifates J-T (1-11), eleven previously undescribed triterpenoids together with five known trinorlanostanoids (12-16) were isolated from the fruiting bodies of G. Cochlear. Among them, ganorbifates N-O (5-6) had a demethylation at C-28 compared to the classic skeleton of 3,4-seco-25,26,27-trinorlanostanoids to form a new group of 3,4-seco-25,26,27,28-tetranorlanostanoids. Based on this, a novel skeleton of ganorbifate M (4) was further established by the arrangement of C-29 from C-4 to C-7. A plausible biosynthetic pathway of compounds 4-6 was proposed. Eight of the sixteen isolates showed neurotrophic activity with the concentration of 10 µM. Furthermore, compound 15 exhibited a dose-dependent neurogenic activity, and also strengthened the expression of the growth-associated protein (GAP-43) in NGF-induced PC-12 cells, whereas 11 showed an inhibitory effect at higher concentration. CONCLUSION: These results demonstrated that 3,4-seco-norlanostanoids had reliable potential in promoting the outgrowth of PC-12 cells and could be used in the prevention and treatment of Alzheimer's disease, which is consist with the beneficial effects of G. Cochlear.

Palm oil consumption and its repercussion on endogenous fatty acids distribution.

The consumption of saturated lipids in combination with a sedentary lifestyle increases the risk of obesity and metabolic syndrome. However, the distribution of endogenous fatty acids (FA) after the consumption of saturated lipids and the connection between FA distribution and lipid metabolism-related genes relative expression have not been fully elucidated to date. In this study, we characterized FA profiles in the liver and visceral fats of Sprague Dawley (SD) rats fed with a high-palm-oil diet. The investigation showed that the levels of C16:0 and C18:1 (n-9) increased significantly (P < 0.05) in the liver of the high-palm-oil group (POG), while C16:1 (n-7) and C18:2 (n-6) accumulated markedly (P < 0.05) in the visceral fats of the control group (CN). A correlation analysis indicated a negative correlation between C16:0 and C16:1 (n-7) in the epididymal fat of POG. Our study also demonstrated that the intake of saturated lipids caused changes in lipid metabolism-related gene expression, especially stearoyl-CoA desaturase (SCD), which was upregulated at the third week but was inhibited in the subsequent weeks in the POG liver and perirenal fat. The SCD had a notable positive correlation with C16:1 (n-7) in the POG liver and perirenal fat but a significant negative correlation with C16:0 in the POG epididymal fat. In conclusion, the results of this study indicate that a high-C16:0 diet may result in adaptive SCD expression, and these findings may help to elucidate the effects of dietary fat on lipid metabolism.

Different dietary lipid consumption affects the serum lipid profiles, colonic short chain fatty acid composition and the gut health of Sprague Dawley rats.

Palm oil (PO), leaf lard oil (LO), rapeseed oil (RO), sunflower oil (SO), and linseed oil (LINO) are the five of the most typical dietary lipids, while few studies have explored and compared their influences on the serum lipid profiles, colonic short chain fatty acids (SCFAs) composition and colon health of Sprague Dawley (SD) rats. Results from the present work showed that PO and LO groups showed significantly higher serum TG and TC level compared with Ctrl group, whereas, the LDL-C/HDL-C and TC/HDL-C ratio were significantly lower in the RO, SO and LINO groups. Different dietary lipid consumption (15% of the normal diet) decreased the colonic SCFAs concentration. The saturated fatty acid (SFA) was negatively correlated, while unsaturated fatty acid (UFA)/SFA ratio was positively correlated, with colonic isobutyric acid concentration. The C18:2ω6 and ω3 fatty acids were positively correlated with colonic butyric acid and isovaleric acid concentration, respectively. Results also demonstrated that PO and LO could decrease the colon villus length and crypt depth, and led to colon injury, which might be due to their high SFAs content. Moreover, results suggested that PO and LO could specifically up-regulate the colon inflammation related gene expression levels and down-regulate the Muc2 expression levels, thus, imposing negative impact on the mucus layers. The present study could provide some information for nutritional evaluation about these dietary lipids.

Effects of wax concentration and carbon chain length on the structural modification of fat crystals.

Natural waxes are cost-effective and potential fat crystallization modifiers; however, there is limited information about their implementation in solid triacylglycerol (TAG) oil. Herein, we investigated the effects of two natural waxes, namely, candelilla wax (CLW) and rice bran wax (RW), with different concentrations (2, 4, 6, and 8 wt%) and carbon chains on the crystal growth and structure of palm kernel stearin (PKS85). CLW significantly accelerated the PKS85 crystallization process. Both waxes could induce a new hydrocarbon chain with the lengths of 3.70 and 4.15 Å during the TAG crystallization, respectively. Particularly, X-ray diffraction (XRD) indicated that PKS85 combined with CLW showed a similar lamellar thickness (d001) and crystal domain size (ξ) with pure PKS85, whereas that of PKS85 containing RW was 1.7-1.8 and 1.5-1.8 fold higher, respectively. This result corresponded to the carbon chain length of CLW and RW, which was double and quadruple that of PKS85, respectively. Further, these variations were reflected in the crystal microstructures of PKS85 with CLW and RW, where the former showed small homogeneous crystals, while the latter displayed large rod-like layered crystals. In addition, the firmness significantly increased when CLW and RW were added, which is possibly attributed to the fact that the waxes became the backbone of the crystal "fence". Our findings give clear insight into the interaction between TAGs and wax molecules in the crystallization process, which can help guide the utilization of natural waxes in the modification of fats.

The partial coalescence behavior of oil-in-water emulsions: Comparison between refrigerated and room temperature storage.

Although storage temperature is important for partial coalescence, the literature is scant on exploring the partial coalescence behavior between refrigerated and room temperature storage. In this study, comparison of the partial coalescence behavior between 4 and 20 °C was investigated towards corresponding oil-in-water emulsions, and subsequently towards the ultimate properties of the aerated colloidal system. As expected, compared to the value of Avrami constant (K) at 20 °C, the value of palm kernel stearin (PKS85) and mixtures of PKS85 and glycerol monostearate (PKS85-GMS) obtained at 4 °C increased by 22 and 14 times, respectively. PKS85 and PKS85-GMS displayed the needlelike appearance (N-type crystal) with a little layer crystal (L-type crystal) at 4 °C and spherical shape formed by L-type crystal along with granular crystal at 20 °C. Interestingly, several unstable air bubbles with irregularly-shape were observed in the aerated emulsions at 20 °C, while these emulsions at 4 °C displayed numerous rounded and uniform air bubbles with glossy surface. This was attributed to the sufficient stiff needle crystals at 4 °C, facilitating the coalescence of fat globules via liquid fat bridges, further forming a rigid crystal-based network and trapping the air bubbles. Therefore, our findings gained an insight into the partial coalescence behavior in emulsion, providing theoretical support for designing and optimizing the production process of foam structure products.

4-Sulfonylcalix[6]Arene Modified Fe3O4@Aspergillus Niger Biosorbents for Effective Removal of Uranium(VI) from Aqueous Solutions.

A biosorbent, 4-sulfonylcalix[6]arene modified Fe3O4@Aspergillus Niger (MFSC), was successfully prepared through a two-step route for the effective removal of uranium (U(VI)) from aqueous solutions with high selectivity. The structure of MFSC was characterized by FT-IR, SEM, XRD, TGA and VSM, respectively. The impacts of various experimental parameters were investigated in detail. The results indicated that the biosorption of U(VI) on MFSC was mainly attributed to the electrostatic attraction (91% within 8 hours for U(VI)). The adsorption kinetics and adsorption isotherm of U(VI) were found to follow the pseudo second-order model and to be fitted by the Langmuir model, respectively. The thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. The findings herein highlight the MFSC with high ability for removal of U(VI) from aqueous solutions.

The Triacylglycerol Profile of Oil Bodies and Oil Extracted from Argania spinosa Using the UPLC Along with the Electrospray Ionization Quadrupole-Time-of-Flight Mass Spectrometry (LC-Q-TOF-MS).

The triacylglycerol (TAG) matrix of argan oil (AO) bodies (AOB) along with the TAGs of AO extracted from the same kernels using an organic solvent, were identified and quantified using the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generally, both samples showed a similar TAGs profile but AO found to have three extra TAGs in low amount. In total 23 and 26 different TAGs were identified in AOBs and AO, respectively. The most abundant TAGs were OOL, POO, OOO, and POL in both samples. Furthermore, oleic acid, linoleic acid, and palmitic acid were the major fatty acids in both AOBs and AO. To the best of our knowledge, this is the first research that studied the TAGs matrix of an oil body revealing no major difference between the TAGs profile protected by the AOBs membrane and the oil extracted from the whole seed. PRACTICAL APPLICATION: Seed and kernels oil bodies emulsion tend to be the new source of emulsified oil in food and cosmetic industries. However, before replacing a product with another, we have to make sure that the new alternative can offer better or at least similar benefits. Our results showed that the triacylglycerols (TAGs) matrix and the argan oil (AO) share the same TAGs profile with a relatively close percentage. Therefore, AO bodies can be the perfect pre-emulsified oil for some food products like sauces and creams.

Development and Validation of a QuEChERS-LC-MS/MS Method for the Analysis of Phenolic Compounds in Rapeseed Oil.

In recent years, the determination of phenolic compounds in vegetable oil has aroused broad attention because these compounds have beneficial effects on health. In this work, a novel method based on the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and LC-MS/MS was developed for the analysis of phenolic compounds. A total of 18 mL of acetonitrile, 3 mL of water, and 270 mg of C18 sorbent were utilized in the optimized QuEChERS procedure. The LC-MS/MS analysis was performed in a C18 column under gradient-elution conditions with eluent of acetonitrile and water with 0.1% acetic acid. The QuEChERS approach achieved decent extraction recoveries (75.32-103.93%) for most phenolic compounds. The QuEChERS-LC-MS/MS method was validated in terms of accuracy, precision, sensitivity, and linearity. The proposed method was further evaluated using different prepared rapeseed oils. The result demonstrated that QuEChERS-LC-MS/MS is a rapid and reliable method for determining phenolic compounds in rapeseed oils.

Lipid composition modulates the intestine digestion rate and serum lipid status of different edible oils: a combination of in vitro and in vivo studies.

The objective of the present study was to investigate the connections between lipid compositions and the digestion and absorption differences of different lipids. Five typical edible oils (palm oil, PO; leaf lard oil, LO; rapeseed oil, RO; sunflower oil, SO; linseed oil, LINO) were selected to conduct in vitro digestion experiments considering the lipid digestion extent and hydrolysis rate before analyzing the fatty acid composition and TAG profiles using GC and UHPLC-Q-TOF-MS/MS. Meanwhile, the postprandial lipid absorption status after gavage administration was examined in adult male Sprague-Dawley rats with respect to serum lipid profiles. The results showed that the maximum FFA release extent decreased in the order: PO > RO > LINO > SO > LO, and the FFA release apparent constants were PO > SO ≈ RO > LO ≈ LINO. This suggested that the fatty acid species and the location of fatty acids within TAG molecules could significantly affect the lipid digestion fates in the gastrointestinal tract, and short chain saturated fatty acids located at the Sn-1, 3 position could favor the lipid digestion process. PO and LO were both shown to be more likely to affect the serum TG levels and LDL-C : HDL-C ratio compared with RO, SO and LINO. Different fatty acids displayed different correlations with serum lipid profiles when examined by Pearson correlation analysis. This suggested that fatty acid composition and TAG profiles may influence first the digestion rate and then the serum lipid profiles. This further confirmed that lipid composition could modulate the digestion and absorption status under the gastrointestinal conditions. These findings may provide some basic understanding of the connections between lipid composition and their functional difference.

The impact of roasting, high pressure homogenization and sterilization on peanut milk and its oil bodies.

The effect of roasting, high-pressure homogenization HPH and thermal treatment on peanut milk and its oil bodies OBs was evaluated. Full-fat peanut milk samples were obtained using aqueous extraction method followed by HPH 150 or 300 MPs and pasteurization or sterilization. Roasting has a pronounced effect on the appearance, functional properties and the OBs protein membrane of peanut milk. The HPH significantly affected the microstructure, particle size, rheology and the color of raw and roasted peanut milk. Where, the size was significantly reduced, consistency index (k) decreased and the flow behavior index (n) increased with the increase in homogenization pressure. However, the raw peanut milk samples became more sensitive to sterilization. On the other hand, the roasted peanut milk samples subjected to homogenization were particularly stable to sterilization. Further, a combination of roasting, HPH and thermal treatment can provide a stable product with better flavor and without additives.

Fatty acid profiles of typical dietary lipids after gastrointestinal digestion and absorbtion: A combination study between in-vitro and in-vivo.

The objective of the present study was to investigate the influences of dietary lipid composition on the gastrointestinal digestion and postprandial serum lipid profiles, and the connections between them. The in-vitro digestion results showed that maximum free fatty acid (FFA) release level of different lipid samples was PO (Palm oil) > RO (Rapeseed oil) > LINO (Linseed oil) > SO (Sunflower oil) > LO (Lard oil), and the first-order kinetics apparent rate constant was PO > SO ≈ RO > LO ≈ LINO, this may probably be ascribed to their specific lipid fatty acid composition and TAG structure. The individual FFA released during 240 min in-vitro digestion time was measured, and it showed that the release rate of short-chain saturated fatty acids (e.g. C16:0 in PO) were higher than the long-chain poly-unsaturated fatty acids (e.g. C18:3n-3 in LINO). Besides, the position of fatty acids within TAG molecules could also impose influences on the lipid hydrolysis process upon pancreas lipase in gastrointestinal tract using in-vitro digestion model. The postprandial serum fatty acid composition of the adult SD male rats were examined within 240 min after oral gavage administration, and the Pearson correlations between lipid fatty acid composition and the serum fatty acid profiles were analyzed. Certain correlations were summarized between lipid compositions (i.e. fatty acid composition and TAG structure), lipid digestion fates and serum fatty acid content in postprandial. The present work may provide some basic understandings of the connections among lipid compositions, lipid gastrointestinal digestion differences and the postprandial serum lipid profiles, and provide useful information about their nutritional and functional evaluation.

Digestion fates of different edible oils vary with their composition specificities and interactions with bile salts.

The digestion fates of different edible oils are different. The objective of this study was to understand the influences of lipid composition on their digestion fates, and investigate the roles of bile salts (BS) played in emulsified lipid system (whey protein isolate as emulsifier) in the in-vitro small intestine digestion stage. Three typical oils (palm oil (PO), rapeseed oil (RO) and linseed oil (LINO)) were chosen. Results showed that with the BS addition increased from 0.0 to 2.0 mg/mL, the increasing magnitude of the different fatty acid (FA) apparent release rate constants were: PO > RO ≈ LINO. Although the maximum FA release extent changed with BS addition, the order were: PO > RO > LINO. These may probably be attributed to palmitic acids, the most abundant FA in PO, was mostly located on the Sn-1, 3 positions of triacylglycerol (TAG) molecules, which contributed to the pancreatic lipase hydrolysis action. The relatively short chain length and the lower hydrophobicity also favored this process. However, Sn-1, 3 positions of TAGs in RO and LINO were mainly long chain mono- or poly-unsaturated FAs, which restricted the continuous lipid hydrolysis. Furthermore, the lipid composition may also affect the BS behavior on the O/W emulsion droplet surface, thus modulating lipase hydrolysis reaction. These findings can provide some basic understandings of the digestion differences of different oils.

Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis.

Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.

Triglyceride Structure Modulates Gastrointestinal Digestion Fates of Lipids: A Comparative Study between Typical Edible Oils and Triglycerides Using Fully Designed in Vitro Digestion Model.

Three typical edible oils (palm oil, PO; leaf lard oil, LO; rapeseed oil, RO) and triacylglycerols (TAGs) (glycerol tripalmitate, GTP; glycerol tristearate, GTS; glycerol trioleate, GTO) were selected to conduct digestion experiments using fully designed in vitro digestion model. The evolutions in mean particle diameter, ζ-potential, and microstructural changes during different digestion stages were investigated. Free fatty acid (FFA) release extent and kinetics were monitored by pH-Stat method. The particle characterization of different lipids during passage through the GIT depended on lipid type and the microenvironment they encountered. Absorbed surface protein can hardly be the obstacle for pancreas lipase to catalyze lipid hydrolysis after gastric digestion. The maximum FFA release level and apparent rate constant in small intestine digestion stage of the three oils and TAGs were: PO > RO > LO, GTP > GTS > GTO, respectively. PO showed the highest FFA release level and rate mainly due to the short chain length saturated palmitic acid (C16:0) specifically located in the Sn-1, 3 positions of TAG molecules in palm oil, while the Sn-1, 3 positions of TAG molecules in RO and LO were mainly mono- or polyunsaturated fatty acids (C18:1 or C18:2), restricting the continuous hydrolysis reaction. These findings can provide some basic understanding of the digestion differences of different lipids, which may be useful for their nutritional and functional evaluation and the applicability in the food area.

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities.

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A-J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal Basidiomycete Cyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K-R (1-8), were isolated from the solid culture of C. africanus cultivated on cooked rice, together with three known congeners (9-11). The structures and the absolute configurations of the new compounds were elucidated through comprehensive NMR and HRESIMS spectroscopic data, electronic circular dichroism (ECD) data, and chemical conversion. Compounds 1 and 2 represent the first reported naturally occurring compounds with 4,9-seco-cyathane carbon skeleton incorporating an unprecedented medium-sized 9/7 fused ring system, while the 3,4-seco-cyathane derivative (3) was isolated from Cyathus species for the first time. All compounds were evaluated for their neurotrophic and anti-neuroinflammatory activity. All the isolates at 1-25 µM displayed differential nerve growth factor (NGF)-induced neurite outgrowth-promoting activity in PC-12 cells, while one of the compounds, allocyathin B2 (11), inhibited NO production in lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. In addition, molecular docking studies showed that compound 11 generated interactions with the inducible nitric oxide synthase (iNOS) protein.

Chronic effects of copper in oysters Crassostrea hongkongensis under different exposure regimes as shown by NMR-based metabolomics.

Traditional metal toxicity tests on organisms have mainly focused on continuous exposure at a fixed concentration. However, organisms are more likely exposed to pollutants intermittently in estuarine environments that are significantly impacted by anthropogenic activity. The present study examined whether different copper (Cu) exposure regimes at an equivalent dose can induce different metabolomics effects on the oysters. An estuarine oyster Crassostrea hongkongensis was exposed to Cu continuously or intermittently at an equal dose (time × concentration) for 6 wk. Continuous exposure regimes included 2 doses of 3.3 µg/L for 24 h and 20 µg/L for 24 h, with corresponding equal doses of 2 intermittent exposure regimes of 20 µg/L for 4 h and 120 µg/L for 4 h, respectively. Time-course measurements suggested that Cu bioaccumulation was comparable at equal low doses between the continuous regime (3.3 µg/L for 24 h) and the intermittent regime (20 µg/L for 4 h), but there was considerable difference for the high dose under different regimes. Nuclear magnetic resonance (NMR)-based metabolomics suggested that continuous and intermittent Cu exposures led to similar metabolite variation pattern in gills at an equal high dose, including decreased amino acids (e.g., aspartate, glycine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine), lower energy-related compounds (e.g., adenosine triphosphate/adenosine diphosphate, acetate, citrate, and glycogen), and altered osmolytes (e.g., homarine and taurine). These biomarkers indicated disturbance of osmotic regulation and energy metabolism induced by Cu exposure regardless of regime. In addition, the 4-h intermittent Cu exposure resulted in slightly fewer adverse effects compared with the corresponding equal-dose continuous exposure. Oysters appeared to recover during the intervals of Cu exposure. The results indicated that metabolomic effects induced by Cu were more dose dependent than the Cu exposure regime. Environ Toxicol Chem 2017;36:2428-2435. © 2017 SETAC.

Electroacupuncture attenuates hepatic lipid accumulation via AMP-activated protein kinase (AMPK) activation in obese rats.

BACKGROUND: Electroacupuncture (EA) may offer an effective alternative approach for the treatment of obesity. EA mobilizes energy stores, but its effect on hepatic lipid metabolism is unknown, and the underlying mechanisms remain unclear. OBJECTIVE: To examine the effect of EA on hepatic lipid accumulation in diet-induced obese (DIO) rats, and to explore potential underlying mechanisms. METHODS: Male Sprague-Dawley rats were fed a normal diet (control group, n=10) or a high-fat diet (HFD) for 12 weeks to induce obesity. Those exhibiting diet-induced obesity were subdivided into two groups, one receiving EA (DIO+EA group, n=10) and one left untreated (DIO group, n=10) and observed for a further 4 weeks. Body, liver and fat pad weight were measured, and liver injury was assessed histologically as well as by measuring serum values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic triglyceride (TG) and total cholesterol were quantified by enzymatic colorimetric methods. Expression of liver AMP-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC), and carnitine palmitoyltransferase (CPT-1) was measured by Western blotting. RESULTS: EA treatment led to a reduction in body, liver and fat pad weight in DIO rats. This was accompanied by decreases in hepatic TG and total cholesterol values, fatty droplet accumulation, and serum concentrations of ALT and AST. Furthermore, EA treatment restored phosphorylation levels of AMPK (Thr(172)) and ACC (Ser(79)) inhibited by HFD, and increased CPT-1 expression. CONCLUSIONS: EA reduces HFD-induced hepatic lipid accumulation, an effect that appears to be mediated through AMPK signalling pathways. Our results shed new light on the mechanisms by which EA may reduce obesity.