Environmental pollution of fluoroquinolones and its relationship with nitrogen cycling mediated by microorganisms.

Fluoroquinolone antibiotics (FQs) are one of the most widely used antibiotics, which are new pollutants with 'pseudo persistence' in the environment, causing great ecological risks. FQs could change the structure and function of microbial communities and affect nitrogen cycling mediated by microorganisms. Consequently, FQs would change the composition of various types of nitrogen in the environment and exert a significant impact on the global nitrogen cycling. We encapsulated the distribution of FQs in the environment and its impacts on nitrogen cycling mediated by microorganisms, explained the role of FQs in each key process of nitrogen cycling, aiming to provide an important reference for revealing the ecological effects of FQs. Generally, FQs could be detected in various environmental media, with significant differences in the concentration and types of FQs in different environments. Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin are the four types of FQs with the highest detection frequency and concentration. The effect of FQs on nitrogen cycling deeply depends on typical characteristics of concentration and species. FQs mainly inhibit nitrification by reducing the abundance of amoA gene related to ammoxidation process and the abundance and composition of ammoxidation bacteria. FQs inhibits nitrification by reducing the abundance and composition of microbial communities. The denitrification process is mainly inhibited due to the reduction of the activity of related enzymes and the abundance of genes such as narG, nirS, norB, and nosZ genes, as well as the abundance and composition of denitrifying functional microorganisms. The process of anammox is restricted due to the reduction of the abundance, composition and hzo gene abundance of anaerobic anammox bacteria. FQs lead to the reduction of active nitrogen removal and the increase of N2O release in the environment, with further environmental problems such as water eutrophication and greenhouse effect. In the future, we should pay attention to the effects of low concentration FQs and complex antibiotics on the nitrogen cycling, and focus on the effects of FQs on the changes of nitrogen cycle-related microbial monomers and communities.

Behavioral and ecotoxicology of sulfonamide metabolites in the aquatic environment.

Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.

Biogeochemical behavior and ecological environmental effects of fluoroquinolones.

Synthetic fluoroquinolones (FQs) are the third most commonly used antibiotics in the world and play an extremely important role in antibacterial drugs. The excessive use and discharge will alter ecological environment, with consequence on human health and global sustainable development. It is therefore of great significance for scientific use and management of FQs to systematically understand their biogeochemical behavior and eco-environmental effects. After drug administration in humans and animals, only a small part of FQs are transformed in vivo. The main transformation processes include formylation, acetylation, oxidation and cleavage of piperazine ring, defluorination and decarboxylation of aromatic core ring, etc. About 70% of the original drug and a small amount of transformed products would be migrated to the environment through excretion. After entering the environment, FQs and their transformation products mainly exist in environmental media such as water, soil and sediment, and undergo migration and transformation processes such as adsorption, photolysis and biodegradation. Adsorption facilitates transfer of FQs from medium to another. The photolysis mainly affects the C7-amine substituents of FQs, whereas the core structure of FQs remains intact. Biodegradation mainly refers to the degradation of FQs by microorganisms and microalgae, including piperazine modification of the piperazine ring such as acetylation and formylation, partial or complete ring cleavage, core structure decarboxylation, defluorination and conjugation formation. The migration and transformation processes of FQs cannot completely eliminate them from the environment. Instead, they would become "pseudo-persistent" pollutants, which seriously affect the behavior, growth and reproduction of algae, crustaceans and fish, change biogeochemical cycle, destroy aquatic environment, and stimulate microbial resistance and the generation of resistance genes. In the future, more in-depth studies should be conducted on the environmental behavior of FQs and their impacts on ecological environment, the risk assessment of microbial resistance and resistance genes of FQs, and the mechanism and effect of micro-biodegradation of FQs.

Epiberberine regulates lipid synthesis through SHP (NR0B2) to improve non-alcoholic steatohepatitis.

Epiberberine (EPI), extracted from Rhizome Coptidis, has been shown to attenuate hyperlipidemia in vivo. Herein we have studied the mechanism by which EPI is active against non-alcoholic steatohepatitis (NASH) using, mice fed on a methionine- and choline-deficient (MCD) diet and HepG2 cells exposed to free fatty acids (FFA). We show that small heterodimer partner (SHP) protein is key in the regulation of lipid synthesis. In HepG2 cells and in the livers of MCD-fed mice, EPI elevated SHP levels, and this was accompanied by a reduction in sterol regulatory element-binding protein-1c (SREBP-1c) and FASN. Therefore, EPI reduced triglyceride (TG) accumulation in steatotic hepatocytes, even in HepG2 cells treated with siRNA-SHP, and also improved microbiota. Thus, EPI suppresses hepatic TG synthesis and ameliorates liver steatosis by upregulating SHP and inhibiting the SREBP1/FASN pathway, and improves gut microbiome.

A map of the spatial distribution and tumour-associated macrophage states in glioblastoma and grade 4 IDH-mutant astrocytoma.

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.

Integrating network pharmacology deciphers the action mechanism of Zuojin capsule in suppressing colorectal cancer.

BACKGROUND AND PURPOSE: Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. METHOD: Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. RESULTS: In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. CONCLUSIONS: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.

A plug-and-play optical fiber SPR sensor for simultaneous measurement of glucose and cholesterol concentrations.

A plug-and-play surface plasmon resonance (SPR) dual-parameter optical fiber biosensor is reported, in which Au film was firstly coated on the fiber surface for exciting SPR and the end half of the Au film was modified with Au nanoparticles to generate double SPR resonance valleys. For simultaneous detecting of glucose and cholesterol concentrations, modified P-mercaptophenylboronic acid (PMBA) and ß-cyclodextrin (ß-CD) were subsequently coated on the surface of sensor probe. Due to the cis-diol structure of glucose, it can interact with PMBA, leading to a red shift of one SPR resonant valley, whose maximum wavelength shift is 11.228 nm in the range of 0-1.7 mM glucose concentration. On the same time, the cholesterol molecules can realize the host-guest combination with ß-CD, leading to a red shift of another SPR resonant valley, and the maximum wavelength shift is 18.893 nm in the cholesterol concentration range of 0-300 nM. The detection limits of the sensor to glucose and cholesterol are 0.00078 mM and 0.012 nM, respectively. The enhances the practical value of the dual-parameter sensor. Both theory and experiment results verify the feasibility of the "plug-and-play" sensor to measure the dual biomass of glucose and cholesterol with ultra-low detection limit and good selectivity. The proposed method provides a huge research value for the optical fiber sensor in multi-parameter measurement.

Effects of diallyl trisulfide, an active substance from garlic essential oil, on structural chemistry of chitin in Sitotroga cerealella (Lepidoptera: Gelechiidae).

The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.

[Compound-specific carbon and nitrogen isotope analysis of amino sugars and their applications]. / æ°¨åŸºç³–å•ä½“ç¢³æ°®åŒä½ç´ çš„åˆ†æžåŠå ¶åº”ç”¨.

Amino sugars (AS) are one of the important biochemical components in the natural organic matter pool. Clarifying the sources and transformations of AS would facilitate our understan-ding of the microbial regulation of organic matter. As an emerging technology, compound-specific isotope analysis of amino sugars (CSIA-AS) provides more detailed dynamic information of indivi-dual AS in natural environment. Here, we systematically summarized the determination methods of CSIA-AS and gave an overview on innovative applications in the cycling of AS. CSIA-AS can be performed by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and ion chromatography-isotope ratio mass spectrometry (IC-IRMS). Each method has its own advantages and disadvantages, but reliable results can be achieved after calibration. The mean residence time of AS is relatively low in soil organic matter, and the bacterial-derived muramic acid possesses a higher minera-lization rate than glucosamine, galactosamine, and mannosamine. The source and metabolic transformation of AS are affected by the substrate, which is related to the specific response of microbial community to different carbon and nitrogen sources. The promotion of CSIA-AS technology requires further optimization of method and integration with other approaches such as microbial screening to decipher the source, transformation, fate and regulatory mechanisms of organic matter.

Effects of Diallyl Trisulfide, an Active Substance from Garlic Essential Oil, on Energy Metabolism in Male Moth Sitotroga cerealella (Olivier).

This study investigated the effects of diallyl trisulfide (DAT), an active substance from garlic essential oil, on the metabolism of the main energy substances of pre- and postmating males of Sitotroga cerealella. Males at 12 h postemergence were fumigated with DAT at a concentration (LC10 = 0.010 µL/L) in a glass jar for 7 h. The main energy metabolites from pre- and postmating males were determined, including protein, triglyceride, glycogen, total soluble sugar, trehalose, and trehalase. The contents of total protein and total soluble sugar and the trehalase activity of premating males were significantly increased following DAT treatment, whereas the contents of protein from the accessory gland, triglyceride, glycogen, and trehalose were significantly decreased after treatment. Additionally, after mating, the total protein and soluble sugar contents were significantly increased and the glycogen content was significantly decreased in the treatment group relative to the levels in controls, but there was no significant difference observed in triglyceride, accessory gland proteins, trehalose content, or trehalase activity between the treatment and control groups. Furthermore, the changes in the main energy substances between pre- and postmating in males after the DAT treatment (∆DAT) were smaller than those in the control group (∆CK). This result indicated that DAT can accelerate the rate of metabolism in males at LC10, leading to the accumulation of greater levels of total soluble sugar to support life activities and to the increased synthesis of proteins to resist an adverse environment.

Hydrogenation of CO to olefins over a supported iron catalyst on MgAl2O4 spinel: effects of the spinel synthesis method.

In the process of CO hydrogenation to olefins by the Fischer-Tropsch synthesis (FTO), the support is a key factor in the activity, selectivity, and thermal and chemical stability of the catalysts, and magnesium aluminate spinel (MgAl2O4) has recently been reported to be very effective. In this work, three methods, namely, citric acid solution combustion (MAC), EDTA sol-gel (MAG) and NH3-coprecipitation (MAP) have been employed to prepare the spinel with detailed characterization of the structure, specific surface area, porosity, and alkalinity properties of both the as-synthesized spinel and the supported catalysts. The results showed that MAC and MAG possessed stronger basicity with more homogeneous particle sizes and narrower distribution of the pore size due to the formation of the metal-nitrate-chelate-complex. This led to a large quantity of gas being released during calcination, however, stronger interactions between the active phase and MAC resulted in lower CO conversion. The catalyst supported on MAP (CMAP) exhibited the highest CO conversion, the highest selectivity of lower olefins, the shortest induction period of reaction, and the lowest AFS chain growth probability; thus, MAP was suggested as an applicable synthetic method. Based on the CMAP catalyst, the effects of the operational conditions were investigated and a 200 hour stability test was carried out with satisfactory performance.

[Total alkaloids of Coptidis Rhizoma combined with exercise inhibits tumor growth of orthotopically transplanted 4T1 breast cancer mice by blocking cell cycle G_1/S transformation].

Breast cancer is one of the leading causes for cancer-related death among women worldwide. Coptidis Rhizoma has antibacterial,anti-inflammatory,anti-tumor and other pharmacological activities,but whether exercise could synergistically promote the role of RC in the treatment of breast cancer has not been reported. In this experiment,the effects and mechanism of total alkaloids of Coptidis Rhizoma combined with exercise on the tumor growth of orthotopically transplanted 4 T1 breast cancer were systemically studied in mice. Balb/C mice transplanted with 4 T1 cells in situ were used as models. The total alkaloids of RC(145 mg·kg-1·d-1) alone or in combination with exercise(10 m·min-1,30 min/time,5 times/week) were given for 28 days,and then the changes in body weight and tumor volume,tumor weight,interleukin-1ß(IL-1ß),serum estradiol(E2) content,and expression levels of estrogen receptor α(ERα),cell cycle related proteins CDK4,CDK6,cyclin D1,CDK2,and cyclin E in tumor tissues. The results showed that total alkaloids of Coptidis Rhizoma could significantly inhibit the growth of 4 T1 breast cancer in mice(P< 0. 01),and exercise significantly promoted the anti-tumor activity of total alkaloids of Coptidis Rhizoma(P<0. 01),and reduced E2 and IL-1ß levels in mice. Western blot and flow cytometry showed that the total alkaloids of Coptidis Rhizoma combined with exercise could down-regulate the protein expression levels of ERα,CDK4,CDK6,cyclin D1,CDK2 and cyclin E in cancer cells,block the transformation of G1/S in 4 T1 cell cycle,and inhibit DNA synthesis in breast cancer cells. The total alkaloids of Coptidis Rhizoma combined with exercise showed synergistic effect in inhibition of tumor growth in mice with orthotopically transplanted 4 T1 breast cancer.

Process and mechanism of nitrogen loss in the ocean oxygen minimum zone.

There is a big imbalance between the input and output of oceanic nitrogen in global ocean nitrogen cycles, because a part of the fixed nitrogen is reduced to N2 or N2O and then lost from the ocean. Oxygen minimum zone (OMZ) is the most important area for nitrogen loss, which could lose fixed nitrogen up to 40 to 450 Tg·a-1 through the denitrification and anammox. A summary of the two main roles of nitrogen loss in the different OMZ sea areas reveals that heterotrophic denitrification dominates in eastern tropical Pacific, Arabian Sea, and marine sediments. The autotrophic denitrification has been found in Chile, Peru's coastal waters, and Arabian waters. In the Black Sea, the Benguela upwelling in southwestern Africa, and the northern coast of Chile, anaerobic ammonia oxidation is strong, with greater effects on the continental shelf than that in the ocean. In addition to the loss of nitrogen, nitrogen fixation, nitrification, and dissimilatory nitrate reduction to ammonium may affect the imbalance of nitrogen budget in the OMZ. The effects of nitrogen fixation can't be ignored. The total amount of nitrogen fixed in the global OMZ can reach 15-40 Tg·a-1, which is an important supplement to the loss of nitrogen in OMZ. Disentangling the relative contribution of denitrification and anammox to the loss of nitrogen, ascertaining the formation mechanism and quantitative evaluation method of N2O (another product of nitrogen loss) are the most important challenges in the current study of OMZ. Focusing on the existing problems, we put forward corresponding research ideas with references for related studies of the OMZs in the ocean.

Deactivation kinetics of individual C6-C9 aromatics' generation from methanol over Zn and P co-modified HZSM-5.

A deactivation kinetic model has been determined for the methanol to aromatic process over a HZSM-5 zeolite catalyst (SiO2/Al2O3 = 30) modified by 1.0 wt% ZnO and 2.0 wt% P, in which the generation rates of C6-C9 aromatics are treated individually while olefins and paraffins are lumped as intermediate and byproduct, respectively. The time-dependent catalytic activity is described by a deactivation coefficient related to the concentration of both methanol and products. The established kinetic model is able to predict the product distribution along with on-stream time under various conditions and is identified to be valid by a model significance test. The effect of operating conditions on catalyst behavior was also investigated: deactivation rate increases dramatically with methanol partial pressure and temperature; higher feed methanol content leads to less aromatics and more paraffin; increasing temperature reduces paraffin generation and results in higher aromatic yield, especially benzene and toluene.

[Amino acids in marine particulate matters and sediments and their role as indicators for organic matter degradation.] / 海洋颗粒物/æ²‰ç§¯ç‰©ä¸­çš„æ°¨åŸºé ¸åŠå ¶å¯¹æœ‰æœºè´¨é™è§£çš„æŒ‡ç¤ºä½œç”¨.

As important components of marine organic matters especially of organic nitrogen, amino acids play an important role in organic matter cycles owing to their lability. The concentration, composition, and distribution of amino acids have been widely used to indicate the degradation state of organic matters in particulates and sediments of marine. Here, the distribution, influencing factors of amino acids and their role in indicating degradation of organic matters were systematically summarized. Gly, Glu, Ala, and Asp were the major components of amino acids in marine particulates and sediments. The contents of amino acids in the particles and sediments showed a decreasing tendency from the coastal waters to the open sea, and adecreased with the water depth. The lower value of %AA-C/TOC, %AA-N/TN and degradation index (DI) based on changes in the composition of amino acids indicated the higher degradation degrees of organic matters. The reactivity index (RI) and ratios of D-AA and L-AA (D/L) based on non-protein amino acids and D-AA were used to indicate the degradation of organic matter according to the bacterial transformation of amino acids, in which RI value closer to 0, higher D/L, and lower ratios of protein amino acids to non-protein amino acids (Asp/ß-Ala and Glu/γ-Aba) indicated the higher degree of degradation in organic matters. The migration and transformation of amino acid were mainly affected by dissolved oxygen, nutrient concentrations, sources of organic matter, depositional environments and microbial activities. Further studies should focus on the synergistic effects of particles and sediments, and also the effects and the specific regulatory roles of microorganisms on amino acids.

Coptisine from Rhizoma coptidis exerts an anti-cancer effect on hepatocellular carcinoma by up-regulating miR-122.

With increasing incidence and mortality, hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. In this study, microRNA-122 (miR-122) mimics and relevant control oligonucleotides were transfected into HepG2 cells in vitro, followed by coptisine (COP) and sorafenib treatments. Cell proliferation, migration, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay, wound-healing assay, Hoechst 33258 staining and flow cytometry, respectively. Histopathology and miR-122 were analyzed by haemotoxylin and eosin (H&E) staining and real-time RT-PCR, respectively; whereas, the relevant protein expressions were detected by western blot. In vivo, COP enhanced the expression of miR-122 by 160% compared to control in male BALB/c nude mice; COP not only protected the liver morphology but also showed a significant anti-cancer effect. Further, there was no remarkable difference between the tumor weights in the COP and sorafenib groups, but there was a striking difference to the tumor control group (p < 0.05). Hence, COP inhibited the proliferation, migration and promoted apoptosis of HCC cells; moreover, it inhibited the tumor growth in nude mice by up-regulating the expression of miR-122.

Protective effect of Coptisine from Rhizoma Coptidis on LPS/D-GalN-induced acute liver failure in mice through up-regulating expression of miR-122.

Coptisine (COP), one of the main active ingredients of Rhizoma Coptidis, reportedly has anti-inflammatory, anti-colon cancer properties, but it remains elusive whether COP owns hepatoprotective activity. Mice were pretreated with COP for 7d prior to lipopolysaccharide/d-galactosamine (LPS/D-GalN) administration to detect the hepatic protective effects of COP. The mechanism was explored in using HepG2 cells with low level of miR-122 and LO2 cells with high level of miR-122, combining with miR-122 agomir transfection by means of detecting the expression of miR-122 and proteins, clinical index and apoptosis. COP ameliorated the LPS/D-GalN-induced liver failure by lowering serum levels of ALT and AST, raising hepatic GSH and SOD levels, and maintaining the morphology of hepatocytes, along with an increase in miR-122 expression in mice. The results in vitro indicated that, after miR-122 mimic administration, the alone treatment of COP and the co-treatment of COP and LPS transfection obviously promoted the apoptosis of HepG2, which was increased by 152.67% and 113.97% compared with NC (P < 0.05 vs NC). LPS significantly induced the apoptosis of L02 cells, but COP treatment attenuated that of L02 cells. Further analysis showed that COP increased the miR-122 level and the expression of Bax, cleaved-casp3 and decreased Bcl-2, Bcl-xL in LPS-treated HepG2 cells. COP increased the miR-122 level but decreased the expression of TLR4, Bcl-2, Bcl-xL in LPS-treated L02 cells. COP attenuated LPS/D-GalN-induced ALF by up-regulating the level of miR-122, synergistically promoting apoptosis, and suggesting COP which showed a potential protective effect on ALF.

The protective effect of coptisine on experimental atherosclerosis ApoE-/- mice is mediated by MAPK/NF-κB-dependent pathway.

Coptisine is one of main bioactive compounds extracted from the traditional Chinese herbal medicine Rhizoma Coptidis. It is reported that coptisine can attenuate obesity-related inflammation and oxidant damage in Syrian golden hamsters. Therefore，coptisine may exhibit beneficial effects for the treatment of atherosclerosis (AS) due to its hypolipidemic and anti-inflammation activities. The present study investigated the anti-atherosclerotic and anti-inflammatory properties of coptisine using apoE-/- mice as AS model. The atherosclerotic plaque area of aorta, serum lipid profile and the expression of inflammatory cytokines were determined. After coptisine treatment, the serum level of TC, TG and LDL-C decreased; the serum level of IL-6, IL-1ß and TNF-α were decreased; the mRNA levels of NF-κBp65, VCAM-1, ICAM-1, IL-6 and IL-1ß in both aorta and liver were down-regulated; the p-p38 and p-JNK1/2 protein expression level were decreased. Coptisine decreased atherosclerotic plaque area significantly through both anti-inflammation and lipid lowering effect. The anti-inflammatory effect of coptisine is achieved through inhibiting activation of MAPK signaling pathways and NF-κB nuclear translocation. Therefore，the combined anti-inflammation and lipid lowering effect of coptisine attributed the decreased atherosclerotic plaque area in coptisine treated apoE-/- mice. The results of this study will afford a novel application for coptisine in the treatment of atherosclerosis and other chronic inflammatory disease.

Effects of ocean acidification on the physiological performance and carbon production of the Antarctic sea ice diatom Nitzschia sp. ICE-H.

Ocean acidification (OA) resulting from increasing atmospheric CO2 strongly influences marine ecosystems, particularly in the polar ocean due to greater CO2 solubility. Here, we grew the Antarctic sea ice diatom Nitzschia sp. ICE-H in a semicontinuous culture under low (~400ppm) and high (1000ppm) CO2 levels. Elevated CO2 resulted in a stimulated physiological response including increased growth rates, chlorophyll a contents, and nitrogen and phosphorus uptake rates. Furthermore, high CO2 enhanced cellular particulate organic carbon production rates, indicating a greater shift from inorganic to organic carbon. However, the cultures grown in high CO2 conditions exhibited a decrease in both extracellular and intracellular carbonic anhydrase activity, suggesting that the carbon concentrating mechanisms of Nitzschia sp. ICE-H may be suppressed by elevated CO2. Our results revealed that OA would be beneficial to the survival of this sea ice diatom strain, with broad implications for global carbon cycles in the future ocean.

Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress.

Coptisine (COP) is one of the main active constituents of Coptidis Rhizoma. Previous studies have clarified that COP possesses antioxidant activity, but its defensive effects against pathological characteristics accompanied by oxidative damage in animal models and antioxidant mechanism are still unclear. Therefore, our purpose was to confirm the antioxidant activity of COP and explore its mechanism of action. We first detected the effects of COP on intracellular reactive oxygen species (ROS), heart beating rate, lipid peroxidation and cell death in zebrafish model with AAPH-induced oxidative stress. The results showed that COP of 10µg/mL significantly reduced ROS production, the increase of heart beating rate, lipid peroxidation and cell death by 41.3%, 24.5%, 26.5% and 30.0%, respectively. In addition, COP of 0.8µg/mL also decreased ROS, increased glutathione (GSH) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 40.1%, 19.8%, 18.3% and 49.3%, respectively in HepG2 cells. Further assays were carried out to explore the mRNA expression in zebrafish and protein expression of key factors in HepG2 cells. We demonstrated that COP up-regulated phase II antioxidant enzymes NAD(P)H/quinone oxidoreductase 1 (NQO1) through activating the nuclear factor erythroid-2 related factor 2 (Nrf2). Moreover, as the upstream signalings of Nrf2, the protein kinase B (Akt) and c-Jun NH2-terminal kinase (JNK) signalings were also induced by COP. And up-regulating Nrf2-mediated NQO1 expression of COP was in Akt and JNK-dependent manner. Taken together, COP exerted its antioxidant activity against AAPH-induced toxicity involving in activating Akt and JNK/Nrf2/NQO1 pathway.