Mechanism Exploration of Euphorbia fischeriana Steud. for Liver Cancer Based on Aspartic Acid Identification in Metabolomics.

OBJECTIVE: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD). METHODS: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups. RESULTS: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD. CONCLUSION: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism.

Tribulus terrestris L. induces cell apoptosis of breast cancer by regulating sphingolipid metabolism signaling pathways.

BACKGROUND: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. PURPOSE: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. METHODS: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. CONCLUSIONS: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.

Promoting liver cancer cell apoptosis effect of Tribulus terrestris L. via reducing sphingosine level was confirmed by network pharmacology with metabolomics.

Background: Tribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups. Results: 12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment. Conclusion: TT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.

MgO coated magnetic Fe3O4@SiO2 nanoparticles with fast and efficient phosphorus removal performance and excellent pH stability.

A regenerable MgO-coated magnetic Fe3O4@SiO2 (FSM) composite effectively avoided the agglomeration of nano-MgO, which was resoundingly used for efficient and rapid phosphorus removal from aqueous solutions. Based on an initial screening of synthesized FSM with different Mg/citric acid molar ratios in terms of phosphorus adsorption capacity, an FSM composite with a Mg-citric acid molar ratio of 1:1 (FSM-1:1) was determined as the optimal choice. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) showed that the prepared Fe3O4 was triumphantly loaded and the nano-MgO nanoparticles were evenly distributed on the surface of magnetic mesoporous silica. N2 adsorption-desorption experiments manifested that FSM-1:1 had a large specific surface area of 124.3 m2/g and the pore size distribution calculated based on the BJH model was centered at 9.36 nm. Furthermore, FSM-1:1 not only exhibited fast adsorption kinetics (60 min) but also had a high maximum theoretical adsorption capacity of 223.6 mg P/g, which was superior to all the other Mg-based adsorbents. Remarkably, due to the coating of MgO, FSM-1:1 exhibited ultra-high stability in the pH range of 3-11, a wider range than many other Mg-modified sorbents. Our adsorbents also showed excellent selectivity for phosphate anions even in the presence of various coexisting anions (e. g. NO3-, Cl- and SO42-) with varying ionic strengths (0.01 and 0.1 M), good recyclability, the removal rate of phosphate still reached 89.0% after three cycles. Electrostatic attraction, Lewis acid-base interaction and the ligand exchange between Mg-OH and phosphate anions were responsible for the phosphate adsorption mechanisms.

Application of High-Throughput Sequencing on the Chinese Herbal Medicine for the Data-Mining of the Bioactive Compounds.

The Chinese Herbal Medicine (CHM) has been used worldwide in clinic to treat the vast majority of human diseases, and the healing effect is remarkable. However, the functional components and the corresponding pharmacological mechanism of the herbs are unclear. As one of the main means, the high-throughput sequencing (HTS) technologies have been employed to discover and parse the active ingredients of CHM. Moreover, a tremendous amount of effort is made to uncover the pharmacodynamic genes associated with the synthesis of active substances. Here, based on the genome-assembly and the downstream bioinformatics analysis, we present a comprehensive summary of the application of HTS on CHM for the synthesis pathways of active ingredients from two aspects: active ingredient properties and disease classification, which are important for pharmacological, herb molecular breeding, and synthetic biology studies.

[Intractable sudden deafness treated with acupuncture on the base of "heart housing the mind"].

Intractable sudden deafness is a kind of primary sudden deafness that is insensitive to the comprehensive treatment in modern medicine. Due to the close relationship between the ear and the "heart", combined with the characteristics of intractable sudden deafness, in the theoretic guidance of "the heart housing the mind", the acupuncture therapy for regulating the mind and nourishing the heart was introduced in treatment of intractable sudden deafness, the relevant theoretic evidences were explored and elaborated with the typical case.

A Non-innocent Magnesium Organoclay-Based Drug Vehicle for Improving the Cancer Therapy Effect of Methotrexate.

A synthetic, dispersible magnesium aminoclay (MgAC) was synthesized in the present study. Besides, structural and spectroscopic detections were conducted to investigate the MgAC nanoclay. With a poor aqueous solubility, methotrexate (MTX) has been applied as a valid antitumor agent in recent years. In our research, an unobtrusive sol-gel process was carried out to manufacture the MgAC-MTX nanohybrids through entrapment of MTX over MgAC in situ. The final product was capable of desquamating and thus dispersed in water, equably. In comparison with rough MTX, the MgAC-MTX nanocomposite with a preferable treatment efficacy against MCF-7 cells was mainly attributed to the preeminent enhanced aqueous solubility, controlled release and the increased cellular uptake capacity. Moreover, with excellent anticancer function and hypotoxicity as vindicated in vivo, the MgAC-MTX nanohybrid was supposed to own the potency in the application of malignant tumors cure as a valid nanomedicine. It turned out that, by virtue of its high bioavailability, the MgAC-MTX nanohybrids with high bioavailability is deserving of further study for the treatment of cancers.

Effects of nano-sized MnO2 on methanogenic propionate and butyrate degradation in anaerobic digestion.

The responses of methanogenic propionate and butyrate degradation to nano-sized MnO2 exposure were explored. The results showed that supplementation with 50 mg/g volatile suspended solids (VSS) of nano-sized MnO2 significantly enhanced the production rate of CH4 in propionate and butyrate degradation by 25.6% and 21.7%, respectively. The stimulatory effects most likely resulted from enhancements in the microbial metabolic activity based on the observed increases in the extracellular polymeric substance (EPS) secretion and activity of the electron transport system. In contrast, the CH4 yields obtained were irreversibly inhibited by the presence of 400 mg/g VSS of nano-sized MnO2, in which just 62.8% and 6.5%, respectively, of the yield obtained from the control. Further investigations indicated that supplementation by nano-sized MnO2 could cause oxidative stress in microbial cells, resulting in the release of reactive oxygen species (ROS). Compared with that of the control, the amount of intracellular ROS generated in the systems increased by 28.3% (fed with propionate) and 42.5% (fed with butyrate), corresponding to approximately 43.9% and 64.8% losses in cell viability, respectively; thus, ROS generation was suggested to be the main factor responsible for the inhibitory effects of nano-sized MnO2 on methanogenic propionate and butyrate degradation.

Transient receptor potential (TRP) channel function in the reproductive axis.

Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i.e. in kisspeptin and gonadotropin-releasing hormone (GnRH) neurons. Kisspeptin neurons are depolarized by leptin via activation of TRPC channels and kisspeptin depolarizes GnRH neurons through TRPC4 activation. Recent studies have functionally identified TRPC channels also in gonadotrope cells in the anterior pituitary gland, which secrete gonadotropins in response to GnRH and thus regulate gonadal function. TRP channel expression in these cells exhibits remarkable plasticity and depends on the hormonal status of the animal. Subsequent functional analyses have demonstrated that TRPC5 in gonadotropes contributes to depolarization of the plasma membrane upon GnRH stimulation and increases the intracellular Ca2+ concentration via its own Ca2+ permeability and via the activation of voltage-gated Ca2+ channels. However, conditional gene targeting experiments will be needed to unambiguously dissect the physiological role of TRPC channels in the different cell types of the reproductive axis in vivo.

CO2 Fixation, Lipid Production, and Power Generation by a Novel Air-Lift-Type Microbial Carbon Capture Cell System.

An air-lift-type microbial carbon capture cell (ALMCC) was constructed for the first time by using an air-lift-type photobioreactor as the cathode chamber. The performance of ALMCC in fixing high concentration of CO2, producing energy (power and biodiesel), and removing COD together with nutrients was investigated and compared with the traditional microbial carbon capture cell (MCC) and air-lift-type photobioreactor (ALP). The ALMCC system produced a maximum power density of 972.5 mW·m(-3) and removed 86.69% of COD, 70.52% of ammonium nitrogen, and 69.24% of phosphorus, which indicate that ALMCC performed better than MCC in terms of power generation and wastewater treatment efficiency. Besides, ALMCC demonstrated 9.98- and 1.88-fold increases over ALP and MCC in the CO2 fixation rate, respectively. Similarly, the ALMCC significantly presented a higher lipid productivity compared to those control reactors. More importantly, the preliminary analysis of energy balance suggested that the net energy of the ALMCC system was significantly superior to other systems and could theoretically produce enough energy to cover its consumption. In this work, the established ALMCC system simultaneously achieved the high level of CO2 fixation, energy recycle, and municipal wastewater treatment effectively and efficiently.

Treatment of high-strength corn steep liquor using cultivated polyvinyl alcohol gel beads in an anaerobic fluidized-bed reactor.

Polyvinyl alcohol (PVA) gel beads cultivated in an upflow anaerobic sludge-blanket reactor treating synthetic corn steep liquor (CSL) wastewater were used to seed a lab-scale anaerobic fluidized-bed (AFB) reactor also treating CSL. Under steady-state conditions in the AFB reactor, a COD removal efficiency in excess of 96% was achieved at an organic loading rate (OLR) of 25 g/l/d with a hydraulic retention time (HRT) of 10 h. Furthermore, a removal efficiency of 91% was achieved at an OLR of 27.5 g/l/d with an HRT of only 6 h. With a biomass attachment 1.02 g VSS/g PVA-gel beads, the biomass concentration in the AFB reactor was approximately 610 g/l, while for natural granules only 100 g/l is considered possible. Over the study period, the granular PVA gel turned from black to gray while the biomass attached on the outer surface of the beads also changed in composition. In addition, observations of the interior of the gel beads showed that colonization had progressed well into the core, indicating that effective substrate diffusion occurred within the PVA-gel matrix under the good substrate-microorganism contact conditions provided by the AFB reactor.