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The action principles of traditional Chinese medicines (TCMs) feature multiactive components, multitarget sites, and weak combination with action targets. In the present study, we performed an integrated analysis of metabonomics, proteomics, and lipidomics to establish a scientific research system on the underlying mechanism of TCMs, and Schisandralignan extract (SLE) was selected as a model TCM. In metabonomics, several metabolic pathways were found to mediate the liver injury induced by acetaminophen (APAP), and SLE could regulate the disorder of lipid metabolism. The proteomic study further proved that the hepatoprotective effect of SLE was closely related to the regulation of lipid metabolism. Indeed, the results of lipidomics demonstrated that SLE dosing has an obvious callback effect on APAP-induced lipidic profile shift. The contents of 25 diglycerides (DAGs) and 21 triglycerides (TAGs) were enhanced significantly by APAP-induced liver injury, which could further induce liver injury and inflammatory response by upregulating protein kinase C (PKCβ, PKCγ, PKCδ, and PKCθ). The upregulated lipids and PKCs could be reversed to the normal level by SLE dosing. More importantly, phosphatidic acid phosphatase, fatty acid transport protein 5, and diacylglycerol acyltransferase 2 were proved to be positively associated with the regulation of DAGs and TAGs.SIGNIFICANCE STATEMENTIntegrated multiomics was first used to reveal the mechanism of APAP-induced acute liver failure (ALF) and the hepatoprotective role of SLE. The results showed that the ALF caused by APAP was closely related to lipid regulation and that SLE dosing could exert a hepatoprotective role by reducing intrahepatic diglyceride and triglyceride levels. Our research can not only promote the application of multicomponent technology in the study of the mechanism of traditional Chinese medicines but also provide an effective approach for the prevention and treatment of ALF.

Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure.

The combinational administration of antioxidants and chemotherapeutic agents during conventional cancer treatment is among one of the most controversial areas in oncology. Although the data on the combinational usage of doxorubicin (DOX) and glutathione (GSH) agents have been explored for over 20 years, the duration, administration route, and authentic rationality have not yet been fully understood yet. In the current study, we systematically investigated the pharmacokinetics (PK) and pharmacodynamics (PD) with both in vivo and in vitro models to elucidate the influence of GSH on the toxicity and efficacy of DOX. We first studied the cardioprotective and hepatoprotective effects of GSH in Balb/c mice, H9c2, and HL7702 cells. We showed that coadministration of exogenous GSH (5, 50, and 500 mg/kg per day, intragastric) significantly attenuated DOX-induced cardiotoxicity and hepatotoxicity by increasing intracellular GSH levels, whereas the elevated GSH concentrations did not affect the exposure of DOX in mouse heart and liver. From PK and PD perspectives, then the influences of GSH on the chemotherapeutic efficacy of DOX were investigated in xenografted nude mice and cancer cell models, including MCF-7, HepG2, and Caco-2 cells, which revealed that administration of exogenous GSH dose-dependently attenuated the anticancer efficacy of DOX in vivo and in vitro, although the elevated GSH levels neither influenced the concentration of DOX in tumors in vivo, nor the uptake of DOX in MCF-7 tumor cells in vitro. Based on the results we suggest that the combined administration of GSH and DOX should be contraindicated during chemotherapy unless DOX has caused serious hepatotoxicity and cardiotoxicity.

Among the somatostatin analogues, octreotide (OCT) is the most commonly used in clinic via intravenous or subcutaneous injection to treat various diseases caused by increased secretion of growth hormone, gastrin or insulin. In order to assesse the feasibility of developing oral formulations of OCT, we conducted systematical pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The pharmacokinetic studies in rats showed that intragastric administration of OCT had extremely low bioavailability (<0.5%), but it could specifically distribute to the gastric mucosa due to the high expression of somatostatin receptor 2 (SSTR2) in the rat stomach. The pharmacodynamic studies revealed that intragastric administration of OCT dose-dependently protected against gastric mucosal injury (GMI) in mice with WIRS-induced mouse gastric ulcers, which were comparable to those achieved by intravenous injection of OCT, and this effect was markedly attenuated by co-administration of CYN-154806, an antagonist of SSTR2. In pyloric ligation-induced ulcer mice, we further demonstrated that OCT significantly reduced the secretion of gastric acid via down-regulating the level of gastrin, which was responsible for the protective effect of OCT against GMI. Overall, we have provided pharmacokinetic and pharmacodynamic evidence for the feasibility of developing an oral formulation of OCT. Most importantly, the influence of SSTR2 on the pharmacokinetics and pharmacodynamics of OCT suggested that an oral formulation of OCT might be applicable for other clinical indications, including neuroendocrine neoplasms and pituitary adenoma due to the overexpression of SSTR2 on these tumor cells.

A bidirectional route of communication between the gastrointestinal tract and the central nervous system, termed the “gut-brain axis,” is becoming increasingly relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although plasma and cerebral exposure levels are extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown. In the present study, the neuroprotective effects of PNE were systematically studied via investigation of the regulation by PNE of the gastrointestinal microbial community and γaminobutyric acid (GABA) receptors. The results demonstrated that pretreatment with PNE exerted a remarkable neuroprotective effect on focal cerebral ischemia/reperfusion (I/R) injury in rats, and the efficiency was attenuated in germ-free rats. Pretreatment with PNE could significantly prevent downregulation of Bifidobacterium longum(B.L) caused by I/R surgery, and colonization by B.L could also exert neuroprotective effects. More importantly, both PNE and B.L could upregulate the expression of GABA receptors in the hippocampus of I/R rats, and coadministration of a GABA-B receptor antagonist could significantly attenuate the neuroprotective effects of PNE and B.L. The study above suggests that the neuroprotective effects of PNE may be largely attributable to its regulation of intestinal flora, and oral treatment with B.L was also useful in therapy of ischemia/reperfusion injury (I/R) by upregulating GABA-B receptors.

Rényi (1961) proposed the Rényi entropy. Ebrahimi and Pellerey (1995) and Ebrahimi (1996) proposed the residual entropy. Recently, Nanda et al. (2014) obtained a quantile version of the Rényi residual entropy, the Rényi residual quantile entropy (RRQE). Based on the RRQE function, they defined a new stochastic order, the Rényi quantile entropy (RQE) order, and studied some properties of this order. In this paper, we focus on further properties of this new order. Some characterizations of the RQE order are investigated, closure and reversed closure properties are obtained, meanwhile, some illustrative examples are shown. As applications of a main result, the preservation of the RQE order in several stochastic models are discussed. [ABSTRACT FROM AUTHOR]

A new stochastic order called dynamic cumulative residual quantile entropy (DCRQE) order is established. Some characterizations of the new order are investigated. Closure and reversed closure properties of the DCRQE order are obtained. Applications of the DCRQE ordering in characterizing the proportional hazard rate model and the k -record values model are considered. [ABSTRACT FROM AUTHOR]

Ebrahimi and Pellerey (1995) and Ebrahimi (1996) proposed the residual entropy. Recently, Sunoj and Sankaran (2012) obtained a quantile version of the residual entropy, the residual quantile entropy (RQE). Based on the RQE function, they defined a new stochastic order, the less quantile entropy (LQE) order, and studied some properties of this order. In this paper, we focus on further properties of this new order. Some characterizations of the LQE order are investigated, closure and reversed closure properties are obtained, meanwhile, some illustrative examples are shown. As applications of a main result, the preservation of the LQE order in several stochastic models is discussed. We give the closure and reversed closure properties of the LQE order for coherent systems with dependent and identically distributed components, and also consider a potential application to insurance of this order. [ABSTRACT FROM AUTHOR]

Asadi and Zohrevand (2007). On the dynamic cumulative residual entropy. J. Statist. Plann. Inference, 137, 1931–1941] define the decreasing dynamic cumulative residual entropy (DDCRE) class of life distributions, some properties of the DDCRE class are studied. Navarro et al. (2010). Some new results on the cumulative residual entropy. J. Statist. Plann. Inference, 140, 310–322] further investigate this class, they get some results concerning the relations between the DDCRE class and other classes of distributions. In the present paper some characterization properties of the DDCRE class are investigated, closure and reversed closure properties of this class are obtained.

Di Crescenzo and Longobardi (2002) introduced the past entropy, Sunoj et al. (2013) gave a quantile version for the past entropy, termed as the past quantile entropy (PQE). Based on the PQE function, they defined a new stochastic order called as less PQE (LPQE) order and studied some properties of this order. In the present paper, we focus our interests on further closure properties of this new order. Some characterizations of the LPQE order are investigated, closure and reversed closure properties are obtained. The preservation of the LPQE order in the proportional failure rate and reversed failure rate models is discussed. [ABSTRACT FROM AUTHOR]

The affecting law of nickel on structure and properties of ferro superalloy, which was cast by intermediate frequency induction furnace, were studied by orthogonal experimental method. The tensile strength and oxidation weight gain rate at 1000℃ were tested. The matrix microstructure and scale morphologies and composition were studied using scanning electron microscope (SEM) and X-ray diffraction (XRD) respectively. It was found that the high temperature tensile strength went up with the increase of nickel by the forming of high temperature strengthening phase of γ’. After 100 hours aging at 1000℃, γ’ phase separated in blocks. Certain content of nickel improved the high temperature oxidation resistance of test alloys, but excess of it caused the higher oxidation weight gain rate and loose structure oxide scales with holes and exfoliating. In considering of high temperature tensile strength and oxidation resistance, the ideal content of nickel in ferro superalloy should be 9wt.%, with which at 1000℃ the tensile strength of test alloys mostly exceeded 70MPa, and the average oxidation weight gain rate was only 0.55g.m-2.h-1, reaching the strong oxidation resistance. Such scale was compounded by Cr2O3 and Fe(Ni)Cr2O4 with compact structure, fine and even oxide grains.