The Modulatory Role of CYP3A4 in Dictamnine-Induced Hepatotoxicity

Dictamni Cortex (DC) has been reported to be associated with acute hepatitis in clinic and may lead to a selective sub-chronic hepatotoxicity in rats. Nevertheless, the potent toxic ingredient and the underlying mechanism remain unknown. Dictamnine (DTN), the main alkaloid from DC, possesses a furan ring which was suspected of being responsible for hepatotoxicity via metabolic activation primarily by CYP3A4. Herein, the present study aimed to evaluate the role of CYP3A4 in DTN-induced liver injury. The in vitro results showed that the EC50 values in primary human hepatocytes (PHH), L02, HepG2 and NIH3T3 cells were correlated with the CYP3A4 expression levels in corresponding cells. Furthermore, the toxicity was increased in CYP3A4-induced PHH by rifampicin, and CYP3A4 over-expressed (OE) HepG2 and L02 cells. Contrarily, the cytotoxicity was decreased in CYP3A4-inhibited PHH and CYP3A4 OE HepG2 and L02 cells inhibited by ketoconazole (KTZ). In addition, the hepatotoxicity of DTN in enzyme induction/inhibition mice was further investigated in the aspects of biochemistry, histopathology, and pharmacokinetics. Administration of DTN in combination with KTZ resulted in attenuated liver injury, including lower alanine transaminase and aspartate transaminase activities and greater AUC and Cmax of serum DTN, whereas, pretreatment with dexamethasone aggravated the injury. Collectively, our findings illustrated that DTN-induced hepatotoxicity correlated well with the expression of CYP3A4, namely inhibition of CYP3A4 alleviated the toxicity both in vitro and in vivo, and induction aggravated the toxicity effects

Electronic Tongue Combined with Chemometrics to Provenance Discrimination for a Green Tea (Anji-White Tea)

This paper aims to provide a stable instrumental method for provenance discrimination of Anji-White tea by its distinctive taste. 180 authentic and 60 counterfeit white tea samples were collected for specific geographical origins detection; all of them were measured by electronic tongue coupled with 7 independent sensors. Therefore, chemometrics methods, principal component analysis (PCA), and partial least squares discriminant analysis (PLSDA) were performed in classification. The PCA distribution shows that, in provenance analysis, PCA is a simple and reliable tool for small sample sets, but for sets with large objects, PCA seems powerless in classification. Therefore, PLSDA was applied to develop a classification model. The prediction sensitivity and specificity of PLSDA, respectively, reached 0.917 and 0.950. This study demonstrates the potential of combining electronic tongue system and chemometrics as an effective tool for specific geographical origins detection in Anji-White tea

Xuebijing Protects Rats from Sepsis Challenged with Acinetobacter baumannii

Xuebijing (XBJ) injection is a herbal medicine that has been widely used in the treatment of sepsis in China; however, its role in the development and progression of Acinetobacter baumannii sepsis and the underlying mechanisms remain uninvestigated. In the present study, fifty-four male Wistar rats were randomly assigned to normal-control group, sepsis-control group, and sepsis + XBJ group, each containing three subgroups of different treatment time periods (6, 12, and 24 hrs following injection, resp.). The sepsis model was established by intraperitoneal injection of A. baumannii ATCC 19606. For XBJ treatment, 4 mL/kg XBJ was administrated simultaneously by intravenous injection through caudal vein every 12 hrs. All animals demonstrated ill state, obvious intestinal dysfunction, histopathological lung damages, and overactive inflammatory responses after A. baumannii infection, and these events could be partially reversed by XBJ treatment from the beginning of infection. XBJ induced an increase in the expression of anti-inflammatory mediator annexin A1; however, two proinflammatory cytokines, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), were decreased at the each monitored time point. These findings suggested that XBJ via its cytokine-mediated anti-inflammatory effects might have a potential role in preventing the progression of A. baumannii infection to sepsis by early administration

Superconducting Fluctuations in Overdoped Bi2Sr2CaCu2O8 + δ

Fluctuating superconductivity—vestigial Cooper pairing in the resistive state of a material—is usually associated with low dimensionality, strong disorder, or low carrier density. Here, we report single-particle spectroscopic, thermodynamic and magnetic evidence for persistent superconducting fluctuations in the heavily hole-doped cuprate superconductor Bi2Sr2CaCu2O8þδ(Tc¼66 K) despite the high carrier density. With a sign-problem-free quantum Monte Carlo calculation, we show how a partially flat band at ðπ;0Þcan help enhance superconducting phase fluctuations. Finally, we discuss the implications of an anisotropic band structure on the phase-coherence-limited superconductivity in overdoped cuprates and other superconductors

Superconducting fluctuations in overdoped Bi2_2Sr2_2CaCu2_2O8+δ_{8+\delta}

Fluctuating superconductivity - vestigial Cooper pairing in the resistive state of a material - is usually associated with low dimensionality, strong disorder or low carrier density. Here, we report single particle spectroscopic, thermodynamic and magnetic evidence for persistent superconducting fluctuations in heavily hole-doped cuprate superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ ($T_c$ = 66~K) despite the high carrier density. With a sign-problem free quantum Monte Carlo calculation, we show how a partially flat band at ($\pi$,0) can help enhance superconducting phase fluctuations. Finally, we discuss the implications of an anisotropic band structure on the phase-coherence-limited superconductivity in overdoped cuprates and other superconductors.Comment: main: 8 pages, 6 figures + supplement: 10 pages, 15 figure

Phylogenetic and Genome Analysis of 17 Novel Senecavirus A Isolates in Guangdong Province, 2017

Senecavirus A (SVA), an emerging RNA virus, is considered to be associated with porcine idiopathic vesicular disease (PIVD). From February to September 2017, 17 novel SVA strains were isolated from samples with the vesicular disease from Guangdong Province, China. Full-length genomes and individual genes of the 17 new SVA isolates were genetically and phylogentically analyzed. Results showed that complete genomes, VP1, 3C, and 3D genes of these 17 novel SVA isolates revealed 96.5–99.8%, 95.1–99.9%, 95.6–100%, and 96.9–99.7% nucleotides identities, respectively. Phylogenetic analyses based on sequences of full-length genomes, VP1, 3C, and 3D genes indicated that 17 novel SVA isolates separated to three well-defined groups. Meanwhile, phylogenetic analysis for all available Chinese SVA strains demonstrated that 45 Chinese SVA strains clustered into five distinct groups with no significant relationship between strains from different provinces and/or years, including a newly emerging branch in China. This is the first comprehensive study of phylogenetic analysis for all available Chinese SVA strains, indicating the appearance of a new type of SVA strains and the complicated circulations with at least five different types of SVA strains in pigs in China