XIAO-CHAI-HU TANG IN TREATING MODEL MICE WITH D-GALACTOSAMINE-INDUCED LIVER INJURY

This study explored the effects of a classical Chinese medicine formula- Xiao-Chai-Hu Tang(XCHT) on the model mice with D-galactosamine -induced liver injury. Sixty male imprinting control region (ICR) mice were used in the present study, and they were separated randomly into 6 groups: a normal control group (Group A, n=10), a model control (Group B, n=10), a positive control (Group C, n=10), a low dose of XCHT group (Group D, n=10), a medium dose of XCHT group (Group E, n=10), and a high dose of XCHT group (Group F, n=10). ELISA was used to detect the IL-6 and TNF-α levels in the serum. Real-time PCR was performed to assess the expression of FasmRNA, Fas-LmRNA, Bcl-2mRNA of the liver tissues. Western blotting was used to detect the Bax protein expression of the liver tissues. The serum IL-6 and TNF-α levels of Group B were significantly higher than the other groups (

Supramolecular assemblies constructed from inverted cucurbit[7]uril and lanthanide cations: synthesis, structure and sorption properties

The interaction of a series of lanthanide cations (Ln³⁺) with inverted cucurbit[7]uril (iQ[7]) in the presence of [ZnCl₄]²⁻ anions as a structure-directing agent have been investigated. Single-crystal X-ray diffraction analysis has revealed that the [ZnCl₄]²⁻ anions surround the iQ[7] molecules via the outer surface interactions of iQ[7]. This results in the formation of honeycomb-like frameworks, and ultimately linear supramolecular chains of iQ[7] in which Ln³⁺ cations occupy voids within the framework. Moreover, these iQ[7]/Ln³⁺-based supramolecular assemblies exhibit excellent thermal stability as well as permanent porosity, and in one case screening revealed a high CH₃OH uptake capacity compared with other porous organic materials assembled solely through hydrogen bonding under ambient conditions

Characteristics of polycyclic aromatic hydrocarbons in PM2.5 emitted from different cooking activities in China

Nineteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 emitted from five different cooking activities were characterized, and their influencing factors were determined. The total quantified particle-bounded PAH concentrations (Sigma PAHs) in the airs from the cooking activities were 4.2-36.5-fold higher than those in corresponding backgrounds. The highest I PAHs pound were seen in cafeteria frying (783 +/- 499 ng/m(3)), followed by meat roasting (420 +/- 191 ng/m(3)), fish roasting (210 +/- 105 ng/m(3)), snack-street boiling (202 +/- 230 ng/m(3)), and cafeteria boiling (150 +/- 65 ng/m(3)). The main influencing factors on the PAH emissions were cooking methods, fat contents in raw materials, and oil consumptions. Four- to six-ringed PAHs had the highest contributions to the Sigma PAHs (avg. 87.5%). Diagnostic ratios of individual PAH were similar between the two charbroiling and other three conventional Chinese cooking methods, respectively, demonstrating the dominance of cooking methods in the PAH emissions. Remarkably high benzo(b)fluoranthene/benzo(k)fluoranthene (BbF/BkF) ratio (8.31) was seen in the snack-street boiling, attributed to the coal combustion as cooking fuel. Both fluoranthene/(fluoranthene + pyrene) [FLT/(FLT + PYR)] and benzo(a)anthracene/(benzo(a)anthracene + chrysene) [BaA/(BaA + CHR)] ratios were higher for the oil-based cooking than those from the water-based ones. In addition, two ratios of indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene + benzo(g,h,i)perylene) [IPY/(IPY + BPE)] and benzo(a)pyrene/(benzo(a)pyrene + benzo(g,h,i)perylene) [BaP/(BaP + BPE)] were higher for two charbroiling than the three conventional Chinese cooking methods. The characterization work in this study is particularly important since cooking is a potential contributor of atmospheric PAHs in urban China. Carcinogenic potencies of PAHs were assessed by comparison with the air quality guideline and health risk estimation. The BaP and BaP equivalent were higher for the oil-based than the water-based cooking activities

Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission

We previously showed that gastrin-releasing peptide receptor (GRPR) in the spinal cord is important for mediating nonhistaminergic itch. Neuromedin B receptor (NMBR), the second member of the mammalian bombesin receptor family, is expressed in a largely nonoverlapping pattern with GRPR in the superficial spinal cord, and its role in itch transmission remains unclear. Here, we report that Nmbr knock-out (KO) mice exhibited normal scratching behavior in response to intradermal injection of pruritogens. However, mice lacking both Nmbr and Grpr (DKO mice) showed significant deficits in histaminergic itch. In contrast, the chloroquine (CQ)-evoked scratching behavior of DKO mice is not further reduced compared with Grpr KO mice. These results suggest that NMBR and GRPR could compensate for the loss of each other to maintain normal histamine-evoked itch, whereas GRPR is exclusively required for CQ-evoked scratching behavior. Interestingly, GRPR activity is enhanced in Nmbr KO mice despite the lack of upregulation of Grpr expression; so is NMBR in Grpr KO mice. We found that NMB acts exclusively through NMBR for itch transmission, whereas GRP can signal through both receptors, albeit to NMBR to a much lesser extent. Although NMBR and NMBR(+) neurons are dispensable for histaminergic itch, GRPR(+) neurons are likely to act downstream of NMBR(+) neurons to integrate NMB-NMBR-encoded histaminergic itch information in normal physiological conditions. Together, we define the respective function of NMBR and GRPR in itch transmission, and reveal an unexpected relationship not only between the two receptors but also between the two populations of interneurons in itch signaling

DISCOVERY OF POTENT, ORALLY ACTIVE COMPOUNDS OF TYROSINE KINASE AND SERINE/THREONINE-PROTEIN KINASE INHIBITOR WITH ANTI-TUMOR ACTIVITY IN PRECLINICAL ASSAYS

Traditional medicines have become the most productive source of leads for drugs development, particularly as anti-cancer agents. Various screening approaches are being applied. Sorafenib, a multikinase inhibitor, is used to treat primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer. A small library of compounds analogous to sorafenib were designed and screened for the treatment of liver cancer. Multiple members of the family in an assay panel of tyrosine kinase family and serine/threonine-protein kinase family, including VEGFR, Abl, Aurora A, p 38, Lck, Src, PDGFR, Flt3, c-RAF, c-KIT, MEK(MAPKK) were selected to test these compounds. Analysis of the selectivity patterns for these compounds shows specificity for many kinase families. IC50 were measured for the selected compounds. Multiple compounds have very similar kinase inhibition profiles of VEGFR, Flt3, FGFR to that of sorafenib. The IC50 of c-RAF of BB1 is lower than sorafenib. The IC50 of c-RAF of BB3-12 is higher than that of sorafenib. For Flt3, IC50 of BB1-4 is less than sorafenib. The IC50 value of KDR of BB1-10 is less than sorafenib. especially against c-RAF, PDGFR, c-KIT, KDR compared to sorafenib. These compounds are potent Raf1 and Flt4 kinase inhibitors

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites

BackgroundThere is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders.MethodThis study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype “All anxiety disorders” to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations.ResultsBidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders.ConclusionOur findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites