[Lignans from stems and leaves of Cephalotaxus fortunei (â ¡)].

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

Berberine Inhibits the Expression of SCT through miR-214-3p Stimulation in Breast Cancer Cells.

In this study, we aimed to evaluate the suppressive abilities of berberine (BBR) on MCF-7 and MDA-MB-231 cells and confirm its underlying mechanisms on miR-214-3p. We first built a panel of 18 miRNAs and 9 lncRNAs that were reported to participate in the mechanism of breast cancer. The RT-qPCR results suggested that BBR illustrated a dosage-dependent pattern in the stimulation to miR-214-3p in both MCF-7 and MDA-MB-231 cells. Then, we performed gain-and-lose function tests to validate the role of miR-214-3p contributing to the anticancer effects of BBR. Both BBR and miR-214-3p mimic reduced the cell viability, repressed migration and invasion capacities, increased rates of total apoptotic cells and ratio of Bax/Bcl-2, and increased the percentage of G2/M cells of MCF-7 and MDA-MB-231 cells by colony formation and CKK8 assay, scratch wound healing and gelatin-based 3D conformation assay, transwell invasion assay, and cell cycle analysis, respectively. However, miR-214-3p inhibitor counteracted all these effects of BBR. Based on the bioinformatics analysis and dual-luciferase reporter test, we identified binding sites between SCT and miR-214-3p. We further confirmed that BBR massively and dose-dependently reduced the mRNA expression and protein levels of SCT in both MCF-7 and MDA-231 cells. We testified that both miR-214-3p mimic and BBR could decrease the mRNA expression and protein levels of SCT, while miR-214-3p inhibitor weakened these reductions. In conclusion, BBR suppressed MCF-7 and MDA-MB-231 breast cancer cells by upregulating miR-214-3p and increasing its inhibition to SCT.

Anisotropic Signal Processing with Trigonal Selenium Nanosheet Synaptic Transistors.

Hardware implementation of an artificial neural network requires neuromorphic devices to process information with low energy consumption and high heterogeneity. Here we demonstrate an electrolyte-gated synaptic transistor (EGT) based on a trigonal selenium (t-Se) nanosheet. Due to the intrinsic low conductivity of the Se channel, the t-Se synaptic transistor exhibits ultralow energy consumption, less than 0.1 pJ per spike. More importantly, the intrinsic low symmetry of t-Se offers a strong anisotropy along its c- and a-axis in electrical conductance with a ratio of up to 8.6. The multiterminal EGT device exhibits an anisotropic response of filtering behavior to the same external stimulus, which enables it to mimic the heterogeneous signal transmission process of the axon-multisynapse biostructure in the human brain. The proof-of-concept device in this work represents an important step to develop neuromorphic electronics for processing complex signals.

Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease.

RATIONALE: A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature. OBJECTIVE: To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD). METHODS AND RESULTS: Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes. CONCLUSIONS: Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

PURPOSE: Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. METHODS: Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. RESULTS: The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. CONCLUSIONS: TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

[Research progress of Chinese herbal medicine and traditional Chinese medicine resulting in liver injury].

The adverse reactions caused by Chinese herbal medicine and traditional Chinese medicine are reported increased in recent years, among which the acute liver injury caused by Chinese herbal medicine accounts for 21.5% of total liver injuries. Despite the misuse of traditional Chinese medicine not in accordance with differentiation of symptoms and signs, the adverse reaction of Chinese herbal medicine itself can't be little to these adverse events. The paper summarizes the most common categories of traditional Chinese medicine resulting in liver injury, the mechanism, pathological characteristics, clinical symptom of liver injury, the reasons of the reaction and how to prevent. The research aims to enhance the clinical physician recognition of liver injury caused by Chinese herbal medicine, in order to ensure the safe and rational usage of traditional Chinese medicine.

[Constituents of Millettia nitida var. hirsutissima].

OBJECTIVE: To separate effective constituents from Millettia nitida var. hirsutissima. METHOD: Compounds were isolated by chromatography methods, structures were identified by spectroscopic means. RESULT: Eight flavonoids (1-8) and two triterpenes (9-10) were isolated from this plant. They were identified as calycosin (1), genistin (2), gliricidin (3), 8-O-methylretusin (4), afromosin-7-O-beta-D-glucopyranoside (5), lanceolarin (6), soliquiritigenin (7), symplocoside (8), lupeol (9), 3beta-friedelanol (10). CONCLUSION: The compounds (1-10) were obtained from M. nitida var. hirsutissima for the first time. The 13C-NMR dada of 1 were correct assignment on the basis of 2D-NMR spectral analysis.

Positron Emission Tomography: applications in drug discovery and drug development.

Positron Emission Tomography (PET) is a sophisticated nuclear imaging modality that affords researchers the ability to conduct both functional and molecular imaging on biological and biochemical processes in vivo. In functional imaging, biological parameters such as metabolic rate and perfusion that can be altered by disease or treatment are monitored. In molecular imaging, PET can be used to examine and quantify cellular events such as cell trafficking, receptor binding and gene expression. Therefore, PET is an important tool to elucidate mechanisms associated with diseases and drug actions. In addition to PET, microPET is designed to image small animals. A great tool to facilitate preclinical studies and basic research, it can eliminate the need of sacrificing the animal by enabling noninvasive, longitudinal, and serial studies. The results from preclinical studies using microPET can be directly correlated with clinical studies using PET, thus bridging the chasm that used to separate the 2 pivotal phases in drug development. This review first describes the basic principles of PET and compares it to other imaging modalities. Then, PET procedures and PET isotopes and tracers synthesis are outlined. Next, functional and molecular PET imaging applications in the fields of oncology, neurology, and cardiology in both humans and animals are presented. Spanning a wide range, these applications demonstrate the versatility of PET and how it can be used to accelerate drug discovery and development. Finally, the advantages and limitations of PET and how it can be used in the future to minimize risks of drug development are discussed.