Identifying Key Node with Motif-Based PageRank on Acupoint-Disease Network.

Existing research combines acupuncture theory with network science and proposes a new paradigm for the study of acupoint selection patterns-a key acupoint mining algorithm based on acupoint networks. However, the basic idea of this study for finding key acupoints is based on binary acupoint synergy relationships, which ignores the higher-order synergy among multiple acupoints and does not truly reflect the implicit patterns of each acupoint among meridian systems. Moreover, the mining results assessment method, which this new paradigm involves, does not have wide applicability and universality. In this paper, with the introduction of higher-order interactions between multiple acupoints, a high-specificity key acupoint mining algorithm based on 3-node motif is proposed in the acupoint-disease network (ADN). In response to the narrow applicability of the new research paradigm involving the evaluation of algorithms' measures, new and widely applicable and universal evaluation criteria are introduced in terms of resolution, network loss, and accuracy, respectively. Based on the principles of acupoint selection involved in acupuncture clinics in Chinese medicine, the acupoints involved in the data were divided into a total of 19 regions according to their distribution characteristics. From these 19 regions, we selected the key acupoints that have a large impact on the global network. Finally, we compared this algorithm with five other acupoint importance assessment algorithms in terms of resolution, network loss, and accuracy, respectively. The comprehensive results show that the algorithm identifies key acupoints with an accuracy of 63%, which is 14% to 21% higher than other existing methods. The key acupoints identified by the algorithm have a significant disruptive effect on the connectivity of the network, indicating that the key acupoints are at the core of the acupoint-disease network topology. They have a significant propagation influence on other acupoints, which means that the key acupoints have high-synergistic cooperation with other acupoints. Meanwhile, the stability and specificity of the algorithm ensure the reliability of the key acupoints. We believe that the key acupoints identified by the algorithm can be used as core acupoints from the perspective of network topology and high synergy of other acupoints, respectively, and help researchers explore targeted and high-impact combinations of acupoints to optimize existing acupuncture prescriptions under condition constraints.

Usenamine A induces apoptosis and autophagic cell death of human hepatoma cells via interference with the Myosin-9/actin-dependent cytoskeleton remodeling.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-associated mortality worldwide. Myosin-9's role in HCC and the anti-HCC effect of the drugs targeting Myosin-9 remain poorly understood so far. Candidate antitumor agents obtained from natural products have attracted worldwide attention. Usenamine A is a novel product, which was first extracted in our laboratory from the lichen Usnea longissima. According to published reports, usenamine A exhibits good antitumor activity, while the mechanisms underlying its antitumor effects remain to be elucidated. PURPOSE: The present study investigated the anti-hepatoma effect of usenamine A and the underlying molecular mechanisms, along with evaluating the therapeutic potential of targeting Myosin-9 in HCC. METHODS: The CCK-8, Hoechst staining, and FACS assays were conducted in the present study to investigate how usenamine A affected the growth and apoptosis of human hepatoma cells. Moreover, TEM, acridine orange staining, and immunofluorescence assay were performed to explore the induction of autophagy by usenamine A in human hepatoma cells. The usenamine A-mediated regulation of protein expression in human hepatoma cells was analyzed using immunoblotting. MS analysis, SPR assay, CETSA, and molecular modeling were performed to identify the direct target of usenamine A. Immunofluorescence assay and co-immunoprecipitation assay were conducted to determine whether usenamine A affected the interaction between Myosin-9 and the actin present in human hepatoma cells. In addition, the anti-hepatoma effect of usenamine A was investigated in vivo using a xenograft tumor model and the IHC analysis. RESULTS: The present study initially revealed that usenamine A could suppress the proliferation of HepG2 and SK-HEP-1 cells (hepatoma cell lines). Furthermore, usenamine A induced cell apoptosis via the activation of caspase-3. In addition, usenamine A enhanced autophagy. Moreover, usenamine A administration could dramatically suppress the carcinogenic ability of HepG2 cells, as evidenced by the nude mouse xenograft tumor model. Importantly, it was initially revealed that Myosin-9 was a direct target of usenamine A. Usenamine A could block cytoskeleton remodeling through the disruption of the interaction between Myosin-9 and actin. Myosin-9 participated in suppressing proliferation while inducing apoptosis and autophagy in response to treatment with usenamine A. In addition, Myosin-9 was revealed as a potential oncogene in HCC. CONCLUSIONS: Usenamine A was initially revealed to suppress human hepatoma cells growth by interfering with the Myosin-9/actin-dependent cytoskeleton remodeling through the direct targeting of Myosin-9. Myosin-9 is, therefore, a promising candidate target for HCC treatment, while usenamine A may be utilized as a possible anti-HCC therapeutic, particularly in the treatment of HCC with aberrant Myosin-9.

Usnic Acid Derivatives with Cytotoxic and Antifungal Activities from the Lichen Usnea longissima.

Eight usnic acid derivatives, that is, usenamines A-F (1-6), usone (7), and isousone (8), together with the known (+)-usnic acid (9), were isolated from the lichen Usnea longissima. Their structures were elucidated using 1D and 2D NMR and MS data, and the absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analyses. Compounds 1, 2, and 8 showed inhibitory effects on the growth of human hepatoma HepG2 cells with IC50 values of 6.0-53.3 µM compared with methotrexate as the positive control, which had an IC50 value of 15.8 µM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-15.0 µM. The isolated compounds were also evaluated for their antifungal and antibacterial activities, with 7 and 8 exhibiting weak inhibitory effects on fungal Trichophyton rubrum spp. with an MIC value of 41.0 µM.

Noralashinol A, a new norlignan from stem barks of Syringa pinnatifolia.

One new norlignan, namely noralashinol A (1), one known analogue (2), together with seven known lignans (3-9) were isolated from the stem barks of Syringa pinnatifolia. Their structures were elucidated extensively by spectroscopic methods, including mass spectrometry and 1D and 2D NMR spectroscopies. Compound 8 significantly inhibited NO production in LPS-induced BV-2 murine microglia cells with its IC50 value of 20.7 µM, compared to a positive control quercetin with its IC50 value of 15.3 µM.

[Phenolic constituents from lichen Usnea longissima].

Sixteen compounds were isolated from lichen Usnea longissima using of various chromatographic techniques including silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. By spectroscopic data analyses, their structures were identified by as useanol(1), lecanorin(2), 3-hydroxy-5-methylphenyl 2-hydroxy-4-methoxy-6-methylbenzoate(3), lecanorin E(4), 3'-methylevernic acid(5), evernic acid(6), barbatinic acid(7), 3,7-dihydroxy-1,9-dimethyldibenzofuran(8), orcinol(9), O-methylorcinol(10), methyl orsellinate(11), methyl everninate(12), 2,5-dimethyl-1,3-benzenediol(13), 2-hydroxy-4-methoxy-3,6-dimethyl benzoic acid(14), ethyl everninate(15), and ethyl 2,4-dihydroxy-6-methylbenzoate(16). Compound 1 was obtained as a natural product for the first time, and 3,4, 8,10,12, and 13 were isolated from Usneaceae family for the first time. Compound 1, 8, and 13 showed significant anti-inflammatory activity against NO production in RAW 267.4 cells with IC50 values of 6.8, 3.9 and 4.8 µmol•L⁻¹, respectively, compared with the positive controls curcumin(IC50 15.3 µmol•L⁻¹) and indomethacin(IC50 42.9 µmol•L⁻¹).

Alkaloids from the tribe Bocconieae (papaveraceae): a chemical and biological review.

The Bocconieae tribe, consisting of only the genera Macleaya and Bocconia, possesses significant economic and medicinal value and plays an important role in health management for people in developing countries. During the past decades, research on metabolites and relative pharmacology, including the isolation and identification of a variety of molecules, has shed light on the tribe. Among those molecules, isoquinoline alkaloids, and their antimicrobial, antifungal, and anti-inflammatory activities are especially noteworthy. This paper presents a comprehensive compilation of current research progress, with emphasis on the alkaloids and their distribution, phytochemical and pharmacological investigation, toxicity and side effects, related chemotaxonomy and future use prospects, and hopefully provides a valuable reference as an effort to promote further exploration and application of this tribe.