Discovery of Two GSK3β Inhibitors from Sophora flavescens Ait. using Structure-based Virtual Screening and Bioactivity Evaluation.

Objective: Kushen (Sophora flavescens Ait.) has a long history of medicinal use in China due to its medicinal values, such as antibacterial, antiviral, and anti-inflammatory. Rapid discovery of the components and the medicinal effects exerted by Kushen will help elucidate the science of Kushen in curing diseases.

Guiqi Baizhu prescription ameliorates cytarabine-induced intestinal mucositis by targeting JAK2 to inhibit M1 macrophage polarization.

Background: Intestinal mucositis (IM) is characterized by damage to the intestinal mucosa resulting from inhibition of epithelial cell division and loss of renewal capacity following anticancer chemotherapy and radiotherapy. Cytarabine (Ara-C), the main chemotherapy drug for the treatment of leukemia and lymphoma, is a frequent cause of IM. Guiqi Baizhu prescription (GQBZP) is a traditional Chinese medicine with anti-cancer and anti-inflammatory effects.

Astragaloside IV alleviates cytarabine-induced intestinal mucositis by remodeling macrophage polarization through AKT signaling.

Background: Intestinal mucositis (IM) is one of the common side effects of chemotherapy with Cytarabine (Ara-C) and contributes to the major dose-limiting factor of chemotherapy, while the effective drug for IM is little. Astragalus, one of the main active components extrated from the roots of Astragalus membranaceus (AS-IV), is a common Chinese herbal medicine used in gastrointestinal diseases. However, the effect and mechanism of AS-IV on IM is unclear.

Engineering piperlongumine-inspired analogs as Nrf2-dependent neuroprotectors against oxidative damage by an electrophilicity-based strategy.

Oxidative stress contributes significantly to the development of neurodegenerative diseases, thus developing nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent neuroprotectors is highly required for either prevention or treatment of these diseases. This work highlights an electrophilicity-based strategy that allows finding more active Nrf2-dependent neuroprotectors than natural piperlongumine (PL). Electrophilic modification was applied on both the exocylic and endocyclic Michael acceptors of PL, which includes placement of an electron-withdrawing trifluoromethyl group on its aromatic ring in the ortho, meta, or para position to the exocyclic olefin, and further introduction of an electron-withdrawing α-chlorine on its lactam ring.

Deciphering the active constituents of Dabushen decoction of ameliorating osteoarthritis PPARγ preservation by targeting DNMT1.

Osteoarthritis (OA) is a multifactorial and chronic degenerative joint disease. Due to the adverse effects of currently used drugs, a safer and more effective therapy for treating OA is needed. Peroxisome proliferator-activated receptor-γ (PPARγ) is a key protein protecting cartilage.

[Animal Model Establishment and Its Mechanism of Cytarabine-Iduced Myelosuppression].

Objective: To establish an optimized model of bone marrow suppression induced by cytarabine (Ara-C) in C57BL/6 mice and preliminarily explore the mechanism of myelosuppression based on the cycle and apoptosis of BMNC.

Methods: C57BL/6 mice were intraperitoneally injected with Ara-C 50, 100 and 200 mg/kg for 7 days, respectively. The survival rate and body weight of C57BL/6 mice were monitored.

Developing dietary curcumin mono-carbonyl piperidinone analogs as Nrf2-dependent cytoprotectors against oxidative damage: Structure-activity relationship and mechanisms.

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, β-unsaturated piperidinone.

[Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design].

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal.

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC.

PEGylated NALC-functionalized gold nanoparticles for colorimetric discrimination of chiral tyrosine.

In this work, acid and matrix-tolerant multifunctionalized gold nanoparticles (AuNPs) with an integrated chiral selector towards tyrosine (Tyr) and polyethylenglycol (PEG) chains were developed for visual chiral discrimination of Tyr in biological samples under acid conditions. In brief, AuNPs multifunctionalized with N-acetyl-l-cysteine (NALC) and PEG (PEG/NALC-AuNPs) were prepared via a simple strategy. In the presence of l-Tyr, the color of PEG/NALC-AuNP solution changed from red to gray, while no obvious color change was observed with the introduction of d-Tyr, which indicated that the introduction of PEG onto the surface of AuNPs has no effect on the chiral recognition between l-Tyr and NALC.

(±)-Alternamgin, a Pair of Enantiomeric Polyketides, from the Endophytic Fungi Alternaria sp. MG1.

A pair of enantiomeric polyketides, (+)- and (-)-alternamgin (1), featuring an unprecedented 6/6/6/6/5/6/6 seven ring backbone, were isolated from the endophytic fungi Alternaria sp. MG1. The relative configuration of 1 was determined using X-ray diffraction, and the absolute configurations of (±)-1 were confirmed by comparing the experimental and calculated ECD data.

Isolation, Identification, and Activity Evaluation of Chemical Constituents from Soil Fungus Fusarium avenaceum SF-1502 and Endophytic Fungus Fusarium proliferatum AF-04.

Fusarium, a large genus of filamentous fungi, is widely distributed in soil and plants. Fusarium is a prolific source of novel chemical constituents with various bioactivities. In search for antibiotics from soil and endophytic fungi, the secondary metabolites of Fusarium avenaceum SF-1502 and Fusarium proliferatum AF-04 were investigated.

Chiral separation and absolute configurations of two pairs of racemic polyprenylated benzophenones from Hypericum sampsonii.

(±) Sampsonins A-B (1-2), two pairs of racemic polyprenylated benzophenones, were isolated from the aerial parts of Hypericum sampsonii and successfully separated by chiral HPLC column. Their structures were elucidated by spectroscopic analyses, X-ray diffraction analysis, and quantum chemical calculation of ECD method. Besides, the plausible biogenetic pathways of 1-2 were proposed, and all of them were evaluated for RXRα transcriptional-inhibitory activities and cytotoxicity against HeLa cells.

Study on a series of novel self-assembly supramolecular solar cells based on a double-layer structured chromophore of Zn-porphyrins.

We prepared in this work an anchoring porphyrin and a series of hat-porphyrins. The zinc atom of the hat-porphyrins can be coordinated axially with the pyridine moiety of the anchoring porphyrin which is anchored on the titania surface by a carboxyl group. The structures of the assemblies were confirmed using computational calculations, transmission electron microscopy (TEM) and energy dispersive spectrometry (EDS).

Sesquiterpenoids and tirucallane triterpenoids from the roots of Scorzonera divaricata.

A sulfated guaiane sesquiterpene lactone, an unusual pyridinium alkaloid with a sulfated guaiane sesquiterpene lactone nucleus, an amino conjugate of a sulfated guaiane sesquiterpene lactone, a bisabolane sesquiterpene, three tirucallane triterpenes, and six known compounds, were isolated from roots of Scorzonera divaricata. Their structures and absolute configurations were established based on chemical and spectroscopic methods, X-ray single crystal crystallography, and also by comparison with experimental and calculated ECD spectra. One of the tirucallane triterpenes exhibited significant cytotoxic activities against four human cancer cell lines (HL60, HeLa, HepG2, and SMMC-7721) in vitro.

MiR-21/miR-375 ratio is an independent prognostic factor in patients with laryngeal squamous cell carcinoma.

We sought to identify microRNAs that exhibit altered expression in laryngeal squamous cell carcinoma (SCC) and to determine whether microRNA expression is predictive of disease. This study was divided into three steps: (1) The expression of six miRNAs, such as up-regulated miR-223, miR-142-3p, miR-21, miR-16, miR-23a and down-regulated miR-375, was evaluated using total RNA isolated from freshly-frozen primary tumors and non-cancerous laryngeal squamous epithelial tissues and analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). (2) We also investigated the mRNA expression levels of processing elements (RNASEN, DGCR8, and DICER1) that participate in miRNA-biogenesis pathway.

Versatile syntheses of hemi-cryptophanes and a metallo-cryptophane from a hexa-functionalized C3v -symmetrical tribenzotriquinacene (TBTQ) derivative.

A number of three-fold C3v -symmetrical tribenzotriquinacene (TBTQ) cavitands were synthesized by a "metamorphosis-to-half" strategy, employing six-fold etherification reactions between the hexakis(chloromethyl)-TBTQ intermediate 2 a and various 5-functionalized resorcinols. X-ray structure analyses of single crystals of the cavitands revealed limited rotational flexibility of the resorcinol bridging units, which enables an apical, nearly co-axial orientation of the three functional groups and, as a consequence, the construction of nanoscale cage-like molecules via covalent or coordination bonding. On this basis, two TBTQ-based hemicryptophanes were prepared from the TBTQ cavitands via covalent bond formation in good yields.

Curcumin suppresses invasiveness and vasculogenic mimicry of squamous cell carcinoma of the larynx through the inhibition of JAK-2/STAT-3 signaling pathway.

To determine the role of JAK-2/STAT-3 signaling pathway in invasion and vasculogenic mimicry of laryngeal squamous cell carcinoma. HEp-2 cells were treated with 1 or 10 μmol/L curcumin and AG490 (the inhibitor of JAK-2) for 48 h, the invasion and vasculogenic mimicry of tumor cells were tested with Transwell chamber test and tube formation experiment. RT-PCR was used to measure the expression of MMP-2 and VEGF.

miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival.

The dismal outcome of laryngeal squamous cell carcinoma (SCC) patients highlights the need for novel prognostic biomarkers. The involvement of microRNAs in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify microRNAs that exhibit altered expression in laryngeal SCC and to determine whether microRNA (miRNA) expression is predictive of disease progression and/or patient survival.

Indoleacetic acid derivatives from the seeds of Ziziphus jujuba var. spinosa.

A pair of diastereoisomers, the N-glycosylated derivatives of dioxindole-3-hydroxy-3-acetic acid 1-2, and their conjugates with flavonoids 3-8, was isolated from the seeds of Ziziphus jujuba var. spinosa. Their structures were elucidated by NMR spectroscopic analyses, and the absolute configurations were determined by circular dichroism method.

Eremophilane-type sesquiterpenoids with diverse skeletons from Ligularia sagitta.

Five new highly oxygenated eremophilane-type sesquiterpenoids, possessing C19 (1 and 2), C15 (3 and 4), and C14 (8) skeletons, along with eight known eremophilenolides were obtained from the aerial parts of Ligularia sagitta. The absolute configuration of 1 was assigned by X-ray diffraction analysis and that of 3 by ECD spectroscopy. Compounds 1-10 were evaluated for their antibacterial activities against Staphyloccocus aureus, Bacillus subtilis, Escherichia coli, Bacillus cereus, and Erwinia carotovora.

New clerodane diterpenoid glycosides from the aerial parts of Nannoglottis carpesioides.

Three new clerodane diterpenoid glycosides with L-arabinose (1-3), together with ten known compounds including phytol-type diterpenes, cycloartane-type, ursane-type, and oleanane-type triterpenes, were isolated from the aerial parts of Nannoglottis carpesioides which a Chinese endemic genus. The structures of the new compounds 1-3 were identified based on chemical and spectroscopic studies, including one- and two-dimensional NMR, HRESIMS, UV, and IR results. Their absolute configurations were determined by the application of theory calculations of optical rotation, which were compared with the experimental data.

Eleven new highly oxygenated triterpenoids from the leaves and stems of Schisandra chinensis.

Eleven new triterpenoids, schinchinenins A–H (1–8) and schinchinenlactones A–C (9–11) together with three known triterpenoids, henrischinins A–C (12–14), were isolated from the leaves and stems of Schisandra chinensis by bioassay-guided fractionation. Schinchinenin A (1) is the first example of a highly oxygenated triterpenoid characterized by a 5/5/7/6/5-fused pentacyclic ring and a 3-one-2-oxabicyclo[3.2.