Composite Graphene for the Dimension- and Pore-Size-Mediated Stem Cell Differentiation to Bone Regenerative Medicine.

As one of the most promising means to repair diseased tissues, stem cell therapy with immense potential to differentiate into mature specialized cells has been rapidly developed. However, the clinical application of stem-cell-dominated regenerative medicine was heavily hindered by the loss of pluripotency during the long-term in vitro expansion. Here, a composite three-dimensional (3D) graphene-based biomaterial, denoted as GO-Por-CMP@CaP, with hierarchical pore structure (micro- to macropore), was developed to guide the directional differentiation of human umbilical cord MSCs (hucMSCs) into osteoblasts.

The Histone Deacetylase Inhibitor I1 Induces Differentiation of Acute Leukemia Cells With MLL Gene Rearrangements Epigenetic Modification.

Acute leukemia (AL) is characterized by excessive proliferation and impaired differentiation of leukemic cells. AL includes acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Previous studies have demonstrated that about 10% of AML and 22% of ALL are mixed lineage leukemia gene rearrangements (MLLr) leukemia.

Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid.

Cholestasis is one of the most severe manifestations of liver injury and has limited therapeutic options. Allopurinol (AP), an inhibitor of uric acid (UA) synthesis, was reported to prevent liver damage in several liver diseases. However, whether AP protects against intrahepatic cholestatic liver injury and what is the role of UA in the pathogenesis of cholestasis remain unknown.

Inhibitory effect of sixteen pharmaceutical excipients on six major organic cation and anion uptake transporters.

To date, relatively little is known about the interactions of pharmaceutical excipients with hepatic and renal drug uptake transporters. The present study was designed to systematically evaluate the effects of 16 commonly consumed excipients on human organic cation transporter 1 and 2 (hOCT1 and hOCT2), human organic anion transporter 1 and 3 (hOAT1 and hOAT3) and human organic anion transporting polypeptide 1B1 and 1B3 (hOATP1B1 and hOATP1B3). The inhibitory effects and mechanisms of excipients on transporters were investigated using uptake studies, cell viability assays, concentration-dependent studies, and the Lineweaver-Burk plot method.

Comparative toxicity analysis of corannulene and benzo[a]pyrene in mice.

Increasing production of corannulene (COR), a non-planar polycyclic aromatic hydrocarbon (PAH) with promising applications in many fields, has raised a concern about its potential toxic effects. However, no study has been undertaken to evaluate its metabolism and toxicity in mammals. In this study, the acute toxicities of COR in mice were compared with benzo[apyrene (BaP), a typical planar PAH with almost the same molecular weight.

Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives.

Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a slower cellular accumulation as well as a weaker induction of cytochrome P450 1 (CYP1/Cyp1) isozymes.

Glucocorticoids Increase Renal Excretion of Urate in Mice by Downregulating Urate Transporter 1.

Both nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids have been widely used for the treatment of gout, a disease promoted by an excess body burden of uric acid (UA); however, their effects on the homeostasis of UA remain poorly understood. The present study showed that 1-week treatments with three NSAIDs (ibuprofen, diclofenac, and indomethacin) had little effect on UA homeostasis in mice, whereas 1-week low doses (1 and 5 mg/kg) of dexamethasone (DEX) significantly decreased serum UA by about 15%. Additionally, low doses of DEX also resulted in increases in hepatic UA concentration and urinary UA excretion, which were associated with an induction of xanthine oxidoreductase (XOR) in the liver and a downregulation of urate transporter 1 (URAT1) in the kidney, respectively.

Parvifoline AA Promotes Susceptibility of Hepatocarcinoma to Natural Killer Cell-Mediated Cytolysis by Targeting Peroxiredoxin.

Natural killer (NK) cells play a crucial role in the surveillance of malignant cells. The engagement of NK group 2 member D (NKG2D) receptor with its ligands on target cells represents a promising therapeutic strategy against cancers. Here, we report that parvifoline AA (PAA), a natural ent-kaurane diterpenoid, markedly stimulates the expression of NKG2D ligands on hepatocellular carcinoma (HCC) cells, considerably enhancing their recognition and lysis by NK cells.

From the Cover: Identification of Natural Products as Inhibitors of Human Organic Anion Transporters (OAT1 and OAT3) and Their Protective Effect on Mercury-Induced Toxicity.

Mercury accumulates in kidneys and produces acute kidney injury. Semen cassiae (SC), a widely consumed tea and herbal medicine in Eastern Asia, has been reported to have protective effects on kidneys. In this study, SC extract was shown to almost abolish the histological alterations induced by mercuric chloride in rat kidneys.

Deciphering the origins of molecular toxicity of combretastatin A4 and its glycoconjugates: interactions with major drug transporters and their safety profiles and .

Cellular uptake and transport mechanisms directly correlate with the drug-like profiles of lead compounds. To decipher the molecular origin of the toxicity of combretastatin A4 (CA4), an important microtubule targeting agent, we investigated the interactions between CA4 and six key drug transporters, namely hOAT1, hOAT3, hOCT1, hOCT2, hOATP1B3, and hOATP2B1. Three combretastatin-based glycoconjugates, namely , , and with glucose, mannose, and galactose respectively, were synthesized and their and biological characteristics were evaluated.

Interactions of 172 plant extracts with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8): a study on herb-drug interactions.

Background: Herb-drug interactions (HDIs) resulting from concomitant use of herbal products with clinical drugs may cause adverse reactions. Organic anion transporter 1 (OAT1) and 3 (OAT3) are highly expressed in the kidney and play a key role in the renal elimination of substrate drugs. So far, little is known about the herbal extracts that could modulate OAT1 and OAT3 activities.

Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata.

Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A (1), 17-epi-rauvovertine A (2), rauvovertine B (3), 17-epi-rauvovertine B (4), and rauvovertine C (5) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata. Compounds 1/2 and 3/4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1-5 were established by spectroscopic analysis and with the aid of molecular modeling.

Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides.

A series of novel 4β-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay shows that most of these compounds show weak cytotoxicity. It was observed that compound 16 shows the highest activity with IC values ranging from 2.

Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives.

A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d-galactopyranoside 8b, epipodophyllotoxin α-d-arabinopyranoside 8e, and podophyllotoxin β-d-glucopyranoside 11a show the highest potency of anticancer activity with their IC50 values ranging from 0.

Design, synthesis, and cytotoxicity of perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives.

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC50 values ranging from 0.

Identification and Cytotoxic Activities of Two New Trichothecenes and a New Cuparane-Type Sesquiterpenoid from the Cultures of the Mushroom Engleromyces goetzii.

Engleromyces goetzii is a traditional medicinal mushroom that is widely used to treat infection, inflammation and cancer in Tibet, Sichuan and Yunnan provinces of China. Two new trichothecenes, engleromycones A and B (1 and 2), one new cuparane-type sesquiterpenoid named infuscol F (11), eight known trichothecene analogs, sambucinol (3), 3-deoxysambucinol (4), trichothecolone (5), trichodermol (6), 8-deoxytrichothecin (7), trichothecin (8), trichothecinol B (9) and trichothecinol A (10), and one known cyclopentanoid sesquiterpene cyclonerodiol (12) were isolated from the cultures of E. goetzii.

Armochaeglobines A and B, two new indole-based alkaloids from the arthropod-derived fungus Chaetomium globosum.

Armochaeglobines A (1) and B (2), two indole-based cytochalasan alkaloids with new carbon skeletons, were obtained from the fungus Chaetomium globosum TW1-1, which was first isolated from the arthropod Armadillidium vulgare. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction analysis. Interestingly, compound 1 featured a unique tetracyclic 5/6/7/5 fused ring system and 2 possessed a rare 12-membered carbon scaffold.

Nine new farnesylphenols from the basidiomycete albatrellus caeruleoporus.

Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1-8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (-)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.

Daphnane-type diterpenoid glucosides and further constituents of Euphorbia pilosa.

Phytochemical investigation of whole plants of Euphorbia pilosa led to the isolation and identification of two new daphnane-diterpenoid glucosides, euphopilosides A and B (1 and 2, resp.), and a new ent-abietane, euphopilolide (3), together with eight known compounds. Compounds 1 and 2 are the first daphnane-type diterpenoid glycosides.

Synthesis and anticancer activity of glucosylated podophyllotoxin derivatives linked via 4β-triazole rings.

A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity.

Labdane diterpenoids and lignans from Calocedrus macrolepis.

Three new labdane diterpenoids, calomacrins A-C (1-3), and a new diaryl butyrolactone-type lignan, calomacrol A (8), as well as four known labdane diterpenoids and six known lignans, were isolated from the twigs and leaves of Calocedrus macrolepis. Structures of the new compounds were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. Compounds 3-14 were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.

Two new diterpenoids from Excoecaria acerifolia.

A new tigliane diterpenoid, acerifolin A (1), and a new isopimarane diterpenoid, acerifolin B (2), together with two known compounds, were isolated from Excoecaria acerifolia. Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control.

Meroterpenoid pigments from the basidiomycete Albatrellus ovinus.

Eight grifolin derivatives, involving three new monomers, albatrelins A-C (1-3), three novel dimers (meroterpenoid pigments), albatrelins D-F (4-6), and two known ones, 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methyl-3-penten-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (7) and confluentin (8), were isolated from Albatrellus ovinus. Their structures were established by extensive spectroscopic analysis. The absolute configurations of compounds 2-4 were determined as 9R by comparing their optical rotations with data reported in the literature.