Highly Modified Sesquiterpene Lactones with Cytotoxic Activities from .

Three new germacranolide sesquiterpene lactones (SLs), strochunolides A-C (-, respectively), and a new guaianolide SL, strochunolide D (), were isolated from and structurally characterized. Compound is the first example of a dihomo-germacranolide SL, characterized by an unprecedented 6/10/5 tricyclic scaffold incorporating an additional fused δ-lactone C-ring. The structure of a known germacranolide SL, spicatolide C (), was revised as its 8-epimer.

Dichapetalins from the Twigs of with Cytotoxic Activities.

Continued efforts to expand the structural diversity of dichapetalins and explore further the cytotoxic structure-activity relationships have led to the isolation of 17 undescribed analogues, dichapelonins A-Q (-), and three known compounds (-) from the twigs of . Compounds - comprise five compound classes as classified by varied C6-C2 conjugates at the A ring of the 13,30-cyclodammarane skeleton, and their structures were determined by spectroscopic data analysis, experimental electronic circular dichroism measurements, and X-ray crystallography. Biological tests revealed compounds - with a phenyl-butadiene appendage to be the most potent cytotoxic compound type of those evaluated.

[Effect of Curcumin on the Proliferation, Apoptosis, and Cell Cycle of Human Acute Myeloid Leukemia Cell Line K562].

Objective: To investigate the effects of curcumin on the proliferation, apoptosis, and cell cycle of human acute myeloid leukemia cell line K562.

Methods: MTT method was used to detect the proliferation inhibition of logarithmic growth phase human acute myeloid leukemia K562 cells, flow cytometry was used to detect the cell cycle, Annexin V-FITC was used to detect the apoptosis rate, and real-time fluorescent quantitative PCR and Western blot were used to detect the expression of Bax, BCL-2 and caspase-3 mRNA and protein, respectively.

Results: The inhibition rate of cell proliferation in curcumin 10, 20, and 40 μmol/L group for 24 h and 48 h were higher than that in the control group (curcumin 0 μmol/L), and the cell proliferation inhibition rate was concentration-time dependent (r=0.

Phorneroids A-M, diverse types of diterpenoids from Euphorbia neriifolia.

A chemical investigation on the aerial parts of Euphorbia neriifolia led to the identification of thirteen undescribed diterpenoids, phorneroids A-M, including ent-abietane (A-D), ent-kaurane (E-G), ent-atisane (H-K), and ent-isopimarane (L and M) types, together with three known compounds. Phorneroid A represents the first example of 8-spiro-fused 9,10-seco-ent-abietane diterpenoid lactone featuring a unique 6/5/6/5 spirocyclic framework. Biological assays showed that some of the compounds displayed moderate cytotoxicity against two human tumor cell lines, A549 and HL-60.

Dolabellane Diterpenoids from the Xisha Soft Coral .

Twelve new members (-) of the dolabellane family, co-occurring with three related known diterpenoids (-), were isolated from the Xisha soft coral . Their structures were determined by extensive spectroscopic analysis, modified Mosher's method, and X-ray diffraction analysis. Clavuperoxylides A () and B () represent the first examples of dolabellanes containing peroxyl groups, especially the novel peroxide bridge in , whereas clavufuranolides A-C (-) are the first example of dolabellane diterpenoids comprising a tetrahydrofuran ring.

Sublyratins A-O, Labdane-Type Diterpenoids from .

Fifteen new labdane-type diterpenoids, sublyratins A-O (-), along with four known analogues (-) were isolated from the aerial parts of . Their structural assignments were challenging due to the stereoisomeric features evident and were achieved by analyzing comprehensively the spectroscopic data and electronic circular dichroism spectra and using X-ray crystallographic analysis. Compounds and - displayed cytotoxic activity against the HL-60 cell line with IC values of 1.

Discovery of four modified classes of triterpenoids delineated a metabolic cascade: compound characterization and biomimetic synthesis.

Chemical studies on have afforded 18 highly modified complex triterpenoids belonging to four compound classes as defined by the newly adapted functional motifs associated with the A ring of the molecules. Their structures were determined by solid data acquired by diverse methods. The biosynthetic pathway for the four compound classes was rationalized cascade modifications involving diverse chemical events.

[Correlation of Blimp1 with ATF4/CHOP Signaling Pathway in Multiple Myeloma U266 Cells].

Objective: To investigate whether Blimp1 plays an anti-apoptosis role in myeloma by interfering with ATF4/CHOP cell apoptosis pathway induced by endoplasmic reticulum stress, and to explore the anti-myeloma mechanism of aspirin.

Methods: The bone marrow fluid of 40 newly diagnosed multiple myeloma patients without treatment and 30 control people with relatively normal bone marrow was collected. Flow cytometry was used to separated the normal and abnormal plasma cells, LV-Blimp1-RNAi (40051-2) recombinant lentivirus down-regulates the expression of Blimp-1 in U266 cell line and detected the changes of the expression of ATF4 and CHOP gene.

lncRNA PCAT18 inhibits proliferation, migration and invasion of gastric cancer cells through miR-135b suppression to promote CLDN11 expression.

Background: Gastric cancer is a severe disease with a high occurrence rate worldwide. And lncRNAs are demonstrated to be responsible for cancer growth and metastasis. So, it is of great importance to explore the lncRNAs involved mechanism of gastric cancer occurrence and development deeply.

Author Correction: Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Expression of Blimp1、ATF4 and CHOP in Multiple Myeloma Cells and Effect of Aspirin on Their Expression].

Objective: To explore the expression of Blimp1, ATF4 and CHOP in bone marrow mononuclear cells from patients with multiple myeloma as well as the effect of aspirin on their expression.

Methods: Sixty untreated patients with multiple myeloma and 30 patients with relatively normal bone marrow were selected. Mononuclear cells from the bone marrow fluid were separated using Ficoll separation solution.

Crokonoids A-C, A Highly Rearranged and Dual-Bridged Spiro Diterpenoid and Two Other Diterpenoids from .

Crokonoid A (), a highly rearranged diterpenoid featuring a dual-bridged tricyclo[4.4.1.

Tetramerized Sesquiterpenoid Ainsliatetramers A and B from and Their Cytotoxic Activities.

Two guaianolide sesquiterpenoid tetramers named ainsliatetramers A and B were separated from . Through spectroscopic analyses, especially the band-selective CT-HSQC and CT-HMBC techniques, the complex skeleton was constructed from four sesquiterpene units via three different linkages. A biosynthetic pathway was proposed featuring a Michael addition and a regular and a hetero-Diels-Alder cycloaddition.

Matrine protects oligodendrocytes by inhibiting their apoptosis and enhancing mitochondrial autophagy.

Stressed oligodendrocytes (OLGs) activate microglia to produce an inflammatory response, and the impairment of mitochondria further aggravates OLG damage, which is the earliest pathological change in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Matrine (MAT), a tetracyclic quinolizine alkaloid derived from the herb radix sophorae flavescentis, has been shown to effectively ameliorate clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the mechanisms underlying the effect of MAT treatment need to be further studied.

17- nor-Cephalotane-Type Diterpenoids from Cephalotaxus fortunei.

Seventeen new 17- nor-cephalotane-type diterpenoids, fortalpinoids A-Q (1-17), were isolated from the seeds of Cephalotaxus fortunei var. alpine. Compound 12 represents the first 17- nor-cephalotane-type diterpenoid featuring an 8-oxabicyclo[3.

Cytotoxic Tigliane Diterpenoids from Croton damayeshu.

Chemical investigation of an EtOH extract of the twigs and leaves of Croton damayeshu afforded 10 new tigliane diterpenoids, crodamoids A-J (1-10), along with five known compounds. Their structures were elucidated by physical data analysis. Compounds 8, 9, and 15 displayed cytotoxic effects against two human tumor cell lines, A549 and HL-60 (IC: 0.

Ainsliatriolides A and B, Two Guaianolide Trimers from Ainsliaea fragrans and Their Cytotoxic Activities.

Ainsliatriolides A (1) and B (2), two guaianolide sesquiterpenoid trimers possessing an unprecedented skeleton, were isolated from Ainsliaea fragrans. Their structures were elucidated through extensive analysis of spectroscopic data and confirmed by single-crystal X-ray diffraction experiment. Ainsliatriolides A and B are first examples of compound trimerized from guaianolide sesquiterpenoids through two different C-C linkages (type A, 4-2'/15-14'; type B, 15'-15″).

Clavuridins A and B, two new trinor-guaiane sesquiterpenes isolated from the Xisha soft coral Clavularia viridis.

In the present study, two new trinor-guaiane sesquiterpenes, named clavuridins B (1), and A (2), along with three known sesquiterpenes (3-5), were isolated from the Xisha soft coral Clavularia viridis. Their structures and absolute configurations were determined on the basis of spectroscopic analysis, X-ray diffraction analysis with Cu Kα radiation and by comparison with related model compounds. Compounds 1 and 3-5 were evaluated for their cytotoxic activity.

Cephanolides A-J, Cephalotane-Type Diterpenoids from Cephalotaxus sinensis.

Ten new cephalotane-type diterpenoids, cephanolides A-J (1-10), and two known analogues were isolated and characterized from Cephalotaxus sinensis. Compounds 1-3 represent the first examples of A-ring-contracted cephalotane-type dinorditerpenoids, and compound 4 is an A-ring-contracted norditerpenoid. The biosynthetic pathways for compounds 1-4 are postulated with the coexisting cephalotane-type troponoids as the precursors.

Phainanolide A, Highly Modified and Oxygenated Triterpenoid from Phyllanthus hainanensis.

Phainanolide A (1), a highly modified triterpenoid incorporating an unprecedented 6/9/6 heterotricyclic system and a highly oxygenated 5,5-spirocyclic ketal lactone, along with three new triterpenoids 2-4 were isolated from Phyllanthus hainanensis. Their structures were completely elucidated by a combination of diverse methods including 2D NMR, quantum chemical NMR and ECD calculations, and NMR data analogy with model compounds. Compounds 1-4 exhibited both remarkable cytotoxic and immunosuppressive activities.

Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease.

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and is involved in pathological angiogenesis associated with chronic liver diseases. However, the precise mechanisms underlying PlGF signalling contributing to liver fibrosis and angiogenesis remain largely unexplored. This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms.

Marine-derived chromopeptide A, a novel class I HDAC inhibitor, suppresses human prostate cancer cell proliferation and migration.

Histone deacetylases (HDACs), especially HDAC1, 2, 3 and 4, are abundantly expressed and over-activated in prostate cancer that is correlated with the poor prognosis. Thus, inhibition of HDAC activity has emerged as a potential alternative option for prostate cancer therapy. Chromopeptide A is a depsipeptide isolated from the marine sediment-derived bacterium Chromobacterium sp.

[Expression of Blimp-1 mRNA in Bone Marrow Mononuclear Cells in Multiple Myeloma Patients and Its Clinical Significance].

Objective: To investigate the expression level of B lymphocyte-induced maturation protein-1(Blimp-1) mRNA in bone marrow mononuclear cells(BMMNC) of multiple myeloma(MM) patients and its clinical significance.

Methods: Fluorescent quantitative real-time PCR(qRT-PCR) was used to measure Blimp-1 mRNA expression in BMMNC and flow cytometry(FCM) was performed to detect the number of malignant plasma cells in bone marrow of MM group (39 newly-diagnosed and untreated patients) and IDA group (5 IDA patients). The clinical data of all the patients' were collected, and the 39 patients in MM group were divided into 2 subgroups: in BD group 20 cases were treated with bortezomib-based regimen and in VOD group 19 patients were treated with VAD regimen.

Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells.

Aim: Inhibition of heat shock protein (Hsp90) has been proven to be effective in overriding primary and acquired resistance of kinase inhibitors. In this study, we investigated the role of FS-108, a newly developed Hsp90 inhibitor, to overcome gefitinib resistance in EGFR mutant non-small cell lung cancer cells.

Methods: Cell proliferation was assessed using the SRB assay.

Mannolides A-C with an Intact Diterpenoid Skeleton Providing Insights on the Biosynthesis of Antitumor Cephalotaxus Troponoids.

Three new diterpenoids, mannolides A-C (1-3), and two new Cephalotaxus troponoids, 4 and 5, were isolated from Cephalotaxus mannii and structurally characterized by spectroscopic data and X-ray crystallography. The discovery of compounds 1-3 featuring a new intact carbon skeleton, proposed as cephalotane, sheds new light on the biogenesis of Cephalotaxus troponoids, a rare class of antitumor C19 norditerpenoids. Antitumor tests showed that the tropone motif is essential for the activity.