Adrenomedullin is a novel adipokine: adrenomedullin in adipocytes and adipose tissues

Adrenomedullin (AM) is a multifunctional regulatory peptide that is produced and secreted by various types of cells. The production and the secretion of AM have been demonstrated in cultured adipocytes and adipose tissues. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide are strong stimulators for AM expression in adipocytes. Furthermore, AM expression in the adipose tissue is increased in obesity, and plasma concentrations of AM are increased in obese subjects. One possible (patho)physiological role of AM secreted by adipose tissue may be actions against complications of the metabolic syndrome characterized by obesity, type 2 diabetic mellitus and hypertension, via its antioxidant and potent vasodilator effects. These findings indicate that AM is a new member of the adipokine family.     

Poecillastrin D: a new cytotoxin of the chondropsin class from marine sponge Jaspis serpentina

Poecillastrin D (2) was isolated together with poecillastrin C (1) from the deep sea sponge, Japsis serpentina. Its structure was elucidated to be that of a macrolide lactam by spectroscopic methods. These compounds showed potent cytotoxicity against various tumor cell lines.     

Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum

Three new Lycopodium alkaloids, lyconadins D (1) and E (2), and complanadine E (3), were isolated from the club moss Lycopodium complanatum. Lyconadin D (1) was the first example of fastigiatine-type alkaloid isolated from Lycopodium complanatum. The structures and relative stereochemistry of 1-3 were elucidated on the basis of spectroscopic data. Complanadine E (3) enhanced mRNA expression for NGF.     

Photocontrollable sequence-specific DNA alkylation by a pyrrole-imidazole polyamide seco-CBI conjugate

We designed and synthesized a Py-Im polyamide seco-CBI conjugate protected by a photocleavable group and demonstrated that it was selectively activated by UV irradiation both in vitro and in vivo. Sequence-specific alkylating Py-Im polyamides containing photolabile linkers may be useful for developing novel chemical- or enzyme-activated anticancer agents and may facilitate spatiotemporal control of gene expression.     

Recognition of 5-methyl-CG and CG base pairs in duplex DNA with high stability using antiparallel-type triplex-forming oligonucleotides with 2-guanidinoethyl-2′-deoxynebularine

The formation of triplex DNA is a site-specific recognition method that directly targets duplex DNA. However, triplex DNA formation is generally formed for the GC and AT base pairs of duplex DNA, and there are no natural nucleotides that recognize the CG and TA base pairs, or even the 5-methyl-CG (^5mCG) base pair. Moreover, duplex DNA, including ^5mCG base pairs, epigenetically regulates gene expression in vivo, and thus targeting strategies are of biological importance. Therefore, the development of triplex-forming oligonucleotides (TFOs) with artificial nucleosides that selectively recognize these base pairs with high affinity is needed. We recently reported that 2′-deoxy-2-aminonebularine derivatives exhibited the ability to recognize ^5mCG and CG base pairs in triplex formation; however, this ability was dependent on sequences. Therefore, we designed and synthesized new nucleoside derivatives based on the 2′-deoxy-nebularine (dN) skeleton to shorten the linker length connecting to the hydrogen-bonding unit in formation of the antiparallel motif triplex. We successfully demonstrated that TFOs with 2-guanidinoethyl-2′-deoxynebularine (guanidino-dN) recognized ^5mCG and CG base pairs with very high affinity in all four DNA sequences with different adjacent nucleobases of guanidino-dN as well as in the promoter sequences of human genes containing ^5mCG base pairs with a high DNA methylation frequency.     

Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats. A study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study Group (MMS)

We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual.     

Unpleasantness and physiological responses in using sanitary napkins

This study investigated the physiological and psychological effects of sanitary napkins (SN) on women in hemorrhage treatment during the menstrual phase. Mesh and non-woven napkins were employed, and the effects were studied during the follicular and menstrual phases; mesh SN presented a higher textural surface-roughness. In both phases, the increases in systolic and diastolic blood pressure were significantly dependent on the application intervals. The low-frequency component of systolic blood pressure variability significantly increased, while the salivary secretion rate decreased with the use of mesh SN during the follicular phase compared with non-woven SN. In addition, the heart rate during the menstrual phase significantly increased in subjects after the replacement of mesh SN compared with non-woven SN. In cases of wearing the unpleasant mesh SN, electroencephalography (EEG) manifested bilateral enhancements in beta and alpha2 waves in the frontal areas increased arousal level during both phases. From the above findings, napkin use increased physiological loading and wearing napkins with higher textural surface-roughness tended to increase activities of the autonomic nervous system and brain arousal level.     

13-Deoxytedanolide, a marine sponge-derived antitumor macrolide, binds to the 60S large ribosomal subunit

13-Deoxytedanolide is a potent antitumor macrolide isolated from the marine sponge Mycale adhaerens. In spite of its remarkable activity, the mode of action of 13-deoxytedanolide has not been elucidated. [11-3H]-(11S)-13-Deoxydihydrotedanolide derived from the macrolide was used for identifying the target molecule from the yeast cell lysate. Fractionation of the binding protein revealed that the labeled 13-deoxytedanolide derivative strongly bound to the 80S ribosome as well as to the 60S large subunit, but not to the 40S small subunit. In agreement with this observation, 13-deoxytedanolide efficiently inhibited the polypeptide elongation. Interestingly, competition studies demonstrated that 13-deoxytedanolide shared the binding site on the 60S large subunit with pederin and its marine-derived analogues. These results indicate that 13-deoxytedanolide is a potent protein synthesis inhibitor and is the first macrolide to inhibit the eukaryotic ribosome.