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Recent findings suggest that co-expression of NOS2 and COX2 is a strong prognostic indicator in triple-negative breast cancer patients. These two key inflammation-associated enzymes are responsible for the biosynthesis of NO and PGE , respectively, and can exert their effect in both an autocrine and paracrine manner. Impairment of their physiological regulation leads to critical changes in both intra-tumoural and intercellular communication with the immune system and their adaptation to the hypoxic tumour micro-environment. Recent studies have also established a key role of NOS2-COX2 in causing metabolic shift. This review provides an extensive overview of the role of NO and PGE in shaping communication between the tumour micro-environment composed of tumour and immune cells that in turn favours tumour progression and metastasis. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.

Immunological challenge experienced in early life can have long-term programming effects on the hypothalamic-pituitary-adrenal axis that permanently influence the stress response. Similarly, neonatal exposure to immunological stress enhances stress-induced suppression of the hypothalamic-pituitary gonadal (HPG) axis in adulthood, but may also affect earlier development, including the timing of puberty. To investigate the timing of the critical window for this programming of the HPG axis, neonatal female rats were injected with lipopolysaccharide (LPS; 50 microg/kg i.p.) or saline on postnatal days 3 + 5, 7 + 9, or 14 + 16 and monitored for vaginal opening and first vaginal oestrus as markers of puberty. We also investigated the effects of neonatal programming on the development of the expression patterns of kisspeptin (Kiss1) and its receptor (Kiss1r) in hypothalamic sites known to contain kisspeptin-expressing neuronal populations critical to reproductive function: the medial preoptic area (mPOA) and the arcuate nucleus in neonatally-stressed animals. We determined that the critical period for a significant delay in puberty as a result of neonatal LPS exposure is before 7 days of age in the female rat, and demonstrated that Kiss1, but not Kiss1r mRNA, expression in the mPOA is down-regulated in pre-pubertal females. These data suggest that the mPOA population of kisspeptin neurones play a pivotal role in controlling the onset of puberty, and that their function can be affected by neonatal stress.

The spectral features of satellite holes are used to investigate 9-aminoacridine-DNA interactions. The hole depths of the outer ring vibronic modes are reduced more than that of the inner ring vibronic modes, implying that inner ring motion is less perturbed than outer ring motion. As a result, the mode coupling between the inner ring and outer ring is reduced upon binding to DNA. However, similar hole frequency and width of the satellite hole corresponding to the NH2 mode upon binding to DNA imply that the amino group of 9-aminoacridine sits outside the DNA.

Silicon carbide whiskers (SiCW) and continuous glass filaments are important components of composite materials having potentially widespread use in the automotive, aerospace, and power generation industries. We determined the in vitro activity of three well-characterized samples of silicon carbide whiskers and a continuous glass filament sample in four different cellular assays and compared this to the activities of UICC crocidolite, JM Code 100 glass microfiber, and erionite in the same assay systems. The SiCW had a diameter range of 0.32-0.75 microns and a length range of 4.5-20.1 microns. The SiCW was significantly toxic; on a mass basis, one SiCW sample was more toxic than crocidolite; however, JM Code 100 glass microfiber, which is not toxic in vivo (i.e., it does not cause fibrogenesis or carcinogenesis when inhaled), was also more toxic than crocidolite. The glass filament sample was the least cytotoxic of all the samples tested. On a fiber number basis, all three SiCW samples were more toxic than crocidolite. The results of our study showed that SiCW exhibits significant in vitro biological reactivity. Thus, despite the caution that must be exercised in extrpolating the results of in vitro studies to conclusions about in vivo health effects, SiCW should be considered toxic until further toxicological data are available.

A rapid nucleophilic displacement reaction of 6-chloropurine, 2-amino-6-chloropurine and 5-bromocytosine with various nucleophiles under focused microwave irradiation is described. Using this method, the desired products were obtained with the yields up to 99% in a short reaction time.

Background To assess the performance, efficiency and optimal removal time of a newly designed temporary retrievable cardia covered stent (TRC-CS) for the treatment of achalasia in a dog model. Methods Eighty-four achalasia-like dog models were randomly divided into seven groups of 12, a control group (CG; no stent insertion), a standard stent control group (NSCG, standard esophageal stent) and five treatment groups (TG, TRC-CS). Stents were retrieved at 4 days after insertion in the NSCG and at 4 days(4 d-TG), 2 weeks(2 w-TG), 1 month(1 m-TG), 3 months(3 m-TG), and 6 months(6 m-TG) in the TGs. Lower esophageal sphincter pressure (LESP) and a timed barium esophagram were assessed before stent insertion, after stent retrieval, and at 1-week, 1-, 3- and 6-month follow-up. Three dogs in NSCG and 4 d-TG were sacrificed for histological examination at each follow-up to investigate the inflammatory reaction after stent insertion. Key Results Stent insertion/removal and the follow-up procedures were well tolerated. At 6-month follow-up, the 2 w-TG and 1 m-TG demonstrated an acceptable stent migration (n = 2 in both TGs vs n = 4 in NSCG, n = 4 in 3 m-TG, and n = 6 in 6 m-TG), improved LESP compared to after benzyl-dimethyltetradecylammonium chloride (BAC) injection (P

Oxidation of α-terpineol by atmospheric air resulted twelve products, which seemed more complicated than the results of the previous works. All the products were identified and rationalized. The mechanisms of some minor reactions were discussed.

From the hexane and acetone extractive of the wood of Keteleeria davidiana Beissner, α-pinene, β-pinene, limonene, α-copaene, bornyl acetate, β-elemene, caryophyllene, caryophyllene oxide, α-selinene, β∼selinene, selin-11-en-4α-o1, laevojunenol, α-cyperone, stigmasterol, β-sitosterol, tetracosyltetracosanoate, docosanyl tetracosanoate, hexacosanyltetracosanoate, tetracosanol, hexacosanol, docosanol, α-conidendrin and 15-hydroxydehydroabietic acid were isolated. Straight chain saturated hydrocarbons (C13, C14, C17-C14) were also obtained.

Oxidations of α-cadinol, T-cadinol, T-muurolol and δ-cadinol with SeO3 gave corresponding ketols and diols. Reductions of the ketols with NaBH4 gave epidiols. NMR data of these sixteen compounds are compared.

From the wood of Taiwania cryptomerioides Hayata, two new sesquiterpenes, cadinan-3β, 9β-diol and cadinan-3β, 9α-diol were isolated as minor components. Their structures were elucidated as (I) and (II), respectively.

A new saturated triol of cadinane type, Cadinan-3α 4α, 9α-triol, was found, identified, and synthesized.

Oxidations of α-cadinol, T-cadinol, T-muurolol and δ-cadinol with SeO3 gave corresponding ketols and diols. Reductions of the ketols with NaBH4 gave epidiols. NMR data of these sixteen compounds are compared.