Accelerated bio‐cognitive aging in Down syndrome: State of the art and possible deceleration strategies

Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age‐associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early‐onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi‐systemic approaches including early‐onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age‐related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS‐associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.     

Tyrosinase‐catalyzed oxidation of resveratrol produces a highly reactive ortho‐quinone: Implications for melanocyte toxicity

trans‐Resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene, RES), a naturally occurring polyphenol, has recently attracted increased interest as a health‐beneficial agent. However, based on its p‐substituted phenol structure, RES is expected to be a substrate for tyrosinase and to produce a toxic o‐quinone metabolite. The results of this study demonstrate that the oxidation of RES by tyrosinase produces 4‐(3′,5′‐dihydroxy‐trans‐styrenyl)‐1,2‐benzoquinone (RES‐quinone), which decays rapidly to an oligomeric product (RES‐oligomer). RES‐quinone was identified after reduction to its corresponding catechol, known as piceatannol. RES‐quinone reacts with N‐acetylcysteine, a small thiol, to form a diadduct and a triadduct, which were identified by NMR and MS analyses. The production of a triadduct is not common for o‐quinones, suggesting a high reactivity of RES‐quinone. RES‐quinone also binds to bovine serum albumin through its cysteine residue. RES‐oligomer can oxidize GSH to GSSG, indicating its pro‐oxidant activity. These results suggest that RES could be cytotoxic to melanocytes due to the binding of RES‐quinone to thiol proteins.     

The dual functionality of antimicrobial peptides Os and Os‐C in human leukocytes

Antimicrobial peptides (AMPs), Os and Os‐C, have been identified as multifunctional peptides with antibacterial, antiendotoxin, and anti‐inflammatory properties. For further development of Os and Os‐C as therapeutic peptides, it is essential to evaluate these effects in human mononuclear (MN) and polymorphonuclear (PMN) leukocytes. The cytotoxicity and the effects of both peptides on MN and PMN morphology were determined with the Alamar‐Blue assay and scanning electron microscopy, respectively. The ability of Os and Os‐C to induce reactive oxygen species (ROS) and to protect against 2,2′‐azobis(2‐amidinopropane) dihydrochloride–induced oxidative damage in both cell populations was evaluated using 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA). Using fluorescently labeled peptides, the ability of the peptides to cross the cell membranes of MN and PMN was also evaluated. At the minimum bactericidal concentrations of Os and Os‐C, neither peptide was cytotoxic. Os caused morphological features of toxicity at 100 μM, entered MN cells, and also protected these cells against oxidative damage. Os‐C caused MN and PMN leukocyte activation associated with ROS formation and was unable to penetrate cell membranes, indicating extracellular membrane interactions. This study confirms that both Os and Os‐C at less than 100 μM are not cytotoxic. The MN‐specific uptake of Os identifies it as a cell‐specific cargo‐carrier peptide, with additional anti‐inflammatory properties. In contrast, the ability of Os‐C to activate MN and PMN cells implies that this peptide should be further evaluated as an AMP, which, in addition to its ability to eradicate infection, can further enhance host immunity. These novel characteristics of Os and Os‐C indicate that these AMPs as peptides can be further developed for specific applications.     

Fat stigmatization in television shows and movies: a content analysis

Objective: To examine the phenomenon of fat stigmatization messages presented in television shows and movies, a content analysis was used to quantify and categorize fat‐specific commentary and humor. Research Methods and Procedures: Fat stigmatization vignettes were identified using a targeted sampling procedure, and 135 scenes were excised from movies and television shows. The material was coded by trained raters. Reliability indices were uniformly high for the seven categories (percentage agreement ranged from 0.90 to 0.98; kappas ranged from 0.66 to 0.94). Results: Results indicated that fat stigmatization commentary and fat humor were often verbal, directed toward another person, and often presented directly in the presence of the overweight target. Results also indicated that male characters were three times more likely to engage in fat stigmatization commentary or fat humor than female characters. Discussion: To our knowledge, these findings provide the first information regarding the specific gender, age, and types of fat stigmatization that occur frequently in movies and television shows. The stimuli should prove useful in future research examining the role of individual difference factors (e.g., BMI) in the reaction to viewing such vignettes.     

三唑酮对黄瓜子叶抗氧化酶活力的影响

黄瓜子叶衰老过程中超氧物歧化酶（ＳＯＤ）、过氧化氢酶（ＣＡＴ）和抗坏血酸－过氧化物酶（ＡＳＡ－ＰＯＤ）活性降低,而过氧化物酶（ＰＯＤ）活性升高。２０ｍｇ／Ｌ三唑酮右明显提高ＳＯＤ,ＡＳＡ－ＰＯＤ,ＣＡＴ活性,抑制ＰＯＤ活性升高。膜脂过氧化产物丙二醛（ＭＤＡ）含量在叶片衰老过程中提高,三唑酮可降低ＭＤＡ含量。表明三唑酮减轻脂氧化程度,延缓了叶片的衰老。     

A bioassay for insect deterrent compounds found in plant and animal tissues

A general field bioassay for detecting biologically active compounds in plants and insects has been developed and tested for efficacy and sensitivity. Methanolic extracts, in sucrose solution, of 20 plant and six caterpillar species were offered to the ponerine ant Paraponera clavata and the feeding preferences observed. The bioassay resulted in the detection of nine plant and three caterpillar species with ant-deterrent extracts, and 11 plant and three caterpillar species with neutral or attractant extracts. All of the plants showing ant-deterrent characteristics which had been chemically investigated in our laboratory, or for which chemical literature was available, contained secondary metabolites of known deterrence. Both naturally occurring and artificial differences in chemical concentrations could be detected using the bioassay. The method provides a means of screening plants and insects for compounds that are insect anti-feedants or that can modify insect behaviour.     

An orb‐weaver spider eludes plant‐defending acacia ants by hiding in plain sight

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Non‐surgical method for the induction of delayed implantation and recovery of viable blastocysts in rats and mice by the use of tamoxifen and Depo‐Provera

Implantational delay in rats and mice is experimentally induced by withdrawal of oestrogen and maintenance of progesterone. The oestrogen is normally removed by ovariectomy. We report here that the use of the antioestrogenic effect of the drug tamoxifen in combination with Depo‐Provera (which counteracts the oestrogenic effects of the tamoxifen) may be used to put the embryos both of rats and mice into delay of implantation. These delayed embryos retain their developmental potential and give rise to live born young when transferred to pseudopregnant recipient females. They are a good source of ES cells. Mol. Reprod. Dev. 52:29–32, 1999. © 1999 Wiley‐Liss, Inc.     

Varicuothiols A and B,New Fungal Metabolites from Aspergillus versicolor with Anti‐Inflammatory Activities

Chemical examination of a coral‐associated fungus Aspergillus versicolor LZD‐44‐03 resulted in the isolation of two new compounds with the trivial names of varicuothiols A ( 1 ) and B ( 2 ) as a unique scaffold. Their structures were determined through extensive spectroscopic analyses in association with the modified Mosher's method and chemical conversion. Both 1 and 2 exhibited significant inhibition against LPS‐induced RAW24.7 cell proliferation, in association with the down regulation of nitrite production and cytokines (MCP‐1, IL‐6, and TNF‐α).