Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation.

Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2'-hydroxy-4',6'-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 µM (IC50 = 6.4 µM) with the lowest cytotoxicity (IC50 > 80 µM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.

Role of human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C3) in the extrahepatic metabolism of the steroidal aromatase inactivator Formestane.

The clinical use of the steroidal aromatase inhibitor Formestane (4-hydroxandrostenedione, 4-OHA) in the treatment of advanced ER+ breast cancer has been discontinued, and therefore, interest in this remarkable drug has vanished. As a C-19 sterol, 4-OHA can undergo extensive intracellular metabolism depending on the expression of specific enzymes in the corresponding cells. We used the metabolites 4ß-hydroxyandrosterone, 4ß-hydroxyepiandrosterone and its 17ß-reduced derivative as standards for the proof of catalytic activity present in the cell culture medium and expressed by the isolated enzymes. All of the aldo-keto reductases AKR1C1, AKR1C2, AKR1C3 and AKR1C4 catalysed the reduction of the 3-keto-group and the Δ4,5 double bond of 4-OHA at the same time. Molecular docking experiments using microscale thermophoresis and the examination of the kinetic behaviour of the isolated enzymes with the substrate 4-OHA proved that AKR1C3 had the highest affinity for the substrate, whereas AKR1C1 was the most efficient enzyme. Both enzymes (AKR1C1and AKR1C3) are highly expressed in adipose tissue and lungs, exhibiting 3ß-HSD activity. The possibility that 4-OHA generates biologically active derivatives such as the androgen 4-hydroxytestosterone or some 17ß-hydroxy derivatives of the 5α-reduced metabolites may reawaken interest in Formestane, provided that a suitable method of administration can be developed, avoiding oral or intramuscular depot-injection administration.

Manual of praying mantis morphology, nomenclature, and practices (Insecta, Mantodea).

This study provides a comprehensive review of historical morphological nomenclature used for praying mantis (Mantodea) morphology, which includes citations, original use, and assignment of homology. All referenced structures across historical works correspond to a proposed standard term for use in all subsequent works pertaining to praying mantis morphology and systematics. The new standards are presented with a verbal description in a glossary as well as indicated on illustrations and images. In the vast majority of cases, originally used terms were adopted as the new standard. In addition, historical morphological topographical homology conjectures are considered with discussion on modern interpretations. A new standardized formulation to present foreleg femoral and tibial spines is proposed for clarity based on previous works. In addition, descriptions for methods of collection, curation, genital complex dissection, and labeling are provided to aid in the proper preservation and storage of specimens for longevity and ease of study. Due to the lack of consistent linear morphometric measurement practices in the literature, we have proposed a series of measurements for taxonomic and morphological research. These measurements are presented with figures to provide visual aids with homologous landmarks to ensure compatibility and comparability across the Order. Finally, our proposed method of pinning mantises is presented with a photographical example as well as a video tutorial available at http://mantodearesearch.com.

Selection for predation, not female fecundity, explains sexual size dimorphism in the orchid mantises.

Here we reconstruct the evolutionary shift towards floral simulation in orchid mantises and suggest female predatory selection as the likely driving force behind the development of extreme sexual size dimorphism. Through analysis of body size data and phylogenetic modelling of trait evolution, we recovered an ancestral shift towards sexual dimorphisms in both size and appearance in a lineage of flower-associated praying mantises. Sedentary female flower mantises dramatically increased in size prior to a transition from camouflaged, ambush predation to a floral simulation strategy, gaining access to, and visually attracting, a novel resource: large pollinating insects. Male flower mantises, however, remained small and mobile to facilitate mate-finding and reproductive success, consistent with ancestral male life strategy. Although moderate sexual size dimorphisms are common in many arthropod lineages, the predominant explanation is female size increase for increased fecundity. However, sex-dependent selective pressures acting outside of female fecundity have been suggested as mechanisms behind niche dimorphisms. Our hypothesised role of predatory selection acting on females to generate both extreme sexual size dimorphism coupled with niche dimorphism is novel among arthropods.

A review of the research on Canary Islands praying mantises (Mantodea).

For many years researchers studying the fauna of the Canary Islands have only sparsely treated the charismatic insect order of praying mantises (Mantodea). By studying the known literature it becomes obvious that there are several inconsistencies regarding mantodean taxonomy as well as the number of actual species and their distribution within the archipelago. In the present contribution, the literature treating the Canary Island Mantodea fauna is thoroughly reviewed, and the distribution of the ten known Mantodea species is presented with additional comments on the taxonomic problems. The taxonomy and distribution of the Canary Island Amelinae has been causing some confusion in the literature and is therefore discussed for a better understanding of the composition of this group. So far, seven species of Amelinae (two species of Ameles Burmeister and five species of Pseudoyersinia Kirby) are recognized for the Canary Islands. A careful survey of the taxonomic literature indicates that there is a substantial degree of variability in this group, which may have led to frequent misidentifications. This is reflected by the inconsistent literature data on the distribution of several Pseudoyersinia species within the archipelago. A crucial amendment and clarification is provided regarding the date of description (1838) of Ameles gracilis (Brullé) and Ameles limbata (Brullé) as it varies in the literature. Nomenclatural changes regarding the homonymy of Mantis limbata Brullé and Mantis limbata Hahn, previously proposed by Koçak & Kemal (2008), are rejected and discussed in detail. One of the Mantodea species, Empusa pennata (Thunberg), is frequently mentioned in the literature to be present on the Canary Islands, but after carefully reviewing the literature data it is evident that this species has never actually been found on any of the islands. The aim of this publication is to lay a basis for future research on the Mantodea fauna of the Canary Islands, their phylogenetic placement and history of dispersal. This is even more important as the archipelago is a European endemism hot spot for praying mantises and these basic parameters are crucial for implementing plans regarding conservation strategies on the islands.

Visual stimuli that elicit visual tracking, approaching and striking behavior from an unusual praying mantis, Euchomenella macrops (Insecta: Mantodea).

In comparison to other similarly sized mantis species examined in previous studies, Euchomenella macrops has a significantly smaller head, shorter foreleg tibia, but longer prothorax which have been interpreted as specializations for the capture of smaller, slower prey. We tested this conjecture by assessing the rates at which computer generated stimuli elicit visual tracking, approaching, and striking behaviors by adult females. When presented with black disks moving erratically against a white background, strike rate rose progressively as disks enlarged up to 44 deg (visual angle) if the disks moved rapidly (e.g., 143 deg/s); at slower speeds (113, 127 deg/s), smaller disks (<27 deg) were preferred. When black moved linearly from the visual periphery to visual field center (at 73 or 143 deg/s) and then stopped, E. macrops struck consistently at disks as small as 5 deg after movement ceased. E. macrops also struck at higher rates in response to 23 deg erratically moving (subjective) red (versus subjective blue or green) disks that were luminance matched to a grey background although they tracked all colors at equally high rates. Unlike some other species, E. macrops did not strike at higher rates in response to elongated rectangular stimuli moving parallel (versus perpendicular) to their long axis, although the former elicited higher rates of approaching. An analysis of tracking behavior revealed that virtually all tracking movements were a result of head (versus) prothorax rotation.

Homoeopathic drug proving: a scientific approach

Many attempts have been made in the past to develop a drug proving concept which should be accepted by at least a number of doctors in a country. This draft of a concept is the crystallization of a great number of discussions with many homoeopathic doctors in Europe. It is presented as a draft for discussion with the hope to finally develop a drug proving protocol which follows a clear method, serves the purpose to get reliable symptoms for the Materia Medica and is practicable. There will be a "Symposium on Homoeopathic Drug Provings in Healthy Persons" on Friday, 12th June 1992 to Sunday, 14th June 1992 in Friedrichrhoda, Eastern part of Germany. The organisers cordially invite you to take part. For further information please contact the author of this article