Aciculatin inhibits lipopolysaccharide-mediated inducible nitric oxide synthase and cyclooxygenase-2 expression via suppressing NF-κB and JNK/p38 MAPK activation pathways

Objectives  

Natural products have played a significant role in drug discovery and development. Inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been suggested to connect with various inflammatory diseases. In this study, we explored the anti-inflammatory potential of aciculatin (8-((2R,4S,5S,6R)-tetrahydro-4,5-dihydroxy-6-methyl-2H-pyran-2-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one), one of main components of Chrysopogon aciculatis, by examining its effects on the expression and activity of iNOS and COX-2 in lipopolysaccharide (LPS)-activated macrophages.     

Changes in salt-marsh carabid assemblages after an invasion by the native grass Elymus athericus (Link) Kerguélen

As a result of an invasion by the native grass Elymus athericus (Link) Kerguélen (Poaceae) in the last 10 years, a major change in vegetation cover has occurred in salt marshes of the Mont Saint-Michel bay, Western France. The impact of such an invasion on carabid assemblages, a dominant group of terrestrial arthropods in these habitats and containing several stenotopic species, is investigated here. In our study site, carabid data are available from 1983 and 1984, allowing a comparison of species distribution ranges in salt marshes before (1983-1984) and after (2002) the Elymus athericus invasion. A total of 16,867 adults belonging to 40 species were caught. By considering the presence-absence of species shared between studies, we show that the invasion by Elymus athericus promoted the progression of non-coastal species (mainly Pterostichus s.l. spp.). This did however not interfere with resident species distributions, finally resulting in higher carabid species richness in the entire area. The species composition and abundances of carabid assemblages were also compared between natural and invaded stations in 2002. The main result is that abundances of some halophilic species decreased in one invaded plot (in case of Pogonus chalceus (Marsham 1802)) whereas the opposite pattern was observed for other species (e.g., Bembidion minimum (Fabricius 1792)). Invaded habitats were characterized by lower percentages of halophilic species and higher total species richness.     

Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations

During chronic kidney disease (CKD), there is a progressive accumulation of toxic solutes due to inadequate renal clearance. Here, the interaction between uremic toxins and two important efflux pumps, viz. multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP) was investigated. Membrane vesicles isolated from MRP4- or BCRP-overexpressing human embryonic kidney cells were used to study the impact of uremic toxins on substrate specific uptake. Furthermore, the concentrations of various uremic toxins were determined in plasma of CKD patients using high performance liquid chromatography and liquid chromatography/tandem mass spectrometry. Our results show that hippuric acid, indoxyl sulfate and kynurenic acid inhibit MRP4-mediated [(3)H]-methotrexate ([(3)H]-MTX) uptake (calculated Ki values: 2.5 mM, 1 mM, 25 μM, respectively) and BCRP-mediated [(3)H]-estrone sulfate ([(3)H]-E1S) uptake (Ki values: 4 mM, 500 μM and 50 μM, respectively), whereas indole-3-acetic acid and phenylacetic acid reduce [(3)H]-MTX uptake by MRP4 only (Ki value: 2 mM and IC(50) value: 7 mM, respectively). In contrast, p-cresol, p-toluenesulfonic acid, putrescine, oxalate and quinolinic acid did not alter transport mediated by MRP4 or BCRP. In addition, our results show that hippuric acid, indole-3-acetic acid, indoxyl sulfate, kynurenic acid and phenylacetic acid accumulate in plasma of end-stage CKD patients with mean concentrations of 160 μM, 4 μM, 129 μM, 1 μM and 18 μM, respectively. Moreover, calculated Ki values are below the maximal plasma concentrations of the tested toxins. In conclusion, this study shows that several uremic toxins inhibit active transport by MRP4 and BCRP at clinically relevant concentrations.     

Shaping mechanisms of metal specificity in a family of metazoan metallothioneins: evolutionary differentiation of mollusc metallothioneins

Background  

The degree of metal binding specificity in metalloproteins such as metallothioneins (MTs) can be crucial for their functional accuracy. Unlike most other animal species, pulmonate molluscs possess homometallic MT isoforms loaded with Cu⁺ or Cd²⁺. They have, so far, been obtained as native metal-MT complexes from snail tissues, where they are involved in the metabolism of the metal ion species bound to the respective isoform. However, it has not as yet been discerned if their specific metal occupation is the result of a rigid control of metal availability, or isoform expression programming in the hosting tissues or of structural differences of the respective peptides determining the coordinative options for the different metal ions. In this study, the Roman snail (Helix pomatia) Cu-loaded and Cd-loaded isoforms (HpCuMT and HpCdMT) were used as model molecules in order to elucidate the biochemical and evolutionary mechanisms permitting pulmonate MTs to achieve specificity for their cognate metal ion.     

Known data on the therapeutic use of Azadiracta indica (neem) for type 2 diabetes mellitus

There has been growing interest for the therapeutic use of traditional herbs in the management of diabetes mellitus (DM) and its complications. Data shows the hypoglycemic activity of Azadiracta indica in diabetes. Therefore, it is of interest to document known data on the therapeutic use of Azadiracta indica (neem) for type 2 diabetes mellitus (T2DM).     

The crystal structure of annexin A8 is similar to that of annexin A3

Annexin A8 is a relatively infrequent and poorly studied member of this large family of calcium-binding and membrane-binding proteins. It is, however, associated with a specific disease, acute promyelocytic leukemia. We have solved its three-dimensional structure, which includes a moderately long and intact N terminus. The structure is closest to that of annexin A3 and highlights several important regions of inherent flexibility in the annexin molecule. The N terminus resembles that of annexin A3, as it lies along the concave surface of the molecule and inserts partially into the hydrophilic channel in its centre. Since both annexins A3 and A8 are expressed in promyelocytic cells during their differentiation, the similarity in their structures might suggest a functional relationship.