Study of Structure–Activity Relationships of the Marine Alkaloid Fascaplysin and Its Derivatives as Potent Anticancer Agents

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.     

Isolation of a novel catechin from Bergenia rhizomes that has pronounced lipase-inhibiting and antioxidative properties

An aqueous ethanol extract of Bergenia crassifolia rhizomes strongly inhibited human pancreatic lipase activity and increased scavenging of DPPH free radicals in vitro. Chromatographic separation of this extract led to isolation of the hydrolysable tannins (+)-catechin 3,5-di-O-gallate () and (+)-catechin 3-O-gallate (). This is the first report of the isolation of compound 1 from plant material. This compound strongly inhibited human pancreatic lipase (with an IC₅₀ value of 0.42 μg/ml) and exhibited a remarkable free radical-scavenging ability (with an SC₅₀ value of 1.04 μg/ml). The chemical structures of 1 and 2 were elucidated using MS, NMR and chemical approaches.     

Understanding physiological and morphological traits contributing to drought tolerance in barley

Drought stress is a major limiting factor for crop production in the arid and semi‐arid regions. Here, we screened eighty barley (Hordeum vulgare L.) genotypes collected from different geographical locations contrasting in drought stress tolerance and quantified a range of physiological and agronomical indices in glasshouse trails. The experiment was conducted in large soil tanks subjected to drought treatment of eighty barley genotypes at three‐leaf stage and gradually brought to severe drought by withholding irrigation for 30 days under glasshouse conditions. Also, root length of the same genotypes was measured from stress‐affected plants growing hydroponically. Drought tolerance was scored 30 days after the drought stress commenced based on the degree of the leaf wilting, fresh and dry biomass and relative water content. These characteristics were related to stomatal conductance, stomatal density, residual transpiration and leaf sap Na, K, Cl contents measured in control (irrigated) plants. Responses to drought stress differed significantly among the genotypes. The overall drought tolerance was significantly correlated with relative water content, stomatal conductance and leaf Na⁺ and K⁺ contents. No significant correlations between drought tolerance and root length of 6‐day‐old seedling, stomatal density, residual transpiration and leaf sap Cl^? content were found. Taking together, these results suggest that drought‐tolerant genotypes have lower stomatal conductance, and lower water content, Na⁺, K⁺ and Cl^? contents in their tissue under control conditions than the drought‐sensitive ones. These traits make them more resilient to the forthcoming drought stress.     

Echinochrome A Treatment Alleviates Atopic Dermatitis-like Skin Lesions in NC/Nga Mice via IL-4 and IL-13 Suppression

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to dryness, pruritus, and erythematous lesions. AD is triggered by immune imbalance and oxidative stress. Echinochrome A (Ech A), a natural pigment isolated from sea urchins, exerts antioxidant and beneficial effects in various inflammatory disease models. In the present study, we tested whether Ech A treatment alleviated AD-like skin lesions. We examined the anti-inflammatory effect of Ech A on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions in an NC/Nga mouse model. AD-like skin symptoms were induced by treatment with 1% DNCB for 1 week and 0.4% DNCB for 5 weeks in NC/Nga mice. The results showed that Ech A alleviated AD clinical symptoms, such as edema, erythema, and dryness. Treatment with Ech A induced the recovery of epidermis skin lesions as observed histologically. Tewameter^® and Corneometer^® measurements indicated that Ech A treatment reduced transepidermal water loss and improved stratum corneum hydration, respectively. Ech A treatment also inhibited inflammatory-response-induced mast cell infiltration in AD-like skin lesions and suppressed the expression of proinflammatory cytokines, such as interferon-γ, interleukin-4, and interleukin-13. Collectively, these results suggest that Ech A may be beneficial for treating AD owing to its anti-inflammatory effects.     

Sex Specificity in Innate Immunity of Insect Larvae

The innate immunity of insects has been widely studied. Although the effect of sex on insect immunity has been extensively discussed, differences in immunity between the sexes of larvae insects remain largely unstudied. Studying larval sex differences in immunity may provide valuable information about the mechanisms underlying the insect immune system, which, in turn, can be valuable for the development and improvement of pest management. Here we compared the antibacterial activity in both the midgut tissue and cell-free hemolymph of Lymantria dispar L. (Lepidoptera: Erebidae) females and males at the larval stage without and after a challenge by entomopathogenic bacterium Bacillus thuringiensis Berliner. We also evaluated the sex-specific mortality of L. dispar induced by B. thuringiensis infection. We find that antibacterial activity in the midgut is activated by infection, but only in females. Thus, sex differences in immunity can have important effects even before sexual differentiation at adulthood.     

Regions of strong coupling between soil moisture and precipitation

Previous estimates of land-atmosphere interaction (the impact of soil moisture on precipitation) have been limited by a lack of observational data and by the model dependence of computational estimates. To counter the second limitation, a dozen climate-modeling groups have recently performed the same highly controlled numerical experiment as part of a coordinated comparison project. This allows a multimodel estimation of the regions on Earth where precipitation is affected by soil moisture anomalies during Northern Hemisphere summer. Potential benefits of this estimation may include improved seasonal rainfall forecasts.     

Molecular Targets of Brown Algae Phlorotannins for the Therapy of Inflammatory Processes of Various Origins

Inflammatory reactions are part of a complex biological response that plays a vital role in the appearance of various stimuli resulting from tissue and cell damage, the invasion of pathogenic bacteria, and the formation of the subsequent adaptive immune response. The production of many triggers and mediators of inflammation, which are inducers of pro-inflammatory factors, is controlled by numerous differentiation programs, through which inflammation is resolved and tissue homeostasis is restored. However, prolonged inflammatory responses or dysregulation of pro-inflammatory mechanisms can lead to chronic inflammation. Modern advances in biotechnology have made it possible to characterize the anti-inflammatory activity of phlorotannins, polyphenolic compounds from brown seaweed, and the mechanisms by which they modulate the inflammatory response. The purpose of this review is to analyze and summarize the results of numerous experimental in vitro and in vivo studies, illustrating the regulatory mechanisms of these compounds, which have a wide range of biological effects on the body. The results of these studies and the need for further research are discussed.     

Birch stands growth increase in Western Siberia

Birch (Betula pendula Roth) growth within the Western Siberia forest-steppe was analyzed based on long-term (1897–2006) inventory data (height, diameter at breast height [dbh], and stand volume). Analysis of biometry parameters showed increased growth at the beginning of twenty-first century compared to similar stands (stands age = 40–60 years) at the end of nineteenth century. Mean height, dbh, and stem volume increased from 14 to 20 m, from 16 to 22 cm, and from ～63 to ～220 m³/ha, respectively. Significant correlations were found between the stands mean height, dbh, and volume on the one hand, and vegetation period length (r_s = 0.71 to 0.74), atmospheric CO₂ concentration (r_s = 0.71 to 0.76), and drought index (Standardized Precipitation-Evapotranspiration Index, r_s = ?0.33 to ?0.51) on the other hand. The results obtained have revealed apparent climate-induced impacts (e.g. increase of vegetation period length and birch habitat drying due to drought increase) on the stands growth. Along with this, a high correlation of birch biometric parameters and [CO₂] in ambient air indicated an effect of CO₂ fertilization. Meanwhile, further drought increase may switch birch stand growth into decline and greater mortality as has already been observed within the Trans-Baikal forest-steppe ecotone.