Small RNA F6 Provides Mycobacterium smegmatis Entry into Dormancy

Regulatory small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. Various stresses such as hypoxia and nutrient starvation cause a reduction in the metabolic activity of Mycobacterium smegmatis, leading to entry into dormancy. We investigated the functional role of F6, a small RNA of M. smegmatis, and constructed an F6 deletion strain of M. smegmatis. Using the RNA-seq approach, we demonstrated that gene expression changes that accompany F6 deletion contributed to bacterial resistance against oxidative stress. We also found that F6 directly interacted with 5′-UTR of MSMEG_4640 mRNA encoding RpfE2, a resuscitation-promoting factor, which led to the downregulation of RpfE2 expression. The F6 deletion strain was characterized by the reduced ability to enter into dormancy (non-culturability) in the potassium deficiency model compared to the wild-type strain, indicating that F6 significantly contributes to bacterial adaptation to non-optimal growth conditions.     

Trophic Transfer of Au Nanoparticles from Soil along a Simulated Terrestrial Food Chain

To determine if nanoparticles (NPs) could be transferred from soil media to invertebrates and then to secondary consumers, we examined the trophic transfer of Au NPs along a simulated terrestrial food chain. Earthworms (Eisenia fetida) were exposed to Au NPs in artificial soil media and fed to juvenile bullfrogs (Rana catesbeina). Earthworm Au concentrations were continuously monitored so that the cumulative dose to bullfrogs could be accurately estimated throughout the experiment. We exposed a second group of bullfrogs to equivalent doses of Au NPs by oral gavage to compare the bioavailability of NPs through direct exposure to trophic exposure. We observed accumulation of Au in liver, kidney, spleen, muscle, stomach, and intestine in both treatment groups. Tissue concentrations decreased on average of approximately 100-fold with each trophic-step. The total assimilated dose averaged only 0.09% of the administered dose for direct exposure (oral gavage), but 0.12% for the trophic exposure. The results suggest that manufactured NPs present in soil may be taken up into food chains and transferred to higher order consumers. They also suggest that Au NPs may be more bioavailable through trophic exposure than direct exposure and that trophic transfer may influence the biodistribution of particles once absorbed.     

Synthesis and pro-apoptotic activity of novel glycyrrhetinic acid derivatives

Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway.     

Photoinduced electron transfer reactions: from the elucidation of old problems in bulk solutions towards the exploration of interfaces

The activities of our research group in the field of photoinduced electron transfer reactions are discussed and illustrated by several examples.     

Potentiometric determination of ketoprofen and piroxicam at a new PVC electrode based on ion associates of Rhodamine 6G

The characteristics, performance and application of ion-selective electrodes for ketoprofen and piroxicam ions based on Rhodamine 6G as electrode-active substances are described. These electrodes respond with sensitivities of (58.0 ± 1.0) and (57.0 ± 2.0) mV/decade over the range 1.0 × 10^? 4–1.0 × 10^? 1 and 1.0 × 10^? 4–5.0 × 10^? 2 mol/l at pH 5–9 and 6–10 and a detection limit of 6.3 × 10^? 5 and 3.2 × 10^? 5 mol/l for ketoprofen and piroxicam, respectively. The electrodes are easily constructed at a relatively low cost, have a fast response time and can be used for a period of 5 months without any considerable divergence in potential. The proposed sensor displayed good selectivity for ketoprofen and piroxicam in the presence of several substances and inorganic anions. It was used for the direct assay of ketoprofen and piroxicam in commercial pharmaceutical preparations.     

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile,Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo

It is known that epoxide-bearing compounds display pronounced pharmacological activities, and the epoxidation of natural metabolites can be a promising strategy to improve their bioactivity. Here, we report the design, synthesis and evaluation of biological properties of αO-SM and βO-SM, novel epoxides of soloxolone methyl (SM), a cyanoenone-bearing derivative of 18βH-glycyrrhetinic acid. We demonstrated that the replacement of a double-bound within the cyanoenone pharmacophore group of SM with α- and β-epoxide moieties did not abrogate the high antitumor and anti-inflammatory potentials of the triterpenoid. It was found that novel SM epoxides induced the death of tumor cells at low micromolar concentrations (IC₅₀^(24h) = 0.7–4.1 µM) via the induction of mitochondrial-mediated apoptosis, reinforced intracellular accumulation of doxorubicin in B16 melanoma cells, probably by direct interaction with key drug efflux pumps (P-glycoprotein, MRP1, MXR1), and the suppressed pro-metastatic phenotype of B16 cells, effectively inhibiting their metastasis in a murine model. Moreover, αO-SM and βO-SM hampered macrophage functionality in vitro (motility, NO production) and significantly suppressed carrageenan-induced peritonitis in vivo. Furthermore, the effect of the stereoisomerism of SM epoxides on the mentioned bioactivities and toxic profiles of these compounds in vivo were evaluated. Considering the comparable antitumor and anti-inflammatory effects of SM epoxides with SM and reference drugs (dacarbazine, dexamethasone), αO-SM and βO-SM can be considered novel promising antitumor and anti-inflammatory drug candidates.     

不同热变形工艺大塑性变形加工超细晶1570C铝合金的组织、强度和超塑性

将Al-5Mg-0.18Mn-0.2Sc-0.08Zr-0.01Fe-0.01Si(质量分数,％)合金铸锭进行多向等温锻造(应变12)或等径角挤压(应变10,325℃),再进行热轧(325℃)和冷轧(20℃),对比研究合金变形后的组织和力学行为.结果表明,对(亚)晶粒尺寸dUFG=2μm的超细晶组织合金进行多向等温锻造...     

Effect of Salinity on Stomatal Conductance,Leaf Hydraulic Conductance,HvPIP2 Aquaporin,and Abscisic Acid Abundance in Barley Leaf Cells

The stomatal closure of salt-stressed plants reduces transpiration bringing about the maintenance of plant tissue hydration. The aim of this work was to test for any involvement of aquaporins (AQPs) in stomatal closure under salinity. The changes in the level of aquaporins in the cells were detected with the help of an immunohistochemical technique using antibodies against HvPIP2;2. In parallel, leaf sections were stained for abscisic acid (ABA). The effects of salinity were compared to those of exogenously applied ABA on leaf HvPIP2;2 levels and the stomatal and leaf hydraulic conductance of barley plants. Salinity reduced the abundance of HvPIP2;2 in the cells of the mestome sheath due to it being the more likely hydraulic barrier due to the deposition of lignin, accompanied by a decline in the hydraulic conductivity, transpiration, and ABA accumulation. The effects of exogenous ABA differed from those of salinity. This hormone decreased transpiration but increased the shoot hydraulic conductivity and PIP2;2 abundance. The difference in the action of the exogenous hormone and salinity may be related to the difference in the ABA distribution between leaf cells, with the hormone accumulating mainly in the mesophyll of salt-stressed plants and in the cells of the bundle sheaths of ABA-treated plants. The obtained results suggest the following succession of events: salinity decreases water flow into the shoots due to the decreased abundance of PIP2;2 and hydraulic conductance, while the decline in leaf hydration leads to the production of ABA in the leaves and stomatal closure.     

Palmoplantar Keratoderma: A Molecular Genetic Analysis of Family Cases

Palmoplantar keratoderma is a clinically polymorphic disorder with a heterogeneous etiology characterized by marked hyperkeratotic lesions on the surface of palms and soles. Hereditary forms of palmoplantar keratoderma usually have autosomal dominant inheritance and are caused by mutations in dozens of genes, most of which belong to the keratin family. We carried out clinical and molecular genetic analysis of the affected and healthy members of four families with autosomal dominant palmoplantar keratoderma. In three out of four family cases of autosomal dominant palmoplantar keratoderma, the following molecular genetic causes were established: in two families—previously non-described missense mutations in the AQP5 gene ({"type":"entrez-nucleotide","attrs":{"text":"NM_001651.4","term_id":"1519473780","term_text":"NM_001651.4"}}NM_001651.4): c.369C>G (p.(Asn123Lys)) and c.103T>G (p.(Trp35Gly)); in one family—a described splice site mutation in the KRT9 gene ({"type":"entrez-nucleotide","attrs":{"text":"NM_000226.4","term_id":"1519245988","term_text":"NM_000226.4"}}NM_000226.4): c.31T>G. In one family, the possible cause of palmoplantar keratoderma was detected—a variant in the KRT1 gene ({"type":"entrez-nucleotide","attrs":{"text":"NM_006121.4","term_id":"1519311739","term_text":"NM_006121.4"}}NM_006121.4): c.931G>A (p.(Glu311Lys)).