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The genus Taxus (yew) is a source of a number of high-value medicinal substances, particularly, paclitaxel (taxol)—a complex diterpenoid compound with a powerful antitumor action (trade name of Taxol®). Paclitaxel is one of the most efficient drugs in chemotherapy owing to its specific ability to suppress proliferation of tumor cells via stabilization of their microtubules. The world-wide demand for taxol is 800–1000 kg a year and these figures annually rise by 20%. The growing need for paclitaxel and its derivatives and the shortage of plant resources necessary for their production made compounds of the taxane group one of the most important objects for development of biotechnological methods of their production. Out of all the possible ways of taxol production (isolation from wild or plantation trees, total chemical synthesis or semisynthesis, use of yew cell cultures, techniques of metabolic engineering, and use of yew endophytic fungi), the most promising is industrial cultivation of Taxus spp. cell cultures. This review examines the papers dealing with investigation of secondary metabolism in dedifferentiated cells in vitro of various yew species and feasibility of industrial use of cell cultures for production of taxoids. We revealed a number of specificity of Taxus spp. cell cultures: (1) from a cytophysiological aspect—difficult initiation of cell cultures, their low growth characteristics, specific media and culturing conditions; (2) from a phytochemical aspect—distinction from intact plants in qualitative composition and content of secondary metabolites accounted for by specificity of cell culture as a biological system; predominant formation of С14-hydroxylated rather than of С13-hydroxylated taxoids; an opportunity for elevation of the content of taxoids—including commercially valuable ones (paclitaxel and baccatin III) with the aid of different tools (elicitation, stress exposures, two-phase cultivation and some others); (3) from a biotechnological aspect—possibility of industrial cultivation of yew cell cultures; existence of several successful industries (Germany and the Republic of Korea).

Taxane diterpenoids (taxoids) are found only in representatives of the Taxaceae family (different yew species); however, the unique structure and therapeutic properties of taxoids, which are in demand in medicine, have made these compounds one of the most studied secondary metabolites of higher plants. In this work, for the first time, a detailed study is performed into the structural diversity of polyesters of 14-hydroxylated taxoids in Taxus canadensis a yew species, for intact plants of which nonpolar 14-hydroxylated taxoids have not been previously described. At the first stage of the work, it was shown using chromato-mass spectrometry that polyesters of 14-hydroxylated taxoids (yunnanxan, taxuyunnanin C, sinenxan B, sinenxan C) are the dominant diterpenoid secondary metabolites in T. canadensis callus cell culture. Based on these results, as well as the similarity of the metabolism of cultivated in vitro plant cells and root cells in planta, it was suggested that polyesters of 14-hydroxylated taxoids will preferentially accumulate in the roots in intact T. canadensis plants. The validity of this hypothesis was confirmed using liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). According to chromato-mass-spectrometric screening in T. canadensis needles, polyesters of 14-hydroxylated taxoids are actually found only in trace amounts, while they are one of the major (quantitatively) diterpenoids in the roots. One of the main 14-hydroxylated taxoids of T. canadensis roots, yunnanxan, was isolated preparatively and uniquely identified using NMR spectroscopy and high-resolution mass spectrometry. This work is the first report on the presence of polyesters of 14-hydroxylated taxoids in intact Canadian yew plants.

This is the first study to show that the formation of 14β-hydroxylated derivatives of taxa-4(20),11-diene is a specific feature of in vitro cultured dedifferentiated yew cells that distinguishes them from intact plant cells. This may be due to a lower toxicity of the 14-OH taxoids for proliferating plant cells compared to the 13-OH derivatives.

Chemotherapy with anthracycline antibiotics is a common method of treating tumors of various etiologies. To create more highly effective cytostatics based on daunorubicin, we used the method of reductive amination using polyalkoxybenzaldehydes. The obtained derivatives of the anthracycline structure have much greater cytotoxicity compared to daunorubicin due to increased affinity for DNA, the ability to disrupt the cell cycle, and their inhibition of the glycolysis process, which is confirmed by data from extensive biological studies and the results of molecular modeling.

IntroductionBiallelic PDX1 variants are a rare cause of isolated pancreatic agenesis and neonatal diabetes (NDM) without exocrine pancreatic insufficiency, with 17 cases reported in the literature.Research design and methodsTo determine the phenotypic variability caused by this rare genetic aetiology, we investigated 19 individuals with NDM resulting from biallelic disease-causing PDX1 variants.ResultsOf the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and/or hepatobiliary tract. Defects in duodenum development are consistent with previous Pdx1 ablation studies in mice which showed abnormal rostral duodenum development.ConclusionsOur findings show that recessive PDX1 variants can cause a syndromic form of NDM, highlighting the need for clinical assessment of extrapancreatic features in individuals with NDM caused by PDX1 variants.

We report here studies on the levels of autoantibodies (aAb) to AMPA glutamate receptors (GluR1 subunit) and NMDA glutamate receptors (NR2A subunit) in serum from 60 children aged 7-16 years with chronic posttraumatic headache (CPTHA) following mild craniocerebral trauma (CCT). The first group consisted of 48 children who had sustained cerebral concussion (CC), of which 34 had single-episode CC (subgroup 1a) and 14 had repeated CC (subgroup 1). The second group included 12 children with mild cerebral contusions (MCC). Serum glutamate receptor aAb levels were measured six months and one year after trauma. Increased aAb levels were expressed as percentages and were regarded as significant when increases were to 120% of the level seen in healthy children of the same age. The highest levels of aAb to NMDA receptors were seen in children with MCC (165 +/- 34%) and single CC (145 +/- 12.6%). Children with repeated CC had NMDA receptor aAb at normal levels (108 +/- 12.4%). Increases in NMDA receptor aAb were seen during the first year after trauma. Increases in AMPA receptor aAb were seen in children with repeated CC and MCC (150 +/- 16.8% and 167 +/- 31.3%). EEG studies showed that 18% of these children had nonspecific paroxysmal changes and 6% showed epileptiform activity. These results provide evidence that children with post-traumatic headache demonstrated hyperstimulation of glutamate receptors and overdevelopment of the autoimmune process. Increases in serum levels of aAb to NMDA glutamate receptors reflected hypoxic-ischemic brain lesions in children with CPTHA and dictate the need for these children to receive metabolic therapy.

A theoretical description of the dynamic phenomena in liquid-crystalline polymeric systems in periodic mechanical disturbances in terms of the shear modulus and the loss modulus has been given. The rheological characteristics (dynamic viscosity, accumulation modulus, loss modulus, and others) of a synthesized sample of a liquid-crystalline polymeric system -- aromatic polyamide -- and the critical concentration of its transition from the isotropic state to a liquid-crystalline phase have been determined experimentally.[PUBLICATION ABSTRACT]