The study of secondary metabolites has led to the discovery of new drugs for treating human diseases. However, consistent plant supply can be challenging, leading to the use of plant tissue culture ...techniques such as hairy root culture. Hairy roots have stable genetics, lateral branching, and can produce secondary metabolites, including alkaloids, flavonoids, and terpenoids. Research on hairy roots as a subject began in the late 19th century, and for the last four decades, hairy roots have been utilized for producing secondary metabolites and recombinant proteins. This article focuses on Rhodiola species - genus of perennial plants that belongs to the family Crassulaceae - and its potential as a source of secondary metabolites using hairy root culture techniques. Rhodiola sp. is widely distributed throughout the Arctic regions of the Northern Hemisphere, with several species having significant medicinal properties. The article discusses the possible use of hairy root cultures for the production of Rhodiola secondary metabolites, including salidroside and rosavins, which have demonstrated significant pharmacological activity in various studies. The use of elicitation and genetic engineering techniques to boost secondary metabolite production in Rhodiola hairy roots is also explored. Overall, the article highlights the potential of Rhodiola hairy root cultures as a valuable source of secondary metabolites with medicinal properties. However, despite some studies Rhodiola hairy root induction and culturing still remains highly unexplored.
The possible role of the naturally occurring deuterium in the regulation of cell division was first described in the 1990s. To investigate the mechanism of influence of deuterium (D) on cell growth, ...expression of 236 cancer-related and 536 kinase genes were tested in deuterium-depleted (40 and 80 ppm) and deuterium-enriched (300 ppm) media compared to natural D level (150 ppm). Among genes with expression changes exceeding 30% and copy numbers over 30 (124 and 135 genes, respectively) 97.3% of them was upregulated at 300 ppm D-concentration. In mice exposed to chemical carcinogen, one-year survival data showed that deuterium-depleted water (DDW) with 30 ppm D as drinking water prevented tumor development. One quarter of the treated male mice survived 344 days, the females 334 days, while one quarter of the control mice survived only 188 and 156 days, respectively. In our human retrospective study 204 previously treated cancer patients with disease in remission, who consumed DDW, were followed. Cumulative follow-up time was 1024 years, and average follow-up time per patient, 5 years (median: 3.6 years). One hundred and fifty-six patients out of 204 (77.9%) did not relapse during their 803 years cumulative follow-up time. Median survival time (MST) was not calculable due to the extremely low death rate (11 cancer-related deaths, 5.4% of the study population). Importantly, 8 out of 11 deaths occurred several years after stopping DDW consumption, confirming that regular consumption of DDW can prevent recurrence of cancer. These findings point to the likely mechanism in which consumption of DDW keeps D-concentration below natural levels, preventing the D/H ratio from increasing to the threshold required for cell division. This in turn can serve as a key to reduce the relapse rate of cancer patients and/or to reduce cancer incidence in healthy populations.
Prevailing models of resistive switching arising from electrochemical formation of conducting filaments across solid state ionic conductors commonly attribute the observed polarity of the ...voltage-biased switching to the sequence of the active and inert electrodes confining the resistive switching memory cell. Here we demonstrate stable switching behaviour in metallic Ag-Ag2S-Ag nanojunctions at room temperature exhibiting similar characteristics. Our experimental results and numerical simulations reveal that the polarity of the switchings is solely determined by the geometrical asymmetry of the electrode surfaces. By the lithographical design of a proof of principle device we demonstrate the merits of simplified fabrication of atomic-scale, robust planar Ag2S memory cells.
New models of graph-bin packing Bujtás, Cs; Dósa, Gy; Imreh, Cs ...
Theoretical computer science,
08/2016, Letnik:
640
Journal Article
Recenzirano
Odprti dostop
In Bujtás et al. (2011) 4 the authors introduced a very general problem called Graph-Bin Packing (GBP). It requires a mapping μ:V(G)→V(H) from the vertex set of an input graph G into a fixed host ...graph H, which, among other conditions, satisfies that for each pair u,v of adjacent vertices the distance of μ(u) and μ(v) in H is between two prescribed bounds. In this paper we propose two online versions of the Graph-Bin Packing problem. In both cases the vertices can arrive in an arbitrary order where each new vertex is adjacent to some of the previous ones. One version is a Maker–Breaker game whose rules are defined by the packing conditions. A subclass of Maker-win input graphs is what we call ‘well-packable’; it means that a packing of G is obtained whenever the mapping μ(u) is generated by selecting an arbitrary feasible vertex of the host graph for the next vertex of G in each step. The other model is connected-online packing where we are looking for an online algorithm which can always find a feasible packing. In both models we present some sufficient and some necessary conditions for packability. In the connected-online version we also give bounds on the size of used part of the host graph.
Organophosphorus Chemistry presents a groundbreaking resource in this branch of organic chemistry that demonstrates how phosphorus-containing compounds can be manipulated in a variety of organic ...reactions. The authors give an overview of the newest trends and synthesis strategies, introduce bioactive and environmentally friendly organophosphorus compounds and show their importance in mainstream organic chemistry.
It was proved by our experiments that on microwave irradiation, the mono‐ or bidentate phosphorus ligands generally applied in the palladium(II)‐catalyzed P–C coupling reaction of aryl bromides and ...dialkyl phosphites or secondary phosphine oxides may be substituted by the excess of the >P(O)H reagent that exists under a tautomeric equilibrium. Taking into account that the reduction of the palladium(II) salt and the ligation of the palladium(0) so formed requires 3 equivalents of the P‐species for the catalyst applied in a quantity of 5–10%, all together, 15–30% of the P‐reagent is necessary beyond its stoichiometric quantity. In the coupling reaction of diphenylphosphine oxide, it was possible to apply diethyl phosphite as the reducing agent and as the P‐ligand. The reactivities of the diethyl phosphite and diphenylphosphine oxide reagents were compared in a competitive reaction. The mechanism and the energetics of this new variation of the Hirao reaction of bromobenzene with Y2P(O)H reagents (Y=EtO and Ph) was explored by quantum chemical calculations. The first detailed study on simple reaction models justified our assumption that, under the conditions of the reaction, the trivalent form of the >P(O)H reagent may serve as the P‐ligand in the palladium(0) catalyst, and shed light on the fine mechanism of the reaction sequence. The existence of the earlier described bis(palladium complex) {H(OPh2P)2PdOAc2} was refuted by high level theoretical calculations. This kind of complex may be formed only with chloride anions instead of the acetate anion. The interaction of palladium acetate and Y2P(O)H may result in only the formation of the (HO)Y2P2Pd complex that is the active catalyst in the Hirao reaction. The new variation of the Hirao reaction is of a more general value, and represents the greenest protocol, as there is no need for the usual P‐ligands. Instead, the >P(O)H reagent should be used in an excess of up to 30%. Hence, the costs and environmental burdens may be decreased.
Schizophrenia is a life-long mental disorder, affecting young adolescents to elderly patients. Antipsychotic treatment is indicated for all patients with schizophrenia, including the very young and ...old as well. Developmental issues in the young and decline in organ functioning in the elderly could influence reactions to the drug, and require different dosing regimens. The aim of the present article was to examine the safety profile and dosing requirements in adolescent (13 to less than 18) and elderly (65 and above) patients treated with cariprazine. Data from two clinical studies (one pharmacokinetic pediatric study and one phase III clinical trial) on 49 adolescent patients and 17 elderly patients (65 years of age or above) treated with cariprazine was examined. Safety measures included assessment of adverse events (AEs), clinical laboratory values, physical examinations, extrapyramidal symptom (EPS)-, depression-, and suicidality rating scales. Safety parameters were summarized using descriptive statistics. Results indicate that cariprazine was generally safe and well tolerated. Adverse events in the marginal age populations were comparable to the adult population, except for less insomnia in the young and no reports of akathisia in the elderly. Laboratory parameters, vital sign values and EEG parameters were comparable to previously published data in the adult population. In conclusion, cariprazine in the approved adult dose-range of 1.5-6 mg might be a safe treatment option also in adolescent and elderly patients with schizophrenia. Further studies are need to verify these preliminary findings.
ABSTRACT
Extracellular ATP binds to and signals through P2X7 receptors (P2X7Rs) to modulate immune function in both inflammasome‐dependent and ‐independent manners. In this study, P2X7‐/‐ mice, the ...pharmacological agonists ATP‐magnesium salt (Mg‐ATP; 100 mg/kg, EC50 ≈ 1.32 mM) and benzoylbenzoyl‐ATP (Bz‐ATP; 10 mg/kg, EC50 ≈ 285 μM), and antagonist oxidized ATP (oxi‐ATP; 40 mg/kg, IC50 ≈ 100 μM) were used to show that P2X7R activation is crucial for the control of mortality, bacterial dissemination, and inflammation in cecal ligation and puncture‐induced polymicrobial sepsis in mice. Our results with P2X7‐/‐ bone marrow chimeric mice, adoptive transfer of peritoneal macrophages, and myeloid‐specific P2X7‐/‐ mice indicate that P2X7R signaling on macrophages is essential for the protective effect of P2X7Rs. P2X7R signaling protects through enhancing bacterial killing by macrophages, which is independent of the inflammasome. By using the connexin (Cx) channel inhibitor Gap27 (0.1 mg/kg, IC50 ≈ 0.25 μM) and pannexin channel inhibitor probenecid (10 mg/kg, IC50 ≈ 11.7 μM), we showed that ATP release through Cx is important for inhibiting inflammation and bacterial burden. In summary, targeting P2X7Rs provides a new opportunity for harnessing an endogenous protective immune mechanism in the treatment of sepsis.—Csóka, B., Németh, Z. H., Törő, G., Idzko, M., Zech, A., Koscsó, B., Spolarics, Z., Antonioli, L., Cseri, K., Erdélyi, K., Pacher, P., Haskó, G. Extracellular ATP protects against sepsis through macrophage P2X7 purinergic receptors by enhancing intracellular bacterial killing. FASEB J. 29, 3626‐3637 (2015). www.fasebj.org
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