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Photocatalysis involving energy transfer (EnT) has become a valuable technique for building intricate organic frameworks mostly through [2+2]-cycloaddition reactions. Herein, we report a synthetic method leading to functionalized cyclohepta[ b ]indoles, an important structural motif in natural products and pharmaceuticals, using gold-mediated energy transfer photocatalysis. The scope of this operationally simple and atom-economical strategy is presented. Density functional theory studies were employed in order to gain insights into the mechanism of formation of the cyclohepta[ b ]indole core.

Energy transfer (EnT) photocatalysis has emerged as a valuable tool for constructing complex organic scaffolds via [2 + 2]-cycloaddition reactions. Herein, we present the use of [Au(SIPr)(Cbz)] as a sensitizer for the [2 + 2]-cycloaddition of coumarins and unactivated alkenes. Widely used in EnT catalysis, iridium and organic sensitizers proved less efficient under the examined catalytic conditions. The developed protocol permits the synthesis of cyclobutane-fused chromanones from readily available starting materials. A wide range of alkenes and substituted coumarins, including naturally occurring compounds, were reacted under mild conditions leading to structurally complex products with good functional group tolerance. Mechanistic studies reveal a previously overlooked reaction pathway for energy transfer catalysis involving coumarins., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Green and sustainable access to chiral and achiral gold-IBiox complexes is reported. The gold complexes were synthesized using a simple, air-tolerant, weak base protocol carried out in a green solvent. Their catalytic activity was examined in the hydroamination of alkynes. The steric protection afforded the gold center by these ligands was quantified using the % V bur model and compared with the most commonly encountered NHCs.

The area of energy transfer photocatalysis to generate four-membered rings is experiencing an unprecedented level of activity. Here, we report an operationally simple method toward azetidines from 2-isoxasoline-3-carboxylates and alkenes, using [Au(cbz)(NHC)] complexes as photocatalysts. The procedure enables the reaction for a wide range of substrates. Mechanistic studies confirm the energy transfer pathway. This contribution adds to the earlier reported use of these gold catalysts as a potentially versatile tool in energy transfer chemistry and catalysis.

Along with bright fluorescence in the near-IR range, heptamethine carbocyanine dyes possess affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery as covalent conjugates with cytotoxic compounds. To test the properties, structure-activity relationship, and scope of such conjugates, we synthesized drug-dye dyads of tricarbocyanine dyes with anthracycline drug daunorubicin. We used hydrophilic zwitterionic and hydrophobic positively charged benzoindoline-benzothiazole-based heptamethine dyes as terminal alkyne derivatives and N-acylated or oxime-linked daunorubicin as azido-derivatives. These two alkynes and two azides were coupled to each other by Cu-catalyzed Huisgen-Meldal-Sharpless cycloaddition (click reaction) to afford four conjugates. Molecules based on hydrophobic dyes possess submicromolar cytotoxicity to HCT116 cells. Cytotoxicity, cell penetration, intracellular distribution, apoptosis induction and the effect of antioxidants on toxicity were evaluated. The results show that the structure of the cyanine-anthracycline conjugate (hydrophilicity/hydrophobicity, charge, linker, attachment site) is important for its biological activity, thus, expansion of the chemical space of such conjugates could provide new molecular research tools for diagnostics and therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

We present the use of gold sensitizers [Au(SIPr)(Cbz)] (PhotAu 1) and [Au(IPr)(Cbz)] (PhotAu 2) as attractive alternatives to state-of-the-art iridium-based systems. These novel photocatalysts are deployed in [2 + 2] cycloadditions of diallyl ethers and N -tosylamides. The reactions proceed in short reaction times and in environmentally friendly solvents. [Au(SIPr)Cbz] and [Au(IPr)(Cbz)] have higher triplet energy ( E T ) values (66.6 and 66.3 kcal mol -1 , respectively) compared to commonly used iridium photosensitizers. These E T values permit the use of these gold complexes as sensitizers enabling energy transfer catalysis involving unprotected indole derivatives, a substrate class previously inaccessible with state-of-the-art Ir photocatalysts. The photosynthesis of unprotected tetracyclic spiroindolines via intramolecular [2 + 2] cycloaddition using our simple mononuclear gold sensitizer is readily achieved. Mechanistic studies support the involvement of triplet-triplet energy transfer (TTEnT) for both [2 + 2] photocycloadditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A simple synthetic pathway to Au-NHC amido complexes is described. Syntheses and isolation of [Au(NHC)(NR 1 R 2 )] complexes, bearing various NHC ligands and NH-containing heterocycles under mild conditions are reported. The in vitro anticancer activity of these gold-complexes was investigated on three human cancer cell lines. A number of these show comparable or even better antiproliferative activity than cisplatin. Noteworthy is the non-toxicity of most of the complexes on normal cells.

The development of novel and operationally simple synthetic routes to carbene-metal-amido (CMA) complexes of copper, silver and gold relevant for photonic applications are reported. A mild base and sustainable solvents allow all reactions to be conducted in air and at room temperature, leading to high yields of the targeted compounds even on multigram scales. The effect of various mild bases on the N-H metallation was studied in silico and experimentally, while a mechanochemical, solvent-free synthetic approach was also developed. Our photophysical studies on [M(NHC)(Cbz)] (Cbz=carbazolyl) indicate that the occurrence of fluorescent or phosphorescent states is determined primarily by the metal, providing control over the excited state properties. Consequently, we demonstrate the potential of the new CMAs beyond luminescence applications by employing a selected CMA as a photocatalyst. The exemplified synthetic ease is expected to accelerate the applications of CMAs in photocatalysis and materials chemistry., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Mechanistic investigations are presented, illustrating the formation of intermediates which are air and moisture stable, prior to the metallation step. Finally, the importance, limitations and future prospects of the weak base route are discussed.

The evaporation of a dicationic ionic liquid, 1,3-bis(3-methylimidazolium-1-yl)propane bis(trifluoromethanesulfonyl)amide ([C 3 (MIm) 2 2+ ][Tf 2 N - ] 2 ), was studied by Knudsen effusion mass spectrometry. Its evaporation is accompanied by a partial thermal decomposition producing monocationic ionic liquids, 1,3-dimethylimidazolium and 1-(2-propenyl)-3-methylimidazolium bis(trifluoromethanesulfonyl)amides, as volatile products. This decomposition does not affect the vaporization characteristics of [C 3 (MIm) 2 2+ ][Tf 2 N - ] 2 , which were established to be as follows. The vaporization enthalpy (550 K) is equal to (155.5 ± 3.2) kJ·mol -1 ; the saturated vapor pressure is described by the equation ln( p/Pa) = -(18699 ± 381)/( T/K) + (30.21 ± 0.82) in the range of 508-583 K. 1,3-Bis(3-methylimidazolium-1-yl)propane bis(trifluoromethanesulfonyl)amide is the first dicationic ionic liquid, the vaporization characteristics of which were determined with an acceptable accuracy.

Aim of the Study: to investigate associations of single nucleotide polymorphisms (SNP) rs499818 (6p24.1), rs619203 of ROS1 gene (6q22), rs10757278 rs1333049 (9p21.3), rs2549513 (16q23.1), rs4804611 of ZNF627 gene (19p13.2) with myocardial infarction in subjects of young age. The group of patients with MI (n=99) aged less than 45 years and the control group (n=111) did not differ significantly by sex (=0,617), age (=0.291), arterial hypertension (=0.766), diabetes mellitus (=0.395), hypercholestolemia (=0.696), excessive body mass and obesity (=0.361), abdominal obesity (=0.831) and history of smoking (=0.400). There was significant difference between groups by burdened heredity (<0.001). Genomic DNA was obtained from venous blood by phenol-chloroform extraction. Genetic testing was performed by real time polymerase chain reaction using 7900HT Fast Real-Time PCR System according to manufacturers protocol. We found significant association between rs1333049 and rs10757278 and myocardial infarction (MI). Odds ratio (OR) of development of MI in carriers of risk allele rs1333049 was 2.4 (95% confidence interval [CI] 1.24 to 4.65), in carriers of G rs10757278 allele - 2.00 (95%CI 1.05 to 3.80). Association of risk alleles rs 1333049 and G rs10757278 with MI remained significant after adjustment for burdened family history (OR 4.25, 95%CI 1.39 to 12.99, and OR 3.04, 95%CI 1.09 to 8.52, respectively). Presence in the genotype of both risk alleles rs1333049 and G rs10757278 was associated with OR of MI development 2.40 (95%CI 1.20 to 4.82) which was not different from that associated with carriage of allele rs1333049 only. Possibly in our population both SNPs belong to one linkage block and correspondingly it is sufficient to genotype one SNP. No significant associations with MI were found for variants rs4804611, rs2549513, rs499818, rs619203. SNPs rs1333049 and rs10757278 of 9p21.3 locus are predictors of MI in young individuals not dependent on both traditional risk factors and presence of burdened family history.

Mycotoxin Fumonisin B1 posseesses the weak DNA-damage activity for the E. coli strain defective in UvrA gene participating in DNA reparation. Fumonisin B1 in the concentration 10(-5) M increases a resistance of wild type E. coli cells to antibiotic doxycycline. Obtained results indicate the influence of fumonisin B1 on the genome of the cultured E. coli cells.

Here we present some information on the role of heat shock proteins participate in the metabolic substance nutrients and energy status cells. These proteins provide the significant role in the regulation of digestion as well as metabolism of whole organism.

Modified maize starches having differences in the number of crosscut lacings in the structure, and in the abilities to be gelatinized in the cold water were used: native maize starch "Novation 4600", acetylated adipat di-starch of the cold swelling "Prejeflo CH 20", acetylated adipat di-starch of the cold swelling "Prejeflo CH 40", acetylated adipat di-starch of the hot swelling "Clearam CH 2020". All investigated starches possessed the ability to activate neutrophils and to increase their phagocytosis 2 h after i.p. administration. Four days after i.p. injection, starches and their hydrolyzet starch products were shown to stimulate the neutrophils and lymphocytes into peritoneal cavity. Starch digest products have the more stimulated capacities compared with native compounds that indicates the possible immune activity of starch carbohydrate chain fragments.

Aim of work was to compare the chemical and biological properties of starches modified by adipinic acid acetylation. Starches in question were: native maize starch "Novation 4600"; acetylated adipat di-starch of the cold swelling "Prejeflo CH 20"; acetylated adipat di-starch of the cold swelling "Prejeflo CH 40"; acetylated adipat di-starch of the hot swelling "Clearam CH 2020". The differences between starches were connected with number of cross-cut lacings in the structure, and with abilities to be gelatinized in the cold water. Rate of hydrolysis and water-retaining capacities were higher for cold swelling starches which contained the smaller number of resistance fractions. Acetyl value of cold swelling starches was higher under elevation of cross-cut lacing.

Energy-proteolysis is the integral part of cell protein turnover Proteolysis controls the quality of protein post-translational modification, folding as well as the structural and functional cell activities. Several proteolytic systems including 26S proteasomes participate in the cell protein degradation. Human diet regulates the rate of protein turnover. Total protein level, amino acid composition, fasting, toxins, etc. modify the receptor expression, signal transduction, factor transcription activity and expression of genes to regulate the cellular response in metabolic stress. Activities of some ATPases are dependent on the nutritional factors. Free amino acid peptides released from proteasomes may control the protein-protein interaction and cellular metabolic pathways.

Modified and resistant starches regulate the colon microbiota metabolism and gene expression. This adaptive response allows bacteria to obtain the new enzymes to metabolize the unusual substrates. The potato starches modify the colon residential microorganisms. It was a reason the study the influence of the modified and resistant potato starches on the E. coli lines defected in the gene reparation system. It allows us to estimate the participation of some components of gene reparation system in the adoptive response of bacteria to the chemical compounds. Potato starches in the concentration 1% have been found to be indifferent to the DNA E. coli lines Wp. RecA. PolA [Russian character: see text] UvrA. High amilose notato starch stimulates these lines growth that indicates to its prebiotic canacities.

This paper reviews evidence for the immune-enhancing effects of prebiotics. The influence of inulin and oligofructose on the immune functions and the structure of immune peripheral organs in male Wistar rats was investigated after 4 months feeding. Rats fed isocaloric purified diets contained 10% inulin or oligofructose. The rats of control group had no feeding any prebiotics. The enlargement of a number of T-cells and increasing of major histocompatibility complex (MHC-II) molecule on the surface of an antigen-presenting cells of spleen, mesenteric lymph nodes, thymus was noted. The increasing of content interleukin-2 and interleukin-4 in blood was noted in rats fed inulin and oligofructose. The increased activity of peritoneal macrophages was confirmed by enhance superoxid anion production and phagocytosis. The dietary prebiotics do not influence on the apoptosis of immunocytes. The immune-enhancing effects of prebiotics was confirmed by morphological investigation of peripheral lymphoid organs.

Intracellular cysteine aspartate-specific proteases (caspases) play both signaling and effector roles in realizing the program of cell death. Caspases function as proteolytic cascades unique for each cell type and signal triggering apoptosis. All parts of the proteolytic cascades are duplicated and controlled by feedback signals. Amplification cycles between pairs of caspases (the third and the sixth, the ninth and the third, the twelfth and the sixth, and others) help multiply the initial apoptotic signal. The presence of physiological inhibitors of apoptosis that directly interact with caspases creates a multilevel regulatory network of apoptosis in cell. The caspase proteolytic cascades are also regulated by sphingolipid secondary messengers, among them ceramide, sphingosine, and their phosphates. Moreover, an association of the caspase signaling with ubiquitin-dependent proteolysis is shown in cells. In particular, the use of extracellular activators and inhibitors of caspases allows irreversible activation of apoptosis in tumor cells or the prevention of neuron death in neurodegenerative diseases.

We compared the effects of maize and potato starch on Wistar rats. The level of oligonucleosomal DNA fragmentation increased in thymic and splenic cells of animals receiving potato starch. The expression of Fas/CD95/Apo-1 apoptosis receptor in lymphocytes and their response to exogenous ceramide was also higher in rats receiving potato starch compared to the reference group. This led to intensification of spontaneous and induced apoptosis and decreased cell content in immune organs. The authors conclude that higher resistance of potato starch to digestive enzymes leads to modification of cell metabolism and induction of ceramide-dependent apoptosis in immune cells.

Unlabelled: TNF is the known death receptor ligand which induce apoptosis and necrosis. Reactive oxygen metabolites, ceramide (synthesized de novo and as a product of sphingomyelin cycle), and caspases have been implicated as potential mediators of cell death. Their mechanistic relationship remains to be elucidated. The presence and activation of executor caspase-3 has been found to be regulated during both TNF-induced apoptosis and necrosis on their early stages. TNF-induced cell damage, suggesting the induction of both, apoptosis and necrosis, depended on the cell cycle. Necrosis induced by TNF was inhibited by denitrophenol (DNP). Pretreatment of these cells with exogenous bacterial sphingomyelinase (SMase) potentiates TNF-alpha induced apoptosis only, suggesting the role of ceramide from sphingomyelin cycle in TNF signaling pathways of apoptosis. DNP was found to initiate necrosis after SMase and TNF common action. The role of ceramide synthesis in enhanced ceramide generation in response to oxidant stress was shown using inhibitor of ceramide synthase--fumonisin B1. Its effect was found to be modulated by mitochondrial chain respiration inhibitors. Monoclonal antibodies to TNF-alpha receptors R1 and R2 exhibit the more high level of necrosis compared with TNF and both regulated by DNP and phospholipase A2. TNF-R2 effect was not found previously., Conclusion: Ceramide synthesis and sphingomyelin breakdown, caspase activation and reactive oxygen metabolites production are required for the TNF-alpha-induced apoptosis and necrosis which may be regulated dependently on cell cycle. TNF-initiated necrosis seems to be the disrupted apoptotic program and may be classified as aponecrosis.

Immune status measured by the flow cytrometric analysis under the ischemic heart disease and IHD with impaired glucose tolerance has been found to be altered in B cells as well as in T lymphocytes in some cases. Having received the diet supplemented by PUFA "Eicolen", IHD patients present with the restored immune status. Patients with IHD and impaired glucose tolerance did not present with any significant modifications in immune status after PUFA "Eicolen" supplementation.

Different absorbtion level is inherent capacities for natural, resistant and hydrolized starches to regulate a volume of non-hydrolyzed starches in colon. This regulates an interaction with intestinal microflora to produce the short chain fatty acids and other bio-active compounds. The T- and B-lymphocyte receptors are targets for starches to disrupt the number and density of plasma membrane receptors CD3, CD4, and CD8. All starches regulate the expression of adhesion molecules LFA-1 and ICAM-1, as well as receptor Mac-1. Maize starch increases the level of spontaneous and ceramide-dependent apoptosis in thymic and spleen cells of experimental animals.

The fungi (Fusarium moniliforme) residing on cereals produce a broad range of mycotoxins, among which fumonisins display a high toxicity alongside with carcinogenic and teratogenic activities. Taking into account the ability of fumonisins to inhibit sphingolipid synthesis, the role of sphingomyelin cycle products in immune reactions was studied with the view of establishing the correlation between the expression of the surface receptor CD3 in immunocompetent organs (spleen, thymus) (T-cell mediated immunity) and the degree of sphingomyelin cycle activation (changes in the activities of sphingomyelinase and sphingomyelin and ceramide content) in the spleen, thymus and liver 2.5 hours after intraperitoneal injection of fumonisin B1 (FB1) (5 and 20 micrograms/animal). Significant sphingomyelinase activation was found in the thymus of animals injected with 20 micrograms of fumonisin. It coincides with a loss of the sphingomyelin and ceramide content. The changes in the sphingomyelinase activity and sphingomyelin content in the spleen and in the liver caused by fumonisin were insignificant, while the ceramide content dropped drastically. Fumonisin decreased the receptor CD3 expression on the surface of thymus cells "in vitro" and "in vivo", which is consistent with the sharp decrease of the ceramide content in this organ. Ceramide accumulation in thymus and spleen cells treated with sphingomyelinase in vitro correlates with the increased affinity of receptor CD3. The putative role of ceramide in the expression of receptors modulating T-cell mediated immunity under the influence of fumonisin is discussed.

Dietary effects of polyunsaturated fatty acids (PUFA) omega-3 on lipid peroxidation (LPO) and antioxidant system were studied in 73 patients with ischemic heart disease, hyperlipoproteinemia (HLPE) type IIa, IIb, IV and essential hypertension. Eiconol-enriched antiatherosclerotic diet has more potent hypolipidemic, hypotensive and thrombolytic action in association with inhibition of LPO, enhances SOD activity, keeps red cell catalase within normal. Vitamin E concentrations were not changed. It is suggested that eiconol addition to antiatherosclerotic diet causes no LPO induction and is pathognomonic for HLPE, hypertension and IHD patients.

An epidemic outbreak of Sonne dysentery has been studied. The data of epidemiological monitoring before and after the epidemic have been analyzed. The real prognostication value of controlling the biological properties of Shigella sonnei and the increase of their intrapopulation heterogeneity at the period of the activation of the epidemic process of Sonne dysentery has been established.

The state of the digestive system was investigated in more than 300 women patients with obesity, aged 16-25 years. Significant shifts have been revealed in the biliferous system and in the gastrointestinal tract of 40% of the investigated patients. The shifts detected necessitate correction of the conventional reduced regimens of nutrition.

The hemodynamic effects of intravenously administered relatively selective mu-(DAGO) and delta-(DADL) opioid agonists were investigated in conscious rats. The radioactive microsphere technique was used to measure regional blood flow in 10 zones before and 5 min after bolus injection of each peptide. Both opioid agonists in a dose of 1 mumol/kg produced transient hypotension, bradycardia and apnoea. DADL injection increased blood flow in the adrenals and decreased it in the muscles; vascular resistance spleen. DAGO administration increased blood flow in the adrenals and decreased it in the pancreas and skin, whereas vascular resistance increased in the pancreas and skin and decreased in the adrenals. Naloxone pretreatment diminished regional blood flow responses to DAGO. Regional hemodynamic changes after peptide administration are suggested to be connected with the activation of peripheral opiate receptors. High differentiation of regional vascular responses may be related to heterogeneous distribution of mu- and delta-opiate receptors in the body.