Which cell death modality wins the contest for photodynamic therapy of cancer?

Photodynamic therapy (PDT) was discovered more than 100 years ago. Since then, many protocols and agents for PDT have been proposed for the treatment of several types of cancer. Traditionally, cell death induced by PDT was categorized into three types: apoptosis, cell death associated with autophagy, and necrosis. However, with the discovery of several other regulated cell death modalities in recent years, it has become clear that this is a rather simple understanding of the mechanisms of action of PDT. New observations revealed that cancer cells exposed to PDT can pass through various non-conventional cell death pathways, such as paraptosis, parthanatos, mitotic catastrophe, pyroptosis, necroptosis, and ferroptosis. Nowadays, immunogenic cell death (ICD) has become one of the most promising ways to eradicate tumor cells by activation of the T-cell adaptive immune response and induction of long-term immunological memory. ICD can be triggered by many anti-cancer treatment methods, including PDT. In this review, we critically discuss recent findings on the non-conventional cell death mechanisms triggered by PDT. Next, we emphasize the role and contribution of ICD in these PDT-induced non-conventional cell death modalities. Finally, we discuss the obstacles and propose several areas of research that will help to overcome these challenges and lead to the development of highly effective anti-cancer therapy based on PDT.Subject terms: Cancer immunotherapy, Cell death and immune response     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Development of neuron-capillary interrelationships in the nuclei of the anterior portion of the human hypothalamus during ontogenesis

Three periods in the formation of the spatial arrangement of the neuronal nuclei have been stated: 1) from the prenatal period, infancy including--pronounced decrease in the density of the neuronal cells arrangement; 2) from the childhood up to adolescence--relative stabilization in the hypothalamic cellular composition; 3) mature and old age--secondary decrease in the dencity of the neuronal cells arrangement. Certain peculiarities in the nuclear capillary composition and in their neuronal-capillary relationships have been revealed: during the prenatal ontogenesis, the dencity of the neuronal cells arrangement decreases and their size increases that is followed by decrease in their capillary loops. In postnatal ontogenesis no proportional relationship between the dencity of neuronal cells arrangement and that of capillary network in the nuclei of the anterior hypothalamus was noted.     

Effect of linker length on the photomodification process of tyrosine residues in N-(tyrosyl)-N'-(5-azido-2-nitrobenzoyl)diaminoalkanes]

N-(Tyrosyl)-N'-(5-azido-2-nitrobenzoyl)-1,4-diaminobutane, containing a Tyr residue connected with the photoreactive aryl azide group through the diaminobutylene linker, was synthesized as a model for studying the photomodification of Tyr residues in proteins. This compound and the compound with a shorter, 1,2-diaminoethylene linker, obtained previously, were subjected to computer modeling to find their minimal-energy conformations. The aromatic rings of Tyr and 5-azido-2-nitrobenzoic acid residues in the latter compound were localized in parallel planes at a distance of approximately 0.3 nm between them and were shown to be implicated in stacking interactions. On the contrary, the planes of aromatic rings of the former compound with a longer, diaminobutylene linker were found to be situated perpendicularly to each other, with the distance between the centers of the rings being approximately 0.6 nm. The computer analysis was confirmed by experimental results: when studying the photomodification of the compound with the diaminobutylene linker, neither stable products of the Tyr photomodification nor unstable products capable of transformation into stable products in the dark were found. On the contrary, such products were previously identified in the case of the compound with diaminoethylene linker. The formation of amino, nitro, azoxy, and azo derivatives was common for the photomodification of both compounds.     

Peripartum Cardiomyopathy Presenting With Ventricular Tachycardia: A Rare Presentation

A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia.     

Integrated mathematical models for describing complex biological processes

This review describes integrated mathematical models of processes, such as calcium homeostasis, pathogen–host interaction (with hepatitis C virus as a pathogen), and the response of the human brain to a stimulating event. It is shown that integrated mathematical models provide a deeper insight into the mechanisms and conditions that lead to the development of diseases of different natures (musculoskeletal disorders, viral infections, and various impairments in brain function) and aid identification of the key targets and conditions for a directed effect of new generation drugs, as well as the interpretation of the results of state-of-theart CT imaging.     

Eulophidae (hymenoptera) parasitoids of Phyllonorycter apparella and phyllonorycter populifoliella (Lepidoptera, Gracillariidae), pests of Populus tremula and populus nigra in Ul’yanovsk province, Russia

Parasitoid complexes of two species of the genus Phyllonorycter (Ph. apparella and Ph. populifoliella) reared from 2 plants (Populus tremula and P. nigra) were studied in Ul’yanovsk Province, Russia. Twenty species of parasitoids are new for Ph. apparella and 12 are new for Ph. populifoliella. Minotetrastichus frontalis and Pnigalio agraules are the dominant species for both parasitoid complexes. The highest relative abundance was observed for Ph. apparella on Populus tremula (75%) and for Ph. populifoliella on P. nigra (61%). The parasitoid complexes of Ph. apparella and Ph. populifoliella show high similarity (the Jaccard coefficient is 0.65).     

A recently silenced, duplicate PgiC locus in Clarkia

Previous electrophoretic analysis showed that 17 diploid species of the wildflower Clarkia (Onagraceae) have two cytosolic isozymes of phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid species have a single PGIC. Molecular studies revealed that the two isozymes in the former species are encoded by duplicate genes, PgiC1 and PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1. Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was silenced four times independently in the genus. Here we describe a psi PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The discovery of the psi PgiC2 is significant because it confirms a formal prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039 nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the intervening introns and 3' nontranslated region. The absence of an increase of nucleotide substitutions in its "exons" suggests that the gene was silenced recently. The present study appears to be the first to establish that a specific duplicate gene locus regularly expressed in a group of related plant species has been silenced in one of them. The multiple independent silencings of PgiC2 suggest that it remained functional but inessential in ancestral lineages. We discuss the possibility that PgiC2 may have been preserved in these lineages by selection against mutants causing defective PGIC1- PGIC2 heterodimers.