Atomic and electronic structure of nanostructured few-layer graphene with self-aligned boundaries synthesized on SiC/Si(001) wafers

This work was partially supported by the Russian Academy of Sciences, Russian Foundation for Basic Research (grant № 17-02-01139, 17-02-01291), Beijing Institute of Technology Research Fund Program for Young Scholars, and Science Foundation Ireland

Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line

Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world, and is characterized by a high mortality rate. The study of the key aspects of colorectal cancer formation and progression is necessary to develop new approaches to its therapy, as well as to search for new diagnostic, prognostic and predictive biomarkers of CRC. In many types of tumors, one of the key changes in metabolism is the  activation of glycolysis, which is associated with alterations in the expression of the main glycolytic enzymes and regulatory molecules. There is often an increase in hexokinase 2 (HK2) exogenous expression in tumor cells, which makes it a promising target for anticancer therapy. Quantitative expression analysis of 15 genes (GAPDH, ADPGK, ALDOA, ENO3, PFKL, PGK1, PGAM1, PKM2, ENO1, PDK1, PDK3, PFKP, ENO2, GPI, and BPGM), encoding the key glycolysis enzymes, as well as HIF1A gene was carried out in a modified RKO cell line, which constantly expresses the short hairpin RNA (shRNA) for the inhibition of hexokinase 2. A significant decrease in the expression of PFKP, BPGM, and GPI genes both at the mRNA (5­, 86­, and 93­fold, respectively) and protein (2.5­, 3.5­, and 19­fold, respectively) levels was revealed. Probably, the downregulation of GPI and PFKP is associated with a decrease in the amount of their substrates, glucose­6­phosphate and fructose6­phosphate, under the inhibition of hexokinase 2. Nevertheless, the cause of a decreased mRNA level of these three enzymes, while the expression level of other glycolytic participants is constant, requires further investigation

ОДНОМОМЕНТНАЯ СУБТОТАЛЬНАЯ ЭЗОФАГЭКТОМИЯ И ВЕРХНЯЯ ЛОБЭКТОМИЯ СПРАВА С РЕЗЕКЦИЕЙ ГЛАВНОГО И ПРОМЕЖУТОЧНОГО БРОНХОВ ПРИ СИНХРОННОМ РАКЕ ПИЩЕВОДА И ЛЕГКОГО

We report a rare case of successful surgical management (simultaneous esophagectomy and upper lobectomy with resection of the main and intermediate bronchi) of synchronous multiple primary cancer of the thoracic esophagus and central cancer of the right lung.    The role of morphological characteristics in differential diagnosis between synchronous neoplasia and metastasis has been described. This clinical case demonstrates successful one-stage surgical management of this disease provided a correct assessment of the extent of cancer involvement and the patient’s functional status.Приводится редкое клиническое наблюдение успешной симультанной операции – эзофагэктомии и верхней лобэктомии с резекцией главного и промежуточного бронхов при первично-множественной синхронной опухолевой патологии: рак грудного отдела пищевода и центральный рак правого легкого. Подробно представлены диагностический комплекс и особенности морфологической диагностики в плане дифференциального диагноза синхронной неоплазии и метастатического процесса. Данное клиническое наблюдение демонстрирует возможность успешного одномоментного хирургического лечения при тяжелой конкурирующей по прогнозу опухолевой патологии, при условии корректной оценки распространенности заболевания и функционального статуса пациента

Alterations in Energy/Redox Metabolism Induced by Mitochondrial and Environmental Toxins: A Specific Role for Glucose-6-Phosphate-Dehydrogenase and the Pentose Phosphate Pathway in Paraquat Toxicity

Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in energy metabolism, which are specific for distinct mitochondiral/environmental toxins, are not bystanders to energy failure but also contribute significant to cell death progression