Security theory and practice: Stablisation and reconstrution of post-conlict areas in the 21st century

Wprowadzenie: Cieszymy się, że możemy skierować do Państwa rąk kolejny numer periodyku „Bezpieczeństwo.Teoria i Praktyka”, tym razem poświęcony problematyce stabilizacji i odbudowy obszarów pokonfliktowych w XXI w. Podjęty temat jest niezwykle ważny, ponieważ żyjemy w czasach nieuporządkowanego świata, w którym liczba konfliktów zbrojnych o różnej skali i charakterze oraz wynikające z nich konsekwencje wpływają destrukcyjnie na ład międzynarodowy.Umiędzynarodowienie konfliktów wewnętrznych pełni często funkcję instrumentalną w grze, której stawką jest zajęcie przez dane państwo właściwego – z punktu widzenia jego decydentów – miejsca w nowym systemie ról międzynarodowych. Przykładem tego jest wojna domowa w Syrii, którą Jerzy Zdanowski w artykule rozpoczynającym tom traktuje jako „wojnę zastępczą”. Krótko przedstawia także istotę rekonstrukcji obszarów pokonfliktowych, czym jako badacz rozwija myśli pułkownika Piotra Gąstała, wieloletniego żołnierza i dowódcy Jednostki Wojskowej GROM, który podczas swojej służby przebywał w niejednym państwie dotkniętym konfliktem zbrojnym i wojną oraz ich skutkami. W udzielonym wywiadzie odnosi się on do zagadnienia stabilizacji ze swojej perspektywy – praktyka, któremu nie raz, na terenie prowadzenia działań wojskowych, przyszło mierzyć się z tym wszystkim, co kryje się pod tym pojęciem. Należy przy tym uwzględnić, że jako żołnierz jednostki specjalnej wykonywał tam specyficzne działania. O tym, jak podchodzą do nich nie tylko praktycy, ale i badacze, pisze Piotr Orłowski, analizując znaczenie sił specjalnych jako narzędzia stabilizacji na obszarach pokonfliktowych

Odpowiedź na uszkodzenia DNA indukowane stresem oksydacyjnym w komórkach w fazie spoczynku oraz po reinicjacji cyklu komórkowego

In response to DNA damage, cells activate a signaling cascade known as the DNA damage response (DDR). DDR can modulate the cell cycle to give the cell prolonged time for DNA repair or to induce apoptosis. Cells residing in G0 phase, out of cell cycle, are deprived of canonical cell cycle checkpoints. G0 cells can be quiescent or terminally differentiated and they are less prone to DNA-damaging factors than cycling cells. Research on quiescent stem cells and terminally differentiated cells, demonstrated their attenuated DDR. To further explore this subject we investigated the role of cell cycle exit and re-entry in DDR induced by oxidative stress. We chemically induced quiescence, differentiation and cell cycle re-entry and studied cell viability, intracellular reactive oxygen species (ROS) production, DNA damage and repair, apoptosis, autophagy and distribution of cells in cell cycle phases. We showed that G0 cells, both quiescent and differentiating were more resistant to DNA damage and apoptosis evoked by oxidative stress than cycling cells. These cells showed similar DNA repair kinetics and distribution of cells in cell cycle phases to cycling cells. Unlike quiescent cells, which reduced the level of intracellular ROS, differentiating cells increased intracellular ROS level in oxidative stress. To further confirm that attenuated DDR was specific to G0, we made quiescent cells re-enter cell cycle and measured the activation of DDR pathways. DDR of cells that re-initiated cell cycle was similar to normally cycling cells followed oxidative stress, including intracellular ROS production, sensitivity to DNA damage and apoptosis. However, autophagy decreased upon cell cycle re-entry. Our results demonstrate that the manipulation of cell cycle status influences DDR: attenuates it in G0 and restores upon cell cycle re-entry. Our study strengthens the conception of DDR regulation via G0 phase induction and cell cycle re-initiation.This study was supported by the National Science Centre (project PRELUDIUM 4 entitled “The role of the re-initiation of cell cycle in postmitotic cells in response to oxidative stress and its role in AMD pathogenesis” decision No. DEC-2012/07/N/NZ3/01755) and funds for young scientists of the University of Lodz

SENP Proteases as Potential Targets for Cancer Therapy

SUMOylation is a reversible post-translational modification (PTM) involving a covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMO-specific proteases (SENPs) are cysteine proteases with isopeptidase activity facilitating the de-conjugation of SUMO proteins and thus participating in maintaining the balance between the pools of SUMOylated and unSUMOylated proteins and in SUMO recycling. Several studies have reported that SENPs’ aberrant expression is associated with the development and progression of cancer. In this review, we will discuss the role of SENPs in the pathogenesis of cancer, focusing on DNA repair and the cell cycle—cellular pathways malfunctioning in most cancer cells. The plausible role of SENPs in carcinogenesis resulted in the design and development of their inhibitors, including synthetic protein-based, peptide-based, and small molecular weight inhibitors, as well as naturally occurring compounds. Computational methods including virtual screening have been implemented to identify a number of lead structures in recent years. Some inhibitors suppressed the proliferation of prostate cancer cells in vitro and in vivo, confirming that SENPs are suitable targets for anti-cancer treatment. Further advances in the development of SENP-oriented inhibitors are anticipated toward SENP isoform-specific molecules with therapeutic potential

The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment

microRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression by targeting specific mRNAs. microRNAs play a role in several physiological processes in the cell, including migration, proliferation, differentiation and apoptosis. Apart from their role in regular metabolism, abnormal profiles of miRNA expression accompany cancer transformation, including colorectal cancer (CRC) metastasis. microRNAs may play a role in each phase of CRC metastasis including angiogenesis, invasion, intravasation, circulation, extravasation and metastatic colonization. microRNA levels may serve as a predictive CRC marker, which was confirmed by the serum level of miR-29a targeting KLF4, a marker of cell stemness, and the plasma level of miR-221 down-regulating c-Kit, Stat5A and ETS1, which are signal transducers and transcription factor, respectively. In turn, the level of miR-143 in CRC cells decreasing the amount of MACC1 (metastasis-associated in colon cancer-1) and oncogenic KRAS protein, may be utilized as a prognostic marker. Also, single nucleotide polymorphisms of genes encoding miRNAs, including miR-423 and miR-608, which correlate with tumor recurrence, may be useful as diagnostic, prognostic and predictive indicators in CRC metastasis. Pre-miR-34a and pre-miR-199a decreased the level of Axl, a tyrosine-protein kinase receptor, so they can be considered as drugs in antimetastatic therapy. On the other hand, miR-222 targeting ADAM-17, a disintegrin and metalloproteinase, and miR-328 interacting with ABCG2, an ABC transporter, may overcome drug resistance of cancer cells. microRNAs may be considered in wide-range application to facilitate CRC metastasis diagnosis, prognosis, prediction and therapy, however, further clinical, epidemiological and in vitro studies should be conducted to verify their utility

Role of mitochondria in carcinogenesis

Mitochondria play the central role in supplying cells with ATP and are also the major source of reactive oxygen species (ROS) - molecules of both regulatory and destructive nature. Dysfunction of mitochondrial metabolism and/or morphology have been frequently reported in human cancers. This dysfunction can be associated with mitochondrial DNA (mtDNA) damage, which may be changed into mutations in mtDNA coding sequences, or the displacement-loop region, changes in the mtDNA copy number or mtDNA microsatellite instability. All these features are frequently associated with human cancers. Mutations in mtDNA can disturb the functioning of the ROS-producing organelle and further affect the entire cell which may contribute to genomic instability typical for cancer cells. Although the association between some mtDNA mutations and cancer is well established, the causative relationship between these two features is largely unknown. A hint suggesting the driving role of mtDNA mutations in carcinogenesis comes from the observation of tumor promotion after mtDNA depletion. Mitochondria with damaged DNA may alter signaling of the mitochondrial apoptosis pathway promoting cancer cell survival and conferring resistance to anticancer drugs. This resistance may be underlined by mtDNA copy number depletion. Therefore, mitochondria are considered a promising target in anticancer therapy and several mitochondria-targeting drugs are in preclinical and clinical trials. Some other aspects of mitochondrial structure and functions, including morphology and redox potential, can also be associated with cancer transformation and constitute new anticancer targets. Recently, several studies have disclosed new mechanisms underlying the association between mitochondria and cancer, including the protection of mtDNA by telomerase, suggesting new approaches in mitochondria-oriented anti-cancer therapy