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- ItemROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities(Austin, Tex. : Landes Bioscience, 2021) Sagwal, Sanjeev Kumar; Bekeschus, SanderMetabolic energy production naturally generates unwanted products such as reactive oxygen species (ROS), causing oxidative damage. Oxidative damage has been linked to several pathologies, including diabetes, premature aging, neurodegenerative diseases, and cancer. ROS were therefore originally anticipated as an imperative evil, a product of an imperfect system. More recently, however, the role of ROS in signaling and tumor treatment is increasingly acknowledged. This review addresses the main types, sources, and pathways of ROS in melanoma by linking their pleiotropic roles in antioxidant and oxidant regulation, hypoxia, metabolism, and cell death. In addition, the implications of ROS in various physical therapy modalities targeting melanoma, such as radiotherapy, electrochemotherapy, hyperthermia, photodynamic therapy, and medical gas plasma, are also discussed. By including ROS in the main picture of melanoma skin cancer and as an integral part of cancer therapies, a greater understanding of melanoma cell biology is presented, which ultimately may elucidate additional clues on targeting therapy resistance of this most deadly form of skin cancer.
- ItemModified wavelet analysis of ECoG-pattern as promising tool for detection of the blood–brain barrier leakage([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Runnova, Anastasiya; Zhuravlev, Maksim; Ukolov, Rodion; Blokhina, Inna; Dubrovski, Alexander; Lezhnev, Nikita; Sitnikova, Evgeniya; Saranceva, Elena; Kiselev, Anton; Karavaev, Anatoly; Selskii, Anton; Semyachkina-Glushkovskaya, Oxana; Penzel, Thomas; Kurths, JurgenA new approach for detection oscillatory patterns and estimation of their dynamics based by a modified CWT skeleton method is presented. The method opens up additional perspectives for the analysis of subtle changes in the oscillatory activity of complex nonstationary signals. The method was applied to analyze unique experimental signals obtained in usual conditions and after the non-invasive increase in the blood–brain barrier (BBB) permeability in 10 male Wistar rats. The results of the wavelet-analysis of electrocorticography (ECoG) recorded in a normal physiological state and after an increase in the BBB permeability of animals demonstrate significant changes between these states during wakefulness of animals and an essential smoothing of these differences during sleep. Sleep is closely related to the processes of observed changes in the BBB permeability.
- ItemAccurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS)(Wyoming, NSW : Ivyspring, 2021) Strobbia, Pietro; Cupil-Garcia, Vanessa; Crawford, Bridget M.; Fales, Andrew M.; Pfefer, T. Joshua; Liu, Yang; Maiwald, Martin; Sumpf, Bernd; Vo-Dinh, TuanFor the majority of cancer patients, surgery is the primary method of treatment. In these cases, accurately removing the entire tumor without harming surrounding tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. Surface-enhanced Raman scattering (SERS) is emerging as a non-invasive optical alternative for intraoperative tumor identification, with high accuracy and stability. However, Raman detection requires dark rooms to work, which is not consistent with surgical settings. Methods: Herein, we used SERS nanoprobes combined with shifted-excitation Raman difference spectroscopy (SERDS) detection, to accurately detect tumors in xenograft murine model. Results: We demonstrate for the first time the use of SERDS for in vivo tumor detection in a murine model under ambient light conditions. We compare traditional Raman detection with SERDS, showing that our method can improve sensitivity and accuracy for this task. Conclusion: Our results show that this method can be used to improve the accuracy and robustness of in vivo Raman/SERS biomedical application, aiding the process of clinical translation of these technologies. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
- ItemHuman spermbots for patient-representative 3D ovarian cancer cell treatment(Cambridge : RSC Publ., 2020) Xu, Haifeng; Medina-Sánchez, Mariana; Zhang, Wunan; Seaton, Melanie P. H.; Brison, Daniel R.; Edmondson, Richard J.; Taylor, Stephen S.; Nelson, Louisa; Zeng, Kang; Bagley, Steven; Ribeiro, Carla; Restrepo, Lina P.; Lucena, Elkin; Schmidt, Christine K.; Schmidt, Oliver G.Cellular micromotors are attractive for locally delivering high concentrations of drug, and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have shown potential to carry drugs toward gynecological cancers. However, due to major differences in the molecular make-up of bovine and human sperm, a key translational bottleneck for bringing this technology closer to the clinic is to transfer this concept to human material. Here, we successfully load human sperm with Doxorubicin (DOX) and perform treatment of 3D cervical cancer and patient-representative ovarian cancer cell cultures, resulting in strong anticancer cell effects. Additionally, we define the subcellular localization of the chemotherapeutic drug within human sperm, using high-resolution optical microscopy. We also assess drug effects on sperm motility and viability over time, employing sperm samples from healthy donors as well as assisted reproduction patients. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer tissues using magnetic microcaps, and show the sperm microcap loaded with a second anticancer drug, camptothecin (CPT), which unlike DOX is not suitable for directly loading into sperm due to its hydrophobic nature. This co-drug delivery approach opens up novel targeted combinatorial drug therapies for future applications. © 2020 The Royal Society of Chemistry.
- ItemTumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen(London : Nature Publishing Group, 2021) Miebach, Lea; Freund, Eric; Horn, Stefan; Niessner, Felix; Sagwal, Sanjeev Kumar; von Woedtke, Thomas; Emmert, Steffen; Weltmann, Klaus-Dieter; Clemen, Ramona; Schmidt, Anke; Gerling, Torsten; Bekeschus, SanderRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
- ItemAssessment of shifted excitation Raman difference spectroscopy in highly fluorescent biological samples(Cambridge : Soc., 2021) Korinth, Florian; Shaik, Tanveer Ahmed; Popp, Jürgen; Krafft, ChristophShifted excitation Raman difference spectroscopy (SERDS) can be used as an instrumental baseline correction technique to retrieve Raman bands in highly fluorescent samples. Genipin (GE) cross-linked equine pericardium (EP) was used as a model system since a blue pigment is formed upon cross-linking, which results in a strong fluorescent background in the Raman spectra. EP was cross-linked with 0.25% GE solution for 0.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h, and compared with corresponding untreated EP. Raman spectra were collected with three different excitation wavelengths. For the assessment of the SERDS technique, the preprocessed SERDS spectra of two excitation wavelengths (784 nm-786 nm) were compared with the mathematical baseline-corrected Raman spectra at 785 nm excitation using extended multiplicative signal correction, rubberband, the sensitive nonlinear iterative peak and polynomial fitting algorithms. Whereas each baseline correction gave poor quality spectra beyond 6 h GE crosslinking with wave-like artefacts, the SERDS technique resulted in difference spectra, that gave superior reconstructed spectra with clear collagen and resonance enhanced GE pigment bands with lower standard deviation. Key for this progress was an advanced difference optimization approach that is described here. Furthermore, the results of the SERDS technique were independent of the intensity calibration because the system transfer response was compensated by calculating the difference spectrum. We conclude that this SERDS strategy can be transferred to Raman studies on biological and non-biological samples with a strong fluorescence background at 785 nm and also shorter excitation wavelengths which benefit from more intense scattering intensities and higher quantum efficiencies of CCD detectors. This journal is
- ItemClimatic windows for human migration out of Africa in the past 300,000 years([London] : Nature Publishing Group UK, 2021) Beyer, Robert M.; Krapp, Mario; Eriksson, Anders; Manica, AndreaWhilst an African origin of modern humans is well established, the timings and routes of their expansions into Eurasia are the subject of heated debate, due to the scarcity of fossils and the lack of suitably old ancient DNA. Here, we use high-resolution palaeoclimate reconstructions to estimate how difficult it would have been for humans in terms of rainfall availability to leave the African continent in the past 300k years. We then combine these results with an anthropologically and ecologically motivated estimate of the minimum level of rainfall required by hunter-gatherers to survive, allowing us to reconstruct when, and along which geographic paths, expansions out of Africa would have been climatically feasible. The estimated timings and routes of potential contact with Eurasia are compatible with archaeological and genetic evidence of human expansions out of Africa, highlighting the key role of palaeoclimate variability for modern human dispersals.
- ItemRepeated exposure of the oral mucosa over 12 months with cold plasma is not carcinogenic in mice(London : Nature Publishing Group, 2021) Evert, K.; Kocher, T.; Schindler, A.; Müller, M.; Müller, K.; Pink, C.; Holtfreter, B.; Schmidt, A.; Dombrowski, F.; Schubert, A.; von Woedtke, T.; Rupf, S.; Calvisi, D. F.; Bekeschus, S.; Jablonowski, L.Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was compared against UV radiation, carcinogen administration, and untreated conditions over 12 months. Histological analysis of 406 animals revealed that repeated CAP exposure did not foster non-invasive lesions or squamous cell carcinoma (SCCs). Carcinogen administration promoted non-invasive lesions and SCCs. Molecular analysis by a qPCR screening of 144 transcripts revealed distinct inflammatory profiles associated with each treatment regimen. Interestingly, CAP treatment of carcinogen-challenged mucosa did not promote but instead left unchanged or reduced the proportion of non-invasive lesions and SCC formation. In conclusion, repeated CAP exposure of murine oral mucosa was well tolerated, and carcinogenic effects did not occur, motivating CAP applications in patients for dental and implant treatments in the future.
- ItemGlobal data on earthworm abundance, biomass, diversity and corresponding environmental properties(London : Nature Publ. Group, 2021) Phillips, Helen R. P.; Bach, Elizabeth M.; Bartz, Marie L. C.; Bennett, Joanne M.; Beugnon, Rémy; Briones, Maria J. I.; Brown, George G.; Ferlian, Olga; Gongalsky, Konstantin B.; Guerra, Carlos A.; König-Ries, Birgitta; López-Hernández, Danilo; Loss, Scott R.; Marichal, Raphael; Matula, Radim; Minamiya, Yukio; Moos, Jan Hendrik; Moreno, Gerardo; Morón-Ríos, Alejandro; Motohiro, Hasegawa; Muys, Bart; Krebs, Julia J.; Neirynck, Johan; Norgrove, Lindsey; Novo, Marta; Nuutinen, Visa; Nuzzo, Victoria; Mujeeb Rahman, P.; Pansu, Johan; Paudel, Shishir; Pérès, Guénola; Pérez-Camacho, Lorenzo; Orgiazzi, Alberto; Ponge, Jean-François; Prietzel, Jörg; Rapoport, Irina B.; Rashid, Muhammad Imtiaz; Rebollo, Salvador; Rodríguez, Miguel Á.; Roth, Alexander M.; Rousseau, Guillaume X.; Rozen, Anna; Sayad, Ehsan; Ramirez, Kelly S.; van Schaik, Loes; Scharenbroch, Bryant; Schirrmann, Michael; Schmidt, Olaf; Schröder, Boris; Seeber, Julia; Shashkov, Maxim P.; Singh, Jaswinder; Smith, Sandy M.; Steinwandter, Michael; Russell, David J.; Szlavecz, Katalin; Talavera, José Antonio; Trigo, Dolores; Tsukamoto, Jiro; Uribe-López, Sheila; de Valença, Anne W.; Virto, Iñigo; Wackett, Adrian A.; Warren, Matthew W.; Webster, Emily R.; Schwarz, Benjamin; Wehr, Nathaniel H.; Whalen, Joann K.; Wironen, Michael B.; Wolters, Volkmar; Wu, Pengfei; Zenkova, Irina V.; Zhang, Weixin; Cameron, Erin K.; Eisenhauer, Nico; Wall, Diana H.; Brose, Ulrich; Decaëns, Thibaud; Lavelle, Patrick; Loreau, Michel; Mathieu, Jérôme; Mulder, Christian; van der Putten, Wim H.; Rillig, Matthias C.; Thakur, Madhav P.; de Vries, Franciska T.; Wardle, David A.; Ammer, Christian; Ammer, Sabine; Arai, Miwa; Ayuke, Fredrick O.; Baker, Geoff H.; Baretta, Dilmar; Barkusky, Dietmar; Beauséjour, Robin; Bedano, Jose C.; Birkhofer, Klaus; Blanchart, Eric; Blossey, Bernd; Bolger, Thomas; Bradley, Robert L.; Brossard, Michel; Burtis, James C.; Capowiez, Yvan; Cavagnaro, Timothy R.; Choi, Amy; Clause, Julia; Cluzeau, Daniel; Coors, Anja; Crotty, Felicity V.; Crumsey, Jasmine M.; Dávalos, Andrea; Cosín, Darío J. Díaz; Dobson, Annise M.; Domínguez, Anahí; Duhour, Andrés Esteban; van Eekeren, Nick; Emmerling, Christoph; Falco, Liliana B.; Fernández, Rosa; Fonte, Steven J.; Fragoso, Carlos; Franco, André L. C.; Fusilero, Abegail; Geraskina, Anna P.; Gholami, Shaieste; González, Grizelle; Gundale, Michael J.; López, Mónica Gutiérrez; Hackenberger, Branimir K.; Hackenberger, Davorka K.; Hernández, Luis M.; Hirth, Jeff R.; Hishi, Takuo; Holdsworth, Andrew R.; Holmstrup, Martin; Hopfensperger, Kristine N.; Lwanga, Esperanza Huerta; Huhta, Veikko; Hurisso, Tunsisa T.; Iannone, Basil V.; Iordache, Madalina; Irmler, Ulrich; Ivask, Mari; Jesús, Juan B.; Johnson-Maynard, Jodi L.; Joschko, Monika; Kaneko, Nobuhiro; Kanianska, Radoslava; Keith, Aidan M.; Kernecker, Maria L.; Koné, Armand W.; Kooch, Yahya; Kukkonen, Sanna T.; Lalthanzara, H.; Lammel, Daniel R.; Lebedev, Iurii M.; Le Cadre, Edith; Lincoln, Noa K.Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.
- ItemCombining Nanotechnology and Gas Plasma as an Emerging Platform for Cancer Therapy: Mechanism and Therapeutic Implication(Austin, Tex. : Landes Bioscience, 2021) Rasouli, Milad; Fallah, Nadia; Bekeschus, SanderNanomedicine and plasma medicine are innovative and multidisciplinary research fields aiming to employ nanotechnology and gas plasma to improve health-related treatments. Especially cancer treatment has been in the focus of both approaches because clinical response rates with traditional methods that remain improvable for many types of tumor entities. Here, we discuss the recent progress of nanotechnology and gas plasma independently as well as in the concomitant modality of nanoplasma as multimodal platforms with unique capabilities for addressing various therapeutic issues in oncological research. The main features, delivery vehicles, and nexus between reactivity and therapeutic outcomes of nanoparticles and the processes, efficacy, and mechanisms of gas plasma are examined. Especially that the unique feature of gas plasma technology, the local and temporally controlled deposition of a plethora of reactive oxygen, and nitrogen species released simultaneously might be a suitable additive treatment to the use of systemic nanotechnology therapy approaches. Finally, we focus on the convergence of plasma and nanotechnology to provide a suitable strategy that may lead to the required therapeutic outcomes.