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End date: 2024 × Start date: 2020 × DDC: 600 × Subject: Male ×

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Now showing 1 - 4 of 4
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    Human 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.
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    Modified 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, Jurgen
    A 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.
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    Repeated 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.
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    Restricted differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice
    (London : Nature Publishing Group, 2021) Wilm, Thomas P.; Tanton, Helen; Mutter, Fiona; Foisor, Veronica; Middlehurst, Ben; Ward, Kelly; Benameur, Tarek; Hastie, Nicholas; Wilm, Bettina
    Previously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal mesothelial cells have a range of differentiative capacities and are the direct progenitors of vascular smooth muscle in the intestine. However, it was not clear whether this was a temporally limited process or continued throughout postnatal life. Here, using a conditional Wt1-based genetic lineage tracing approach, we demonstrate that the postnatal and adult peritoneum covering intestine, mesentery and body wall only maintained itself and failed to contribute to other visceral tissues. Pulse-chase experiments of up to 6 months revealed that Wt1-expressing cells remained confined to the peritoneum and failed to differentiate into cellular components of blood vessels or other tissues underlying the peritoneum. Our data confirmed that the Wt1-lineage system also labelled submesothelial cells. Ablation of Wt1 in adult mice did not result in changes to the intestinal wall architecture. In the heart, we observed that Wt1-expressing cells maintained the epicardium and contributed to coronary vessels in newborn and adult mice. Our results demonstrate that Wt1-expressing cells in the peritoneum have limited differentiation capacities, and that contribution of Wt1-expressing cells to cardiac vasculature is based on organ-specific mechanisms.