Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although ...bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxidative stress, and alterations of transcriptional programs in both the peripheral and central nervous systems. Moreover, we describe the necessity of advancing studies that identify the potential efficacy of approved drugs on the basis of pathological mechanisms, as this is a convincing strategy for rapid translation to patients with cancer and BIPN.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The original activity of epidermal growth factor (EGF) is to promote cell growth or block their apoptosis. However, its activity changes to proapoptotic, completely opposite to the original one, upon ...conjugation to nanoparticles. We have recently identified that this unique activity conversion was mediated by the confinement of EGF receptor (EGFR) within membrane rafts and signal condensation therein. In this study, we investigated the effect of interfacial parameters between the EGF molecule immobilized at the nanoparticle surface and the cell-surface membrane receptors and analyzed how their interactions were transduced to downstream signaling leading to apoptotic responses. We also studied the cell-type selective apoptotic responses and compared them with EGFR expression level to demonstrate the potential of the nanoparticle conjugate as a new type of anti-cancer drug activating EGFR rather than conventional blocking approaches.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We experimentally examine a laser-induced underwater shock wave paying special attention to the pressure impulse, the time integral of the pressure evolution. Plasma formation, shock-wave expansion ...and the pressure in water are observed simultaneously using a combined measurement system that obtains high-resolution nanosecond-order image sequences. These detailed measurements reveal a distribution of the pressure peak which is not spherically symmetric. In contrast, remarkably, the pressure impulse is found to be symmetrically distributed for a wide range of experimental parameters, even when the shock waves are emitted from an elongated region. The structure is determined to be a collection of multiple spherical shock waves originating from point-like plasmas in the elongated region.
Cell‐picking technology is essential for cell culturing. Although the recently developed tools enable single‐cell‐level picking, they rely on special skills or additional devices. In this work, a dry ...powder that encapsulates single to several cells with a >95% aqueous culture medium, thereby acting as a powerful cell‐picking tool, is reported. The proposed “drycells” are formed by spraying a cell suspension onto a powder bed of hydrophobic fumed silica nanoparticles. The particles adsorb to the droplet surface and form a superhydrophobic shell, which prevents the drycells from coalescence. The number of encapsulated cells per drycell can be controlled by adjusting the drycell size and cell‐suspension concentration. Moreover, it is possible to encapsulate a pair of normal or cancerous cells and create several cell colonies within a single drycell. A sieving process can be used to sort the drycells according to size. The size of the droplet can range from one to hundreds of micrometers. The drycells are sufficiently stiff to be collected using tweezers; however, centrifugation separates them into nanoparticles and cell‐suspension layers, with the separated particles being recyclable. Various handling techniques, such as splitting coalescence and inner liquid replacement, can be used. It is believed that the application of the proposed drycells will greatly improve the accessibility and productivity of single‐cell analysis.
A dry powder encapsulating single to several cells is formed by covering cell‐suspension microdroplets with hydrophobic fumed silica nanoparticles. Owing to their suitability for mass production, high handling performance, and facile regulation of single‐cell‐level encapsulation, these proposed drycells can be used as a powerful cell‐picking tool for tissue engineering and regenerative medicine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect observed in most patients treated with neurotoxic anti-cancer drugs. Currently, there are no therapeutic options available ...for the prevention of CIPN. Furthermore, few drugs are recommended for the treatment of existing neuropathies because the mechanisms of CIPN remain unclear. Each chemotherapeutic drug induces neuropathy by distinct mechanisms, and thus we need to understand the characteristics of CIPN specific to individual drugs. Here, we review the known pathogenic mechanisms of oxaliplatin- and paclitaxel-induced CIPN, highlighting recent findings. Cancer chemotherapy is performed in a planned manner; therefore, preventive strategies can be planned for CIPN. Drug repositioning studies, which identify the unexpected actions of already approved drugs, have increased in recent years. We have also focused on drug repositioning studies, especially for prevention, because they should be rapidly translated to patients suffering from CIPN.
β3-Adrenoceptor (AR) agonists are used to treat patients with an overactive bladder (OAB). Clinical proof-of-concept data have been obtained for the β3-AR agonists vibegron, mirabegron, solabegron, ...and ritobegron; however, the selectivities of these agents have not been compared directly under the same experimental conditions. Moreover, the bladders of some patients express lower β3-AR densities than those of healthy individuals, and the β3-AR density might be expected to affect agonist activity. This study assessed the β3-AR selectivities of four β3-AR agonists and examined the effects of β-AR density on their pharmacological profiles. Functional cellular assays were performed using Chinese hamster ovary-K1 cells expressing three human β-AR subtypes transfected with different amounts of plasmid DNA (0.1, 0.05, 0.025 μg/well). The half-maximal effective concentration values, intrinsic activities (IAs), and β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were calculated to assess their pharmacological profiles. The β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were >7937-, 517-, 21.3-, and >124-fold higher than for β1-ARs, and >7937-, 496-, >362- and 28.1-fold higher than for β2-ARs, respectively, under the same experimental conditions. The IAs of mirabegron, solabegron, and ritobegron decreased in line with decreasing receptor density, while the IA of vibegron was maintained at the same level as that of the full agonist isoproterenol at various β3-AR densities. Vibegron has high β3-AR selectivity and exhibits full agonist activity, regardless of the β3-AR density. These results suggest that vibegron is a highly effective and safe drug for treating OAB.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent progress in mechanobiology has highlighted the importance of physical cues, such as mechanics, geometry (size), topography, and porosity, in the determination of cellular activities and fates, ...in addition to biochemical factors derived from their surroundings. In this review, we will first provide an overview of how such fundamental insights are identified by synchronizing the hierarchical nature of biological systems and static materials with tunable physical cues. Thereafter, we will explain the photoresponsive dynamic biomaterials to dissect the spatiotemporal aspects of the dependence of biological functions on physical cues.
Matrix physical properties determine cellular fates and activities. This can be studied by sophisticated static and photoresponsive dynamic biomaterials.
A high-resolution background-oriented schlieren (BOS) technique, which utilizes a high-resolution camera and a microdot background pattern, is proposed and used to measure the pressure field of an ...underwater shock wave in a microtube. The propagation of the shock wave subsequently reaches a concave water–air interface set in the microtube resulting in the ejection of a focused microjet. This high spatial-resolution BOS technique can measure the pressure field of a shock front with a width as narrow as the order of only
10
1
μ
m with a peak pressure as large as almost 3 MPa. This significant breakthrough has enabled the simultaneous measurement of the pressure impulse of the shock front and the velocity of the microjet tip. As a result, we have experimentally observed the linear relation between the velocity of the microjet tip and the pressure impulse of the shock front for the cases without secondary cavitation in the liquid bulk. Such relation was theoretically/numerically predicted by Peters et al. (J Fluid Mech 719:587–605, 2013). This study demonstrated the capability of the proposed high-resolution BOS technique as a microscale contactless pressure measurement tool for underwater shock waves and potentially other micro- and nanofluids.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular ...energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.
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