Pulpitis causes significant changes in the peripheral nervous system, which induce hyperalgesia. However, the relationship between neuronal activity and Nav1.7 expression following pulpal noxious ...pain has not yet been investigated in the trigeminal ganglion (TG). The aim of our study was to verify whether experimentally induced pulpitis activates the expression of Nav1.7 peripherally and the neuronal activities of the TGs can be affected by Nav1.7 channel inhibition. Acute pulpitis was induced through allyl isothiocyanate (AITC) application to the rat maxillary molar tooth pulp. Three days after AITC application, abnormal pain behaviors were recorded, and the rats were euthanized to allow for immunohistochemical, optical imaging, and western blot analyses of the Nav1.7 expression in the TG. A significant increase in AITC-induced pain-like behaviors and histological evidence of pulpitis were observed. In addition, histological and western blot data showed that Nav1.7 expressions in the TGs were significantly higher in the AITC group than in the naive and saline group rats. Optical imaging showed that the AITC group showed higher neuronal activity after electrical stimulation of the TGs. Additionally, treatment of ProTxII, selective Nav1.7 blocker, on to the TGs in the AITC group effectively suppressed the hyperpolarized activity after electrical stimulation. These findings indicate that the inhibition of the Nav1.7 channel could modulate nociceptive signal processing in the TG following pulp inflammation.
Simultaneous monitoring of electrophysiology and magnetic resonance imaging (MRI) could guide the innovative diagnosis and treatment of various neurodegenerative diseases that are previously ...impossible. However, this technique is difficult because the existing metal‐based implantable neural interface for electrophysiology is not free from signal distortions from its intrinsic magnetic susceptibility while performing an MRI of the implanted area of the neural interface. Moreover, brain tissue heating from neural implants generated by the radiofrequency field from MRI poses potential hazards for patients. Previous studies with soft polymer‐based electrode arrays provide relatively suitable MRI compatibility but does not guarantee high‐resolution electrophysiological signal acquisition and stimulation performance. Here, MRI compatible, optically transparent flexible implantable device capable of electrophysiological multichannel mapping and electrical stimulation is introduced. Using the device, neuropathic pain (NP) relief with a 30‐channel electrophysiological mapping of the somatosensory area before and after motor cortex stimulation (MCS) in allodynia rats after noxious stimulation is confirmed. Additionally, artifact‐free manganese‐enhanced MRI of dramatic relief of pain‐related region activity by MCS is demonstrated. Furthermore, artifact‐free optogenetics with transgenic mice is also investigated by recording light‐evoked potentials. These results suggest a promising neuro‐prosthetic for analyzing and modulating spatiotemporal neurodynamic without MRI or optical modality resolution constraints.
Integration of electrophysiology with magnetic resonance imaging (MRI) is achieved by MRI compatible, transparent Poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) neural implantable device. The neuropathic pain alleviation is demonstrated by this MRI compatible electrode array, simultaneously recording/stimulating the brain with manganese‐enhanced MRI. This work highlights a future technology that eliminates the potential risks and inconveniences of medical imaging of patients with conventional neural implants.
Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells ...(NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)-scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC-scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC-scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI.
This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model ...of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free drop contusion at the T9 level. The SCI rats were then classified into three groups; MSCs, NMSCs, and phosphate-buffered saline (PBS)-treated groups. The cells or PBS were administrated 1 week after SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scores were measured at 1-week intervals for 9 weeks. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were also recorded 8 weeks after transplantation. While transplantation of MSCs led to a clear tendency of motor recovery, NMSC-treated rats had significantly improved BBB scores and showed significantly shortened initial latency, N1 latency, and P1 latency of the SSEPs compared to PBS controls. In addition, 5-bromo-2-deoxyuridine (BrdU)-prelabeled MSCs costained for BrdU and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) were found rostrally and caudally 5 mm each from the epicenter of the necrotic cavity 4 weeks after transplantation. These results suggest that neurally differentiated cells might be an effective therapeutic source for functional recovery after SCI.
Conventionally, Te has primarily been used to improve the machinability of steel and its alloys. In this work, Te was used to refine the grains of an oxide-dispersion-strengthened (ODS) steel ...produced by additive manufacturing (AM) with fixed processing parameters. Addition of Te to the raw powder produced an ODS steel with a fine-grained microstructure, in contrast to the ODS steel manufactured without Te. Moreover, the addition of Te resulted in superior yield strength and ultimate tensile strength, which was attributed to the combined effects of grain refinement and the finer nanoparticles (NPs) composed of Te-rich composite NPs and Cr-rich NPs. For the first time, the AM technique was used to obtain grain and nanoparticle sizes of ~3.4 µm and 6 nm, respectively, from the Te-added ODS steel
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Electrospinning is a common and versatile process to produce nanofibers and deposit them on a collector as a two-dimensional nanofiber mat or a three-dimensional (3D) macroscopic arrangement. ...However, 3D electroconductive collectors with complex geometries, including protruded, curved, and recessed regions, generally caused hampering of a conformal deposition and incomplete covering of electrospun nanofibers. In this study, we suggested a conformal fabrication of an electrospun nanofiber mat on a 3D ear cartilage-shaped hydrogel collector based on hydrogel-assisted electrospinning. To relieve the influence of the complex geometries, we flattened the protruded parts of the 3D ear cartilage-shaped hydrogel collector by exploiting the flexibility of the hydrogel. We found that the suggested fabrication technique could significantly decrease an unevenly focused electric field, caused by the complex geometries of the 3D collector, by alleviating the standard deviation by more than 70% through numerical simulation. Furthermore, it was experimentally confirmed that an electrospun nanofiber mat conformally covered the flattened hydrogel collector with a uniform thickness, which was not achieved with the original hydrogel collector. Given that this study established the conformal electrospinning technique on 3D electroconductive collectors, it will contribute to various studies related to electrospinning, including tissue engineering, drug/cell delivery, environmental filter, and clothing.
A previous study highlighted that mastoparan V1 (MP-V1), a mastoparan from the venom of the social wasp
, is a potent antimicrobial peptide against
infection, which causes enteric diseases. However, ...there exist some limits for its practical application due to the loss of its activity in an increased bacterial density and the difficulty of its efficient production. In this study, we first modulated successfully the antimicrobial activity of synthetic MP-V1 against an increased
population using protease inhibitors, and developed an
secretion system efficiently producing active MP-V1. The protease inhibitors used, except pepstatin A, significantly increased the antimicrobial activity of the synthetic MP-V1 at minimum inhibitory concentrations (determined against 10⁶ cfu/mL of population) against an increased population (10⁸ cfu/mL) of three different
serotypes, Gallinarum, Typhimurium and Enteritidis. Meanwhile, the
strain harboring
was identified to successfully secrete active MP-V1 into cell-free supernatant, whose antimicrobial activity disappeared in the increased population (10⁸ cfu/mL) of
Typhimurium recovered by adding a protease inhibitor cocktail. Therefore, it has been concluded that our challenge using the
secretion system with the protease inhibitors is an attractive strategy for practical application of peptide toxins, such as MP-V1.
Background. Boston Scientific INGEVITY+ pacing lead (Boston Scientific, Marlborough, MA, USA) has been upgraded to INGEVITY. The performance of the INGEVITY+ pacing lead has not yet been reported. ...This study aimed to evaluate the short- and long-term safety, effectiveness, and handling experience of INGEVITY+ leads. Methods. Consecutive patients were included from 9 institutions in Korea, where 400 leads (200 right ventricular active fixation leads and 200 right atrial active fixation leads) were implanted or attempted in 200 subjects. Results. During the implantation, only one patient required a lead change because of lead screw failure. The handling questionnaires of the lead received very positive feedback with 88% of operators agreeing that it is easy for leads to pass through small vessels or vessels with multiple leads. At the 3-month follow-up, 95.7% of RA leads and 99.5% of RV leads had pacing thresholds less than 1.5 V. A total of 92.4% of atrial leads had amplitudes greater than 1.5 mV, and 96.5% of ventricular leads had sensing amplitudes greater than 5 mV at 3 months. A total of 99.8% had impedances between 300 and 1,300 ohms. The lead-related complication-free rate for all leads during follow-up was 100%, and the overall rates of lead dislodgment, perforation, and pericardial effusion were all 0.0%. Conclusions. The INGEVITY+ pacing lead exhibited exceptional clinical performance, with a high complication-free rate throughout the 3-month follow-up period. In addition, the lead displayed excellent electrical characteristics, and the lead-handling experience was reported to be very good.
This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model ...of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free drop contusion at the T9 level. The SCI rats were then classified into three groups; MSCs, NMSCs, and phosphate-buffered saline (PBS)-treated groups. The cells or PBS were administrated 1 week after SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scores were measured at 1-week intervals for 9 weeks. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were also recorded 8 weeks after transplantation. While transplantation of MSCs led to a clear tendency of motor recovery, NMSC-treated rats had significantly improved BBB scores and showed significantly shortened initial latency, N1 latency, and P1 latency of the SSEPs compared to PBS controls. In addition, 5-bromo-2-deoxyuridine (BrdU)-prelabeled MSCs costained for BrdU and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) were found rostrally and caudally 5 mm each from the epicenter of the necrotic cavity 4 weeks after transplantation. These results suggest that neurally differentiated cells might be an effective therapeutic source for functional recovery after SCI.
Oxidative stress and oxidative photodamage induced by UV radiation can cause serious skin damage that is characterized by wrinkling, roughness, laxity and pigmentation. The effects of a sea buckthorn ...(Hippophae rhamnoides L.) fruit blend (SFB) containing sea buckthorn fruit extract, blueberry extract and collagen on UV-induced skin aging were examined by treating hairless mice for 6 weeks with UV irradiation and SFB administered orally. The effects of SFB were measured in the skin of these mice by phenotypical and histological analysis and western blotting. According to wrinkle formation analysis, the oral intake of SFB induced a decrease in wrinkle formation in the damaged skin of UV-irradiated mice. The thickness of the epidermis and dermis in the vitamin extracts (Vit)- and SFB-treated group was lower than that in the vehicle-treated group, but the group treated with SFB50 was the most effective group. The mice treated with the Vit- or SFB solution maintained a normal moisture content through the inhibition of transdermal water loss (TEWL) and an increase in skin moisture content. Furthermore, the levels of matrix metalloproteinase (MMP) and collagen protein expression were assessed in five groups to examine the mechanisms underlying the effects of SFB oral intake. The application of SFB induced a decrease in MMP-1 and -9 expression to the levels observed in the vehicle-treated group, but MMP-9 expression showed a much larger decrease than MMP-1. Furthermore, the expression of collagen-1 in the skin corresponded to MMP expression except for the SFB30-treated group, whereas the superoxide dismutase (SOD) activity was increased dramatically in the SFB50-treated group. These results suggest that SFB has potential as a protective and therapeutic drug candidate against skin aging that functions by regulating the moisture content, MMP expression levels and SOD activity.
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