Deafferentation and weight offloading can increase brain and spinal motor neuron excitability, respectively. End-effector gait robots (EEGRs) can blend these effects with stereotyped movement-induced ...neuroplasticity. The authors aimed to evaluate the usefulness of EEGRs as a postoperative neuro-muscular rehabilitation tool. This prospective randomized controlled trial included patients who had undergone unilateral total knee arthroplasty (TKA). Patients were randomly allocated into two groups: one using a 200-step rehabilitation program in an EEGR or the other using a walker on a floor (WF) three times a day for five weekdays. The two groups were compared by electrophysiological and biomechanical methods. Since there were no more enrollments due to funding issues, interim analysis was performed. Twelve patients were assigned to the EEGR group and eight patients were assigned to the WF group. Although the muscle volume of the quadriceps and hamstring did not differ between the two groups, the normalized peak torque of the operated knee flexors (11.28 ± 16.04 Nm/kg) was improved in the EEGR group compared to that of the operated knee flexors in the WF group (4.25 ± 14.26 Nm/kg) (p = 0.04). The normalized compound motor action potentials of the vastus medialis (VM) and biceps femoris (BF) were improved in the EEGR group (p < 0.05). However, the normalized real-time peak amplitude and total, mean area under the curve of VM were decreased during rehabilitation in the EEGR group (p < 0.05). No significant differences were found between operated and non-operated knees in the EEGR group. Five-day EEGR-assisted rehabilitation induced strengthening in the knee flexors and the muscular reactivation of the BF and VM after TKA, while reducing the real-time use of the VM. This observation may suggest the feasibility of this technique: EEGR modulated the neuronal system of the patients rather than training their muscles. However, because the study was underpowered, all of the findings should be interpreted with the utmost caution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood–brain barrier and tight junction markers in the rat hippocampus. ...Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood–brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood–brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction.
Abstract
In lymphedema, proinflammatory cytokine-mediated progressive cascades always occur, leading to macroscopic fibrosis. However, no methods are practically available for measuring ...lymphedema-induced fibrosis before its deterioration. Technically, CT can visualize fibrosis in superficial and deep locations. For standardized measurement, verification of deep learning (DL)-based recognition was performed. A cross-sectional, observational cohort trial was conducted. After narrowing window width of the absorptive values in CT images, SegNet-based semantic segmentation model of every pixel into 5 classes (air, skin, muscle/water, fat, and fibrosis) was trained (65%), validated (15%), and tested (20%). Then, 4 indices were formulated and compared with the standardized circumference difference ratio (SCDR) and bioelectrical impedance (BEI) results. In total, 2138 CT images of 27 chronic unilateral lymphedema patients were analyzed. Regarding fibrosis segmentation, the mean boundary F1 score and accuracy were 0.868 and 0.776, respectively. Among 19 subindices of the 4 indices, 73.7% were correlated with the BEI (partial correlation coefficient: 0.420–0.875), and 13.2% were correlated with the SCDR (0.406–0.460). The mean subindex of Index 2
$$\left( {\frac{{P_{Fibrosis\, in\, Affected} - P_{Fibrosis\, in\, Unaffected} }}{{P_{Limb\, in\, Unaffected} }}} \right)$$
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presented the highest correlation. DL has potential applications in CT image-based lymphedema-induced fibrosis recognition. The subtraction-type formula might be the most promising estimation method.
The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles ...remain a controversial area of research with respect to their toxicity in biological and ecological systems.
This study tested the oral toxicity of silver nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following Organization for Economic Cooperation and Development (OECD) test guideline 408 and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure, although there were no significant changes in food or water consumption during the study period. Significant dose-dependent changes were found in alkaline phosphatase and cholesterol for the male and female rats, indicating that exposure to more than 125 mg/kg of silver nanoparticles may result in slight liver damage. Histopathologic examination revealed a higher incidence of bile-duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in treated animals. There was also a dose-dependent accumulation of silver in all tissues examined. A gender-related difference in the accumulation of silver was noted in the kidneys, with a twofold increase in female kidneys compared to male kidneys.
The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of 125 mg/kg are suggested from the present study.
Three-dimensional (3D) cell culture technology has been steadily studied since the 1990′s due to its superior biocompatibility compared to the conventional two-dimensional (2D) cell culture ...technology, and has recently developed into an organoid culture technology that further improved biocompatibility. Since the 3D culture of human cell lines in artificial scaffolds was demonstrated in the early 90′s, 3D cell culture technology has been actively developed owing to various needs in the areas of disease research, precision medicine, new drug development, and some of these technologies have been commercialized. In particular, 3D cell culture technology is actively being applied and utilized in drug development and cancer-related precision medicine research. Drug development is a long and expensive process that involves multiple steps—from target identification to lead discovery and optimization, preclinical studies, and clinical trials for approval for clinical use. Cancer ranks first among life-threatening diseases owing to intra-tumoral heterogeneity associated with metastasis, recurrence, and treatment resistance, ultimately contributing to treatment failure and adverse prognoses. Therefore, there is an urgent need for the development of efficient drugs using 3D cell culture techniques that can closely mimic in vivo cellular environments and customized tumor models that faithfully represent the tumor heterogeneity of individual patients. This review discusses 3D cell culture technology focusing on research trends, commercialization status, and expected effects developed until recently. We aim to summarize the great potential of 3D cell culture technology and contribute to expanding the base of this technology.
To overcome the limitation of short-term efficacy of virtual reality (VR), an enhanced reality (ER) analgesia, (combination of the VR, real-time motion capture, mirror therapy MT) involving a high ...degree of patients' presence or embodiment was explored. Patients, who underwent unilateral total knee arthroplasty (TKA), received ER analgesia. The duration was 5 times a week, for 2 weeks for one group and 5 times a week, for 1 week in the other. Visual Analogue Scale (VAS) at rest and during movement, active knee range of motion (ROM) for flexion and extension were measured repeatedly. After screening 157 patients, 60 were included. Pre-interventional evaluation was performed at 6.7 days and ER was initiated at 12.4 days after surgery. Evaluation was performed at 5, 12, 33 days after the initiation of ER. Analgesia in the 2 week therapy group was effective until the third evaluation (p = 0.000), whereas in the other group, it was effective only until the second evaluation (p = 0.010). Improvement in ROM in the 2 week group was also maintained until the third evaluation (p = 0.037, p = 0.009). It could lay the foundations for the development of safe and long-lasting analgesic tools.
Currently, neurointervention, surgery, medication, and central nervous system (CNS) stimulation are the main treatments used in CNS diseases. These approaches are used to overcome the blood brain ...barrier (BBB), but they have limitations that necessitate the development of targeted delivery methods. Thus, recent research has focused on spatiotemporally direct and indirect targeted delivery methods because they decrease the effect on nontarget cells, thus minimizing side effects and increasing the patient's quality of life. Methods that enable therapeutics to be directly passed through the BBB to facilitate delivery to target cells include the use of nanomedicine (nanoparticles and extracellular vesicles), and magnetic field-mediated delivery. Nanoparticles are divided into organic, inorganic types depending on their outer shell composition. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes. Magnetic field-mediated delivery methods include magnetic field-mediated passive/actively-assisted navigation, magnetotactic bacteria, magnetic resonance navigation, and magnetic nanobots-in developmental chronological order of when they were developed. Indirect methods increase the BBB permeability, allowing therapeutics to reach the CNS, and include chemical delivery and mechanical delivery (focused ultrasound and LASER therapy). Chemical methods (chemical permeation enhancers) include mannitol, a prevalent BBB permeabilizer, and other chemicals-bradykinin and 1-O-pentylglycerol-to resolve the limitations of mannitol. Focused ultrasound is in either high intensity or low intensity. LASER therapies includes three types: laser interstitial therapy, photodynamic therapy, and photobiomodulation therapy. The combination of direct and indirect methods is not as common as their individual use but represents an area for further research in the field. This review aims to analyze the advantages and disadvantages of these methods, describe the combined use of direct and indirect deliveries, and provide the future prospects of each targeted delivery method. We conclude that the most promising method is the nose-to-CNS delivery of hybrid nanomedicine, multiple combination of organic, inorganic nanoparticles and exosomes, via magnetic resonance navigation following preconditioning treatment with photobiomodulation therapy or focused ultrasound in low intensity as a strategy for differentiating this review from others on targeted CNS delivery; however, additional studies are needed to demonstrate the application of this approach in more complex
pathways.
Purpurin has various effects, including anti-inflammatory effects, and can efficiently cross the blood–brain barrier. In the present study, we investigated the effects of purpurin on oxidative stress ...in HT22 cells and mild brain damage in the gerbil hippocampal CA1 region induced by transient forebrain ischemia. Oxidative stress induced by H
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was significantly ameliorated by treatment with purpurin, based on changes in cell death, DNA fragmentation, formation of reactive oxygen species, and pro-apoptotic (Bax)/anti-apoptotic (Bcl-2) protein levels. In addition, treatment with purpurin significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK), and p38 signaling in HT22 cells. Transient forebrain ischemia in gerbils led to a significant increase in locomotor activity 1 day after ischemia and significant decrease in number of surviving cells in the CA1 region 4 days after ischemia. Administration of purpurin reduced the travel distance 1 day after ischemia and abrogates the neuronal death in the hippocampal CA1 region 4 days after ischemia based on immunohistochemical and histochemical staining for NeuN and Fluoro-Jade C, respectively. Purpurin treatment significantly decreased the activation of microglia and astrocytes as well as the increases of nuclear factor kappa-light-chain-enhancer of activated B cells p65 in the hippocampal CA1 region 4 days after ischemia and ameliorated the ischemia-induced transient increases of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus 6 h after ischemia. In addition, purpurin significantly alleviated the ischemia-induced phosphorylation of JNK, ERK, and p38 in the hippocampus 1 day after ischemia. Furthermore, purpurin treatment significantly mitigated the increases of Bax in the hippocampus 1 day after ischemia and the lipid peroxidation based on malondialdehyde and hydroperoxides levels 2 days after ischemia. These results suggest that purpurin can be one of the potential candidates to reduce neuronal damage and inflammatory responses after oxidative stress in HT22 cells or ischemic damage in gerbils.
Abstract
Carboxyl terminus of Hsc70-interacting protein (CHIP) is highly conserved and is linked to the connection between molecular chaperones and proteasomes to degrade chaperone-bound proteins. In ...this study, we synthesized the transactivator of transcription (Tat)-CHIP fusion protein for effective delivery into the brain and examined the effects of CHIP against oxidative stress in HT22 cells induced by hydrogen peroxide (H
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) treatment and ischemic damage in gerbils by 5 min of occlusion of both common carotid arteries, to elucidate the possibility of using Tat-CHIP as a therapeutic agent against ischemic damage. Tat-CHIP was effectively delivered to HT22 hippocampal cells in a concentration- and time-dependent manner, and protein degradation was confirmed in HT22 cells. In addition, Tat-CHIP significantly ameliorated the oxidative damage induced by 200 μM H
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and decreased DNA fragmentation and reactive oxygen species formation. In addition, Tat-CHIP showed neuroprotective effects against ischemic damage in a dose-dependent manner and significant ameliorative effects against ischemia-induced glial activation, oxidative stress (hydroperoxide and malondialdehyde), pro-inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) release, and glutathione and its redox enzymes (glutathione peroxidase and glutathione reductase) in the hippocampus. These results suggest that Tat-CHIP could be a therapeutic agent that can protect neurons from ischemic damage.
Cuprizone is commonly used to induce neuronal demyelination in mice. In the present study, we compared the cuprizone-induced demyelination in the corpus callosum and investigated the effects of ...cuprizone on proliferating cells and neuroblasts in the dentate gyrus of young adult and aged mice. 5-week- and 23-month-old mice were fed a normal diet or a 0.2% cuprizone-enriched diet for 5 weeks. Mice fed a cuprizone-supplemented diet showed a significant reduction in myelin basic protein-positive structures in the corpus callosum, with the reduction in myelinated fibers being confirmed by electron microscopic analysis. In addition, we observed a marked increase in Ki67-positive proliferating cells and doublecortin-immunoreactive neuroblasts in young adult mice in response to cuprizone treatment, although not in aged mice, as the basal levels of these cells were significantly lower in these older mice. Furthermore, Ser133-phosphorylated cAMP response element-binding protein (pCREB)-positive nuclei and brain-derived neurotrophic factor (BDNF) protein levels were significantly reduced in young adult mice following cuprizone treatment in young adult, although again not in the aged mice. However, in both young adult and aged mice, there were no significant reductions in hippocampal mature neurons in response to cuprizone treatment. These observations indicate that in the mice of both age groups a cuprizone-supplemented diet contributes to an increase in demyelination in the corpus callosum and neural progenitor cells in the dentate gyrus, although the damage is more pronounced in young adult mice. This demyelination and reduction in neural progenitor cells may be associated with changes in the levels of BDNF and pCREB in the dentate gyrus.
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