Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD. RESULTS: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved. CONCLUSIONS: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

N-methylene phosphonic acid chitosan/graphene sheets decorated with silver nanoparticles as green antimicrobial agents.

A green and scalable approach for the preparation of few-layered graphene utilizing the biowaste of potato peels has been developed. The potato peels have been dried and carbonized to obtain a new graphite structure that has been exfoliated in N-methylene phosphonic acid chitosan (MPC). The exfoliation process assisted the formation of graphene sheets with a high size diameter and quality of 50% based on the weight of graphite structure. The graphene sheets were green decorated with silver nanoparticles using microwave power to obtain new nanocomposites. The mass ratio between the graphite and silver nitrate was optimized and observed to change the morphology and size diameter of silver nanoparticles. The as-prepared MPC structure, graphene, and silver decorated graphene nanocomposites were characterized using 1HNMR, FTIR, XRD, UV/Vis spectrophotometer, SEM, and TEM besides tested as antimicrobial agents. The bacterial performance was also controlled by changing the number of AgNPs distributed on graphene sheets based on the mass ratios of graphite/AgNO3. The inhibition diameter of silver decorated graphene was considerably increased to 24.8, and 20.1 mm as in the case of MPC-GRP-Ag30 composite compared to the pure graphene (11.2, 13.5 mm) for E. coli and S. aureus, consecutively proposing that the blade edge of graphene sheets can destroy the bacteria membrane and release silver cations promptly that are directed for the interaction with the cytoplasmic parts of the bacteria cell. Such findings offer green and biocompatible antibacterial agents based on the graphene derived from the biowaste products.

Ceria-Zirconia Antioxidant Nanoparticles Attenuate Hypoxia-Induced Acute Kidney Injury by Restoring Autophagy Flux and Alleviating Mitochondrial Damage.

Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.

Effects of Exercise on Neuropathy in Streptozotocin-Induced Diabetic Rats.

OBJECTIVE: To evaluate the effects of early regular exercise and to assess the electrophysiological and histopathological findings of the rat tail nerve in relation to the timing of exercise training for swimming exercise in rats with diabetic neuropathy. METHODS: We used 70 Sprague-Dawley male rats, and the experimental group comprised 60 rats, and the control group comprised 10 rats. Diabetes was induced by intraperitoneal injection of streptozotocin. Blood glucose concentrations were measured in tail vein blood samples. The experimental group was divided into 6 subgroups according to insulin treatment and swimming exercise: group 1, diabetic control; group 2, insulin treated; group 3, insulin untreated with early swimming exercise; group 4, insulin treated and early swimming exercise; group 5, insulin treated and late swimming exercise; and group 6, insulin untreated with late swimming exercise. Sensory and motor nerve conduction studies were performed weekly up to the 13th week using rat tail nerves. The effect on structural diabetic neuropathy was assessed by morphometry and ultrastructural examination of the rat tail nerve fiber at the 14th week. RESULTS: An exercise effect was observed in the insulin treated groups, but it was not observed in the insulin untreated groups. The sensory nerve conduction study in the rat tail revealed significantly prolonged latency and decreased amplitude in groups 1 and 6, and a further delay was observed in group 5 when compared to group 4. Decreased thickness of myelin was found in groups 1 and 6 through morphometry. CONCLUSION: Early regular exercise programs in addition to conventional insulin treatment may retard the progression of diabetic peripheral neuropathy.

Changes in Resting Calcaneal Stance Position Angle Following Insole Fitting in Children With Flexible Flatfoot.

OBJECTIVE: To clarify the relationship of the initial radiologic and a biomechanical parameter at first clinical visit, and define the effectiveness of modified insole, following insole fitting in children with flexible flatfoot. METHODS: Children aged less than 13 years with flexible flatfoot were enrolled. The total number of subjects was 66 (33 boys, 33 girls). The subjects were divided into 5 subgroups, based on age: 1-2, 3-4, 5-6, 7-9, and 10-12 years. The mean time period between the initial & final examination for their resting calcaneal stance position angle (RCSPA) was 24 months. Radiography quantified the deformity by measuring angles, including the talometatarsal angle, the metatarsal angle, and the calcaneal pitch angle. RESULTS: From the angles measured on radiographs, only the talometatarsal angle showed a statistically significant correlation to the initial RCSPA (r=-0.578 for right side, r=-0.524 for left side; p<0.01). The mean RCSPA improved in all subgroups of subjects following insole fitting. Moreover, in children younger than 7 years, the improvement in RCSPA from the insole fitting was greater compared to children aged 7 years and older. CONCLUSION: The insole has additionally beneficial effects in all populations younger than 13 years. However, there might exist a hidden effect of normal structural pedal alignment during growth accompanied with bony maturation and developmental process. To date, it is controversial whether the treatment of flexible flatfoot is necessary in the vast majority of cases, or simple observation and advice to parents would suffice.

Effect of a Caregiver's Education Program on Stroke Rehabilitation.

OBJECTIVE: To evaluate effects of caregiver's education program on their satisfaction, as well as patient functional recovery, performed in addition to daily conventional rehabilitation treatment. METHODS: Three hundred eleven subjects diagnosed with first-onset stroke and transferred to the Department of Physical Medicine and Rehabilitation of Inha University Hospital were surveyed. In 2015, caregivers attended an education program for acute and subacute stroke patients. Patients who received an additional rehabilitation therapy were assigned to the experimental group (n=81), whereas the control group (n=100) consisted of transfer cases in 2014 with only conventional treatment. The experimental group was classified by severity using the Korean version of the National Institutes of Health Stroke Scale (K-NIHSS), which was administered to all 181 subjects, in addition to, the Korean version of the Mini Mental Status Examination (K-MMSE), a Modified Barthel Index (K-MBI), and the Berg Balance Scale (K-BBS). Caregiver satisfaction and burden before and after education programs were assessed using the Canadian Occupational Performance Measure (COPM), as well as family burden and caregiver burnout scales. RESULTS: No significant intergroup difference was observed between initial K-NIHSS, K-MMSE, K-BBS, K-MBI scores, and times from admission to transfer. Those with moderate or severe strokes under the experimental condition showed a more significant improvement than the control group as determined by the K-NIHSS and K-BBS, as well as tendential K-MMSE and K-MBI score increases. Satisfaction was significantly greater for family members and formal caregivers of patients with strokes of moderate severity in the experimental group. CONCLUSION: The caregiver's education program for stroke subjects had a positive outcome on patients' functional improvement and caregiver satisfaction. The authors believe that the additional rehabilitation therapy with the education program aids patients to achieve functional improvements for an optimal return to social life.

Chemical Synthesis of Sea-Urchin Shaped 3D-MnO2 Nano Structures and Their Application in Supercapacitors.

Sea-urchin shaped α-MnO2 hierarchical nano structures have been synthesized by facile thermal method without using any hard or soft template under the mild conditions. The structural and morphology of the 3D-MnO2 was characterized by X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). From the XRD analysis indicates that MnO2 present in the α form. Morphology analysis shows that α-MnO2 sea-urchins are made by stacked nanorods, the diameter and length of the stacked nanorods present in the range of 50-120 nm and 200-400 nm respectively. The electrochemical behaviour of α-MnO2 has been investigated by cyclic voltammetry (CV) and charge-discharge (CD). The specific capacitance, energy density and power density are 212.0 F g(-1), 21.2 Wh kg(-1) and 1200 W kg(-1) respectively at the current density of 2 A g(-1). The retention of the specific capacitance after completion of 1000 charge-discharge cycles is around 97%. The results reveal that the prepared Sea-urchin shaped α-MnO2 has high specific capacitance and exhibit excellent cycle life.

Monitoring of Functioning Status in Subjects With Chronic Stroke in South Korea Using WHODAS II.

OBJECTIVE: To follow up the long-term functioning in a community through assessing personal background and status based on the International Classification of Functioning, Disability and Health (ICF) after a stroke, by using a Korean version of World Health Organization Disability Assessment Scale II (K-WHODAS II). METHODS: We surveyed 146 patients diagnosed at the first-onset of acute stroke and discharged after Inha University Hospital, and 101 patients answered the K-WHODAS II survey. We analyzed the relationship of six functioning domains of K-WHODAS II with K-MMSE (Korean version of Mini-Mental State Examination) and K-MBI (Korean version of Modified Barthel Index) at admission and discharge, and personal background. All subjects were divided into five groups, according to the disease durations, to assess the functional changes and the differences of K-MMSE and K-MBI at the admission and discharge. RESULTS: K-MBI and K-MMSE at admission and discharge showed no significant differences in all five groups, respectively (p>0.05), reflecting no baseline disparity for long-term follow-up. All subjects showed positive gains of K-MBI and K-MMSE at discharge (p<0.05). The six functioning domains and total scores of K-WHODAS II had decreasing trends until 3 years after the stroke onset, but rose thereafter. Higher scores of K-MBI and K-MMSE, younger age, women, working status, higher educational level, and living with a partner were correlated with lower scores of K-WHODAS II (p<0.05). CONCLUSION: The long-term functioning after stroke was affected not only by cognitive and motor status in hospital, but also by certain kinds of personal background. K-WHODAS II may be used to monitor functioning status in a community and to assess personal backgrounds in subjects with chronic stroke.