Angiogenic and Neurotrophic Effects of Human Bone Marrow Mesenchymal Stem Cell-Derived Conditioned Medium for Erectile Dysfunction

Department of Biomedical EngineeringA three-dimensional spheroid culture system to harvest conditioned medium (CM) from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) with high efficiency were introduced and investigated the therapeutic effects of hBM-MSC-CM on erectile dysfunction (ED). In order to harvest CM with higher protein concentration than CM harvested by conventional method in 2D culture system, a variable parameter study considering the culture conditions such as spheroid diameter and centrifugation time was performed. As a result, it was confirmed that CM harvested from 3D spheroid culture system had much more proteins than those cultured in 2D environment. In addition, the total protein concentration in CM increased in proportion to the centrifugation time using a centrifugal filter. Additionally, ELISA and secretome assay showed that CM contained growth factors that help in angiogenesis such as angiogenin (ANG) and vascular endothelial growth factor (VEGF), and in nerve regeneration like glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Also, it was identified that angiogenic effects of CM contributing to tube, node and mesh formation of endothelial cells was proportional to the concentration of CM in vitro tube formation assay. Then, histomorphometric studies such as immunohistochemistry and immunofluorescence were performed using the cavernous nerve (CN) injury rat model. In result, histomorphometric analysis showed that neural regeneration and vascular regeneration increased along with CM concentration. To sum up, we established an efficient method to obtain hBM-MSC-CM containing high concentration of growth factors, which is expected to be one of the promising methods of regenerative medicine for treating ED disease.clos

Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats

AbstractAimsAlcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats.Main methodOLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6weeks. At 6weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated.Key findingsPrior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group.SignificanceThese results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels

Potassium ions as a kinetic controller in ionic double layers for hysteresis-free perovskite solar cells

Since ion migration and interaction with external contacts has been regarded as one of the origins for photocurrent density (J)–voltage (V) hysteresis and phase segregation in perovskite solar cells (PSCs) under operational condition, control of ionic movement in organic–inorganic halide perovskites presents a big challenge for achieving hysteresis-free and stable PSCs. As a universal method, potassium doping into bulk perovskite films to minimize or eliminate the hysteresis was proposed. Here, we report direct observation of moderately retarded ion migration in K+-doped (FAPbI3)0.875(CsPbBr3)0.125 perovskite by in situ photoluminescence (PL) imaging. However, more impressive is the effect on the kinetics for generation of the ionic double layer in the vicinity of the contacts as it is reduced by two orders of magnitude on the time scale when devices are doped with K+ as detected by impedance spectroscopy. A significantly reduced hysteresis in the K+-doped perovskite is responsible for more prolonged stability exhibiting ∼96% of initial power conversion efficiency (PCE) after 22 days than relatively short-lived perovskites undoped with K+ ions. This work highlights the clear correlation of ion migration and a fast generation of the double layer close to the contacts with severe hysteresis and long-term instability in PSCs and the importance of K+ ions in reducing the kinetics affecting the ionic attachment to the contact surface

Highly Sensitive Hydrazine Chemical Sensor Based on CNT-PdPt Nanocomposites

Bimetallic PdPt nanoparticles were prepared using the chemical reduction method. The PdPt nanoparticles were successfully deposited on thiolated carbon nanotubes (CNTs) to form a CNT-PdPt nanocomposite as an electron mediator for the fabrication of a hydrazine sensor. The PdPt nanoparticles had an average particle size of 2.3 nm and were well dispersed on the surfaces of the CNTs in the prepared CNT-PdPt nanocomposite, as demonstrated using transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Based on X-ray photoelectron spectroscopy (XPS) results, the estimated proportions of Pd and Pt in the CNT-PdPt nanocomposite were approximately 3.0% and 3.2%, respectively. A fabricated chemical sensor based on CNT-PdPt was found to exhibit better amperometric activity with respect to the hydrazine oxidation reaction than CNT-Pd, CNT-Pt, and commercial Pd/C and Pt/C catalysts. This sensor exhibited a linear range of 0.55–1,200 μM and a detection limit of 0.28 μM (S/N = 3) with a fast response time (within 5 s). Furthermore, the sensor could be used repeatedly for the consecutive detection of hydrazine with good reusability and storage stability. These properties demonstrate that the CNT-PdPt nanocomposite is a promising electron mediator for the fabrication of amperometric hydrazine sensors

Factors associated with acute kidney injury among preterm infants administered vancomycin: a retrospective cohort study

Background Vancomycin (VCM) is a widely used antibiotic for the treatment of gram-positive microorganisms, with some nephrotoxic effects. Recent studies have suggested that piperacillin-tazobactam (TZP) aggravates VCM-induced nephrotoxicity in adults and adolescents. However, there is a lack of research investigating these effects in the newborn population. Therefore, this study investigates whether the concomitant use of TZP with VCM use increases the risk of acute kidney injury (AKI) and to explore the factors associated with AKI in preterm infants treated with VCM. Methods This retrospective study included preterm infants with birth weight < 1,500 g in a single tertiary center who were born between 2018 and 2021 and received VCM for a minimum of 3 days. AKI was defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL and an increase in SCr of at least 1.5 times baseline during and up to 1 week after discontinuation of VCM. The study population was categorized as those with or without concomitant use of TZP. Data on perinatal and postnatal factors associated with AKI were collected and analyzed. Results Of the 70 infants, 17 died before 7 postnatal days or antecedent AKI and were excluded, while among the remaining participants, 25 received VCM with TZP (VCM + TZP) and 28 VCM without TZP (VCM—TZP). Gestational age (GA) at birth (26.4 ± 2.8 weeks vs. 26.5 ± 2.6 weeks, p = 0.859) and birthweight (750.4 ± 232.2 g vs. 838.1 ± 268.7 g, p = 0.212) were comparable between the two groups. There were no significant differences in the incidence of AKI between groups. Multivariate analysis showed that GA (adjusted OR: 0.58, 95% CI: 0.35–0.98, p = 0.042), patent ductus arteriosus (PDA) (adjusted OR: 5.23, 95% CI: 0.67–41.05, p = 0.115), and necrotizing enterocolitis (NEC) (adjusted OR: 37.65, 95% CI: 3.08–459.96, p = 0.005) were associated with AKI in the study population. Conclusions In very low birthweight infants, concomitant use of TZP did not increase the risk of AKI during VCM administration. Instead, a lower GA, and NEC were associated with AKI in this population

A new marine ciliate, Metaurostylopsis antarctica nov. spec. (Ciliophora, Urostylida) from the Antarctic Ocean

In this study, a new marine urostylid ciliate, Metaurostylopsis antarctica nov. spec. collected from the Antarctic Ocean was investigated using morphological, morphometrical, and molecular methods. Metaurostylopsis antarctica nov. spec. is characterized as follows: slender to ellipsoid form in body shape; two types of cortical granules, ellipsoid large one (type I, yellow-green, 1.5 × 1 μm) in rows along dorsal kineties and cirri, circular small one (type II, colourless, 0.3 μm in diameter) scattered throughout whole body; 19–24 adoral membranelles, 4 frontal cirri, 2–5 frontoterminal cirri, 1 buccal and 2 transverse cirri; 3–5 midventral pairs, 10–15 cirri of midventral row; 1 right and 2 left marginal rows; 3 dorsal kineties; about 43 macronuclear nodules. This new species mainly differs from the congeners by the number of marginal rows (1 vs. 3 or more on right side; 2 vs. 3 or more on left side). In addition, proter’s oral primordium  developed on the right side of the oral cavity (vs. in center of oral cavity), and the rightmost anlage splits into two parts, nam ely, the frontoterminal cirri and a transverse cirrus (vs. only frontoterminal cirri). Inter-specific dissimilarities of the SSU rRNA gene between the congeners range from 3.3 to 4.4%

Neurodevelopmental Outcomes and Brain Volumetric Analysis of Low-Grade Intraventricular Hemorrhage

Purpose Extremely preterm infants are prone to brain injury and underdevelopment. Intraventricular hemorrhage (IVH) is the most common cause of brain injury and a significant risk factor for neurodevelopmental delay in preterm infants. Severe IVH is known to have a poor outcome; however, the outcomes of low-grade IVH remain controversial. This study aimed to evaluate neurodevelopmental outcomes and brain segmental volumes of preterm infants with low-grade IVH. Methods This retrospective cohort study included 109 extremely preterm infants who underwent term equivalent age-magnetic resonance imaging and neurodevelopmental evaluation at a corrected age of 18 to 24 months. We compared infants with and without low-grade IVH. Results Among the 109 extremely preterm infants, 25 had low-grade IVH and 84 had no IVH. There were no significant differences in the neurodevelopmental outcomes between the low-grade and no IVH groups. In multivariate analysis, low-grade IVH was associated with a smaller medullary volume (adjusted odds ratio, 0.575; 95% confidence interval, 0.346 to 0.957; P=0.034). Conclusion We found no significant differences in the neurodevelopmental outcomes of extremely preterm infants at a corrected age of 18 to 24 months between those with low-grade IVH and those without IVH. Low-grade IVH was associated with a smaller medullary volume

Vitrification for cryopreservation of 2D and 3D stem cells culture using high concentration of cryoprotective agents

Abstract Background Vitrification is the most promising technology for successful cryopreservation of living organisms without ice crystal formation. However, high concentrations (up to ~ 6–8 M) of cryoprotective agents (CPAs) used in stem cell induce osmotic and metabolic injuries. Moreover, the application of conventional slow-freezing methods to cultures of 3-D organoids of stem cells in various studies, is limited by their size. Results In this study, we evaluated the effect of high concentrations of CPAs including cytotoxicity and characterized human mesenchymal stem cell (MSC) at single cell level. The cell viability, cellular damage, and apoptotic mechanisms as well as the proliferation capacity and multipotency of cells subjected to vitrification were similar to those in the slow-freezing group. Furthermore, we identified the possibility of vitrification of size-controlled 3-D spheroids for cryopreservation of organoid with high survivability. Conclusions Our results demonstrate successful vitrification of both single cell and spheroid using high concentration of CPAs in vitro without cytotoxicity

Stratifying non-small cell lung cancer patients using an inverse of the treatment decision rules: validation using electronic health records with application to an administrative database

To validate a stratification method using an inverse of treatment decision rules that can classify non-small cell lung cancer (NSCLC) patients in real-world treatment records. (1) To validate the index classifier against the TNM 7th edition, we analyzed electronic health records of NSCLC patients diagnosed from 2011 to 2015 in a tertiary referral hospital in Seoul, Korea. Predictive accuracy, stage-specific sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and c-statistic were measured. (2) To apply the index classifier in an administrative database, we analyzed NSCLC patients in Korean National Health Insurance Database, 2002–2013. Differential survival rates among the classes were examined with the log-rank test, and class-specific survival rates were compared with the reference survival rates. (1) In the validation study (N = 1375), the overall accuracy was 93.8% (95% CI: 92.5–95.0%). Stage-specific c-statistic was the highest for stage I (0.97, 95% CI: 0.96–0.98) and the lowest for stage III (0.82, 95% CI: 0.77–0.87). (2) In the application study (N = 71,593), the index classifier showed a tendency for differentiating survival probabilities among classes. Compared to the reference TNM survival rates, the index classification under-estimated the survival probability for stages IA, IIIB, and IV, and over-estimated it for stages IIA and IIB. The inverse of the treatment decision rules has a potential to supplement a routinely collected database with information encoded in the treatment decision rules to classify NSCLC patients. It requires further validation and replication in multiple clinical settings

Neuroprotective Effects of Cuscutae Semen in a Mouse Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain’s immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD