Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease

BACKGROUND@#Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. @*METHODS@#To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. @*RESULTS@#T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dosedependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. @*CONCLUSIONS@#Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Preoperative Magnetic Resonance Imaging Evaluation in Patients with Adolescent Idiopathic Scoliosis

STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to examine the incidence of neural axis abnormalities and the relevant risk factors in patients with adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: The use of preoperative magnetic resonance imaging (MRI) to assess the whole spine in patients with idiopathic scoliosis is controversial, and indications for such MRI evaluations have not been definitively established. However, we routinely use whole-spine MRI in patients with scoliosis who are scheduled to undergo surgical correction. METHODS: A total of 378 consecutive patients with presumed AIS who were admitted for spinal surgery were examined for neural axis abnormalities using MRI. To differentiate patients with normal and abnormal MRI findings, the following clinical parameters were evaluated: age, sex, menarcheal status, rotation angle (using a scoliometer), coronal balance, shoulder height difference, and low back pain. We radiographically evaluated curve type, thoracic or thoracolumbar curve direction, curve magnitude and flexibility, apical vertebral rotation, curve length, coronal balance, sagittal balance, shoulder height difference, thoracic kyphosis, and the Risser sign. RESULTS: Neural axis abnormalities were detected in 24 patients (6.3%). Abnormal MRI findings were significantly more common in males than in females and were associated with increased thoracic kyphosis. However, there were no significant differences in terms of the other measured parameters. CONCLUSIONS: Among the patients with presumed AIS who received preoperative whole-spine MRI, 6.3% had neural axis abnormalities. Males and patients with increased thoracic kyphosis were at a higher risk.

Association between electronic cigarette smoking and allergic rhinitis – The Korea National Health and Nutrition Examination Survey (2015)

PURPOSE: Allergic rhinitis (AR) is one of the common chronic diseases. Although it is not a life-threatening disease, its persistent symptoms may cause fatigue, mood change, discomfort at work, and academic disability as well as the decrease of quality of life. The prevalence of AR has been increasing steadily due to the Westernized lifestyle and environmental change. In previous studies, it has been found that AR has a clear relationship with smoking. However, there is no relationship study between AR and electronic cigarettes smoking (ECS). METHODS: The study was conducted on >19-year-old adults who participated in the 2015 Korea National Health and Nutrition Examination Survey. Sex, age, residence status, tobacco smoking, alcohol drinking, stress level, economic status, and diagnosis of AR were analyzed by using univariate and multivariate logistic regression analyses. RESULTS: AR tended to be associated with ECS in the Korean adult population in univariate analysis, but ECS was not statistically significant in multivariate analysis. By multivariate analysis, AR was significantly related with younger age, male sex, alcohol consumption, and stress. Moreover, the prevalence of AR was linearly decreased as age increased from 19 to 69 years. CONCLUSION: A diagnosis of AR was not significantly associated with ECS. Instead, AR showed an increased prevalence in adults at younger age, of male sex, and with alcohol consumption and high stress. To derive statistically significant results of relationship between AR and ECS, more well-designed studies focusing on the temporal causal are needed.

Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of three major ginsenosides from mountain ginseng as anticancer substance and explore the underlying mechanism involved in lung cancer.</p><p><b>METHODS</b>The inhibitory proliferation of lung cancer by major five ginsenosides (Rb1, Rb2, Rg1, Rc, and Re) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Calculated 50% inhibition (IC50) values of five ginsenosides were determined and compared each other. Apoptosis by the treatment of single ginsenoside was performed by fluorescence-assisted cytometric spectroscopy. The alterations of apoptosis-related proteins were evaluated by Western blot analysis.</p><p><b>RESULTS</b>The abundance of ginsenosides in butanol extract of mountain ginseng (BX-MG) was revealed in the order of Rb1, Rg1, Re, Rc and Rb2. Among them, Rb1 was the most effective to lung cancer cell, followed by Rb2 and Rg1 on the basis of relative IC50 values of IMR90 versus A549 cell. The alterations of apoptotic proteins were confirmed in lung cancer A549 cells according to the administration of Rb1, Rb2 and Rg1. The expression levels of caspase-3 and caspase-8 were increased upon the treatment of three ginsenosides, however, the levels of caspase-9 and anti-apoptotic protein Bax were not changed.</p><p><b>CONCLUSION</b>Major ginsenosides such as Rb1, Rb2 and Rg1 comprising BX-MG induced apoptosis in lung cancer cells via extrinsic apoptotic pathway rather than intrinsic mitochondrial pathway.</p>

Preventive Effects of Oligomerized Polyphenol on Estradiol-Induced Prostatitis in Rats

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. MATERIALS AND METHODS: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. RESULTS: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. CONCLUSION: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.