Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model.

Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

3'-Sialyllactose alleviates bone loss by regulating bone homeostasis.

Osteoporosis is a common skeletal disease that results in an increased risk of fractures. However, there is no definitive cure, warranting the development of potential therapeutic agents. 3'-Sialyllactose (3'-SL) in human milk regulates many biological functions. However, its effect on bone metabolism remains unknown. This study aimed to investigate the molecular mechanisms underlying the effect of 3'-SL on bone homeostasis. Treatment of human bone marrow stromal cells (hBMSCs) with 3'-SL enhanced osteogenic differentiation and inhibited adipogenic differentiation of hBMSCs. RNA sequencing showed that 3'-SL enhanced laminin subunit gamma-2 expression and promoted osteogenic differentiation via the phosphatidylinositol 3­kinase/protein kinase B signaling pathway. Furthermore, 3'-SL inhibited the receptor activator of nuclear factor κB ligand-induced osteoclast differentiation of bone marrow-derived macrophages through the nuclear factor κB and mitogen­activated protein kinase signaling pathway, ameliorated osteoporosis in ovariectomized mice, and positively regulated bone remodeling. Our findings suggest 3'-SL as a potential drug for osteoporosis.

Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury.

Polydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.

Efficacy and safety of temperature-sensitive acellular dermal matrix in prevention of postoperative adhesion after thyroidectomy: A randomized, multicenter, double-blind, non-inferiority study.

INTRODUCTION: MegaShield® is a newly developed temperature-sensitive anti-adhesive containing micronized acellular dermal matrix. The aim of this study was to investigate the efficacy and safety of MegaShield® compared with Guardix-SG® in the prevention of adhesions in patients undergoing bilateral total thyroidectomy. METHOD: We conducted a multicenter trial between October 2018 and March 2020 in patients undergoing total thyroidectomy. The patients were randomly assigned to either the MegaShield® group or the Guardix-SG® group. The primary outcome was the esophageal movement using marshmallow six weeks after the surgery and the secondary outcome was the assessed adhesion score. The safety assessment was also evaluated. RESULTS: The study included 70 patients each in the MegaShield® and control (Guardix-SG®) groups. Baseline clinical characteristics, the mean score of marshmallow esophagography, and the sum of adhesion scores were not statistically different between the two groups. Inferiority test demonstrated that the efficacy of MegaShield® is not inferior to that of Guardix-SG®. There were no device-related complications in both groups. CONCLUSION: The efficacy and safety of MegaShield® were not inferior than those of Guardix-SG®. MegaShield® demonstrated the potential of ADM as a potential future anti-adhesive agent. TRIAL REGISTRATION: The name of trial registry CRIS (Clinical Research Information Service) https://cris.nih.go.kr/cris/index.jsp. (The full trial protocol can be accessed) Registration number: KCT0003204.

Low-frequency repetitive magnetic stimulation suppresses neuroblastoma progression by downregulating the Wnt/ß-catenin signaling pathway.

Repetitive magnetic stimulation (rMS) has been suggested as a non-invasive treatment for various neurological or psychiatric diseases. Contrary to the application previously used, the purpose of the present study was to elucidate whether low-frequency rMS could suppress tumor progression in in vitro and in vivo neuroblastoma models, and to explore the underlying mechanisms. The results demonstrated that low-frequency rMS treatment significantly suppressed cell proliferation and tumor progression in the models. Moreover, low-frequency rMS treatment downregulated the Wnt/ß-catenin signaling pathway and induced apoptosis. The Wnt/ß-catenin signaling pathway activator, Wnt agonist, was found to counteract the effect of low-frequency rMS treatment, while the Wnt/ß-catenin signaling pathway inhibitor, Wnt antagonist, exhibited a tumor suppression effect, similar to the effect of low-frequency rMS treatment. Taken together, our data demonstrated that low-frequency rMS treatment suppressed neuroblastoma progression by downregulating the Wnt/ß-catenin signaling pathway, suggesting that low-frequency rMS treatment may be a potential therapeutic strategy for the tumor suppression.

Therapeutic Singing as a Swallowing Intervention in Head and Neck Cancer Patients With Dysphagia.

BACKGROUND: Head and neck cancer patients often suffer from dysphagia after surgery and radiotherapy. A singing-enhanced swallowing protocol was established to improve their swallowing function. This study aimed to evaluate the beneficial effects of therapeutic singing on dysphagia in head and neck cancer (HNC) patients. METHODS: Patients who participated in this study were allocated to the intervention group (15 patients) and the control group (13 patients). Patients assigned to the intervention group received therapeutic singing 3 times per week for 4 weeks. Each group was divided into 2 subgroups, including the oral cavity cancer group and the pharyngeal cancer group. The patients' vocal functions were evaluated in maximum phonation time, pitch, intensity, jitter, shimmer, harmonics to noise ratio, and laryngeal diadochokinesis (L-DDK). To evaluate swallowing function, videofluoroscopic swallowing study was done, and the results were analyzed by videofluoroscopic dysphagia scale (VDS) and dynamic imaging grade of swallowing toxicity (DIGEST). RESULTS: Among the voice parameters, L-DDK of the intervention group significantly increased compared to that of the control group. Swallowing functions of the intervention group were significantly improved in VDS and DIGEST after the intervention. Detailed items of VDS and DIGEST showed improvements especially in the pharyngeal phase score of VDS, such as laryngeal elevation, pharyngeal transit time, and aspiration. In addition, the pharyngeal cancer group showed significant improvements in VDS and DIGEST scores after the intervention. CONCLUSIONS: Our outcomes highlight the beneficial effects of singing for HNC patients with dysphagia. The notable improvements in the pharyngeal phase suggest that therapeutic singing would be more appropriate for HNC patients who need to improve their intrinsic muscle movements of vocal fold and laryngeal elevation.

3'-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1ß-Induced Oxidative Stress and Inflammation.

Osteoarthritis (OA) is a major degenerative joint disease. Oxidative stress and inflammation play key roles in the pathogenesis of OA. 3'-Sialyllactose (3'-SL) is derived from human milk and is known to regulate a variety of biological functions related to immune homeostasis. This study aimed to investigate the therapeutic mechanisms of 3'-SL in interleukin-1ß (IL-1ß)-treated SW1353 chondrocytic cells. 3'-SL potently suppressed IL-1ß-induced oxidative stress by increasing the levels of enzymatic antioxidants. 3'-SL significantly reversed the IL-1ß mediated expression levels of reactive oxygen species in IL-1ß-stimulated chondrocytic cells. In addition, 3'-SL could reverse the increased levels of inflammatory markers such as nitrite, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1ß, and IL-6 in IL-1ß-stimulated chondrocytic cells. Moreover, 3'-SL significantly inhibited the apoptotic process, as indicated by the downregulation of the pro-apoptotic protein Bax, upregulation of the anti-apoptotic protein Bcl-2 expression, and significant reduction in the number of TUNEL-positive cells in the IL-1ß-treated chondrocytic cells. Furthermore, 3'-SL reversed cartilage destruction by decreasing the release of matrix metalloproteinases (MMP), such as MMP1, MMP3, and MMP13. In contrast, 3'-SL significantly increased the expression levels of matrix synthesis proteins, such as collagen II and aggrecan, in IL-1ß-treated chondrocytic cells. 3'-SL dramatically suppressed the activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, which are related to the pathogenesis of OA. Taken together, our data suggest that 3'-SL alleviates IL-1ß-induced OA pathogenesis via inhibition of activated MAPK and PI3K/AKT/NF-κB signaling cascades with the downregulation of oxidative stress and inflammation. Therefore, 3'-SL has the potential to be used as a natural compound for OA therapy owing to its ability to activate the antioxidant defense system and suppress inflammatory responses.

Association of premature hair graying with family history, smoking, and obesity: a cross-sectional study.

BACKGROUND: Many researchers have been concerned about the association of hair graying with systemic diseases. However, the common factors associated with hair graying and systemic diseases have not been elucidated. OBJECTIVE: This study aimed to identify risk factors for premature hair graying (PHG) in young men. METHODS: We conducted a cross-sectional study using questionnaires in young men. After a pilot study that included 1069 men, we surveyed 6390 men younger than 30 years about their gray hair status and various socioclinical characteristics. RESULTS: The age of participants in the main survey was 20.2 ± 1.3 years (mean ± SD). Of the 6390 participants, 1618 (25.3%) presented with PHG. Family history of PHG (odds ratio [OR], 12.82), obesity (OR, 2.61), and >5 pack-years history of smoking (OR, 1.61) were significantly associated with PHG. In the multivariate analysis, family history of PHG (OR, 2.63) and obesity (OR, 2.22) correlated with the severity of PHG. LIMITATIONS: Owing to the use of questionnaires, the possibility of recall bias exists. Women were not evaluated in this study. CONCLUSION: Smoking, family history of PHG, and obesity are important factors associated with PHG.

Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy.

The aim of this study was to investigate the duration of remission periods in psoriasis after narrowband ultraviolet B (NB-UVB) phototherapy, especially during multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating marked improvement after NB-UVB phototherapy. The remission period was defined as the duration of time from the end of phototherapy until treatment using either phototherapy or systemic treatments was required again. It was found that an age of 60 years or older, history of systemic therapy within 6 months and three or more phototherapy cycles were significantly associated with shorter remission periods. Furthermore, multivariate analysis confirmed that three or more phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73-9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27-3.95; P = 0.005) were independently associated with the shorter remission period. In conclusion, when planning NB-UVB phototherapy for psoriatic patients who have undergone multiple phototherapy cycles, clinicians should consider the possibility of shorter remission periods.