Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated β-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence.Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

Objectives: . This study evaluated the surgical outcomes of patients with Beckwith-Wiedemann syndrome who underwent tongue-reduction surgery and analyzed whether the malocclusion and mandibular prognathism caused by macroglossia could be improved. Methods: . A retrospective medical record review was performed for 11 patients with Beckwith-Wiedemann syndrome whose macroglossia was surgically treated. Demographic data, symptoms and signs, and intraoperative and postoperative surgical outcomes were evaluated. Surgery was performed by a single surgeon using the “keyhole” technique, involving midline elliptical excision and anterior wedge resection. Preoperative and postoperative plain skull lateral X-rays were evaluated to assess prognathism improvement. Results: . The median age at the time of surgery was 35.09 months, and the ratio of males to females was 4:7. The median surgical time was 98±31.45 minutes, and the median duration of the postoperative intensive care unit stay was 3.81±2.4 days. There were no airway complications. Two patients (18.2%) had postoperative wound dehiscence; however, there was no nerve damage, recurrence, or other complications. Among the five patients who underwent postoperative speech evaluation, all showed normal speech development, except one patient who had brain dysfunction and developmental delay. Measurements of the A point-nasion-B point (ANB) angles and sella-nasion-B point (SNB) angles (point A is the most concave point of the anterior maxilla; point B is the most concave point on the mandibular symphysis) on plain X-rays showed a significant decrease in the postoperative SNB angle (P <0.001) and a significant increase in the ANB angle (P <0.011). Conclusion . Tongue-reduction surgery is an effective and safe technique for severe forms of macroglossia associated with Beckwith-Wiedemann syndrome. In addition, it improves mandibular prognathism in young Beckwith-Wiedemann syndrome patients with macroglossia.

Background: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. Methods: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. Results: We compared the planned vs. insertion trajectory of IBI to the hippocampus.With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. Conclusion Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

To accurately interpret knee MRI, it is important not only to know the basic meniscal anatomy but also to distinguish it from that under pathological conditions. Thus, it would be helpful to know the normal meniscus variants (false positives) that could be mistaken for meniscal tears, and tears that could easily be missed and incorrectly diagnosed as normal (false negatives).False positives include synovial recesses, meniscal flounce, the relationship between the popliteus tendon and lateral meniscus, transverse ligament, the anterior root of the meniscus, and meniscofemoral ligament. False negatives include focal radial tears, flap tears, posterior root tears, meniscocapsular separation, and discoid meniscal tears. In this pictorial essay, we reviewed the imaging data obtained in the aforementioned cases.

Background/Aims: There have been few multicenter studies on colonic polyps conducted by primary medical institutions. This study examined the detection rate of colonic polyps in primary health care institutions and the related factors while following the guidelines. Methods: The medical records of 14,029 patients who underwent colonoscopy between January-June 2020 at 40 primary medical institutions in Korea were analyzed. High-risk adenoma was defined as advanced adenoma, carcinoma, or ≥3 adenomas. Results: Most patients (71.2%) aged ≥50 years underwent re-colonoscopy within 5 years (51.3%) for diagnostic purposes (61.3%) in Korean primary medical institutions. The detection rates of colon polyps, adenoma, advanced adenoma, high-risk adenoma, and carcinoma was 59.9%, 38.9%, 5.9%, 11.4%, and 0.3% in all subjects and 59.8%, 37.5%, 8.5%, 12.9%, and 0.3% in average-risk patients, respectively. The incidences of adenoma in average-risk patients increased significantly with age (30s/40s/50s: 20.1%/29.4%/43% for adenoma, 4.4%/6.7%/10.3% for advanced adenoma, and 5.6%/9.5%/14.6% for high-risk adenoma; p<0.05). Before 50 years of age, high-risk adenoma was detected in 9.1% of patients in the first-time screening group, and the significant risk factors were being male and ≥40 years of age. The detection rate of high-risk adenoma in the normal index colonoscopy group within 5 years was 9.0%. The significant risk factors included older age, male sex, positive fecal occult blood test, stool form changes, and nonspecific symptoms (gas and indigestion). Conclusions More colonic adenoma studies targeting real-world clinical practice will be needed to revise the Korean guidelines for colorectal cancer screening and surveillance.

Objectives: . The transcutaneous approach is a good option for office-based vocal fold injection (VFI). However, precise localization requires extensive experience because the needle tip is invisible in small and complex laryngeal spaces. Recently, real-time light-guided VFI (RL-VFI) was proposed as a new technique that allows simultaneous injection under precise needle localization by light guidance. Herein, we aimed to verify the feasibility of RL-VFI in an in vivo canine model and explored its clinical usefulness. Methods: . The device for RL-VFI comprised a light source (light-emitting diode modules [10 W] of red color [650 nm]) and injectors (1.5 inches, 23 gauge). An adult male beagle was used for the experiment. After tracheostomy, a rigid laryngoscope was inserted and suspended to expose the larynx. A flexible naso-laryngoscopy system was used to visualize the vocal folds. Results: . RL-VFI was performed using various transcutaneous approaches, including the cricothyroid, transthyroid, and transhyoid approaches. Light guidance helped identify the path of the needle and prevent inadvertent penetration. The location of the needle tip was accurately indicated by the light. The illuminated needle could be easily placed at the intended points in the vocal fold with real-time visual-motor feedback. Hyaluronic acid could be simultaneously injected lateral to the vocal process under light guidance without manipulation of the device. Conclusion . RL-VFI was found to be safe and feasible in an in vivo canine model, providing precise localization and visualmotor feedback. The clinical application of RL-VFI is expected to improve the safety and precision of VFI.

Objectives: . The transcutaneous approach is a good option for office-based vocal fold injection (VFI). However, precise localization requires extensive experience because the needle tip is invisible in small and complex laryngeal spaces. Recently, real-time light-guided VFI (RL-VFI) was proposed as a new technique that allows simultaneous injection under precise needle localization by light guidance. Herein, we aimed to verify the feasibility of RL-VFI in an in vivo canine model and explored its clinical usefulness. Methods: . The device for RL-VFI comprised a light source (light-emitting diode modules [10 W] of red color [650 nm]) and injectors (1.5 inches, 23 gauge). An adult male beagle was used for the experiment. After tracheostomy, a rigid laryngoscope was inserted and suspended to expose the larynx. A flexible naso-laryngoscopy system was used to visualize the vocal folds. Results: . RL-VFI was performed using various transcutaneous approaches, including the cricothyroid, transthyroid, and transhyoid approaches. Light guidance helped identify the path of the needle and prevent inadvertent penetration. The location of the needle tip was accurately indicated by the light. The illuminated needle could be easily placed at the intended points in the vocal fold with real-time visual-motor feedback. Hyaluronic acid could be simultaneously injected lateral to the vocal process under light guidance without manipulation of the device. Conclusion . RL-VFI was found to be safe and feasible in an in vivo canine model, providing precise localization and visualmotor feedback. The clinical application of RL-VFI is expected to improve the safety and precision of VFI.

PURPOSE: To evaluate the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) classification, a clinical scoring system, for predicting disease control status in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate prognostic factors. MATERIALS AND METHODS: In total, 134 CRSwNP patients who underwent functional endoscopic sinus surgery after maximal medical treatment were enrolled. These patients were categorized into four groups according to JESREC classification: 1) non-eosinophilic CRSwNP (non-ECRSwNP), 2) mild eosinophilic CRSwNP (ECRSwNP), 3) moderate ECRSwNP, and 4) severe ECRSwNP. Disease control status among the patients was evaluated at 1 year after surgery, and the patients were divided into two groups (disease-controlled and disease-uncontrolled groups) for the investigation of prognostic factors. RESULTS: There was no significant difference in disease control status between non-ECRSwNP and ECRSwNP groups (p=0.970). Age, Lund-Mackay CT scores, global osteitis scores, tissue neutrophil count, and tissue eosinophil count were associated with disease control status. In subgroup analysis of the non-ECRSwNP group, only high tissue neutrophil count was related with disease control status, whereas for the ECRSwNP group, young age, high Lund-Mackay CT scores, high global osteitis scores, and high tissue and blood eosinophil counts were associated with disease control status. CONCLUSION: No difference in disease control status was identified between non-ECRSwNP and ECRSwNP cases. Tissue neutrophilia, however, appeared to be associated with disease control status in non-ECRSwNP cases, whereas tissue and blood eosinophilia was associated with ECRSwNP cases.
Asian Continental Ancestry Group ; Classification ; Eosinophilia ; Eosinophils ; Humans ; Nasal Polyps ; Neutrophils ; Osteitis ; Prognosis ; Sinusitis

BACKGROUND/AIMS: To use serological and multiplex polymerase chain reaction (PCR) assays to examine sputum samples from patients experiencing acute exacerbation of chronic obstructive pulmonary disease (AECOPD) for the presence of atypical pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. METHODS: From September 2012 to February 2014, 341 patients with AECOPD attending outpatient clinics were enrolled as part of a randomized, double-blind, multicenter study. A commercial enzyme-linked immunosorbent assay was used to measure serum immunoglobulin M (IgM) and IgG antibody titers on the first day of the study and at 36 days post-enrollment. Multiplex PCR was used to test sputum samples for the presence of atypical pathogens. A urinary antigen test for L. pneumophila was performed on the first day. RESULTS: Nineteen patients (5.6%) showed serological evidence of acute infection with M. pneumoniae. Also, one and seven patients (2%) showed serological evidence of acute infection with C. pneumoniae and L. pneumophila, respectively. All DNA samples were negative for M. pneumoniae, C. pneumoniae, and L. pneumophila according to PCR. Only one urine sample was positive for L. pneumophila antigen, but serologic evidence was lacking. CONCLUSIONS: Serological testing suggested that infection by atypical pathogens during AECOPD was relatively uncommon. In addition, PCR provided no direct evidence of infection by atypical pathogens. Thus, atypical pathogens may not be a major cause of AECOPD in South Korea.
Ambulatory Care Facilities ; Chlamydophila pneumoniae ; DNA ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Korea ; Legionella pneumophila ; Multiplex Polymerase Chain Reaction ; Mycoplasma pneumoniae ; Pneumonia ; Pneumonia, Mycoplasma ; Polymerase Chain Reaction* ; Pulmonary Disease, Chronic Obstructive* ; Serologic Tests ; Sputum

Angiogenesis has an essential role in many pathophysiologies. Here, we show that phospholipase C-β3 (PLC-β3) isoform regulates endothelial cell function and retinal angiogenesis. Silencing of PLC-β3 in human umbilical vein endothelial cells (HUVECs) significantly delayed proliferation, migration and capillary-like tube formation. In addition, mice lacking PLC-β3 showed impaired retinal angiogenesis with delayed endothelial proliferation, reduced endothelial cell activation, abnormal vessel formation and hemorrhage. Finally, tumor formation was significantly reduced in mice lacking PLC-β3 and showed irregular size and shape of blood vessels. These results suggest that regulation of endothelial function by PLC-β3 may contribute to angiogenesis.
Animals ; Blood Vessels ; Endothelial Cells ; Hemorrhage ; Human Umbilical Vein Endothelial Cells ; Mice ; Phospholipases* ; Retinaldehyde*