Effectiveness of the Novel Herbal Medicine, KIOM-MA, and Its Bioconversion Product, KIOM-MA128, on the Treatment of Atopic Dermatitis

This study was conducted to determine if oral administration of the novel herbal medicine, KIOM-MA, and its Lactobacillus acidophilus-fermented product, KIOM-MA128, has therapeutic properties for the treatment of atopic dermatitis (AD). Using AD-induced BALB/c mice by Ovalbumin and aluminum hydroxide, the effectiveness of KIOM-MA and KIOM-MA128 on AD was evaluated. Oral administration of KIOM-MA and KIOM-MA128 reduced major clinical signs of AD including erythema/darkening, edema/papulation, excoriations, lichenification/prurigo, and dryness. Interestingly, KIOM-MA128 more significantly improved AD-related symptoms including decrease of IgE level in the plasma as well as reduction of scratching behavior, skin severity in the AD BALB/c model. HPLC analysis showed the significant changes in the constituent patterns between KIOM-MA and KIOM-MA128. Our results suggest that both KIOM-MA and KIOM-MA128 have potential for therapeutic reagent for the treatment of AD, and further, the efficacy is significantly enhanced by L. acidophilus fermentation via increases in its indicator molecule

Fargesin Inhibits EGF-Induced Cell Transformation and Colon Cancer Cell Growth by Suppression of CDK2/Cyclin E Signaling Pathway

Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G1/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by fargesin treatment in colon cancer cells. We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. Simultaneously, the suppression of CDK2/cyclin E and induction of p21WAF1/Cip1 were correlated with Rb phosphorylation and c-Myc suppression. Taken together, we conclude that fargesin-mediated c-Myc suppression inhibits EGF-induced cell transformation and colon cancer cell colony growth by the suppression of retinoblastoma (Rb)-E2F and CDK/cyclin signaling pathways, which are mainly regulated by MAPK and PKB signaling pathways

Accuracy of Administrative Claim Data for Gastric Adenoma After Endoscopic Resection

BACKGROUND/AIMS: Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. METHODS: Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. RESULTS: Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. CONCLUSION: Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future

Effects of Early Surgical Exploration in Suspected Barotraumatic Perilymph Fistulas

ObjectivesTreatment of traumatic perilymph fistula (PLF) remains controversial between surgical repair and conservative therapy. The aim of this study is to analyze the outcomes of early surgical exploration in suspected barotraumatic PLF.MethodsNine patients (10 cases) who developed sudden sensorineural hearing loss and dizziness following barotrauma and underwent surgical exploration with the clinical impression of PLF were enrolled. Types of antecedent trauma, operative findings, control of dizziness after surgery, postoperative hearing outcomes, and relations to the time interval between traumatic event and surgery were assessed retrospectively.ResultsAll patients had sudden or progressive hearing loss and dizziness following trauma. Types of barotrauma were classified by the origin of the trauma: 4 external (car accident, slap injury) and 6 internal traumas (lifting, nasal blowing, straining). Surgical exploration was performed whenever PLF was suspected with the time interval of 2 to 47 days after the trauma. The possible evidence of PLF was found during surgery in 9 cases: a fibrous web around the oval window (n=3), fluid collection in the round window (RW; n=6) and bulging of the RW pseudomembrane (n=1). In every patient, vestibular symptoms disappeared immediately after surgery. The hearing was improved with a mean gain of 27.0±14.9 dB. When the surgical exploration was performed as early as less than 10 days after the trauma, serviceable hearing (≤40 dB) was obtained in 4 out of 7 cases (57.1%).ConclusionSudden or progressive sensorineural hearing loss accompanied by dizziness following barotrauma should prompt consideration of PLF. Early surgical exploration is recommended to improve hearing and vestibular symptoms

Airway epithelial cells initiate the allergen response through transglutaminase 2 by inducing IL-33 expression and a subsequent Th2 response

Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens. Methods We induced allergic asthma by ovalbumin sensitization and intranasal challenge in wild-type (WT) BALB/c and TG2-deficient mice. Broncheoalveolar lavage fluid cells and intracellular cytokine production were analyzed by flow cytometry. Interleukin (IL)-33 and TG2 expression in lung epithelial cells was detected by confocal microscopy. Results Airway responsiveness was attenuated in TG2-deficient mice compared to that in the WT control. In addition, recruitment of eosinophils and Th2 and Th17 differentiation decreased in TG2-deficient mice. Treatment with cysteamine, a transglutaminase inhibitor, also reduced airway hypersensitivity, inflammatory cell recruitment, and T helper cell differentiation. TG2-deficient mice showed reduced IL-33 expression following induction of allergic asthma compared to those in the WT control. Conclusions We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system.Peer Reviewe

Expanded natural killer cells potentiate the antimyeloma activity of daratumumab, lenalidomide, and dexamethasone in a myeloma xenograft model.

The development of new treatment agents in recent decades has significantly improved the survival of patients with multiple myeloma (MM). Nonetheless, MM remains an incurable disease; therefore, novel combination therapies are required. Natural killer (NK) cells are one of the safest immunotherapeutic options. In this study, we found that the anti-myeloma activity of expanded NK cells (eNKs) was improved by daratumumab, lenalidomide, and dexamethasone (DRd) in an MM xenograft mouse model. NK cells expanded from peripheral blood mononuclear cells collected from MM patients were highly cytotoxic against DRd pretreated tumor cells in vitro. To mimic the clinical protocol, a human MM xenograft model was developed using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull (NSG) mice. MM bearing mice were randomly divided into six groups: no treatment, eNK, Rd, Rd + eNKs, DRd, and DRd + eNKs. DRd significantly enhanced the cytotoxicity of eNKs by upregulating NK cell activation ligands and effector function. DRd in combination with eNKs significantly reduced the serum M-protein level and prolonged mouse survival. In addition, DRd significantly increased the persistence of eNK and homing to MM sites. These results show that the anti-myeloma activity of ex vivo-expanded and activated NK cells is augmented by the immunomodulatory effect of DRd in MM-bearing mice, suggesting the therapeutic potential of this combination for MM patients

LOWER EXTREMITY KINEMATICS OF SKI MOTION ON HILLS

This research study aimed to collect thre- dimensional joint angles of the lower extremity during a basic ski motion in order to provide more quantitative teaching guide-lines for ski instructors. Eleven infrared cameras were placed to cover the capture volume of three different stopping movements (e.g. “Pflug Fahren”) on hills. Six ski instructors participated in the test. Three trials of each stop were selected for comparison. Based on the results, skiers tended to use the edge of the ski and maintain a wider “V” shape at the shortest stop distance (e.g. 2m) compared to the other stops. Also, each skier had to invert the foot with a less flexed and more abducted knee and hip position as the stopping distance was decreased. This information will be useful for the development of more objective teaching guide-lines for beginner skiers

Endoscopic Submucosal Dissection Followed by Concurrent Chemoradiotherapy in Patients with Early Esophageal Cancer with a High Risk of Lymph Node Metastasis

Endoscopic submucosal dissection is recommended as an alternative therapy for early esophageal cancer. However, achieving curative resection in this procedure remains controversial since precise prediction of lymph node metastasis can be difficult. Here, we present the preliminary results of endoscopic submucosal dissection followed by concurrent chemoradiotherapy for early esophageal cancer with a high risk of lymph node metastasis. From May 2006 to January 2014, six patients underwent concurrent chemoradiotherapy after endoscopic submucosal dissection with a median follow-up period of 63 months. No complications were encountered during concurrent chemoradiotherapy. Although local recurrence did not occur in all patients, two patients were diagnosed with metachronous cancer. Overall, the survival rate was 100%. Thus, endoscopic submucosal dissection followed by concurrent chemoradiotherapy may be a feasible treatment for early esophageal cancer in patients with a high risk of lymph node metastasis. Future prospective large-scale studies are warranted to confirm our results