Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Background: Patients with malignant brain tumors are often accompanied by progressive loss of consciousness, aphasia, and paralysis, and often miss the time to make decisions on their own. Methods: In an acute neurosurgical unit, a multidisciplinary conference was held to support decision-making, and a brain tumor-specific advance care planning (ACP) leaflet was created and operated. The attainment rate of the five steps of ACP and the number of times the ACP process was repeated during hospitalization were evaluated for 79 inpatients before and after the introduction of the leaflet. Results: Forty-eight patients received decision-making support with the leaflet, while 31 did not. The rate of achievement of the discussion (38.7% vs 89.6%, p<0.001) and writing down (6.5% vs 33.3%, p=0.006) in ACP significantly increased after the introduction of the leaflet. Conclusion: The newly developed brain tumor-specific ACP leaflet was useful in promoting ACP for patients with brain tumors and providing decision support. In addition, a multidisciplinary ACP support framework for brain tumor patients has been established through ACP conferences.

Objective: We investigated the effects of Coix-seed Reactive Derivatives (CRD) on fibroblast proliferation and collagen production. Methods: Various concentrations of CRD (0.00001%, 0.0001%, 0.001%, 0.01%, 0.1%, 1%) were added to human fibroblasts, and changes in cell count and extracellular collagen production were measured. Results: Fibroblasts proliferated by the addition of CRD, peaked at about 1.7 times when the CRD concentration was 0.0001%, and then decreased as the addition concentration increased. On the other hand, the collagen concentration in the extracellular matrix of fibroblasts increased as the CRD addition concentration increased, and the collagen concentration increased sharply at 0.1% of CRD concentration or more. Conclusion: It was suggested that CRD has a function of increasing the proliferation of fibroblasts and collagen production.

We evaluated the long-term safety of eight adult volunteers (male 7, female 1: average age 47.4 years) ingesting powdered foods containing Coix-seed Reactive Derivatives (CRD/2.2g/day or 4.4g/day) for 1 year 8 months to 5 years (average 2 years 9 months). Body weight, vital signs (blood pressure, pulse rate), peripheral blood test, blood biochemical test, etc. were observed. We also investigated the presence or absence of side effects. The results showed no notable changes in vital signs or blood test results. From the above, it was speculated that long-term intake of CRD would not pose a safety problem. We plan to continue the study by increasing the number of observation cases in the future.

To clarify the functions of Coix-seed Reactive Derivatives(CRD), we analyzed 13 kinds of phenolic compounds and coixol(an alkaloid) in CRD powder by using Liquid Chromatography/Mass Spectrometry(LC-MS).The following are the results: p -Coumaric acid 275.0 (μg/g), p -Hydroxybenzaldehyde 50.2 (μg/g), Caffeic acid 36.9 (μg/g), Protocatechuic acid 31.9 (μg/g), Ferulic acid 27.1 (μg/g), Quercetin 16.2 (μg/g), Syringaldehyde 12.1 (μg/g), Chlorogenic acid 11.3 (μg/g), Naringenin 11.1 (μg/g), Vanillin 9.2 (μg/g), trans -Coniferylaldehyde 9.1 (μg/g), Tricin 0.7 (μg/g), Luteolin 0.5 (μg/g) and Coixol(6-Methoxy-2-benzoxazolinone) 5.5 (μg/g). CRD is composed of many substances other than these phenoic compounds. Therefore, further studies are needed to understand the various clinical features associated with CRD intake.

We evaluated the effect of Coix-seed Reactive Derivatives (CRD) on cold sensitivity of female hands and feet. Ninety females were assigned randomly to 3 groups and CRD(2g/day, 4g/day or placebo) was administrated for 8weeks. Significant improvement of cold sensitivity was observed in both the 2g/day and 4g/day groups. It was speculated that a naringenin and a quercetin as active ingredients of adlay hull may play a critical role in ameliorating effect on blood flow.

Background: Adlay (Coix lacryma-jobi L. var. ma-yuen Stapf) has been used both in traditional Chinese medicine and as a nourishing food based on its unique biological effects and highly nutritional values. In the present study, we investigated the anti-tumor effect of a hot-water adlay extract in sarcoma mice model. Materials and Methods: The hot water extract of whole adlay was orally administered to mice for one week, after which Sarcoma-180 cells (1×106) were subcutaneously implanted into the abdomen. Thereafter, the tumor growth was monitored and mouse survival was examined. Results: Tumor weights measured at 18 days were significantly lower in mice treated with extract (100 and 300 mg/kg/day) than those in control group (p<0.01). Moreover, mice treated with extract (100 mg/kg/day) showed apparently longer survival than control group evaluated until 32 days (p<0.05). Conclusion: These findings indicate that hot water adlay extract appears to have some anti-tumor effects in vivo insarcoma cells.

Objective: In this study, we evaluated the safety of intake of Coix-seed Reactive Derivatives (CRD) in healthy adult volunteers.Methods: Eight subjects (4 males and 4 females, ages 26.6 ± 4.7) consumed 2.0g CRD/day for 4weeks. We observed weight, vital signs(blood pressure, pulse, body temperature), complete blood count(red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white blood cell count, and platelet count), hemogram, blood chemistry(Na, K, Cl, AST, ALT, γ-GTP, LDH, ALP, total protein, albumin, A/G, total bilirubin, urea nitrogen, creatinine, cholinesterase, total cholesterol, HDL cholesterol, LDL cholesterol, and neutral fats), coagulation examination (prothrombin time and partial prothrombin time), and urinalysis (sugar, protein, and occult blood in urine).Results: Although several laboratory data (MCHC, MCV and serum creatinine) changed slightly, all of these values were within normal range. Furthermore, no severe adverse effect was observed.　Conclusion: These results suggest that CRD intake up to 2g/day is safe in healthy adults. Further study will be needed to define the safety of long-term administration of CRD.

Kaempferia parviflora rhizome is used folk medicines for treatment of various symptoms in Thailand since anticent times.Several types of methoxyflavones has been identified in this plant and their physiological functions have been reported.We determined that six kinds of methoxyflavones (5,7,3',4'-tetramethoxyflavone, 3,5,7,3',4'-pentamethoxyflavone, 5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, 3,5,7-trimethoxyflavone, 3,5,7,4'-tetramethoxyflavone) were included in the 80% ethanol extract of K. parviflora rhizome.The safety of six methoxyflavones mixture was evaluated with 28-day repeated oral dose toxicity test in mice.These results indicated no significant toxicity on body weight, blood analyses, organ weight, blood biochemical analyses.

Kaempferia parviflora rhizome is used in traditional folk medicines for the treatments of various symptoms in Thailand since ancient times. Several types of methoxyflavones were identified from that plant and the functions of some of those were reported. We determined that five kinds of methoxyflavones (5-hydroxy-3,7,3’,4’-tetramethoxyflavone, 5-hydroxy-7-methoxyflavone, 5-hydroxy-3,7-dimethoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, 5-hydroxy-7,4’-dimethoxyflavone) were included the following treatments of K. parviflora rhizome. The 80 %ethanol extract of that were adsorbed resin, removed 70 % ethanol elution and the rest adsorbed materials were eluted with 99.5 % ethanol. The safety of that five methoxyflavones mixture was evaluated. We performed a 28-day repeated dose of oral toxicity test and a mouse micronucleus test. The former results showed no significant toxicity on body weight, blood analyses, organ weight, blood biochemical analyses. The latter results showed negative, believed that the sample has no mutagenicity for living bodies.