1.High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction
Shun-ichiro ASAHARA ; Hiroyuki INOUE ; Yuka IHARA ; Kyoko TERUYAMA ; Asuka IMAI ; Chisako HARA ; Mizuki HARA ; Masako SEIKE ; Aisha YOKOI ; Nozomi KIDO ; Hirotaka SUZUKI ; Ayumi KANNO ; Yuka INABA ; Hitoshi WATANABE ; Go SHIOI ; Maki KIMURA-KOYANAGI ; Michihiro MATSUMOTO ; Hiroshi INOUE ; Keiichi I. NAKAYAMA ; Wataru OGAWA ; Masato KASUGA ; Yoshiaki KIDO
Diabetes & Metabolism Journal 2026;50(1):77-89
Background:
The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe.
Methods:
We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass.
Results:
In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass.
Conclusion
This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.
2.Analysis of Lateral Straddling Motion of the Bathtub by the Differences in the First Leg of Patients after THA
Hirotaka HENMI ; Yuya TAKAKUBO ; Miyuki MURAKAWA ; Katsuhiko SUZUKI ; Michiaki TAKAGI ; Toshiaki SATO
The Japanese Journal of Rehabilitation Medicine 2023;60(8):714-722
Objective:The movement of an elderly person involving stepping over a bathtub makes them prone to falls and requires caution. Gait analysis suggested that the risk of falling increases with time spent in supporting both legs. A similar relationship was expected for side-straddling motion. This study aims to analyze differences in the side-straddling movements between THA patients who did not fully recover their functional balance, mobility, or walking ability from the viewpoint of the ratio of time spent supporting both legs.Methods:Eleven patients with hip osteoarthritis underwent initial unilateral THA via a posterior approach. Using a portable three-dimensional motion analyzer, we calculated the percentages of time spent supporting both legs while entering the bathtub, and exiting the bathtub with a handrail and examined the factors associated with percent of the time spent supporting both legs.Results:The percentage of time spent supporting both legs when exiting the bathtub was significantly lesser when exiting using the nonoperative than the operated side. A negative correlation was found between the percentages of time spent supporting both legs. while exiting the bathtub, and the percentage of handrail load values.Conclusion:The risk of falling may be reduced by using the nonoperative leg as the leading leg when exiting a bathtub. Use of handrails contributes to a reduction in fall risk.
3.A Preliminary Study for the Effect of Coix-seed Reactive Derivatives (CRD) on Human Skin Fibroblast Proliferation and Collagen Production
Nobutaka SUZUKI ; Hirotaka OKUWA-HAYASHI ; Hoko KYO
Japanese Journal of Complementary and Alternative Medicine 2022;19(1):61-64
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.
4.An Observational Study on the Safety of Long-term Intake of Coix-seed Reactive Derivatives (CRD) in Adults
Nobutaka SUZUKI ; Hirotaka OKUWA-HAYASHI ; Hoko KYO
Japanese Journal of Complementary and Alternative Medicine 2022;19(1):9-13
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.
5.Analysis of Phenolic Compounds in Coix-seed Reactive Derivatives(CRD) by Using Liquid Chromatography/Mass Spectrometry(LC-MS)
Nobutaka SUZUKI ; Masahiko TAKINO ; Hirotaka OKUWA-HAYASHI
Japanese Journal of Complementary and Alternative Medicine 2020;17(1):11-22
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.
6.Effect of Coix-seed Reactive Derivatives(CRD) on Cold Sensitivity of Female Hands and Feet: A Randomized Controlled Trial
Nobutaka SUZUKI ; Hoko KYO ; Hirotaka OKUWA-HAYASHI ; Kazuo UEBABA ; Shintaro HASHIMOTO
Japanese Journal of Complementary and Alternative Medicine 2020;17(1):33-36
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.
7.Anti-tumor Activity and Survival Impact of Whole Adlay Hot Water Extract in Sarcoma Mouse Model
Hirotaka OKUWA-HAYASHI ; Tomihisa OHTA ; Satoshi OHNO ; Satoru KYO ; Nobutaka SUZUKI
Japanese Journal of Complementary and Alternative Medicine 2020;17(1):37-42
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.
8.Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry
Katsuhiro ARAI ; Reiko KUNISAKI ; Fumihiko KAKUTA ; Shin-ichiro HAGIWARA ; Takatsugu MURAKOSHI ; Tadahiro YANAGI ; Toshiaki SHIMIZU ; Sawako KATO ; Takashi ISHIGE ; Tomoki AOMATSU ; Mikihiro INOUE ; Takeshi SAITO ; Itaru IWAMA ; Hisashi KAWASHIMA ; Hideki KUMAGAI ; Hitoshi TAJIRI ; Naomi IWATA ; Takahiro MOCHIZUKI ; Atsuko NOGUCHI ; Toshihiko KASHIWABARA ; Hirotaka SHIMIZU ; Yasuo SUZUKI ; Yuri HIRANO ; Takeo FUJIWARA
Intestinal Research 2020;18(4):412-420
Background/Aims:
There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children.
Methods:
This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data.
Results:
A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn’s disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturingon-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01).
Conclusions
Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.
9.The Clinical Safety Test of the Intake of Coix-seed Reactive Derivatives (CRD) in Healthy Adult Volunteers
Nobutaka SUZUKI ; Hirotaka OKUWA-HAYASHI ; Hoko KYO ; Kazuo UEBABA
Japanese Journal of Complementary and Alternative Medicine 2019;16(2):113-117
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.
10.Evaluation of Community Health Medical Education:The Elderly Home Visit Program
Masayo KOJIMA ; Daisaku ASAI ; Daiki ISHIKAWA ; Yuki KIMURA ; Keiko AKASHI ; Hiroyasu AKATSU ; Hirotaka OHARA ; Yoshihiro KAWADE ; Kazunori KIMURA ; Masumi SUZUI ; Tadashi SUZUKI ; Tadahiro HASHITA ; Jyunichiro HAYANO ; Satona MURAKAMI ; Miyuki YAMAMOTO ; Kiyofumi ASAI
Medical Education 2019;48(4):221-235
Introduction: Research was carried out using a mixed method approach in order to evaluate the educational effects of medical students' visit of an elderly home.Methods: Focus group interviews were conducted with 5 medical students and 5 elderlies. All interviewees had experienced the visitation program more than three times. Self-administrative questionnaires were built based on the results of the focus group interview. The questionnaire was then distributed to medical students and elderlies who participated in the program.Results: A total of 84 medical students and 30 elderlies provided informed consent to participate in the study and returned the questionnaire. Nearly 70 percent of the students answered that they had gotten to know about the life of elderly people and sixty percent of the elderlies answered they had experienced some favorable changes after joining the program. While ninety percent of the elderly were satisfied with the program, only half of the students showed positive comments toward it.Discussion: To help all students participate in this program more actively, more organized planning is necessary so that students can have more chances to build communication skills and clarify their own objectives when visiting the elderly.


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