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.Bevacizumab in frontline chemotherapy improved the survival outcome for advanced ovarian clear cell carcinoma:a multicenter retrospective analysis
Shinichi TATE ; Toshiyuki SEKI ; Kyoko NISHIKIMI ; Youichi UNNO ; Mizue ITOI ; Sadatomo IKEDA ; Nobuhisa YOSHIKAWA ; Hidehiko AKASHI ; Eitaro SUZUKI ; Naotake TANAKA ; Takashi HIRAKAWA ; Hiroaki KAJIYAMA ; Hirokuni TAKANO ; Kosuke YOSHIHARA ; Kaori KOGA ; Aikou OKAMOTO ; Makio SHOZU
Journal of Gynecologic Oncology 2025;36(5):e80-
Objective:
Advanced ovarian clear cell carcinoma (OCCC) is associated with poor outcomes owing to chemoresistance. Bevacizumab (Bev) is increasingly being used to treat advanced ovarian cancer; however, its efficacy in OCCC remains unclear. This study evaluated the treatment outcomes of frontline bevacizumab chemotherapy in patients with OCCC.
Methods:
This retrospective multi-institutional study included patients diagnosed with advanced OCCC at eight institutions in Japan between 2008 and 2018. Patients were categorized into pre and post-market groups based on the Bev approval dates. Progressionfree survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate methods. Additionally, patients were classified into Bev-treated (Bev+) and non-Bev-treated (Bev−) groups, and their prognoses were compared.
Results:
A total of 96 patients were in the pre-market group and 82 in the post-market group. The post-market group had a significantly higher proportion of patients with poor performance status and patients who underwent interval debulking surgery (p<0.01 and p<0.01, respectively). Univariate analysis demonstrated a better PFS in the post-market group (p=0.041). In multivariate analysis, better PFS (hazard ratio [HR]=0.52; p=0.002) and OS (HR=0.47; p=0.002) were observed in the post-market group than in the pre-market group.Bev+ patients had significantly better PFS and OS than Bev− patients in univariate (p<0.001 and p<0.001, respectively) and multivariate analyses (PFS: HR=0.36; p<0.001 and OS:HR=0.21; p=0.001, respectively).
Conclusion
Incorporating Bev into frontline chemotherapy may improve outcomes in patients with advanced OCCC.
3.Analysis of Related Factors that Make Daikenchuto Useful for Constipation During Pregnancy
Takeshi NAKAYAMA ; Aki MUKAI ; Kyoko SUZUKI ; Shuhei SO ; Nao MURABAYASHI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Hiroaki ITOH
Kampo Medicine 2022;73(1):1-7
The purpose of this study is to clarify factors related to the effect of daikenchuto on constipation during pregnancy. The subjects were 21 patients who had constipation during pregnancy and received 15 g/day of daikenchuto. Based on the constipation score that was created independently, the score values before administration, 2 weeks and 4 weeks after administration were retrospectively investigated. Furthermore, from the outcome of the oral status at 4 weeks, we divided the patients into 2 groups (12 in the improvement group and 11 in the non-improvement group), and attempted to extract factors that were considered to be related to efficacy. The total constipation score decreased significantly before and after administration of daikenchuto, and the concomitant symptoms of constipation scores were low, especially such as abdominal distension and abdominal pain. A comparison of the backgrounds of the improved group and the non-improved group revealed that the proportion of the patients with a history of surgery (laparotomy or laparoscopic surgery) was significantly higher in the improvement group. In addition, there were no particular problems with the pregnancy and delivery course of the 23 patients. Daikenchuto was considered to be highly effective against constipation during pregnancy, especially in pregnant women with a history of surgery.
4.Evaluation of Publicity Activities to the COVID-19 Website for Community Pharmacists
Kazuaki MORI ; Hiroshi OKADA ; Shota SUZUKI ; Megumi YAMASHITA ; Kyoko MATSUZAWA ; Emiko IGARASHI
Japanese Journal of Drug Informatics 2021;23(3):143-147
Objective: The worldwide spread of the COVID-19 pandemic since 2020 led to a lack of information even at Japanese pharmacies, which are at the forefront of community medicine. Therefore, the Kyoto University Graduate School of Public Health Pharmacy Information Group has developed information materials related to COVID-19 for pharmacies0and released them on the COVID-19 countermeasure website, which was launched in haste. However, these days in the information society, the amount of information distributed is explosively expanding. Therefore, it is not possible to reach the target people just by publishing the countermeasure website. Therefore, we set up a public relations team to carry out publicity activities for pharmacists and analyzed the effectiveness of these activities by focusing on changes in the number of page views (PV) on the countermeasure website.Methods: PV and public relations(Facebook, industry media , e-mail) activities during the first 18 days(EARLY period), which is half of the total PV, and the remaining 164 days(MIDDLE period), covering 182 days from the day before the countermeasure website was opened. The changes in quantity were compared. Furthermore, we also compared the changes in the level of interest in the new coronavirus during the target period using Google Trends.Results: PV was remarkably large in the EARLY period, and the amount of public relations activity was generally concentrated in the EARLY period and PV. The number of searches for related words on Google Trends was almost the same as PV except for some. Conclusion: The study revealed the importance of establishing a pandemic countermeasure website for pharmacists at an appropriate time and conducting intensive public relations activities in the early stages.
5.Assessment of Cognitive Function
The Japanese Journal of Rehabilitation Medicine 2021;58(7):780-786
6.Epidemiology of injury in a male collegiate volleyball team in Japan
Nozomi SUZUKI ; Kyoko SHIRAHATA ; Izuho ISHIMARU ; Yutaro NAKAMURA ; Hiroki UCHINO ; Masahiro OHNUMA ; Masahiro SAKURAI
Japanese Journal of Physical Fitness and Sports Medicine 2021;70(2):165-173
The purpose of this study was to examine epidemiology of injury in a male collegiate volleyball team in Japan during 2019 season. Thirty-six collegiate male volleyball players were followed during 2019 season. Injuries that required more than 24 hours to recover were classified as Time Loss (TL) injury, and those that required less than 24 hours were classified as Non-Time Loss (NTL) injury. Exposure was calculated by total number of players and hours of participation. Then, we computed injury rate per 1000 Player Hour (PH) and 1000 Athlete Exposure (AE) as outcome measures. A chi-square test was utilized to statistically compare. Eighteen injuries occurred and the overall injury rate was 1.28/1000PH and 2.05/1000AE, respectively. Of which, 11 cases were NTL injuries (0.78/1000PH, 1.26/1000AE) and 7 cases were TL injuries (0.50/1000PH, 0.80/1000AE). Within the 7 TL injuries, 5 (0.36/1000PH, 0.57/1000AE) were of minor severity. Most TL injury were classified as chronic in nature (n=5, 0.36/1000PH, 0.57/1000AE). There was no statistically significant difference between injury rate of match (n=2, 1.33/1000PH, 2.88/1000AE) and training (n=16, 1.27/1000PH, 1.98/1000AE). The most frequently injured body part in training was lower back (n=7, 0.56/1000PH, 0.87/1000AE). In match, highest injury rate was observed in ankle (n=2, 1.33/1000PH, 2.88/1000AE). In conclusion, our results showed relatively low injury rate, and majority of reported injuries were categorized as minor severity. Our study also demonstrated injury characteristics of Japanese male collegiate players that lower back injuries were prevalent in training, and acute ankle injury rate was highest in match.
7.A Case of Secondary Amenorrhea with Polycystic Ovary Syndrome Successfully Treated with Shokenchuto
Takeshi NAKAYAMA ; Aki MUKAI ; Kyoko SUZUKI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Hiroaki ITOH
Kampo Medicine 2021;72(2):177-181
Here, we report a case of adolescent woman with secondary amenorrhea complicated with polycystic ovary syndrome, which had a normal menstrual period after prescribed shokenchuto under the therapy based on Kampo diagnosis. The case is 14-year-old woman, who had already hormonal therapy due to the secondary amenorrhea, and was difficult to treat because of edema and weight gain. Secondary amenorrhea, multiple cysts in the ovary, and hypertestosteroneemia were confirmed, and the patient was diagnosed with polycystic ovary syndrome. Abdominal pattern was weak and the abnormalities of the abdominal strength were prominent. Therefore, we administered her shokenchuto. After two weeks, menstruation began, and thereafter the menstruation had progressed without any irregularities. Blood examination also showed normal testosterone level. It was suggested that it would be important to focus on the preparation for digestive function and to treat the secondary amenorrhea of adolescent women.
8.Significance of Combined Use of Kamishoyosan and Tokishakuyakusan for General Infertility Treatment
Takeshi NAKAYAMA ; Fumiko TAWARA ; Nao MURABAYASHI ; Shuhei SO ; Wakasa YAMAGUCHI ; Naomi MIYANO ; Kensuke UETA ; Kyoko SUZUKI ; Yoshimasa HORIKOSHI ; Rui KOIZUMI ; Aki MUKAI ; Naoaki TAMURA ; Hiroaki ITOH ; Naohiro KANAYAMA
Kampo Medicine 2021;72(4):361-367
We aimed to clarify the significance of using Kampo therapy centered on kamishoyosan and tokishakuyakusan together with general infertility treatment. The subjects were 41 women who visited a Kampo outpatient clinic for infertility and received general infertility treatment with Kampo therapy (Kampo group). The control group was 781 women who received only general infertility treatment at the same time (non-Kampo group). In comparing both groups, we conducted a retrospective survey on the pregnancy rate by cycle and the pregnancy rate by prescription. The pregnancy rate in the first cycle was 24.4% in the Kampo group and 8.5% in the non-Kampo group, and the pregnancy rate was higher in the Kampo group (P = 0.003). There was no difference in pregnancy rates after the second cycle. The pregnancy rate by prescription was 26.7% for kamishoyosan, 22.2% for tokishakuyakusan, and 8.5% for the non-Kampo group. In the comparison between the first cycle pregnant group and the non-pregnant group, the qi counter flow score was clearly higher in the first cycle pregnant group (P = 0.012). It is suggested that combined use of Kampo therapy including kamishoyosan and tokishakuyakusan may be effective from an early stage. Meanwhile, if pregnancy does not occur even after the combined use of Kamp therapy, it would be an opportunity to consider stepping up as Western medical therapy.
9.Difficulties in daily life of post thoracic esophagectomy cancer patients after hospital discharge
Shigeaki Watanuki ; Keiko Iino ; Yurie Koyama ; Miho Kurihara ; Chisato Ichikawa ; Kyoko Okada ; Hideo Uesugi ; Chie Asanuma ; Hiroyuki Daiko ; Takeo Fujita ; Kyoko Suzuki ; Chihoko Wada ; Michiko Mori ; Yoko Hisabe ; Kaori Yagasaki ; Hiroko Komatsu
Palliative Care Research 2014;9(2):128-135
Purpose: This study aimed at identifying difficulties among post thoracic esophagectomy cancer patients during outpatient follow-up. Methods: Patients who had radical esophagectomy at a cancer center hospital in Japan were prospectively observed and were interviewed by a certified nurse assigned at esophageal surgical outpatient division. Their responses were documented in medical records and were analyzed by content analysis method. This study was approved by the study hospital's research ethics committee. Results: The data from 66 patients were obtained. Content analysis yielded 221 extracts, 25 categories, and 65 codes of difficulties, including: concerns or signs/symptoms associated with dietary intake, physical activity, and anxiety. Implications: The majority of post-thoracoabdominal esophagectomy patients experienced multiple dysfunctions and symptoms after discharge. The results underscore the significance of nurses' role in assessing and instructing patients to address these issues.
10.Content analysis of nurses' interventions for post thoracic esophagectomy cancer patients at the outpatient clinic
Keiko Iino ; Shigeaki Watanuki ; Yurie Koyama ; Miho Kurihara ; Chisato Ichikawa ; Kyoko Okada ; Hideo Uesugi ; Chie Asanuma ; Hiroyuki Daiko ; Takeo Fujita ; Kyoko Suzuki ; Chihoko Wada ; Michiko Mori ; Yoko Hisabe ; Kaori Yagasaki ; Hiroko Komatsu
Palliative Care Research 2014;9(3):110-117
Background: Patients having thoracic esophagectomy, a standardized treatment for esophageal cancer patients in Japan, are known to have various postsurgical signs and symptoms for a period of time. The current status of nursing interventions at outpatients need to be clarified. Purpose: This study aimed at identifying the nurses' interventions for cancer patients at the outpatient setting who previously had thoracic radical esophagectomy. Methods: Patients who had esophagectomy at a cancer center hospital in Japan were prospectively observed and interviewed by outpatient nurses between January 2009 and December 2010. Their documented responses in medical record were prospectively investigated and were qualitatively analyzed via content analysis method. This study was approved by the study hospital's research ethics committee. Results and discussion: The data analysis of nursing interventions for 66 patients yielded 372 extracts, 12 categories, and 74 codes. Nurses were assessing patients' signs and symptoms affected by postsurgical changes, and were utilizing patients' active self-monitoring skills. The results also showed the significance of facilitating postsurgical recovery in relation to nutritional intake and physical activity in patients' daily life. Implications: Based upon the study results, the development of a systematic program is underway, which facilitates esophageal cancer patients' postsurgical recovery.


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