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Consumption of 2 Green Kiwifruits Daily Improves Constipation and Abdominal Comfort-Results of an International Multicenter Randomized Controlled Trial.
Gearry, R, Fukudo, S, Barbara, G, Kuhn-Sherlock, B, Ansell, J, Blatchford, P, Eady, S, Wallace, A, Butts, C, Cremon, C, et al
The American journal of gastroenterology. 2023;118(6):1058-1068
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Plain language summary
Functional gastrointestinal disorders (FGID) are now termed disorders of gut-brain interaction. Several studies support the consumption of individual foods to improve laxation and gastrointestinal (GI) comfort. The aim of this study was to investigate the effects of the daily consumption of 2 Zespri green kiwifruits compared with those of 7.5 g of psyllium for 4 weeks on parameters of bowel habit and GI comfort. This study was a prospective randomised, single-blinded, crossover, controlled 16-week trial undertaken in 3 countries. The participants were randomised to consume either of the interventions. Results showed that consumption of 2 Zespri green kiwifruits per day is associated with a clinically significant increase in complete spontaneous bowel movements, improvements in abdominal comfort, straining and stool form, and increases in quality of life. Authors concluded that consumption of 2 green kiwifruits can be safely recommended as an effective treatment for constipation in those with functional GI disorders that will also provide improvements in symptoms of GI comfort.
Abstract
INTRODUCTION Consumption of green kiwifruit is known to relieve constipation. Previous studies have also reported improvements in gastrointestinal (GI) comfort. We investigated the effect of consuming green kiwifruit on GI function and comfort. METHODS Participants included healthy controls (n = 63), patients with functional constipation (FC, n = 60), and patients with constipation-predominant irritable bowel syndrome (IBS-C, n = 61) randomly assigned to consume 2 green kiwifruits or psyllium (7.5 g) per day for 4 weeks, followed by a 4-week washout, and then the other treatment for 4 weeks. The primary outcome was the number of complete spontaneous bowel movements (CSBM) per week. Secondary outcomes included GI comfort which was measured using the GI symptom rating scale, a validated instrument. Data (intent-to-treat) were analyzed as difference from baseline using repeated measures analysis of variance suitable for AB/BA crossover design. RESULTS Consumption of green kiwifruit was associated with a clinically relevant increase of ≥ 1.5 CSBM per week (FC; 1.53, P < 0.0001, IBS-C; 1.73, P = 0.0003) and significantly improved measures of GI comfort (GI symptom rating scale total score) in constipated participants (FC, P < 0.0001; IBS-C, P < 0.0001). No significant adverse events were observed. DISCUSSION This study provides original evidence that the consumption of a fresh whole fruit has demonstrated clinically relevant increases in CSBM and improved measures of GI comfort in constipated populations. Green kiwifruits are a suitable dietary treatment for relief of constipation and associated GI comfort.
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HDL Functions-Current Status and Future Perspectives.
Endo, Y, Fujita, M, Ikewaki, K
Biomolecules. 2023;(1)
Abstract
Cardiovascular disease (CVD) is the leading cause of death in Western countries. A low HDL-C is associated with the development of CVD. However, recent epidemiology studies have shown U-shaped curves between HDL-C and CVD mortality, with paradoxically increased CVD mortality in patients with extremely high HDL-C levels. Furthermore, HDL-C raising therapy using nicotinic acids or CETP inhibitors mostly failed to reduce CVD events. Based on this background, HDL functions rather than HDL-C could be a novel biomarker; research on the clinical utility of HDL functionality is ongoing. In this review, we summarize the current status of HDL functions and their future perspectives from the findings of basic research and clinical trials.
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Lipid metabolism in Th17 cell function.
Kanno, T, Nakajima, T, Miyako, K, Endo, Y
Pharmacology & therapeutics. 2023;:108411
Abstract
Among the subset of T helper cells, Th17 cells are known to play a crucial role in the pathogenesis of various autoimmune disorders, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. The master transcription factor retinoid-related orphan receptor gamma t (RORγt), a nuclear hormone receptor, plays a vital role in inducing Th17-cell differentiation. Recent findings suggest that metabolic control is critical for Th17-cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Inhibition of lipid biosynthesis, either through the use of pharmacological inhibitors or by the deficiency of related enzymes in CD4+ T cells, results in significant suppression of Th17-cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic pathways are essential for controlling RORγt activity through the generation of a lipid ligand of RORγt. This review highlights recent findings that underscore the significant role of lipid metabolism in the differentiation and function of Th17 cells, as well as elucidating the distinctive molecular pathways that drive the activation of RORγt by cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach for ameliorating autoimmune disorders via the inhibition of RORγt.
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Effects of Dietary Education Program for the Japan Diet on Cholesterol Efflux Capacity: A Randomized Controlled Trial.
Umezawa, A, Maruyama, C, Endo, Y, Suenaga, Y, Shijo, Y, Kameyama, N, Sato, A, Nishitani, A, Ayaori, M, Waki, M, et al
Journal of atherosclerosis and thrombosis. 2022;(6):881-893
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Abstract
AIM: Improving cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) has been regarded as a novel target for preventing cardiovascular disease. HDL reportedly has antioxidant properties which may contribute to its functions. We investigated changes in CEC with intake of the Japan Diet (JD) recommended by the Japan Atherosclerosis Society and the relationship of these changes to serum antioxidant concentrations. METHODS A randomized parallel controlled clinical trial on JD intake was performed in Japanese patients with dyslipidemia. Ninety-eight participants were randomly divided into the JD (n=49) or the partial JD (PJD) (n=49) group. Nutrition education, based on each diet at baseline and at 3 months, was provided and the participants were followed up for 6 months. RESULTS Mean CEC was 1.05 in total and correlated positively with HDL-cholesterol (p<0.001) at baseline. CEC did not change while oxygen radical absorbance capacity (ORAC) was decreased in both groups (p<0.001). Although serum total carotenoid increased in both groups, serum α-tocopherol decreased in the JD group as compared to the PJD group (p<0.05). CEC correlated positively with HDL ORAC at baseline (p=0.021) and with serum total carotenoid at 3 and 6 months (p=0.005, 0.035). Changes in CEC correlated positively with changes in HDL ORAC at 3 months and serum total tocopherol at 3 and 6 months (p<0.001). CONCLUSION CEC was not changed by JD education in Japanese patients with dyslipidemia who already had normal CEC at baseline. CEC was suggested to be positively associated with serum α- and γ-tocopherol and HDL ORAC.
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Antiwrinkle efficacy of 1-ethyl-β-N-acetylglucosaminide, an inducer of epidermal hyaluronan production.
Endo, Y, Yoshida, H, Akazawa, Y, Yamazaki, K, Ota, Y, Sayo, T, Takahashi, Y
Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI). 2022;(1):58-65
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BACKGROUND Hyaluronan (HA) has a unique hydration capacity that contributes to firmness and bounciness of the skin. Epidermal HA declines with skin aging, which may lead to clinical signs of aging including skin wrinkles and loss of hydration and elasticity. Recently, we developed a new cosmetic agent 1-ethyl-β-N-acetylglucosaminide (β-NAG2), which enhances HA production in cultured human keratinocytes. The aim of this study was to explore antiaging potential of β-NAG2 in reconstructed human epidermal models and human clinical trial. MATERIALS AND METHODS The amount of HA in β-NAG2-treated epidermal models by topical application was analyzed by enzyme-linked immunosorbent assay (ELISA)-like assay. A randomized, double-blind and placebo-controlled study was conducted in Japanese females (n = 33) by topically treating each side of the face with a lotion formulated with β-NAG2 or placebo for 8 weeks. RESULTS Topically applied β-NAG2 dose dependently increased HA production in epidermal models. Treatment with β-NAG2-formulated lotion significantly improved skin hydration and elasticity and reduced skin wrinkling in crow's foot areas when compared to the placebo formulation. CONCLUSION Topically applied β-NAG2 promoted epidermal HA production in vitro and showed antiwrinkle activity in vivo accompanying the improvement in skin hydration and elasticity. Our study provides a novel strategy for antiwrinkle care through β-NAG2-induced epidermal HA production.
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Predictive factors requiring high-dose evocalcet in hemodialysis patients with secondary hyperparathyroidism.
Tokumoto, M, Tokunaga, S, Asada, S, Endo, Y, Kurita, N, Fukagawa, M, Akizawa, T
PloS one. 2022;(12):e0279078
Abstract
The dosage of evocalcet required to control serum parathyroid hormone (PTH) levels varies among secondary hyperparathyroidism (SHPT) patients. This post hoc analysis evaluated the dose-dependent efficacy of evocalcet on serum intact PTH (iPTH) levels, corrected calcium (Ca) and phosphate (P) levels, and safety, in an evaluation period (week 28 to week 30) by stratifying the previous phase 3 data with the final evocalcet dosages (low 1-2 mg [131 patients], medium 3-4 mg [90 patients], high 5-8 mg [92 patients]), and identified pre-treatment patient characteristics predicting the use of higher final evocalcet dosages via univariate and multivariate logistic regression models. At the end of the study at week 30, the median serum iPTH level was higher and the achievement ratio for the target range of Japanese Society for Dialysis Therapy (60-240 pg/mL) was lower in the final high-dose subgroup (216 pg/mL and 58%, respectively) than in the other subgroups (low: 149 pg/mL and 79%; medium: 149 pg/mL and 73%, respectively). Among the three subgroups, the mean serum corrected Ca and P levels demonstrated similar trends, and similar ratio of patients achieved the target range (corrected Ca, 8.4-10 mg/dL; P, 3.5-6.0 mg/dL) from week 28 to week 30. No dose-dependent safety concerns were identified. Younger age, prior cinacalcet use, higher serum levels of iPTH and corrected Ca, procollagen type 1 N-terminal propeptide, intact fibroblast growth factor-23, and larger maximum parathyroid gland volume were significantly associated with final high-dose evocalcet (p < 0.05 in all cases). Patients requiring final high-dose evocalcet had pre-treatment characteristics indicating severe SHPT, leading to a lower final achievement rate for the target PTH levels of Japanese Society for Dialysis Therapy. Therefore, the early initiation of evocalcet treatment for SHPT is critical. Trial registration: This trial was registered as follows: ClinicalTrials.gov: NCT02549391 and JAPIC JapicCTI-153013.
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Evocalcet with vitamin D receptor activator treatment for secondary hyperparathyroidism.
Shigematsu, T, Asada, S, Endo, Y, Kawata, T, Fukagawa, M, Akizawa, T
PloS one. 2022;(2):e0262829
Abstract
This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 μg], and high [≥ 1.5 μg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28-30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group (p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group (p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration: ClinicalTrials.gov (NCT02549391) and JAPIC (JapicCTI-153013).
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Idiopathic multicentric Castleman disease with novel heterozygous Ile729Met mutation in exon 10 of familial Mediterranean fever gene.
Endo, Y, Koga, T, Otaki, H, Sasaki, D, Sumiyoshi, R, Furukawa, K, Tanaka, Y, Katsunori, Y, Kawakami, A
Rheumatology (Oxford, England). 2021;(1):445-450
Abstract
OBJECTIVE While the aetiology of idiopathic multicentric Castleman disease (iMCD) remains unclear, the involvement of autoinflammatory mechanisms has been suggested. Herein we report a Japanese patient with iMCD with a novel heterozygous Ile729Met mutation in exon 10 of the Mediterranean fever (MEFV) gene. METHODS We performed genetic analysis via targeted next-generation sequencing analysis and Sanger sequencing and conducted molecular dynamics simulations to investigate the hydrophobic interactions around the 729th amino acid in human pyrin. RESULTS In February 2011, a 59-year-old man was diagnosed with IgG4-related disease at our department based on the findings of cervical and hilar lymphadenopathies, typical lung lesions and cervical lymph node biopsy. The patient was followed up without treatment, as he was asymptomatic. However, he had been experiencing prolonged fatigue and fever with high levels of CRP since June 2017. Axillary lymph node biopsy findings led to the diagnosis of iMCD. He was successfully treated with an IL-6 inhibitor and has been in remission for 12 months. Genetic analyses for hereditary autoinflammatory disease-related genes were performed, revealing a novel heterozygous Ile729Met mutation in exon 10 of the MEFV gene. We identified that this novel mutation significantly altered the local interaction of the human pyrin B30.2 domain by molecular dynamics simulation analysis and experimentally had the potential for inflammasome activation with increased inflammatory cytokines. CONCLUSION The abnormal function of pyrin due to a mutation in the MEFV gene in this patient may have contributed to the development of MCD by inducing IL-6 production via inflammasome signalling.
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Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease.
Endo, Y, Koga, T, Ubara, Y, Sumiyoshi, R, Furukawa, K, Kawakami, A
Clinical and experimental immunology. 2021;(1):91-98
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Abstract
Four cases of idiopathic multi-centric Castleman disease (iMCD) reportedly have variants in hereditary autoinflammatory disease-related genes; however, the frequency and role of these variants in iMCD is still unknown. We therefore investigated such gene variants among patients with iMCD and aimed to reveal the relationship between iMCD and autoinflammatory disease-related genes. We reviewed 14 Japanese iMCD patients who were recruited between January 2015 and September 2019. All patients met both the Japanese tentative diagnostic criteria for Castleman disease and the international consensus diagnostic criteria for iMCD. We performed genetic analyses for 31 autoinflammatory disease-related genes by targeted next-generation sequencing. The MEFV gene variants were observed in 10 of 14 patients with iMCD. Although iMCD had a high percentage of exons 2 or 3 variants of MEFV, comparison of data from healthy Japanese subjects indicated that there was no significant difference in the percentage between healthy Japanese subjects and patients with iMCD. Variants of uncertain significance (VUS) in the TNFRSF1A and CECR1 genes were observed in two of the patients, respectively. We divided patients into two groups-those with MEFV variants (excluding E148Q variants) and those without MEFV variants-and compared the clinical characteristics between these two groups. Patients with MEFV variants, excluding E148Q variants, exhibited a significantly higher likelihood of fever and significantly lower levels of hemoglobin than those lacking MEFV variants. Our results indicated that patients with iMCD tended to have a high frequency of MEFV gene variants and the presence of such variants can affect iMCD clinical phenotypes.
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The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.
Abe, T, Matsuo, H, Abe, R, Abe, S, Asada, H, Ashida, A, Baba, A, Eguchi, K, Eguchi, Y, Endo, Y, et al
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(6):728-876
Abstract
Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.